Dr. Matthew Hill: How Cannabis Impacts Health & the Potential Risks
Andrew Huberman:
安德鲁·休伯曼：
Welcome to the Huberman Lab podcast, where we discuss science and science-based tools for everyday life.
欢迎来到休伯曼实验室播客，我们在这里讨论科学和基于科学的日常生活工具。
I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine.
我是安德鲁·胡伯曼，斯坦福大学医学院神经生物学和眼科教授。
My guest today is Dr. Matthew Hill.
今天我的客人是马修·希尔博士。
Dr. Matthew Hill is a professor of cell biology and anatomy at the University of Calgary.
马修·希尔博士是卡尔加里大学细胞生物学和解剖学教授。
His laboratory studies cannabis and its effects on stress, its effects on feeding, and its effects on the behavioral impacts of cannabis exposure at different stages of development.
他的实验室研究大麻及其对压力的影响、对喂养的影响以及在不同发育阶段接触大麻对行为的影响。
The origin of today's podcast episode is a bit unique, so I'd like to share a little bit of that background with you.
今天播客节目的起源有点独特，所以我想与大家分享一些背景知识。
Previously, I did a solo episode of the Huberman Lab podcast about cannabis, the biology of cannabis, some of its medical applications and uses, as well as some of its potential harms.
此前，我在 Huberman Lab 播客中制作了一集关于大麻、大麻生物学、其一些医疗应用和用途以及其一些潜在危害的个人节目。
That episode came out several years ago now and remains a very popular episode.
该集几年前就已经播出，至今仍然非常受欢迎。
It's had millions of views and millions of listens.
它已经有数百万次浏览和数百万次收听。
Several months ago, we posted a clip of that episode to X, formerly known as Twitter, and Dr. Matthew Hill responded to that clip on X with criticism about the specific points made within that clip.
几个月前，我们在 X（以前称为 Twitter）上发布了该集的剪辑，马修·希尔博士在 X 上对该剪辑做出了回应，对该剪辑中提出的具体观点提出了批评。
Most notably, my discussion of the data that cannabis use can, in some individuals, cause psychosis.
最值得注意的是，我对大麻使用数据的讨论可能在某些人中引起精神病。
He also took issue with some of the specific points I made in that clip related to potential differences in the biology of the effects of different strains of cannabis, most notably indica versus sativa strains, and a few other points as well.
他还对我在该剪辑中提出的一些具体观点提出了异议，这些观点涉及不同大麻品种（最显着的是籼稻与苜蓿品种）的生物学影响的潜在差异，以及其他一些观点。
Now, as somebody who's been in the field of science for several decades now, I'm very familiar with the fact that every field, every single field within science, has debates within it, controversies, and sometimes outright battles.
现在，作为一个在科学领域工作了几十年的人，我非常熟悉这样一个事实：科学中的每个领域、每个领域都存在争论、争论，有时甚至是彻底的战斗。
And to me, that's part of what makes science interesting.
对我来说，这就是科学变得有趣的部分原因。
It's an evolving process.
这是一个不断发展的过程。
It's something for which we should all be very curious to try and understand what we know, what we don't know, and try and get to the real answers.
我们都应该对此感到非常好奇，尝试了解我们所知道的、我们不知道的，并尝试找到真正的答案。
So right off the bat on X, I invited Dr. Hill onto the podcast, and he accepted the invitation.
因此，我立即邀请希尔博士加入播客，他接受了邀请。
So today's episode is really a unique one in that, first of all, we cover an enormous amount of biology and clinical data as it relates to cannabis, meaning today's discussion is not a debate.
所以今天的节目确实是一个独特的节目，因为首先，我们涵盖了大量与大麻相关的生物学和临床数据，这意味着今天的讨论不是一场辩论。
It is really an up-to-date discussion about how cannabis works.
这确实是关于大麻如何发挥作用的最新讨论。
So we talk about THC versus CBD.
所以我们谈论 THC 与 CBD。
We address the question of whether or not indicas versus sativas have different biological and subjective effects or not.
我们解决了籼稻与苜蓿是否具有不同的生物学和主观影响的问题。
We, of course, talk about the potential correlation, maybe even causation, between cannabis use and psychosis.
当然，我们谈论大麻使用和精神病之间的潜在相关性，甚至可能是因果关系。
I think you'll find that discussion very interesting.
我想你会发现这个讨论非常有趣。
And we talk about how cannabis relates to hunger, to memory, to anxiety, and to the treatment of anxiety.
我们讨论大麻与饥饿、记忆、焦虑以及焦虑治疗的关系。
I'm certain that given the widespread use of cannabis nowadays, that you'll find the discussion to be both an informative and potentially useful one that could help guide decisions as to whether or not you or others should or should not use or avoid cannabis, as well as one that can simply inform about this very interesting compound.
我确信，考虑到当今大麻的广泛使用，您会发现这次讨论既内容丰富，又可能有用，可以帮助指导您或其他人是否应该或不应该使用或避免使用大麻的决定，并且可以简单地介绍这种非常有趣的化合物。
And of course, you'll learn a lot of neuroscience and biology along the way.
当然，在此过程中您将学到很多神经科学和生物学知识。
Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford.
在开始之前，我想强调一下，这个播客与我在斯坦福大学的教学和研究角色是分开的。
It is, however, part of my desire and effort to bring zero cost to consumer information about science and science-related tools to the general public.
然而，我的愿望和努力的一部分是向公众提供有关科学和科学相关工具的零成本消费者信息。
In keeping with that theme, I'd like to thank the sponsors of today's podcast.
为了与这个主题保持一致，我要感谢今天播客的赞助商。
Our first sponsor is Eight Sleep.
我们的第一个赞助商是八睡。
Eight Sleep makes smart mattress covers with cooling, heating, and sleep tracking capacity.
August Sleep 生产具有冷却、加热和睡眠跟踪功能的智能床垫套。
I've spoken many times before on this podcast about the critical need to get sleep, both enough sleep and enough quality sleep.
我之前在这个播客上多次谈到过睡眠的迫切需要，包括充足的睡眠和足够的高质量睡眠。
Now, one of the key things to getting a great night's sleep is that your body temperature actually has to drop by about one to three degrees in order for you to fall and stay deeply asleep.
现在，获得良好睡眠的关键之一是，您的体温实际上必须下降约一到三度，才能让您入睡并保持深度睡眠。
And to wake up feeling refreshed, your body temperature actually has to increase by about one to three degrees.
为了醒来时感觉神清气爽，您的体温实际上必须升高约一到三度。
One of the best ways to ensure all of that happens is to control the temperature of your sleeping environment.
确保这一切发生的最佳方法之一是控制睡眠环境的温度。
And with Eight Sleep, it's very easy to do that.
而有了八睡眠，做到这一点非常容易。
You program the temperature that you want at the beginning, middle, and the end of the night, and that's the temperature that you're going to sleep at.
您可以设定晚上开始、中间和结束时所需的温度，这就是您睡觉时的温度。
And it will track your sleep.
它会追踪你的睡眠。
It tells you how much slow-wave sleep you're getting, how much rapid eye movement sleep you're getting, which is critical, and all of that also helps you dial in the exact parameters you need in order to get the best possible night's sleep for you.
它会告诉您您获得了多少慢波睡眠，您获得了多少快速眼动睡眠，这一点至关重要，所有这些还可以帮助您输入所需的准确参数，以便为您获得最佳的夜间睡眠。
I've been sleeping on an Eight Sleep mattress cover for well over three years now, and it has completely transformed my sleep for the better.
我已经睡在八睡眠床垫罩上三年多了，它彻底改变了我的睡眠质量。
Eight Sleep recently launched their newest generation pod cover, the Pod 4 Ultra.
八睡眠最近推出了他们最新一代的 Pod 4 Ultra。
The Pod 4 Ultra cover has improved cooling and heating capacity, higher fidelity sleep tracking technology, and the Pod 4 cover has snoring detection that will automatically lift your head a few degrees to improve airflow and stop your snoring.
Pod 4 Ultra 保护套具有改进的冷却和加热能力、更高保真度的睡眠跟踪技术，Pod 4 保护套具有打鼾检测功能，可自动将您的头部抬起几度，以改善气流并停止打鼾。
If you'd like to try an Eight Sleep mattress cover, you can go to eightsleep.com/huberman to save $350 off their Pod 4 Ultra.
如果您想尝试八睡眠床垫套，您可以访问八睡眠.com/huberman，在 Pod 4 Ultra 上可节省 350 美元。
Eight Sleep currently ships to the USA, Canada, UK, select countries in the EU, and Australia.
八睡眠目前运往美国、加拿大、英国、欧盟部分国家和澳大利亚。
Again, that's eightsleep.com/huberman.
再说一遍，这是八睡眠.com/huberman。
Today's episode is also brought to us by LMNT.
今天的节目也是LMNT给我们带来的。
LMNT is an electrolyte drink that has everything you need and nothing you don't.
LMNT 是一种电解质饮料，拥有您需要的一切，没有您不需要的东西。
That means the electrolytes, sodium, magnesium, and potassium, in the correct ratios, but no sugar.
这意味着电解质、钠、镁和钾的比例正确，但不含糖。
Now, I and others on the podcast have talked a lot about the critical importance of hydration for proper brain and bodily function.
现在，我和播客上的其他人已经谈论了很多关于水合作用对于大脑和身体正常功能的至关重要性。
Research shows that even a slight degree of dehydration can really diminish cognitive and physical performance.
研究表明，即使是轻微程度的脱水也会确实降低认知和身体表现。
It's also important that you get adequate electrolytes in order for your body and brain to function at their best.
获得足够的电解质也很重要，这样您的身体和大脑才能发挥最佳功能。
The electrolytes, sodium, magnesium, and potassium, are critical for the functioning of all the cells in your body, especially your neurons or nerve cells.
电解质（钠、镁和钾）对于体内所有细胞（尤其是神经元或神经细胞）的功能至关重要。
To make sure that I'm getting proper amounts of hydration and electrolytes, I dissolve one packet of LMNT in about 16 to 32 ounces of water when I wake up in the morning, and I drink that basically first thing in the morning.
为了确保我获得适量的水合作用和电解质，当我早上醒来时，我将一包 LMNT 溶解在大约 16 至 32 盎司的水中，并且我基本上早上第一件事就是喝它。
I also drink LMNT dissolved in water during any kind of physical exercise I'm doing, especially on hot days if I'm sweating a lot and losing water and electrolytes.
我还会在进行任何体育锻炼时饮用溶解在水中的 LMNT，尤其是在炎热的天气里，如果我大量出汗并失去水分和电解质。
If you'd like to try LMNT, you can go to drinklmnt.com/huberman, spelled drink L-M-N-T.com/huberman, to claim a free LMNT sample pack with the purchase of any LMNT drink mix.
如果您想尝试 LMNT，可以访问 Drinklmnt.com/huberman（拼写为 Drink L-M-N-T.com/huberman），购买任何 LMNT 混合饮料即可领取免费 LMNT 样品包。
Again, that's drinklmnt.com/huberman to claim a free sample pack.
再次强调，请访问 Drinklmnt.com/huberman 索取免费样品包。
Today's episode is also brought to us by BetterHelp.
今天的节目也是由 BetterHelp 为我们带来的。
BetterHelp offers professional therapy with a licensed therapist carried out entirely online.
BetterHelp 提供由持证治疗师完全在线进行的专业治疗。
There are essentially three things that make up great therapy.
伟大的治疗本质上由三件事组成。
First of all, great therapy consists of having good rapport with somebody that you can really trust and talk to about the issues that you're dealing with.
首先，良好的治疗包括与您真正信任的人建立良好的融洽关系并谈论您正在处理的问题。
Second of all, that therapist should provide support in the form of emotional support or directed guidance.
其次，治疗师应该以情感支持或定向指导的形式提供支持。
And third, expert therapy should provide useful insights, insights that allow you to better understand not just your emotional life and your relationship life, but of course, also your relationship to yourself and to career goals and school goals, meaning excellent therapy should also inspire positive action.
第三，专家治疗应该提供有用的见解，这些见解不仅可以让您更好地了解您的情感生活和人际关系生活，当然还有您与自己的关系以及与职业目标和学校目标的关系，这意味着优秀的治疗还应该激发积极的行动。
BetterHelp makes it very easy for you to find an expert therapist with whom you really resonate with and that can provide the benefits that I just described.
BetterHelp 让您可以轻松找到与您真正产生共鸣的专家治疗师，并且可以提供我刚才描述的好处。
Also, because BetterHelp therapy is done entirely online, it's very time efficient, and it's easy to fit into a busy schedule because it involves no commuting to a therapist's office, finding a parking spot, or sitting in a waiting room.
此外，由于 BetterHelp 治疗完全在线完成，因此非常省时，并且很容易适应繁忙的日程，因为它不需要通勤到治疗师办公室、寻找停车位或坐在候诊室。
If you'd like to try BetterHelp, you can go to betterhelp.com/huberman to get 10% off your first month.
如果您想尝试 BetterHelp，可以访问 betterhelp.com/huberman，第一个月可享受 10% 的折扣。
Again, that's betterhelp.com/huberman.
再说一次，这是 betterhelp.com/huberman。
And now for my discussion with Dr. Matthew Hill.
现在我与马修·希尔博士进行讨论。
Dr. Matt Hill, welcome.
马特·希尔博士，欢迎光临。
Dr. Matthew Hill:
马修·希尔博士：
Thanks for having me.
谢谢你有我。
Andrew Huberman:
安德鲁·休伯曼：
Delighted to have you here because you're an expert in the biology of cannabis, a topic that many people are curious about for a variety of reasons.
很高兴您来到这里，因为您是大麻生物学方面的专家，这是许多人出于各种原因感到好奇的话题。
So just to kick things off, maybe we can get people up to speed on what cannabis is, a little bit about how it works in the brain and body to produce the various effects that it produces, and how some of that comes to be, and then we can dig into some of the nuance.
因此，首先，也许我们可以让人们快速了解大麻是什么，了解一下它如何在大脑和身体中发挥作用，产生其产生的各种效果，以及其中一些效果是如何产生的，然后我们可以深入研究一些细微差别。
I have a lot of questions about different types, if you will, of cannabis-
如果你愿意的话，我对不同类型的大麻有很多疑问-
Dr. Matthew Hill:
马修·希尔博士：
Mm-hmm
嗯嗯
Andrew Huberman:
安德鲁·休伯曼：
...
...
the relationship to mental health, potentially to mental illness.
与心理健康的关系，可能与精神疾病的关系。
We're going to drill into all of that.
我们将深入研究所有这些。
So just to kick things off, what is cannabis?
首先，什么是大麻？
Dr. Matthew Hill:
马修·希尔博士：
Cannabis is a plant that has been around for some time.
大麻是一种已经存在了一段时间的植物。
It's kind of got a very rich history of use around the world for different cultures, for both kind of medicinal and spiritual and recreational purposes over several centuries.
几个世纪以来，它在世界各地的不同文化中有着非常丰富的使用历史，用于医疗、精神和娱乐目的。
The plant has kind of become, in the West, it really wasn't a thing mainstream-wise until about the '60s.
在西方，直到 60 年代左右，这种植物才真正成为主流。
And then it became kind of introduced as a drug of choice that a lot of people started using during the rise of the hippie era, and I think that was a lot of the time that cannabis got popularized.
然后它成为一种首选药物，在嬉皮士时代的兴起期间很多人开始使用，我认为大麻在很多时候都得到了普及。
And then I'd say more recently, cannabis has, into the '90s and on, has become kind of a very heavily used drug by a large swath of people, ranging from teenagers on up.
我想说的是，最近，进入 90 年代及以后，大麻已经成为一种被很多人（从青少年到青少年）大量使用的药物。
In terms of what it is inside it, it's a plant with a lot of very complex chemistry and biology behind it.
就其内部成分而言，它是一种背后有许多非常复杂的化学和生物学的植物。
So there are a lot of molecules that it carries in it.
所以它携带了很多分子。
We call these cannabinoids, and they come in a lot of different flavors.
我们称这些为大麻素，它们有多种不同的口味。
But the main one that's the most important one when we talk about cannabis and what drives the kind of intoxicating and what I would refer to as psychoactive effects of cannabis is delta-9-tetrahydrocannabinol, or what we call THC.
但当我们谈论大麻时，最重要的一个是 δ-9-四氢大麻酚，或者我们所说的 THC。
And that really is what dictates the psychoactive and intoxicating properties of the plant.
这确实决定了该植物的精神活性和醉人特性。
And so the amount of THC that is within the cannabis plant will influence how high a person's going to get when they consume it.
因此，大麻植物中四氢大麻酚的含量将影响人们食用大麻时的浓度。
There are probably 70 to 100 and some odd other cannabinoids that are within cannabis.
大麻中可能含有 70 到 100 种大麻素以及一些奇怪的其他大麻素。
Most of them are pretty trace levels, and they vary from different types of cannabis from one another.
其中大多数都是相当微量的，并且它们因不同类型的大麻而异。
But the other one that's had a lot of attention is cannabidiol, or what we call CBD.
但另一种备受关注的物质是大麻二酚，即我们所说的 CBD。
CBD structurally looks pretty similar to THC but doesn't behave anything like THC.
CBD 在结构上看起来与 THC 非常相似，但行为却不像 THC。
It's not intoxicating at all.
它一点也不令人陶醉。
I'm not sure.
我不知道。
I would probably say it's not psychoactive in the sense that people can't tell if they're on it or not, but some people still say it's psychoactive because people claim it can affect anxiety state or a mood state or other things.
我可能会说它不是精神活性的，因为人们无法判断他们是否在服用它，但有些人仍然说它是精神活性的，因为人们声称它可以影响焦虑状态或情绪状态或其他事物。
So in that context, maybe psychoactive is still somewhat appropriate of a word to use.
因此，在这种情况下，也许“精神活性”这个词用起来还是比较合适的。
And then there's a whole bunch of other things like cannabinol, cannabigerol, and these other minor cannabinoids, most of which we really don't understand any of the biology of.
还有一大堆其他物质，比如大麻酚、大麻醇和其他次要大麻素，其中大多数我们真的不了解其生物学原理。
We don't know what they're doing.
我们不知道他们在做什么。
They may influence some of the effects of THC.
它们可能会影响 THC 的一些效果。
They may not.
他们可能不会。
But they're there, and they vary in their composition from different flavor of different cannabis to different flavor.
但它们就在那里，而且它们的成分各不相同，从不同大麻的不同味道到不同的味道。
And then there are those other things called terpenes-
还有其他一些叫做萜烯的东西-
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm
嗯嗯
Dr. Matthew Hill:
马修·希尔博士：
...
...
which are kind of highly volatile compounds, but they're not specific to cannabis.
它们是一种高度挥发性的化合物，但它们并不是大麻特有的。
They're found in tons of other plants.
它们存在于大量其他植物中。
So this is a lot of which seems to contribute at least to some of the smell and the flavors of cannabis.
因此，其中很多似乎至少对大麻的某些气味和味道有贡献。
So these are things like limonene, which gives some cannabis kind of a citrusy odor or flavor to it, pinene, which gives things more of an earthy tree kind of smell, beta-caryophyllene, myrcene.
比如柠檬烯，它给大麻带来一种柑橘味或味道，蒎烯，它给东西更多的泥土树味，β-石竹烯，月桂烯。
And these terpenes are also some of which do have known biological activity, some don't, and they vary quite heavily across different kinds of cannabis as well.
这些萜烯也有一些确实具有已知的生物活性，有些则没有，而且它们在不同种类的大麻中也有很大差异。
And again, there's some thought that they may be influencing some of the psychoactive or intoxicating properties of cannabis, but the reality is we really don't know a lot about them at this point.
再次，有人认为它们可能会影响大麻的一些精神活性或令人陶醉的特性，但现实是我们目前对它们了解不多。
There's kind of some emerging work that's starting to come out now that kind of plays with giving someone THC and adding in one other terpene or one other minor cannabinoid and seeing how it influences things.
现在开始出现一些新兴的工作，即给某人 THC 并添加另一种萜烯或另一种次要大麻素，然后看看它如何影响事物。
And so you can imagine with the plethora of molecules that exist in cannabis, doing this in a piecewise manner could take decades to kind of really get to a point where we understand all the interactive components of cannabis.
因此，你可以想象一下，大麻中存在大量的分子，以分段的方式进行这项工作可能需要几十年的时间才能真正达到我们了解大麻所有相互作用成分的程度。
But people tend to refer to this as an entourage effect.
但人们倾向于将此称为随行效应。
That's kind of a phrase that gets used quite widely in the cannabis world.
这是一个在大麻世界中广泛使用的短语。
And the idea behind that is that if you took pure THC, and so there are some distillate pens and things that exist out there now in the product market, which are basically isolated THC with trace levels of anything of other stuff, would be very different than if you had THC in combination with some of these other molecules and how they might influence how THC itself is working or not.
其背后的想法是，如果你服用纯 THC，那么现在产品市场上存在一些蒸馏笔和其他东西，它们基本上是分离的 THC，其中含有微量的其他物质，这与你将 THC 与其他一些分子结合使用以及它们如何影响 THC 本身的作用或不发挥作用会有很大不同。
So-
所以——
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm Fascinating plant.
嗯嗯，迷人的植物。
You mentioned the psychoactive effects.
你提到了精神作用。
Some people listening to this and watching this presumably have experienced those psychoactive effects.
有些听过这个或看过这个的人可能已经经历过这些精神影响。
Others perhaps have not.
其他人也许还没有。
How could we describe, for both groups, what the "psychoactive effects" are?
对于这两个群体，我们如何描述“精神影响”是什么？
You mentioned the higher the concentration of THC, the "higher" someone will get, right?
您提到 THC 浓度越高，某人的“水平”就越高，对吗？
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
The greater the intensity of the high.
强度越大强度越高。
What is the high?
什么是高？
And I know people are probably chuckling saying, does Huberman not know because he's never done it?
我知道人们可能会笑着说，休伯曼难道不知道，因为他从来没有这样做过吗？
I mean, that's my own business.
我的意思是，那是我自己的事。
I just want people to understand what you mean by psychoactive effects.
我只是想让人们理解你所说的精神作用是什么意思。
Dr. Matthew Hill:
马修·希尔博士：
So, the way that people would usually describe the intoxicating effects of cannabis is, people often refer to it as there being some euphoria or some positive mood.
因此，人们通常描述大麻的醉人效果的方式是，人们经常将其称为某种欣快感或某种积极情绪。
Not on the same order as what people would describe with, say, cocaine or some other stimulants, but there certainly is some kind of positive aspect.
与人们描述的可卡因或其他兴奋剂不同，但肯定有某种积极的方面。
If there wasn't, people wouldn't be using it, if they didn't feel positive about it afterwards.
如果没有，人们就不会使用它，如果他们事后对此感觉不积极的话。
There can be other aspects, in terms of changes in feeding behavior.
就喂养行为的变化而言，可能还有其他方面。
People might find things funnier than they found things.
人们可能会发现事情比他们发现的事情更有趣。
It might change the way they perceive various environmental stimuli.
它可能会改变他们感知各种环境刺激的方式。
But it can also, for some people, create a bit of a dissociative state to some degree, where people might feel a little bit out of body.
但对于某些人来说，它也会在某种程度上造成一种分离状态，人们可能会感到有点脱离身体。
So it's kind of a complicated, intoxicating state to describe, I would say.
所以我想说，这是一种复杂的、令人陶醉的状态。
Because usually if someone's referring to something like a stimulant, they're just like, oh, people feel like they're God.
因为通常如果有人指的是兴奋剂之类的东西，他们就会说，哦，人们感觉自己是上帝。
They're like, you know, jacked up.
他们就像，你知道，很兴奋。
Andrew Huberman:
安德鲁·休伯曼：
Possibility everywhere.
可能性无处不在。
Dr. Matthew Hill:
马修·希尔博士：
Yeah, exactly.
是的，完全正确。
They're very happy and they're kind of jacked up.
他们非常高兴，而且有点兴奋。
And I think with cannabis, the way people would describe it would be very different.
我认为对于大麻，人们描述它的方式会非常不同。
It's an introspective state.
这是一种内省的状态。
You might be more aware of your bodily feelings and states that are going on inside of you, your kind of internal state.
您可能会更加了解自己的身体感受和内心状态，以及您的内部状态。
But you also have a different perspective on external stimuli.
但你对外部刺激也有不同的看法。
You might process information a bit differently, focus on things a bit differently.
您可能会以不同的方式处理信息，以不同的方式关注事物。
So it's kind of a complicated state to describe, I would say.
所以我想说，这是一种难以描述的复杂状态。
Usually, when people are assessing if someone's intoxicated, the kind of lab work where people get someone high, they just use what we call a visual analog scale, which is a one to 100 or something, or a zero to 100, and say, "Do you feel high?
通常，当人们评估某人是否喝醉时，在实验室工作中，人们会让人感到兴奋，他们只是使用我们所说的视觉模拟量表，即从 1 到 100 或类似的数字，或者从 0 到 100，然后说：“你感觉兴奋吗？
Do you enjoy this?
你喜欢这个吗？
Would you say you feel euphoric?
你会说你感到欣快吗？
Is your mood elevated?" So they're scaling things like that.
你的心情高涨了吗？”所以他们正在扩大这样的规模。
So I think that's more typically in a lab setting, how you would define if someone's high or not from it.
所以我认为这更典型的是在实验室环境中，你如何定义某人是否兴奋。
And this is why when people do studies with something like a placebo cannabis or a very low THC cannabis, you'll see a scaling.
这就是为什么当人们使用安慰剂大麻或 THC 含量极低的大麻进行研究时，您会看到比例变化。
So, even if you give someone a placebo cannabis, if they think that they're getting cannabis, a lot of people still respond by saying they feel a bit high.
因此，即使你给某人服用安慰剂大麻，如果他们认为自己正在服用大麻，很多人仍然会说他们感觉有点兴奋。
Andrew Huberman:
安德鲁·休伯曼：
That's interesting.
这很有趣。
Is that true even if they've never used cannabis before?
即使他们以前从未使用过大麻，这是真的吗？
Dr. Matthew Hill:
马修·希尔博士：
I'm not actually certain if you are allowed to have someone in a drug study if they've never done something before.
我实际上不确定是否允许某人参与药物研究，如果他们以前从未做过某事。
I think they have to have had some previous experience with the drug-
我认为他们以前一定有过使用这种药物的经验-
Andrew Huberman:
安德鲁·休伯曼：
And they pay you-
他们付钱给你-
Dr. Matthew Hill:
马修·希尔博士：
...
...
to be enrolled.
被录取。
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
So now pot smokers everywhere are running to look at studies.
所以现在世界各地的吸大麻者都跑去看研究。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
I don't think you can use drug naive people.
我认为你不能使用没有吸毒经验的人。
I don't run human clinical lab studies, so I can't explicitly say it, but that's my understanding, is that someone has to have had even limited, not much, but at least once or twice, they have to have experienced the drug before.
我不进行人体临床实验室研究，所以我不能明确地说出来，但这是我的理解，就是有人必须曾经使用过这种药物，甚至是有限的，不多，但至少一次或两次，他们必须以前经历过这种药物。
So I don't know if you would take someone who was completely blind, because I don't know how they would replicate that state-
所以我不知道你是否会接受一个完全失明的人，因为我不知道他们会如何复制那种状态-
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Interesting
有趣
Dr. Matthew Hill:
马修·希尔博士：
...
...
if they're not expecting it.
如果他们没有预料到的话。
Andrew Huberman:
安德鲁·休伯曼：
What about the effects of cannabis on time perception?
大麻对时间感知的影响如何？
There's this reputation that cannabis has for disrupting time perception, that people will think a long period of time has passed, when in fact-
大麻因扰乱时间感知而闻名，人们会认为已经过去了很长一段时间，而事实上——
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
very little time has passed.
时间已经过去了很短的时间。
Maybe it's sometimes even the reverse.
也许有时甚至是相反的。
Is the mechanism by which cannabis can adjust time perception known?
大麻调节时间感知的机制是否已知？
Dr. Matthew Hill:
马修·希尔博士：
I wouldn't say it's well worked out.
我不会说它做得很好。
There definitely seems to be some temporal dilation, like you're saying, where people think things of, someone will be high, and someone will ask them, "How long do you think time has passed?" They would report usually longer periods of time have passed than actually have.
肯定会有一些时间膨胀，就像你说的，当人们想到事情时，有人会兴奋，有人会问他们，“你认为时间过去了多久？”他们报告的时间通常比实际时间更长。
I feel like there is some older work I could dig up to see if I could find that is either in, it might even be in pigeons, but it might be in rodents.
我觉得我可以挖掘一些较旧的工作，看看我是否能找到它，甚至可能在鸽子身上，但也可能在啮齿动物身上。
It's looking at temporal ordering, and they give animals cannabinoids, and that's kind of a cleaner way of seeing, because they are very good at learning, like if I wait 10 minutes and then I engage in a behavior, I get a reward.
它着眼于时间顺序，他们给动物提供大麻素，这是一种更清晰的看待方式，因为它们非常善于学习，就像如果我等 10 分钟然后进行某种行为，我就会得到奖励。
And so you can really train animals to have this ordinal timing where they kind of know distinct periods of time.
所以你真的可以训练动物有这种顺序计时，让它们知道不同的时间段。
And if they give them cannabinoids, they respond differently.
如果他们给他们大麻素，他们的反应就会不同。
So in that context, it does still seem to produce some state where there's an altered perception of time passing.
因此，在这种情况下，它似乎仍然会产生某种对时间流逝的感知发生改变的状态。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
And so I think if we were going to really understand the mechanism of it, that would probably be the way to go.
所以我认为如果我们要真正理解它的机制，这可能就是我们要走的路。
But I'm not super familiar with the work, because no one's-- Anything I can think of is pretty old.
但我对这项工作不是很熟悉，因为没有人——我能想到的任何东西都相当古老。
I can't think of anything modern where people have actually looked at this.
我想不出有什么现代的东西能让人们真正看到这一点。
Andrew Huberman:
安德鲁·休伯曼：
Interesting.
有趣。
You mentioned effects of cannabis on appetite, and I know one of the medical uses of cannabis is in people that are undergoing treatment for cancer.
您提到大麻对食欲的影响，我知道大麻的医疗用途之一是用于正在接受癌症治疗的人。
Dr. Matthew Hill:
马修·希尔博士：
Mm-hmm.
嗯嗯。
Andrew Huberman:
安德鲁·休伯曼：
In order to stimulate appetite, because oftentimes they have very low or even no appetite due to the cancer treatment.
为了刺激食欲，因为很多时候他们因为癌症治疗而食欲很低，甚至没有食欲。
Is the mechanism by which cannabis can stimulate appetite known?
大麻刺激食欲的机制已知吗？
And if so, what is the general trend of effect?
如果是的话，效果的总体趋势是什么？
Makes people hungrier, obviously, but we hear again in kind of recreational terms of people getting the munchies.
显然，这会让人们更加饥饿，但我们再次以娱乐的方式听到人们得到了零食。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Becoming exceedingly hungry.
变得极度饥饿。
Is that related to some cannabis induced effect on, say, blood sugar, like insulin or glucose regulation?
这是否与大麻对血糖（例如胰岛素或血糖调节）的影响有关？
Or is it happening at a different level?
或者它发生在不同的层面？
Dr. Matthew Hill:
马修·希尔博士：
I think we almost need to take a step back, actually, to talk about how cannabis works in the brain-
我认为实际上我们几乎需要退后一步来讨论大麻如何在大脑中发挥作用 -
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm
嗯嗯
Dr. Matthew Hill:
马修·希尔博士：
...
...
before we go into that.
在我们开始讨论之前。
Andrew Huberman:
安德鲁·休伯曼：
Great.
太棒了。
Dr. Matthew Hill:
马修·希尔博士：
So THC as a molecule exerts almost all its effects.
因此 THC 作为一个分子发挥了几乎所有的作用。
They're acting at this one receptor, for the most part, that's widely expressed through the brain, called the cannabinoid type one receptor.
它们主要作用于一种在大脑中广泛表达的受体，称为大麻素一型受体。
Andrew Huberman:
安德鲁·休伯曼：
CB1.
CB1。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
CB1 is the shorthand for it.
CB1是它的简写。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
And I think, as people tend to create analogies to describe what receptors are, for those of you who don't know, most people use a lock and key analogy.
我认为，由于人们倾向于创建类比来描述受体是什么，对于那些不知道的人来说，大多数人都会使用锁和钥匙的类比。
That a receptor would be a protein that sits on a cell, and a molecule that binds to it, like THC, is the key that fits in that lock.
受体是一种位于细胞上的蛋白质，而与其结合的分子（如四氢大麻酚）是打开这把锁的钥匙。
When it activates it, it triggers some biological process in the cell, in this case a neuron, that changes its activity in some capacity.
当它激活它时，它会触发细胞（在本例中为神经元）中的一些生物过程，从而以某种能力改变其活动。
And so THC acts on these CB1 receptors, which are very widely expressed.
因此 THC 作用于这些表达非常广泛的 CB1 受体。
In fact, outside of like ...
事实上，除了像...
kind of ion channels that are expressed in the brain.
在大脑中表达的一种离子通道。
The CB1 is, I think, one of the most, if not the most widely expressed receptor in the brain.
我认为，CB1 即便不是大脑中表达最广泛的受体，也是表达最多的受体之一。
It's everywhere.
它无处不在。
Andrew Huberman:
安德鲁·休伯曼：
Wow.
哇。
Dr. Matthew Hill:
马修·希尔博士：
So it's really important.
所以这真的很重要。
And I think as you had alluded to previously, this didn't evolve in humans in the hopes that one day humans would find cannabis.
我认为正如您之前提到的，人类进化出这种技术并不是为了希望有一天人类能够找到大麻。
This is just-
这只是——
Andrew Huberman:
安德鲁·休伯曼：
Although cannabis users everywhere use that argument.
尽管世界各地的大麻使用者都使用这个论点。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
I know people love to leverage things.
我知道人们喜欢利用事物。
If it's a plant, it's natural and safe.
如果它是植物，那么它就是天然且安全的。
And there's obviously issues we'll talk about with that.
显然我们会讨论一些问题。
But really, this is just biological redundancy.
但实际上，这只是生物冗余。
Nature only has so many ways to create something, and so there's going to be things that end up overlapping in the way that they function.
大自然创造某种东西的方式只有这么多，所以最终会有一些东西在它们的功能方式上重叠。
And so the receptor that's in the brain and throughout the body, the CB1, and there is also a CB2 receptor, it's not really expressed in the brain.
因此，大脑和全身的受体 CB1 和 CB2 受体并没有真正在大脑中表达。
It's in some of the immune cells in the brain and maybe some limited distribution in actual brain cell neurons.
它存在于大脑中的一些免疫细胞中，并且可能分布在实际脑细胞神经元中。
Andrew Huberman:
安德鲁·休伯曼：
Where in the body is it expressed?
表达在身体的哪个部位？
Dr. Matthew Hill:
马修·希尔博士：
It's mostly immune cells.
主要是免疫细胞。
So you'll see CB2s mostly on macrophages or other kind of immune cells.
因此，您会在巨噬细胞或其他类型的免疫细胞上看到 CB2。
Andrew Huberman:
安德鲁·休伯曼：
Cells that gobble up debris.
吞噬碎片的细胞。
Dr. Matthew Hill:
马修·希尔博士：
Yeah, and that basically regulate inflammatory processes.
是的，这基本上可以调节炎症过程。
And so the main role of CB2 seems to be much more about regulating inflammation.
因此，CB2 的主要作用似乎更多的是调节炎症。
So that's kind of a separate role.
所以这是一个单独的角色。
That can certainly impact the brain in different ways.
这肯定会以不同的方式影响大脑。
But when we talk about the effects on the central nervous system and the brain and behavior, we're talking almost entirely about CB1.
但当我们谈论对中枢神经系统、大脑和行为的影响时，我们谈论的几乎都是 CB1。
And so both the CB1 and CB2 receptors, like I said, don't exist because nature was like, "Humans are going to find cannabis.
因此，正如我所说，CB1 和 CB2 受体都不存在，因为大自然就像是，“人类将会找到大麻。
This will all work together now." So there are molecules our body produces, which we call endocannabinoids.
现在这一切都将共同发挥作用。”我们的身体会产生一些分子，我们称之为内源性大麻素。
And they are kind of funny little molecules because they don't really behave, certainly in the brain, they don't behave like a normal neurotransmitter.
它们是一种有趣的小分子，因为它们并没有真正的行为，当然在大脑中，它们的行为不像正常的神经递质。
So, I assume most people who listen to your podcast are relatively adept with the basic idea of how neurons work.
因此，我认为大多数听你播客的人都相对熟悉神经元如何工作的基本概念。
So you have neuron A, let's call it the presynaptic neuron, because you have that gap between the two cells where they communicate called the synapse.
所以你有神经元 A，我们称之为突触前神经元，因为两个细胞之间有一个间隙，它们在其中进行通信，称为突触。
So neuron A releases a transmitter, and it can be something that excites the neighboring cell, neuron B, or it can inhibit it.
因此，神经元 A 释放一种递质，它可以兴奋邻近的细胞（神经元 B），也可以抑制它。
And so the way that we always talk about neurotransmission in the brain is neuron A releases a chemical that crosses the synapse, acts on neuron B, and it can either jack that neuron's activity up, or it can scale it down.
因此，我们总是谈论大脑中的神经传递，神经元 A 释放一种化学物质，穿过突触，作用于神经元 B，它可以增强或减弱神经元的活动。
And that affects brain-wide patterns of activity.
这会影响全脑的活动模式。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
And we call that anterograde because it moves from neuron A to neuron B, which is kind of the general flow of things and how we usually think about it.
我们称之为顺行，因为它从神经元 A 移动到神经元 B，这是事物的一般流程以及我们通常如何思考它。
So endocannabinoids are kind of this little bit of an oddity in the sense that they could do the reverse.
因此，内源性大麻素有点奇怪，因为它们可以起到相反的作用。
And so endocannabinoids are actually made in neuron B on the postsynaptic side, and then they go backwards and act on neuron A to regulate how much transmitter is released.
因此，内源性大麻素实际上是在突触后侧的神经元 B 中产生的，然后它们向后作用于神经元 A 来调节递质的释放量。
And so in many ways, this is like, I kind of liken it to a thermostat model for the most part.
因此，在很多方面，这就像，我在很大程度上将其比作恒温器模型。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
Certainly if we're talking about something like excitability.
当然，如果我们谈论的是兴奋性之类的东西。
So if neuron A is dumping out something that excites neuron B, like glutamate, which is an excitatory neurotransmitter, as neuron B gets too excited, it's going to start releasing endocannabinoids to go back and tell neuron A to stop driving it.
因此，如果神经元 A 排出一些刺激神经元 B 的东西，比如谷氨酸，这是一种兴奋性神经递质，当神经元 B 变得过于兴奋时，它就会开始释放内源性大麻素，以返回并告诉神经元 A 停止驱动它。
So-
所以——
Andrew Huberman:
安德鲁·休伯曼：
So sort of a homeostatic scale-
有点像稳态量表——
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
and trying to maintain a middle range.
并努力保持中间范围。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
At the end of the day, no matter how you discuss it and what system you discuss it, I think the majority of people in the cannabinoid field would agree that the primary physiological role of endocannabinoids is to maintain homeostasis.
归根结底，无论您如何讨论它以及讨论什么系统，我认为大麻素领域的大多数人都会同意内源性大麻素的主要生理作用是维持体内平衡。
That's what they do.
这就是他们所做的。
They keep everything in its happy place, let's say.
比方说，他们把所有东西都放在快乐的地方。
So like, uh-
所以就像，呃-
Andrew Huberman:
安德鲁·休伯曼：
And that's probably why the CB1 receptor is so widely distributed-
这可能就是 CB1 受体分布如此广泛的原因——
Dr. Matthew Hill:
马修·希尔博士：
Exactly
正是如此
Andrew Huberman:
安德鲁·休伯曼：
...
...
is that neurons can excite or inhibit each other, that is raise or reduce the amount of electrical activity in the, let's say, nearby neuron.
神经元可以相互兴奋或抑制，即增加或减少附近神经元的电活动量。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Because we're talking about retrograde signaling.
因为我们正在谈论逆行信号。
But ultimately you don't want runaway excitation-
但最终你不想要失控的兴奋——
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
because that looks like epilepsy.
因为这看起来像癫痫病。
Dr. Matthew Hill:
马修·希尔博士：
Exactly.
正是如此。
Andrew Huberman:
安德鲁·休伯曼：
And you don't want runaway inhibition because that looks like suppression of-
你不希望失控的抑制，因为这看起来像是对-
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
ability to think, move, et cetera.
思考、移动等的能力。
Dr. Matthew Hill:
马修·希尔博士：
Exactly.
正是如此。
Andrew Huberman:
安德鲁·休伯曼：
Okay.
好的。
Dr. Matthew Hill:
马修·希尔博士：
So you want to keep things in where they should be.
所以你想把东西放在它们应该在的地方。
And so you want neurons to get excited, but you don't want them to get overexcited.
所以你希望神经元兴奋，但又不希望它们过度兴奋。
So endocannabinoids in kind of a very prototypical sense act as this circuit breaker, essentially.
因此，内源性大麻素在一种非常典型的意义上本质上充当了这种断路器。
Andrew Huberman:
安德鲁·休伯曼：
Mm.
嗯。
Dr. Matthew Hill:
马修·希尔博士：
Where they go back and gate how much is coming in.
他们返回并控制进入的数量。
And they do this through various mechanisms, essentially turning off the electrical activity of that presynaptic neuron so that it stops releasing neurotransmitter.
他们通过各种机制来做到这一点，本质上是关闭突触前神经元的电活动，使其停止释放神经递质。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
They can also regulate, though, inhibitory neurotransmitter release as well, and this is usually done through a little bit more of a complex process, where it's driven by excitation, but then it regulates the inhibitory pathway.
不过，它们也可以调节抑制性神经递质的释放，这通常是通过一个更复杂的过程来完成的，其中它是由兴奋驱动的，但随后它会调节抑制途径。
Andrew Huberman:
安德鲁·休伯曼：
So inhibiting the inhibitor-
所以抑制抑制剂-
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
leads to more excitation.
导致更多的兴奋。
Dr. Matthew Hill:
马修·希尔博士：
Exactly.
正是如此。
I usually liken it to basically taking the brakes off of a car while you're going downhill kind of thing.
我通常把它比作下坡时松开汽车的刹车。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
You'd use your braking system to keep things in check, but if you want to go faster, you take the foot off the brakes, and you let things accelerate.
你会使用刹车系统来控制一切，但如果你想开得更快，你就把脚从刹车上移开，然后让一切加速。
And so this can be really important for things like forms of synaptic plasticity or neuroplasticity, let's say, where you want synaptic strengthening to happen.
因此，这对于突触可塑性或神经可塑性等形式非常重要，比如说，您希望发生突触强化。
So under a learning event or something, you want that synapse to really hardwire better.
因此，在学习活动或其他活动中，您希望突触真正更好地进行硬连线。
And so having endocannabinoids kind of turn off the inhibitory component is one of the mechanisms to facilitate that.
因此，内源性大麻素可以关闭抑制成分，这是促进这一过程的机制之一。
But at the same time, if you want to have a bit more adaptive flexibility, endocannabinoids can weaken that synapse at the same time by acting right at the excitatory terminal itself.
但与此同时，如果你想要有更多的适应性灵活性，内源性大麻素可以通过作用于兴奋性末端本身来同时削弱突触。
And so their ability to kind of play with the relative activity of a circuit is really dependent on which neuron they're acting on.
因此，它们玩弄电路相对活动的能力实际上取决于它们作用于哪个神经元。
And so they can regulate excitation or inhibition differentially.
因此它们可以差异性地调节兴奋或抑制。
And CB1 receptors are found on virtually every single kind of neuron in the brain, except one.
CB1 受体几乎存在于大脑中的每一种神经元上，只有一种神经元除外。
I think you'll find this interesting because it's dopamine.
我想你会发现这很有趣，因为它是多巴胺。
And dopamine neurons are basically the only neurons in the brain that don't really, at least as far as we've been able to characterize to date, express cannabinoid receptors.
多巴胺神经元基本上是大脑中唯一不真正表达大麻素受体的神经元，至少到目前为止我们已经能够表征。
Andrew Huberman:
安德鲁·休伯曼：
Interesting.
有趣。
If I may, earlier you mentioned one of the potential psychoactive effects of cannabis is euphoria.
如果可以的话，您之前提到过大麻的潜在精神作用之一是欣快感。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Does that mean that the euphoria associated with cannabis use is independent of dopamine and is more reliant on something like perhaps the opioid receptor system or the serotonergic receptor system?
这是否意味着与大麻使用相关的欣快感独立于多巴胺，并且更依赖于阿片受体系统或血清素受体系统之类的东西？
Dr. Matthew Hill:
马修·希尔博士：
So, yeah, I wouldn't say that cannabinoids don't affect dopamine-
所以，是的，我不会说大麻素不会影响多巴胺-
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm
嗯嗯
Dr. Matthew Hill:
马修·希尔博士：
What we understand in the ventral tegmental area, which is kind of the hotspot of dopamine neurons, or at least the ones that are involved in motivation and stuff, those neurons are regulated by a lot of inhibitory neurons that dump out inhibitory transmitter and keep those neurons kind of quiet.
据我们所知，腹侧被盖区是多巴胺神经元的热点，或者至少是那些与动机等相关的神经元，这些神经元受到许多抑制性神经元的调节，这些抑制性神经元会释放出抑制性递质，使这些神经元保持安静。
Or at least-
或者至少——
Andrew Huberman:
安德鲁·休伯曼：
So there's an opportunity for indirect regulation.
因此，存在间接监管的机会。
Dr. Matthew Hill:
马修·希尔博士：
Exactly.
正是如此。
So what you have is those neurons that regulate the dopamine neurons are very rich in cannabinoid receptors.
所以，那些调节多巴胺神经元的神经元富含大麻素受体。
This is actually kind of similar to how mu opioid receptors work for things like morphine or heroin.
这实际上有点类似于 mu 阿片受体对吗啡或海洛因等药物的作用。
And essentially what the cannabinoid receptors will do is when they're activated, they'll turn off that inhibitory control, and that allows dopamine neurons to kind of move into a state where they're more prone to go into burst firing and have big dumps of dopamine.
本质上，大麻素受体的作用是，当它们被激活时，它们会关闭抑制控制，这使得多巴胺神经元进入一种更容易爆发并产生大量多巴胺的状态。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
Whether or not that relates to the positive affect or the euphoria, I don't think anyone has cleanly demonstrated that.
无论这是否与积极情绪或欣快感有关，我认为没有人清楚地证明了这一点。
Obviously, dopamine's very complicated in terms of its relation to endpoints and whether it's reward or motivation.
显然，多巴胺与终点的关系以及奖励或动机的关系非常复杂。
But cannabinoids definitely do have an influence on dopamine transmission.
但大麻素确实对多巴胺的传递有影响。
They just don't tend to do it directly.
他们只是不倾向于直接这样做。
And I think that's this very bizarre and interesting component of cannabinoid signaling, is why the brain would've evolved in a way to allow every other neurotransmitter system to be actively and directly regulated by endocannabinoids, but dopamine is kind of spared from this.
我认为这就是大麻素信号传导中非常奇怪和有趣的组成部分，这就是为什么大脑会以某种方式进化，允许所有其他神经递质系统受到内源性大麻素的主动和直接调节，但多巴胺却不受此影响。
So I don't know.
所以我不知道。
Obviously, you can always just theoretically guess as to why somebody would do that.
显然，你总是可以从理论上猜测为什么有人会这样做。
I don't know what the reason for it would be, but it is something that has kind of intrigued a lot of people because every other system in the brain is so tightly controlled, to some degree, by endocannabinoids, and then this one circuit is kind of free of it.
我不知道其原因是什么，但这引起了很多人的兴趣，因为大脑中的所有其他系统在某种程度上都受到内源性大麻素的严格控制，而这个回路却不受内源性大麻素的控制。
But yeah, so the main role of endocannabinoids is really to regulate plasticity or homeostasis, allow flexibility of circuits to either goose up their activity or ramp it down if they need to, depending on the environment, depending on the experience of the organism.
但是，是的，内源性大麻素的主要作用实际上是调节可塑性或体内平衡，允许电路灵活地提高其活性或在需要时降低其活性，这取决于环境，取决于生物体的经验。
So there's a lot of kind of roles that endocannabinoids play in that domain.
因此，内源性大麻素在该领域发挥着多种作用。
But even within the endocannabinoids, there's two primary endocannabinoids.
但即使在内源性大麻素中，也有两种主要的内源性大麻素。
And again, this is one of the weird things about how endocannabinoids work because if you talk about things like serotonin or dopamine, you have a single molecule that gets released in the typical anterograde way, and it diversifies at the level of a receptor.
再说一遍，这是内源性大麻素如何发挥作用的奇怪之处之一，因为如果你谈论血清素或多巴胺之类的东西，你就会有一个以典型的顺行方式释放的分子，并且它在受体水平上多样化。
So serotonin has, like, I don't know, 15 receptors or 20 or something now.
所以血清素现在有 15 个或 20 个受体，我不知道。
Dopamine has at least five.
多巴胺至少有五个。
And so the different actions that serotonin or dopamine will have is all driven by the diversification of the receptors.
因此，血清素或多巴胺的不同作用都是由受体的多样化驱动的。
It's one molecule.
它是一个分子。
Whereas cannabinoids are the reverse.
而大麻素则相反。
Not only do they work backwards across the synapse and work in this retrograde fashion, but really you have one receptor that is regulated by two molecules.
它们不仅在突触中反向工作并以这种逆行方式工作，而且实际上你有一个由两个分子调节的受体。
So the diversification happens more at the level of the molecule than at the receptor, which is, again, very unique.
因此，多样化更多地发生在分子水平而不是受体，这又是非常独特的。
And the two molecules that we know are kind of the bonafide endocannabinoids.
我们知道这两种分子是真正的内源性大麻素。
There could be more.
可能还有更多。
They're called anandamide, which is actually a kind of a funny name because it comes from the Sanskrit word anand for bliss.
它们被称为 anandamide，这实际上是一个有趣的名字，因为它来自梵文单词 anand，意为极乐。
And so-
所以——
Andrew Huberman:
安德鲁·休伯曼：
Mm
毫米
Dr. Matthew Hill:
马修·希尔博士：
...
...
Rafi Mechoulam, who was in Israel when he discovered the molecule 30-odd years ago, wanted it to reflect inner bliss and so he named it anandamide.
三十多年前，Rafi Mechoulam 在以色列发现了这种分子，他希望它能够反映内心的幸福，因此他将其命名为 anandamide。
So it's like inner bliss with an amide bond, is kind of the joke he had for it.
所以这就像酰胺键带来的内心幸福，这是他开的玩笑。
And so-
所以——
Andrew Huberman:
安德鲁·休伯曼：
He discovered anandamide and decided to call it bliss because he had familiarity with cannabis or because-
他发现了 anandamide 并决定将其称为幸福，因为他熟悉大麻或因为 -
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
he took anandamide as a direct experience, and then-
他把 anandamide 作为一种直接体验，然后——
Dr. Matthew Hill:
马修·希尔博士：
No, I mean he-
不，我的意思是他——
Andrew Huberman:
安德鲁·休伯曼：
Because it takes a lot for a scientist to discover a molecule, but then for a scientist to discover a molecule and then name it bliss for a particular reason, you have to speculate that they had some familiarity with the compound.
因为科学家需要付出很多努力才能发现一种分子，但对于一名科学家来说，发现一种分子，然后出于特定原因将其命名为“幸福”，你必须推测他们对这种化合物有一定的熟悉程度。
Dr. Matthew Hill:
马修·希尔博士：
Rafi Mechoulam was also the guy who isolated and discovered THC.
Rafi Mechoulam 也是分离并发现 THC 的人。
So, he's kind of the grandfather of the whole cannabinoid field.
所以，他是整个大麻素领域的祖父。
So he has a landmark paper from 1964, which ironically, and this is one of these weird pop culture things.
因此，他在 1964 年发表了一篇具有里程碑意义的论文，具有讽刺意味的是，这就是这些奇怪的流行文化事物之一。
I don't know if this is true.
我不知道这是不是真的。
That paper was published on April 20th, 1964 and so the joke is, is this where 4/20 came from?
那篇论文发表于 1964 年 4 月 20 日，所以笑话是，4/20 是从这里来的吗？
Because the original birth date of the first THC paper was 4/20, 1964.
因为第一篇THC论文的最初诞生日期是1964年4月20日。
Andrew Huberman:
安德鲁·休伯曼：
Well, now that potential myth is definitely going to propagate.
好吧，现在这个潜在的神话肯定会传播。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Interesting.
有趣。
Dr. Matthew Hill:
马修·希尔博士：
But yeah.
但是是的。
So he had been in the field for a while, and so he had studied cannabis on that side, and then in 1990, his lab isolated anandamide as being the first molecule that activated the receptor endogenously.
所以他已经在这个领域工作了一段时间，所以他研究了大麻的这方面，然后在 1990 年，他的实验室分离出了大麻素，这是第一个内源性激活受体的分子。
And so, I think it was a little tongue in cheek that he named it the way he did.
所以，我认为他这样命名有点开玩笑。
A few years later, the second molecule, which is just called 2-Arachidonoylglycerol or what we call 2-AG, that was discovered kind of in tandem, both again by Mechoulam, but also by a Japanese group.
几年后，第二种分子，即 2-花生四烯酰甘油或我们所说的 2-AG，是由 Mechoulam 和一个日本研究小组同时发现的。
And so we understand these two molecules don't do the same thing, like they are a bit different.
所以我们知道这两个分子不会做同样的事情，就像它们有点不同一样。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
So the way anandamide binds the receptor is it's what we would call a high affinity but low efficacy agonist or molecule at least.
因此，anandamide 结合受体的方式至少是我们所说的高亲和力但低功效的激动剂或分子。
And what I mean by that is very low levels of anandamide are required to actually bind to the receptor, but once it binds, its ability to stimulate a biological response in that neuron kind of caps out pretty fast.
我的意思是，实际与受体结合需要非常低水平的大麻素，但一旦结合，它刺激神经元生物反应的能力就会很快消失。
So it doesn't have a sledgehammer effect.
所以它不具有大锤效应。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
Whereas 2-AG seems to require a bit more concentration in the synapse to be able to bind to the receptor, so it has a lower affinity for the receptor.
而 2-AG 似乎需要突触中更高的浓度才能与受体结合，因此它对受体的亲和力较低。
But once it binds to the receptor, it's pretty heavy duty, so it evokes a very robust intracellular signaling response.
但一旦它与受体结合，它的作用就相当大，因此它会引起非常强大的细胞内信号反应。
And so why we have two endocannabinoids, we're not totally sure.
那么为什么我们有两种内源性大麻素，我们并不完全确定。
Some of us have theories.
我们中的一些人有理论。
I'm of the camp that I think they may play somewhat differential roles, either based on the synapse or the circuit that they're working in, or this idea that maybe anandamide might be more of a tonic molecule.
我属于这个阵营，我认为它们可能会发挥一些不同的作用，要么基于突触或它们正在工作的电路，要么基于这种想法，也许 anandamide 可能更像是一种补品分子。
And what I mean by that is, we'll say it's like a stage setter.
我的意思是，我们会说它就像一个舞台设置者。
So anandamide might just be kind of made by neurons on an ongoing basis and just released, and its job may be to kind of keep the steady state of a brain circuit in a desired range, so that under resting conditions it's not too active or too quiet.
因此，大麻素可能是由神经元持续产生并释放的，它的作用可能是将大脑回路的稳定状态保持在所需的范围内，这样在休息条件下它就不会太活跃或太安静。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Your thermostat analogy is perfect here.
你的恒温器比喻在这里是完美的。
Dr. Matthew Hill:
马修·希尔博士：
Exactly.
正是如此。
So in that context, it kind of is like just the thermostat of the house.
所以在这种情况下，它有点像房子的恒温器。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
Whereas 2-AG is like, let's say, the pinch hitter who gets brought in to do the heavy lifting.
而 2-AG 就像是替补击球手，负责承担重任。
And so 2-AG, during a situation like, let's say, something even like a seizure as an extreme example, where you have a huge amount of neural activity, those neurons that are getting heavily activated during massive amounts of neural activity start dumping out huge amounts of 2-AG, and that acts as the, "Okay, we really need to turn off this circuit very quickly in this situation." And in most of these forms of synaptic plasticity like I was saying earlier, where you need to either strengthen or weaken a synapse in response to a change in the environment or in response to an experience or something that's going on, most of that is driven by 2-AG signaling.
因此，2-AG，在像癫痫发作这样的极端情况下，你有大量的神经活动，那些在大量神经活动期间被严重激活的神经元开始倾倒出大量的 2-AG，这就像，“好吧，在这种情况下我们真的需要非常快地关闭这个电路。”在大多数形式的突触可塑性中，就像我之前所说的，你需要加强或削弱突触以响应环境的变化或响应经历或正在发生的事情，其中大部分是由 2-AG 信号驱动的。
And so all these forms of turning things up or down in a kind of rapid and on-demand manner, that's mostly 2-AG.
因此，所有这些以快速和按需方式调整事物的形式，主要是 2-AG。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
So most people who study neurophysiology and record activity in neurons and look at endocannabinoids, they're almost entirely talking about 2-AG when they play with stuff.
因此，大多数研究神经生理学、记录神经元活动并研究内源性大麻素的人，在玩东西时几乎都在谈论 2-AG。
So Yeah, that's one of the ways we do it.
是的，这就是我们这样做的方式之一。
We say that anandamide may be more tonic, and 2-AG might be more phasic-
我们说 anandamide 可能更具补品性，而 2-AG 可能更具阶段性-
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm
嗯嗯
Dr. Matthew Hill:
马修·希尔博士：
...
...
and brought online when needed, but doesn't do a lot.
并在需要时上线，但作用不大。
There is some evidence that 2-AG may also have a role to regulate some circuits under resting conditions as well, and there certainly are some situations where anandamide might get brought into play to affect plasticity.
有一些证据表明 2-AG 也可能在静息条件下发挥调节某些回路的作用，并且肯定在某些情况下 anandamide 可能会发挥作用来影响可塑性。
But as an umbrella idea of how we look at it, that's often how we divide those two up.
但作为我们如何看待它的总体想法，这通常就是我们将两者分开的方式。
So we kind of have these two molecules.
所以我们有这两种分子。
They, end of the day, do the same thing.
归根结底，他们做同样的事情。
They're regulating neurotransmitter release through retrograde signaling, but what stimulation brings them online or what drives their activity may differentiate, and we don't really understand all the details behind that, outside of the fact that we very clearly know 2-AG is activity dependent.
它们通过逆行信号传导调节神经递质释放，但是什么刺激使它们上线或什么驱动它们的活动可能会有所不同，除了我们非常清楚地知道 2-AG 是活动依赖性的事实之外，我们并不真正了解其背后的所有细节。
So as that neuron becomes more active, it's going to make 2-AG to regulate its inputs.
因此，当神经元变得更加活跃时，它将产生 2-AG 来调节其输入。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
So yeah, you have this very complex system, and it's really widely distributed, it's everywhere.
所以，是的，你有一个非常复杂的系统，而且它分布非常广泛，无处不在。
The cannabinoid receptors and the endocannabinoid molecules are in the cortex, they're in the hypothalamus, they're in the striatum, the hippocampus, the cerebellum.
大麻素受体和内源性大麻素分子位于皮质、下丘脑、纹状体、海马体和小脑中。
Andrew Huberman:
安德鲁·休伯曼：
All over the brain.
满脑子都是。
Dr. Matthew Hill:
马修·希尔博士：
Except the one area where it's really interesting, actually, where you don't really see much receptor is in brain stem populations that regulate unconscious cardiac and respiratory function.
事实上，除了一个真正有趣的区域外，你在脑干群体中看不到太多受体，它调节无意识的心脏和呼吸功能。
Andrew Huberman:
安德鲁·休伯曼：
Hmm.
嗯。
Dr. Matthew Hill:
马修·希尔博士：
So this is one of the things that really differentiates cannabis from opiates, because a lot of the signaling mechanisms between opioid receptors and cannabinoid receptors are quite similar.
所以这是大麻与阿片类药物的真正区别之一，因为阿片受体和大麻素受体之间的许多信号机制非常相似。
But, as it's been well established, people can overdose fatally and die from opiates relatively easily.
但是，众所周知，人们服用过量阿片类药物可能会致命，并且相对容易死于阿片类药物。
And the way that that tends to happen is when you activate the opiate receptors in the cardiorespiratory parts of the brain stem, it depresses neural activity.
这种情况往往会发生，当你激活脑干心肺部分的阿片受体时，它就会抑制神经活动。
So as the person loses consciousness, they also unconsciously will stop regulating their own heart and breathing, and it can be a fatal response.
因此，当人失去意识时，他们也会无意识地停止调节自己的心脏和呼吸，这可能是致命的反应。
Because cannabinoid receptors don't really exist in those regions, you don't get the same kind of impact in terms of suppressing heart rate and breathing function.
由于大麻素受体并不真正存在于这些区域，因此在抑制心率和呼吸功能方面不会产生同样的影响。
There's always the saying, there's never been an account of someone actually dying from a cannabis overdose or a THC overdose.
总是有这样一种说法，从来没有人真正死于大麻过量或四氢大麻酚过量。
Certainly, people can do stupid things while they're intoxicated that result in their death, but in the same manner that someone can die from consuming too much opiates, that doesn't seem to be physically possible with cannabinoids as far as we've seen so far.
当然，人们在喝醉时可能会做一些愚蠢的事情，从而导致死亡，但就像有人会因服用过多的阿片类药物而死亡一样，就我们目前所见，大麻素在物理上似乎不可能做到这一点。
And a lot of that is just because of the localization.
这很大程度上是因为本地化。
For some reason, it's just not the receptors in that part of the brain.
出于某种原因，它只是不是大脑那部分的受体。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Very interesting.
非常有趣。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
A lot of aficionado questions about the receptor biology.
许多爱好者对受体生物学提出疑问。
I'll just spare everyone the details by just highlighting something that you already said far more eloquently than I will.
我只是强调一些你们已经说过的比我更雄辩的事情，从而让大家省去细节。
Which is, I think it is fascinating that this whole system has both a tonic, like a steady release capability, and a phasic, so the ability to spike, forgive the pun-
我认为令人着迷的是，整个系统既具有补品（如稳定的释放能力），又具有阶段性（因此具有峰值能力，请原谅双关语）
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
the neuroscientists will know what I'm talking about, to spike more activity of the system superimposed on that tonic activity.
神经科学家会知道我在说什么，以激发更多叠加在补品活动上的系统活动。
Because this is something that you see in the dopamine system.
因为这是你在多巴胺系统中看到的东西。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
This is something that you see in essentially every neuromodulator neurotransmitter system.
这基本上在每个神经调节器神经递质系统中都可以看到。
But it seems that the endocannabinoid system has accomplished this quite a bit differently.
但内源性大麻素系统似乎以完全不同的方式完成了这一任务。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
So very interesting, unique system-
非常有趣、独特的系统-
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
in a number of ways that raise a number of key questions.
以多种方式提出了一些关键问题。
Dr. Matthew Hill:
马修·希尔博士：
So yeah, if you go back to the munchies question you had.
所以，是的，如果你回到你的零食问题。
So if we tie into that, so there's a few ways.
因此，如果我们结合这一点，那么有几种方法。
Cannabinoids and feeding are a really interesting thing because if you ask people the prototypical responses to consuming cannabis, most people would usually say munchies is one of the things that pops up pretty regularly.
大麻素和喂养是一件非常有趣的事情，因为如果你问人们对消费大麻的典型反应，大多数人通常会说零食是经常出现的事情之一。
And so, the cannabinoid receptors, they are expressed in these feeding circuits in the hypothalamus.
因此，大麻素受体在下丘脑的这些喂养回路中表达。
There's a lot of complex circuitry there that can regulate food-seeking behavior and-
那里有很多复杂的电路可以调节寻找食物的行为并且——
Andrew Huberman:
安德鲁·休伯曼：
Yeah, we just had an episode with Zach Knight-
是的，我们刚刚和扎克·奈特一起看了一集-
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
from HHMI and UCSF, where he talked about the AgRP neurons-
来自 HHMI 和 UCSF，他在那里谈论了 AgRP 神经元 -
Dr. Matthew Hill:
马修·希尔博士：
Yeah, exactly
是的，正是如此
Andrew Huberman:
安德鲁·休伯曼：
...
...
and different neurons of the hypothalamus.
和下丘脑的不同神经元。
We can link to that in the show note captions.
我们可以在节目注释标题中链接到该链接。
Nowadays, a rich understanding of the neurons that stimulate food seeking-
如今，人们对刺激食物寻找的神经元有了丰富的了解——
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
craving, and then eating.
渴望，然后吃。
Dr. Matthew Hill:
马修·希尔博士：
And so we know that cannabinoids, they regulate, again, those inhibitory inputs around AgRP neurons, for example, and so one thing they can do is disinhibit those AgRP neurons so they become more active, and that can drive food-seeking behavior.
因此，我们知道大麻素会再次调节 AgRP 神经元周围的抑制性输入，因此它们能做的一件事就是解除对 AgRP 神经元的抑制，使它们变得更加活跃，从而驱动觅食行为。
So that's certainly one mechanism of it, but there's also a huge reward component to this in terms of the munchies.
所以这当然是它的一种机制，但就零食而言，这也有一个巨大的奖励成分。
And so we know that you can also just dump anandamide, for example.
因此，我们知道您也可以直接丢弃大麻素。
Steve Muller and Kent Berridge did this work years ago, where they just put anandamide into the nucleus accumbens, and that can also stimulate palatable food intake.
史蒂夫·穆勒（Steve Muller）和肯特·贝里奇（Kent Berridge）几年前就做过这项工作，他们只是将大麻素放入伏隔核中，这也可以刺激可口的食物摄入。
So you also have this ability to integrate with the reward circuitry.
所以你也有能力与奖励电路集成。
And then there was also this fascinating paper from a Japanese group in PNAS, I think about 12 years ago.
然后，PNAS 上的一个日本小组发表了一篇引人入胜的论文，我想是 12 年前的事了。
And what they found was they would give a rodent a cannabinoid, and then they would stimulate different taste bud populations.
他们发现，他们会给啮齿类动物注射大麻素，然后刺激不同的味蕾群体。
And then they would look at the gustatory cortical response to stimulating the populations.
然后他们会观察味觉皮质对刺激人群的反应。
And what they found is, under the influence of a cannabinoid, if you stimulated sweet taste buds, you got an enhanced response in the gustatory cortex.
他们发现，在大麻素的影响下，如果刺激甜味味蕾，味觉皮层的反应就会增强。
But not if you did salty, bitter, or sour, or I don't know if they did umami in that one.
但如果你做了咸的、苦的或酸的，或者我不知道他们是否在其中做了鲜味，那就不行了。
But it was very explicit to sweet tasting, and so you have this kind of ability to jack up the way the brain is processing sweet-tasting foods.
但它对甜味的味道非常明确，所以你有这种能力来提高大脑处理甜味食物的方式。
You have this engagement of the reward circuitry, and then you also have this ability to regulate AgRP neurons as well as the POMC neurons.
你有这种奖励电路的参与，然后你也有这种能力来调节 AgRP 神经元以及 POMC 神经元。
There's both sides to that in the arcuate nucleus to regulate multiple components of feeding.
弓状核的两侧都可以调节进食的多种成分。
But a big question is, my lab has become kind of interested in this as well because we have a component of my lab that studies feeding behavior, and one of my postdocs has been doing these projects for years now, trying to understand almost like at a behavioral mechanism level, what the munchies are.
但一个大问题是，我的实验室也对此产生了兴趣，因为我的实验室有一个研究喂养行为的组成部分，我的一位博士后多年来一直在做这些项目，试图在行为机制层面上理解零食是什么。
And what she's been looking at is we kind of started thinking about the idea that what is it that...
她一直在关注的是我们开始思考这个想法：那是什么......
Because it's not just food seeking, and it's not just you just want to consume something.
因为这不仅仅是寻找食物，也不仅仅是你想吃东西。
There's a maintenance of eating, and so we know from humans and animals, you can satiate them.
饮食是有维持的，所以我们从人类和动物那里知道，你可以让他们吃饱。
You can make someone full and then get them high on cannabis, and they'll reinitiate eating.
你可以让某人吃饱，然后让他们吸食大麻，然后他们就会重新开始进食。
So That's an interesting thing in and of itself, because that means you're disrupting either the ability of the brain to detect satiety, or you're messing with a process we call reward devaluation.
这本身就是一件有趣的事情，因为这意味着你要么破坏了大脑检测饱腹感的能力，要么扰乱了我们称之为奖励贬值的过程。
And so reward devaluation is like, if you haven't eaten for a day and you see a picture of a pizza, or someone brings a pizza in front of you, it just looks delicious.
所以奖励贬值就像，如果你一天没吃东西，你看到一张披萨的照片，或者有人把披萨放在你面前，它看起来很美味。
And that first slice tastes amazing.
第一片味道棒极了。
It's salty, it's fatty, it's delicious.
它又咸又肥，很好吃。
You eat five of those slices, it feels greasy and nasty.
你吃了五片，感觉又油腻又恶心。
And so that process of how you perceive the food and its reward salience degrades as you eat and as your brain basically shifts into a thing of we don't need to consume calories and food anymore.
因此，当你吃东西时，当你的大脑基本上转变为我们不再需要消耗卡路里和食物时，你如何感知食物及其奖励显着性的过程就会退化。
We're okay.
我们没事。
We're full now.
我们现在已经满了。
And so we've done a series of experiments in the lab where you'd get the animals and either satiated in advance, where they have already devalued the food, and under a normal state, they won't eat it anymore, they won't work to get access to it.
所以我们在实验室里做了一系列的实验，你会让动物提前吃饱，它们已经让食物贬值了，在正常状态下，它们不会再吃它，也不会努力去获取它。
And you get them high on a cannabis extract.
大麻提取物会让他们兴奋。
We have these vape chambers that are like, I don't know how else to describe it outside of a little hot box.
我们有这些电子烟室，我不知道如何在一个小热箱之外描述它。
It's probably the best way to describe, because it's essentially a locked, airtight box that the rat goes in, and it gets vapor puffs, and it fills up, and then they inhale this, and then it clears out, and they get another puff, and then it fills up.
这可能是最好的描述方式，因为它本质上是一个上锁的密封盒子，老鼠进去后，它会吸入蒸汽，然后它会充满，然后它们吸入它，然后它会清除，然后它们会再次吸入蒸汽，然后它会充满。
And we do this for 15 minutes.
我们这样做 15 分钟。
And we've titrated all this to get exactly blood levels of THC that you would achieve in someone who's consuming cannabis through smoking.
我们已经对所有这些进行了滴定，以准确获得通过吸烟吸食大麻的人所达到的四氢大麻酚血液浓度。
And so we get them to that point and then give them access to food, and they will go gangbusters.
所以我们让他们达到那个程度，然后给他们食物，他们就会表现出色。
They eat food.
他们吃食物。
Doesn't matter what you give them.
你给他们什么并不重要。
You give them plain chow, they go to town.
你给他们简单的食物，他们就进城去。
You give them fatty, you give them sweet, they love it all.
你给他们肥的，你给他们甜的，他们都喜欢。
But you pre-satiate them, and they get them stoned, they will reinitiate eating again.
但你预先让他们吃饱了，他们就会吸毒，然后他们就会重新开始吃东西。
And you make them work for it, where they have to lever press, and you get them stoned, and they will go to town on that, and they will work.
你让他们为此工作，他们必须按下杠杆，你让他们被扔石头，他们会为此而进城，他们会工作。
And-
还有——
Andrew Huberman:
安德鲁·休伯曼：
Proof that even under the influence of cannabis, animals will work hard.
证明即使在大麻的影响下，动物也会努力工作。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
For food.
为了食物。
I don't know about other stuff, but for food, they certainly will.
其他的我不知道，但是对于食物，他们肯定会的。
I mean, and Elise Wirtz and Cassie Moore have done this at Hopkins as well.
我的意思是，埃莉斯·维尔茨 (Elise Wirtz) 和卡西·摩尔 (Cassie Moore) 在霍普金斯大学也做到了这一点。
They've shown similarly using what we call progressive ratio, which is essentially a thing where it's like the first time you press a lever, you immediately get a sugar.
他们使用我们所说的渐进比率进行了类似的展示，这本质上就像你第一次按下杠杆时，你立即得到糖。
Next time, you got to hit it twice to get a pellet.
下次，你必须击中两次才能获得颗粒。
Then you have to hit it four times to get one.
然后你必须击中四次才能得到一个。
Andrew Huberman:
安德鲁·休伯曼：
It's like life.
这就像生活。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Then you got to hit it 16, and it scales exponentially up.
然后你必须达到 16，它就会呈指数级增长。
We've had this one female we joke about in the lab, this one female rat, and you get her high, and she'll do 300 lever presses to get one sugar pellet.
我们在实验室里调侃过一只雌性老鼠，这只雌性老鼠，你让她兴奋起来，她会按下 300 次杠杆来得到一颗糖丸。
She really wants it.
她真的想要它。
So you can really goose up their motivation to eat.
所以你可以真正提高他们吃饭的动力。
And so there's clearly a rewarding aspect to this because they're motivated to engage enough in working to get access to the food.
因此，这显然有一个有益的方面，因为他们有动力投入足够的工作来获得食物。
But you can also do another way of testing this question, which is you compare a food with something that will make the animal feel nauseous, like lithium chloride.
但你也可以用另一种方法来测试这个问题，即将食物与会让动物感到恶心的东西（例如氯化锂）进行比较。
This is the way that you would test conditioned taste aversion.
这是测试条件性味觉厌恶的方法。
So you give them access to a food, and then you give them something that makes them feel nauseous, and the animals will avoid that food.
所以你给它们提供食物，然后给它们一些让它们感到恶心的东西，动物就会避开这种食物。
And so that's another way to devalue a food is by pairing it with a nauseant so the animal no longer likes it.
因此，贬低食物价值的另一种方法是将其与恶心剂搭配，这样动物就不再喜欢它。
So again, same situation.
再次，同样的情况。
You can get the animal stoned, and it will reengage in eating that food that it had devalued through being paired with a nauseant.
你可以让动物被扔石头，它会重新吃那些因与恶心剂搭配而贬值的食物。
So through either satiety or making it a negative associated flavor because the animal got nauseous before, you can override these effects by giving THC.
因此，无论是通过饱足感还是因为动物之前感到恶心而使其成为一种负面的相关味道，您都可以通过给予 THC 来克服这些影响。
And so that could be a complex process that either involves changes in the reward circuitry.
因此，这可能是一个复杂的过程，要么涉及奖励电路的变化。
This could be something that's from the orbital frontal cortex, which is a very important part of the brain that scales reward and assesses how much someone wants to work or an organism wants to work to achieve a reward at the end.
这可能来自眶额皮质，它是大脑中非常重要的部分，可以衡量奖励并评估某人想要工作或有机体想要工作以最终获得奖励的程度。
So we haven't figured out the circuitry of this and where exactly it's acting, but I would say a lot of the stuff that we and others have done supports this idea that a lot of what the munchies is, is this ability to almost lock in the reward value of food so that it doesn't decay.
所以我们还没有弄清楚它的电路以及它到底在哪里起作用，但我想说，我们和其他人所做的很多事情都支持这个想法，即很多零食就是这种几乎锁定食物奖励价值以使其不会腐烂的能力。
Despite satiety, despite eating over time, it just keeps it highly salient so that they want to work for it still.
尽管有饱腹感，尽管吃得时间很长，但这只是让它保持高度突出，这样他们仍然想为之努力。
And then similarly, we and others have also done work to show we can block satiety signals.
同样，我们和其他人也做了工作来证明我们可以阻止饱腹感信号。
So we know endocannabinoids at least are capable of overriding leptin.
所以我们知道内源性大麻素至少能够超越瘦素。
So leptin is an anorectic molecule, comes out from the fat, and usually we release it when we've eaten a lot, and it's one of these things that tells our brain, "Stop eating." It works through, again, populations in the arcuate nucleus and changes the way those neurons function to drive food-seeking behavior.
因此，瘦素是一种厌食分子，来自脂肪，通常我们在吃得很多时会释放它，它是告诉我们的大脑“停止进食”的东西之一。它再次通过弓状核中的群体起作用，并改变这些神经元驱动觅食行为的功能方式。
And we and others have shown previously that if you elevate endocannabinoids, you can override that.
我们和其他人之前已经表明，如果你提高内源性大麻素的水平，你就可以克服它。
And actually, one of the mechanisms by which leptin seems to suppress feeding is actually by turning on the metabolism of endocannabinoids so that their levels decline.
事实上，瘦素似乎抑制摄食的机制之一实际上是通过开启内源性大麻素的新陈代谢，使其水平下降。
And so as you lose that endocannabinoid function, the animal is less interested in eating.
因此，当你失去内源性大麻素功能时，动物对进食的兴趣就会降低。
And so you can prevent these anorectic effects of leptin by goosing up endocannabinoid activity.
因此，您可以通过提高内源性大麻素活性来预防瘦素的这些厌食作用。
Andrew Huberman:
安德鲁·休伯曼：
As many of you know, I've been taking AG1 for more than 10 years now, so I'm delighted that they're sponsoring this podcast.
你们很多人都知道，我服用 AG1 已有 10 多年了，所以我很高兴他们赞助这个播客。
To be clear, I don't take AG1 because they're a sponsor.
需要明确的是，我选择 AG1 并不是因为他们是赞助商。
Rather, they are a sponsor because I take AG1.
相反，他们是赞助商，因为我选择了 AG1。
In fact, I take AG1 once and often twice every single day, and I've done that since starting way back in 2012.
事实上，我每天服用一次 AG1，经常服用两次，早在 2012 年我就开始这样做了。
There is so much conflicting information out there nowadays about what proper nutrition is, but here's what there seems to be a general consensus on.
关于什么是适当的营养，现在有很多相互矛盾的信息，但以下是似乎达成的普遍共识。
Whether you're an omnivore, a carnivore, a vegetarian, or a vegan, I think it's generally agreed that you should get most of your food from unprocessed or minimally processed sources, which allows you to eat enough but not overeat, get plenty of vitamins and minerals, probiotics, and micronutrients that we all need for physical and mental health.
无论你是杂食动物、肉食动物、素食主义者还是纯素食主义者，我认为人们普遍认为你应该从未经加工或最低限度加工的来源获取大部分食物，这样你就可以吃得足够但不过量，获得充足的维生素和矿物质、益生菌和微量营养素，这些都是我们身心健康所需的。
Now, I personally am an omnivore, and I strive to get most of my food from unprocessed or minimally processed sources.
现在，我个人是杂食动物，我努力从未加工或最低限度加工的来源获取大部分食物。
But the reason I still take AG1 once and often twice every day is that it ensures I get all of those vitamins, minerals, probiotics, et cetera, but it also has adaptogens to help me cope with stress.
但我仍然每天服用一次 AG1（通常是两次）的原因是它可以确保我获得所有维生素、矿物质、益生菌等，而且它还含有适应原来帮助我应对压力。
It's basically a nutritional insurance policy meant to augment, not replace quality food.
它基本上是一项营养保险政策，旨在增强而不是取代优质食品。
So by drinking a serving of AG1 in the morning and again in the afternoon or evening, I cover all of my foundational nutritional needs.
因此，通过早上喝一份 AG1，然后在下午或晚上再喝一次，我就可以满足我所有的基本营养需求。
And I, like so many other people that take AG1, report feeling much better in a number of important ways, such as energy levels, digestion, sleep, and more.
和许多其他服用 AG1 的人一样，我报告在许多重要方面感觉好多了，例如能量水平、消化、睡眠等。
So while many supplements out there are really directed towards obtaining one specific outcome, AG1 is foundational nutrition designed to support all aspects of wellbeing related to mental health and physical health.
因此，虽然许多补充剂实际上是为了获得一种特定的结果，但 AG1 是基础营养，旨在支持与心理健康和身体健康相关的各个方面的福祉。
If you'd like to try AG1, you can go to drinkag1.com/huberman to claim a special offer.
如果您想尝试 AG1，可以访问 Drinkag1.com/huberman 申请特别优惠。
They'll give you five free travel packs with your order, plus a year's supply of vitamin D3 K2.
您订购后，他们将赠送 5 个免费旅行套装，以及一年的维生素 D3 K2。
Again, that's drinkag1.com/huberman.
再说一遍，这是 Drinkag1.com/huberman。
You're talking about increasing endocannabinoid activity, and we've said all this in the context of cannabis.
你说的是增加内源性大麻素的活性，我们已经在大麻的背景下说了这一切。
Dr. Matthew Hill:
马修·希尔博士：
Mm-hmm.
嗯嗯。
Andrew Huberman:
安德鲁·休伯曼：
So maybe we could talk a little bit about how the components in cannabis, THC mainly, but also CBD, impact these receptors, the CB1 and let's just leave CB2 out for the moment-
所以也许我们可以谈谈大麻中的成分（主要是 THC，还有 CBD）如何影响这些受体 CB1，让我们暂时将 CB2 排除在外 -
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
because it sounds like it's more of an immune system thing.
因为听起来这更像是免疫系统的事情。
But just to make it very clear, is there a way to increase the activity of endocannabinoids without ingesting THC?
但要说清楚的是，有没有一种方法可以在不摄入 THC 的情况下增加内源性大麻素的活性？
Dr. Matthew Hill:
马修·希尔博士：
Yes.
是的。
They dynamically change all the time.
它们一直在动态变化。
Andrew Huberman:
安德鲁·休伯曼：
But you're talking about experimentally or recreationally-
但你说的是实验性的或娱乐性的-
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
adjusting their levels, but how does one do that without using THC?
调整它们的水平，但是如何在不使用 THC 的情况下做到这一点呢？
Dr. Matthew Hill:
马修·希尔博士：
So, okay.
那么，好吧。
A few things there.
那里有一些东西。
We'll take a step back.
我们将退后一步。
So THC itself isn't going to...
所以 THC 本身不会...
It does its thing by acting directly on the cannabinoid receptor, not-
它通过直接作用于大麻素受体来发挥作用，而不是-
Andrew Huberman:
安德鲁·休伯曼：
So it sort of mimics the-
所以它有点模仿-
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
anandamide and 2-AG.
anandamide 和 2-AG。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
So THC, going back to the pharmacology of this, so THC, if you look at how it interacts with the receptor, it's not a heavy-duty molecule.
所以四氢大麻酚，回到它的药理学，所以四氢大麻酚，如果你看看它是如何与受体相互作用的，它不是一个重型分子。
So this was one of the things that came up before as well, is this idea that THC is a sledgehammer and it overrides the endocannabinoids.
所以这也是之前出现的问题之一，即 THC 是一把大锤，它会凌驾于内源性大麻素之上。
Andrew Huberman:
安德鲁·休伯曼：
By the way, Matt's referring to the fact that I said that in a previous solo episode about this, and there I was nesting it in the concentrations of THC that can be found in high-THC cannabis.
顺便说一句，马特指的是我在之前的个人剧集中说过的事实，我将其嵌套在高 THC 大麻中可以找到的 THC 浓度中。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
So essentially what I was saying is that at very high THC concentrations, maybe not the binding affinity, but the amount of THC that is available to the CB1 receptors-
所以本质上我想说的是，在非常高的 THC 浓度下，可能不是结合亲和力，而是 CB1 受体可用的 THC 量 -
Dr. Matthew Hill:
马修·希尔博士：
Is high
很高
Andrew Huberman:
安德鲁·休伯曼：
...
...
is going to exceed what's normally found in terms of the amount of anandamide that can bind to CB1 receptors because what you're talking about is a super physiological condition.
与 CB1 受体结合的 anandamide 的量将超过通常发现的量，因为你所说的是一种超级生理状况。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
You don't really actually need much THC in the brain to produce psychoactivity.
实际上，大脑中并不需要太多的 THC 来产生精神活动。
It's a little bit of a mystery, to be honest, exactly how it works.
老实说，它到底是如何工作的，这有点神秘。
I think the main way that most people in the cannabinoid theory field would look at this is that THC is not a very strong agonist.
我认为大麻素理论领域的大多数人看待这一问题的主要方式是 THC 不是一种很强的激动剂。
Even if you look at its ability to trigger an intracellular response, it's much lower than 2-AG.
即使你看看它触发细胞内反应的能力，它也比 2-AG 低得多。
Andrew Huberman:
安德鲁·休伯曼：
So-
所以——
Dr. Matthew Hill:
马修·希尔博士：
It's actually more like anandamide.
它实际上更像是 anandamide。
Andrew Huberman:
安德鲁·休伯曼：
So you said anandamide is high affinity, low efficacy.
所以你说anandamide是高亲和力，低功效。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
So THC is the same.
所以THC是一样的。
THC is actually only a partial agonist.
THC实际上只是部分激动剂。
It's not even a full agonist at CB1.
它甚至不是 CB1 的完全激动剂。
Andrew Huberman:
安德鲁·休伯曼：
But it is high affinity.
但亲和力却很高。
Dr. Matthew Hill:
马修·希尔博士：
It's high affinity, so it has the ability...
亲和力高，所以有能力……
But the tricky thing with that is it can outcompete 2-AG, but because it's a lower efficacy agonist than 2-AG, in that sense, it's almost blocking the effects, not amplifying them.
但棘手的是它可以超越 2-AG，但因为它是比 2-AG 功效更低的激动剂，从这个意义上说，它几乎阻止了效应，而不是放大它们。
Andrew Huberman:
安德鲁·休伯曼：
Blocking the effects of 2-AG-
阻断 2-AG- 的作用
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
but does it block the effects of anandamide?
但它会阻止 anandamide 的作用吗？
Dr. Matthew Hill:
马修·希尔博士：
THC and anandamide, the way I would visualize it is because they seem to have relatively similar affinities and efficacies of the receptor, they might, let's say, dance around.
THC 和 anandamide，我想象的方式是因为它们似乎对受体具有相对相似的亲和力和功效，可以说，它们可能会跳舞。
So it would be somewhat interchangeable.
所以它在某种程度上是可以互换的。
The difference there is, and this I think is the big point about what THC does versus endocannabinoids, because we know now through the pharmaceutical development of drugs that can boost anandamide levels, which exist.
差异是存在的，我认为这是 THC 与内源性大麻素的作用的重点，因为我们现在通过药物开发知道可以提高现有的 anandamide 水平。
We have inhibitors that prevent their metabolism.
我们有阻止它们新陈代谢的抑制剂。
We can elevate them.
我们可以提升他们。
There's no intoxication and no psychoactivity associated with elevating anandamide.
提高阿那达酰胺浓度不会导致中毒，也不会产生精神活动。
Andrew Huberman:
安德鲁·休伯曼：
That's a very interesting point that we should highlight.
这是我们应该强调的非常有趣的一点。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
So there are drugs that now exist that can block the breakdown of anandamide-
所以现在有一些药物可以阻止 anandamide 的分解-
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
make more available, presumably by disrupting some enzymatic breakdown.
可能是通过破坏某些酶分解来提供更多可用的。
Dr. Matthew Hill:
马修·希尔博士：
Yeah, exactly.
是的，完全正确。
Andrew Huberman:
安德鲁·休伯曼：
And therefore, lead to more binding of the now elevated levels of anandamide that are available to CB1, and you see no psychoactive effects.
因此，导致 CB1 可用的现在升高水平的 anandamide 的更多结合，并且您看不到精神作用。
Dr. Matthew Hill:
马修·希尔博士：
No. No psychoactive.
不，没有精神活性。
Andrew Huberman:
安德鲁·休伯曼：
People are not aware that they-
人们没有意识到他们——
Dr. Matthew Hill:
马修·希尔博士：
No. Yeah, you can do-
不，是的，你可以-
Andrew Huberman:
安德鲁·休伯曼：
There's no euphoria.
没有欣快感。
Dr. Matthew Hill:
马修·希尔博士：
No one can guess.
没有人能猜出来。
Yeah.
是的。
No one can guess.
没有人能猜出来。
Andrew Huberman:
安德鲁·休伯曼：
What is it used for?
它有什么用？
Dr. Matthew Hill:
马修·希尔博士：
Well, the first molecule really was developed by Pfizer to look at if it could work on pain.
嗯，第一个分子确实是由辉瑞公司开发的，目的是看看它是否可以缓解疼痛。
The first trial that was done did not work.
第一次试验没有成功。
It was a kind of strange osteoarthritic knee pain trial that was like, even in that trial, the positive control of naproxen barely worked.
这是一种奇怪的骨关节炎膝盖疼痛试验，即使在那次试验中，萘普生的阳性对照也几乎不起作用。
But because the FAAH inhibitor, which is, take a step back, FAAH's the enzyme that chews up anandamide.
但因为 FAAH 抑制剂，也就是退一步说，FAAH 是咀嚼 anandamide 的酶。
So the drug that is developed inhibits that enzyme, so you prevent the enzymatic breakdown of anandamide.
因此，开发的药物会抑制该酶，从而防止 anandamide 的酶促分解。
So we just call them FAAH inhibitors.
所以我们就称它们为 FAAH 抑制剂。
So this drug will boost anandamide levels quite high, and an animal research showed some efficacy in modulating pain, and so they put it in a trial, and it didn't work against the positive control of naproxen, which is like an NSAID, just like Advil, basically.
因此，这种药物将提高 anandamide 水平相当高，并且动物研究表明在调节疼痛方面有一定功效，因此他们将其投入试验，并且它对萘普生的阳性对照不起作用，萘普生基本上就像 NSAID 一样，就像 Advil 一样。
Andrew Huberman:
安德鲁·休伯曼：
Aleve.
阿莱夫。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Essentially, yeah.
本质上是的。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
Dr. Matthew Hill:
马修·希尔博士：
And that drug didn't work that great to begin with, so it was maybe some issues with the trial, but it essentially killed the development of the drug from that point on because everyone's like, "Oh, it's not going to work." So it kind of shelved for a while.
这种药物一开始并没有那么有效，所以可能是试验中出现了一些问题，但从那时起它基本上扼杀了该药物的开发，因为每个人都会说，“哦，它不会起作用。”所以就这样搁置了一段时间。
A colleague of mine, Markus Heilig and Leah Mayo, Leah's now a colleague of mine in Calgary, but at the time she was a postdoc with Markus in Sweden, and they were able to get access to this molecule right before COVID, essentially.
我的同事 Markus Heilig 和 Leah Mayo，Leah 现在是我在卡尔加里的同事，但当时她是 Markus 在瑞典的博士后，他们基本上在新冠疫情之前就获得了这种分子。
And they did a trial on just healthy controls with it, which again, this is kind of jumping the gun on some of the other stuff I'll talk about, so I'll tether back to that, but what they did was they dosed people for 10 days on this drug, and then we looked at stress and fear because this is something that I study.
他们对健康对照进行了一项试验，这又是对我要讨论的其他一些东西的一种过早的尝试，所以我会回到这一点，但他们所做的是给人们服用这种药物 10 天，然后我们观察压力和恐惧，因为这是我研究的东西。
This is something that they were interested in.
这是他们感兴趣的事情。
And we did find that boosting anandamide with this drug over 10 days, was sufficiently capable of dampening stress-induced autonomic responses, so looking at heart rate or skin conductance.
我们确实发现，用这种药物增强 anandamide 超过 10 天，足以抑制压力引起的自主反应，因此观察心率或皮肤电导。
I think skin conductance was the measure we did in there, but it's a proxy for adrenaline release.
我认为皮肤电导是我们在那里进行的测量，但它是肾上腺素释放的代表。
So it blunted that, and it blunted subjective feelings of stress as well, so people had lower levels of saying they actually felt stressed.
所以它削弱了这一点，也削弱了压力的主观感受，所以人们说他们实际上感到压力的程度较低。
And it kind of helped remove this conditioned fear memory that they had trained people to do.
这在某种程度上有助于消除他们训练人们去做的条件性恐惧记忆。
And so I worked with them on doing the biochemistry of this to make sure the drug was working properly.
所以我和他们一起进行了生物化学研究，以确保药物正常发挥作用。
But it was very interesting because we did see in that situation where elevating anandamide produced kind of like A reduction in stress perception, a reduction in stress physiology responses, and help reduce fear.
但这非常有趣，因为我们确实看到，在这种情况下，提高大麻素的摄入量会产生类似压力感知的减少、压力生理反应的减少，并有助于减少恐惧。
And so that is an interesting outcome because it tracks with some of the stuff we know about cannabis, and I'm sure we'll talk about some of the PTSD stuff and anxiety later.
所以这是一个有趣的结果，因为它跟踪了我们对大麻的一些了解，我相信我们稍后会讨论一些创伤后应激障碍和焦虑的内容。
So that's one of the things.
这就是其中之一。
The drug has not really been used that widely yet.
该药物尚未真正广泛使用。
It's one of the frustrations I have as a scientist who does a lot of translational work and with clinical partners like Leah, is that getting access to these molecules is not easy when they're not out in the market, so you can just go and get them.
作为一名从事大量转化工作的科学家以及像 Leah 这样的临床合作伙伴，我所遇到的挫折之一是，当这些分子还没有上市时，获得这些分子并不容易，所以你可以直接去获取它们。
You really have to try and get access from the drug companies to be able to do trials with them.
你确实必须尝试从制药公司获得许可才能与他们进行试验。
And so we are in the midst of trying to do that.
因此，我们正在努力做到这一点。
We did just complete a trial that Leah and Marcus ran that I worked with them on as well, that was on PTSD.
我们刚刚完成了利亚和马库斯进行的一项试验，我也和他们一起进行了这项试验，该试验是关于创伤后应激障碍（PTSD）的。
And so there are various potential indications for this.
因此，有各种潜在的迹象表明这一点。
Johnson & Johnson developed one as well, and they looked at it in social anxiety disorder.
强生公司也开发了一种药物，他们将其用于治疗社交焦虑症。
They had some moderate efficacy in their trial.
他们在试验中取得了一定的效果。
So I'd say the jury's still out on exactly what we're going to do with these, but they have some potential, I think, in certain clinical settings.
因此，我想说，对于我们将如何处理这些药物，目前还没有定论，但我认为，它们在某些临床环境中具有一定的潜力。
We just have to figure that out exactly.
我们只需要准确地弄清楚这一点。
But I think going back to where we started this from, they're not psychoactive.
但我认为回到我们开始的地方，它们不具有精神活性。
And so, when Pfizer first made the drug, they were actually initially concerned that it wasn't getting in the brain because no one could tell they were on the drug.
因此，当辉瑞公司第一次制造这种药物时，他们实际上最初担心它不会进入大脑，因为没有人知道他们正在服用这种药物。
This was the Wild West at this point.
这就是当时的狂野西部。
No one had any idea what endocannabinoids were actually going to do.
没有人知道内源性大麻素到底会做什么。
People were basing it on what we knew about THC, so the assumption was people would have psychoactivity, but they didn't.
人们基于我们对 THC 的了解，所以假设人们会有精神活动，但他们没有。
Pfizer then actually had to do a sleep study to show that it did have some effects on sleep cycle, the same way THC does.
辉瑞公司随后实际上必须进行一项睡眠研究，以证明它确实对睡眠周期有一些影响，就像 THC 一样。
And then they also did an in vivo PET binding study to show that they could displace a radioactive molecule that would bind to the enzyme in the brain.
然后他们还进行了体内 PET 结合研究，表明他们可以取代与大脑中的酶结合的放射性分子。
Andrew Huberman:
安德鲁·休伯曼：
Seems like a lot of gymnastics to basically confirm what they already knew, which is that even greatly elevating the anandamide by blocking this enzymatic breakdown of anandamide leads to, at least from what I'm understanding, vastly different-
似乎很多体操运动员基本上都证实了他们已经知道的事情，那就是，即使通过阻止 anandamide 的这种酶促分解来大大提高 anandamide 也会导致，至少从我的理解来看，会产生很大的不同-
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
subjective experience than-
主观体验比
Dr. Matthew Hill:
马修·希尔博士：
THC
四氢大麻酚
Andrew Huberman:
安德鲁·休伯曼：
...
...
ingesting or smoking THC.
摄入或吸食 THC。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Which brings us back to THC-
这让我们回到 THC——
Dr. Matthew Hill:
马修·希尔博士：
So what's it doing?
那么它在做什么呢？
Andrew Huberman:
安德鲁·休伯曼：
...
...
and cannabis.
和大麻。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
It seems that this thing that we call cannabis and THC are overlapping with the endogenous effects of anandamide.
看来我们称之为大麻和 THC 的东西与 anandamide 的内源性作用重叠。
But here you're not talking about endogenous normal levels, you're talking about pharmacologically greatly increasing anandamide.
但这里你谈论的不是内源性正常水平，而是药理学上大大增加的anandamide。
No psychoactive effect, no euphoria-
无精神作用，无欣快感
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
no munchies, et cetera.
没有零食等等。
Then people smoke or take an edible of-
然后人们吸烟或食用-
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
THC or cannabis, and you get a vastly different set of effects.
THC 或大麻，你会得到截然不同的效果。
So maybe we could talk about THC and the CB1 receptor.
所以也许我们可以谈谈 THC 和 CB1 受体。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And since we're here, we might as well talk about CBD-
既然我们在这里，我们不妨谈谈 CBD——
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
and I think you're going to tell us the lack of interaction with CB1 receptor, right?
我想你会告诉我们与 CB1 受体缺乏相互作用，对吧？
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And what is cannabis doing at the level of these receptors?
大麻在这些受体水平上有何作用？
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Because it makes me wonder whether or not these receptors are the whole story or whether or not cannabis is, as you mentioned, 70 plus active molecules in there, terpenes, and a bunch of other things that may modify their action.
因为这让我想知道这些受体是否就是整个故事的全部，或者大麻是否如你所提到的那样，其中有 70 多种活性分子、萜烯和许多其他可能改变其作用的物质。
That this thing we call cannabis has many more actions than just mimicking the endogenous cannabinoid system.
我们称之为大麻的东西不仅仅模仿内源性大麻素系统，还有更多的作用。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
I would say the main way that we think about this is the difference between endocannabinoids and THC is endocannabinoids are going to be released in a very specific spatial and temporal manner.
我想说，我们思考这个问题的主要方式是内源性大麻素和四氢大麻酚之间的区别是内源性大麻素将以非常特定的空间和时间方式释放。
Andrew Huberman:
安德鲁·休伯曼：
They evolve to do that.
他们进化来做到这一点。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
And I think it's very clear that anandamide, for example, is not active at every synapse that has CB1.
我认为很明显，例如 anandamide 并不是每个具有 CB1 的突触都活跃。
And so when we boost anandamide signaling by inhibiting its metabolism, all we're doing is amplifying anandamide signaling at the synapses it already exists.
因此，当我们通过抑制 anandamide 代谢来增强 anandamide 信号传导时，我们所做的就是在已经存在的突触处放大 anandamide 信号传导。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
Whereas THC, when you consume it orally or inhalation-wise, and it gets into your blood and into your brain, it's just blanket activation.
而 THC，当您口服或吸入时，它会进入您的血液和大脑，这只是全面激活。
You're just carpet bombing the whole system indiscriminately.
你只是不分青红皂白地对整个系统进行地毯式轰炸。
And so-
所以——
Andrew Huberman:
安德鲁·休伯曼：
You're introducing the ligand, the thing that binds-
你正在引入配体，即结合的东西-
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
the receptor.
受体。
This is far and away different than, say, the actions of amphetamines-
这与安非他明等药物的作用截然不同——
Dr. Matthew Hill:
马修·希尔博士：
Yes
是的
Andrew Huberman:
安德鲁·休伯曼：
...
...
which are disrupting the normal biology in a way that's giving you an amplification of an endogenous mechanism.
它们以某种方式破坏正常的生物学，从而放大内源性机制。
Dr. Matthew Hill:
马修·希尔博士：
Yes.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Right?
对吗？
If that was all just nerd speak for those listening.
如果这只是书呆子为那些倾听的人说话的话。
In the context of amphetamines, what you're doing is you're taking an endogenous system, a naturally occurring system, and you're greatly amplifying the amount of dopamine, the amount of norepinephrine that's available.
在安非他明的背景下，你所做的是你正在服用一个内源性系统，一个自然发生的系统，并且你大大增加了多巴胺的量，即可用的去甲肾上腺素的量。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
With what we're discussing today, the endocannabinoid system seems to be producing a set of effects that might overlap with the THC effects, but THC is doing a bunch of other things.
根据我们今天讨论的内容，内源性大麻素系统似乎正在产生一系列可能与 THC 效果重叠的效果，但 THC 正在做很多其他事情。
And that's because THC, and we'll talk about CBD, but at least THC is acting as the ligand.
那是因为 THC，我们将讨论 CBD，但至少 THC 充当配体。
It's in some sense, we don't want to say replacing, but it's masking the effects of anandamide.
从某种意义上说，我们不想说替代，但它掩盖了 anandamide 的作用。
Dr. Matthew Hill:
马修·希尔博士：
I think the problem is when you just blanket activate all the CB1 receptors in the brain indiscriminately like you do when you consume cannabis with THC, the resulting effect is the intoxicating state, and it's probably because there's a lot of CB1 receptors in the cortex, and those are going to be differentially regulated at different times by endocannabinoids.
我认为问题是，当你不加区别地激活大脑中的所有 CB1 受体时，就像你在服用含有 THC 的大麻时所做的那样，所产生的效果就是令人陶醉的状态，这可能是因为皮质中有很多 CB1 受体，而这些受体会在不同时间受到内源性大麻素的不同调节。
Whereas when THC hits them, all of them are going to get affected at once.
然而，当 THC 袭击他们时，他们所有人都会立即受到影响。
And if you think of the way that I had described how cannabinoid receptors work by essentially, at its simplest form, what cannabinoid receptors do is they change the way that two neurons talk to each other.
如果你想想我所描述的大麻素受体如何工作的方式，从本质上讲，以最简单的形式，大麻素受体的作用是改变两个神经元彼此交谈的方式。
Andrew Huberman:
安德鲁·休伯曼：
So you're changing all the networks simultaneously.
所以你要同时改变所有的网络。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
So if you hit a whole bunch of networks simultaneously, you're just going to change the way that information processing and perception occurs, and I think as a consequence of that, that's what produces the intoxicating state, not that THC is a super-duper version of an endocannabinoid, or that it's boosting endocannabinoids.
因此，如果你同时接触一大堆网络，你只会改变信息处理和感知发生的方式，我认为这就是产生令人陶醉状态的原因，而不是 THC 是内源性大麻素的超级版本，或者它会增强内源性大麻素。
It's kind of like Just indiscriminately activating all the receptors as opposed to a system that's very finely tuned-
这有点像不加区别地激活所有受体，而不是一个非常精细调整的系统-
Andrew Huberman:
安德鲁·休伯曼：
Got it
明白了
Dr. Matthew Hill:
马修·希尔博士：
...
...
to do very specific things at very specific times.
在非常特定的时间做非常特定的事情。
Andrew Huberman:
安德鲁·休伯曼：
That's very helpful.
这非常有帮助。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
So the analogy that I was considering using coming in here, like the difference between endogenous testosterone or estrogen versus pharmacologic testosterone or estrogen-
因此，我正在考虑使用这里的类比，例如内源性睾酮或雌激素与药理学睾酮或雌激素之间的差异-
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
given as a therapy-
作为一种疗法给予-
Dr. Matthew Hill:
马修·希尔博士：
Yeah, it doesn't apply
是的，它不适用
Andrew Huberman:
安德鲁·休伯曼：
...
...
is very different because that's-
非常不同，因为那是——
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
a levels issue.
一个级别的问题。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
This is a levels and an extent issue.
这是一个层次和程度的问题。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
This is a lot more to do with just, yeah, the nature of how it hits everything.
是的，这更多地与它如何影响一切的本质有关。
Because, so for example, if we talk about feeding, we know it's been established at this point that, for example, if an organism doesn't eat for a day, so you fasted.
因为，例如，如果我们谈论喂养，我们知道此时已经确定，例如，如果一个有机体一天不吃东西，那么你就禁食了。
At that point in those feeding circuits in your brain, like the arcuate area where these AgRP neurons and stuff are, you'll start seeing elevations in endocannabinoids.
那时，在你大脑中的供给回路中，比如这些 AgRP 神经元和物质所在的弓形区域，你会开始看到内源性大麻素的升高。
So endocannabinoid levels start going up and up following fasting periods.
因此，禁食期后内源性大麻素水平开始上升。
And part of this is because they're trying to engage that feeding circuitry now, and they're shifting the activity of those neurons to promote food-seeking behavior.
部分原因是它们现在正试图参与进食回路，并且它们正在改变这些神经元的活动以促进寻找食物的行为。
Because an organism is basically energy detecting its periphery and saying, "Oh, we might be burning through our energy reserves.
因为有机体基本上是在检测其外围的能量并说：“哦，我们可能正在耗尽我们的能量储备。
We should probably eat more." And so there are obviously a few mechanisms that do this.
我们或许应该多吃点。”显然有一些机制可以做到这一点。
NPY is another one, and ghrelin and things like that.
NPY 是另一种，还有胃饥饿素之类的东西。
So there's a lot of redundancy in these systems, but endocannabinoids are just one of the molecules that seem to fine-tune the feeding circuitry.
因此，这些系统中有很多冗余，但内源性大麻素只是似乎可以微调喂养电路的分子之一。
And so in states of fasting, endocannabinoids go up explicitly in that circuit, and there's some evidence they also go up in the nucleus accumbens and affect some of the reward circuitry.
因此，在禁食状态下，内源性大麻素在该回路中明显上升，并且有一些证据表明它们也在伏隔核中上升并影响某些奖励回路。
So they're probably driving food-seeking behavior and enhancing the rewarding aspects of food at the same time.
因此，它们可能会推动寻找食物的行为，同时增强食物的奖励性。
And so that's a natural endogenous mechanism to regulate feeding based on nutritional state.
因此，这是一种根据营养状态调节喂养的自然内源机制。
THC, on the other hand, it hits the brain.
另一方面，THC 会影响大脑。
Yeah, some of it's going to be the intoxication, but in tandem, you're going to hit the CB1 receptors that are in those feeding circuits as well.
是的，其中一些是中毒，但同时，你也会攻击那些喂养回路中的 CB1 受体。
And the consequence of that is going to be, the way I analogize it to people is I say it's almost like tricking the brain into thinking that you've been fasting because you're now activating receptors that are normally activated following a fasting state.
其后果将是，我将其与人们进行类比的方式是，这几乎就像欺骗大脑认为您一直在禁食，因为您现在正在激活通常在禁食状态后激活的受体。
And as a consequence of that, it pushes someone or an organism or human or whatever into a state of food-seeking behavior because now food also has high reward value, and the way their food circuitry is responding in the brain at least seems to be similar to what would happen if they've been fasted.
因此，它会将某人、有机体、人类或其他任何东西推向一种寻求食物的行为状态，因为现在食物也具有很高的奖励价值，而且他们的食物回路在大脑中的反应方式至少看起来与禁食时会发生的情况相似。
And the thought is that's why when someone gets stoned, they're not going to eat lettuce.
我们的想法是，这就是为什么当有人喝醉时，他们不会吃生菜。
They want high-calorie food.
他们想要高热量的食物。
They tend to like things that are high carb, high fat.
他们倾向于喜欢高碳水化合物、高脂肪的食物。
That combo seems to be what people like when they're intoxicated with cannabis, and that comes with a lot of calories.
这种组合似乎是人们沉醉于大麻时所喜欢的，而且含有大量卡路里。
And the point of that would be you're trying to replenish lost energy stores.
重点是你正在努力补充失去的能量储存。
And so this at least is the theory that I have about what it is that it's doing is, and I think you can make this analogy for multiple different things.
所以这至少是我关于它正在做什么的理论，我认为你可以对多种不同的事情进行类比。
If we talk about pain or stress, we can say similar kinds of things are going on, is that endocannabinoids normally do one thing, but when THC hits the brain, it's still activating these circuits in addition to everything else it hits.
如果我们谈论疼痛或压力，我们可以说类似的事情正在发生，内源性大麻素通常会做一件事，但是当 THC 击中大脑时，除了它击中的其他所有东西之外，它仍然会激活这些回路。
So you still drive that response that the endocannabinoid system normally physiologically controls, but you're almost tricking the brain into thinking you're in that state now.
因此，你仍然会驱动内源性大麻素系统通常在生理上控制的反应，但你几乎欺骗了大脑，让大脑认为你现在处于这种状态。
Andrew Huberman:
安德鲁·休伯曼：
Very interesting.
非常有趣。
Dr. Matthew Hill:
马修·希尔博士：
And so then, yeah, you go into food-seeking behavior mode.
然后，是的，你进入了寻找食物的行为模式。
Andrew Huberman:
安德鲁·休伯曼：
Super interesting.
超级有趣。
Well, I have to imagine that there are many people who use cannabis not to stimulate appetite, but for other reasons.
好吧，我不得不想象有很多人吸食大麻不是为了刺激食欲，而是出于其他原因。
They either like the euphoria or to adjust their anxiety.
他们要么喜欢这种欣快感，要么为了调整自己的焦虑。
What are some other known mechanisms by which cannabis can change people's psychology?
大麻可以通过哪些其他已知机制改变人们的心理？
Let me focus in on one particular aspect of subjective experience, which is focus.
让我集中讨论主观体验的一个特定方面，那就是焦点。
Do you think that some people use cannabis because it allows them to focus better?
您认为有些人吸食大麻是因为大麻可以让他们更好地集中注意力吗？
And I raise this specifically because I think that in the past, cannabis has had a bit of a reputation for making people spacey.
我特别提出这个问题是因为我认为过去大麻因让人精神恍惚而享有盛誉。
Dr. Matthew Hill:
马修·希尔博士：
Mm-hmm.
嗯嗯。
Andrew Huberman:
安德鲁·休伯曼：
You used the word stoned.
你用了“石头砸死”这个词。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Kind of out of it.
有点脱离它了。
And yet I've heard of some potential uses for enhancing focus.
但我听说过一些增强注意力的潜在用途。
Dr. Matthew Hill:
马修·希尔博士：
Honestly, this is a bit of a tricky one to speak to because I just don't think there's good evidence for it.
老实说，这个问题有点棘手，因为我认为没有充分的证据证明这一点。
Andrew Huberman:
安德鲁·休伯曼：
Either way, or?
不管怎样，还是？
Dr. Matthew Hill:
马修·希尔博士：
As far as I'm aware, it hasn't been studied in a lot of depth.
据我所知，尚未对其进行深入研究。
There's some things, a lot of the stuff that's been done is usually more acute memory tasks, like a working memory or recall or something like this, as opposed to explicitly studying focus.
有些事情，很多已经完成的事情通常是更敏锐的记忆任务，比如工作记忆或回忆或类似的东西，而不是明确地研究焦点。
Anecdotally, there is certainly a lot of people that report that.
有趣的是，肯定有很多人报告这一点。
So-
所以——
Andrew Huberman:
安德鲁·休伯曼：
My understanding is that people who use cannabis have poorer certain forms of memory, but not necessarily poorer memory across the board.
我的理解是，吸食大麻的人某些形式的记忆力较差，但不一定全面较差。
Is that correct?
这是正确的吗？
Dr. Matthew Hill:
马修·希尔博士：
I don't think I would say that.
我想我不会这么说。
I don't think you could lump anything in that context.
我认为在这种情况下你不能把任何事情混为一谈。
I would say the only thing you can say confidently that I would be comfortable saying is that acutely, while someone's intoxicated on cannabis, there is definitely short-term effects on memory processing.
我想说，你唯一可以自信地说，我会很舒服地说的是，严重的是，当某人沉迷于大麻时，记忆处理肯定会受到短期影响。
So people tend to-
所以人们倾向于——
Andrew Huberman:
安德鲁·休伯曼：
Negative effects or enhancements or decrements?
负面影响或增强或减弱？
Dr. Matthew Hill:
马修·希尔博士：
I would say most of it has to do with recall or consolidation.
我想说大部分与回忆或巩固有关。
So there does seem to be some, certainly the animal evidence is very compelling there, but again, we can talk to what some of the limitations of that are.
因此，似乎确实有一些动物证据非常令人信服，但我们可以再次讨论其中的一些局限性。
But in humans, I would say most of the work that's been done would suggest there is some short-term memory deficits that are present during the intoxicated state.
但在人类中，我想说的是，大部分已完成的工作都表明，在醉酒状态下存在一些短期记忆缺陷。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
I have not seen very much compelling evidence of long-term effects that emerge, like when someone's not intoxicated, but they use cannabis somewhat regularly.
我还没有看到非常令人信服的证据表明出现长期影响，例如当某人没有喝醉时，但他们经常使用大麻。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
I don't think there's anything compelling for that.
我不认为有什么令人信服的事情。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
And even in that case, like Kerry Cutler, who's at Washington State, she's done a lot of this stuff looking at cognitive processing and different kinds of memory tasks in users while they're stoned often.
即使在这种情况下，就像华盛顿州的克里卡特勒一样，她也做了很多这样的事情，研究用户在经常吸毒时的认知处理和不同类型的记忆任务。
And within a person, either they have adapted to using it as much as they do, or they've developed some form of tolerance to it.
在一个人体内，要么他们已经适应了尽可能多地使用它，要么他们已经对它产生了某种形式的耐受性。
But even in regular users, the impact on memory processing is usually not super robust.
但即使对于普通用户，对内存处理的影响通常也不是非常强大。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
It's still there.
它还在那里。
I think the effects that are more often seen in, let's say, smaller laboratory studies where they're using people who've used cannabis but aren't regular users might be a little bit more profound because they may not be ...
我认为在较小的实验室研究中更常见的效果可能会更深远一些，因为他们可能不是……
used to that state, let's say.
可以说，已经习惯了那种状态。
There's certainly something we call state-dependent learning, which I'm sure you're familiar with.
当然有一种我们称之为状态依赖学习的东西，我相信你很熟悉。
And this is something people-- I remember learning about this in undergrad through alcohol.
这是人们的事——我记得在本科时通过酒精了解到这一点。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
So, someone, first time they get drunk, tries doing something, they're very bad at the task.
所以，有人第一次喝醉时尝试做某事，但他们做得很糟糕。
But if every time they're drunk, they do that task, they become better at doing it under the influence.
但如果他们每次喝醉时都执行这项任务，那么他们在酒后会做得更好。
And so then all of a sudden, they regularly do this task while they're drunk, and someone tests them, and they don't look like they're impaired at all because they've done it so much.
突然之间，他们经常在喝醉的时候做这项任务，有人对他们进行了测试，他们看起来根本没有受到损害，因为他们已经做了太多次了。
And so-
所以——
Andrew Huberman:
安德鲁·休伯曼：
I should just say this point has often been confused by undergraduates and others to assume that just because one can gain proficiency at a task while under the influence of a substance does not mean that you have higher proficiency-
我只想说，这一点经常被本科生和其他人混淆，认为仅仅因为一个人在某种物质的影响下能够熟练地完成一项任务，并不意味着你有更高的熟练程度——
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
at that particular task-
在那个特定的任务中-
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
while under the influence.
当受到影响时。
In fact, the way it was presented to me when I was an undergraduate was incorrect.
事实上，当我还是一名本科生时，它向我呈现的方式是不正确的。
I remember the lecturer said and later corrected it himself, I won't call him out here because that's unfair.
我记得讲师说过，后来自己更正了，我不会把他叫到这里来，因为那不公平。
He's not here to defend himself, but it happens in lectures, that people who studied drunk would be better off coming to the exam drunk.
他不是来为自己辩护的，但在讲座中，喝醉了学习的人最好还是喝醉了去考试。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
That is not true-
这不是真的——
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
from what I understand.
据我了解。
Dr. Matthew Hill:
马修·希尔博士：
I don't think better off, no. But they would probably score better than someone who had never studied drunk and came to the test drunk.
我不认为情况会更好，不。但他们可能会比那些从未学习过醉酒但喝醉了参加考试的人得分更高。
Andrew Huberman:
安德鲁·休伯曼：
Correct.
正确。
Dr. Matthew Hill:
马修·希尔博士：
Just because they had had some state-dependent learning.
只是因为他们接受过一些依赖于国家的学习。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
And so I think if you're talking about someone who's a chronic cannabis user, they're going to have done a lot of cognitive tasks while they're under the influence.
所以我认为，如果你谈论的是长期吸食大麻的人，他们在吸食大麻的影响下会完成很多认知任务。
And so if you acutely test them, the impairment you might see in them is probably less than you would see in someone who's relatively naive or a much less experienced user.
因此，如果您仔细地测试它们，您可能会发现它们造成的损害可能比在相对天真或经验不足的用户中看到的损害要小。
That being said, I think it's relatively well established, most people would agree that acutely intoxication with cannabis does impair memory processes in some capacity.
话虽这么说，我认为这是相对充分的，大多数人都会同意大麻的严重中毒确实会在某种程度上损害记忆过程。
What explicit form of memory, I don't think I could speak to comfortably just because I'm not a memory researcher, and I know there's very specific things of episodic-
我不认为我可以轻松地谈论什么外显形式的记忆，因为我不是记忆研究者，而且我知道有一些非常具体的情景-
Andrew Huberman:
安德鲁·休伯曼：
Sure
当然可以
Dr. Matthew Hill:
马修·希尔博士：
...
...
and declarative and whatnot.
以及声明性等等。
So, I can't say that, but I'd say it's kind of generally, and again, you can replicate this in animals where if you train them on a task while they're under the influence, they don't seem to have consolidated that information as well.
所以，我不能这么说，但我会说这是一般性的，而且，你可以在动物身上复制这一点，如果你在它们受到影响时训练它们完成一项任务，它们似乎也没有巩固这些信息。
But again, I don't really think there's super compelling evidence that there's kind of long-term permanent effects on cognitive function in individuals who use cannabis.
但同样，我并不认为有超级令人信服的证据表明吸食大麻的人的认知功能会受到长期、永久的影响。
At least I've never seen anything that's replicable or reliable or stable in any way.
至少我从未见过任何可以复制、可靠或稳定的东西。
So, yeah.
所以，是的。
Andrew Huberman:
安德鲁·休伯曼：
Thanks for clarifying that.
感谢您澄清这一点。
And also thank you for clarifying the discrepancy between endogenous cannabinoid binding and affinity for CB1 versus THC.
还要感谢您澄清内源性大麻素结合和 CB1 与 THC 亲和力之间的差异。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
I really appreciate that because that's something that you and I discussed in light of the solo episode I did about cannabis, and now you've made it clear that THC does not bind with much higher affinity.
我真的很感激，因为这是你和我根据我对大麻所做的单独一集讨论的事情，现在你已经明确表示 THC 不会以更高的亲和力结合。
It's just, I think your words were it, assuming high THC levels in the cannabis, carpet bombs all the networks as opposed to binding more with higher affinity at particular receptors.
只是，我认为你的话是这样的，假设大麻中的四氢大麻酚含量很高，地毯式炸弹所有的网络，而不是在特定受体上以更高的亲和力结合更多。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Okay.
好的。
Dr. Matthew Hill:
马修·希尔博士：
I don't actually even think it matters if it's high THC in the cannabis.
事实上，我什至认为大麻中的四氢大麻酚含量高并不重要。
I think some people can get very intoxicated off of very, very low doses of cannabis.
我认为有些人服用非常非常低剂量的大麻就会非常陶醉。
Andrew Huberman:
安德鲁·休伯曼：
Is that right?
是这样吗？
Dr. Matthew Hill:
马修·希尔博士：
You look at edibles, for example.
例如，你看看食物。
This may be an interesting segue into route of administration stuff because I think it's an important point that a lot of people don't recognize, is the difference between someone inhaling cannabis versus someone orally consuming cannabis is a different game.
这可能是一个有趣的管理途径，因为我认为这是很多人没有意识到的重要一点，吸入大麻与口服大麻之间的区别是不同的游戏。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
Let's talk about this because I know that you and I arrived at different understanding of the fastest, typical, and slowest-
我们来谈谈这个，因为我知道你和我对最快、典型和最慢的理解不同——
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
routes of entry for THC into the system to arrive at the brain.
THC 进入系统到达大脑的途径。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Right?
对吗？
The numbers I gave in the previous discussion about this were related to how quickly inhaled smoke moves from the lungs to the bloodstream and crosses the blood-brain barrier.
我在之前的讨论中给出的数字与吸入的烟雾从肺部移动到血液并穿过血脑屏障的速度有关。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Which is very fast.
这非常快。
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Right.
对。
Which is very fast.
这非常快。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
I don't know if it's different than nicotine.
不知道和尼古丁有什么区别
I'm not sure.
我不知道。
Again, I don't know if I would say that, but yeah.
再说一次，我不知道我是否会这么说，但是是的。
It's very fast.
速度非常快。
Andrew Huberman:
安德鲁·休伯曼：
Okay.
好的。
So it may be that it is the same as nicotine, it may be that it's faster, but importantly, it can be fast.
所以它可能和尼古丁一样，可能更快，但重要的是，它可以更快。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
But typically, how fast is the onset of the subjective experience of, okay, somebody takes a hit off a joint or a bong hit, and they start to experience the subjective effects of euphoria, et cetera.
但通常情况下，主观体验的开始速度有多快，好吧，有人敲了一下大麻烟或敲了一下烟枪，他们开始体验到欣快感等的主观效果。
How quickly after?
之后多久？
Dr. Matthew Hill:
马修·希尔博士：
Two to five minutes, I would say.
我想说两到五分钟。
Andrew Huberman:
安德鲁·休伯曼：
Two to five minutes.
两到五分钟。
Dr. Matthew Hill:
马修·希尔博士：
It's pretty fast.
速度相当快。
So this is one of the things with cannabis is, and again, this will kind of go into this idea of the change in potency of the plant as well.
所以这是大麻的问题之一，而且，这也将涉及到植物效力变化的想法。
It's pretty quick, and people titrate cannabis pretty well, at least people who've used it a couple of times and understand this tend-
它非常快，人们滴定大麻的效果也很好，至少那些使用过几次并了解这种趋势的人是这样的——
Andrew Huberman:
安德鲁·休伯曼：
I know.
我知道。
I've seen some people not titrate it very well.
我见过有些人滴定得不好。
Dr. Matthew Hill:
马修·希尔博士：
Depending again on how you-- So again, this can vary.
再次取决于您的方式——同样，这可能会有所不同。
So, cannabis from the '70s was like, I don't know, 5% THC, let's say.
所以，70 年代的大麻就像，我不知道，5% THC，可以这么说。
It was pretty low.
这是相当低的。
And nowadays, cannabis is, a lot of the commercial stuff is between 20 and 30.
如今，大麻，很多商业大麻的含量都在 20 到 30 之间。
Although whether those are super accurate numbers, not entirely clear.
尽管这些是否是超级准确的数字，尚不完全清楚。
Andrew Huberman:
安德鲁·休伯曼：
Wow.
哇。
Dr. Matthew Hill:
马修·希尔博士：
But so it's gone up a fair amount.
但它已经上涨了相当多的金额。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
That's not just a fair amount.
这不仅仅是一个合理的数额。
If we were talking about alcohol concentration-
如果我们谈论酒精浓度-
Dr. Matthew Hill:
马修·希尔博士：
It's a beer to vodka.
这是伏特加的啤酒。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Basically, you're talking about a beer or a wine to a spirit.
基本上，您谈论的是啤酒或葡萄酒或烈酒。
Andrew Huberman:
安德鲁·休伯曼：
And there are aquavit varieties-
还有阿夸维特品种——
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
so to speak.
可以这么说。
By the way, I think when people hear me talk about any kind of drug that can be used recreationally or alcohol, I think some people assume that I'm ultra anti all these things.
顺便说一句，我认为当人们听到我谈论任何可以娱乐性使用的药物或酒精时，我认为有些人会认为我极端反对所有这些事情。
I'm actually not.
我其实不是。
Right?
正确的？
I'm non-alcoholic, so I can drink a little bit, and I have.
我不喝酒，所以我可以喝一点，而且我也喝了。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
I just don't tend to.
我只是不倾向于。
And we could discuss cannabis in a different venue.
我们可以在不同的场所讨论大麻。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
But the point here is we're not trying to frame this as what people should or shouldn't do.
但这里的要点是，我们并不是试图将其界定为人们应该做什么或不应该做什么。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
We're just trying to inform people.
我们只是想告诉人们。
Dr. Matthew Hill:
马修·希尔博士：
No, exactly.
不，确切地说。
Andrew Huberman:
安德鲁·休伯曼：
I want to be very, very clear about that.
我想非常非常清楚地说明这一点。
Dr. Matthew Hill:
马修·希尔博士：
So I think-
所以我认为——
Andrew Huberman:
安德鲁·休伯曼：
But when I hear about 20% to 30% concentration as opposed to-
但当我听到大约 20% 到 30% 的浓度而不是-
Dr. Matthew Hill:
马修·希尔博士：
Five
五
Andrew Huberman:
安德鲁·休伯曼：
...
...
5% concentration, that's significant.
5%的浓度，意义重大。
Dr. Matthew Hill:
马修·希尔博士：
So I would say this is what's super interesting And this was something that came out of the way that cannabis research is done, certainly in the States.
所以我想说这是非常有趣的，这是大麻研究的结果，当然是在美国。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
And Canada's been quite behind on this.
而加拿大在这方面却相当落后。
Even with legalization, we haven't caught up.
即使合法化，我们还没有赶上。
But they have been doing lab-based studies of cannabis.
但他们一直在对大麻进行实验室研究。
Meg Haney, Harriet de Wit, this cluster of researchers around the country, Ziva Cooper at UCLA here, have all done this where you have people come into the lab, you give them cannabis, you measure subjective outcomes or neuroimaging outcomes or whatnot.
梅格·哈尼 (Meg Haney)、哈里特·德威特 (Harriet de Wit)、全国各地的这群研究人员、加州大学洛杉矶分校 (UCLA) 的齐瓦·库珀 (Ziva Cooper) 都做过这样的事情，让人们进入实验室，给他们大麻，测量主观结果或神经影像结果等等。
So to do this, you can't use commercial cannabis, and even the state-by-state legalizations hasn't changed this.
因此，要做到这一点，你不能使用商业大麻，甚至各州的合法化也没有改变这一点。
So if you are doing cannabis research in humans and you're funded by NIDA, which is National Institute of Drug Abuse, you get all your cannabis sourced.
因此，如果您正在进行人类大麻研究，并且您得到 NIDA（国家药物滥用研究所）的资助，那么您所有的大麻都将获得来源。
This may be changing.
这可能正在改变。
I think there are some shifts that are happening.
我认为一些转变正在发生。
But historically, in all the literature that we would talk about that's pre the last couple of years, all that cannabis came from one source, which was, I believe, a farm in Mississippi that was essentially funded by NIDA to produce cannabis.
但从历史上看，在过去几年之前我们谈论的所有文献中，所有大麻都来自一个来源，我相信是密西西比州的一个农场，该农场基本上是由 NIDA 资助生产大麻的。
Andrew Huberman:
安德鲁·休伯曼：
Lucky farm.
幸运农场。
Dr. Matthew Hill:
马修·希尔博士：
And well, the cannabis that came out of it, though, and this is one of the reasons a lot of the clinical stuff people have been like, "Oh, I don't know how representative this is," because it reflects cannabis that I would say is more from the '70s or '80s.
好吧，不过，从中产生的大麻，这就是很多临床材料人们喜欢的原因之一，“哦，我不知道这有多大代表性，”因为它反映了我认为更多是来自 70 年代或 80 年代的大麻。
So it would be five to 9% kind of THC cannabis.
所以这将是 5% 到 9% 的 THC 大麻。
Now, when you put someone in a lab setting and you get them to smoke to level of intoxication, people would take, whatever, eight tokes, let's say, something like that, and that's where they would stop.
现在，当你把某人放在实验室环境中，让他们吸烟到中毒的程度时，人们会吸食八支烟，比如说类似的东西，然后他们就会停下来。
And so a lot of the labs that use this have always been like, our people who are regular cannabis users are getting high off of it.
因此，许多使用这种药物的实验室一直都在说，我们那些经常使用大麻的人正在从中获得乐趣。
It's not as potent as the stuff that's on the street, but they're clearly getting intoxicated from it and it's giving us reliable data.
它不像街上的东西那么有效，但他们显然已经陶醉其中，并且它为我们提供了可靠的数据。
So when they started looking at the blood levels of THC that you achieve, it was around 100 nanograms per ml of THC, give or take.
因此，当他们开始观察您所达到的血液 THC 水平时，无论给予或服用，THC 的含量约为每毫升 100 纳克。
That seemed to be where it was.
那似乎就是它所在的地方。
Now, because of the way that you can legally study cannabis in the States, you couldn't just go down to a dispensary and buy the products that everyone on the street are using, which is like, it's been a weird thing for a lot of people because they're like, "Why wouldn't you study what we're using?" But because of the legal aspects of this, you couldn't bring those products into the lab.
现在，由于你可以在美国合法研究大麻，你不能只是去药房购买街上每个人都在使用的产品，这对很多人来说是一件奇怪的事情，因为他们会说，“你为什么不研究我们正在使用的东西呢？”但由于法律方面的原因，你不能将这些产品带入实验室。
They'd never been standardized.
它们从未被标准化。
No one knew exactly what was in them, pesticides, all this other stuff that could influence it.
没有人确切知道它们里面有什么，农药，以及所有其他可能影响它的东西。
So from a safety perspective, it was always like, no, you use the cannabis that's sourced from NIDA.
因此，从安全角度来看，你总是会说，不，你使用的是来自 NIDA 的大麻。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
So it was a group in Colorado, so Kent Hutchison and Angela Bryan and Cinnamon Bidwell have kind of, I would say, became very creative, actually, to figure out how to study cannabis that's being used, I call it, in the wild, in kind of an ecological setting, let's say.
这是科罗拉多州的一个小组，所以我想说，肯特·哈奇森（Kent Hutchison）、安吉拉·布莱恩（Angela Bryan）和肉桂·比德韦尔（Cinnamon Bidwell）实际上变得非常有创造力，以弄清楚如何研究正在使用的大麻，我称之为，在野外，在某种生态环境中，可以这么说。
And so they created what was called the Canavan.
因此他们创造了所谓的“Canavan”。
And the Canavan was a way to study people using products on the street, but not have them come into a laboratory setting where it was complicated.
Canavan 是一种研究人们在街上使用产品的方法，而不是让他们进入复杂的实验室环境。
And so what they would do is they would drive the Canavan to someone's house, but they'd be parked on the street, and someone would use the product, whatever it was, in their own property, on their own time, and then come into the Canavan to have blood taken to look at what their THC levels are and to undergo testing.
所以他们会做的是，他们会把 Canavan 开到某人的家里，但他们会把车停在街上，有人会在自己的财产上、在自己的时间使用该产品，无论它是什么，然后进入 Canavan 抽血，看看他们的 THC 水平是多少，并接受测试。
And so it was actually like, I think this was a great advance in the field because it was this huge, innovative approach that allowed us to start comparing what we've learned from lab-based settings with this kind of old school weed that was coming from NIDA with what is being used on the street.
所以实际上，我认为这是该领域的一个巨大进步，因为正是这种巨大的创新方法使我们能够开始将我们从实验室环境中学到的知识与来自 NIDA 的老式大麻和街上使用的大麻进行比较。
Andrew Huberman:
安德鲁·休伯曼：
I love this.
我喜欢这个。
As somebody whose lab has done a in-laboratory, VR-based experiment on human anxiety and fear, and then compared that to a clinical study that we did sort of en masse where people were at home doing specific respiration practices.
作为一个人，他的实验室在实验室中对人类焦虑和恐惧进行了基于 VR 的实验，然后将其与我们集体进行的一项临床研究进行了比较，其中人们在家里进行特定的呼吸练习。
You have many more subjects, but of course, they're reporting back their effects.
你有更多的主题，但当然，他们正在报告其效果。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Well, you can monitor them by device, look at HRV, look at heart rate, et cetera.
嗯，您可以通过设备监控它们，查看 HRV、查看心率等等。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
I think having the ability to compare and contrast in-laboratory and ex-laboratory data is extremely valuable.
我认为能够比较和对比实验室内和实验室外的数据是非常有价值的。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
And my view is you need both because you need the in-laboratory for the control, because we all need control over various things.
我的观点是，两者都需要，因为你需要实验室进行控制，因为我们都需要控制各种事物。
But you also need the ecological validity to see how it shakes out and make sure it looks the same.
但你还需要生态有效性来观察它如何变化并确保它看起来一样。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
For people that have never been to a laboratory or tried to find a parking spot at a university-
对于那些从未去过实验室或试图在大学里找到停车位的人来说——
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
that's an anxiety-inducing experience in and of itself.
这本身就是一种引起焦虑的经历。
Dr. Matthew Hill:
马修·希尔博士：
Well, and a novel experience while someone's intoxicated with cannabis can also create a very different altered state.
好吧，当某人沉迷于大麻时的新奇体验也可以创造出一种非常不同的改变状态。
Andrew Huberman:
安德鲁·休伯曼：
I wouldn't want to be stoned in a laboratory.
我不想在实验室里被石头砸死。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
I'll tell you that much.
我就告诉你这么多。
Dr. Matthew Hill:
马修·希尔博士：
I feel like there's pluses and minuses to both sides, but I think the data together is very compelling, and that's where we get a lot of advance in the field.
我觉得双方都有优点和缺点，但我认为数据放在一起非常引人注目，这就是我们在该领域取得很大进展的地方。
So what Kent, Angela, and Cinnamon did with the Canavan was kind of create this situation that allowed this research to occur.
所以肯特、安吉拉和辛纳蒙对卡纳万所做的就是创造了一种允许这项研究进行的情况。
And what we found fascinating, I remember talking to Meg Haney about this because all the people in her lab studies tended to always hit around 100 nanograms per ml using this relatively lower potency cannabis.
我们发现令人着迷的是，我记得与 Meg Haney 谈论过这个问题，因为她的实验室研究中的所有人都倾向于使用这种相对较低效力的大麻达到每毫升 100 纳克左右。
When Kent and Angela and Cinnamon started studying this in the people and taking blood, despite the fact that these people are now using cannabis that's 20% to 30%, their blood levels are the same.
当 Kent、Angela 和 Cinnamon 开始对人们进行研究并采集血液时，尽管这些人现在使用的大麻含量为 20% 到 30%，但他们的血液水平是相同的。
So they're still coming in around 100 nanograms per ml because people are really good at self-titrating.
因此，它们的浓度仍约为每毫升 100 纳克，因为人们非常擅长自我滴定。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
Now, where things fall apart is with the concentrates.
现在，问题出在浓缩物上。
So then you go into things like dabs or these high potency products that are now like...
然后你就开始研究诸如轻拍或这些高效产品之类的东西，现在就像......
Because cannabis itself, realistically, from what I understand from the botanist that I've talked to, you can't really grow a plant that's going to exceed more than 25% to 30% THC just by sheer biology.
因为大麻本身，实际上，根据我从与我交谈过的植物学家那里了解到的情况，仅凭纯粹的生物学原理，你不可能真正种植出一种 THC 含量超过 25% 至 30% 的植物。
So it taps out there.
所以它就在那里敲击。
That's about as high as it's going to go.
这大约是它能达到的最高值。
Concentrates can go up to like 90%, 98%.
浓缩度可高达 90%、98%。
So you can get really, really-
所以你可以真的、真的——
Andrew Huberman:
安德鲁·休伯曼：
These are tinctures?
这些是酊剂吗？
Dr. Matthew Hill:
马修·希尔博士：
Distillates, yeah.
蒸馏物，是的。
Various just in oil-based forms that are very, very high potency products.
各种油基形式都是非常非常高效的产品。
Those are incredibly challenging to titrate.
这些对于滴定来说是非常具有挑战性的。
They cannot be titrated because the sheer volume of THC that hits the system, even from a single hit, is so overwhelming.
它们无法被滴定，因为进入系统的 THC 的绝对量，即使是一次攻击，也是如此巨大。
And so when the Colorado group looked at those, their blood levels were closer to 200, 300 nanograms per ml.
因此，当科罗拉多州的研究小组观察这些数据时，他们的血液浓度接近每毫升 200、300 纳克。
So With cannabis plant, there does seem to be this ability for people to relatively self-titrate.
因此，对于大麻植物来说，人们似乎确实有这种相对自我滴定的能力。
And then my buddy Ryan McLaughlin, who's also at Washington State, he was really one of the ones that pioneered these vape chambers in rats and created this really cool model of self-administration, which was a very important thing to actually establish because it was very challenging to get rodents to self-administer cannabis if you were doing an IV approach or something else, because they found it quite aversive.
然后我的朋友 Ryan McLaughlin，也在华盛顿州，他确实是在老鼠身上开创这些电子烟室并创建了这种非常酷的自我管理模型的人之一，这对于实际建立来说是一件非常重要的事情，因为如果你正在进行静脉注射或其他方法，那么让啮齿类动物自我管理大麻是非常具有挑战性的，因为他们发现它非常令人厌恶。
But when you let rodents actually titer their ability to get vape hits, they will work for this, the same way they will other reinforcing drugs.
但是，当你让啮齿类动物真正提高其吸电子烟的能力时，它们就会发挥作用，就像使用其他强化药物一样。
So it was a really important finding that you could do this.
所以这是一个非常重要的发现，你可以做到这一点。
And what Ryan found was he actually did one study where he gave them access to a low-potency product, we'll call it medium, and then a high.
瑞安发现，他实际上做了一项研究，让他们接触到低效产品，我们称之为中效产品，然后是高效产品。
And what you ended up, if you look at the data, is the one the rats liked the best was the medium-potency product.
如果你查看数据，你最终会发现老鼠最喜欢的是中等效力的产品。
Andrew Huberman:
安德鲁·休伯曼：
Interesting.
有趣。
Dr. Matthew Hill:
马修·希尔博士：
And if you gave them the high-potency product, they would actually take less vape hits off of that than they would off the lower ones.
如果你给他们提供高效力的产品，他们实际上会比低效产品吸收更少的电子烟。
And again, all their blood levels tended to cluster in the same range because they titrated.
而且，由于滴定，他们所有的血液浓度都倾向于聚集在同一范围内。
Even at the rodent level, they're able to titrate because of the lag between inhalation and feeling the effects is only on the order of a couple of minutes, people can titrate better.
即使在啮齿动物水平上，他们也能够进行滴定，因为吸入和感觉效果之间的滞后时间仅为几分钟，人们可以更好地滴定。
Not just people, it seems like the rodents can as well.
不仅仅是人类，啮齿动物似乎也可以。
So the higher potency cannabis, where it becomes a problem is if someone's highly inexperienced and they consume a whole bunch of it without allowing that time lag to occur, and then they can probably exceed the levels they intended to and consume too much and then have probably an adverse response.
因此，对于效力较高的大麻来说，问题在于，如果某人非常缺乏经验，并且他们在没有允许时间延迟发生的情况下消耗了一大堆大麻，那么他们可能会超出他们预期的水平并消耗太多，然后可能会产生不良反应。
Andrew Huberman:
安德鲁·休伯曼：
So does that mean that cannabis use rarely leads to tolerance of cannabis use?
那么这是否意味着大麻的使用很少会导致对大麻使用的耐受性？
Dr. Matthew Hill:
马修·希尔博士：
I wouldn't say that.
我不会这么说。
There's definitely some degree of tolerance.
肯定有一定程度的容忍度。
The tolerance is definitely more prominent when people start using concentrates.
当人们开始使用浓缩物时，耐受性肯定会更加突出。
There's no question about that.
毫无疑问。
We can talk about the concentrates, I guess, separately after.
我想，我们可以在之后单独讨论浓缩物。
Because I would say if we're talking about a harm reduction thing, that's more where we need to focus a lot more, is this idea of these high-potency products.
因为我想说，如果我们谈论的是减少伤害的事情，那么我们更需要更加关注的是这些高效产品的想法。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
It sounds like those are precarious.
听起来这些都是不稳定的。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
That somebody who thinks they have a lot of experience or, God forbid, no experience, takes a concentrate and is, what?
那些自认为拥有丰富经验或者（上帝保佑，没有经验）的人集中注意力，然后发现，什么？
No longer getting the euphoric experience that they anticipated, but instead are getting, what, a paranoid anxiety attack?
不再获得他们预期的欣快体验，而是获得，什么，偏执性焦虑发作？
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
I think you're far more likely to go overboard and have an adverse response.
我认为你更有可能做得太过火并产生不良反应。
But also, I think the problem is if you're using a product of that potency and that much THC floods your system on a regular basis, the biological changes from that are going to be very different than what you get if, again, you're titrating your THC from inhaling plant at roughly the same level, whether that's a 10%, 5%, or 25%, people generally tend to scale.
而且，我认为问题是，如果你使用这种效力的产品，并且有那么多 THC 定期涌入你的系统，那么由此产生的生物变化将与你所得到的生物变化非常不同，如果你从吸入植物中滴定 THC 的水平大致相同，无论是 10%、5% 还是 25%，人们通常倾向于按比例调整。
Andrew Huberman:
安德鲁·休伯曼：
All right.
好吧。
This is a very important point, and I'm going to highlight it because I think it's very, very important, although you're making it very clearly already, which is these days we hear a lot about the quote, unquote "problems" with high-THC containing cannabis as relative to what was present in the '70s and '80s, and presumably '90s as well.
这是非常重要的一点，我要强调这一点，因为我认为它非常非常重要，尽管您已经说得很清楚了，这些天我们听到了很多关于这句话的内容，取消引用含有高 THC 的大麻的“问题”，相对于 70 年代和 80 年代，大概还有 90 年代存在的问题。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
I was a teen in the '90s, so maybe I'm alluding to something there.
我当时是 90 年代的青少年，所以也许我指的是那里的一些事情。
But what you're saying is that unless one is talking about concentrates, that people and animals in the laboratory will self-regulate the amount of intake in a way that leads to approximately the same blood levels of THC.
但你所说的是，除非人们谈论的是浓缩物，否则实验室中的人和动物会自我调节摄入量，从而导致血液中四氢大麻酚的水平大致相同。
So it may not be as much of a concern, at least in light of-
所以这可能不是那么令人担忧，至少考虑到-
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
the concerns about, oh, these levels are so high that people are overwhelming their system with THC.
人们担心，哦，这些水平是如此之高，以至于人们用四氢大麻酚淹没了他们的系统。
Basically, this could be stated in real-world terms as people are taking fewer tokes of the higher concentration stuff that allow them to match blood levels that were present in the person taking many more tokes-
基本上，这可以用现实世界的术语来表述，因为人们服用的浓度较高的物质较少，这使他们能够与服用更多药物的人体内存在的血液水平相匹配——
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
in the '70s.
在 70 年代。
Dr. Matthew Hill:
马修·希尔博士：
So the joke I always make to people is I say, "Go watch a Cheech and Chong movie from the late '70s.
所以我总是对人们开的玩笑是：“去看一部 70 年代末的 Cheech and Chong 电影。
Look at the size of the joints that they smoke in movies like that relative to what you would see someone on the street consuming nowadays." So the advantage that existed from a titration perspective was with '70s weed, there's a large window to titrate.
看看他们在电影中抽的大麻烟和现在街上看到的人抽的烟大麻的大小。”因此，从滴定的角度来看，70 年代的杂草存在的优势是，有一个很大的滴定窗口。
So people could take small amounts and not over-consume, let's say, because there was a much lower concentration of THC in the plant, so they were able to consume, even if they were doing it relatively fast, because of how little THC was coming into the system, it was a little easier to scale that.
所以人们可以少量服用而不是过度消费，因为植物中的 THC 浓度要低得多，所以他们能够消费，即使他们相对较快，因为进入系统的 THC 很少，所以更容易扩大规模。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
So there certainly is the propensity for people to over-consume higher potency cannabis, even independent of concentrates, if they're not allowing that titration to occur.
因此，如果人们不允许这种滴定发生，那么他们肯定有过度消费高效大麻的倾向，即使不考虑浓缩物。
Also, if you have someone who's just exquisitely sensitive to THC for various reasons, even one or two tokes could be too much for them because at the higher potency, they may not have that ability to titrate quite as well.
此外，如果您的某人由于各种原因对 THC 非常敏感，即使一两次对他们来说也可能太多了，因为在较高的效力下，他们可能不具备滴定的能力。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
And so a lot of people, anecdotally, you talk to people about cannabis, and a lot of people who don't like cannabis have said, "Oh, I've tried the new stuff, it's too strong." And if there's someone who's more in our age range who grew up in an earlier decade where things were a bit different, they may be referencing their own experience from when they were younger and what they were able to consume, and now they try doing the same and it hits them like a sledgehammer.
有趣的是，很多人在与人们谈论大麻时，很多不喜欢大麻的人都会说，“哦，我已经尝试过新东西了，它太强了。”如果有人在我们这个年龄段长大，在过去的十年里，情况有点不同，他们可能会参考自己年轻时的经历和他们能够消费的东西，现在他们尝试做同样的事情，这就像大锤一样打击他们。
Andrew Huberman:
安德鲁·休伯曼：
Got it.
明白了。
Dr. Matthew Hill:
马修·希尔博士：
So it's a little different in that sense.
所以从这个意义上来说有点不同。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
And I don't think it's to say it's not concerning that cannabis is as high as THC as it is.
我不认为这意味着大麻的 THC 含量与它一样高。
I just think if I'm going to put my efforts into public health perspectives of this, I would be digging my feet in much more about the access to concentrates and the issues and the potential harms that are going to come with them than I would about the cannabis flower myself.
我只是想，如果我要把我的努力投入到公共卫生的角度，我会比我自己对大麻花的关注更多地关注浓缩物的获取以及随之而来的问题和潜在危害。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
That's just my opinion based on what I see with the concerns and what we've seen from the data in humans.
这只是我的观点，基于我所看到的担忧以及我们从人类数据中看到的情况。
And I think the real world ecological studies that the Colorado group have done have been very informative in this sense because, yeah, if the blood levels of THC you achieve from concentrates are double to triple of what you get even from higher potency flower, that's a concern.
我认为科罗拉多小组所做的现实世界生态研究在这个意义上非常有用，因为，是的，如果你从浓缩物中获得的四氢大麻酚血液水平是你从更高效力的花中获得的两倍到三倍，那就是一个问题。
I think that's where problems start arising, because then you're going to start seeing a lot higher degree of tolerance.
我认为这就是问题开始出现的地方，因为那时你将开始看到更高程度的宽容。
There used to be more of a debate in the field as to whether people develop tolerance, because one of the things with cannabis that I do find very interesting is with a lot of chronic users, they don't escalate the way you would see with cocaine or alcohol, where there's very profound tolerance that develops.
关于人们是否会产生耐受性，该领域曾经有更多的争论，因为我确实发现大麻非常有趣的一件事是，对于许多长期吸食大麻的人来说，他们不会像可卡因或酒精那样升级，而可卡因或酒精会产生非常深刻的耐受性。
And so, people definitely see this in cocaine, where people can become tolerant almost immediately.
因此，人们肯定在可卡因中看到了这一点，人们几乎可以立即变得宽容。
And so dosing starts scaling up very fast.
因此剂量开始快速增加。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
Usually, it's the life destruction that thwarts their-
通常，是生命的毁灭阻碍了他们——
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
progressive increase.
逐步增加。
Seriously.
严重地。
Dr. Matthew Hill:
马修·希尔博士：
Or the cost.
或者成本。
Andrew Huberman:
安德鲁·休伯曼：
Right.
对。
Dr. Matthew Hill:
马修·希尔博士：
The sheer cost.
纯粹的成本。
Andrew Huberman:
安德鲁·休伯曼：
Another form of life-
另一种生命形式——
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
deterioration.
恶化。
Dr. Matthew Hill:
马修·希尔博士：
Yeah, that is required to be able to maintain that.
是的，这需要能够维持这一点。
But with cannabis- It seems like there is some degree of tolerance that people exhibit.
但对于大麻——人们似乎表现出一定程度的耐受性。
It varies from person to person.
这因人而异。
But as Meg has said to me many times, the guys that come in her studies, these are very heavy users, and then they will use this relatively low potency product and still get high off of it.
但正如梅格多次对我说的那样，参与她研究的人都是非常重度用户，他们会使用这种效力相对较低的产品，但仍然会从中获得乐趣。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
And so it's not to say that there's no tolerance, it's just not as profound as I think we see with a lot of other drugs.
所以这并不是说没有耐受性，只是没有我认为我们在许多其他药物中看到的那么深刻。
And this is probably due to the fact of just, we definitely see, if we look at some PET imaging studies, chronic cannabis users do have some downregulation-
这可能是因为，如果我们看一些 PET 成像研究，我们肯定会发现，长期吸食大麻的人确实有一些下调——
Andrew Huberman:
安德鲁·休伯曼：
Sorry, I have to interrupt.
抱歉，我必须打断一下。
PET, positron emission tomography-
PET，正电子发射断层扫描-
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
not pets.
不是宠物。
Although people get their pets high, and we don't know what those pets think about that.
尽管人们让他们的宠物兴奋，但我们不知道那些宠物对此有何看法。
Dr. Matthew Hill:
马修·希尔博士：
Not good.
不好。
Andrew Huberman:
安德鲁·休伯曼：
Although-
虽然——
Dr. Matthew Hill:
马修·希尔博士：
Don't get dogs high.
不要让狗兴奋。
Andrew Huberman:
安德鲁·休伯曼：
Although if also high, one can assume a lot of things about what your pet is thinking-
虽然如果也很高，人们可以推测你的宠物在想什么——
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
while also high.
同时也高。
Sort of half joke there.
有点半开玩笑的意思。
But yes, positron emission tomography is one way to assess the binding of drugs within the brain, as well as activity of endogenous neurotransmitters, neuromodulators, such as anandamide, dopamine, et cetera.
但是，是的，正电子发射断层扫描是评估大脑内药物结合以及内源性神经递质、神经调节剂（如阿那达酰胺、多巴胺等）活性的一种方法。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
Dr. Matthew Hill:
马修·希尔博士：
So a typical PET study in a human looking at this, they'd give a molecule that's radiolabeled that will bind to CB1 receptors.
因此，在人体中进行典型的 PET 研究时，他们会提供一种放射性标记的分子，该分子将与 CB1 受体结合。
You can scan them, and then look at the emission rates of the radiation to get an idea of the density of receptors that are in the brain.
您可以扫描它们，然后查看辐射的发射率，以了解大脑中受体的密度。
Chronic cannabis users tend to have less.
长期吸食大麻的人往往吸食的大麻较少。
What that means in terms of the functional outcome is unclear.
这对于功能结果意味着什么尚不清楚。
There's a lot of evidence that there's some degree of a reservoir of CB1 receptors that there might be a lot more receptors there than we necessarily always need or are always using, let's say.
有大量证据表明存在一定程度的 CB1 受体库，其中可能存在比我们总是需要或总是使用的受体多得多的受体。
So we might be down-regulating a component of this, but maybe not all of the ones that are required to produce the psychoactive effects, because there's clearly some maintenance of the system that allows someone to continue to get intoxicated.
因此，我们可能会下调其中的一个组成部分，但可能不是产生精神作用所需的全部组成部分，因为显然有一些系统维护可以让某人继续陶醉。
And so with cannabis users, we do see that.
对于大麻使用者来说，我们确实看到了这一点。
But you do see much more profound tolerance with people using high potency extracts and concentrates and things like this.
但你确实看到人们对使用高效提取物和浓缩物之类的东西有更深刻的耐受性。
And again, surely I think as a response to the biology of hitting the system that heavily with that much THC as it comes in because they can't titrate it the same way.
再说一次，我当然认为这是对系统的生物学反应，因为系统中含有大量的 THC，因为他们不能以同样的方式滴定它。
Andrew Huberman:
安德鲁·休伯曼：
It makes sense.
这是有道理的。
Yeah, these concentrates sound like something to at least pay attention to as a potential problem.
是的，这些浓缩物听起来至少是一个值得关注的潜在问题。
I'd like to take a quick break and acknowledge our sponsor, InsideTracker.
我想稍微休息一下并感谢我们的赞助商 InsideTracker。
InsideTracker is a personalized nutrition platform that analyzes data from your blood and DNA to help you better understand your body and help you reach your health goals.
InsideTracker 是一个个性化营养平台，可分析您的血液和 DNA 数据，帮助您更好地了解您的身体并帮助您实现健康目标。
Now, I've long been a believer in getting regular blood work done for the simple reason that many of the factors that impact your immediate and long-term health can only be analyzed from a quality blood test.
现在，我长期以来一直相信定期进行血液检查，原因很简单，影响您当前和长期健康的许多因素只能通过高质量的血液测试来分析。
Now, a major problem with a lot of blood tests out there is that you get information back about metabolic factors and hormones and lipids and so forth, but you don't know what to do with that information.
现在，大量血液测试的一个主要问题是，您获得有关代谢因素、激素和脂质等的信息，但您不知道如何处理这些信息。
With InsideTracker, they make it very easy to know what to do with those numbers because they have a personalized platform that allows you to see the levels of those metabolic factors, lipids, hormones, et cetera.
通过 InsideTracker，他们可以很容易地知道如何处理这些数字，因为他们有一个个性化的平台，可以让您查看这些代谢因素、脂质、激素等的水平。
And they give you specific directives that you can follow related to nutrition, behavioral modification, supplementation, and more, that can help you bring those numbers into the ranges that are optimal for you.
他们为您提供了与营养、行为改变、补充剂等相关的具体指示，您可以遵循这些指示，这可以帮助您将这些数字调整到最适合您的范围。
If you'd like to try InsideTracker, you can go to insidetracker.com/huberman to get 10% off their new membership program.
如果您想尝试 InsideTracker，您可以访问 insidetracker.com/huberman 享受其新会员计划 10% 的折扣。
InsideTracker membership offers significantly reduced prices on InsideTracker's comprehensive blood panels.
InsideTracker 会员资格可大幅降低 InsideTracker 综合血液检测的价格。
Again, that's insidetracker.com/huberman to get 10% off.
再次强调，访问 insidetracker.com/huberman 可以获得 10% 的折扣。
Along the lines of use tolerance, et cetera, is cannabis addictive and/or habit-forming?
沿着使用耐受性等方面，大麻是否会上瘾和/或形成习惯？
And I think it's probably important that we distinguish between the two.
我认为区分两者可能很重要。
I may have made this joke in the previous episode I did on cannabis.
我可能在上一集关于大麻的节目中开过这个玩笑。
I've known a lot of chronic cannabis users, and none of them admit to being addicted.
我认识很多长期吸食大麻的人，但他们都不承认自己上瘾了。
It's not my place to challenge them on that.
我没有资格在这方面挑战他们。
But they do seem, in my experience, this is not an experiment, but in my experience, more irritable when they don't have access to what they call their "medicine."
但根据我的经验，他们确实似乎不是一个实验，但根据我的经验，当他们无法获得他们所谓的“药物”时，他们会更加烦躁。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
So, that speaks to a dependence or something.
所以，这说明了依赖性或其他什么。
But then we need to be careful because in the classic sense, addiction, I've defined, and others in the field of addiction have defined it as a progressive narrowing of the things that bring you pleasure, such that it causes disruption to other areas of life, and your life becomes maladaptive.
但我们需要小心，因为在经典意义上，我已经定义了成瘾，而成瘾领域的其他人也将其定义为逐渐缩小给你带来快乐的事物，从而对生活的其他领域造成干扰，你的生活变得适应不良。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
I'm not going to play with the definition of addiction.
我不会玩弄成瘾的定义。
I feel like I have enough friends in the addiction space that it's a very contentious-
我觉得我在成瘾领域有足够的朋友，这是一个非常有争议的-
Andrew Huberman:
安德鲁·休伯曼：
Sure
当然可以
Dr. Matthew Hill:
马修·希尔博士：
...
...
field.
场。
So, I will try and not use that word, although I understand talking to the general public, if you say someone has a use disorder versus an addiction, that may not make sense to them.
所以，我会尽量不使用这个词，尽管我理解与公众交谈，如果你说某人有使用障碍而不是成瘾，这对他们来说可能没有意义。
Andrew Huberman:
安德鲁·休伯曼：
Right.
对。
But that's the nomenclature now that people are using.
但这是人们现在使用的术语。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Alcohol use disorder.
酒精使用障碍。
Dr. Matthew Hill:
马修·希尔博士：
Yeah, exactly.
是的，完全正确。
So-
所以——
Andrew Huberman:
安德鲁·休伯曼：
Cannabis use disorder.
大麻使用障碍。
Dr. Matthew Hill:
马修·希尔博士：
Yes.
是的。
Andrew Huberman:
安德鲁·休伯曼：
This is what you start to see now instead of saying being addicted to pot or being addicted to alcohol.
这就是你现在开始看到的，而不是说对大麻上瘾或对酒精上瘾。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
And so an addiction is obviously a very complex thing that, again, I don't want to touch it simply because it's not my space.
因此，成瘾显然是一件非常复杂的事情，我不想再碰它，因为这不是我的空间。
But that being said, there's no question that people can develop cannabis use disorder.
但话虽这么说，毫无疑问人们可能会患上大麻使用障碍。
It's definitely a thing.
这绝对是一件事。
So if we say, is cannabis addictive in kind of a normal lay speak, I would say yes, it is addictive.
因此，如果我们用正常的外行话说，大麻是否会让人上瘾，我会说是的，它会让人上瘾。
What does that look like?
那看起来像什么？
How does that relate to other substances of abuse?
这与其他滥用药物有何关系？
Certainly, the outcomes associated with it are going to be slightly different than something like opiates or alcohol because that's a totally different beast because you have fatality potential.
当然，与之相关的结果将与阿片类药物或酒精等药物略有不同，因为那是一种完全不同的野兽，因为你有致命的潜力。
There's a whole bunch of other health consequences.
还有一大堆其他健康后果。
But if we look at how we would define a use disorder, the criteria for someone hitting cannabis use disorder is really no different than how someone would hit alcohol use disorder or opiate use disorder in the sense that it can consume their life, it can shift the way that they behave.
但如果我们看看如何定义使用障碍，就会发现大麻使用障碍的标准实际上与酒精使用障碍或鸦片使用障碍的标准没有什么不同，因为它可以消耗他们的生命，它可以改变他们的行为方式。
They can put themselves in risky positions to get access to a drug.
他们可能会将自己置于危险境地以获得药物。
It can consume their time and their energy to have it.
拥有它会消耗他们的时间和精力。
Like you said, if they don't have access to it, it can trigger ...
就像你说的，如果他们无法访问它，它可能会触发......
an assembly of behaviors that looks like irritability, anger, frustration, things like that.
一系列看起来像烦躁、愤怒、沮丧等行为的集合。
So, the numbers in terms of the conversion rate of use to developing use disorder, I would say, are not entirely clear.
因此，我想说，从使用到发展使用障碍的转化率方面的数字并不完全清楚。
The old numbers that used to get tossed around were 9 to 11% of people that would start initiating cannabis use would probably transition to develop use disorder.
过去人们常说的数字是，在开始吸食大麻的人中，有 9% 至 11% 可能会发展为使用障碍。
The more modern numbers, I would say, if we're looking at people who are already using weekly, we're talking probably closer to 30%.
我想说的是，如果我们观察已经每周使用的人，我们所说的更现代的数字可能接近 30%。
Andrew Huberman:
安德鲁·休伯曼：
30%.
30%。
Dr. Matthew Hill:
马修·希尔博士：
So it's a much higher-- When you're using that frequently, then the rates of people who would qualify as having cannabis use disorder probably go higher.
因此，当您经常使用大麻时，患有大麻使用障碍的人的比例可能会更高。
Andrew Huberman:
安德鲁·休伯曼：
So I just want to make sure I'm understanding clearly.
所以我只是想确保我理解清楚。
For people that use cannabis weekly, the propensity for developing cannabis use disorder is on the order of about 30%?
对于每周吸食大麻的人来说，患大麻使用障碍的可能性约为 30%？
Dr. Matthew Hill:
马修·希尔博士：
Yeah, I'd say in that neighborhood, they would probably qualify as meeting criteria for a cannabis use disorder.
是的，我想说在那个社区，他们可能符合大麻使用障碍的标准。
Andrew Huberman:
安德鲁·休伯曼：
Because weekly doesn't seem like that often.
因为每周一次似乎并不常见。
Dr. Matthew Hill:
马修·希尔博士：
No. It depends, again, on how you vary this.
不。这又取决于你如何改变这一点。
I've had a lot of conversations with the public, and I think depending on someone's experience in their own or in their own inner circle's life with cannabis, the way they would view it is very differently, because I think a lot of people, again, regardless of anyone's opinion of alcohol, if someone told you they had a glass of wine with dinner every night, I don't think people would say you have an alcohol use disorder.
我与公众进行了很多对话，我认为，根据某人在自己或自己的核心圈子中对大麻的生活经历，他们对大麻的看法是非常不同的，因为我认为很多人，无论任何人对酒精的看法如何，如果有人告诉你他们每晚晚餐时喝一杯酒，我不认为人们会说你患有酒精使用障碍。
Andrew Huberman:
安德鲁·休伯曼：
No.
不。
Dr. Matthew Hill:
马修·希尔博士：
I think that's not uncommon.
我认为这并不罕见。
Andrew Huberman:
安德鲁·休伯曼：
No, I don't think they would.
不，我认为他们不会。
Dr. Matthew Hill:
马修·希尔博士：
Similarly, if someone had a brandy at the end of the night, or a nightcap to go to bed, and they did it on a nightly basis, I don't think anyone would say that they have a use disorder.
同样，如果有人在晚上结束时喝了一杯白兰地，或者睡前喝了一杯睡前饮料，并且他们每晚都这样做，我认为没有人会说他们有使用障碍。
And I think with cannabis, there are a lot of people that fall into that bracket, that would use it even daily, but relatively infrequently and as an end of the day thing.
我认为对于大麻，有很多人属于这一类，他们甚至每天都会使用它，但相对不频繁，并且作为一天结束时的事情。
I think some of them certainly would fall under the criteria of cannabis use disorder, because if you start looking and say, well, if you travel to Egypt, are you going to go put yourself at risk of going to jail to get access to cannabis because you can't function without it?
我认为其中一些肯定会符合大麻使用障碍的标准，因为如果你开始寻找并说，好吧，如果你去埃及旅行，你是否会冒着入狱的风险来获得大麻，因为没有大麻你就无法工作？
If you do, then yeah, you've got cannabis use disorder.
如果你这样做，那么是的，你患有大麻使用障碍。
Are you going to burn relationships?
你会毁掉人际关系吗？
Are you going to start failing at meeting responsibilities or getting things done on time because you're preoccupied with cannabis?
您是否会因为沉迷于大麻而开始无法履行职责或按时完成工作？
Yes, you're going to hit the criteria for cannabis use disorder.
是的，您将达到大麻使用障碍的标准。
If it's someone who's just intermittently using it, the same way that a lot of people casually use alcohol, I would say a lot of them probably wouldn't hit criteria.
如果有人只是间歇性地使用它，就像很多人随意饮酒一样，我想说他们中的很多人可能不会达到标准。
But I think to someone who has never had cannabis in their inner circle or in their life, they look at it like a drug like cocaine, whereas they're like, "Wow, if you were using cocaine on a daily basis, we'd be super concerned about you." Mm-hmm.
但我认为，对于那些在他们的核心圈子或生活中从未吸过大麻的人来说，他们将其视为可卡因之类的药物，而他们会说，“哇，如果你每天都使用可卡因，我们会非常担心你。”嗯嗯。
It's just as you go, cannabis is in this really weird transitionary period, I would say, of going from illicit to not, just because of the changes in the legal regulatory framework.
就像你所说的那样，我想说，大麻正处于这个非常奇怪的过渡时期，从非法到非法，只是因为法律监管框架的变化。
In Canada now, we're five and a half years into legalization, so in many ways, I would say the transition has happened where a lot of people view cannabis very similarly to alcohol, whereas you go to some states and the perspective is still very different.
现在在加拿大，我们的合法化已经五年半了，所以在很多方面，我想说，这种转变已经发生，很多人认为大麻与酒精非常相似，而你去一些州，观点仍然非常不同。
And certainly, if you're still in one of the states where there's no legal access, people still look at cannabis the same way they look at a lot of other illicit drugs like cocaine or amphetamines or things.
当然，如果你仍然处于没有合法渠道的州之一，人们仍然会像看待可卡因或安非他明等许多其他非法药物一样看待大麻。
And I think-
我认为——
Andrew Huberman:
安德鲁·休伯曼：
That's interesting.
这很有趣。
I was under the impression this had really changed over the last five, 10 years.
我的印象是，在过去的五年、十年里，情况确实发生了变化。
Growing up, I think there are still people in jail now-
长大后，我认为现在仍然有人在监狱里-
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
because of possession and sale of cannabis.
因为拥有和出售大麻。
And then of course, there are stores not far from here where people are selling cannabis.
当然，离这里不远的地方也有一些商店，人们在卖大麻。
Dr. Matthew Hill:
马修·希尔博士：
Ironic, yeah.
讽刺的是，是的。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
Dr. Matthew Hill:
马修·希尔博士：
Sadly.
可悲的是。
Obviously, a big push for legalization is not endorsement of the safety of cannabis.
显然，大力推动合法化并不是对大麻安全性的认可。
It's more the harms associated with prohibition outweigh the harms associated with legalization.
与禁止相关的危害比与合法化相关的危害更重要。
I think that's generally the public health perspective.
我认为这通常是公共卫生的观点。
That's certainly what motivated it in Canada.
这当然是加拿大的动机。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
And there was some attempts, let's say, at restorative justice in terms of removing criminal records and things.
比如说，在消除犯罪记录等方面进行了一些恢复性司法的尝试。
May not have been entirely as successful as people had hoped it would be, but it certainly has changed things.
也许并不完全像人们希望的那样成功，但它确实改变了一切。
We can look at our federal data and see that arrest rates related to cannabis are obviously very low compared to what they were.
我们可以查看联邦数据，发现与大麻相关的逮捕率与原来相比显然非常低。
That obviously becomes very important because there are clearly minoritized communities, they get hit more with this than other communities.
这显然变得非常重要，因为显然存在少数群体，他们比其他社区受到的打击更大。
And so the perpetual disenfranchisement that happens with a prohibition model in communities that are already suffering from various other things that affect them, just potentiates all that.
因此，在已经遭受各种影响他们的其他事情的社区中，禁止模式所发生的永久剥夺公民权只会加剧这一切。
So-
所以——
Andrew Huberman:
安德鲁·休伯曼：
Got it
明白了
Dr. Matthew Hill:
马修·希尔博士：
...
...
I can understand the legal framework behind why there would be a move to a legalization state over a prohibition state.
我可以理解为什么会从禁止状态转向合法化状态背后的法律框架。
Which again, a lot of people confuse legality with safety, which is a weird-- Alcohol is the perfect example of this.
同样，很多人将合法性与安全性混为一谈，这很奇怪——酒精就是一个很好的例子。
You look at the scale of harms on a public health level, alcohol stacks at the top.
从公共健康层面的危害程度来看，酒精排在首位。
Across the board, in terms of harms to the individual, harms to society, it's a lot.
总的来说，对个人的危害，对社会的危害，都很多。
Cannabis has harms, there's no question on that.
大麻有危害，这是毫无疑问的。
It just would fall lower than alcohol.
它只会比酒精含量低。
But the way that people view it, a lot of people are like, alcohol is legal, therefore it's safe and it's not something to judge people on.
但人们的看法是，很多人都认为，酒精是合法的，因此它是安全的，不能用来评判人们。
Cannabis, at least historically, was illegal and in some states still is.
大麻至少在历史上是非法的，并且在某些州仍然是非法的。
So people view it very differently, and I think it's an interesting thing, because I feel like, despite the fact that some people hate the government and hate the way that it regulates their life, there's this weird passive belief that if the government dictates something is legal, that means it's safe.
所以人们的看法非常不同，我认为这是一件有趣的事情，因为我觉得，尽管有些人讨厌政府并讨厌它规范他们生活的方式，但有一种奇怪的被动信念，即如果政府规定某件事是合法的，那就意味着它是安全的。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Is the legalization of cannabis leading to more cannabis users or fewer, and/or incidents of people going into the emergency room suffering from cannabis-induced psychosis, something that I hope we can also talk about.
大麻合法化是否会导致更多或更少的大麻使用者，和/或人们因大麻引起的精神病而进入急诊室的事件，我希望我们也可以讨论这一点。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
So it depends on how you break this down.
所以这取决于你如何分解它。
So what we've seen in Canada is, I would say there's demographic differences.
所以我们在加拿大看到的是，我想说存在人口差异。
Proportionately, when we look at the biggest change in use, it's actually elderly communities.
按比例来说，当我们看使用变化最大的时候，其实是老年社区。
It's like 55 plus.
好像是55+。
Especially women over 55 tend to be the-
尤其是 55 岁以上的女性往往是——
Andrew Huberman:
安德鲁·休伯曼：
More cannabis use.
更多使用大麻。
Dr. Matthew Hill:
马修·希尔博士：
More cannabis use.
更多使用大麻。
Now, granted, their baseline was quite low pre-legalization, so if you look at a fold change, it looks like a very dramatic ...
现在，当然，他们的基线在合法化前相当低，所以如果你看一下倍数变化，它看起来非常戏剧性......
increase.
增加。
Raw numbers, it's probably not that high, but it was one to 2% or something before, and now it's gone up to 8% or something.
原始数字，可能没有那么高，但以前是一到2%左右，现在已经上升到8%左右了。
So it's a fourfold increase kind of thing.
所以这是四倍的增长。
So we do see the magnitude of that seems to be the biggest in terms of where the use has come from.
因此，我们确实看到，就使用来源而言，其规模似乎是最大的。
Definitely the young adult population, like 20, 24, that group has definitely seen increased use as well.
当然，年轻人，比如 20 岁、24 岁的年轻人，这一群体的使用也肯定有所增加。
Andrew Huberman:
安德鲁·休伯曼：
Does it split male, female?
会分男、女吗？
Dr. Matthew Hill:
马修·希尔博士：
Historically, cannabis tended to be more male-biased.
从历史上看，大麻往往更偏向男性。
I'd say the gender separation there has narrowed quite a bit, where you do see a lot more females use than historically had.
我想说，那里的性别差距已经缩小了很多，你确实看到女性使用的人数比历史上多得多。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
There is a little bit of difference.
有一点区别。
Females tend to prefer edibles over males.
女性比男性更喜欢食物。
Andrew Huberman:
安德鲁·休伯曼：
Mm.
嗯。
Dr. Matthew Hill:
马修·希尔博士：
So, males tend to like inhalation over females.
因此，男性比女性更喜欢吸入。
So, roots of administration vary a little bit based on who someone is, but yeah.
因此，管理的根源因人而异，但是是的。
Interestingly, we don't have a lot of actual indication that teenagers have used more.
有趣的是，我们没有太多实际迹象表明青少年使用了更多。
So you look at 14 to 18-year-olds, now granted, our baseline going in was pretty high, as is down here in the States.
所以你看看 14 到 18 岁的人，现在我们承认，我们的基线相当高，就像美国的情况一样。
Canada and the States both hover, you look at grade 12ers, and it's somewhere between 35% and 40% of them have used cannabis.
加拿大和美国都在徘徊，你看看 12 年级的学生，其中 35% 到 40% 的人吸食过大麻。
Now, you even have some that are probably around 5% are probably almost daily users.
现在，甚至有 5% 左右的人几乎是日常用户。
So, you do have a pretty high baseline to begin with in that group, but that has remained relatively unchanged.
因此，在该组中一开始确实有相当高的基线，但相对保持不变。
If anything, some of the states, when they legalized, saw slight dips in teenage use of cannabis.
如果说有什么不同的话，那就是一些州在大麻合法化后，青少年吸食大麻的人数略有下降。
So, I think that's obviously an important demographic to have tracked.
所以，我认为这显然是一个需要追踪的重要人群。
This was one of the concerns with legalization was you'd increase access.
这是合法化的担忧之一是你会增加访问权限。
Teenagers would get it from their parents and whatnot, or had just other siblings and stuff, and so you get this big boost in consumption.
青少年会从他们的父母那里得到它，或者有其他兄弟姐妹之类的东西，所以你的消费得到了巨大的推动。
But we don't seem to see that in terms of raw numbers of teenagers who are using cannabis.
但我们似乎并没有看到使用大麻的青少年的原始数量。
So that's good.
所以这样很好。
ER visits.
急诊室就诊。
So we did an interesting roll out in Canada.
所以我们在加拿大做了一次有趣的推广。
We legalized flower for a year before edibles came online.
在食品上线之前，我们已经将花卉合法化了一年。
So we have a before and after.
所以我们有之前和之后。
Once edibles became available, there was a notable increase in unintentional pediatric consumption that resulted in ER visits because a lot of these look like gummies and candies.
一旦食品变得可用，儿童无意识消费就会显着增加，导致急诊室就诊，因为其中很多看起来像软糖和糖果。
People are buying them, not storing them properly.
人们只是购买它们，而不是妥善储存它们。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
Kids would find them and eat them and become very intoxicated.
孩子们会找到它们并吃掉它们，然后变得非常陶醉。
Andrew Huberman:
安德鲁·休伯曼：
I want to make mention of something along those lines.
我想提一下类似的事情。
I actually know somebody whose child accidentally ate THC-containing gummies.
事实上，我认识一个人，他的孩子不小心吃了含有四氢大麻酚的软糖。
Fortunately, the child was fine.
幸运的是，孩子没事。
But there are actually pretty serious ramifications for this.
但这实际上会产生相当严重的后果。
The parents actually are quite susceptible to legal action-
父母实际上很容易受到法律诉讼——
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
if this happens.
如果发生这种情况。
Right?
正确的？
So this is something to really keep in mind.
所以这是需要真正记住的事情。
There are a million other health-related reasons why this is probably-
还有一百万个其他与健康相关的原因，这可能是——
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
I don't know if that's true in Canada the same way.
我不知道加拿大是否也是如此。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
Dr. Matthew Hill:
马修·希尔博士：
But in the States, yeah.
但在美国，是的。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
If your kid gets into a stash of THC-containing gummies and ends up in the emergency room, there will also be, most likely, there'll be a police visit to that emergency room also.
如果您的孩子吃了一堆含有 THC 的软糖并最终被送进了急诊室，那么很可能警察也会前往该急诊室。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And it doesn't bode well for the parents.
这对父母来说不是一个好兆头。
Dr. Matthew Hill:
马修·希尔博士：
So this is-
所以这是——
Andrew Huberman:
安德鲁·休伯曼：
It's a very serious issue.
这是一个非常严重的问题。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And again, this was highlighted to me by someone that I know who didn't anticipate any of this, but kids are good at finding candy.
再一次，我认识的一个人向我强调了这一点，他没有预料到这一切，但孩子们很擅长寻找糖果。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And if that candy contains THC and they end up in the emergency room, serious issues.
如果糖果中含有四氢大麻酚，它们最终会被送进急诊室，那就是严重的问题了。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Nonetheless, if your kid is acting strange because you think they ingested THC-containing anything, take them to the emergency room anyway.
尽管如此，如果你的孩子表现得很奇怪，因为你认为他们摄入了含有 THC 的任何东西，无论如何都要带他们去急诊室。
Dr. Matthew Hill:
马修·希尔博士：
Well, so this was one of the things that also was influenced by legalization is in Canada, some of the increase in the ER visits was because of the shift in legalization and the change in policy.
嗯，所以这是加拿大也受到合法化影响的事情之一，急诊室就诊次数的增加部分是由于合法化的转变和政策的变化。
And so, if your kid ends up drunk underage, it's not the same ramifications as if your kid used an illegal substance underage.
因此，如果您的孩子最终在未成年时喝醉，其后果与您的孩子在未成年时使用非法药物的后果不同。
And so once cannabis was legal, people were more likely to actually go into the ER because the consequences were different.
因此，一旦大麻合法化，人们就更有可能真正进入急诊室，因为后果是不同的。
Andrew Huberman:
安德鲁·休伯曼：
I see.
我明白了。
Dr. Matthew Hill:
马修·希尔博士：
And so sure, some of this is availability, and some of it is just like, "Okay, I'm not as concerned now about something happening because I've taken my kid in.
可以肯定的是，其中一些是可用性，还有一些就像，“好吧，我现在不那么担心发生的事情，因为我已经带了我的孩子进来。
I'm not going to have my kid taken away from me," or whatnot.
我不会让我的孩子从我身边被夺走，”或者诸如此类的事情。
So, both those factors I think have contributed to it, but we definitely see the majority, at least, of kids ending up in the ER is almost all based on edibles.
所以，我认为这两个因素都造成了这种情况，但我们肯定看到，至少，大多数最终进入急诊室的孩子几乎都是以食物为基础的。
I can't imagine a situation where that would happen from inhalation.
我无法想象吸入会发生这种情况。
It would be very rare if it would.
如果有的话，那就非常罕见了。
It's almost always edibles because kids find them.
它几乎总是可以食用的，因为孩子们会找到它们。
Andrew Huberman:
安德鲁·休伯曼：
So as long as we're talking about edibles, is there any fundamental difference between the dose regulation that you talked about earlier of-
因此，只要我们谈论的是食品，您之前谈到的剂量调节之间有什么根本区别吗？
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
inhalants versus edibles?
吸入剂与食用剂？
Meaning earlier you said that even if it's high-THC containing cannabis, people will self-regulate to achieve approximately the same blood concentrations.
意思是说，您之前说过，即使大麻含有高 THC，人们也会自我调节以达到大致相同的血液浓度。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
But with edibles, I imagine you eat half a cookie, a quarter of a cookie-
但是对于食物来说，我想你会吃半块饼干，四分之一块饼干——
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
and you can end up in a vastly different place than you expected.
你最终可能会到达一个与你预期截然不同的地方。
Dr. Matthew Hill:
马修·希尔博士：
So edibles, so this throws a wrench in the whole system, and I'll say this in the context of blood levels, and then what that means from a regulatory capacity as well because of the impact this has.
因此，这是可食用的，这会给整个系统带来麻烦，我会在血液水平的背景下说这一点，然后从监管能力的角度来说这意味着什么，因为它所产生的影响。
So edibles are very low doses, for the most part.
因此，大多数情况下，食品的剂量非常低。
In Canada at least, you cannot buy a pack of edibles, and I think this law might be changing, at least when they first brought it in.
至少在加拿大，你不能购买一包食品，我认为这项法律可能会改变，至少在他们第一次引入它时是这样。
No pack could have more than 10 milligrams of THC in it.
任何包装中的 THC 含量不得超过 10 毫克。
So that either meant one 10mg gummy or two five mg gummies, or four 2.5mg gummies.
因此，这意味着要么一颗 10 毫克软糖，要么两颗 5 毫克软糖，要么四颗 2.5 毫克软糖。
You get it.
你明白了。
So you couldn't, in one package, have more than 10 milligrams of THC.
因此，一包中的 THC 含量不能超过 10 毫克。
Now, for people who are, I would say, relatively naive to cannabis or THC, even people who might use it intermittently, most people will feel five milligrams.
现在，我想说，对于那些对大麻或 THC 相对幼稚的人来说，即使是那些可能间歇性使用它的人，大多数人都会感觉到 5 毫克。
They'll feel some form of intoxication.
他们会感到某种形式的陶醉。
Some will even feel it at 2.5 mgs.
有些人甚至在 2.5 毫克时就能感觉到。
Most people will feel it at five.
大多数人五点钟就会有这种感觉。
Virtually everyone will feel it at 10.
几乎每个人在 10 点都会有这种感觉。
Now, if you look at the blood levels these produce, we're now talking blood levels of two to five nanograms per mil.
现在，如果你观察这些物质产生的血液浓度，我们现在谈论的血液浓度为每密耳 2 至 5 纳克。
So ...
所以...
folds lower than what you get from inhalation.
折叠程度低于吸入的程度。
Andrew Huberman:
安德鲁·休伯曼：
Right.
对。
Before you said 100.
在你说100之前。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
So this is dramatically lower.
所以这个数字要低得多。
And so, also the time course of this is fundamentally different.
因此，其时间进程也根本不同。
So in oral consumption, you're looking at a minimum of 30 to 45 minutes for onset of intoxication, for some people, up to 90 minutes after they've eaten.
因此，在口服食用时，至少要在 30 到 45 分钟内才会出现中毒症状，对于某些人来说，可能会在进食后长达 90 分钟内出现中毒症状。
Now, this is also the reason why the majority of adverse events that happen with cannabis happen with edibles, because people don't understand this, and so they eat a cookie or a gummy, they wait half an hour, like, "I'm not feeling anything.
现在，这也是大麻发生的大多数不良事件发生在食用食品上的原因，因为人们不理解这一点，所以他们吃了一块饼干或软糖，他们等了半个小时，就像，“我没有任何感觉。
I clearly didn't take enough." And then they'll double their dose, and then 15 minutes later it starts hitting them, and then once it fully kicks in, it's just like a steamroller.
我显然没有吃够。”然后他们会将剂量加倍，然后 15 分钟后它开始击中他们，然后一旦完全发挥作用，它就像压路机一样。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
I've heard of this happening.
我听说过这样的事情发生。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
There was that New York, I think it was Maureen Dowd or someone, went down to Colorado and she ate an insane amount of THC in a chocolate bar, something like 50 or 100 milligrams, and spent the weekend on the floor of a hotel room being like, "This was the most aversive experience.
纽约，我想是 Maureen Dowd 之类的人，去了科罗拉多州，她在巧克力棒中吃了大量的 THC，大约 50 或 100 毫克，然后在酒店房间的地板上度过了周末，她说：“这是最令人厌恶的经历。
Why would anyone do this?" And again, I think people just don't understand the dosing around this.
为什么有人会这样做？”再说一次，我认为人们只是不理解这方面的剂量。
And so this is one of the things we're trying to do in Canada, and that was create this idea of standardized dosing units so that people have an-- like we with alcohol, we always say one beer is the equivalent to one glass of wine versus a shot of tequila or something, so that there's some comparator that people understand how many drinks are, say two drinks you do, you're going to hit legal limit kind of thing.
所以这是我们在加拿大试图做的事情之一，那就是创造标准化剂量单位的想法，这样人们就可以像酒精一样，我们总是说一杯啤酒相当于一杯葡萄酒与一杯龙舌兰酒之类的东西，这样就有了一些比较器，人们可以了解有多少饮料，比如说你喝了两杯，你就会达到法律限制之类的事情。
Andrew Huberman:
安德鲁·休伯曼：
Yeah, it seems very important.
是啊，看来非常重要。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
And so this is very difficult to do with cannabis because the dosing with oral consumption is just a different ballgame than it is with inhalation.
因此，这对于大麻来说是非常困难的，因为口服给药与吸入给药是不同的。
But what happens with oral consumption is it very slowly leaks out of the GI tract.
但口服摄入后会发生的情况是，它会非常缓慢地从胃肠道中泄漏出来。
And it also goes through first pass metabolism in the liver.
它还在肝脏中进行首过代谢。
And what happens there is you get a metabolite called 11-hydroxyTHC, which seems to be a bit more potent than THC is in terms of its ability to activate the receptor.
在那里你会得到一种叫做 11-羟基四氢大麻酚 (11-HydroxyTHC) 的代谢物，就其激活受体的能力而言，它似乎比四氢大麻酚 (THC) 更有效。
So, and its efficacy, at least, at driving a response through CB1 receptors seems to be higher than what you would get with just the parent molecule of THC itself.
因此，它的功效至少在通过 CB1 受体驱动反应方面似乎比仅使用 THC 本身的母体分子所得到的要高。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
And it seems to accumulate a lot more as well.
而且似乎还积累了很多。
So at any given time, you've got THC kind of leaking out of the gut, going through the liver, making 11-hydroxy, and it progressively accumulates in the brain, and that's one of the reasons why it takes 45 to 90 minutes to kick in, but then the high itself also lasts six hours, four to six, sometimes eight, depending on the person, what they've eaten.
因此，在任何特定时间，THC 都会从肠道中漏出，通过肝脏，形成 11-羟基，并逐渐在大脑中积累，这就是为什么需要 45 到 90 分钟才能发挥作用的原因之一，但随后兴奋本身也会持续 6 小时，4 到 6 小时，有时是 8 小时，具体取决于个人和他们吃的东西。
Versus inhalation is just this spike, so you get this very rapid, because it goes right through the lungs into the blood, goes into the brain, but it also clears out.
与吸入只是这种尖峰，所以你会非常快，因为它直接通过肺部进入血液，进入大脑，但它也会被清除。
And so, yeah, people will start feeling intoxicated two to five minutes.
所以，是的，人们会开始感到陶醉两到五分钟。
Their peak high is 15 to 30 minutes maybe from consumption, and then they'll start to come back down.
它们的峰值可能会在消耗后 15 到 30 分钟内达到，然后就会开始回落。
And you will still see some indications of intoxication that can go on for three to four hours.
您仍然会看到一些可能持续三到四个小时的中毒迹象。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
But the bulk of the intoxication from inhalation is done by two hours-
但大部分吸入中毒是在两个小时内完成的——
Andrew Huberman:
安德鲁·休伯曼：
Got it
明白了
Dr. Matthew Hill:
马修·希尔博士：
...
...
for the most part.
大多数情况下。
Andrew Huberman:
安德鲁·休伯曼：
As long as we're on the topic of time course, based on what I was able to find, I believed, and tell me if I was wrong, that cannabis can stay in one's system for as long as 80 days.
只要我们讨论时间进程的话题，根据我所能找到的，我相信，并告诉我我是否错了，大麻可以在一个人的系统中停留长达 80 天。
The reason I brought this up-
我提出这个问题的原因是——
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
previously was there are a number of people who have used cannabis, are going to take a drug test, and want to know how fast it can clear from their system.
以前有许多使用过大麻的人将要进行药物测试，并想知道它能以多快的速度从他们的系统中清除。
But based on conversations we had offline, sounds like that 80 days might be a bit too long.
但根据我们线下的对话，听起来 80 天可能有点太长了。
Dr. Matthew Hill:
马修·希尔博士：
You could still fail a drug test at 80 days.
80 天后您仍有可能未通过药检。
I would say, I feel like, I think the way it was worded more it was like that you made it sound like that was the standard.
我想说，我觉得，我认为它的措辞方式更像是你让它听起来像是标准。
Andrew Huberman:
安德鲁·休伯曼：
Got it.
明白了。
Dr. Matthew Hill:
马修·希尔博士：
I wouldn't say that was the standard at all.
我根本不会说那是标准。
Andrew Huberman:
安德鲁·休伯曼：
Okay.
好的。
Dr. Matthew Hill:
马修·希尔博士：
I would say for the majority of people, 30 days probably after that-
我想说，对于大多数人来说，可能是 30 天之后——
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm
嗯嗯
Dr. Matthew Hill:
马修·希尔博士：
...
...
they would not pass, or they would be able to pass a drug test.
他们不会通过，或者他们能够通过药检。
But that being-
但那是——
Andrew Huberman:
安德鲁·休伯曼：
So abstinence for 30 days.
于是禁欲30天。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
After abstaining for 30 days.
戒酒30天后。
And it's going to be highly variable depending on how much you consume.
而且根据您的消费量，它会存在很大差异。
If you're talking about someone who's used it once, I don't imagine it would be in your system that long.
如果你说的是曾经使用过它的人，我不认为它会在你的系统中存在那么久。
That'd be surprising.
那会很令人惊讶。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
The thing is, THC is a lipophilic molecule.
事实是，THC 是一种亲脂性分子。
Andrew Huberman:
安德鲁·休伯曼：
It's fat soluble.
它是脂溶性的。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
So it's fat soluble.
所以它是脂溶性的。
It likes to store.
它喜欢储存。
It doesn't like the blood.
它不喜欢血。
The blood is aqueous and watery.
血液是水性的、水样的。
It likes fat.
它喜欢脂肪。
So it goes into the brain, it goes into the fat, and it kind of resides there.
所以它进入大脑，进入脂肪，并且驻留在那里。
And it can essentially slowly leak back.
而且它基本上可以慢慢地泄漏回来。
As THC concentrations in the blood would reduce, THC that's in the fat will start leaking back into the blood still.
随着血液中四氢大麻酚的浓度降低，脂肪中的四氢大麻酚将开始渗漏回血液中。
So detectably, you will still have THC for quite some time.
因此，可以检测到，您在相当长的一段时间内仍会含有 THC。
Some of this, again, it's going to be dependent on how much cannabis someone's used, how much THC they've consumed, how long it's been in their system for.
其中一些，再次，这将取决于某人使用了多少大麻，他们消耗了多少 THC，以及它在他们的系统中存在了多长时间。
I would've thought this was going to be somewhat reflective of people's body fat content, although talking to colleagues who do this, they say not always.
我本以为这会在某种程度上反映人们的身体脂肪含量，尽管与这样做的同事交谈，他们说并不总是如此。
But we do know certain things like exercise, for example.
但我们确实知道某些事情，例如锻炼。
Anything that's going to trigger adrenaline, because adrenaline is lipolytic, so adrenaline causes fat to metabolize and release stuff that's inside it.
任何会触发肾上腺素的东西，因为肾上腺素具有脂解作用，所以肾上腺素会导致脂肪代谢并释放其中的物质。
So there are plenty of cases I've heard from people where they were testing themselves and were negative and then went for a run or went to the gym, and then tested positive.
因此，我从人们那里听说过很多案例，他们进行了自我检测，结果呈阴性，然后去跑步或去健身房，然后检测结果呈阳性。
Andrew Huberman:
安德鲁·休伯曼：
Or lost weight.
或者减肥了。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Or they've lost weight.
或者他们减肥了。
And anything that's going to cause the lipolysis to occur so that it releases that THC, you can certainly all of a sudden test positive again when someone had tested negative previously, just because of the fact that there still is some in the fat.
任何会导致脂肪分解发生从而释放 THC 的东西，当有人之前测试呈阴性时，你肯定会突然再次测试呈阳性，只是因为脂肪中仍然有一些 THC。
And so this is where something like, and this is what I mean by standardization of regulatory issues become very complicated, was I remember right when legalization happened in Canada, all these kind of chemists were talking to me about they're going to create a breathalyzer for cannabis because this way they'll be able to do roadside detection the same way they could do with alcohol.
因此，这就是我所说的监管问题标准化变得非常复杂的地方，我记得在加拿大合法化时，所有这些化学家都跟我说他们将制造大麻呼气分析仪，因为这样他们就能够像处理酒精一样进行路边检测。
And I kept trying to say to them, I'm like, "The rate-limiting step here is not the science of detection thresholds.
我一直试图对他们说，“这里的速率限制步骤不是检测阈值的科学。
It's the biology of how the body processes cannabis."
这是身体如何处理大麻的生物学原理。”
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
And you're never going to get a test that works because you can take someone who has eaten an edible and is profoundly intoxicated, and they will Have possibly under five nanograms per ml of THC in their blood.
而且你永远不会得到有效的测试，因为你可以拿一个吃过食物并深度中毒的人，他们的血液中可能含有每毫升五纳克的四氢大麻酚。
Andrew Huberman:
安德鲁·休伯曼：
But you were talking about this metabolite that can come from the edibles that doesn't come from inhalants, that can have a much more potent effect.
但你谈论的是这种代谢物，它可以来自非吸入剂的食物，它可以产生更有效的效果。
Dr. Matthew Hill:
马修·希尔博士：
You get a bit of it from inhalant, but not nearly as much as you get from edibles.
您可以从吸入中获得一点，但不如从食物中获得的那么多。
But that's-
但那是——
Andrew Huberman:
安德鲁·休伯曼：
So it's sort of a different situation altogether.
所以这是完全不同的情况。
Dr. Matthew Hill:
马修·希尔博士：
It is, but it's also the timeline.
是的，但这也是时间表。
Because of the fact that with inhalation, it's like a bolus that hits you at once, so you get a high blood level.
因为吸入时，它就像一团药丸立刻击中你，所以你的血液浓度很高。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
With edibles, it's like the time course.
对于食物来说，这就像时间进程。
So, it's going to be like five nanograms per ml, let's say, but it would be like that for a long time.
所以，可以说，它会是每毫升五纳克，但会在很长一段时间内保持这种状态。
Whereas the 100 nanogram per ml from smoking is, like, for 20 minutes, and then it starts dropping.
而吸烟产生的每毫升 100 纳克的浓度大约持续 20 分钟，然后开始下降。
But the problem is with the way that you detect it, is you can take someone who's a chronic cannabis user and is completely sober and hasn't consumed in a day or two, and their basal levels of THC in their blood may be higher than someone who's profoundly intoxicated by an edible.
但问题在于你检测它的方式，你可以拿一个长期吸食大麻、完全清醒、一两天没有吸食大麻的人，他们血液中四氢大麻酚的基础水平可能比那些因食物而深度中毒的人要高。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
Just by the sheer nature of the fact that it would reside in their fat tissue or their brain, it would leak back into the blood.
就其本质而言，它会驻留在他们的脂肪组织或大脑中，因此它会渗回血液中。
And so you have this issue where, let's say your cutoff was five nanograms per ml, which is for some of the stuff detection thresholds would hover around that area.
所以你会遇到这个问题，假设你的截止值是每毫升五纳克，这是因为某些物质检测阈值会徘徊在该区域附近。
So you could have someone who's dead sober that tests positive and someone who's profoundly intoxicated who tests negative.
因此，可能会有一个完全清醒的人测试结果呈阳性，而另一个人喝醉了的时候测试结果呈阴性。
So it's like, what's the value in this?
那么这有什么价值呢？
Andrew Huberman:
安德鲁·休伯曼：
Right.
对。
Dr. Matthew Hill:
马修·希尔博士：
It's not telling us anything.
它没有告诉我们任何事情。
Andrew Huberman:
安德鲁·休伯曼：
Well, I guess it sounds like the drug tests either have to be revised or discarded, and it also sounds like if somebody is going to take a drug test for cannabis and they have used cannabis in any form in the previous 90 days, let's say, going for a run right before your test-
嗯，我想这听起来药物测试要么必须修改，要么被放弃，而且听起来如果有人要接受大麻药物测试，并且他们在过去 90 天内以任何形式使用过大麻，比如说，在测试前跑步 -
Dr. Matthew Hill:
马修·希尔博士：
Yeah, probably not a good idea
是的，可能不是一个好主意
Andrew Huberman:
安德鲁·休伯曼：
...
...
is going to liberate whatever THC resides in the fat stores.
将释放脂肪储存中的任何 THC。
Dr. Matthew Hill:
马修·希尔博士：
Potentially, yeah.
有可能，是的。
Andrew Huberman:
安德鲁·休伯曼：
Okay.
好的。
Dr. Matthew Hill:
马修·希尔博士：
So, it is complicated.
所以，情况很复杂。
Andrew Huberman:
安德鲁·休伯曼：
A lot of people are writing this down.
很多人都在写下这个。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Along the lines of what's known and not known, I'm curious what is known and not known about the effects of cannabis, THC in particular, on hormones.
沿着已知和未知的线索，我很好奇大麻（特别是四氢大麻酚）对激素的影响有哪些已知和未知。
I've seen studies that cite increases in testosterone from cannabis use.
我见过一些研究指出使用大麻会增加睾酮水平。
I've seen studies that cite increases in estrogen from cannabis use, and they argue for increased aromatization of testosterone into estrogen as the mechanism.
我见过一些研究引用大麻的使用会增加雌激素，他们认为增加睾酮芳香化为雌激素是其机制。
Dr. Matthew Hill:
马修·希尔博士：
Mm-hmm.
嗯嗯。
Andrew Huberman:
安德鲁·休伯曼：
I've also seen studies that say the exact opposite.
我也看到过一些研究，结果恰恰相反。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
So, is there any global takeaway message yet, or is it just highly variable, or it depends too much on dose and individual age, et cetera, that we just really can't say?
那么，是否有任何全球性的外卖信息，或者它只是高度可变，或者它过多地取决于剂量和个人年龄等等，而我们真的不能说？
Dr. Matthew Hill:
马修·希尔博士：
I would say there's nothing that's super clean cut.
我想说没有什么是超级干净的。
I know in the previous podcast you talked about a prolactin thing.
我知道在之前的播客中你谈到了催乳素的事情。
Andrew Huberman:
安德鲁·休伯曼：
Right.
对。
And this is where I think it's important that people understand that on this podcast, we cover science and studies, but we also pull from common experience that people want explained-
这就是我认为重要的是让人们理解，在这个播客中，我们涵盖科学和研究，但我们也从人们想要解释的共同经验中汲取经验——
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
if we can.
如果可以的话。
And one of the experiences that is talked about a lot in certain, let's just say online communities, is the experience of people who had no preexisting gynecomastia, male breast development-
在某些网上社区中，人们经常谈论的经历之一是那些没有预先存在男性乳房发育症、男性乳房发育的人的经历——
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
will smoke marijuana.
会吸大麻。
Do we call it marijuana these days?
现在我们称其为大麻吗？
Dr. Matthew Hill:
马修·希尔博士：
No. We'll go with cannabis.
不，我们会选择大麻。
Andrew Huberman:
安德鲁·休伯曼：
I got a lot of comments that said marijuana is an inappropriate term.
我收到很多评论说大麻是一个不恰当的术语。
Dr. Matthew Hill:
马修·希尔博士：
It is.
是的。
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Okay.
好的。
We'll go back to that.
我们会回到那个。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
That was new to me.
这对我来说是新的。
I didn't know.
我不知道。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
So forgive me if I-
所以请原谅我，如果我——
Dr. Matthew Hill:
马修·希尔博士：
No. I understand it, but yeah, a lot of people don't know that.
不，我明白，但是，是的，很多人不知道。
Andrew Huberman:
安德鲁·休伯曼：
Okay.
好的。
So will smoke cannabis and experience gynecomastia, or in females...
因此，吸食大麻会导致男性乳房发育症，或者女性......
So males and females both have breast tissue, but in males it's not hypertrophied.
因此，男性和女性都有乳腺组织，但男性的乳腺组织并不肥大。
But they'll smoke cannabis and get a gynecomastia, a growth of the male breast tissue, that's sometimes reversible, sometimes not, presumably through the aromatization of testosterone into estrogen, which then acts on the tissue, makes it grow.
但他们会吸大麻并患上男性乳房发育症，即男性乳房组织的生长，有时是可逆的，有时则不可逆，大概是通过将睾酮芳香化为雌激素，然后作用于组织，使其生长。
As well as reports of breast tissue tenderness after cannabis use in females.
以及女性使用大麻后乳房组织压痛的报告。
So, that was sort of the origin of that discussion around does cannabis impact aromatization of testosterone into estrogen?
那么，这就是围绕大麻是否影响睾酮芳香化为雌激素的讨论的起源？
And you can find a little bit of evidence for that, but you can also find evidence to the contrary in the scientific literature.
你可以找到一点证据来证明这一点，但你也可以在科学文献中找到相反的证据。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
So I'm just curious your thoughts on this.
所以我只是好奇你对此的想法。
Dr. Matthew Hill:
马修·希尔博士：
It's super mixed.
这是超级混合。
So you're talking about something like prolactin, for example.
例如，您谈论的是催乳素之类的东西。
That is another one that's obviously involved in this whole cascade stuff.
这是另一个显然与整个级联相关的问题。
Generally, I would say the bulk of the literature actually says that cannabis would suppress prolactin, not increase it.
一般来说，我想说的是，大部分文献实际上都说大麻会抑制催乳素，而不是增加它。
That's the majority of the literature that's out there.
这是现有的大部分文献。
Andrew Huberman:
安德鲁·休伯曼：
Interesting, because dopamine is one of the main ways that prolactin is suppressed.
有趣的是，因为多巴胺是抑制催乳素的主要方式之一。
Dr. Matthew Hill:
马修·希尔博士：
Turned off, yeah.
关掉了，是的。
Andrew Huberman:
安德鲁·休伯曼：
They're kind of in a seesaw.
他们有点像跷跷板。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
They work in somewhat seesaw fashion.
他们的工作方式有点跷跷板。
Dr. Matthew Hill:
马修·希尔博士：
And it probably, the rodent work, would suggest it's through dopamine that it's turning off prolactin, because you can reverse some of these effects by playing with dopamine signaling.
啮齿类动物的研究可能表明，它是通过多巴胺来关闭催乳素的，因为你可以通过多巴胺信号传导来逆转其中一些影响。
Andrew Huberman:
安德鲁·休伯曼：
Interesting.
有趣。
Dr. Matthew Hill:
马修·希尔博士：
So I don't doubt that's the mechanism.
所以我毫不怀疑这就是机制。
So typically, I would say more often, there's studies with inhalation and IV that have generally found reduced prolactin, and in chronic cannabis users, they find somewhat lower resting states of prolactin.
因此，我更常说的是，吸入和静脉注射的研究通常发现催乳素降低，而在长期吸食大麻的人中，他们发现催乳素的静息状态有所降低。
That's been found in one study that came out of Yale.
耶鲁大学的一项研究发现了这一点。
Andrew Huberman:
安德鲁·休伯曼：
Interesting.
有趣。
Dr. Matthew Hill:
马修·希尔博士：
Testosterone gets a little bit more complicated because there are a lot of studies that find, A, to begin with, cannabis users may have higher levels of testosterone just at rest.
睾酮变得有点复杂，因为有很多研究发现，首先，大麻使用者在休息时可能有更高水平的睾酮。
Now, whether that's a preexisting thing-
现在，这是否是一个预先存在的事情——
Andrew Huberman:
安德鲁·休伯曼：
Is there any reason to think that would be the case?
有什么理由认为情况会是这样吗？
Dr. Matthew Hill:
马修·希尔博士：
I don't know.
我不知道。
Yeah.
是的。
That being said, a lot of the stuff, now granted, this was mostly done in the '70s, and this is from my previous life because my undergrad and graduate supervisor, he was a neuroendocrinologist, focused much more on sex hormones and reproductive hormones.
话虽这么说，很多东西，现在理所当然，这主要是在 70 年代完成的，这是我以前的生活，因为我的本科生和研究生导师，他是一名神经内分泌学家，更多地关注性激素和生殖激素。
So we've written a few reviews, so I've done reviews on this area, and I know the literature somewhat.
所以我们写了一些评论，所以我也对这个领域做了评论，并且我对文献有所了解。
It's mixed, but generally, from the '70s studies, what they would often see is that if they would serially look at testosterone after someone consumed, they would have little dips.
情况好坏参半，但总的来说，从 70 年代的研究来看，他们经常看到的是，如果他们在某人食用后连续观察睾酮水平，他们的水平会略有下降。
That wasn't uncommon for them to find it.
对他们来说找到它并不罕见。
Not every study found it.
并非所有研究都发现了这一点。
That being said, the kind of range that testosterone stayed in was always the normative range.
话虽这么说，睾酮保持的范围始终是正常范围。
It was never that it went so low that someone would've classified as being hypogonadal or would lead to something like gynecomastia, at least from a testosterone deficiency side, in terms of the balance between testosterone and estradiol.
就睾酮和雌二醇之间的平衡而言，它从来没有低到有人被归类为性腺功能减退症或导致男性乳房发育症之类的情况，至少从睾酮缺乏的角度来看。
I don't know as much about the aromatization side of it.
我对它的芳香化方面不太了解。
Again, I'd say it's pretty mixed.
我再说一遍，情况很复杂。
I don't think the gynecomastia stuff is-- Certainly, people online might be talking about it, and there might be some other components to this.
我不认为男性乳房发育症是——当然，网上的人可能会谈论它，而且可能还有其他一些因素。
I've also heard, and again, this isn't science, this is just the same kind of stuff you see on random internet communities, people talking about, "Oh, well, it has plant estrogen," so maybe they're subbing in and having estrogenic effects.
我也听说过，这不是科学，这只是你在随机互联网社区上看到的同一类东西，人们谈论，“哦，好吧，它含有植物雌激素”，所以也许它们正在替代并具有雌激素作用。
I don't know how valid any of this is.
我不知道这有多有效。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
There are phytoestrogens in tons of different plants.
许多不同的植物中都含有植物雌激素。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
So I don't-
所以我不-
Andrew Huberman:
安德鲁·休伯曼：
The sort of attacks on soy and the attacks on-- This, I think, grew out of the soy versus meat communities-
对大豆的攻击以及对——我认为，这源于大豆与肉类社区——
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
and plant-based versus carnivore.
植物性食品与肉食性食品的比较。
This podcast has always been agnostic with respect to nutrition, and if we encourage anything, it's that people consume unprocessed and minimally processed foods as the bulk of their food intake.
这个播客在营养方面一直是不可知论的，如果我们鼓励什么的话，那就是人们食用未经加工和最低限度加工的食物作为其食物摄入的大部分。
There seems to be enough data on that.
这方面似乎有足够的数据。
But whether or not people choose to be vegan and-
但无论人们是否选择成为素食主义者——
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
eat a lot of plants or carnivore and eat just meat, we've essentially stepped out of that debate because, let's just say, it's as futile as about any other debate.
吃大量植物或肉食动物而只吃肉，我们基本上已经退出了这场辩论，因为，可以说，它和任何其他辩论一样徒劳。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
It's completely circular.
它是完全圆形的。
You end up right back in Twitter.
你最终会回到 Twitter。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
And I think that when it comes to something like this, I've not seen any compelling evidence for it.
我认为，当谈到这样的事情时，我还没有看到任何令人信服的证据。
I certainly wouldn't say that it's a typical side effect that men would experience, is developing breast tissue in response to cannabis.
我当然不会说这是男性会经历的典型副作用，即乳房组织因大麻而发育。
I feel like if that was the case, it would be very known in the scientific community as something that comes out.
我觉得如果是这样的话，它将会在科学界广为人知。
Andrew Huberman:
安德鲁·休伯曼：
So this seems to be something that purportedly occurs on a backdrop of elevated androgens, meaning in puberty, or a backdrop of some other form of androgen increase.
因此，这似乎是在雄激素升高的背景下发生的，也就是说在青春期，或者是在某种其他形式的雄激素增加的背景下发生的。
Dr. Matthew Hill:
马修·希尔博士：
Like someone who's on steroids or something.
就像服用类固醇之类的人一样。
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Yeah, but that's not the community I'm referring to.
是的，但这不是我指的社区。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Because transient gynecomastia during puberty is actually fairly common, because there's just so much androgen being produced-
因为青春期短暂的男性乳房发育实际上相当常见，因为产生了太多的雄激素——
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
in puberty that some gets aromatized and that the idea, I'm not stating this as fact, is that it may exacerbate that.
在青春期，有些人会变得芳香化，我并不是说这是事实，而是它可能会加剧这种情况。
In any case, it sounds like the takeaway from this is that there aren't a lot of conclusive studies about the effects of cannabis on testosterone or estrogen or aromatization in any direction.
无论如何，这听起来像是关于大麻对睾酮或雌激素或芳构化在任何方向上的影响的结论性研究。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
I'd say, yeah, enough studies to suggest that you might see transient drops in testosterone from cannabis, and it seems to be relatively short-lived.
我想说，是的，足够的研究表明你可能会看到大麻中睾丸激素的短暂下降，而且它似乎相对短暂。
But again, a lot of these studies also find that the basal testosterone is already high to begin with.
但同样，许多研究还发现基础睾酮一开始就已经很高了。
So you're staying in a normal dynamic range.
所以你保持在正常的动态范围内。
Andrew Huberman:
安德鲁·休伯曼：
There it is again.
又来了。
It's homeostatic.
这是稳态的。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Just like the endocannabinoids.
就像内源性大麻素一样。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
And that's the thing, testosterone fluctuates across the day-
事情就是这样，睾丸激素在一天中会波动——
Andrew Huberman:
安德鲁·休伯曼：
Sure
当然可以
Dr. Matthew Hill:
马修·希尔博士：
...
...
anyways, so there's other things that fluctuate.
无论如何，还有其他事情会波动。
It's like cortisol.
它就像皮质醇。
These hormones have cycles, so as long as you're in this normal range, there really shouldn't be any kind of behavioral, in terms of sex drive, for testosterone, or physiological, like gynecomastia or some change in-- Now, there are potentially effects of THC directly on the testes that could affect sperm.
这些激素有周期，所以只要你处于这个正常范围内，就性欲、睾酮、或生理方面（如男性乳房发育症或某些变化）而言，确实不应该有任何行为。现在，THC 可能直接对睾丸产生影响，从而影响精子。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
That could happen independent of changes in testosterone.
这可能独立于睾酮的变化而发生。
Andrew Huberman:
安德鲁·休伯曼：
Are those positive or negative changes?
这些变化是积极的还是消极的？
I'm assuming that the studies you're referring to saw disrupted what they call sperm quality, which has to do with motility, et cetera.
我假设你提到的研究破坏了所谓的精子质量，这与活力等有关。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
A lot of the in vitro stuff definitely would suggest that.
很多体外研究肯定会表明这一点。
Some of the animal stuff as well.
还有一些动物的东西。
The human stuff is definitely a bit mixed.
人类的东西肯定有点混杂。
But again, if anything, it would be like, yeah, could have some effect on sperm.
但同样，如果有的话，那就是，是的，可能会对精子产生一些影响。
So I have like a-
所以我有一个-
Andrew Huberman:
安德鲁·休伯曼：
As we say this, I'm just chuckling to myself because anytime this conversation comes up about a substance and sperm quality or egg quality, I always get a barrage of comments of people telling me how many children they conceived-
当我们这么说时，我只是暗自窃笑，因为每当谈论到某种物质和精子质量或卵子质量时，我总是会收到一连串的评论，人们告诉我他们怀了多少个孩子——
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
while under the influence.
当受到影响时。
No one is saying that you're going to be infertile.
没有人说你会不孕。
But if people are having challenges conceiving, it might be something to think about.
但如果人们在怀孕时遇到困难，这可能是值得考虑的事情。
Dr. Matthew Hill:
马修·希尔博士：
I would say that.
我会这么说。
I would agree on that.
我同意这一点。
So I would say if someone was asking me this and they were trying to get pregnant and struggling, I would say, well, definitely cut cannabis because some people may be more impacted by it than others.
所以我想说，如果有人问我这个问题，并且他们试图怀孕并陷入困境，我会说，好吧，绝对要减少大麻，因为有些人可能比其他人更容易受到大麻的影响。
So for some various biological reasons that we don't have a biomarker for, there may be some men that use cannabis, and it has a profound effect on their sperm quality, their sperm capacitance, their ability to maintain fertility.
因此，由于我们没有生物标志物的各种生物学原因，可能有一些男性使用大麻，这对他们的精子质量、精子容量和维持生育能力产生深远的影响。
And for the bulk majority of men, I'd say it's probably not the case.
对于大多数男性来说，我想说情况可能并非如此。
But again, if you're someone who is struggling and you use cannabis, male or female, I would say cut that out and see if that has an effect for you.
但同样，如果你是一个正在挣扎的人，并且你使用大麻，无论男性还是女性，我会建议不要使用大麻，看看这对你是否有影响。
Andrew Huberman:
安德鲁·休伯曼：
Along those lines, I saw a jaw-dropping statistic, and I'm not sure I still believe it, but you tell me what you know about this, which is that up to 15% of pregnant women in the US have used cannabis during pregnancy.
沿着这些思路，我看到了一个令人瞠目结舌的统计数据，我不确定我是否仍然相信它，但你告诉我你对此的了解，那就是美国多达 15% 的孕妇在怀孕期间使用过大麻。
That number just seems too high, and yet, it exists out there.
这个数字似乎太高了，但它确实存在。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
I've heard higher numbers than that.
我听说过比这个数字更高的数字。
Andrew Huberman:
安德鲁·休伯曼：
In the research literature.
在研究文献中。
Dr. Matthew Hill:
马修·希尔博士：
No, I've heard higher numbers than that as well.
不，我也听说过比这个数字更高的数字。
Andrew Huberman:
安德鲁·休伯曼：
Okay.
好的。
So I'm on the low end of this.
所以我处于这个低端。
Dr. Matthew Hill:
马修·希尔博士：
Well, so I've heard as low as two, and I've heard as high as 20.
嗯，我听说过低至 2 的，也听说过高至 20 的。
Andrew Huberman:
安德鲁·休伯曼：
Okay.
好的。
Two sounds like, okay, that I could imagine.
两个听起来，好吧，我可以想象。
But as high as 20.
但高达20。
And do we know what the effects on the developing fetus are?
我们知道这对发育中的胎儿有什么影响吗？
Dr. Matthew Hill:
马修·希尔博士：
There's a lot to unpack there.
那里有很多东西需要解压。
So first thing, going back to the levels.
首先，回到层面。
That's challenging because, again, this depends on are you talking about self-report, or are you talking about verified blood levels, because those have varied.
这具有挑战性，因为这又取决于您是在谈论自我报告，还是在谈论经过验证的血液水平，因为这些水平各不相同。
So some of the higher numbers actually come from blood levels, where they've taken blood samples and found THC, but the women have reported not using cannabis.
因此，一些较高的数字实际上来自血液水平，他们采集了血液样本并发现了四氢大麻酚，但这些女性报告说没有使用大麻。
And so the idea that it's like the self-report numbers tend to come in around 2% or 3%.
因此，自我报告数字的想法往往在 2% 或 3% 左右。
My guess is the real number is probably somewhere around 10%, but that also is going to vary depending on what you're talking about.
我的猜测是实际数字可能在 10% 左右，但这也会根据你所谈论的内容而有所不同。
Because there are a proportion of people who are using cannabis and become pregnant and are unaware they're pregnant and are still using cannabis, and that would still qualify under the way that it's defined that someone used cannabis while pregnant.
因为有一部分人正在使用大麻并怀孕，但他们不知道自己怀孕了并且仍在使用大麻，并且根据有人在怀孕期间使用大麻的定义，这仍然符合资格。
So the majority, I would say the overwhelming majority of people, once they learn they're pregnant, now that can be all the way up to almost the end of the first trimester, typically stop using cannabis.
因此，我想说的是，绝大多数人，一旦得知自己怀孕了，一直到妊娠前三个月结束，通常都会停止使用大麻。
That seems to be ...
这似乎是...
the norm, I would say.
我想说，这是常态。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
Important point there.
那里很重要。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
And I think also the number that carry on through the entire gestational period is going to be a lot less, I would guess.
而且我猜想，整个妊娠期持续的数量也会少得多。
Now, the motivations for this, quite often, are more in the capacity of the kind of anti-nauseant, qualities that cannabis can have for some people, and for women struggling with morning sickness.
现在，这样做的动机通常更多地在于大麻对某些人以及与孕吐作斗争的女性具有的抗恶心作用。
Now, anecdotally, I have heard women say, with a history of things like thalidomide and other anti-nauseant drugs that had profound teratogenic effects on the fetuses.
现在，有传闻说，我听到一些女性说，沙利度胺和其他抗恶心药物对胎儿有严重的致畸作用。
Women have said that they would rather use cannabis than one of these other compounds because they're less concerned about the impacts of cannabis than they are because of the thalidomide effects that happened and caused-
女性表示，她们宁愿使用大麻，也不愿使用其他化合物，因为她们不太担心大麻的影响，而是因为发生并导致了沙利度胺的影响——
Andrew Huberman:
安德鲁·休伯曼：
Thalidomide effects are malformation of the limbs and other bodily structures in fetuses.
沙利度胺效应会导致胎儿四肢和其他身体结构畸形。
It was a absolute tragedy of medicine that this occurred in-
这绝对是医学界的悲剧——
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
even one birth.
甚至一出生。
But, yeah, it's the reason why thalidomide is now, I believe, banned as a drug for use during pregnancy.
但是，是的，我相信这就是沙利度胺现在被禁止作为怀孕期间使用的药物的原因。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
I actually have no idea, but I would imagine.
其实我也不知道，但我会想象。
I think it would be one of those hard things to sell, given its history, especially.
我认为这将是很难出售的东西之一，尤其是考虑到它的历史。
So I think there's a reticence of a lot of people to consider using pharmaceuticals to regulate nausea because they're uncertain of the consequences of it, and they feel that cannabis may be safer.
因此，我认为很多人不愿考虑使用药物来调节恶心，因为他们不确定药物的后果，而且他们认为大麻可能更安全。
Now, that in and of itself could present some problems, in terms of that thought process.
现在，就思维过程而言，这本身可能会带来一些问题。
Now, there was also a study that I thought was like...
现在，还有一项我认为是这样的研究......
Some of these things just frustrate you.
其中一些事情只会让你感到沮丧。
It's where they actually decided to call, this was done in Colorado, where they called dispensaries and just acted naive and asked what their recommendations were, and it was something like 80 to 85% of them were actually recommending that people would use cannabis to manage morning sickness.
他们实际上决定打电话给科罗拉多州，他们打电话给药房，只是表现得很天真，询问他们的建议是什么，大约 80% 到 85% 的人实际上建议人们使用大麻来控制孕吐。
And I thought that was, it's just one of these disappointing things where you're like, "Why are you being so wildly irresponsible to kind of promote these things?" And this is-
我认为这只是令人失望的事情之一，你会想，“为什么你如此不负责任地推广这些东西？”这是——
Andrew Huberman:
安德鲁·休伯曼：
You're talking about the irresponsible that the dispensaries would say that?
你是说药房这么说是不负责任的吗？
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Or irresponsible that the study was carried out that way?
或者说这样的研究是不负责任的？
Because it's a little bit of-
因为这有点——
Dr. Matthew Hill:
马修·希尔博士：
Entrapment?
诱捕？
Andrew Huberman:
安德鲁·休伯曼：
You said it, not me.
你说的，不是我说的。
Dr. Matthew Hill:
马修·希尔博士：
Could be.
可能是。
You can balk at either side of this.
你可以在这方面犹豫不决。
I have a lot of frustration in general with the information that budtenders put out into the world.
总的来说，我对budtenders向世界发布的信息感到非常沮丧。
Andrew Huberman:
安德鲁·休伯曼：
Is that what they're called, budtenders?
这就是他们所谓的，budtenders吗？
Dr. Matthew Hill:
马修·希尔博士：
Yeah, budtenders.
是的，伙计们。
That's kind of the colloquial term that people will use for someone who sells cannabis at a dispensary.
这是人们对在药房销售大麻的人使用的口语术语。
We say this in Canada, and I've heard this throughout the States as well.
我们在加拿大这么说，我在美国各地也听到过这样的说法。
I personally have been a huge advocate for the fact that I think...
我个人一直大力倡导这样一个事实：我认为......
So, I worked in restaurants and bars and stuff when I was younger, and for me to serve alcohol, I had to undergo, I don't know if you do this in the States.
所以，我年轻的时候在餐馆和酒吧工作过，为了提供酒类服务，我必须经历，我不知道你在美国是否这样做。
In Canada, you have to do a weekend course essentially, called Serving It Right or some other terminology, where you learn the basics of alcohol, harms, blah, blah, blah, how to tell if someone's intoxicated, when you have to cut them off, all these things that you have to do to be able to serve alcohol.
在加拿大，你基本上必须参加一个周末课程，称为“正确服务”或其他一些术语，在那里你学习酒精的基础知识、危害、废话、废话、废话，如何判断某人是否喝醉了，何时必须切断他们，所有这些你必须做的事情才能提供酒。
I have no idea if this exists in the States, but-
我不知道美国是否存在这种情况，但是-
Andrew Huberman:
安德鲁·休伯曼：
I don't know
我不知道
Dr. Matthew Hill:
马修·希尔博士：
...
...
it was a thing in Canada.
这是加拿大的事情。
Andrew Huberman:
安德鲁·休伯曼：
Bartenders in the US, put in the comments on YouTube.
美国调酒师在 YouTube 上发表评论。
Do you have to undergo training about alcohol to be a bartender?
成为调酒师必须接受有关酒精的培训吗？
Dr. Matthew Hill:
马修·希尔博士：
Like anything, even if it's just an online quiz.
就像任何事情一样，即使这只是一个在线测验。
So my perspective is because pre-legalization, at least in Canada, there was somewhat of a misguided thought that people would leverage their physicians for knowledge about cannabis.
所以我的观点是，因为在大麻合法化之前，至少在加拿大，人们有一种错误的想法，认为人们会利用医生来获取有关大麻的知识。
And what's become very apparent is that the overwhelming majority of people talk to the people selling them the cannabis.
显而易见的是，绝大多数人都会与向他们出售大麻的人交谈。
And yet, those people selling cannabis don't need to have undergone any form of education.
然而，那些销售大麻的人不需要接受任何形式的教育。
And so, this kind of kills me because we've worked very hard to try and create educational platforms that are agnostic in terms of our position on cannabis, that are just based on the science.
因此，这让我很伤心，因为我们非常努力地尝试创建教育平台，这些平台对我们对大麻的立场是不可知的，而这些平台只是基于科学。
I'm an executive director of an organization called the Canadian Consortium for the Investigation of Cannabinoids, the CCIC, and we've done CME courses for physicians to try and train them about cannabis because I think it's important that physicians understand this.
我是加拿大大麻素调查联盟（CCIC）的执行董事，我们为医生开设了 CME 课程，尝试对他们进行有关大麻的培训，因为我认为医生了解这一点很重要。
But I've tried suggesting that I think that anyone selling cannabis should undergo a course like this, just so that there's some consensus in the informed level that someone who comes in, because a lot of people going to buy cannabis are quite naive about it, and they just...
但我曾尝试建议，我认为任何销售大麻的人都应该接受这样的课程，这样在知情的情况下，进来的人就可以达成一些共识，因为很多打算购买大麻的人对此都非常天真，他们只是……
Even when we're talking about dosing and what we've talked about with edibles or smoking or how people consume it, you need to have a reliable source of information at the frontline that is able to relay that to people.
即使当我们谈论剂量以及我们谈论的食物或吸烟或人们如何消费它们时，您也需要在第一线拥有可靠的信息来源，能够将这些信息传达给人们。
And it becomes very frustrating to me that they have become the main source of information that people go, and I'm uncertain of what their level of training is.
让我感到非常沮丧的是，他们已经成为人们获取信息的主要来源，而且我不确定他们的培训水平如何。
Andrew Huberman:
安德鲁·休伯曼：
You're certainly doing your part to provide the public education about cannabis now, so we all appreciate your highly informed and broad distribution of this information.
您现在肯定正在尽自己的一份力量来提供有关大麻的公众教育，因此我们都感谢您对这些信息的高度知情和广泛传播。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Because this is also an issue with psychedelics-
因为这也是迷幻药的一个问题——
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
which currently don't have legal status in the US.
目前在美国不具有合法地位。
This is an ongoing process of whether or not it will.
这是一个持续的过程，无论它是否会。
Right now, things are really on the teeter-totter-
现在的情况确实是岌岌可危——
Dr. Matthew Hill:
马修·希尔博士：
Little dicey, yeah
有点冒险，是的
Andrew Huberman:
安德鲁·休伯曼：
...
...
with MDMA, where we await the decision from the FDA, but the early recommendation to the FDA was to not approve MDMA as a treatment for PTSD.
对于 MDMA，我们正在等待 FDA 的决定，但 FDA 的早期建议是不批准 MDMA 作为 PTSD 的治疗方法。
That's as of today and mid to late June 2024.
截至今天和 2024 年 6 月中下旬。
We'll see what happens.
我们会看看会发生什么。
But this is also the case for ketamine, which has legal status, but many people are accessing ketamine not through a physician-
但氯胺酮也是如此，它具有合法地位，但许多人并不是通过医生获取氯胺酮——
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
but through online sources.
但通过在线资源。
So what you're speaking to here is a much larger issue, and I absolutely agree with you.
所以你在这里所说的是一个更大的问题，我完全同意你的观点。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
I think most people are probably not aware, except by experience, positive or negative in some cases, about the differences in blood concentration as it relates to number of tokes versus concentration versus edible.
我认为大多数人可能不知道，除了经验，在某些情况下是积极的或消极的，血液浓度的差异，因为它与代币数量、浓度和可食用量有关。
These are critical themes, especially for where we're going to go next, which is all the discussion about high THC and psychosis.
这些都是关键主题，特别是对于我们下一步要去的地方，这是所有关于高 THC 和精神病的讨论。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Exactly.
确切地。
So I think that I just wish, again, even if this was just an online course that wasn't that much, but at least had some consensus of information that was the basics about how to have conversations.
所以我想我再次希望，即使这只是一门在线课程，内容并不多，但至少对信息达成了一些共识，这些信息是如何进行对话的基础知识。
And our system, at least, is somewhat provincially regulated.
我们的系统至少在某种程度上受到省级监管。
So our organization has worked with the Ontario group that deals with cannabis distribution, like the OCS, which is Ontario Cannabis Stores, and helped to create some information pamphlets and stuff.
因此，我们的组织与处理大麻分销的安大略省组织（例如 OCS，即安大略省大麻商店）合作，并帮助制作了一些信息小册子和其他东西。
Again, it's not the same as a teaching course But at least it's like these little infographic stuff that kind of gives people rough breakdowns of things.
再说一遍，它与教学课程不同，但至少它就像这些小信息图表一样，可以让人们对事物进行粗略的细分。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
And kind of gives you a little bit of information about dosing and understanding things, especially with something like edibles, how long you should wait, just stuff like this.
会给你一些关于剂量和理解事物的信息，特别是像食物这样的东西，你应该等待多长时间，就像这样的东西。
And then-
然后——
Andrew Huberman:
安德鲁·休伯曼：
It sounds like the take-home message is, proceed with caution, low and slow, right?
听起来，最重要的信息是，谨慎行事，低速缓慢，对吧？
Dr. Matthew Hill:
马修·希尔博士：
That's the, yeah.
就是这样，是的。
I mean, we have-
我的意思是，我们有-
Andrew Huberman:
安德鲁·休伯曼：
Don't ingest too much too quickly.
不要摄入太多太快。
Really, if one is going to explore this, legally of course, take a little bit, wait, take a little bit, wait.
真的，如果有人要探索这个，当然是合法的，花一点点，等等，花一点点，等等。
Because otherwise you're going to get the...
因为否则你将会得到...
What, who was the reporter?
什么，记者是谁？
Dr. Matthew Hill:
马修·希尔博士：
Oh, I think it was Maureen Dowd, but I-
哦，我想是莫林·多德，但我——
Andrew Huberman:
安德鲁·休伯曼：
Right.
对。
You're going to hit-
你会击中——
Dr. Matthew Hill:
马修·希尔博士：
I don't know, actually, when I say that.
事实上，我不知道当我这么说的时候。
Maybe it was-
也许是——
Andrew Huberman:
安德鲁·休伯曼：
Is she still on the floor in a Colorado hotel?
她还在科罗拉多酒店的地板上吗？
Dr. Matthew Hill:
马修·希尔博士：
She may have recovered by now.
她现在可能已经康复了。
Andrew Huberman:
安德鲁·休伯曼：
Reporting from the floor in Colorado.
从科罗拉多州现场报道。
Dr. Matthew Hill:
马修·希尔博士：
But it can become very frustrating.
但这可能会变得非常令人沮丧。
It's just the kind of lack of understanding that exists-
这只是一种缺乏理解的存在——
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm
嗯嗯
Dr. Matthew Hill:
马修·希尔博士：
...
...
in this space.
在这个空间里。
And so I think this is one of the reasons why we've really kind of tried to push the public health side of this a lot more.
所以我认为这就是我们真正尝试更多地推动公共卫生方面的原因之一。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
And we have, there was the Center for Addiction and Mental Health in Canada, which does a lot of the organization of these things.
我们有加拿大的成瘾和心理健康中心，它负责组织这些事情。
They did kind of put together what I found to be really useful, which again, could be leveraged in the States.
他们确实把我认为真正有用的东西放在一起，这些东西再次可以在美国利用。
These are all accessible online.
这些都可以在线访问。
It's called the Lower Risk Cannabis Use Guidelines.
它被称为“低风险大麻使用指南”。
They kind of tried to create a framework that is similar to how people have done stuff with alcohol.
他们试图创建一个类似于人们用酒精做事的框架。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
That just kind of goes through, and a lot of it is this low and slow approach, but it's like, obviously you want no risk, you abstain.
这就是一种经历，很多都是这种低级和缓慢的方法，但显然你不想冒险，你就放弃了。
If you're going to use, these are the different ways to engage in harm reduction.
如果您打算使用，这些是减少伤害的不同方法。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
Obviously, oral consumption has, you avoid the issue of lung damage that you could get from smoking.
显然，口服消费可以避免吸烟引起的肺部损伤问题。
But then, with oral consumption, you have to be aware of dosing and timing and all these other considerations, but-
但是，对于口服消费，您必须注意剂量和时间以及所有其他考虑因素，但是-
Andrew Huberman:
安德鲁·休伯曼：
What about vaping?
抽电子烟怎么样？
Can people self-regulate their THC concentration in the blood by vaping as well as they can by joint or bong or other form of smoking?
人们是否可以通过电子烟来自我调节血液中的 THC 浓度，就像通过联合吸烟、烟枪或其他形式吸烟一样？
Dr. Matthew Hill:
马修·希尔博士：
I think that would depend on exactly what you're vaping.
我认为这具体取决于你抽的是什么。
So, in the States, I've noticed when people say vaping, they almost exclusively refer to some kind of oil-based product that's in a pen.
因此，在美国，我注意到当人们说电子烟时，他们几乎专门指的是笔中的某种油基产品。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
So, in those situations, that's going to really heavily depend on what the concentration of THC in that product is.
因此，在这些情况下，这在很大程度上取决于该产品中 THC 的浓度。
Now, the other form of vaping that I think is a little bit more common in Canada maybe, is vaping of the plant matter itself.
现在，我认为在加拿大可能更常见的另一种电子烟形式是植物本身的电子烟。
And so this is where they have a vaporizer device that heats the cannabis to a point that will essentially hit the lift point-
因此，他们有一个蒸发器装置，可以将大麻加热到基本上达到升力点的程度 -
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm
嗯嗯
Dr. Matthew Hill:
马修·希尔博士：
...
...
to vaporize THC and the cannabinoids.
蒸发 THC 和大麻素。
Andrew Huberman:
安德鲁·休伯曼：
Yeah, the big bag.
是啊，大包。
Dr. Matthew Hill:
马修·希尔博士：
Yeah, yeah.
是啊，是啊。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
Dr. Matthew Hill:
马修·希尔博士：
Like a volcano.
就像一座火山。
Andrew Huberman:
安德鲁·休伯曼：
I've seen it.
我见过。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
But it doesn't create any plant combustion.
但它不会产生任何植物燃烧。
And so there are studies that have been run on that, that have shown that you avoid the combustion byproducts.
因此，对此进行的研究表明，可以避免燃烧副产品。
So people don't exhale carbon monoxide or these other things that we know can be damaging, if they're vaping plant matter.
因此，如果人们吸食植物物质，就不会呼出一氧化碳或其他我们知道可能有害的物质。
That was actually somewhat approved as a medical device.
这实际上在某种程度上被批准为医疗设备。
Pre-legalization when cannabis in Canada was only under medical authorization.
当加拿大的大麻仅获得医疗授权时，才进行预合法化。
Because of the reduced harm associated with vaporizing the plant matter versus smoking it, that is, I would say, a safe guideline for harm reduction, that if you're going to try and avoid...
因为与吸烟相比，蒸发植物物质会减少危害，也就是说，我想说，这是一个减少危害的安全指南，如果你想尝试避免……
There's still going to be some issues that happen with vaporization of plant matter, but it's not the same as combustion.
植物物质的汽化仍然会出现一些问题，但这与燃烧不同。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
So you avoid some of the other issues that come out.
这样您就可以避免出现的一些其他问题。
When we're talking about oil-based vapor products or whatever they're in, they're usually in some kind of oil-based solution.
当我们谈论油基蒸气产品或它们所含的任何产品时，它们通常处于某种油基溶液中。
Who knows?
谁知道？
We don't have the research on this.
我们没有这方面的研究。
We just don't know.
我们只是不知道。
We certainly know there have been some pretty big errors of the things that happened in the States.
我们当然知道美国发生的事情存在一些相当大的错误。
There was that problem where all those people developed, I don't know, popcorn lung or that lung inflammation where several people died from vaping products, which seemed to be a byproduct, I believe, of them adding vitamin E acetate or something into the...
问题是，所有这些人都患上了，我不知道，爆米花肺或肺部炎症，有几个人死于电子烟产品，我相信，这似乎是他们在电子烟中添加维生素 E 醋酸酯或其他东西的副产品。
Because again, everyone just assumes it's inert.
因为同样，每个人都认为它是惰性的。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
But then when it combusts through the vaporization process, it creates a massive irritant on lung tissue.
但当它通过汽化过程燃烧时，会对肺组织产生巨大的刺激。
And so that was just, again, in my mind, this is a problem with a lack of a federal regulatory framework because stuff like this happens.
所以，在我看来，这是一个缺乏联邦监管框架的问题，因为这样的事情发生了。
You would not see that on a federal landscape because you would have to go through testing.
在联邦环境中你不会看到这种情况，因为你必须经过测试。
It's kind of the Wild West you get down here.
这里有点像狂野的西部。
Every state has its own rules.
每个州都有自己的规则。
There's not really a lot of-
确实没有很多——
Andrew Huberman:
安德鲁·休伯曼：
Well
嗯
Dr. Matthew Hill:
马修·希尔博士：
...
...
regulation of things.
对事物的监管。
Andrew Huberman:
安德鲁·休伯曼：
Well, and if you go overseas, it's even more wild.
好吧，如果你去海外，那就更疯狂了。
I mean-
我的意思是——
Dr. Matthew Hill:
马修·希尔博士：
Then you have no idea what you're consuming anywhere, I would say.
我想说，那么你就不知道自己在任何地方消费了什么。
Just because outside, again, Netherlands is a little bit of a different situation.
只是因为在外面，荷兰的情况又有点不同。
They're not legal, they're decriminalized.
它们不合法，它们已被非刑事化。
I don't know how well the regulation over there of the product is.
不知道那边的产品监管怎么样。
Andrew Huberman:
安德鲁·休伯曼：
No, we're going to be doing episodes on stem cells, and you've got people flying out of country to do stem cell injections.
不，我们将制作有关干细胞的剧集，并且有人飞出国门进行干细胞注射。
People were getting them down in Florida who went blind from the injections of stem cells into the eye-
佛罗里达州的人们因向眼睛注射干细胞而失明——
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
in an attempt to save what little vision they already had.
试图挽救他们已经拥有的一点点愿景。
Probably don't want to get me started on that one.
可能不想让我开始那件事。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
I'm in total agreement with you, by the way.
顺便说一句，我完全同意你的观点。
I want to make sure that I ask about psychosis and paranoia.
我想确保我询问的是精神病和偏执症。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
I've previously said, and I wasn't joking, but I have observed in my history that when people started to experience some degree of anxiety or paranoia when smoking cannabis, that sometimes the message they would receive back is to take more to just adjust the subjective experience.
我之前说过，我不是在开玩笑，但我在我的历史中观察到，当人们在吸食大麻时开始经历某种程度的焦虑或偏执时，有时他们收到的信息是采取更多措施来调整主观体验。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
I think that's a terrible idea.
我认为这是一个糟糕的主意。
Terrible idea.
糟糕的主意。
Dr. Matthew Hill:
马修·希尔博士：
I'm baffled that you heard that.
我很困惑你听到了这个。
I have no idea who on earth-
我不知道到底是谁——
Andrew Huberman:
安德鲁·休伯曼：
Let's just say I did more than hear it.
这么说吧，我所做的不仅仅是听到的。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
See, I've observed it many times over.
你看，我已经观察过很多次了。
Dr. Matthew Hill:
马修·希尔博士：
I cannot even understand that.
我什至无法理解这一点。
That is the strangest thing I've ever heard, but okay, yeah.
这是我听过的最奇怪的事情，但是好吧，是的。
Andrew Huberman:
安德鲁·休伯曼：
Well, usually the advice of people in terms of, that was recreational drug taking, is rarely excellent advice.
嗯，通常人们关于消遣性吸毒的建议很少是很好的建议。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
No, no. That's-
不，不。那是——
Andrew Huberman:
安德鲁·休伯曼：
So, I didn't-
所以，我没有-
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
I mean, I agree with you on that point, for sure, that you should not be consuming more if you're having a bad reaction to it, because that will just grease the wheels going downhill, for sure.
我的意思是，我同意你的观点，当然，如果你对它有不良反应，你不应该消耗更多，因为这肯定只会润滑下坡的轮子。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
I also am aware that there are some very high-profile papers that have been published in the last really five years or so, pointing to potential increased risk for psychosis of lasting duration-
我还知道，在过去五年左右的时间里发表了一些非常引人注目的论文，指出持续精神病的潜在风险增加——
Dr. Matthew Hill:
马修·希尔博士：
Mm-hmm
嗯嗯
Andrew Huberman:
安德鲁·休伯曼：
...
...
even after the effects of cannabis have worn off, in high-THC cannabis users.
即使大麻的作用已经消失，对于高 THC 大麻使用者来说也是如此。
In particular high THC cannabis users that initiate that cannabis use young, and this might be preferentially impacting males.
特别是高 THC 大麻使用者开始使用大麻，这可能会优先影响男性。
I want to make clear that what I just said is not a statement of absolute fact.
我想澄清的是，我刚才所说的并不是绝对事实的陈述。
It's my understanding of the conclusions of these papers.
这是我对这些论文结论的理解。
There are other conclusions in these papers also, but that particular conclusion seems to be important enough that they place it in the abstract, and it's reached major press headlines.
这些论文中还有其他结论，但这个特定的结论似乎足够重要，以至于他们将其放在摘要中，并且成为了主要媒体的头条新闻。
So I guess the simple question, which probably doesn't have a simple answer, is does THC cause psychosis?
所以我想这个简单的问题（可能没有简单的答案）是 THC 会导致精神病吗？
Dr. Matthew Hill:
马修·希尔博士：
So yeah, there's not a simple answer to that, and I think that also is a question over whether you're talking about acute drug-induced psychotic episode versus the development of a chronic psychotic disease like schizophrenia.
所以，是的，这个问题没有一个简单的答案，我认为这也是一个问题，即你是在谈论急性药物引起的精神病发作还是精神分裂症等慢性精神病的发展。
So the first arm of that is just can people acutely have a psychotic episode to THC or cannabis?
那么第一个方面是人们是否会对四氢大麻酚或大麻产生严重的精神病发作？
And the answer to that is yes.
答案是肯定的。
It's not common.
这并不常见。
I would say in terms of adverse events that happen with people consuming cannabis, it's on the rarer side, but it definitely can happen.
我想说的是，就食用大麻的人发生的不良事件而言，这种情况比较罕见，但肯定有可能发生。
Andrew Huberman:
安德鲁·休伯曼：
So less than 5% of people that-
所以只有不到 5% 的人认为——
Dr. Matthew Hill:
马修·希尔博士：
Oh, much less than that.
哦，比那少得多。
Andrew Huberman:
安德鲁·休伯曼：
Okay.
好的。
Dr. Matthew Hill:
马修·希尔博士：
And certainly, if something like this was happening at a regular frequency, it would be very well-known.
当然，如果这样的事情经常发生，那将会是众所周知的。
Andrew Huberman:
安德鲁·休伯曼：
What about anxiety attack?
焦虑症发作怎么办？
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Anxiety attack is, I'd say, more of a standard indication that someone's kind of gone overboard.
我想说，焦虑症更多的是一种标准的迹象，表明某人有点太过分了。
Andrew Huberman:
安德鲁·休伯曼：
Dosage overboard, or does it carry the same set and setting considerations that psychedelics like psilocybin have?
剂量过多，或者它是否具有与裸盖菇素等迷幻药相同的设置和设置考虑因素？
Dr. Matthew Hill:
马修·希尔博士：
Both.
两者皆有。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
So I think there's some contextual component to it.
所以我认为它有一些上下文成分。
Back in the '70s when they did more, let's say, interesting studies, there's one where basically they dosed people on THC and then had them undergo oral surgery, which seems like, in hindsight, a very bad idea, and I think virtually everyone in that study had a panic attack.
早在 70 年代，当他们做了更多有趣的研究时，有一项基本上是给人们服用 THC，然后让他们接受口腔手术，事后看来，这似乎是一个非常糟糕的主意，我认为该研究中几乎每个人都惊恐发作。
So it really potentiated the stress of what they were undergoing, and had they been given that same dose in a different setting, I'm not sure it would've evoked that kind of response.
因此，这确实加剧了他们所经历的压力，如果他们在不同的环境中接受相同的剂量，我不确定是否会引起这种反应。
But there is definitely a dose effect to this in terms of the kind of classic low-dose aspects of THC or cannabis that are usually considered more the positive, pleasurable responses that are why people use.
但就 THC 或大麻的经典低剂量方面而言，这肯定存在剂量效应，这些方面通常被认为更积极、令人愉悦的反应，这就是人们使用的原因。
It reduces anxiety, it relaxes, blah, blah, blah.
它减少焦虑，放松，等等，等等。
That is more of a low to normal-ish dose, let's say, of what someone consumes to produce those responses.
比方说，这更多的是一个低到正常的剂量，是一个人产生这些反应所消耗的剂量。
If they start going upwards, though, it's not like it's graded.
然而，如果他们开始向上，那就不像是分级的。
It's like a full flip.
这就像一个完整的翻转。
It's not linear at all.
它根本不是线性的。
It's almost like it goes in the opposite direction.
几乎就像是朝相反的方向发展。
So someone can use cannabis to reduce anxiety, but then cannabis can also trigger anxiety in other people, and even in the same person if they consume too much.
因此，有人可以使用大麻来减少焦虑，但大麻也会引发其他人的焦虑，甚至同一个人如果摄入过多也会引发焦虑。
And a lot of this, at least we think, has to do with the ability of it to regulate both excitatory neurotransmission and inhibitory.
至少我们认为，这很大程度上与它调节兴奋性神经传递和抑制性神经传递的能力有关。
And so for reasons that we don't totally understand, there's way more cannabinoid receptors on inhibitory neurons than there is on excitatory neurons.
因此，由于我们不完全了解的原因，抑制性神经元上的大麻素受体比兴奋性神经元上的大麻素受体多得多。
But in the early days of creating the genetic lines, Giovanni Marsicano and Beat Lutz were over in Europe, created deletion of CB1 only from excitatory neurons or only from inhibitory neurons.
但在创建遗传系的早期，Giovanni Marsicano 和 Beat Lutz 在欧洲，仅从兴奋性神经元或仅从抑制性神经元中删除 CB1。
Andrew Huberman:
安德鲁·休伯曼：
Okay.
好的。
So to just clarify for people, these are laboratory mice that are genetically modified so that they contain or lack specific receptors on particular neuron types so that researchers can parse the effects of THC on what we're referring to as inhibitory neurons, which quiet other neurons, versus excitatory neurons, which excite other neurons and so forth.
因此，为了向人们澄清，这些是经过基因改造的实验室小鼠，因此它们含有或缺乏特定神经元类型的特定受体，以便研究人员可以解析 THC 对我们所说的抑制性神经元的影响，抑制性神经元使其他神经元安静，而兴奋性神经元则兴奋其他神经元等等。
And in doing so, to understand some of the network biology.
并在这样做的过程中，了解一些网络生物学。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Which is basically impossible to do in a typical mouse-
这对于典型的鼠标来说基本上是不可能做到的——
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
what's called a wild-type mouse, or a human, because when one ingests the drug or when the mouse is given the drug, it affects potentially any site in the brain where the CB1 receptor is expressed.
所谓的野生型小鼠或人类，因为当一个人摄入该药物或给小鼠注射该药物时，它可能会影响大脑中表达 CB1 受体的任何部位。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
So if you do a full body deletion of CB1 and you give a mouse THC, doesn't respond to it at all.
因此，如果你对 CB1 进行全身删除，然后给老鼠注射 THC，它根本不会有反应。
Not surprisingly.
不足为奇。
Andrew Huberman:
安德鲁·休伯曼：
That's a comforting experiment.
这是一个令人欣慰的实验。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
You want to see that result.
你想看到那个结果。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Exactly.
确切地。
So that's how we know CB1 drives all the kind of psychoactive effects of THC.
这就是我们如何知道 CB1 驱动 THC 的所有类型的精神作用。
So if you delete CB1 off of inhibitory GABA neurons, even though that removes like 70% of the CB1 receptors in the brain, those animals look just like wild type.
因此，如果你从抑制性 GABA 神经元中删除 CB1，即使这删除了大脑中大约 70% 的 CB1 受体，这些动物看起来就像野生型一样。
They still exhibit all the classic signs of intoxication in terms of how they would respond to pain sensitivity or locomotion or these other assays we use in mice to tell if they're high.
它们仍然表现出所有典型的中毒迹象，比如它们对疼痛敏感性或运动的反应，或者我们在小鼠身上使用的其他检测来判断它们是否处于兴奋状态。
If you delete the CB1 only off of excitatory neurons, the glutamate neurons, then you see what looks like the full knockout.
如果你只删除兴奋性神经元（即谷氨酸神经元）上的 CB1，那么你会看到看起来像是完全敲除的情况。
So now the animals don't seem to get high.
所以现在动物们似乎并没有兴奋起来。
So even though the majority of CB1 receptors seem to be on these inhibitory GABA neurons, it's the CB1 on the glutamatergic excitatory neurons that mediate most of the classic signs of what we would consider intoxication from THC or cannabis.
因此，尽管大多数 CB1 受体似乎位于这些抑制性 GABA 神经元上，但谷氨酸能兴奋性神经元上的 CB1 介导了我们认为的 THC 或大麻中毒的大多数经典症状。
But what's interesting is Beat worked with a Spanish group 10, 12 years ago.
但有趣的是，Beat 在 10、12 年前就与一个西班牙乐队合作过。
Then they showed they're looking at anxiety, that if you delete CB1 only off of excitatory neurons, you lose the anti-anxiety, anxiolytic effects of THC, but you still have the panicky, anxiogenic effects of high dose.
然后他们表明他们正在研究焦虑，如果你只删除兴奋性神经元上的 CB1，你就会失去 THC 的抗焦虑、抗焦虑作用，但仍然会产生高剂量的恐慌、致焦虑作用。
If you delete CB1 off of only the inhibitory GABA neurons, you still have the low-dose anti-anxiety effect, but now you don't have the high-dose anxiogenic panicky effect.
如果你只删除抑制性 GABA 神经元中的 CB1，你仍然具有低剂量的抗焦虑作用，但现在你不再具有高剂量的致焦虑恐慌作用。
Andrew Huberman:
安德鲁·休伯曼：
Interesting.
有趣。
Dr. Matthew Hill:
马修·希尔博士：
So what that was suggesting was that for some reason, THC will initially hit CB1 on kind of glutamatergic neurons, and essentially the thought is this will reduce excitatory transmission and probably quiet down circuits, and if we're talking about something like the amygdala, this is probably how it's reducing anxiety.
所以这表明，出于某种原因，THC 首先会在某种谷氨酸能神经元上攻击 CB1，本质上，我们的想法是这会减少兴奋性传递，并可能使回路安静下来，如果我们谈论的是杏仁核之类的东西，这可能就是它减少焦虑的方式。
Whereas as dosing starts to increase and you start to saturate the CB1 on the GABA neurons and turn off inhibition, then the network effect is more of an amplification, and that seems to result in the development of kind of an anxiogenic-
然而，当剂量开始增加，并且开始使 GABA 神经元上的 CB1 饱和并关闭抑制时，网络效应更多的是放大，这似乎会导致某种致焦虑的发展——
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm
嗯嗯
Dr. Matthew Hill:
马修·希尔博士：
...
...
pro-anxiety response that's obviously undesirable.
亲焦虑的反应显然是不可取的。
Why there's this differential shift, it's not exactly clear.
为什么会出现这种差异性转变，目前尚不清楚。
It's probably either due to some of the biology of exactly where the CB1 receptors sit on excitatory or inhibitory neurons relative to all the machinery that regulates transmitter release.
这可能是由于 CB1 受体相对于所有调节递质释放的机制位于兴奋性或抑制性神经元上的确切位置的一些生物学原因。
Beat Lutz has definitely done some stuff looking at the ability of cannabinoid receptors to evoke signaling responses in a cell, and on glutamate neurons, they're much more sensitive than they are in GABA neurons, so there's probably a dose threshold.
Beat Lutz 确实做了一些研究，研究大麻素受体在细胞中引发信号反应的能力，并且在谷氨酸神经元上，它们比在 GABA 神经元中敏感得多，因此可能存在剂量阈值。
So it does look like this kind of low dosing, what most people are trying to achieve, I would assume, when they consume cannabis, is probably these effects mediated by quieting down excitatory transmission.
所以它看起来确实像这种低剂量，我认为大多数人在消费大麻时试图实现的效果可能是通过平息兴奋性传播来介导的。
And then the adverse effects when someone consumes too much and they have a negative response, that's probably due to the higher dose starting to saturate on the inhibitory neurons.
然后，当某人摄入过多并且产生负面反应时会产生副作用，这可能是由于较高的剂量开始对抑制性神经元造成饱和。
Now, we obviously can never test something like that in humans, because we can't know.
现在，我们显然永远无法在人类身上测试类似的东西，因为我们无法知道。
But based on what we've seen in animals, that's my theory of how this is working and why we see these classic biphasic effects.
但根据我们在动物身上看到的情况，这就是我关于其如何运作以及为什么我们会看到这些经典双相效应的理论。
So, yeah, too much THC, not a good thing, because then you start maybe disinhibiting things like the amygdala and producing these kind of panicky, anxiogenic-like outcomes.
所以，是的，太多的四氢大麻酚，不是一件好事，因为那时你可能会开始抑制杏仁核等东西，并产生这种恐慌、焦虑的结果。
On that scale, though, paranoia, obviously, that's a hard-- I don't know how you study that in a rodent.
不过，在这种规模上，显然，偏执是很难的——我不知道你是如何在啮齿类动物身上研究这一点的。
That's just a strange thing.
这真是一件奇怪的事情。
But, that's the precedent of when you start going into the psychosis, because obviously paranoia would be a big component of that.
但是，这是你开始陷入精神病的先例，因为显然偏执是其中的一个重要组成部分。
Someone once asked me a question about what happens in the brain, imaging-wise, when someone's having a psychotic episode from cannabis, and I was thinking, like, how would that study get done?
有人曾经问我一个问题，当某人因大麻而出现精神病发作时，大脑中会发生什么，从成像角度来看，我在想，这项研究将如何完成？
Andrew Huberman:
安德鲁·休伯曼：
Probably on accident because somebody takes cannabis, is in the scanner, and then starts-
可能是偶然，因为有人服用了大麻，进入扫描仪，然后开始-
Dr. Matthew Hill:
马修·希尔博士：
Having-
拥有-
Andrew Huberman:
安德鲁·休伯曼：
...
...
having a psychotic episode.
有精神病发作。
But chances are they're going to try and get it out.
但他们很可能会尝试把它弄出来。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
For those that don't know, I don't want to scare people out of doing MRI or fMRI, but you're typically told to stay extremely still.
对于那些不知道的人，我不想吓唬人们不要做 MRI 或 fMRI，但通常会告诉你要保持绝对静止。
There's sometimes even a bite bar.
有时甚至还有小吃吧。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
This is a very controlled environment, not an environment that you would want to be in during a psychotic episode.
这是一个非常受控制的环境，而不是您在精神病发作期间想要处于的环境。
Dr. Matthew Hill:
马修·希尔博士：
No. I can't actually even imagine how that would go down, so this is something I don't think we're ever going to have an answer to because I don't think you can actually ever test it.
不，我什至无法想象这会如何发展，所以我认为我们永远不会有答案，因为我认为你无法真正测试它。
But in terms of people having this kind of psychotic response, it is pretty rare.
但对于有这种精神病反应的人来说，这是相当罕见的。
And I say this because I can think of, in Canada, whenever it's happened and someone has actually done something wildly unpredictable because they've had a psychotic response to cannabis, it tends to make headlines, so it's not common.
我这么说是因为我能想到，在加拿大，每当发生这种情况，并且有人实际上做了一些非常不可预测的事情，因为他们对大麻产生了精神病反应，它往往会成为头条新闻，所以它并不常见。
I could not give you an actual number, but it's certainly not a frequent thing because we would hear about this a lot more if we did.
我无法给你一个实际的数字，但这肯定不是经常发生的事情，因为如果我们这样做的话，我们会听到更多这样的事情。
Andrew Huberman:
安德鲁·休伯曼：
And there's also the issue of polypharmacology, which is simply when people take one drug, then there's often the tendency to take another drug, either because it's available in those conditions or because their threshold to saying yes is a little bit lower.
还有一个多重药理学的问题，就是当人们服用一种药物时，通常会倾向于服用另一种药物，要么是因为在这些情况下可以使用这种药物，要么是因为他们说“是”的门槛有点低。
Do most people who take cannabis and achieve the high have a tendency to do other drugs?
大多数吸食大麻并获得快感的人是否有吸食其他毒品的倾向？
It doesn't seem like a drug that people combine with a lot of other drugs.
它看起来不像是一种需要与许多其他药物混合使用的药物。
Dr. Matthew Hill:
马修·希尔博士：
Cannabis is used in tandem with other drugs, alcohol, psychedelics, at times, for sure.
当然，大麻有时会与其他药物、酒精、致幻剂一起使用。
But that being said, there is clearly a population of people that use cannabis as their only drug that they use.
但话虽这么说，显然有一群人将大麻作为他们使用的唯一药物。
I don't think that's that uncommon.
我认为这并不罕见。
But in the context of the psychosis stuff, I would definitely say, sure, if someone mixed it with amphetamine or something, you could have a very unpredictable response there.
但在精神病的背景下，我肯定会说，当然，如果有人将它与安非他命或其他东西混合，你可能会产生非常不可预测的反应。
Andrew Huberman:
安德鲁·休伯曼：
Yikes.
哎呀。
Dr. Matthew Hill:
马修·希尔博士：
But I think the psychotic responses that have been documented there are usually purely due to cannabis.
但我认为那里记录的精神病反应通常纯粹是由大麻引起的。
It's not necessarily due to some kind of drug interaction there.
这不一定是由于某种药物相互作用造成的。
There is something about the way that cannabis is changing the way the brain functions in a way that for people who seem to be prone to this, they can have a psychotic response.
大麻正在改变大脑的运作方式，对于那些似乎容易出现这种情况的人来说，他们可能会产生精神病反应。
Again, I don't think that's a very typical thing.
再说一次，我认为这不是一件非常典型的事情。
But when we're talking about what that means in the context of an actual disorder, like a chronic disorder like schizophrenia, which is characterized by psychosis, I think we're talking about a whole different ballgame here.
但是，当我们谈论这在实际疾病的背景下意味着什么时，例如精神分裂症等以精神病为特征的慢性疾病，我认为我们在这里谈论的是完全不同的游戏。
And this is an area that is an important thing to discuss in the context of science because you can't establish causality.
这是一个在科学背景下需要讨论的重要领域，因为你无法建立因果关系。
In my view, it's virtually impossible because there's just no way to control all the variables that play into this.
在我看来，这几乎是不可能的，因为没有办法控制所有参与其中的变量。
What we can say definitively is individuals who have schizophrenia, first of all, they use cannabis at a higher rate than the general population.
我们可以肯定地说，患有精神分裂症的人，首先，他们使用大麻的比例高于一般人群。
Andrew Huberman:
安德鲁·休伯曼：
Oh, right.
哦，对了。
Dr. Matthew Hill:
马修·希尔博士：
That's very clear, yeah.
这非常清楚，是的。
They definitely use cannabis at a higher rate than the general population.
他们使用大麻的比例肯定高于一般人群。
There is definitely a relationship between using cannabis and having the initiation of the development of schizophrenia.
使用大麻与精神分裂症的发生之间肯定存在关系。
And this is where a lot of the statistics that have been used to develop the risk assessment, essentially, so that you have a greater risk if, like you were saying, if you've used cannabis as a teenager, you use high potency, as a lot of the research has shown, though they've done these studies and they say it relates to a greater risk of schizophrenia.
这就是用于进行风险评估的大量统计数据的地方，本质上，如果像你所说的那样，如果你在青少年时期使用过大麻，那么你会面临更大的风险，正如许多研究表明的那样，尽管他们已经完成了这些研究，并且他们说这与精神分裂症的更大风险有关。
Essentially, this is just a statistical association that they've found, that people who use cannabis, the conversion into schizophrenia happens at a higher rate, and there's more people with schizophrenia who are using cannabis.
从本质上讲，这只是他们发现的一个统计关联，使用大麻的人转化为精神分裂症的几率更高，而且使用大麻的精神分裂症患者也更多。
Andrew Huberman:
安德鲁·休伯曼：
Is there a bias towards males developing psychosis?
是否存在对男性患精神病的偏见？
I know there may be a bias initially toward males in schizophrenia that could confound this, so we want to be careful.
我知道精神分裂症患者最初可能对男性存在偏见，这可能会混淆这一点，所以我们要小心。
Dr. Matthew Hill:
马修·希尔博士：
To be honest, in all the research I've, in all the literature I've read on this, I don't ever remember there being clear sex descriptions of the differences of males and females.
老实说，在我所做的所有研究中，在我读过的所有有关这方面的文献中，我不记得有关于男性和女性差异的明确的性别描述。
Again, historically, cannabis was more used by males than females, so that could-
同样，从历史上看，男性使用大麻的比例多于女性，因此可以-
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm
嗯嗯
Dr. Matthew Hill:
马修·希尔博士：
...
...
lean towards any bias that may be out there in the media or just in general, what people talk about.
倾向于媒体中可能存在的任何偏见，或者一般来说，人们谈论的内容。
I can't think of any study that I've ever read that explicitly said this was male-biased per se.
我想不出我读过的任何研究明确表示这本身就是男性偏见。
They usually just report numbers or proportions of people.
他们通常只报告人数或人数比例。
The issue is So yes, there's this relationship that exists, and yes, we know that cannabis can trigger psychotic episodes.
问题是，是的，存在这种关系，是的，我们知道大麻会引发精神病发作。
So if there's an individual who has schizophrenia, we know for certain that cannabis can lead to the onset of increases in positive symptoms like hallucinations and delusions, and a full-blown psychotic episode.
因此，如果有人患有精神分裂症，我们可以肯定地知道大麻会导致幻觉和妄想等阳性症状的增加，以及全面的精神病发作。
So I think the first thing to say, which is very clear, is, in my view, if someone has schizophrenia, cannabis is contraindicated.
所以我认为首先要说的是，非常明确的是，在我看来，如果有人患有精神分裂症，大麻是禁忌的。
You shouldn't be using cannabis if you have schizophrenia.
如果您患有精神分裂症，则不应使用大麻。
I think that's a risk across the board.
我认为这是一个全面的风险。
Andrew Huberman:
安德鲁·休伯曼：
What about a first relative who has schizophrenia?
第一位亲属患有精神分裂症怎么办？
Dr. Matthew Hill:
马修·希尔博士：
So-
所以——
Andrew Huberman:
安德鲁·休伯曼：
Because there's a strong genetic-
因为有很强的基因——
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
component to schizophrenia.
精神分裂症的组成部分。
Dr. Matthew Hill:
马修·希尔博士：
So I was going to say, then the next question is, knowing who's going to develop schizophrenia, obviously we don't know this.
所以我想说，那么下一个问题是，知道谁会患上精神分裂症，显然我们不知道这一点。
And as you say, the only real predictive variable that we know of is a first-degree family member that has schizophrenia, means that you have a higher risk of developing schizophrenia.
正如你所说，我们所知道的唯一真正的预测变量是患有精神分裂症的一级家庭成员，这意味着你患精神分裂症的风险更高。
So again, same with bipolar.
再说一次，双相情感障碍也是如此。
I would say if there's bipolar or schizophrenia in a family, to me those are the people who should avoid cannabis.
我想说，如果一个家庭中有躁郁症或精神分裂症患者，对我来说，这些人应该避免使用大麻。
Just in terms of the likelihood, there's a much greater likelihood that they'd have-- It would relate to the onset of a disease or could accelerate its presentation in some capacity.
就可能性而言，他们有更大的可能性——它与疾病的发作有关，或者可能以某种方式加速其表现。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
I think where things get really complicated in this whole cannabis schizophrenia story is the causality.
我认为在整个大麻精神分裂症故事中，事情变得真正复杂的是因果关系。
And there is a camp of people who have looked at this literature and definitively believe that cannabis causes schizophrenia.
有一群人看过这些文献并明确认为大麻会导致精神分裂症。
And they attribute a proportion of people who have schizophrenia to only having that schizophrenia because of the fact that they used cannabis.
他们将一部分患有精神分裂症的人归因于仅因为他们使用大麻而患有精神分裂症。
And I think you'd had some discussion about this in the last podcast.
我想你在上一个播客中对此进行了一些讨论。
I can't remember exactly the way that you described it.
我不记得你具体描述的方式了。
Andrew Huberman:
安德鲁·休伯曼：
Yeah, I was looking toward some of the recent studies in Lancet, JAMA Psychiatry.
是的，我正在寻找《柳叶刀》和《美国医学会精神病学》杂志最近的一些研究。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
I believe we can provide links to these again.
我相信我们可以再次提供这些链接。
And now more recently, there's been a lot of, let's just call it mainstream media coverage of this potential-
最近，有很多，让我们称之为主流媒体对这种潜力的报道——
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
I think is the right way to refer to it, potential linkage between adolescent, teen, and young adult use of high-THC cannabis and lasting psychosis.
我认为正确的说法是，青少年和年轻人使用高 THC 大麻与持久精神病之间存在潜在联系。
But the more I hear you talk about this, the more I'm wondering if that idea is being amplified more than perhaps we ought to let it be amplified.
但我越听你谈论这个，我就越想知道这个想法是否被放大得超过了我们应该让它被放大的程度。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
I think this is what happens when you have-- Obviously, you're familiar with this.
我认为这就是当你——显然，你对此很熟悉时会发生的情况。
In science, there's different...
在科学上，有不同的...
There's some things that we can be a little bit more definitive about, and then there's some things that we just can't know for certain.
有些事情我们可以更加确定，但有些事情我们无法确定。
It's just the way it is.
事情就是这样。
Because of the way that we gather data and because of the way humans are, and this isn't a question I believe we can ask from an animal model perspective in the same capacity.
由于我们收集数据的方式以及人类的生活方式，我认为我们不能以同样的能力从动物模型的角度提出这个问题。
So I don't think anyone would deny, at least anyone who's read the literature, that there's this relationship between cannabis use, especially in adolescents, and the development of schizophrenia.
因此，我认为没有人会否认，至少读过文献的人都会否认，吸食大麻（尤其是青少年）与精神分裂症的发展之间存在这种关系。
Now, my perspective on this is, and I'll explain why I have this perspective and how I justify it, is to me, cannabis is fuel on a fire.
现在，我对此的观点是，我将解释为什么我有这个观点以及我如何证明它的合理性，对我来说，大麻是火上浇油。
So if someone is prone to developing schizophrenia, adding cannabis into the mix, I think, will make it kick in faster and harder.
因此，如果有人容易患上精神分裂症，我认为在混合物中添加大麻会使其发病更快、更难。
So if there is a genetic vulnerability for developing schizophrenia or some biological predisposition that's there, I would say in that situation, cannabis can trigger an initial onset of the first episode, and it can make the prognosis of the disease in the long term a lot worse, let's say.
因此，如果存在罹患精神分裂症的遗传脆弱性或存在某种生物易感性，我想说在这种情况下，大麻可能会引发第一次发作，并且从长远来看，它可能会使该疾病的预后变得更糟。
Andrew Huberman:
安德鲁·休伯曼：
As I recall, and I may have this incorrectly, but as I recall from my undergraduate years, what you just said is also true for military service, for people that have a predisposition to develop schizophrenia, that active military duty can exacerbate it as well.
我记得，也许我的理解是错误的，但正如我在大学期间回忆的那样，你刚才所说的对于服兵役来说也是正确的，对于那些有患精神分裂症倾向的人来说，现役服役也会加剧这种情况。
Dr. Matthew Hill:
马修·希尔博士：
Oh.
哦。
I've never heard that, but that would be a stressor, and stressors are other ways.
我从来没有听说过，但这会是一个压力源，而压力源还有其他方式。
There's situations where some of it's the age, but for example, if someone is prone to develop schizophrenia, they move away to college.
在某些情况下，其中一些是年龄，但例如，如果某人容易患上精神分裂症，他们就会搬去上大学。
Even that stressor can be something that brings on an episode.
即使是压力源也可能会引发事件。
But cannabis very specifically, different than any other drugs, like alcohol or cigarettes, as far as I understand it at least, the temporal relationship between cannabis use and the development of a first episode can be pretty linked.
但大麻非常具体，与酒精或香烟等任何其他药物不同，至少据我了解，大麻的使用和第一阶段的发展之间的时间关系可以非常相关。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
But the arguments that I've always had with people in this area who are very definitive on their end of the spectrum that this is a causal relationship is, first of all, we have a few things that I would leverage as real-world evidence that makes this questionable.
但我一直与这个领域的人们争论，他们非常明确地认为这是一种因果关系，首先，我们有一些东西可以作为现实世界的证据，使这一点值得怀疑。
So the first one is, like I was saying earlier in the episode, we really didn't have cannabis use in the West as a normal thing, as one of the drugs that was part of the repertoire of what people use recreationally, until the '60s.
所以第一个是，就像我在本集早些时候所说的那样，直到 60 年代，我们在西方并没有将大麻作为一种正常的事情使用，作为人们娱乐性使用的药物之一。
So unlike alcohol, which has been there for centuries, we have a little bit of a before and after, what we can look at.
因此，与已经存在了几个世纪的酒精不同，我们可以了解一些之前和之后的情况。
Now-
现在——
Andrew Huberman:
安德鲁·休伯曼：
The Grateful Dead.
感恩的死者。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
So now granted, we don't have really good prevalence data of what schizophrenia was in the era prior.
因此，现在我们确实没有关于前一个时代精神分裂症患病率的确切数据。
Even nowadays, our prevalence data's not perfect.
即使在今天，我们的患病率数据也并不完美。
But if cannabis as a solitary variable was driving the genesis of schizophrenia de novo, in the absence of any kind of biological predisposition or genetic predisposition, I find it very hard to believe that we wouldn't have seen a shift in the prevalence of the disease as cannabis became more mainstream and more widely used.
但是，如果大麻作为一个孤立变量推动了精神分裂症的发生，那么在没有任何生物倾向或遗传倾向的情况下，我很难相信随着大麻变得更加主流和更广泛使用，我们不会看到这种疾病的患病率发生变化。
And generally, schizophrenia rates have remained largely stable.
一般来说，精神分裂症发病率基本保持稳定。
People can make arguments about that, better care, other things to challenge that argument, sure.
当然，人们可以就这一点、更好的护理、其他事情提出争论来挑战这一论点。
So another modern perspective would be, okay, well, let's look at Canada and the States, let's say, where we have, as I said earlier, teenagers in Canada and the States, by grade 12, 35% to 40% of teenagers have at least used cannabis somewhat sporadically, and somewhere around 5%-ish are probably using almost daily.
因此，另一个现代观点是，好吧，让我们看看加拿大和美国，正如我之前所说，加拿大和美国的青少年，到 12 年级时，35% 到 40% 的青少年至少偶尔使用大麻，大约 5% 左右的青少年可能几乎每天都使用大麻。
So we have a concentrated group of what would be the high-risk population here that are using at a pretty high rate.
因此，我们这里有一个集中的高风险人群，他们的使用率相当高。
And then we compare that to somewhere like, let's say, Norway or Sweden or any of the Scandinavian countries where cannabis is not a thing.
然后我们将其与挪威、瑞典或任何斯堪的纳维亚国家等地方进行比较，在这些地方大麻不是一个东西。
Andrew Huberman:
安德鲁·休伯曼：
Hmm.
嗯。
Dr. Matthew Hill:
马修·希尔博士：
Certainly not at a recreational level and not in teenagers.
当然不是在娱乐层面，也不是在青少年中。
And the use rates there are probably under 5%, globally, for teenagers.
全球青少年的使用率可能低于 5%。
Probably closer to 2% or 3%.
可能接近2%或3%。
Andrew Huberman:
安德鲁·休伯曼：
Wow.
哇。
Dr. Matthew Hill:
马修·希尔博士：
So you have two countries that have pretty similar Social structures and other capacities of things.
因此，两个国家的社会结构和其他事物能力非常相似。
We're both Western countries, and yet our schizophrenia rates, prevalence-wise, are relatively comparable, and yet in Canada and the States, our cannabis use rates in adolescents are wildly amplified compared to those countries.
我们都是西方国家，但我们的精神分裂症患病率相对可比，但在加拿大和美国，与这些国家相比，我们青少年的大麻使用率大大增加。
So again, if this was causing schizophrenia to develop as a disease out of nowhere, how would that not track?
那么，如果这导致精神分裂症突然发展为一种疾病，那怎么会不被追踪呢？
How would that not be seen when you just look at individual variances across countries and prevalence rates?
当你只看不同国家之间的个体差异和患病率时，怎么会看不到这一点呢？
Andrew Huberman:
安德鲁·休伯曼：
Yeah, I hear your point loud and clear.
是的，我清楚地听到你的观点。
I seem to recall that there is a higher incidence of schizophrenia independent of cannabis use closer to the poles and less so at the equator.
我似乎记得，在靠近两极的地方，与吸食大麻无关的精神分裂症发病率较高，而在赤道地区则较少。
I don't know if those statistics still hold up, but-
我不知道这些统计数据是否仍然成立，但是-
Dr. Matthew Hill:
马修·希尔博士：
I have no idea.
我不知道。
Andrew Huberman:
安德鲁·休伯曼：
Okay.
好的。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
I don't know the data.
我不知道数据。
Andrew Huberman:
安德鲁·休伯曼：
It'd be interesting for us to look into that because then it would argue that since we're comparing very northern locations to less northern locations, that perhaps cannabis was sort of exacerbating the-
我们对此进行研究会很有趣，因为这样一来，由于我们将非常北部的地区与较不北部的地区进行比较，大麻也许会加剧-
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
You could probably use Greece or Italy.
您可能会使用希腊或意大利。
They're going to have cannabis use higher than Scandinavian countries, but it's going to be way lower than North America still.
他们的大麻使用量将高于斯堪的纳维亚国家，但仍将远低于北美。
Because it's just-
因为这只是——
Andrew Huberman:
安德鲁·休伯曼：
What is it about North Americans and cannabis use?
北美人和大麻使用有何关系？
Dr. Matthew Hill:
马修·希尔博士：
I have no idea.
我不知道。
I think it's just part of the culture here.
我认为这只是这里文化的一部分。
It's just evolved totally differently.
它只是进化得完全不同。
Andrew Huberman:
安德鲁·休伯曼：
The Grateful Dead.
感恩的死者。
No, I'm just kidding.
不，我只是开玩笑。
I'm not picking on the Grateful Dead.
我不是在指责感恩而死乐队。
Dr. Matthew Hill:
马修·希尔博士：
No, no.
不，不。
Andrew Huberman:
安德鲁·休伯曼：
I like the Grateful Dead.
我喜欢《感恩而死》。
Rick Rubin convinced me to start listening to them again because my sister used to listen to them and there's some great songs, and they're from Menlo Park, Palo Alto, so I've done my duty to listen.
里克·鲁宾（Rick Rubin）说服我再次开始听他们，因为我姐姐以前听过他们，里面有一些很棒的歌曲，而且他们来自帕洛阿尔托的门洛帕克，所以我已经尽了听的义务。
There's some great songs, so I'm not picking on them, but-
有一些很棒的歌曲，所以我不会挑剔它们，但是-
Dr. Matthew Hill:
马修·希尔博士：
But you also have in Europe, though, alcohol is also much more normalized in general.
但在欧洲，酒精总体上也更加正常化。
Kids will drink.
小孩子都会喝。
It's not abnormal for kids who are teenagers to drink out.
对于十几岁的孩子来说，出去喝酒并不奇怪。
Alcohol is just much more of a cultural thing as well, and there are just differences.
酒精更多地也是一种文化，并且存在差异。
It's the same thing.
这是同样的事情。
You look at the opioid crisis that we're going through.
你看看我们正在经历的阿片类药物危机。
Sure, it's there to some degree in Europe, but it's nothing like it is in North America.
当然，欧洲在某种程度上存在这种情况，但与北美不同。
We are just a different beast for a lot of drug use.
对于大量吸毒，我们只是一个不同的野兽。
Andrew Huberman:
安德鲁·休伯曼：
Do you see differences between United States and Canada with respect to either cannabis or opioid use?
您认为美国和加拿大在大麻或阿片类药物的使用方面存在差异吗？
Dr. Matthew Hill:
马修·希尔博士：
I don't think dramatically.
我不认为戏剧性。
I think we're pretty comparable.
我觉得我们很有可比性
For cannabis rates, I would say they're almost the same.
对于大麻费率，我想说它们几乎是一样的。
Sure, you might get some regional differences.
当然，您可能会遇到一些地区差异。
I think Quebec has much lower rates of cannabis use than some other parts of Canada, and you guys probably in some southern states maybe are a bit different than other states.
我认为魁北克省的大麻使用率比加拿大其他一些地区低得多，而且你们可能在南部一些州与其他州有些不同。
So, I don't know about that.
所以，我对此一无所知。
But again, overall, at a federal level, which is where most of the data aggregates, I would say that they're pretty comparable with each other.
但总的来说，在联邦层面，也就是大多数数据聚合的地方，我想说它们彼此之间相当具有可比性。
So they're not wildly different at all.
所以它们根本没有太大不同。
And again, even if you talk about climate, a lot of the US is a lot warmer than Canada, and you guys are certainly closer to the equator than we are.
再说一次，即使你谈论气候，美国的很多地方都比加拿大温暖得多，而且你们肯定比我们更靠近赤道。
So, we know you do see higher rates of schizophrenia in urban settings than you do in rural settings, and so-
所以，我们知道城市中的精神分裂症发病率确实比农村中更高，所以-
Andrew Huberman:
安德鲁·休伯曼：
It's the stressor argument.
这是压力源的争论。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
There's a lot of transitory populations that come in and out of cities that you don't see as much in rural communities.
有很多流动人口进出城市，而这在农村社区是看不到的。
There's a lot more mental health services.
还有更多的心理健康服务。
There's other variables that can influence that.
还有其他变量可以影响这一点。
No one's really, I think, sussed out a mechanism to explain why you see that.
我认为，没有人真正想出一种机制来解释为什么你会看到这一点。
But, so there are things that shift across places, but I don't think it has anything to do with the rates of cannabis use.
但是，有些事情会随着地方的不同而变化，但我认为这与大麻的使用率没有任何关系。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
And the other thing that became very interesting in this whole debate over the last 15 odd years, that people have really been talking about this a lot more, is the fact that there's also been several studies now that have done genetics, either at the GWAS level or just even just looking at polygenic risk scores.
在过去 15 多年的整个争论中，另一件变得非常有趣的事情是，人们确实更多地谈论了这个问题，事实上现在也有几项研究已经完成了遗传学，要么是在 GWAS 水平上，要么只是关注多基因风险评分。
And there's at least three papers that I can think of off the top of my head that I could put the citations down for sure after this, that do look at this from a somewhat, let's say, unbiased perspective, where they see there's certainly some genetic architecture that relates to people either initiating cannabis use or people developing cannabis use disorder, and there's clearly some genetic architecture that relates to risk for schizophrenia.
我脑子里至少能想到三篇论文，在这之后我可以肯定地把引文记下来，它们确实从某种程度上，比如说，公正的角度来看待这个问题，他们认为肯定有一些基因结构与开始使用大麻的人或发展大麻使用障碍的人有关，而且显然有一些基因结构与精神分裂症的风险有关。
And what these studies have found across the three of them was quite similar, which was from their analysis, the directionality suggested much more that having genetic risk for schizophrenia predicted cannabis use, more so than cannabis use predicted the development of schizophrenia.
这些研究在这三者中发现的情况非常相似，从他们的分析来看，方向性表明，精神分裂症的遗传风险更多地预测了大麻的使用，而不是大麻的使用预测了精神分裂症的发展。
Andrew Huberman:
安德鲁·休伯曼：
Interesting.
有趣。
Dr. Matthew Hill:
马修·希尔博士：
So what that would mean is that there is some underlying biology that might be shared between a biological vulnerability to develop schizophrenia and some factor that relates to people using and/or liking and/or excessively using cannabis.
因此，这意味着，发展精神分裂症的生物学脆弱性和与人们使用和/或喜欢和/或过度使用大麻相关的某些因素之间可能存在一些潜在的生物学共同点。
Andrew Huberman:
安德鲁·休伯曼：
I've spoken to many psychiatrists in an effort to find someone expert in ADHD.
我曾与许多精神科医生交谈过，试图找到多动症方面的专家。
We've done two episodes on ADHD, focusing on everything from behavioral to nutritional, but also prescription drug treatments for ADHD.
我们已经做了两集关于多动症的节目，重点关注从行为到营养的各个方面，还有多动症的处方药治疗。
And what's interesting is that all of them have relayed the fact that many people, not just young people, but adults with ADHD, will often use, not necessarily abuse, but will use stimulants-
有趣的是，他们所有人都转述了这样一个事实：许多人，不仅仅是年轻人，还有患有多动症的成年人，都会经常使用，不一定是滥用，但会使用兴奋剂——
Dr. Matthew Hill:
马修·希尔博士：
Mm-hmm
嗯嗯
Andrew Huberman:
安德鲁·休伯曼：
...
...
like coffee and other forms of stimulants to a high degree.
高度喜欢咖啡和其他形式的兴奋剂。
And then, of course, you can say, well, perhaps the stimulants are causing-
然后，当然，你可以说，好吧，也许兴奋剂正在导致——
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
ADHD.
多动症。
But they actually argue for the opposite, which is that people are attempting to self-medicate.
但他们实际上主张相反的观点，即人们正在尝试自我治疗。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And then it's perhaps no surprise that most, not all, but most of the medications that are approved for the treatment of ADHD are variants of an amphetamine or similar.
因此，大多数（不是全部）但大多数被批准用于治疗多动症的药物都是安非他明或类似药物的变体，这也许并不奇怪。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
So it's another case where depending on whether or not you look through the lens of the drug leading to the condition or the-
所以这是另一种情况，取决于你是否通过药物的镜头来看待导致病情或-
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
or through the lens of the condition leading to the use of the drug, you can end up in two very different places.
或者通过导致使用药物的病症的镜头，您可能最终会陷入两个截然不同的境地。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
But it looks exactly the same through each lens, so to speak.
但可以这么说，通过每个镜头看起来都完全相同。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
And I've debated with other researchers in the area in print and in person about the different interpretations of this, and one of the possibilities is, again, this idea of self-medication.
我已经与该领域的其他研究人员通过印刷品和面对面的方式就对此的不同解释进行了辩论，其中一种可能性就是自我药疗的想法。
Independent of there being some underlying biological thing that just is a third variable that explains the relationship between cannabis and schizophrenia, the other possibility is self-medication, and there are some studies that suggest this and others that don't support it.
除了存在一些潜在的生物学因素（只是解释大麻和精神分裂症之间关系的第三个变量）之外，另一种可能性是自我药疗，并且有一些研究表明这一点，而另一些研究则不支持这一点。
Anecdotally, from having done work in the community and talked to individuals who have schizophrenia who use cannabis, what their perspective on it is, what I've heard from a few of them is the medications that they're provided to manage the disease are relatively effective at managing, let's say, the positive symptoms, like hallucinations, delusions.
有趣的是，根据我在社区所做的工作以及与使用大麻的精神分裂症患者的交谈，他们对此的看法是什么，我从他们中的一些人那里听到的是，他们提供的用于控制疾病的药物在控制阳性症状（如幻觉、妄想）方面相对有效。
That aspect of the disease is somewhat well-managed.
这种疾病的这一方面在某种程度上得到了很好的控制。
But then there's another component, which is the negative symptoms, which is things like avolitions.
但还有另一个组成部分，那就是阴性症状，比如意志力之类的东西。
They don't like engaging in stuff.
他们不喜欢参与事情。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
There's some anxiety, some depression, some social withdrawal, and a lot of the medications don't manage that component of the disease, and they have said that they find cannabis helps that side of it, or it helps them de-arouse a little bit.
有一些焦虑，一些抑郁，一些社交退缩，很多药物都不能控制这种疾病的这一部分，他们说他们发现大麻有助于缓解这一方面，或者帮助他们稍微消除兴奋。
Even though a lot of them recognize it may trigger the development of some of the positive symptoms, they feel that they don't have any tool in their kit to manage the negative symptoms.
尽管他们中的许多人认识到它可能会引发一些阳性症状的发展，但他们觉得自己的工具箱中没有任何工具来控制阴性症状。
And so It could be, in my mind, when I look at that, it could be a bit of a vicious cycle where someone's using it to band-aid one aspect, but making other aspects of the disease worse at the same time.
所以，在我看来，当我看到这一点时，这可能有点恶性循环，有人用它来创可贴一个方面，但同时使疾病的其他方面变得更糟。
So-
所以——
Andrew Huberman:
安德鲁·休伯曼：
Mm
毫米
Dr. Matthew Hill:
马修·希尔博士：
...
...
it can get very complicated.
它可能会变得非常复杂。
There are various ways of looking at this.
看待这个问题有多种方式。
So it's either you could say there's a causal argument, which is made by many, saying cannabis causes schizophrenia, and therefore if we eradicated it, and I think you had alluded to something like that in the last podcast.
所以，要么你可以说有一个因果论点，这是很多人提出的，说大麻会导致精神分裂症，因此如果我们根除它，我认为你在上一个播客中提到了类似的事情。
That if you removed it, it would have this big effect in terms of reducing schizophrenia rates.
如果你去掉它，它将对降低精神分裂症发病率产生巨大的影响。
And that's similar to the argument that a lot of the researchers in Britain have made, and I'm not personally convinced of that.
这与英国许多研究人员提出的论点类似，但我个人并不相信这一点。
And I say that simply because I look at the data from Scandinavia, and I'm like, well, there you have a population that barely uses any cannabis, and yet their schizophrenia rates are the same.
我这么说只是因为我查看了斯堪的纳维亚半岛的数据，我想，那里的人口几乎不使用任何大麻，但他们的精神分裂症发病率是相同的。
So the only way, in my mind, if I look at this scientifically from a data perspective, that cannabis could be causing schizophrenia de novo in a subset of people, is that there must be an equal proportion of people for whom, for some reason and somehow, cannabis is preventing them from developing schizophrenia, so that it's a zero-sum game at the end of the day, and there's no change in rates.
因此，在我看来，如果我从数据的角度科学地看待这个问题，大麻可能会在一部分人中重新引起精神分裂症，那就是必须有同等比例的人，出于某种原因和某种方式，大麻正在阻止他们患上精神分裂症，所以归根结底这是一场零和游戏，而且比率没有变化。
I can't actually understand any other model that could explain this.
我实际上无法理解任何其他模型可以解释这一点。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
No, the way you're explaining it now makes perfect sense.
不，你现在解释的方式非常有道理。
I do want to make sure that we distinguish between schizophrenia, like psychosis or schizophrenia itself induced by cannabis-
我确实想确保我们区分精神分裂症，例如精神病或由大麻引起的精神分裂症本身 -
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
and manic bipolar episodes.
和躁狂躁郁症发作。
So people who have a predisposition or full-blown manic bipolar, sometimes called manic depression.
因此，具有躁狂倾向或全面躁狂双相的人，有时称为躁狂抑郁症。
Dr. Matthew Hill:
马修·希尔博士：
Mm-hmm.
嗯嗯。
Andrew Huberman:
安德鲁·休伯曼：
There's still a lot of nuance there.
那里仍然有很多细微差别。
We did an episode about this that people can also find linked in the show note captions.
我们制作了一个关于此的剧集，人们也可以在节目注释标题中找到链接。
But in any case, is there any evidence for the fact that people who suffer from or have a predisposition to manic bipolar conditions like bipolar depression, for instance, should avoid high-THC cannabis?
但无论如何，是否有任何证据表明，患有躁郁症或有躁狂躁郁症倾向的人（例如躁郁症）应该避免使用高 THC 大麻？
Dr. Matthew Hill:
马修·希尔博士：
So first of all, in heritability family trees, for example, where you look at something like bipolar schizophrenia, the two do track together.
首先，在遗传性家谱中，例如，当你观察双相精神分裂症等疾病时，两者确实是一起追踪的。
Andrew Huberman:
安德鲁·休伯曼：
Sure.
当然。
Dr. Matthew Hill:
马修·希尔博士：
I think it's hard to separate these in some capacity because I remember years ago at Society for Neuroscience, Glenn Close was one of the-- I don't know if you were at that meeting, but Glenn Close was one of the-
我认为很难以某种方式将这些分开，因为我记得几年前在神经科学学会，格伦·克洛斯是其中之一——我不知道你是否参加了那次会议，但格伦·克洛斯是其中之一——
Andrew Huberman:
安德鲁·休伯曼：
The actress Glenn Close?
女演员格伦·克洛斯？
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
She was one of the public speakers, and she had talked about schizophrenia in her family tree, and she put up this family tree of her family and the previous relatives in her family and showed the individuals who had schizophrenia and bipolar as well.
她是一位公共演讲者，她在她的家谱中谈到了精神分裂症，她把她的家族和她家族中以前的亲戚的家谱放了出来，并展示了患有精神分裂症和双相情感障碍的人。
And this is something I think that's been seen a fair amount is there is some co-relationship in the way that these track at a heritability level.
我认为人们已经看到了相当多的事情，即这些在遗传水平上的追踪方式存在某种相互关系。
And so I don't know that area really well enough to be able to comment on it.
所以我不太了解这个领域，无法对此发表评论。
And from the cannabis perspective, bipolar is definitely much less studied and focused on than schizophrenia is.
从大麻的角度来看，双相情感障碍的研究和关注肯定比精神分裂症少得多。
But I think also to the comment about the high-THC thing, I think this is the other part of the argument that's emerged out of this, and this is the other part where I see a lot of the causality arguments crumble onto themself to some degree.
但我也认为，对于高 THC 问题的评论，我认为这是由此产生的争论的另一部分，也是我看到许多因果关系争论在某种程度上崩溃的另一部分。
And there's been others who've made these very similar arguments to what I'm making here, which is the push that came out of this, out of the UK at least, was much more that it's this high-potency skunk cannabis they referred to.
还有其他人提出了与我在这里提出的非常相似的论点，这是由此产生的推动力，至少是来自英国的推动力，远不止他们提到的这种高效臭鼬大麻。
Which first of all, was based on a smell, which they really hadn't done a lot of analytics on.
首先，这是基于气味，他们确实没有对此进行大量分析。
So people make the assumption if it smells stronger, it's more potent cannabis.
因此，人们假设如果闻起来更浓，则大麻的药效更强。
That's not really true because THC doesn't dictate the odor.
这并不是真的，因为四氢大麻酚并不能决定气味。
That's, as I was saying, more of a terpene thing.
正如我所说，这更多的是萜烯的东西。
But certainly, I'm sure some of the skunk cannabis they were referring to is high-potency cannabis.
但当然，我确信他们所指的一些臭鼬大麻是高效大麻。
And so the analysis on this, if you actually go back to those papers and read, is they often use hash or low-potency cannabis as their control, where they show no association with cannabis.
因此，如果你真的回到这些论文并阅读，对此的分析是他们经常使用哈希或低效大麻作为他们的控制，它们与大麻没有任何关联。
And so that's what's used as this argument that it's the high-potency cannabis that has driven this.
这就是这个论点，即高效大麻推动了这一点。
So now the problem with this argument, in my view, again, I look for what is the answer that fits in with the data.
所以现在这个论点的问题，在我看来，我再次寻找适合数据的答案。
What's the most parsimonious explanation here that everything can be explained by?
一切都可以解释的最简洁的解释是什么？
And so the problem with that argument is if you look at the cannabis schizophrenia literature, everything goes back to this one 1987 Lancet paper out of Sweden, where in that paper, they essentially looked at, they have really detailed life records and health records, and this was Swedish conscripts.
所以这个论点的问题是，如果你看一下关于大麻精神分裂症的文献，一切都可以追溯到 1987 年瑞典发表的《柳叶刀》论文，在那篇论文中，他们基本上看到了，他们有非常详细的生活记录和健康记录，而这就是瑞典应征入伍的士兵。
And they essentially found that if someone had used cannabis, the risk of developing schizophrenia had gone up and up.
他们基本上发现，如果有人使用大麻，患精神分裂症的风险就会不断上升。
And so this was based on a cohort of people, when it was published in '87, that the data would've been collected through the '60s, '70s, early '80s.
所以这是基于一群人，当它在 87 年发表时，数据是在 60 年代、70 年代和 80 年代初收集的。
So we're talking about Sweden and cannabis, where it's not a country that has high cannabis use rates, and in an era when cannabis was hovering in a 2% to 5% THC range.
所以我们谈论的是瑞典和大麻，它不是一个大麻使用率很高的国家，而且在大麻的 THC 含量徘徊在 2% 至 5% 的时代。
That was the initial finding that provided this association between it.
这是提供两者之间关联的初步发现。
And yet the cannabis in that study that they would've been referring to would've been incredibly low potency compared to what has happened, or what it is today.
然而，他们所指的那项研究中的大麻与已经发生的情况或今天的情况相比，其效力低得令人难以置信。
So if the argument is that it's only related to high potency, how would that initial finding have ever been found?
因此，如果争论是它仅与高效力有关，那么最初的发现是如何被发现的呢？
Because it doesn't make any sense.
因为它没有任何意义。
Whereas the alternate explanation that others have put forward, which I agree with and is far more sound, is that there is some biological reason why individuals who are either prone to develop or who have schizophrenia like cannabis, and they will tend to seek out the highest potency product they can get access to.
而其他人提出的另一种解释（我同意并且更合理）是，存在一些生物学原因，导致容易患精神分裂症或患有大麻等精神分裂症的人倾向于寻找他们可以获得的最高效力的产品。
So in the '70s in Sweden, that would've been 2% to 5% THC cannabis.
因此，在 70 年代的瑞典，大麻中的 THC 含量为 2% 至 5%。
Nowadays, it's higher potency cannabis.
如今，它是效力更高的大麻。
Andrew Huberman:
安德鲁·休伯曼：
Mm.
嗯。
Or maybe they seek out lots of different forms of recreational drugs, and cannabis just happens to be one that they land on.
或者他们可能会寻找许多不同形式的娱乐性毒品，而大麻恰好是他们找到的一种。
Which raises the other question, which is it's hard to imagine that these people who develop psychosis, who happen to be using cannabis, are only using cannabis.
这就提出了另一个问题，那就是很难想象这些患有精神病的人碰巧吸食大麻，却只吸食大麻。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
It could be, but presumably-
可能是，但大概——
Dr. Matthew Hill:
马修·希尔博士：
There's no question there's a lot of nicotine consumption.
毫无疑问，尼古丁的消费量很大。
Individuals with schizophrenia, they smoke a lot of cigarettes.
患有精神分裂症的人会吸很多香烟。
That's also-
这也是——
Andrew Huberman:
安德鲁·休伯曼：
That's well established
这是既定的
Dr. Matthew Hill:
马修·希尔博士：
...
...
much higher than the general population rates as well.
也远高于一般人口的比率。
Andrew Huberman:
安德鲁·休伯曼：
Which is known to stimulate dopaminergic-
众所周知，它可以刺激多巴胺能-
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
and other pathways.
和其他途径。
Dr. Matthew Hill:
马修·希尔博士：
And there could be other reasons.
可能还有其他原因。
Again, there may be some reason why they like it.
同样，他们喜欢它可能有一些原因。
And I think this is Something that I think we just don't understand.
我认为这是我们不理解的事情。
It's a very challenging thing to figure out why it is that individuals that have certain diseases may like certain substances.
弄清楚为什么患有某些疾病的人可能喜欢某些物质是一件非常具有挑战性的事情。
Is it helping them?
对他们有帮助吗？
Some people have argued that perhaps nicotine, for example, might enhance cognition in individuals with schizophrenia, and that may be why they like it.
例如，有些人认为尼古丁可能会增强精神分裂症患者的认知能力，这可能就是他们喜欢尼古丁的原因。
Andrew Huberman:
安德鲁·休伯曼：
I think it enhances cognition in everybody.
我认为它可以增强每个人的认知能力。
It just carries certain health concerns.
它只是带来某些健康问题。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And by the way, it doesn't enhance all forms of cognition, but there is a nice body of work to support the idea that nicotine delivered in any number of different forms can improve cognitive function to some extent.
顺便说一句，它并不能增强所有形式的认知功能，但有大量的工作支持这样的观点，即以多种不同形式传递的尼古丁可以在一定程度上改善认知功能。
But I don't suggest people run out and do it.
但我不建议人们跑出去这样做。
And in fact, it's one of the more quickly abused drugs nowadays because of the non-smoking delivery routes that are becoming really popular, pouches and-
事实上，它是当今最容易被滥用的药物之一，因为非吸烟给药途径变得非常流行，袋装和——
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
and things.
和事情。
In fact, I was chewing a little bit of Nicorette gum to do an experiment.
事实上，我嚼了一点尼古丁口香糖来做实验。
I liked it a lot, and then I decided to stop completely recently because it wasn't having the same effect, and I found myself reaching for more, and that's the time when I usually back out.
我非常喜欢它，然后我最近决定完全停止，因为它没有达到相同的效果，而且我发现自己追求更多，而那是我通常退出的时候。
Dr. Matthew Hill:
马修·希尔博士：
Well, yeah.
嗯，是的。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
Dr. Matthew Hill:
马修·希尔博士：
Nicotine's a whole other thing.
尼古丁完全是另一回事。
Andrew Huberman:
安德鲁·休伯曼：
Sure.
当然。
Dr. Matthew Hill:
马修·希尔博士：
Which I, yeah.
我，是的。
Andrew Huberman:
安德鲁·休伯曼：
We'll have you back to talk about nicotine.
我们会让你回来谈论尼古丁。
Dr. Matthew Hill:
马修·希尔博士：
No, I definitely do not know enough about that to have any kind of informed conversation.
不，我对此绝对了解不够，无法进行任何形式的知情对话。
So I don't know.
所以我不知道。
I would say, to me, at the end of the day, if I put all the data together, the perspective that I have on this is, for some reason, be it genetic architecture or biological predisposition, individuals who are prone to develop schizophrenia also seem to be prone to use cannabis, and use it possibly at excessive levels or possibly at higher potency products they seek out.
我想说，归根结底，如果我把所有数据放在一起，我对此的看法是，出于某种原因，无论是遗传结构还是生物倾向，容易患精神分裂症的人似乎也容易使用大麻，并且可能过量使用大麻，或者可能使用他们寻求的更高效力的产品。
Using cannabis, if someone is prone to develop it, may initiate or trigger the onset of the disease.
如果有人容易患上大麻，使用大麻可能会引发或引发疾病的发作。
And I think in the long term, it will likely make the prognosis of the disease worse.
我认为从长远来看，这可能会使疾病的预后变得更糟。
So if you were a psychiatrist in a clinic and you consistently see patients presenting saying, "I didn't have psychosis, I used cannabis, now I have psychosis," and it converts into schizophrenia, I can understand why the association would be made regularly that there's kind of a domino effect here and causality becomes attributed.
因此，如果你是诊所的精神科医生，你总是看到病人说，“我没有精神病，我吸过大麻，现在我有精神病”，然后它转化为精神分裂症，我就能理解为什么这种关联会定期出现，这里有一种多米诺骨牌效应，并且因果关系被归因。
But I think when we take a step back and look at the larger data in its entirety, to me, it's a very tricky argument to make because there's a lot of things that you just can't explain from that perspective.
但我认为，当我们退后一步，全面审视更大的数据时，对我来说，这是一个非常棘手的论点，因为有很多事情你无法从这个角度解释。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
And this is also one of the things that I find absolutely bizarre about cannabis in general is it's a wildly polarizing topic of conversation.
这也是我发现大麻绝对奇怪的事情之一，因为它是一个极其两极分化的话题。
And people have incredibly deep-rooted opinions on both sides of the spectrum.
人们在两个方面都有极其根深蒂固的观点。
And for some reason, if I don't say cannabis is the devil and causes disease, that means I'm an advocate.
出于某种原因，如果我不说大麻是魔鬼并导致疾病，那就意味着我是拥护者。
And then on the other side of the coin, if I don't say cannabis cures everything, I'm a prohibitionist.
另一方面，如果我不说大麻包治百病，我就是一个禁酒主义者。
So I'm in this fun position where I get hate mail from both sides, and everyone just generally, depending on their perspective, thinks that I have a bias going in one way or the other, and I'm very want it this way, or want it this way, when at the end of the day, I'm just like, "No, I just like data." So I'm like, "I'm going to try and answer things as best as I can with data." And to me, that's the perspective I've maintained.
所以我处于一个有趣的境地，我收到了来自双方的仇恨邮件，每个人一般都根据他们的观点，认为我在某一方面存在偏见，我非常想要这种方式，或者想要这种方式，但在一天结束时，我只是想，“不，我只是喜欢数据。”所以我想，“我将尝试用数据尽可能最好地回答问题。”对我来说，这就是我一直坚持的观点。
And I do think that these aren't trivial questions, because when we went through the legalization process in Canada, this was something that came up again and again and again.
我确实认为这些不是微不足道的问题，因为当我们在加拿大经历合法化过程时，这个问题一次又一次地出现。
Was this association with schizophrenia.
这与精神分裂症有关吗？
And in the UK, this is something that comes up again and again and again, because whenever there's any discussion about the UK moving forward to legalization, these ideas come back.
在英国，这种情况会一次又一次地出现，因为每当有任何关于英国迈向合法化的讨论时，这些想法都会回来。
And so the public health consequence of this is not intangible.
因此，这对公共卫生的影响并不是无形的。
And so for people to be making these very strong causality arguments and having this kind of opinion that a lot of people just take up, I think can have a lot of influence.
因此，对于人们提出这些非常有力的因果关系论证并拥有很多人接受的这种观点，我认为可以产生很大的影响。
And so that's why there's literally no reason I should have a dog in this fight.
所以这就是为什么我根本没有理由在这场战斗中养狗。
I don't study schizophrenia in any capacity.
我不以任何身份研究精神分裂症。
And it's not my area of research, but because I am in the cannabis field, I always feel very strongly that we need to maintain clarity over what the data says and not get caught in these opinion-based arguments.
这不是我的研究领域，但因为我在大麻领域，我总是强烈地感到我们需要保持数据的清晰度，而不是陷入这些基于观点的争论中。
And I feel like this is one of these areas that has just kind of-- The amount of people I talk to that regularly tell me that they know that cannabis causes schizophrenia, and they're terrified if someone uses it because it's going to cause them to become schizophrenic, I am just kind of shocked by.
我觉得这是这些领域之一——与我交谈的很多人经常告诉我，他们知道大麻会导致精神分裂症，如果有人使用大麻，他们会感到害怕，因为这会导致他们患上精神分裂症，我只是有点震惊。
So this has clearly permeated the general population, that there's a widespread belief of this.
所以这显然已经渗透到普通民众中，人们普遍相信这一点。
Andrew Huberman:
安德鲁·休伯曼：
I think it's because of these very high-profile papers and the way those were picked up by traditional media.
我认为这是因为这些非常引人注目的论文以及传统媒体报道这些论文的方式。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And this seems to be something that every couple of years, there's a resurgence of this idea.
似乎每隔几年，这个想法就会重新兴起。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Clearly, people are curious about it.
显然，人们对此感到好奇。
And so I just want to say thank you for clarifying what is now, to me, obvious that it could be that there's a relationship there.
所以我只想说谢谢你澄清了现在对我来说很明显可能存在某种关系。
It's clearly not the case yet.
显然情况还不是这样。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And it may never be the case that there's a causal relationship there, and it could just as well be that people who have a predisposition to schizophrenia are seeking out cannabis use and engaging in cannabis use.
那里可能永远不会存在因果关系，也可能是有精神分裂症倾向的人正在寻求大麻的使用并参与大麻的使用。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And I think that's a very important principle for our listeners and viewers to just hear and understand anytime we're talking about a substance and a condition.
我认为这是一个非常重要的原则，让我们的听众和观众在任何时候都能听到并理解我们谈论的物质和条件。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
And I think, again, this is no endorsement.
我再次认为，这并不是认可。
That doesn't mean that it's safe and that it's without harm.
这并不意味着它是安全的并且没有伤害。
I'm just strong of the opinion that I don't think individuals with schizophrenia or who have first-degree relatives should use cannabis because I think there's a high degree of risk there.
我只是强烈认为，我认为患有精神分裂症或有一级亲属的人不应该使用大麻，因为我认为那里的风险很高。
But that's a very different argument than making saying cannabis causes schizophrenia, and if we remove it from society, we'll see drops in rates of schizophrenia.
但这与大麻导致精神分裂症的论点截然不同，如果我们将大麻从社会中剔除，我们就会看到精神分裂症的发病率下降。
I don't believe there's any evidence that actually could support that.
我不相信有任何证据可以真正支持这一点。
So it's just a nuanced argument, and this is a good thing about more of a long-form podcast is it allows for nuance.
所以这只是一个微妙的论点，对于长篇播客来说，这是一件好事，因为它允许细微差别。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
Absolutely.
绝对地。
Let's talk about strains of cannabis.
我们来谈谈大麻品种。
I've spoken before about the sativa versus the indica strains, and certainly there is a lot, a lot of Subjective anecdotal descriptions about differences in the "effects" of those-
我之前已经谈到过苜蓿与籼稻品种的比较，当然有很多很多关于这些品种“效果”差异的主观轶事描述——
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
as reported by users.
据用户报告。
When I talked about this before in the cannabis episode, I leaned on a paper that took those subjective reports of arguably many, many people, pushed those subjective reports through what was known about the strains they claimed to have used.
当我之前在大麻事件中谈到这一点时，我依靠了一篇论文，该论文记录了可以说很多很多人的主观报告，通过他们声称使用的菌株的已知信息来推动这些主观报告。
So this is people are reporting their use.
这就是人们报告的使用情况。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
We assume honestly, but you always have to assume that, I guess people could be lying about which strains, or misinformed.
我们诚实地假设，但你总是必须假设，我猜人们可能在哪些菌株上撒谎，或者误导。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And then using machine learning to couple their subjective experiences, as they report them, to indica versus sativa strains, and then by looking at the chemical composition of those different products, because these were products that they had consumed, trying to tack chemical composition to strain, in this case, mainly the indica/sativa discrepancy, to subjective experience.
然后使用机器学习将他们报告的主观体验与籼稻和苜蓿菌株结合起来，然后通过查看这些不同产品的化学成分，因为这些是他们消费过的产品，试图将化学成分与菌株（在这种情况下，主要是籼稻/苜蓿差异）与主观体验相结合。
And I know that you, and presumably others in the field of cannabis research, take real issue to that sort of approach, and perhaps, I have the feeling this is what you're going to say, rest on the idea that we, at least at this point in time, really can't say anything about the different biological effects of sativas versus indicas.
我知道你，大概还有大麻研究领域的其他人，对这种方法提出了真正的问题，也许，我有感觉这就是你要说的，基于这样的想法，我们，至少在这个时间点，真的不能说出苜蓿与籼稻的不同生物效应。
And yet at the beginning of the episode, you said that there are many, many different cannabinoid compounds in cannabis.
然而在本集开始时，你说大麻中有很多很多不同的大麻素化合物。
So three questions, and I'll keep these very short.
这是三个问题，我会保持简短。
One, do you think that there are different subjective effects of different strains of cannabis that can be attributed to the different strains, right, not just to individual differences in experience?
第一，您是否认为不同品种的大麻有不同的主观影响，这可以归因于不同的品种，对吧，而不仅仅是个体经验的差异？
And then the second is, do you think that there will ever be a time in which we can understand this plant flower, right, to the extent that we can engineer it to provide specific subjective experiences, perhaps more positive than negative, et cetera?
第二个问题是，你认为我们是否会有一天能够理解这种植物花，对吧，我们可以设计它来提供特定的主观体验，也许比消极的更积极，等等？
And then there's a third question, but I'll hold off.
然后还有第三个问题，但我先等等再说。
Dr. Matthew Hill:
马修·希尔博士：
Okay.
好的。
So, yes.
所以，是的。
So going back to just the idea with the indica/sativa thing.
那么回到关于籼稻/苜蓿的想法。
So the indica and sativa names, at least from everything I've understood from everyone that I talk to and being in this field, is those are botanical terms that largely refer to shape of the plant, the way the bud grows, blah, blah, blah.
所以，籼稻和苜蓿的名字，至少从我从与我交谈过的以及在这个领域的每个人那里了解到的一切来看，这些都是植物学术语，主要指的是植物的形状，芽的生长方式，等等。
They do not track with chemical composition in any way.
它们不以任何方式追踪化学成分。
In fact, Nick Jacomus has done a lot of analysis of thousands and thousands of different kinds of cannabis that have been submitted for biochemical analysis to understand THC, CBD, terpenes, minor cannabinoid content.
事实上，Nick Jacomus 对成千上万种不同种类的大麻进行了大量分析，这些大麻已提交进行生化分析，以了解 THC、CBD、萜烯和次要大麻素的含量。
And essentially, his work, as well as from all the people who have done the genetics on this, is the variability that exists within what someone calls an indica or a sativa is greater than the variability that there is between them.
从本质上讲，他的工作以及所有对此进行遗传学研究的人的工作是，人们所说的籼稻或苜蓿中存在的变异性大于它们之间存在的变异性。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
And there is no such thing as a chemical profile that exists in something that's a sativa versus something that's an indica.
苜蓿和籼稻之间不存在化学特征。
Andrew Huberman:
安德鲁·休伯曼：
Is it possible that there's a chemical profile that relates to the most common indicas or most common sativas?
是否有可能存在与最常见的籼稻或最常见的苜蓿相关的化学特征？
Dr. Matthew Hill:
马修·希尔博士：
I think in Nick's analysis, there was a couple of terpenes that may have loaded on a little bit onto things that were sativas, but there was tons of sativas that didn't fall into that bracket.
我认为在尼克的分析中，有一些萜烯可能加载了一点苜蓿的东西，但有大量的苜蓿不属于这个范围。
Andrew Huberman:
安德鲁·休伯曼：
Okay.
好的。
Well, then that immediately, to me, negates the premise of this paper that I was referring to that divides according to indica/sativa, and yet the paper is also trying to distinguish among all the different types or products of cannabis.
好吧，那么对我来说，这立即否定了本文的前提，即我指的是根据籼稻/苜蓿进行划分，但本文还试图区分大麻的所有不同类型或产品。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Meaning, is there some other feature of the cannabis plant that does relate to these different subjective effects?
意思是，大麻植物是否还有其他一些特征与这些不同的主观影响有关？
Because people do seem to get different subjective effects from different products that relate in some way to things other than the concentration of THC.
因为人们似乎确实从不同的产品中获得了不同的主观效果，这些效果在某种程度上与 THC 浓度以外的其他因素有关。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
My honest opinion is this is expectancy bias.
我的诚实观点是这是期望偏差。
This is all expectancy bias.
这都是预期偏差。
Andrew Huberman:
安德鲁·休伯曼：
I see.
我明白了。
So they purchase something that they think is going to make them calm, and it makes them feel calm.
所以他们购买一些他们认为能让他们平静的东西，这让他们感到平静。
Dr. Matthew Hill:
马修·希尔博士：
If 20 people tell you that taking this makes you calm, you cannot remove your expectation bias from the fact that when you consume it, you feel calm.
如果 20 个人告诉你服用此药可以让你平静，那么你无法消除你的预期偏差，因为当你服用它时，你会感到平静。
And this has been, I think, one of the most common things with cannabis, is this whole area is so ripe with these expectancy biases that people have about what they assume.
我认为，大麻最常见的问题之一是，整个领域已经成熟，充满了人们对他们的假设的预期偏差。
If someone goes in, and a budtender tells them, "This is a sativa, it's going to energize you," there's no way to remove that expectancy bias from what you get.
如果有人进去，服务员告诉他们，“这是苜蓿，它会让你充满活力”，那么就没有办法消除你所得到的期望偏差。
And from talking to a lot of people that study this more explicitly, they always say the biggest predictor of what someone feels when they consume cannabis is what they're told on the label it's going to do to them.
通过与许多更明确地研究这一问题的人交谈，他们总是说，人们在吸食大麻时的感受的最大预测因素是标签上告诉他们的大麻会对他们产生的影响。
And a lot of this-
还有很多这样的——
Andrew Huberman:
安德鲁·休伯曼：
That's pretty wild.
这真是太疯狂了。
I did an episode on the placebo effect.
我做了一个关于安慰剂效应的剧集。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
It's similar, yeah.
是的，很相似。
Andrew Huberman:
安德鲁·休伯曼：
And a lot of people hear placebo effect, and they go, "Okay, well, then everything's a..." Placebo effect is amazing.
很多人听到安慰剂效应，然后他们说，“好吧，那么一切都是......”安慰剂效应是惊人的。
There's dose response-
有剂量反应-
Dr. Matthew Hill:
马修·希尔博士：
Yes
是的
Andrew Huberman:
安德鲁·休伯曼：
...
...
in the placebo effect of nicotine on cognition.
尼古丁对认知的安慰剂效应。
Dr. Matthew Hill:
马修·希尔博士：
Interesting.
有趣。
Andrew Huberman:
安德鲁·休伯曼：
Dose response.
剂量反应。
If you're told you got a high dose when you actually got a low dose, you will exhibit the high dose neurocognitive enhancement effect.
如果您被告知您服用了高剂量，而实际上您服用了低剂量，那么您将表现出高剂量的神经认知增强效果。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And by brain imaging, it shows a high dose-like enhancement of the relevant brain areas.
通过大脑成像，它显示出相关大脑区域的高剂量样增强。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
In other words, the expectancy drives changes in brain activity.
换句话说，预期会驱动大脑活动的变化。
Dr. Matthew Hill:
马修·希尔博士：
It's across the board.
这是全面的。
Again, this is not unique to cannabis in any way.
同样，这无论如何都不是大麻所独有的。
It's just cannabis is so ripe for this because of the lore that it just exists.
只是因为大麻的存在，所以它已经成熟了。
People say this.
人们这样说。
The issue has been, and I just asked Ryan Vandrey this, as far as I know, I don't believe there's actually ever been a clinical trial that has blinded people and given them sativas or indicas and actually had them predict what they are or been able to characterize any kind of phenotypical description of what that intoxicated state feels like.
问题是，我刚刚问过 Ryan Vandrey，据我所知，我不相信实际上有过一项临床试验让人们失明，给他们苜蓿或籼稻，并让他们预测自己是什么，或者能够对醉酒状态的感觉进行任何表型描述。
And because the paper that you were referring to where it was users who had got the product, they can't remove their own inherent biases from their own experience.
而且因为您提到的论文是用户获得产品的地方，所以他们无法从自己的体验中消除自己固有的偏见。
It's going to influence it.
它会影响它。
There's no way around it.
没有办法解决这个问题。
And so People kind of lean into this and probably not consciously, but the amount of people I've talked to that really genuinely believe this to their core, that sativa does this and indica does this is fascinating to me because, again, you have these two...
所以人们有点倾向于这一点，可能不是有意识的，但我采访过的很多人都真正相信这一点，苜蓿能做到这一点，籼稻能做到这一点，这对我来说很着迷，因为，再一次，你有这两种......
THC is what drives the high.
THC 是推动高潮的因素。
That's very clear.
这非常清楚。
And you can take a sativa and an indica that have virtually identical levels of THC, and yet people will report very different intoxicating states that come out of that.
苜蓿和籼稻的 THC 含量几乎相同，但人们会报告由此产生的截然不同的醉人状态。
Andrew Huberman:
安德鲁·休伯曼：
Do you think this also explains the lore, or perhaps it's real, that different alcohols produce different drunks?
您认为这是否也解释了传说，或者也许这是真实的，即不同的酒精会产生不同的醉酒者？
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
I've got friends who will swear that whiskey makes them feel aggressive-
我有一些朋友发誓威士忌让他们感到好斗——
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
and vodka is mellow, and that white tequilas feel different than the other tequilas.
伏特加味道醇厚，白龙舌兰酒的感觉与其他龙舌兰酒不同。
And, for people listening to this thinking, "Okay, well, that's not science," I agree.
而且，对于听到这种想法的人来说，“好吧，这不是科学，”我同意。
That's not science.
那不是科学。
That's just anecdote.
这只是轶事。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And yet, the chemical composition of these different drinks is different, but ultimately, we're talking about alcohol, right?
然而，这些不同饮料的化学成分是不同的，但最终，我们谈论的是酒精，对吗？
Dr. Matthew Hill:
马修·希尔博士：
Alcohol.
酒精。
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Different sugar contents.
含糖量不同。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Different hangover propensity.
不同的宿醉倾向。
Dr. Matthew Hill:
马修·希尔博士：
I have to believe the majority of that's an expectancy bias.
我不得不相信其中大部分是预期偏差。
Andrew Huberman:
安德鲁·休伯曼：
Wow, okay.
哇，好吧。
Dr. Matthew Hill:
马修·希尔博士：
I have a hard time believing that these things are really driven by fundamental biological differences within.
我很难相信这些事情真的是由内在的基本生物学差异驱动的。
Because anything else, that's the thing.
因为其他的事情，就是这样。
Sure, some of the labs now, there is a movement to start looking at can certain compositions of other things in cannabis start to maybe modulate or influence?
当然，现在一些实验室正在采取行动，开始研究大麻中其他物质的某些成分是否可能开始调节或影响？
This is called, I think I've said this before, the entourage effect.
我想我之前已经说过，这就是所谓的随从效应。
This idea that THC alone might do one thing, but then layering in other terpenes or minor cannabinoids may influence that effect.
这种想法认为，单独的 THC 可能会起到一定作用，但与其他萜烯或次要大麻素分层可能会影响这种效果。
That is a theory.
这是一个理论。
That's not a thing that we know definitively in any way, and in fact, there's virtually no research that's ever been done to test this.
这不是我们以任何方式明确知道的事情，事实上，几乎没有任何研究来测试这一点。
There's some stuff that's starting to come out now.
现在有些东西已经开始出现了。
Like Ryan Vandrey at Hopkins recently published a paper where they, in a dose-dependent manner, added limonene, which is one of these terpenes, like I said, I think gives it a citrusy odor, into the THC.
就像霍普金斯大学的 Ryan Vandrey 最近发表的一篇论文一样，他们以剂量依赖的方式在 THC 中添加了柠檬烯，柠檬烯是这些萜烯之一，就像我说的，我认为它具有柑橘味。
And did find at a really high dose, probably a dose that I don't think you could actually find in cannabis, it's a little bit higher than what you would've gotten there, but limonene did seem to be able to curb the ability of high-dose THC to make someone feel anxious.
并且确实发现了非常高的剂量，可能是我认为你实际上在大麻中找不到的剂量，它比你在那里得到的剂量要高一点，但柠檬烯似乎确实能够抑制高剂量 THC 让人感到焦虑的能力。
And this was done in a blinded manner, so there's, I think, some validity to the interaction.
这是以盲目的方式完成的，所以我认为这种互动有一定的有效性。
Whether that's occurring in cannabis naturally because of the levels of THC to limonene, I don't know.
我不知道这是否是由于大麻中四氢大麻酚和柠檬烯的含量而自然发生的。
But it really was one of the first demonstrations that adding in a terpene could actually influence a component of the intoxicated state in a blinded manner.
但这确实是第一个证明添加萜烯实际上可以以盲目的方式影响醉酒状态的一个组成部分。
I think is interesting.
我觉得很有趣。
And Ziva Cooper, who's here at UCLA, is doing some work with beta-caryophyllene, which is probably the second most abundant terpene, I think, from Nick Jakomis's work.
加州大学洛杉矶分校的 Ziva Cooper 正在对 β-石竹烯进行一些研究，我认为这可能是 Nick Jakomis 工作中第二丰富的萜烯。
I think myrcene may have been the highest prevalent terpene across all types of cannabis.
我认为月桂烯可能是所有类型大麻中最常见的萜烯。
Beta-caryophyllene is probably the second, and limonene, I think, is probably the third.
β-石竹烯可能是第二个，柠檬烯，我认为，可能是第三个。
And so they're looking at, I think Ziva's work is in the context of pain, so they're trying to look at if a fixed dose of THC, if you add in varying levels of beta-caryophyllene, does this influence this?
所以他们正在研究，我认为 Ziva 的工作是在疼痛的背景下进行的，所以他们正在尝试研究固定剂量的 THC，如果添加不同水平的 β-石竹烯，是否会对此产生影响？
Because again, you do see this in patient communities where they say, "Well, this strain helps my pain better than that strain."
因为，你确实在患者社区中看到了这一点，他们说：“嗯，这种压力比那种压力更好地缓解我的疼痛。”
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
And so it's like, okay, is there actual legitimacy to this?
And so it's like, okay, is there actual legitimacy to this?
Or again, is this just an expectancy bias because someone who sold this to you told you that this strain is better for pain?
Or again, is this just an expectancy bias because someone who sold this to you told you that this strain is better for pain?
And the problem is these are all subjective endpoints.
问题是这些都是主观终点。
This is pain, sleep, anxiety.
This is pain, sleep, anxiety.
These are all how someone personally experiences it.
这些都是某人亲身经历的。
And we know from all the clinical trials that study pain, sleep, and anxiety, there's massive placebo effects that happen in all these conditions.
我们从所有研究疼痛、睡眠和焦虑的临床试验中知道，在所有这些情况下都会发生大量的安慰剂效应。
And so it's very difficult to actually make any kind of sound statements about this in the absence of there being clinical trials that have clearly started to do this.
因此，在没有明确开始这样做的临床试验的情况下，很难对此做出任何合理的陈述。
But it's like, as you can imagine when you start doing the math, given the amount of terpenes, the amount of combinations at different levels, how overwhelming this could become.
但这就像，正如你可以想象的那样，当你开始进行数学计算时，考虑到萜烯的数量，不同水平的组合数量，这会变得多么令人难以承受。
Because maybe there's a few that you need in there that interact with THC, not just one.
Because maybe there's a few that you need in there that interact with THC, not just one.
There is a lot of work that's happened in the last few years that has really started to try and look at if these terpenes or minor cannabinoids act at the cannabinoid receptor, which none of them seem to.
过去几年发生了很多工作，真正开始尝试研究这些萜烯或次要大麻素是否对大麻素受体起作用，但似乎没有一个对大麻素受体起作用。
So this isn't like you've got things that modulate how THC is binding to CB1.
So this isn't like you've got things that modulate how THC is binding to CB1.
If they're doing something else, it's probably through an interaction with another neurochemical system that's influencing what THC is doing.
If they're doing something else, it's probably through an interaction with another neurochemical system that's influencing what THC is doing.
So I'm not against the idea that different chemovars, or what people call strains of cannabis, could do different things subjectively.
所以我并不反对不同的化学变体，或者人们所说的大麻品种，可以主观地做不同的事情。
I just am remiss to believe this until I see some blinded data because I think outside of that, we know how powerful an expectancy bias is, so it makes it very, very challenging to make any kind of firm statements.
在我看到一些盲目的数据之前，我只是不相信这一点，因为我认为除此之外，我们知道预期偏差有多么强大，因此做出任何坚定的声明都变得非常非常具有挑战性。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
And so in the context of how you introduced this, that was, again, I think one of the issues that I took with the other podcast was because, as you've said, I understand the thought process you went through.
因此，在您如何介绍这一点的背景下，我认为我在另一个播客中遇到的问题之一是因为，正如您所说，我理解您所经历的思维过程。
You had this paper where people were reporting subjective effects.
You had this paper where people were reporting subjective effects.
There's some neuroimaging data that's been done with cannabis, so you said, "Okay, this is what that was, and that was what sativa did versus this is what indica did." So I think it's important that you explain that because I do think that-
有一些用大麻进行的神经影像数据，所以你说，“好吧，这就是事实，这就是苜蓿所做的，而这就是籼稻所做的。”所以我认为你解释这一点很重要，因为我确实认为-
Andrew Huberman:
安德鲁·休伯曼：
Well, that's what the data pointed to.
Well, that's what the data pointed to.
But now what I'm realizing is that any time we're talking about cannabis, because of the 70 plus cannabinoids present that could modify or join, so work in parallel with the effects of THC, we're really talking about polypharmacology.
但现在我意识到，每当我们谈论大麻时，因为存在 70 多种大麻素，它们可以改变或加入，因此与 THC 的作用同时发挥作用，我们实际上是在谈论多药理学。
Dr. Matthew Hill:
马修·希尔博士：
Possibly.
可能吧。
Andrew Huberman:
安德鲁·休伯曼：
It's not a pure substance.
它不是纯净物。
It's not like giving anandamide.
It's not like giving anandamide.
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Or it's not like adjusting levels of endogenous anandamide.
或者它不像调整内源性大麻素的水平。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
This raises, I think, an equally important issue for us to resolve, which is CBD-
This raises, I think, an equally important issue for us to resolve, which is CBD-
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
which we didn't talk about earlier.
which we didn't talk about earlier.
When Nolan Williams, who's a psychiatrist, he's one of these phenoms, triple board certified psychiatry, neurology, colleague of mine from Stanford School of Medicine who mainly works on ibogaine and transcranial magnetic stimulation.
诺兰·威廉姆斯是一名精神病学家，他是这些杰出人物之一，经过三重委员会认证的精神病学、神经病学，我在斯坦福大学医学院的同事，主要研究伊博加因和经颅磁刺激。
But we talked about cannabis a bit when he was on the podcast, and he mentioned a strain of cannabis that is available in Colorado, which is pure CBD.
但当他在播客上时，我们谈到了大麻，他提到了科罗拉多州有一种大麻品种，它是纯 CBD。
I think it's called Charlotte's Web.
我想它叫夏洛特的网。
And the parents of Children who have epilepsy-
还有患有癫痫病的孩子的父母——
Dr. Matthew Hill:
马修·希尔博士：
Mm-hmm
嗯嗯
Andrew Huberman:
安德鲁·休伯曼：
...
...
will move there or go there just to get this strain because it seems to help their epileptic seizures.
will move there or go there just to get this strain because it seems to help their epileptic seizures.
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
I would say that's definitely not true nowadays.
I would say that's definitely not true nowadays.
Pre-legalization anywhere outside of Colorado, that was true.
Pre-legalization anywhere outside of Colorado, that was true.
People were gravitating there towards it.
人们被它所吸引。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
So the questions are, could you tell us a little bit about the biology of the CBD receptor, mainly as it relates to CB1 or not?
So the questions are, could you tell us a little bit about the biology of the CBD receptor, mainly as it relates to CB1 or not?
Does it bind CB1 as well?
它也结合CB1吗？
If not, how is it working?
If not, how is it working?
And you mentioned that people will not report any subjective effect of taking a pure CBD compound, so lacking THC, but it sounds like it may have some usefulness for treatment of epilepsy.
你提到人们不会报告服用纯 CBD 化合物的任何主观效果，因此缺乏 THC，但听起来它可能对治疗癫痫有一些用处。
And what are some other established, meaning clinical trials and/or lab data to support the use of CBD for any type of either psychiatric condition, pain, et cetera?
还有哪些其他已建立的临床试验和/或实验室数据来支持 CBD 用于任何类型的精神疾病、疼痛等？
Dr. Matthew Hill:
马修·希尔博士：
So, the first thing that's interesting that I think a lot of people don't understand about CBD is CBD doesn't really exist in any form of street cannabis, and it hasn't for a very long time.
因此，我认为很多人不了解 CBD 的第一件有趣的事情是 CBD 并不真正存在于任何形式的街头大麻中，而且已经很长一段时间了。
Andrew Huberman:
安德鲁·休伯曼：
You mean there's no CBD in there?
你的意思是里面没有CBD？
Dr. Matthew Hill:
马修·希尔博士：
There's some.
有一些。
There's very low levels of CBD.
CBD 含量非常低。
And the reason that is, is because THC and CBD are both made from the same precursor molecule, and which direction it goes in is based purely on which synthetic enzyme converts it to either THC or CBD.
原因是 THC 和 CBD 都是由相同的前体分子制成的，其进入的方向纯粹取决于哪种合成酶将其转化为 THC 或 CBD。
And so as people have clearly chased THC and wanted cannabis that's rich in THC, and so cannabis has been bred to become higher content in THC, by default, CBD has been bred out of the plant, and it has largely been bred out of the plant for quite some time.
因此，由于人们显然追逐 THC 并想要富含 THC 的大麻，因此大麻已被培育成 THC 含量更高的大麻，默认情况下，CBD 已从植物中培育出来，并且很大程度上已经从植物中培育出相当长一段时间了。
I always find it interesting that there's this community that's like, "Oh, well, THC is the recreational cannabis and CBD is the medical cannabis." I'm always like, that's bizarre, because historically, THC has been what people have bred cannabis for.
我总是觉得很有趣的是，有这样一个社区，“哦，好吧，THC 是休闲大麻，CBD 是医用大麻。” I'm always like, that's bizarre, because historically, THC has been what people have bred cannabis for.
And so any medical benefits that people have reported from cannabis per se usually are THC and CB1 driven.
因此，人们报告的大麻本身的任何医疗益处通常都是 THC 和 CB1 驱动的。
CBD is this other molecule that we can go into the pharmacology in a second, but again, I think in the analysis that Nick Jacoma did of all these strains and types of cannabis that exist in the United States when they went through their thing of thousands and thousands of kinds of cannabis, it was like 3% of them maybe had more than 1% CBD.
CBD 是我们可以立即进入药理学的另一种分子，但我再次认为，在 Nick Jacoma 对美国存在的所有这些大麻品种和类型进行的分析中，当他们经历了成千上万种大麻时，其中 3% 的大麻可能含有超过 1% 的 CBD。
It's very low.
这是非常低的。
There's almost none.
几乎没有。
And in Canada, to get a CBD-rich strain, you have to basically explicitly buy it because it has to be bred to make CBD.
And in Canada, to get a CBD-rich strain, you have to basically explicitly buy it because it has to be bred to make CBD.
And so this is the kind of chemo of our distinction, I think you did allude to this last time, which is the type one, type two, type three.
And so this is the kind of chemo of our distinction, I think you did allude to this last time, which is the type one, type two, type three.
So type one is high THC, type two is somewhat balanced, and type three is high CBD.
So type one is high THC, type two is somewhat balanced, and type three is high CBD.
And now, I think like 90 to 90 something low percent of all cannabises that are out there are type one.
And now, I think like 90 to 90 something low percent of all cannabises that are out there are type one.
They're all high THC because that's what's been bred.
They're all high THC because that's what's been bred.
There's a few that have been mixed, and so are equal proportions, but you're never going to get high equal proportions.
There's a few that have been mixed, and so are equal proportions, but you're never going to get high equal proportions.
So a high THC cannabis is like 20 to 30%.
因此，高 THC 大麻的含量约为 20% 至 30%。
If you go for type two, which is mixed, they're both going to fall around 12%.
If you go for type two, which is mixed, they're both going to fall around 12%.
Maybe a little more, but in that range, and then same if you've got a type three, it's high CBD, it's going to be 20-ish percent CBD and very low THC.
也许多一点，但在这个范围内，如果你有第三类，同样，它的 CBD 含量很高，CBD 含量将达到 20%左右，THC 含量非常低。
And so no one has ever grown CBD-rich cannabis outside of this recent boom in the last decade that's happened about people wanting CBD because of the Charlotte's Web, which was popularized by, I think, Sanjay Gupta on CNN in like 2012 or something.
因此，除了过去十年中最近的繁荣之外，没有人种植过富含 CBD 的大麻，人们因为夏洛特的网而想要 CBD，我认为夏洛特网是由桑杰·古普塔 (Sanjay Gupta) 在 CNN 上于 2012 年或其他时间普及的。
It was a while ago.
那是不久前的事了。
But that was what got a huge movement going around this idea of CBD.
But that was what got a huge movement going around this idea of CBD.
And yeah, so the Charlotte's Web was, I believe that was what they had named that kind of cannabis that they'd extracted it from.
And yeah, so the Charlotte's Web was, I believe that was what they had named that kind of cannabis that they'd extracted it from.
And so it was a tincture that they were using that was very high CBD content that they were finding was controlling pediatric seizures in kids.
And so it was a tincture that they were using that was very high CBD content that they were finding was controlling pediatric seizures in kids.
Now, this has actually been studied pretty effectively.
Now, this has actually been studied pretty effectively.
Most of it's come out of Boston.
大部分来自波士顿。
Elizabeth Thiele has been one of the main leads on this, and she's a neurologist there that has done a lot of the work on this.
Elizabeth Thiele has been one of the main leads on this, and she's a neurologist there that has done a lot of the work on this.
And so they have, I think, very clearly, and the data is incredibly compelling.
And so they have, I think, very clearly, and the data is incredibly compelling.
Their research is one of the reasons why CBD has been descheduled or changed in its scheduling down to a, what is it?
Their research is one of the reasons why CBD has been descheduled or changed in its scheduling down to a, what is it?
A five?
五？
What is a class?
什么是班级？
Andrew Huberman:
安德鲁·休伯曼：
CBD?
CBD？
Dr. Matthew Hill:
马修·希尔博士：
Yeah, like CBD.
是的，就像 CBD 一样。
Andrew Huberman:
安德鲁·休伯曼：
Oh, CBD.
哦，CBD。
Given the availability of CBD everywhere-
鉴于 CBD 无处不在 -
Dr. Matthew Hill:
马修·希尔博士：
Yeah, it's-
是的，这是——
Andrew Huberman:
安德鲁·休伯曼：
...
...
in gummies and drinks and you can get it in a convenience store.
in gummies and drinks and you can get it in a convenience store.
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
So a lot of it's been shifted in its classification status, because it actually has been shown very clearly to have medical benefit.
So a lot of it's been shifted in its classification status, because it actually has been shown very clearly to have medical benefit.
And it was a very specific form of pediatric epilepsy called Dravet syndrome.
And it was a very specific form of pediatric epilepsy called Dravet syndrome.
Now, there's other forms of pediatric epilepsy I know Elizabeth has studied in addition that has found comparable levels of efficacy.
Now, there's other forms of pediatric epilepsy I know Elizabeth has studied in addition that has found comparable levels of efficacy.
But essentially what they have shown is that very high doses of CBD are relatively effective at calming down the seizures.
但本质上他们所表明的是，非常高剂量的 CBD 在平息癫痫发作方面相对有效。
In some kids, it's profound.
对于一些孩子来说，这是深刻的。
In some kids, you're talking about kids that were having dozens of seizures a day to essentially none.
在一些孩子中，你谈论的是每天有数十次癫痫发作的孩子，甚至基本上没有。
And so, and I can understand.
所以，我可以理解。
Andrew Huberman:
安德鲁·休伯曼：
That's impressive.
这令人印象深刻。
Yeah, that's super impressive.
是的，这太令人印象深刻了。
Dr. Matthew Hill:
马修·希尔博士：
From a grassroots perspective, I can understand if you were a parent who had a child with a disease like this that was largely intractable and not that well-controlled from the medications they were on, and then something came around that showed this level of efficacy, you would gravitate towards it.
从基层的角度来看，我可以理解，如果你是一位父母，你的孩子患有这样的疾病，这种疾病在很大程度上是顽固性的，并且无法通过他们所服用的药物得到很好的控制，然后出现了一些显示出这种疗效的药物，你就会倾向于它。
That makes sense to me.
这对我来说很有意义。
And I think the work that Elizabeth and her colleagues have done has been really important to establish the efficacy of CBD in these disease states.
我认为伊丽莎白和她的同事所做的工作对于确定 CBD 在这些疾病状态下的功效非常重要。
And so I don't think at this point there's a lot of controversy around that.
所以我认为目前这方面还没有太多争议。
The question that comes out, though, is so how is it working?
The question that comes out, though, is so how is it working?
And we don't have a mechanism.
而且我们没有机制。
So as you had said, CBD receptor, there's no receptor that CBD binds to.
So as you had said, CBD receptor, there's no receptor that CBD binds to.
Andrew Huberman:
安德鲁·休伯曼：
I was under the impression that CBD also bound to the CB1 receptor.
我的印象是 CBD 也与 CB1 受体结合。
Dr. Matthew Hill:
马修·希尔博士：
No. Certainly not-
不，当然不是——
Andrew Huberman:
安德鲁·休伯曼：
Or that under some conditions it can modulate ...
或者说在某些条件下它可以调节......
the shape of the receptor to adjust THC binding.
受体的形状来调整 THC 结合。
But now you're telling me that these two things-
但现在你告诉我这两件事——
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
rarely coexist together.
很少共存在一起。
So I guess the question then would be-
所以我想接下来的问题是——
Dr. Matthew Hill:
马修·希尔博士：
You can dose them.
你可以给它们服药。
You can have products that are made that are oil-based products at least, that have a certain amount of CBD and a certain amount of THC, and people do go for those.
你可以拥有至少是油基产品制成的产品，含有一定量的 CBD 和一定量的 THC，人们确实会购买这些产品。
One of the arguments people make is they say, "Oh, introducing CBD reduces the adverse effects to THC." Well, if you're using it in a strain, that's simply because the strain of cannabis has less THC now.
人们提出的论点之一是他们说，“哦，引入 CBD 可以减少对 THC 的不利影响。” Well, if you're using it in a strain, that's simply because the strain of cannabis has less THC now.
Andrew Huberman:
安德鲁·休伯曼：
Right.
对。
So it's impossible to separate.
所以说是不可能分开的。
Dr. Matthew Hill:
马修·希尔博士：
So you've bred it out.
所以你已经把它培育出来了。
But a lot of this was based on some work that came out a long time ago from Brazil, where they showed that giving CBD with a relatively high dose of THC could curb some anxiety that came out from high-dose THC.
但这在很大程度上是基于很久以前在巴西发表的一些研究，他们表明，给予 CBD 与相对较高剂量的 THC 可以抑制高剂量 THC 产生的一些焦虑。
Andrew Huberman:
安德鲁·休伯曼：
I thought the explanation for that was that CBD can modify the CB1 receptor in some way that makes THC less able to engage with the THC receptor.
我认为对此的解释是 CBD 可以以某种方式修改 CB1 受体，从而使 THC 不太能够与 THC 受体结合。
Dr. Matthew Hill:
马修·希尔博士：
There is some evidence to support that, that we would call these allosteric modulators.
有一些证据支持这一点，我们将这些称为变构调节剂。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
There's some evidence to suggest that CBD may interact with a allosteric site on the cannabinoid receptor that makes THC bind less.
有一些证据表明 CBD 可能与大麻素受体上的变构位点相互作用，从而减少 THC 的结合。
Andrew Huberman:
安德鲁·休伯曼：
Doesn't sound like you're particularly convinced by that evidence.
听起来你并不特别相信这些证据。
Dr. Matthew Hill:
马修·希尔博士：
I think that, I mean, like the paper-
我认为，我的意思是，就像报纸一样——
Andrew Huberman:
安德鲁·休伯曼：
I'm looking at the look on your face.
我正在看着你脸上的表情。
For those listening, I'm looking at Matt, and I think he's being generous here.
对于那些倾听的人，我正在看着马特，我认为他在这里很慷慨。
Let me ask it a little differently.
让我换个方式问一下。
Dr. Matthew Hill:
马修·希尔博士：
It's definitely more complex than that.
它肯定比这更复杂。
Andrew Huberman:
安德鲁·休伯曼：
Does anyone know what CBD binds to?
有谁知道CBD与什么结合？
Dr. Matthew Hill:
马修·希尔博士：
So, the most convincing thing that I've seen that CBD binds to is the work that C.C.
因此，我所看到的 CBD 所结合的最令人信服的事情是 C.C.
Hilliard has done, looking at its ability to essentially block adenosine uptake.
希利亚德已经这样做了，研究了它从根本上阻止腺苷吸收的能力。
And so it can inhibit the adenosine transporter, so it causes-
所以它可以抑制腺苷转运蛋白，所以它会导致-
Andrew Huberman:
安德鲁·休伯曼：
So that should make people feel more alert.
所以这应该会让人们感到更加警觉。
Dr. Matthew Hill:
马修·希尔博士：
No, because you're getting more adenosine, so you get an accumulation.
不，因为你得到了更多的腺苷，所以你会积累。
It blocks the adenosine transport mechanism.
它阻断腺苷转运机制。
Andrew Huberman:
安德鲁·休伯曼：
I see.
我明白了。
Oh, so, okay.
哦，那么，好吧。
Dr. Matthew Hill:
马修·希尔博士：
So you get an accumulation of adenosine-
所以你会积累腺苷-
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm
嗯嗯
Dr. Matthew Hill:
马修·希尔博士：
...
...
which is more sedative.
哪个更镇静。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
And that, in the PNAS paper that C.C.'s lab had from 2006, they showed that that also mediated, it was the adenosine, I think 2A receptor, that drove the anti-inflammatory effects of CBD.
而且，在 C.C. 实验室 2006 年发表的 PNAS 论文中，他们表明，腺苷（我认为是 2A 受体）也介导了 CBD 的抗炎作用。
So it was this secondary effect by-
所以这就是这种二次效应——
Andrew Huberman:
安德鲁·休伯曼：
Sort of the opposite of-
有点相反——
Dr. Matthew Hill:
马修·希尔博士：
Caffeine
咖啡因
Andrew Huberman:
安德鲁·休伯曼：
...
...
of caffeine.
咖啡因。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
No, if I'm ever doing like-
不，如果我曾经这样做过——
Andrew Huberman:
安德鲁·休伯曼：
Now, the way you're describing this, it sounds like the anti-caffeine.
现在，按照你描述的方式，它听起来像是抗咖啡因药物。
Dr. Matthew Hill:
马修·希尔博士：
That's kind of how I describe to people if they ever ask me for what the pharmacology of CBD is.
如果人们问我 CBD 的药理学是什么，我就是这样向他们描述的。
Andrew Huberman:
安德鲁·休伯曼：
Interesting.
有趣。
Dr. Matthew Hill:
马修·希尔博士：
I'm like, that's not the only mechanism, but the thing that was important in C.C.'s studies that I think is relevant is that it was not super high concentrations of CBD that caused that.
我想，这不是唯一的机制，但在 C.C. 的研究中，我认为相关的重要一点是，导致这种情况的并不是超高浓度的 CBD。
So you could get this adenosine accumulation at, you're not talking like micromolar levels of CBD, which is what a lot of studies have done.
所以你可以得到这种腺苷积累，你说的不是微摩尔水平的 CBD，这是很多研究所做的。
And so even when we're talking about the allosteric modulatory site, yes, there's evidence for it, and it is convincing evidence, it's just the dose range in there, you're kind of like-
所以即使当我们谈论变构调节位点时，是的，有证据证明它，而且这是令人信服的证据，这只是那里的剂量范围，你有点像-
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm
嗯嗯
Dr. Matthew Hill:
马修·希尔博士：
...
...
who's getting hit with CBD at that level where you're getting these effects?
谁会受到 CBD 的影响而达到这些效果？
And more so when they've done the blinded work, like when Ryan Vandrey at Hopkins again, who is one of the main people who's done a lot of this work, has actually blindly given people CBD dosing with THC, finds the opposite, that it actually amplifies some of the effects of THC.
更重要的是，当他们完成了盲目的工作时，就像霍普金斯大学的 Ryan Vandrey 再次，他是做了很多这项工作的主要人员之一，实际上盲目地给人们服用 CBD 和 THC 剂量，发现相反，它实际上放大了 THC 的一些影响。
And this was something we learned from the pediatric epilepsy world, was that when you start giving CBD at relatively high doses, one of the things it does is saturate a lot of liver enzymes.
这是我们从儿科癫痫领域学到的东西，当你开始以相对较高剂量给予 CBD 时，它所做的事情之一就是使大量肝酶饱和。
And so some of the efficacy in the pediatric epilepsy space may be a secondary effect due to an accumulation of some of the antiepileptics as well, because they're not being metabolized the same way.
因此，在小儿癫痫领域的一些功效可能是由于一些抗癫痫药的积累而产生的次要效应，因为它们的代谢方式不同。
And this has now been very well replicated.
现在这一点已经得到了很好的复制。
We know that once you start taking CBD, when they hit doses that are at the clinical level, you're going to start having hepatic effects.
我们知道，一旦您开始服用 CBD，当达到临床水平的剂量时，您就会开始产生肝脏影响。
So it's going to affect the liver, and it's going to affect the ability of the liver to chew up other drugs.
所以它会影响肝脏，并且会影响肝脏咀嚼其他药物的能力。
Andrew Huberman:
安德鲁·休伯曼：
Not good.
不好。
Dr. Matthew Hill:
马修·希尔博士：
And there's very specific CYP enzymes, like the cluster of enzymes that metabolize things.
还有非常特殊的 CYP 酶，例如代谢物质的酶簇。
There's very specific ones that CBD hits.
CBD 有一些非常具体的目标。
And so as a consequence, one of them is what chews THC up.
因此，其中之一就是吞噬 THC 的物质。
So you can get a potentiation of THC by inhibiting its metabolism if you have high enough CBD on board.
因此，如果您体内的 CBD 含量足够高，您可以通过抑制 THC 的新陈代谢来增强 THC 的作用。
Andrew Huberman:
安德鲁·休伯曼：
Given the effects on adenosine that you described before, that it's sort of the, what we're calling, just for sake of discussion, the anti-caffeine, how do we explain the preponderance of CBD added to energy drinks that also contain caffeine?
鉴于您之前描述的对腺苷的影响，我们称之为抗咖啡因，只是为了讨论，我们如何解释 CBD 添加到也含有咖啡因的能量饮料中的优势？
There's no logic there.
那里没有逻辑。
Dr. Matthew Hill:
马修·希尔博士：
Expectancy bias.
预期偏差。
Andrew Huberman:
安德鲁·休伯曼：
There you go.
就这样吧。
Dr. Matthew Hill:
马修·希尔博士：
I mean, yeah.
我的意思是，是的。
Andrew Huberman:
安德鲁·休伯曼：
Everything can't be expectancy bias.
一切都不能是期望偏差。
Dr. Matthew Hill:
马修·希尔博士：
I mean-
我的意思是——
Andrew Huberman:
安德鲁·休伯曼：
I have a feeling it's going to be interesting to see in the comment section on YouTube.
我有预感，在 YouTube 的评论部分看到它会很有趣。
Presumably there's some regular pot smokers listening to this, and the expectancy bias is so strong, as-
想必有一些经常吸大麻的人在听这个，并且期望偏差是如此之大，因为-
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
I allude to in the placebo episode, and we've been talking about here.
我在安慰剂情节中提到过，我们一直在这里讨论。
And yet it's so strong that I think people will also be convinced that there are real differences between different strains because they've maybe done the non-formal blind, someone gave them their weed and someone else-
然而它是如此强烈，以至于我认为人们也会相信不同菌株之间存在真正的差异，因为他们可能已经进行了非正式的盲测，有人给了他们大麻，而其他人则-
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
and then they got a completely different effect, right?
然后他们得到了完全不同的效果，对吧？
They're not expecting something different necessarily-
他们不一定期待不同的事情-
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
or in a particular direction, but they get a very different effect.
或朝某个特定方向，但它们会得到截然不同的效果。
But that to me just speaks to the idea that, again, cannabis sounds like polypharmacology.
但对我来说，这再次说明了大麻听起来像多重药物学。
70 different cannabinoids.
70 种不同的大麻素。
Dr. Matthew Hill:
马修·希尔博士：
In some ways, yeah.
在某些方面，是的。
Andrew Huberman:
安德鲁·休伯曼：
THC being among the more powerful components, but it's yoked in the sense that, as you said, people self-regulate their intake, provided they're smoking, not ingesting it by edible.
THC 是更强大的成分之一，但它的作用是，正如你所说，人们会自我调节摄入量，前提是他们吸烟，而不是通过食物摄入。
And so it's almost like THC is being held constant, and then there's this constellation of other things around it that are modified, and people eventually veer towards what they like, what they can afford, what works with their-
所以这几乎就像 THC 保持不变，然后周围有一系列其他东西被修改，人们最终转向他们喜欢的、他们能买得起的、适合他们的——
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
lifestyle, and then they come up with a bunch of theories based on packaging, what they're told, but presumably also some real effects of these terpenes, the CBD component, et cetera.
生活方式，然后他们根据包装、他们被告知的内容提出了一系列理论，但也可能是这些萜烯、CBD 成分等的一些实际影响。
Dr. Matthew Hill:
马修·希尔博士：
It's possible.
这是有可能的。
I mean-
我的意思是——
Andrew Huberman:
安德鲁·休伯曼：
It can't all be just psychological expectation.
这不可能全是心理预期。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
So what you're saying is like what we said is the entourage effect, and I think that is a theory that is held by a lot of people that this exists.
所以你所说的就像我们所说的随从效应一样，我认为这是一个很多人都认为存在的理论。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
The reality is these terpenes and minor cannabinoids exist at such low levels that there's a couple of kinds of cannabis that might have a high enough level where you're seeing something, but yeah.
事实上，这些萜烯和次要大麻素的含量非常低，以至于有几种大麻的含量可能足够高，你会看到一些东西，但是是的。
I agree to the extent that it would be a little wild if everyone's subjective experience across different kinds of cannabis was entirely driven by some kind of expectancy, which I can't imagine is accounting for all of it.
我同意，如果每个人对不同种类大麻的主观体验完全是由某种预期驱动的，那就有点疯狂了，我无法想象这能解释这一切。
But I think when we talk about sativa versus indica, I think there's a huge bias that's going into there.
但我认为，当我们谈论苜蓿与籼稻时，我认为其中存在巨大的偏见。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm
嗯嗯
Dr. Matthew Hill:
马修·希尔博士：
But one of the things with CBD that's interesting, unlike THC, is you can actually do pretty clean blinded studies, because it's really hard to give someone THC and them not know they're on THC.
但与 THC 不同，CBD 的有趣之处在于，你实际上可以进行非常干净的盲法研究，因为很难给某人 THC 并且他们不知道自己在服用 THC。
Andrew Huberman:
安德鲁·休伯曼：
Right.
对。
This was the big problem with the MDMA trial-
这是 MDMA 试验的大问题 -
Dr. Matthew Hill:
马修·希尔博士：
Yes
是的
Andrew Huberman:
安德鲁·休伯曼：
...
...
that happened recently, is that people who got the placebo knew they got placebo.
最近发生的事情是，服用安慰剂的人知道他们服用了安慰剂。
Dr. Matthew Hill:
马修·希尔博士：
Yes.
是的。
Andrew Huberman:
安德鲁·休伯曼：
People who got the drug-
拿到药的人——
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
knew they got the drug.
知道他们拿到了药物。
It's very hard.
这很难。
You could do a dose response-
你可以做一个剂量反应-
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
but it's very difficult.
但这非常困难。
Dr. Matthew Hill:
马修·希尔博士：
It's very challenging to give someone a psychoactive drug and a placebo and them not know which one they have.
给某人服用一种精神活性药物和一种安慰剂是非常具有挑战性的，而且他们不知道自己拥有的是哪一种。
Whereas because CBD doesn't produce an intoxicating state, and it's not really perceptible from the person who's taken it that it's doing anything, that actually does make it far more amenable to do blinded trials with.
然而，由于 CBD 不会产生令人陶醉的状态，而且服用者并不能真正察觉到它在做任何事情，这实际上使它更适合进行盲法试验。
And so, the interesting thing with CBD, and this is where I get a lot of people that get angry at me as well, is that I would argue that the overwhelming majority of the effects of CBD that people report are all placebo effects.
因此，CBD 的有趣之处在于，我认为人们报告的 CBD 的绝大多数效果都是安慰剂效应，这也是我让很多人对我感到愤怒的地方。
And I say that because people leverage the epilepsy stuff and some of the clinical work and say, "But we know it does things." And my response to them is, "Do you know what dose those people are getting?" Because this is something that for some reason has not made the transition from science into pop culture.
我这么说是因为人们利用癫痫的资料和一些临床工作并说，“但我们知道它确实有作用。”我对他们的回答是：“你知道那些人服用的剂量是多少吗？”因为由于某种原因，这种东西还没有从科学过渡到流行文化。
So-
所以——
Andrew Huberman:
安德鲁·休伯曼：
This is a similar phenomenon with GLP-1.
这与GLP-1有类似的现象。
I and other people have pointed to the fact that certain food products or certain drinks or certain activities can increase GLP-1, glucagon-like peptide, which is now becoming more commonplace knowledge because of Ozempic, Mounjaro, et cetera, as very powerful weight loss tools, although there's questions about muscle loss, et cetera.
我和其他人指出，某些食品或某些饮料或某些活动可以增加 GLP-1（胰高血糖素样肽），由于 Ozempic、Mounjaro 等，GLP-1 现已成为更常见的知识，作为非常强大的减肥工具，尽管存在关于肌肉损失等的问题。
And then we had Dr. Zachary Knight on, who explained that even a fourfold increase in GLP-1 brought about through a prescription drug or ingestion of a particular food or drink does not lead to any appreciable weight loss.
然后 Zachary Knight 博士解释说，即使通过处方药或摄入特定食物或饮料使 GLP-1 增加四倍，也不会导致任何明显的体重减轻。
Dr. Matthew Hill:
马修·希尔博士：
Mm-hmm.
嗯嗯。
Andrew Huberman:
安德鲁·休伯曼：
However, when one achieves thousandfold increases in GLP-1 through the use of things like Ozempic, Mounjaro, you see profound weight loss.
然而，当人们通过使用 Ozempic、Mounjaro 等药物使 GLP-1 增加数千倍时，您会看到显着的体重减轻。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Meaning that you need enormous effects in order to see-
这意味着你需要巨大的效果才能看到-
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
the clinically relevant changes in that case, weight loss.
在这种情况下，临床相关的变化是体重减轻。
So it sounds like a similar thing with CBD.
所以这听起来和 CBD 很相似。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
It's-
这是——
Andrew Huberman:
安德鲁·休伯曼：
So if somebody takes a CBD gummy, and they feel that they sleep better, you would argue that that's entirely expectation bias.
因此，如果有人服用 CBD 软糖，并且他们觉得自己睡得更好，你会说这完全是期望偏差。
Dr. Matthew Hill:
马修·希尔博士：
I think that's a placebo effect.
我认为这是安慰剂效应。
And I say that because the majority of gummies are what?
我这么说是因为大多数软糖是什么？
Like two mgs, five mgs, 20 mgs maybe?
比如 2 毫克、5 毫克、20 毫克？
Andrew Huberman:
安德鲁·休伯曼：
I don't know.
我不知道。
I've never taken a CBD product.
我从未服用过 CBD 产品。
Dr. Matthew Hill:
马修·希尔博士：
So-
所以——
Andrew Huberman:
安德鲁·休伯曼：
I know a few years ago they were all the rage.
我知道几年前它们很流行。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
I was never tempted to do it.
我从来没有想过这样做。
And I'm aware, and we'll talk about this a little bit more, that there is evidence, according to Matt Walker, who did a six-episode series with us on sleep, that THC does help certain people fall asleep, but it can dramatically alter the architecture of sleep-
我知道，我们将进一步讨论这一点，据与我们一起制作了六集睡眠系列节目的马特·沃克 (Matt Walker) 表示，有证据表明 THC 确实有助于某些人入睡，但它可以极大地改变睡眠的结构——
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
in ways that are probably not great.
以可能不太好的方式。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
THC and sleep is definitely a whole other thing.
THC 和睡眠绝对是另一回事。
Andrew Huberman:
安德鲁·休伯曼：
Sure.
当然。
Dr. Matthew Hill:
马修·希尔博士：
But sure, a lot of people report this with CBD.
但可以肯定的是，很多人都向 CBD 报告了这一点。
But again, so most CBD edibles or things that people take that are sold through commercial markets are in the range of two to 25 mgs of CBD.
但同样，大多数通过商业市场销售的 CBD 食品或人们服用的东西都含有 2 至 25 毫克 CBD。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
So then I say to them, "So you're aware that in the pediatric epilepsy studies, the dose ranges are like 1,500 to 2,000 mgs?"
然后我对他们说：“所以你知道在儿科癫痫研究中，剂量范围约为 1,500 至 2,000 毫克？”
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
There we go.
我们开始吧。
Yeah.
是的。
Dr. Matthew Hill:
马修·希尔博士：
And then you're talking about a child who weighs on the order of what?
然后你说的是一个孩子的体重是多少？
20 kilos, maybe?
大概20公斤吧？
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
Like 40, 60 pounds, somewhere in that range.
比如 40、60 磅，在这个范围内。
So if you start dosing by weight, which is how most of these things are done, where they'll say 20 mgs per kg or whatnot.
因此，如果你开始按体重给药，这就是大多数药物的做法，他们会说每公斤 20 毫克或诸如此类。
So someone my size, so I weigh a bit over 200 pounds, for me to take that dose of CBD at let's say 20 mgs per kg at like 90 odd kilos, you're talking about me taking an-
所以像我这样大的人，所以我的体重超过 200 磅，对于我来说，以每公斤 20 毫克的剂量服用 CBD，大约 90 多公斤，你是在谈论我服用 -
Andrew Huberman:
安德鲁·休伯曼：
A liver damaging dosage
损害肝脏的剂量
Dr. Matthew Hill:
马修·希尔博士：
...
...
an insane...
一个疯狂的...
Or maybe I wouldn't say damaging.
或者也许我不会说有破坏性。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
Dr. Matthew Hill:
马修·希尔博士：
It's definitely influencing how the liver metabolizes other things because it's going to saturate those enzymes.
它肯定会影响肝脏代谢其他物质的方式，因为它会使这些酶饱和。
But you're taking a very high dose.
但你服用的剂量非常高。
Andrew Huberman:
安德鲁·休伯曼：
So if, for instance, you were to take a high dose of CBD and then maybe have a couple alcohol-containing drinks, that could be problematic, right?
因此，例如，如果您服用高剂量的 CBD，然后可能喝了几杯含酒精的饮料，那可能会出现问题，对吗？
Because now you're talking about the two-hit model.
因为现在你谈论的是两次打击模型。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
I can't speak to that because I actually do not know the metabolism of alcohol well enough.
我不能这么说，因为我实际上不太了解酒精的新陈代谢。
I don't believe so, because that's alcohol dehydrogenase.
我不相信，因为那是乙醇脱氢酶。
So that would probably be a separate enzyme pathway than the CYP.
所以这可能是一个与 CYP 不同的酶途径。
This is more like-
这更像是——
Andrew Huberman:
安德鲁·休伯曼：
Separate enzyme pathway, but you're challenging the liver.
单独的酶途径，但你正在挑战肝脏。
Dr. Matthew Hill:
马修·希尔博士：
Yeah, but I don't know if it would have an effect in that capacity.
是的，但我不知道这是否会对这种能力产生影响。
They've definitely seen this, they know the list of medications-
他们肯定见过这个，他们知道药物清单-
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm
嗯嗯
Dr. Matthew Hill:
马修·希尔博士：
...
...
that this is a problem for.
这是一个问题。
So it's things like warfarin-
所以就像华法林这样的东西-
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm
嗯嗯
Dr. Matthew Hill:
马修·希尔博士：
...
...
and like blood thinners.
和血液稀释剂。
Andrew Huberman:
安德鲁·休伯曼：
Blood thinner.
血液稀释剂。
Yeah.
是的。
Dr. Matthew Hill:
马修·希尔博士：
And the antiepileptics funnel into the same metabolic pathway as this THC.
抗癫痫药与 THC 进入相同的代谢途径。
So there's certain things that this would influence.
所以这会影响某些事情。
I don't know if I would say this would in the context of alcohol, but I think more so, what I try and point out to people repeatedly is, I have yet to see a blinded clinical study that has found any effective CBD that's efficacious that's under 300 to 500 milligrams.
我不知道我是否会在酒精的背景下这么说，但我认为更重要的是，我试图反复向人们指出的是，我还没有看到一项盲法临床研究发现任何有效的 CBD 在 300 到 500 毫克以下。
And yet, in the wild, in people who are using it on their own, were using doses of 10 to 20 milligrams and reporting these effects.
然而，在野外，单独使用它的人使用的剂量为 10 至 20 毫克，并报告了这些影响。
And the thing is that I think a lot of people don't also realize is CBD has absolutely horrific bioavailability.
问题是，我认为很多人也没有意识到 CBD 具有绝对可怕的生物利用度。
So if you take it orally in an oil or in a gummy or whatever you consume it in, now this might be different with some of these beverages that are out there.
因此，如果您以油或软糖或其他任何形式口服它，那么现在的情况可能与市面上的一些饮料有所不同。
I don't know if anyone's actually ever done the pharmacokinetics on them.
我不知道是否有人真正做过它们的药代动力学。
At least I've never seen it.
至少我没见过。
But standard routes, we're talking 4%, like very little.
但标准路线，我们说的是 4%，好像很少。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
Actually leaves your gut into your bloodstream.
实际上将你的肠道留在你的血液中。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
Now, we do know from the studies from GW, who created the pharmaceutical version of CBD that was used for a lot of the pediatric epilepsy studies, that they did, I don't know if it was random or intentional find, that opposite to something like alcohol, if you had just eaten a fatty meal, that actually enhanced the bioavailability of CBD dramatically.
现在，我们确实从 GW 的研究中得知，他们创造了用于许多儿科癫痫研究的 CBD 药物版本，我不知道这是随机还是有意发现，与酒精之类的东西相反，如果你刚刚吃了一顿脂肪餐，实际上会显着提高 CBD 的生物利用度。
So then it went up to maybe 20% got into the blood.
然后它进入血液的比例可能高达 20%。
But that's probably because, again, CBD is a fatty molecule.
但这可能是因为 CBD 是一种脂肪分子。
It likes fatty environments, and for some reason, having fat in the stomach and in the gut seems to promote its ability to get into the bloodstream.
它喜欢脂肪环境，并且出于某种原因，胃和肠道中的脂肪似乎会促进其进入血液的能力。
Andrew Huberman:
安德鲁·休伯曼：
I can see it now.
我现在可以看到了。
It's the steak and CBD-
这是牛排和 CBD-
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
...
...
or the CBD with omelet protocol.
或带有煎蛋卷协议的 CBD。
Dr. Matthew Hill:
马修·希尔博士：
But it's-
但它是——
Andrew Huberman:
安德鲁·休伯曼：
I'm just kidding, folks.
我只是开玩笑，伙计们。
I'm not suggesting that protocol.
我并不是在建议该协议。
Dr. Matthew Hill:
马修·希尔博士：
But yeah.
但是是的。
And so because of this, it's like you're taking very low doses of CBD that have very poor bioavailability, and then people really stand by the effects of these.
正因为如此，就好像你服用了非常低剂量的 CBD，其生物利用度非常差，然后人们真的支持这些效果。
And so I'm like, what I would always say is if it works for you, there's no reason to stop it.
所以我想，我总是会说，如果它对你有用，就没有理由停止它。
But Because you're having benefit from it.
但因为你从中受益。
But would I ever recommend someone do this?
但我会建议有人这样做吗？
No, I wouldn't, because I can't say that I think that this has any biological activity.
不，我不会，因为我不能说我认为这有任何生物活性。
Because even when we start looking at these potential targets of what CBD could interact with, there's a couple of receptors people have said it might interact with the serotonin receptor.
因为即使当我们开始研究 CBD 可能相互作用的这些潜在目标时，人们也表示它可能与血清素受体相互作用。
There's some of these random orphan receptors that we don't know a lot of what they do that CBD might interact with, but the concentrations you need to hit those are reasonable, and you're not getting that in the blood and certainly not in the brain of people from consuming incredibly low doses of CBD.
其中有一些随机的孤儿受体，我们对 CBD 可能与之相互作用的作用知之甚少，但是达到这些受体所需的浓度是合理的，并且您不会在血液中获得这种浓度，当然也不会在人们摄入极低剂量的 CBD 时在大脑中获得这种浓度。
So the whole market that exists for CBD, to me, is a little bizarre.
因此，对我来说，CBD 存在的整个市场有点奇怪。
And I think for a lot of us in the cannabis field, this has been one of the most bizarre social experiments we've ever watched because if you asked me in 2010 to walk into a room and ask how many people knew what CBD is, maybe one out of 100.
我认为对于我们大麻领域的许多人来说，这是我们见过的最奇怪的社会实验之一，因为如果你在 2010 年让我走进一个房间，问有多少人知道 CBD 是什么，可能是百分之一。
No one knew what CBD was.
没有人知道 CBD 是什么。
And now it's like 80 to 90% would know what it is because you can't walk down a street in any city in North America and not see CBD products, whether it's some kind of cream, or a shake, or some random concoction that people have added CBD because now you're seeing the energy drinks.
现在好像 80% 到 90% 的人都知道它是什么，因为你走在北美任何城市的街道上都不会看到 CBD 产品，无论是某种奶油、奶昔，还是人们添加 CBD 的一些随机混合物，因为现在你看到的是能量饮料。
It's bizarre to me how much this has taken off, because it seems to have somehow migrated into being a health product in some capacity, so.
对我来说，这已经取得了如此大的成功，这很奇怪，因为它似乎已经以某种方式转变为某种功能的保健产品，所以。
Andrew Huberman:
安德鲁·休伯曼：
Yeah, I've never tried any of these CBD-containing products.
是的，我从未尝试过任何含有 CBD 的产品。
I think a lot of what you're describing speaks to the fact that people are eager for things that can help them adjust their anxiety and sleep better.
我认为你所描述的很多内容都说明了这样一个事实：人们渴望能够帮助他们调整焦虑和睡得更好的东西。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Which is a large reason why a lot of this podcast has focused on respiration-based tools and other base tools that can help people with anxiety.
这就是为什么这个播客的大部分内容都专注于基于呼吸的工具和其他可以帮助焦虑症患者的基本工具的一个重要原因。
I think that many people suffer from just too much activation in their autonomic nervous system.
我认为许多人的自主神经系统过度活跃。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And I would argue there are much better things that are not of a ingestible type, things that one can do that are science supported, right?
我认为有很多更好的东西不是可摄入类型的，人们可以做的事情是有科学支持的，对吗？
There are clinical studies, meditation, breathwork.
有临床研究、冥想、呼吸。
Not so much breathwork, I would argue, but certain patterns of breathing, meditation, cognitive behavioral therapy.
我认为，与其说是呼吸，不如说是某些呼吸模式、冥想、认知行为疗法。
There are a whole bunch of different things, as you know.
如您所知，有很多不同的事情。
So I don't know what explains the CBD craze, but you certainly have shed light on what is and mainly what is not known about CBD.
所以我不知道如何解释 CBD 热潮，但你肯定已经阐明了 CBD 的主要内容和未知内容。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And I think it's really important for people to hear.
我认为人们听到这真的很重要。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Again, I think from my point of view, it's an ethical thing as well, because this isn't covered by insurance.
同样，我认为从我的角度来看，这也是一件道德的事情，因为这不在保险范围内。
People are spending their own money on this.
人们为此花自己的钱。
And so I find it really challenging to recommend someone to be spending what can...
因此，我发现推荐某人花尽可能多的钱真的很有挑战性……
Especially if we're talking about an actual clinical dose.
特别是如果我们谈论的是实际的临床剂量。
For someone to take CBD at the level where it could actually be shown to have some benefit and some condition, of which currently it really is just pediatric epilepsy.
对于某人来说，服用 CBD 的水平实际上可以证明它有一些好处和一些条件，其中目前它实际上只是小儿癫痫。
This idea with sleep, pain, anxiety, there's not a lot of super conclusive data, and I'd say most of the trials that have been done have not found really good evidence of benefit in any capacity.
这个想法与睡眠、疼痛、焦虑有关，没有很多超级确凿的数据，我想说的是，大多数已经完成的试验都没有发现任何能力都有益的真正良好的证据。
So it makes it very challenging to recommend this in any capacity.
因此，以任何身份推荐这一点都非常具有挑战性。
Especially, if finances aren't an issue, sure, go for it.
特别是，如果财务不是问题，当然，就去吧。
But I understand people are, like you say, looking for solutions, so it makes-
但我知道人们就像你说的那样，正在寻找解决方案，所以它使得-
Andrew Huberman:
安德鲁·休伯曼：
It doesn't sound like CBD is the solution.
听起来 CBD 并不是解决方案。
Dr. Matthew Hill:
马修·希尔博士：
I am not convinced by the data that exists that it's really doing what a lot of people claim it's doing.
我不相信现有的数据表明它真的做了很多人声称它正在做的事情。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Except supporting the placebo effect, perhaps.
也许除了支持安慰剂效应。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Perhaps.
也许吧。
Dr. Matthew Hill:
马修·希尔博士：
It's a great study of the placebo effect.
这是对安慰剂效应的一项伟大研究。
Andrew Huberman:
安德鲁·休伯曼：
I want to make sure before we close that we touch on some of the potential harms or asserted harms of THC, because I think there's a lot of misunderstanding about this.
我想在结束之前确保我们触及 THC 的一些潜在危害或声称的危害，因为我认为对此存在很多误解。
We talked about psychosis and the lack of evidence for a direct causal effect.
我们讨论了精神病和缺乏直接因果效应的证据。
You give a beautiful description as to how we should think about all of that based on the current literature.
您对我们应该如何根据当前文献思考所有这些问题给出了精彩的描述。
But cannabis and driving is a potential hazard.
但大麻和驾驶是一个潜在的危险。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Right?
对吗？
And some people will laugh.
有些人会笑。
They'll be like, "Oh, driving too slow," as opposed to driving drunk or driving too fast.
他们会说，“哦，开得太慢了”，而不是酒后驾车或开得太快。
Okay.
好的。
We can talk about that.
我们可以谈谈这个。
We talked about the potential for addiction-
我们讨论了成瘾的可能性——
Dr. Matthew Hill:
马修·希尔博士：
Mm-hmm
嗯嗯
Andrew Huberman:
安德鲁·休伯曼：
...
...
and the evidence potentially for and against that, right?
以及可能支持和反对这一点的证据，对吧？
There's also the big black or gray box of all the things we don't know about what regular cannabis use could do.
还有一个黑色或灰色的大盒子，里面装着我们不知道常规使用大麻能做什么的所有事情。
And yet I know a lot of people who've used cannabis for years, mainly as a replacement for alcohol, at least that's how they describe it.
然而我知道很多人多年来一直使用大麻，主要是作为酒精的替代品，至少他们是这么描述的。
"Well, it's not as bad as alcohol."
“嗯，它不像酒精那么糟糕。”
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
You hear that a lot.
你经常听到这样的说法。
Okay?
好的？
But what are some actual, if any, what are some actual harms of cannabis use that people need to take into account and just weigh against the fact that every compound, caffeine, even water, can kill you if you drink too much of it?
但是，人们需要考虑使用大麻的一些实际危害（如果有的话），并权衡一下这样一个事实：如果喝太多大麻，每种化合物、咖啡因，甚至水都会杀死你？
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And then let's make sure that we touch on this issue of cannabis and driving or operating machinery, but I think the machine most people are thinking about these days is driving.
然后让我们确保我们触及大麻和驾驶或操作机器的问题，但我认为现在大多数人想到的机器是驾驶。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
So health harms, someone's smoking, obviously there's risks for lung damage.
因此，健康受到损害，有人吸烟，显然存在肺部损伤的风险。
I would say the evidence for things like lung cancer certainly don't hold the way they do with cigarette smoke.
我想说，肺癌等疾病的证据肯定不像香烟烟雾那样成立。
Andrew Huberman:
安德鲁·休伯曼：
Because people are smoking less of it, or there are just fewer carcinogens in there?
是因为人们吸烟量减少了，还是里面的致癌物质减少了？
Dr. Matthew Hill:
马修·希尔博士：
I don't think you could make the argument about fewer carcinogens per se.
我认为你不能就致癌物本身较少的问题提出论点。
I think probably it relates more to the frequency.
我认为这可能与频率更多相关。
Donald Tashkin, who's in California here, I think he was at UCLA, I'm not 100% sure, but I know he was in California.
唐纳德·塔什金（Donald Tashkin）在加利福尼亚州，我想他在加州大学洛杉矶分校（UCLA），我不能百分百确定，但我知道他在加利福尼亚州。
He did very long-term studies tracking cannabis smokers and basically did not find associations with lung cancer the way that you do with cigarette smoking.
他对大麻吸烟者进行了非常长期的研究，基本上没有像吸烟那样发现与肺癌的关联。
Why that's the case, I don't think anyone has...
为什么会这样呢，我想没有人...
People have theories.
人们有理论。
Some suggest because a lot of this in vitro animal work with really high dosing suggests it could have anti-proliferative effects for tumors.
一些人认为，因为许多这种体外动物的剂量非常高，这表明它可能对肿瘤具有抗增殖作用。
Whether that's real or not, I don't know, but I think more likely it's because most people who smoke cigarettes, at least the relationship with lung cancer, were people who were smoking regularly throughout the day, and it's very rare someone smokes cannabis at that frequency.
不管这是真的还是假的，我不知道，但我认为更有可能的是因为大多数吸烟的人，至少是与肺癌有关的人，都是整天经常吸烟的人，而且很少有人以这种频率吸食大麻。
Maybe if they isolated that population, they would see relationships with lung cancer.
也许如果他们隔离该人群，他们会发现与肺癌的关系。
I just don't think it's been borne out by the data the same way.
我只是认为数据并没有以同样的方式证明这一点。
Certainly lung damage, emphysema, things like that are on par.
当然，肺损伤、肺气肿之类的事情也同样如此。
If you have any combustion product, you're going to have damage there.
如果有任何燃烧产物，那里就会受到损害。
There's no question about that.
毫无疑问。
So again, harm reduction perspective would be oral routes of administration bypass lung damage.
因此，减少危害的观点是口服给药途径，绕过肺损伤。
They come with their own issues with dosing and whatnot, but if you're talking about physical harms, that's one thing to avoid that you could bypass that aspect of it with.
他们在剂量等方面有自己的问题，但如果你谈论的是身体伤害，这是需要避免的一件事，你可以绕过它的这一方面。
I don't think we are at a point where we can say the state of it.
我认为我们还没有到可以说出现状的地步。
There is something with cardiovascular function in cannabis that relates to higher frequency of strokes perhaps, or cardiac events in some capacity.
大麻中含有一种具有心血管功能的物质，可能与中风的发生频率较高或某种程度的心脏事件有关。
The data's not entirely clear in this sense yet.
从这个意义上说，数据还不完全清楚。
Again, it's not super clean relationships like we're seeing that were there when they established cigarette smoking and lung cancer kind of thing.
再说一次，这并不是我们所看到的那种超级干净的关系，就像他们建立吸烟和肺癌之类的事情时那样。
I think that effect was so profound, and the population of smokers used to be so high.
我认为这种影响是如此深远，而且吸烟者的数量曾经如此之多。
Andrew Huberman:
安德鲁·休伯曼：
Can this potential, I want to highlight potential, relationship between cannabis use and cardiovascular issues be bypassed, no pun intended, by using edibles, not inhalants, or is it related to THC itself?
我想强调的是，大麻使用和心血管问题之间的这种潜在关系是否可以通过使用食品而不是吸入剂来绕过（没有双关语），还是与 THC 本身有关？
Dr. Matthew Hill:
马修·希尔博士：
I would probably guess, and this is a guess, that anything, again, combustion smoke-wise, maybe not vaping plant matter, but at least the combustion from smoking probably exacerbates this, just because any kind of combustion product is going to have some vascular effects to some degree on the system.
我可能会猜测，这只是一个猜测，任何东西，再一次，燃烧烟雾，可能不会蒸发植物物质，但至少吸烟引起的燃烧可能会加剧这种情况，只是因为任何种类的燃烧产物都会在某种程度上对系统产生一些血管影响。
So I imagine it would make it worse.
所以我想这会让情况变得更糟。
But THC itself has a very complex effect on cardiovascular function because it tends to cause, typically, vasodilation, so you get widening of the blood vessels.
但四氢大麻酚本身对心血管功能有非常复杂的影响，因为它通常会引起血管舒张，从而使血管扩张。
Which is why it relates to a lot of people will experience postural hypotension.
这就是为什么很多人会经历体位性低血压。
So sometimes what that is, is if you stand up and your blood pressure doesn't catch up with you, so you get really lightheaded and people will collapse.
所以有时候，如果你站起来，你的血压跟不上，你就会感到头晕，人们就会崩溃。
And so this is not uncommon to happen to people, and with edibles as well, so it's not just from smoking.
因此，这种情况发生在人们身上并不少见，食物也是如此，所以这不仅仅是吸烟造成的。
But when they've consumed cannabis in some capacity, there are some people that seem to be very sensitive to the vasodilating effects.
但是，当他们以某种方式消费大麻时，有些人似乎对血管舒张作用非常敏感。
And so when they stand up, their blood pressure can't match the shift in gravity that happens, and so not enough blood perfuses the brain, and they go down.
因此，当他们站起来时，他们的血压无法与重力的变化相匹配，因此没有足够的血液灌注大脑，他们就会倒下。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
And that can be transient.
这可能是暂时的。
They'll come to a minute or two later, but it happens.
他们会在一两分钟后出现，但它确实发生了。
But as a consequence of the vasodilation is it triggers tachycardia, which is an accelerated heart rate.
但血管舒张的结果是引发心动过速，即心率加快。
And so that's a very reliable physiological response for a lot of people who use cannabis.
因此，对于许多吸食大麻的人来说，这是一种非常可靠的生理反应。
And so it's a bit of a tricky thing because obviously if there is some underlying heart or a cardiac sensitivity or issue, the tachycardia itself can be a problem.
所以这是一件有点棘手的事情，因为显然如果存在一些潜在的心脏或心脏敏感性或问题，心动过速本身可能就是一个问题。
So if someone has an underlying heart condition where at rest it may not present itself, but the shifts into that kind of beating faster to compensate for the fact that you've got a drop in blood pressure, can put strain on the heart in a way that could unmask a vulnerability or an event.
因此，如果某人患有潜在的心脏病，在休息时它可能不会表现出来，但为了补偿血压下降的事实而更快地转变为这种跳动，可能会给心脏带来压力，从而暴露出脆弱性或事件。
And again, this is me theorizing what I think it could be based on what we understand to some degree about how it affects cardiovascular function.
再说一次，这是我的理论，我认为它可能是基于我们在某种程度上了解它如何影响心血管功能。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
There are occasionally people who have reported having elevated blood pressure.
偶尔有人报告血压升高。
Some of that also could be from an anxiety state or whatnot coming around.
其中一些也可能是由于焦虑状态或其他原因造成的。
But the typical response, and this is usually driven by cannabinoid receptors that are in the vascular beds themselves, that it causes a vasodilatory response.
但典型的反应通常是由血管床本身的大麻素受体驱动的，它会引起血管舒张反应。
And so that is usually the first step.
这通常是第一步。
The second is the uptick in the heart rate.
第二个是心率的上升。
So you get these kind of effects over time.
所以随着时间的推移你会得到这些效果。
There's some work looking at vascular stiffness that can evolve over time in cannabis users.
有一些研究研究大麻使用者的血管僵硬度会随着时间的推移而变化。
There's some evidence to suggest that you might get more of that emerging.
有一些证据表明您可能会遇到更多这样的情况。
Andrew Huberman:
安德鲁·休伯曼：
Mm.
嗯。
Dr. Matthew Hill:
马修·希尔博士：
And so again, that could relate to a vulnerability to have strokes or other kind of cardiovascular events in that sense.
同样，从这个意义上来说，这可能与中风或其他类型的心血管事件的脆弱性有关。
So I think the issue in terms of why it is more difficult for us to say anything definitively at this point is just obviously the timeline of this.
所以我认为，为什么我们现在更难明确地说任何事情的问题显然是这个时间表。
Cigarette smoking was an easier thing to establish in that context because once antibiotics and medicine advanced in the '40s and the '30s and stuff and people started living longer, you started seeing a lot of these effects of cigarette smoking emerge because-
在这种情况下，吸烟是更容易确定的事情，因为一旦抗生素和药物在 40 年代和 30 年代取得进步，人们的寿命开始延长，你就会开始看到吸烟的许多影响出现，因为——
Andrew Huberman:
安德鲁·休伯曼：
And yet, it took a while for the-
然而，花了一段时间才——
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
medical community to adopt the idea-
医学界采纳了这个想法——
Dr. Matthew Hill:
马修·希尔博士：
Exactly
正是如此
Andrew Huberman:
安德鲁·休伯曼：
...
...
that cigarette smoking was bad.
吸烟不好。
Dr. Matthew Hill:
马修·希尔博士：
Oh, I know.
哦，我知道。
It's wild to look back on it.
回想起来真是疯狂。
Andrew Huberman:
安德鲁·休伯曼：
Physicians would smoke in clinic.
医生会在诊所吸烟。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
There were ashtrays in the doctor's office.
医生办公室里有烟灰缸。
Dr. Matthew Hill:
马修·希尔博士：
My grandparents grew up in Belfast.
我的祖父母在贝尔法斯特长大。
They had smoked for years, and they had even said when they were younger, doctors would say, "Oh, have a cigarette after a meal.
他们已经抽烟多年了，他们甚至说，当他们年轻的时候，医生会说，“哦，饭后抽一支烟。
It promotes digestion." So it's kind of wild to hear that stuff when you think of how cigarettes are viewed nowadays.
它可以促进消化。”因此，当你想到当今人们如何看待香烟时，听到这些东西有点疯狂。
But I don't think we've been able to track this long enough to be able to say with certainty what we're seeing.
但我认为我们追踪这一事件的时间还不够长，还不足以确定我们所看到的情况。
If people ask me about risks and harms of cannabis, the first thing I always say is schizophrenia and bipolar.
如果人们问我大麻的风险和危害，我总是说的第一句话是精神分裂症和躁郁症。
Those are the main concern areas, I think, where you want to avoid cannabis.
我认为这些是您想要避免使用大麻的主要关注领域。
And I would also say if anyone has cardiovascular issues, they should avoid cannabis.
我还想说，如果有人有心血管问题，他们应该避免使用大麻。
Just because that's more of, I would say, a being safe, because I don't know how to actually explicitly say what I would say the harms associated with it are.
我想说，这更多的是一种安全，因为我不知道如何真正明确地说出与之相关的危害。
But I think there is something there.
但我认为那里有一些东西。
I've seen enough evidence that's starting to coalesce into a story that's like, there's something here.
我已经看到了足够的证据，这些证据开始融合成一个故事，就像，这里有东西。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
So that's where I would say that I think there's risk.
所以我想说我认为存在风险。
There's also things like this bizarre cyclic vomiting syndrome, which is this really strange thing that has become really apparent.
还有像这种奇怪的周期性呕吐综合症这样的事情，这是一种非常奇怪的事情，而且已经变得非常明显。
We've seen this in Canada a bit more now with legalization, again, because people are going into ERs more.
随着合法化，我们在加拿大再次看到了这种情况，因为人们更多地进入急诊室。
Where it's this somewhat strange phenomenon where it's usually people who are pretty excess cannabis users.
这是一种有点奇怪的现象，通常人们都是相当过量的大麻使用者。
They just start puking, and they can't stop it.
他们只是开始呕吐，而且无法停止。
And it's like this intractable vomiting that they get into.
就像他们陷入的顽固性呕吐一样。
And then bizarrely, one of the things that seems to cure it is a hot shower, which I can't even begin to understand this.
然后奇怪的是，似乎可以治愈它的方法之一就是洗热水澡，我什至无法理解这一点。
There's also-
还有——
Andrew Huberman:
安德鲁·休伯曼：
I'm chuckling at the example because you are so very clearly rooted in science, but that just came out of nowhere.
我对这个例子笑了，因为你非常明显地植根于科学，但这只是突然出现的。
Like, okay, cool.
就像，好吧，酷。
Hot shower.
热水淋浴。
Deliberate heat exposure, folks.
伙计们，故意暴露在高温下。
There it is.
就在那里。
Dr. Matthew Hill:
马修·希尔博士：
I have been trying to understand how this was-
我一直试图理解这是怎么回事-
Andrew Huberman:
安德鲁·休伯曼：
I'm not enjoying it because it's deliberate heat exposure, but it just speaks to the fact that we're talking about smoking being a ...
我不喜欢它，因为它是故意暴露在高温下，但这只是说明了这样一个事实：我们正在谈论吸烟是......
a regular part of the medical community's behaviors up until a few decades ago.
直到几十年前，这仍然是医学界行为的常规部分。
And then, a hot shower being the treatment for this chronic vomiting.
然后，用热水淋浴来治疗这种慢性呕吐。
And it speaks to the fact that with science and medicine, we do know a ton.
它说明了这样一个事实：通过科学和医学，我们确实知道很多。
It's amazing how much we've progressed, especially in the last 100 years, the last 25 years even.
我们取得的进步令人惊叹，尤其是在过去 100 年，甚至在过去 25 年。
But it's also astounding how these seemingly surprising antidotes to uncomfortable conditions can hold up over time in the absence of any randomized control trials-
但令人惊讶的是，在没有任何随机对照试验的情况下，这些看似令人惊讶的针对不适症状的解毒剂如何能够随着时间的推移而保持作用——
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
or mechanistic data.
或机械数据。
Dr. Matthew Hill:
马修·希尔博士：
I really struggle to understand, because certainly, I don't think it was doctors that figured this out.
我真的很难理解，因为当然，我不认为是医生解决了这个问题。
This was people, I think, who were experiencing this, and then they started telling doctors this.
我认为这些人正在经历这种情况，然后他们开始告诉医生这一点。
And I could only imagine, I'm like, "Maybe they're going in the shower because they're vomiting on themselves?"
我只能想象，“也许他们去洗澡是因为他们呕吐了？”
Andrew Huberman:
安德鲁·休伯曼：
Probably.
可能吧。
Dr. Matthew Hill:
马修·希尔博士：
And then inadvertently realized that being in a hot shower somehow seemed to calm this down.
然后无意中意识到洗个热水澡似乎可以让这种情况平静下来。
I have seen a study where they actually applied capsaicin cream, and that also seemed to provide benefit.
我看过一项研究，他们实际上使用了辣椒素霜，这似乎也有好处。
Andrew Huberman:
安德鲁·休伯曼：
So something about activation of the heat, thermal-
所以关于热的激活，热-
Dr. Matthew Hill:
马修·希尔博士：
It's something with thermoregulation, because the other thing that seems to have shown some benefit is propranolol, which again would suggest some kind of sympathetic.
它与体温调节有关，因为另一种似乎显示出一些益处的物质是普萘洛尔，它再次表明某种交感神经。
Andrew Huberman:
安德鲁·休伯曼：
Which is a beta blocker.
这是一种β受体阻滞剂。
Dr. Matthew Hill:
马修·希尔博士：
It's a beta blocker, so yeah, it's your effect.
它是一种β受体阻滞剂，所以是的，这就是你的作用。
So there's something with autonomic.
所以有一些自主性的东西。
It must be messing up some kind of autonomic balance or something with thermoregulation.
它一定是扰乱了某种自主平衡或体温调节的东西。
Andrew Huberman:
安德鲁·休伯曼：
Wild.
狂野。
Dr. Matthew Hill:
马修·希尔博士：
Why that results in this bizarre vomiting syndrome, I have no idea.
我不知道为什么会导致这种奇怪的呕吐综合症。
But I remember when I first started hearing the stories of this years ago, and I was just like, "How?" Because it is, again, surprisingly counterintuitive because one of the medical uses that people have used cannabis for is as an anti-nauseant, especially in the context of chemotherapy.
但我记得当我几年前第一次开始听到这些故事时，我就想，“怎么样？”因为它再次令人惊讶地违反直觉，因为人们使用大麻的医疗用途之一是作为抗恶心剂，特别是在化疗的情况下。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
And so something that typically has anti-nauseant qualities suddenly triggering a vomiting syndrome is kind of paradoxical.
因此，通常具有抗恶心特性的东西突然引发呕吐综合症，这有点自相矛盾。
Andrew Huberman:
安德鲁·休伯曼：
And yet, we started off today's conversation with you explaining beautifully how activation of these CB1 receptors are homeostatic in some sense, the thermostat analogy.
然而，我们在今天的对话中向您完美地解释了这些 CB1 受体的激活如何在某种意义上实现稳态（类似于恒温器）。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And maybe after chronic use, the seesaw-
也许在长期使用之后，跷跷板-
Dr. Matthew Hill:
马修·希尔博士：
They've messed it up
他们把事情搞砸了
Andrew Huberman:
安德鲁·休伯曼：
...
...
sort of gets flipped to one side-
有点被翻转到一侧-
Dr. Matthew Hill:
马修·希尔博士：
I think, yeah
我想，是的
Andrew Huberman:
安德鲁·休伯曼：
...
...
and gets stuck there.
并被困在那里。
Dr. Matthew Hill:
马修·希尔博士：
I think that's how most people have tried to conceptualize what's going on, is maybe, and it seems to involve the insular cortex.
我认为这就是大多数人试图概念化正在发生的事情、可能发生的事情的方式，而且它似乎涉及岛叶皮质。
At least the anti-nauseant effects of cannabinoids are involved through the insular cortex.
至少大麻素的抗恶心作用是通过岛叶皮质发挥作用的。
And so maybe you have burned out those receptors from chronic use, and so that endogenous mechanism isn't working, or it's somehow flipped in the other direction, now and that circuit becomes sensitized.
因此，也许你已经因长期使用而耗尽了这些受体，因此内源性机制不起作用，或者它以某种方式转向另一个方向，现在该电路变得敏感。
But it is a very bizarre but very real thing that seems to happen.
但这似乎是一件非常奇怪但又非常真实的事情。
Again, this isn't common.
再说一遍，这种情况并不常见。
I've heard a couple of people I've met describe it, but it's not like it's happening to every 10th or 20th person or something.
我听过几个我认识的人描述过这种情况，但并不是每 10 个人或 20 个人都会遇到这种情况。
It's a little more infrequent, but it's certainly happening enough that we've now captured it at a federal data level, that this is a thing that people are showing up in the ER for.
这种情况比较少见，但这种情况确实发生得足够多，以至于我们现在已经在联邦数据层面捕获了它，这就是人们出现在急诊室的原因。
Andrew Huberman:
安德鲁·休伯曼：
Interesting.
有趣。
Dr. Matthew Hill:
马修·希尔博士：
It is, yeah.
是的，是的。
Andrew Huberman:
安德鲁·休伯曼：
So a hot shower.
所以洗个热水澡。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
Dr. Matthew Hill:
马修·希尔博士：
So apparently, if it happens, a hot shower is what people claim.
显然，如果发生这种情况，人们就会声称洗个热水澡。
Andrew Huberman:
安德鲁·休伯曼：
Shower yourself in the shower.
在淋浴间淋浴。
Dr. Matthew Hill:
马修·希尔博士：
So yeah.
所以是的。
So for me, I would say the main harms that people need to be aware of are the schizophrenia, bipolar, possible cardiovascular effects, and then this is one of these syndromes that can come out of it, as well as possible lung damage from smoking.
所以对我来说，我想说，人们需要意识到的主要危害是精神分裂症、躁郁症、可能的心血管影响，这是可能产生的综合症之一，以及吸烟可能造成的肺损伤。
Those are the main, I think, genuine, bona fide health issues associated with cannabis that people should be aware of.
我认为，这些是人们应该意识到的与大麻相关的主要健康问题。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
Dr. Matthew Hill:
马修·希尔博士：
I know we're not going to probably go into depth with it.
我知道我们可能不会深入探讨它。
On the other side, with the medical stuff, it's a little bit more challenging.
另一方面，在医疗方面，则更具挑战性。
A lot of this is just because we really don't have good studies that have been done in any capacity that have really definitively told us if cannabis has really bona fide medical benefit.
这很大程度上是因为我们确实没有以任何方式进行的良好研究能够真正明确地告诉我们大麻是否真正具有真正的医疗益处。
Andrew Huberman:
安德鲁·休伯曼：
Yeah, I was going to ask you about that.
是的，我正想问你这个问题。
It's always nice to end on a positive side, and we don't want to demonize cannabis, nor do we want to glorify it.
以积极的一面结束总是好的，我们不想妖魔化大麻，也不想美化它。
But the examples that I've heard of medical uses for cannabis include appetite stimulation.
但我听说过的大麻医疗用途的例子包括刺激食欲。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
We talked about that.
我们讨论过这个。
For glaucoma, lowering eye pressure-
对于青光眼，降低眼压-
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
and glaucoma, the age and age-related increase in eye pressure are two of the major risk factors for glaucoma, which is the most common blinding disease second to cataract.
和青光眼一样，年龄和与年龄相关的眼压升高是青光眼的两个主要危险因素，青光眼是仅次于白内障的最常见的致盲疾病。
More than 70 million people suffer from it.
超过 7000 万人患有此病。
Everybody, regardless of age, get your eye pressures checked.
每个人，无论年龄大小，都应该检查眼压。
There are drops for this, but okay, cannabis can reduce eye pressure in glaucoma.
有一些滴眼液可以解决这个问题，但是没关系，大麻可以降低青光眼患者的眼压。
Nausea, you mentioned.
恶心，你提到过。
Dr. Matthew Hill:
马修·希尔博士：
Mm-hmm.
嗯嗯。
Andrew Huberman:
安德鲁·休伯曼：
And then anxiety.
然后是焦虑。
It sounds like if people get the-
听起来好像如果人们得到-
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
dose right and it's right for them, that in some cases, it can help them with their anxiety.
剂量正确并且适合他们，在某些情况下，它可以帮助他们缓解焦虑。
And the reason I raise that one is because it seems that most people who decide to use cannabis regularly are using it perhaps for its euphoric effects, but as a kind of a mild sedative, a way to relax in the same way that they would use a glass or two of wine.
我之所以提出这个问题，是因为似乎大多数决定定期使用大麻的人可能是因为它的欣快作用而使用它，但它是一种温和的镇静剂，一种放松的方式，就像他们喝一两杯酒一样。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
What are your thoughts on that?
您对此有何看法？
Because I think this is the most common use case.
因为我认为这是最常见的用例。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
The other one that wasn't on there, but you've mentioned this before, and I have as well, is pain.
另一个不在其中的问题是疼痛，但你之前已经提到过，我也提到过。
So chronic pain is-
所以慢性疼痛是——
Andrew Huberman:
安德鲁·休伯曼：
Oh, pain.
哦，痛苦。
Thank you
谢谢你
Dr. Matthew Hill:
马修·希尔博士：
...
...
pain is, I would say, the number one.
我想说，痛苦是第一位的。
So pain is certainly the one that there's the most amount of evidence for, and-
所以疼痛肯定是有最多证据支持的一种疼痛，而且——
Andrew Huberman:
安德鲁·休伯曼：
Thank you
谢谢你
Dr. Matthew Hill:
马修·希尔博士：
...
...
I would say when you talked about this in the previous podcast, you were mostly correct about this component of it in the sense that it's not that cannabis is a profound analgesic.
我想说，当您在之前的播客中谈到这一点时，您对它的这一部分的看法基本上是正确的，因为大麻并不是一种深刻的镇痛药。
It's that cannabis, it has some analgesic properties, but it's not super sledgehammer in that sense.
就是大麻，它有一定的镇痛作用，但从这个意义上来说，它并不是超级大锤。
But what it does seem to do is, it seems to strip away the affective component of pain to some degree.
但它似乎确实在某种程度上消除了疼痛的情感成分。
And so what I have consistently heard from chronic pain patients when they use cannabis is they say, "Yeah, my pain's still there, but now the pain's background noise.
因此，当慢性疼痛患者使用大麻时，我一直听到他们说：“是的，我的疼痛仍然存在，但现在疼痛已成为背景噪音。
So I can sleep at night." And just being able to sleep, I think, is actually providing a huge amount of the benefit to that community.
这样我晚上就可以睡觉了。”我认为，只要能够睡觉，实际上就为该社区带来了巨大的好处。
But it's the day-to-day.
但这是日复一日的。
They're able to function with the pain because they don't become focused on it the same way because they're able to kind of push it to the background.
他们能够忍受痛苦，因为他们不会以同样的方式专注于它，因为他们能够将它推到后台。
That seems to be the main ability of cannabis.
这似乎是大麻的主要能力。
Yes, there's some mild analgesic properties to it to some degree, but it really seems to be much more that component of it.
是的，它在某种程度上有一些温和的镇痛作用，但它似乎确实是它的组成部分。
And I think you'd alluded to something like that in the previous podcast.
我想你在之前的播客中提到过类似的事情。
You'd said something about how it's changing the emotional state of pain.
你说过它如何改变痛苦的情绪状态。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
And we know from the biopsychosocial model of pain that Emotions and interpretation of-
我们从疼痛的生物心理社会模型中知道，情绪和解释-
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
the sensation of pain is a huge component of what people refer to as chronic and acute pain.
疼痛感是人们所说的慢性和急性疼痛的重要组成部分。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
So, the pain thing, I think, is a central one, and that's one of the only ones that there's a little bit of actual research on.
所以，我认为，痛苦是一个核心问题，也是唯一有一点实际研究的问题之一。
Most of it's either with isolated THC, I think there's one or two studies that have actually looked at smoked cannabis and found small signals of benefit.
大部分都是与分离的四氢大麻酚有关，我认为有一两项研究实际上研究了吸食大麻并发现了微小的有益信号。
But so, anxiety is an interesting one.
但焦虑是一个有趣的问题。
And so, obviously this is more near and dear to my heart because I study stress and anxiety as my primary area, and cannabinoids and endocannabinoids in that space.
因此，显然这更贴近我的心，因为我研究压力和焦虑作为我的主要领域，以及该领域的大麻素和内源性大麻素。
And yeah, you look at questionnaire-based studies about why people smoke cannabis, and 85% of them will say, "Because it reduces stress and it makes me feel less anxious." That was a big impetus as to why we started studying endocannabinoid regulation of it, because similar to feeding and pain, where we know endocannabinoids are involved in regulating feeding circuits and endocannabinoids are also integrated into pain circuitry and can provide some endogenous analgesic signals, we figured the same was going to be true for stress and anxiety, which to some degree it is.
是的，你看看关于人们吸食大麻原因的问卷调查，你会发现 85% 的人会说，“因为它可以减轻压力，让我感觉不那么焦虑。”这是我们开始研究内源性大麻素对其调节的巨大推动力，因为与喂养和疼痛类似，我们知道内源性大麻素参与调节喂养回路，内源性大麻素也整合到疼痛回路中，并可以提供一些内源性镇痛信号，我们认为压力和焦虑也是如此，在某种程度上确实如此。
But it's very complicated because it can be, like I said before, biphasic, where some lower doses are anxiolytic, higher doses can promote anxiety.
但这非常复杂，因为正如我之前所说，它可能是双相的，其中一些较低剂量具有抗焦虑作用，而较高剂量会促进焦虑。
But for the majority of people who use cannabis regularly, it's because it helps reduce anxiety.
但对于大多数经常使用大麻的人来说，这是因为它有助于减少焦虑。
Now, whether that would hold weight in a clinical trial is a different story.
现在，这在临床试验中是否有效则是另一回事了。
There is some old evidence from, I'd say the '70s or early '80s, where they were using synthetic forms of THC, like nabilone, which is something you can get in Canada, or Marinol or dronabinol, which I think is what's accessible in the States, where they did find some evidence to suggest it was on par with a benzodiazepine, like diazepam or something.
有一些旧的证据，我想说的是 70 年代或 80 年代初，他们使用合成形式的 THC，比如大麻隆（在加拿大可以买到），或者马里诺（Marinol）或屈大麻酚（我认为在美国也可以买到），他们确实发现了一些证据表明它与苯二氮卓类药物（如地西泮或其他药物）相当。
I can't remember exactly what the comparator they'd used there, but there was some evidence for there being some anti-anxiety properties of THC.
我记不清他们在那里使用的比较器是什么，但有一些证据表明 THC 具有一些抗焦虑特性。
And that tracks generally well with the self-reported literature that's out there.
这与现有的自我报告文献总体吻合。
Now, whether that's the same as an ability to have benefit in something like PTSD is a different question.
现在，这是否与从创伤后应激障碍（PTSD）中获益的能力相同是一个不同的问题。
It gets a little bit more complicated because obviously PTSD has an anxiety component to it, but there's a lot more to it as well.
它变得有点复杂，因为显然创伤后应激障碍有焦虑的成分，但还有更多的成分。
And again, there's very little research in this space.
再说一遍，这个领域的研究很少。
There was one really, really small study done by the Canadian military.
加拿大军方进行了一项非常非常小的研究。
First, they did one version of it that was an open label.
首先，他们做了一个开放标签的版本。
Open label trials, for people who don't know, is just basically everyone knows what they're getting.
对于那些不知道的人来说，开放标签试验基本上每个人都知道他们得到了什么。
It's not blinded in any way.
它在任何方面都没有被蒙蔽。
But because of the self-reported data from the veteran population about cannabis helping, especially with sleep, and the big thing that they reported was that it suppressed their nightmares.
但由于退伍军人的自我报告数据表明大麻有帮助，尤其是对睡眠的帮助，他们报告的最重要的一点是大麻抑制了他们的噩梦。
And so, post-traumatic stress disorder is a very complex disease for many reasons, and one component of it is the re-experiencing events that happen during sleep, where there's a lot of nightmares and individuals will kind of re-experience the trauma that led to the development of the PTSD.
因此，创伤后应激障碍是一种非常复杂的疾病，原因有很多，其中一个组成部分是在睡眠期间重新经历事件，其中有很多噩梦，个人会重新经历导致 PTSD 发展的创伤。
And there does seem to be some suggestion that because they're remembering it and maybe changing the details because they're in a dreamscape space, that they reconsolidate it a little bit more, and there's often a high degree of sympathetic activation and arousal that goes on with these nightmares.
似乎确实有一些建议，因为他们正在记住它，并且可能会因为他们处于梦境空间而改变细节，所以他们会更多地重新巩固它，并且这些噩梦通常会伴随着高度的交感神经激活和唤醒。
And some of the belief is that this is part of the sensitization process that can happen in PTSD, where the disease can worsen over time because the re-experiencing and the reconsolidation and the sensitization of the disease that happens over time in this kind of sleep state can make it worse.
一些人认为，这是 PTSD 中可能发生的致敏过程的一部分，随着时间的推移，疾病可能会恶化，因为在这种睡眠状态下，随着时间的推移，重新体验、重新巩固和疾病的致敏可能会使情况变得更糟。
And so the majority of veterans who have used cannabis and report benefit, if you actually talk to them about it, as I've done in a few different situations, and also just look at the anecdotal data, almost all of it talks explicitly about sleep.
因此，大多数使用过大麻并报告受益的退伍军人，如果你真的与他们谈论大麻，就像我在几种不同情况下所做的那样，并且也只是看看轶事数据，几乎所有这些都明确谈论了睡眠。
And they say, "Oh, we use cannabis or THC before bed.
他们说，“哦，我们在睡觉前使用大麻或四氢大麻酚。
We find we don't have the nightmares." And just the simple trickle-down effect of that is hugely beneficial for them.
我们发现我们不再做噩梦了。”仅仅这种简单的涓滴效应就对他们非常有利。
And so the Canadian military did an open label trial on this.
因此加拿大军方对此进行了公开标签试验。
Again, not blinded, it was small numbers, but they basically found as soon as they put people on nabilone, this synthetic version of THC, in a large proportion, I think like 85% of them almost stopped having these nightmares.
再说一遍，不是盲目的，这是很小的数字，但他们基本上发现，一旦他们让人们服用大麻隆，这种合成版本的 THC，占很大比例，我认为 85% 的人几乎不再做这些噩梦。
And this was a treatment-resistant population that was pretty severe, so this was a big benefit.
这是一个相当严重的难治性人群，所以这是一个很大的好处。
So they then took the open label and did what you should and moved forward to do a double-blind placebo-controlled.
因此，他们随后采取了开放标签并做了你应该做的事情，然后继续进行双盲安慰剂对照。
Now, it was a very small sampled studies, and that is obviously always a problem with human work, is this was like 15 or 17 people.
现在，这是一项非常小的抽样研究，这显然始终是人类工作的一个问题，是不是有 15 或 17 个人。
So not powered enough to really make any kind of firm conclusions, but interesting in the sense that at least it was done in a proper crossover design, where they got placebo at one point, they got nabilone at one point, it was switched.
因此，没有足够的力量来真正做出任何确定的结论，但有趣的是，至少它是在适当的交叉设计中完成的，他们在某个时刻得到了安慰剂，在某个时刻得到了大麻龙，它被转换了。
They didn't know which one they were on.
他们不知道自己在哪一站。
Because they're taking it right before bed, maybe that will remove some of the subjective bias.
因为他们在睡觉前服用，也许这会消除一些主观偏见。
Again, you can't totally remove it, but if someone's taking it within an hour or so of going to sleep, they may not feel the high the same way.
再说一次，你不能完全去除它，但如果有人在睡觉前一个小时左右服用它，他们可能不会感觉同样的快感。
But even under the double-blinded conditions, they found a very effective suppression of the nightmares and the re-experiencing.
但即使在双盲条件下，他们也发现了对噩梦和重新体验的非常有效的抑制。
And then they also, at the same time, found this increase in quality of life measures, which tracked with the fact that they were probably sleeping better.
与此同时，他们还发现生活质量指标有所提高，这与他们可能睡得更好这一事实相一致。
I don't think they actually reported any change or even looked at maybe the overall PTSD score.
我认为他们实际上没有报告任何变化，甚至没有考虑创伤后应激障碍的总体得分。
They only reported or really focused on the nightmare component of it, because that was the primary outcome of the study.
他们只报告或真正关注其中的噩梦部分，因为这是研究的主要结果。
So I thought that was interesting because if you look at the anecdotal data in PTSD, that's where a lot of it is focused on, is using it as kind of, I wouldn't maybe call it a sleep aid because it's really more of a modulator of the dream state.
所以我认为这很有趣，因为如果你看一下 PTSD 中的轶事数据，那就是很多人关注的地方，将其用作一种，我可能不会称其为睡眠辅助剂，因为它实际上更像是梦境状态的调节器。
And I think this is-
我认为这是——
Andrew Huberman:
安德鲁·休伯曼：
Right.
对。
Presumably because it's reducing the amount of rapid eye movement sleep you're getting, which most people will probably hear and interpret as bad.
大概是因为它会减少你的快速动眼睡眠时间，大多数人可能会听到并认为这是不好的。
But REM deprivation is actually one treatment for depression.
但快速眼动睡眠剥夺实际上是治疗抑郁症的一种方法。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
So there are certain case conditions where dreaming and REM is not advantageous, and you're describing one.
因此，在某些情况下，做梦和快速眼动睡眠并不有利，而您正在描述其中一种情况。
Dr. Matthew Hill:
马修·希尔博士：
I mean, and depression and PTSD are both two disorders that are characterized by changes in REM.
我的意思是，抑郁症和创伤后应激障碍（PTSD）都是两种以快速眼动睡眠（REM）变化为特征的疾病。
Like, they have earlier onset to REM, so they go into REM faster.
比如，他们进入快速眼动睡眠的时间较早，因此他们更快地进入快速眼动睡眠。
They tend to have some altered architecture of the REM component of their sleep.
他们的睡眠中快速眼动睡眠部分的结构往往会发生一些改变。
So in those states, maybe suppressing REM isn't actually a bad thing.
所以在这些州，也许抑制快速眼动睡眠实际上并不是一件坏事。
Andrew Huberman:
安德鲁·休伯曼：
Right.
对。
Dr. Matthew Hill:
马修·希尔博士：
At least, certainly for PTSD, I would imagine in terms of the context of the nightmares, that's providing some benefit.
至少，对于创伤后应激障碍（PTSD），我认为就噩梦的背景而言，这确实提供了一些好处。
Whether or not it globally is changing the disease severity or improving the disease, I don't think we really have any evidence to say.
无论它是否在全球范围内改变疾病的严重程度或改善疾病，我认为我们没有任何证据可以证明。
But again, I can understand the ...
但话又说回来，我能理解...
the desire for people to self-medicate, let's say, by using this as an approach to try and reduce that component of their sleep so that they sleep better, they feel better.
人们渴望自我治疗，比方说，通过使用这种方法来尝试减少睡眠的这一部分，以便他们睡得更好，感觉更好。
Maybe down the road, it would help the prognosis of the disease long term if it's not sensitizing the same way.
也许在未来，如果它不以同样的方式敏感，它将有助于疾病的长期预后。
But I don't think we have any strong data that we can leverage in that capacity to be able to say it.
但我认为我们没有任何强有力的数据可以利用来表达这一点。
But to me, it's one of the more interesting areas.
但对我来说，这是更有趣的领域之一。
I think anxiety disorders in general, there's definitely some potential.
我认为总的来说，焦虑症肯定有一些潜力。
So as I'd mentioned earlier, the FAAH inhibitor that elevates anandamide levels.
正如我之前提到的，FAAH 抑制剂可以提高 anandamide 水平。
So Johnson & Johnson did do a trial on social anxiety disorder.
所以强生公司确实做了一项针对社交焦虑症的试验。
It's published, I think, from a few years ago, in '21 or something, I can pull up the reference for that, where they did find some benefit.
我想，它是几年前发布的，在 21 年左右，我可以找到相关的参考资料，他们确实发现了一些好处。
It wasn't huge, and some of this had to do with the design of the study because they kind of underdosed the patients a bit.
这个数字并不大，其中一些与研究的设计有关，因为他们给病人的剂量有点不足。
And so not everyone actually showed the elevation in anandamide when they went back and looked.
因此，当他们回去观察时，并不是每个人都真正表现出大麻素的升高。
But when they actually isolated the group of people that had higher anandamide, in that proportion of the patients, they did see some symptom improvement.
但当他们真正隔离出大麻素含量较高的人群时，在该比例的患者中，他们确实看到了一些症状改善。
So it did support it.
所以它确实支持它。
And this is very similar, for us, this is a big thing because all of the work that we focused on is looking at how stress and stress hormones regulate largely anandamide signaling.
这非常相似，对我们来说，这是一件大事，因为我们关注的所有工作都是研究压力和应激激素如何在很大程度上调节大麻素信号传导。
And one of the main things that we've demonstrated that's been replicated relatively well over the years is that stress exposure can actually cause a rapid loss of anandamide signaling, and it's that loss of anandamide signaling that seems to facilitate some synaptic strengthening in the amygdala and promote activity in areas that are involved in these anxiety circuits.
我们已经证明，多年来得到相对较好复制的主要事情之一是，压力暴露实际上会导致 anandamide 信号的快速丧失，而 anandamide 信号的丧失似乎促进了杏仁核中的一些突触强化，并促进了参与这些焦虑回路的区域的活动。
Andrew Huberman:
安德鲁·休伯曼：
Mm.
嗯。
Dr. Matthew Hill:
马修·希尔博士：
And so, the thought has always been, well, if anandamide, it's that job as its kind of tonic housekeeper, keeping things in that homeostatic range, let's say we're talking about explicitly an anxiety circuit.
因此，人们一直以来的想法是，好吧，如果大麻素，它就是一种补品管家，将事物保持在稳态范围内，假设我们正在明确地谈论焦虑回路。
There's individual variation that exists in humans across everything.
人类在所有事情上都存在个体差异。
So one of our predictions has been maybe people who are on the high end of the anxiety spectrum might be on the low end of their tonic anandamide signaling spectrum.
因此，我们的预测之一是，处于焦虑谱高端的人可能处于其强效大麻素信号谱的低端。
And we've gotten a little bit of support from that from animal work where we've screened animals based on anxiety and looked at endocannabinoid levels in the amygdala and found lower anandamide.
我们从动物工作中得到了一些支持，我们根据焦虑对动物进行了筛选，并观察了杏仁核中的内源性大麻素水平，发现大麻素含量较低。
Andrew Huberman:
安德鲁·休伯曼：
That's extremely interesting because it squares with my, again, non-laboratory observation that a lot of people use cannabis to deal with their anxiety.
这非常有趣，因为它与我的非实验室观察结果相符，即很多人使用大麻来应对焦虑。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Right?
对吗？
So what you're saying is that there's a range of, let's just say baseline circuit activation within the amygdala and related structures in mice and humans, presumably in other animals also.
所以你的意思是，在小鼠和人类（可能在其他动物中）的杏仁核和相关结构内存在一系列的基线回路激活。
If people take a compound that adjusts the homeostatic level of what's considered low, moderate, and high activation of those circuits that include the amygdala, then perhaps they're bringing their anxiety into range-
如果人们服用一种化合物来调节包括杏仁核在内的那些回路的低、中和高激活的稳态水平，那么也许他们正在将焦虑控制在一定范围内——
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
in a way that perhaps is different than with alcohol, which is more acute.
在某种程度上可能与酒精不同，酒精更严重。
People have a couple drinks, they'll feel relaxed, but then there's this phenomenon of hangxiety-
人们喝了几杯，会感到放松，但随之而来的是一种焦虑的现象——
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
the next day, feeling a little anxious when they're not drinking.
第二天，当他们不喝酒时感到有点焦虑。
Whereas, it's interesting that many people who use cannabis for this purpose are not using it all day long.
然而有趣的是，许多为此目的使用大麻的人并不是整天使用它。
They are perfectly able to wait until the nighttime or evening.
他们完全能够等到夜间或晚上。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And of course, people can wait for happy hour for a drink as well.
当然，人们也可以等待欢乐时光来喝一杯。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
But it's far and away different than the way we envision something like alcohol use disorder, where somebody discovers that alcohol really helps with their anxiety, and then they're drinking maybe one at lunch, maybe a couple at dinner, and then in the evening to fall asleep at night.
但这与我们想象的酒精使用障碍的方式有很大不同，在酒精使用障碍中，有人发现酒精确实有助于缓解焦虑，然后他们可能在午餐时喝一杯，可能在晚餐时喝几杯，然后在晚上入睡。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
I'm describing extremes here, but I find your hypothesis to square really well with the real-world observations.
我在这里描述的是极端情况，但我发现你的假设与现实世界的观察非常吻合。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And it's an interesting one.
这是一件有趣的事。
Dr. Matthew Hill:
马修·希尔博士：
There is some evidence to actually support.
有一些证据确实支持。
So my buddy Sachin Patel, who's at Northwestern now, but he was at Vanderbilt when he did this study.
我的朋友萨钦·帕特尔（Sachin Patel）现在在西北大学，但他做这项研究时在范德比尔特大学。
They basically played with these drugs that you can use to prevent endocannabinoid synthesis.
他们基本上使用这些可以用来阻止内源性大麻素合成的药物。
So you can create a state of impaired endocannabinoid function.
因此，您可能会造成内源性大麻素功能受损的状态。
And-
还有——
Andrew Huberman:
安德鲁·休伯曼：
In humans
在人类中
Dr. Matthew Hill:
马修·希尔博士：
...
...
and they did this in rodents.
他们在啮齿类动物身上做到了这一点。
Andrew Huberman:
安德鲁·休伯曼：
Okay.
好的。
Dr. Matthew Hill:
马修·希尔博士：
So this was done in mice.
所以这是在老鼠身上完成的。
One of the questions was is, so A, does reductions in endocannabinoid function produce states of anxiety?
问题之一是，那么，内源性大麻素功能的减少是否会产生焦虑状态？
And they did demonstrate that.
他们确实证明了这一点。
So you could deplete endocannabinoid levels, and you got the emergence of an anxiety state.
所以你可能会耗尽内源性大麻素水平，然后你就会出现焦虑状态。
So then you could give drugs that would boost the endocannabinoids to normalize this.
因此，您可以服用可增强内源性大麻素水平的药物，使其正常化。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Matthew Hill:
马修·希尔博士：
So again, it kind of fit with the idea.
再说一次，这与这个想法相符。
But then they did one key study where then they gave THC and saw could THC fill in the gap.
但后来他们做了一项关键研究，然后他们给予 THC，看看 THC 能否填补空白。
And they found that like boosting endocannabinoids, giving THC on a background of low endocannabinoids was able to reverse that anxiety phenotype and bring it back into more of the normal range.
他们发现，就像增强内源性大麻素一样，在低内源性大麻素背景下给予 THC 能够逆转焦虑表型，使其恢复到正常范围。
So again, maybe for some people, again, this is theoretical, so I don't know how much of a spectrum there is, if there are people that are at this low end.
所以，也许对于某些人来说，这只是理论上的，所以我不知道如果有人处于这个低端，那么我不知道有多少范围。
But certainly, I think from the animal literature, there's some foundation for making a theory that's similar to what you're saying, which is maybe some people are trying to fill in a gap of something that's deficient in them, and therefore, that can help them feel less anxious.
但当然，我认为从动物文献中，有一些基础可以提出与你所说的类似的理论，这可能是有些人试图填补他们所缺乏的东西的空白，因此，这可以帮助他们减少焦虑。
And that, again, may be very different than someone who is very anxious for different reasons or has normal endocannabinoid function, or something else might be at play there.
同样，这可能与因不同原因而非常焦虑或具有正常内源性大麻素功能的人有很大不同，或者可能有其他因素在起作用。
So-
所以——
Andrew Huberman:
安德鲁·休伯曼：
Very interesting
很有趣
Dr. Matthew Hill:
马修·希尔博士：
...
...
yeah, I think it could explain some of the heterogeneity that exists out there for sure, yeah.
是的，我认为它可以肯定地解释一些存在的异质性，是的。
Andrew Huberman:
安德鲁·休伯曼：
So perhaps genetic differences in baseline levels of anxiety perhaps map to endogenous levels of anandamide and might predict propensity for THC use.
因此，焦虑基线水平的遗传差异可能与大麻素的内源水平有关，并可能预测 THC 使用的倾向。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
We have definitely found in human populations through work I've done with a lot of clinical collaborators and others, we look at endocannabinoids in the blood, and it's not in the brain, but they are lipids that can move pretty easily back and forth.
通过我与许多临床合作者和其他人所做的工作，我们确实在人群中发现了，我们观察血液中的内源性大麻素，它不在大脑中，但它们是可以很容易地来回移动的脂质。
And we have found relationships between peripheral endocannabinoid levels and mood states, both anxiety and kind of depressive measures, which does somewhat relate to the possibility that this could be real.
我们发现了外周内源性大麻素水平与情绪状态（包括焦虑和抑郁措施）之间的关系，这在一定程度上与这可能是真实的可能性有关。
We don't know.
我们不知道。
It's been hard, obviously, for various reasons, to really track this.
显然，由于各种原因，真正追踪这一点很困难。
But we've never looked at an anxiety disorder population.
但我们从未研究过焦虑症人群。
We've done some work with post-traumatic stress disorder populations.
我们针对创伤后应激障碍人群做了一些工作。
There's been work in depression populations that have found some relationships that are pretty similar.
在抑郁症人群中进行的研究发现了一些非常相似的关系。
So it's certainly a possibility.
所以这当然是有可能的。
But again, this is all our theory at this point.
但同样，这就是我们目前的全部理论。
So we'll see as things move forward if they pan out.
因此，如果事情成功，我们将拭目以待。
But yeah.
但是是的。
Andrew Huberman:
安德鲁·休伯曼：
Fantastic.
太棒了。
And I really appreciate that you're able to share some of what your laboratory is working directly on now and looking into the future.
我非常感谢您能够分享您的实验室目前正在直接开展的一些工作以及对未来的展望。
And I want to thank you for what has been an incredibly clear, precise, and in many cases actionable, whether or not it leads to a yes or a no, actionable information here, because cannabis and CBD, as you pointed out, are kind of everywhere around us.
我要感谢您提供了令人难以置信的清晰、精确且在许多情况下可操作的信息，无论它是否会导致是或否，在这里，因为大麻和 CBD，正如您所指出的，在我们周围无处不在。
Dr. Matthew Hill:
马修·希尔博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And people are making decisions about cannabis and CBD.
人们正在对大麻和 CBD 做出决定。
And I also want to thank you because what initially started off as a bit of a confrontation online- ...
我还要感谢你们，因为最初是网上的一场对抗——……
which I alluded to in the introduction that I gave, has now evolved into a collaboration that I'm certain, based on the exquisitely clear and generous information that you've provided, has led to better education, more clarity, and therefore better informed choices for all the people listening and watching.
我在介绍中提到的合作现在已经发展成为一种合作，我确信，基于你们提供的极其清晰和慷慨的信息，已经为所有听众和观看者带来了更好的教育、更清晰的信息，从而做出更明智的选择。
So I really truly appreciate you coming out here, sitting down with me, discussing these issues, clarifying points that were unclear before, and also pointing to the fact that this is a complex system-
因此，我真的非常感谢您来到这里，与我坐下来讨论这些问题，澄清以前不清楚的观点，并指出这是一个复杂的系统这一事实-
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
a complex biology.
复杂的生物学。
There are a lot of things about psychosis, about negative effects, about potential positive uses of cannabis that just are not yet clear, and thanks to excellent researchers like you, are likely going to be clarified in the years to come.
关于精神病、关于大麻的负面影响、关于大麻潜在的积极用途的很多事情尚不清楚，感谢像您这样优秀的研究人员，这些事情可能会在未来几年得到澄清。
So thank you ever so much for your time, for your research, and for your attention to the public health education effort-
非常感谢您的宝贵时间、您的研究以及您对公共卫生教育工作的关注——
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
around cannabis.
围绕大麻。
Thank you.
谢谢。
Dr. Matthew Hill:
马修·希尔博士：
Thanks, and I think it's also important, I think it's good, as you had said, that for people to see that scientists can have disagreements.
谢谢，我认为这也很重要，我认为这很好，正如你所说，让人们看到科学家可以有分歧。
Andrew Huberman:
安德鲁·休伯曼：
Absolutely.
绝对的。
Dr. Matthew Hill:
马修·希尔博士：
I think it's important.
我认为这很重要。
I think it's good that you provided me an opportunity to correct the record and did so in a very appropriate manner.
我认为您为我提供了纠正记录的机会并且以非常适当的方式进行了纠正，这很好。
I think this was a great discussion for people to understand different perspectives.
我认为这是一次很好的讨论，让人们了解不同的观点。
Also good to highlight where it was that I had had issue with your previous podcast, and I think the discussions that came out of that were for the better.
也很高兴强调我对你之前的播客有疑问的地方，我认为由此产生的讨论是为了更好。
So that's all the best.
这样就最好了。
And hopefully, if there's other contentious issues that happen down the road, similar things move forward, and you chat with people in that area as well.
希望如果以后发生其他有争议的问题，类似的事情会继续下去，并且您也可以与该地区的人们聊天。
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Yeah, if somebody who is expert in a particular area takes issue with something specific and can substantiate it with something that can foster better understanding, without fail, I'll reach out to them.
是的，如果某个特定领域的专家对特定的问题提出疑问，并且可以用可以促进更好理解的东西来证实它，我一定会联系他们。
Now, how quickly we're able to get them here, et cetera, is always an issue.
现在，我们能够以多快的速度将它们送到这里等等，始终是一个问题。
Sometimes we can put an addendum to a podcast.
有时我们可以在播客中添加附录。
Nowadays that's easier using what's called dynamic insertion, where we can go back and actually make a correction.
如今，使用所谓的动态插入更容易，我们可以返回并实际进行更正。
Dr. Matthew Hill:
马修·希尔博士：
Mm-hmm.
嗯嗯。
Andrew Huberman:
安德鲁·休伯曼：
But listen, the best situation is always when this podcast can mimic the real world of research science as you and I both know it to exist, where if we had been in a meeting and you presented data, I presented data, and we disagreed, what we would probably do would be to head, well, traditionally it would be to the bar, but we'd grab a cup-
但是听着，最好的情况总是当这个播客可以模仿研究科学研究的真实世界时，正如你和我都知道它存在的那样，如果我们参加会议，你提供数据，我提供数据，而我们不同意，我们可能会做的就是前往，好吧，传统上是去酒吧，但我们会拿一杯 -
Dr. Matthew Hill:
马修·希尔博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
of coffee or go for a walk, and we would talk about it, hash it out, and then potentially bring it up again at the next meeting.
喝杯咖啡或者去散步，我们会讨论它，讨论一下，然后可能在下次会议上再次提到它。
So in some sense, what we've done here over the last month or so, and certainly during today's podcast, is to do something to that effect.
因此，从某种意义上说，我们在过去一个月左右的时间里所做的事情，当然还有今天的播客中，都是为了实现这一目标而做的。
So yeah.
所以是的。
Dr. Matthew Hill:
马修·希尔博士：
And I think it's really good for people in the public to know this is how science progresses.
我认为让公众知道科学是如何进步的真的很有好处。
Someone says something, someone disagrees with it.
有人说某事，有人不同意。
You get an opportunity to clarify things, and I think that that's really good just to move things forward.
你有机会澄清事情，我认为这对于推动事情向前发展真的很好。
So I think that was a good process that we've gone through.
所以我认为这是我们经历过的一个很好的过程。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
Likewise, and it's certainly within the spirit of the podcast.
同样，这当然符合播客的精神。
In no way, shape, or form do I purport to get everything right, and where I've made mistakes, I really strive to correct them.
我决不声称自己把一切都做对了，在我犯了错误的地方，我真的努力改正它们。
And listen, it's been a real honor and privilege to have you out here.
听着，您来到这里真是一种荣幸。
Thanks for coming all the way from Canada, and I do hope to have you back again as the research evolves and we can learn more about these topics and more.
感谢您从加拿大远道而来，我确实希望随着研究的进展您能再次回来，我们可以了解更多有关这些主题的信息以及更多信息。
So thank you so much, Matt.
非常感谢你，马特。
Appreciate you.
感谢你。
Dr. Matthew Hill:
马修·希尔博士：
Great.
太棒了。
Andrew Huberman:
安德鲁·休伯曼：
Thank you for joining me for today's discussion about cannabis with Dr. Matthew Hill.
感谢您今天与我一起与 Matthew Hill 博士讨论大麻。
I hope you found the discussion to be as informative as I did.
我希望您能像我一样发现这次讨论内容丰富。
If you're learning from and/or enjoying this podcast, please subscribe to our YouTube channel.
如果您正在学习和/或喜欢此播客，请订阅我们的 YouTube 频道。
Please also subscribe to the podcast on both Spotify and Apple.
另请在 Spotify 和 Apple 上订阅该播客。
That's a terrific zero-cost way to support us.
这是支持我们的绝佳零成本方式。
And on both Spotify and Apple, you can leave us up to a five-star review.
在 Spotify 和 Apple 上，您都可以给我们五星级的评价。
Please also check out the sponsors that I mentioned at the beginning and throughout today's episode.
另请查看我在今天节目开头和整个节目中提到的赞助商。
That's the best way to support this podcast.
这是支持这个播客的最佳方式。
If you have questions for me or comments about the podcast or topics or guests you'd like me to consider for the Huberman Lab Podcast, please put those in the comments section on YouTube.
如果您对我有疑问或对播客有意见，或者希望我在 Huberman 实验室播客中考虑的主题或嘉宾，请将这些意见放入 YouTube 的评论部分。
I do read all the comments.
我确实阅读了所有评论。
For those of you that haven't heard, I have a new book coming out.
对于那些还没有听说过的人，我即将出版一本新书。
It's my very first book.
这是我的第一本书。
It's entitled "Protocols: An Operating Manual for the Human Body." This is a book that I've been working on for more than five years, and that's based on more than 30 years of research and experience.
它的标题是“协议：人体操作手册”。这本书是我花了五年多时间编写的，它基于 30 多年的研究和经验。
And it covers protocols for everything from sleep to exercise to stress control, protocols related to focus and motivation, and of course, I provide the scientific substantiation for the protocols that are included.
它涵盖了从睡眠到运动再到压力控制的所有协议，以及与注意力和动机相关的协议，当然，我为所包含的协议提供了科学依据。
The book is now available by presale at protocolsbook.com.
该书现已在protocolbook.com 上预售。
There you can find links to various vendors.
在那里您可以找到各个供应商的链接。
You can pick the one that you like best.
您可以选择您最喜欢的一个。
Again, the book is called "Protocols: An Operating Manual for the Human Body." If you're not already following me on social media, I am hubermanlab on all social media channels.
同样，这本书的名字是“协议：人体操作手册”。如果您还没有在社交媒体上关注我，我是所有社交媒体渠道上的 hubermanlab。
So that's Instagram, X, formerly known as Twitter, Threads, LinkedIn, and Facebook.
这就是 Instagram、X，以前称为 Twitter、Threads、LinkedIn 和 Facebook。
And on all those platforms, I discuss science and science-related tools, some of which overlap with the contents of the Huberman Lab Podcast, but much of which is distinct from the contents of the Huberman Lab Podcast.
在所有这些平台上，我讨论科学和与科学相关的工具，其中一些与胡伯曼实验室播客的内容重叠，但其中大部分与胡伯曼实验室播客的内容不同。
Again, that's hubermanlab on all social media channels.
同样，这是所有社交媒体渠道上的 hubermanlab。
If you haven't already subscribed to our Neural Network Newsletter, our Neural Network Newsletter is a zero-cost monthly newsletter that includes podcast summaries as well as protocols in the form of brief PDFs of one to three pages where I spell out the specific dos and in some cases do nots, but mostly dos related to things like how to optimize your sleep, how to regulate your dopamine levels.
如果您还没有订阅我们的神经网络时事通讯，我们的神经网络时事通讯是一份零成本的月度时事通讯，其中包括播客摘要以及一到三页的简短 PDF 形式的协议，其中我会详细说明具体的注意事项，在某些情况下不包括的注意事项，但大多数注意事项与如何优化您的睡眠、如何调节多巴胺水平等相关。
There's a protocol for neuroplasticity and learning, as well as protocols for fitness, which we call the foundational fitness protocol, includes everything, sets, reps, cardiovascular training.
有神经可塑性和学习的协议，以及健身协议，我们称之为基础健身协议，包括所有内容、组数、次数、心血管训练。
Again, all available completely zero cost.
再次强调，所有这些都是完全零成本的。
You simply go to hubermanlab.com, go to the Menu tab, scroll down to Newsletter, and provide us your email.
您只需访问 hubermanlab.com，转到菜单选项卡，向下滚动到新闻通讯，然后向我们提供您的电子邮件。
But I should point out, we do not share your email with anybody.
但我应该指出，我们不会与任何人分享您的电子邮件。
Thank you once again for joining me for today's discussion with Dr. Matthew Hill.
再次感谢您参加今天与马修·希尔博士的讨论。
And last but certainly not least, thank you for your interest in science.
最后但并非最不重要的一点是，感谢您对科学的兴趣。