How Psilocybin Can Rewire Our Brain, Its Therapeutic Benefits & Its Risks

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。

Today, we are discussing psilocybin.

今天，我们讨论的是裸盖菇素。

Psilocybin is a psychedelic, meaning it modifies the psyche, and in doing so, it changes our level of consciousness.

赛洛西宾是一种致幻剂，这意味着它可以改变心灵，从而改变我们的意识水平。

Psychedelics such as psilocybin change the way that we perceive the outside world and our internal world, our memories, our thoughts, our feelings, et cetera, not just while one is under the influence of psilocybin, but it can also fundamentally change all of those things afterwards and for a very long period of time afterwards as well.

诸如裸盖菇素之类的迷幻药改变了我们感知外部世界和内部世界、我们的记忆、我们的思想、我们的感受等的方式，不仅是在一个人受到裸盖菇素的影响时，而且它还可以在之后的很长一段时间内从根本上改变所有这些事情。

Which is one of the reasons why there's growing excitement about the application of psilocybin and other psychedelics for the treatment of various mental health issues, such as depression, alcohol abuse disorder, and addictions of various kinds, as well as things like OCD and eating disorders.

这就是为什么人们越来越热衷于使用裸盖菇素和其他迷幻药来治疗各种心理健康问题，例如抑郁症、酒精滥用障碍和各种成瘾，以及强迫症和饮食失调等。

Today, we will discuss psilocybin, talking about what it is.

今天，我们将讨论裸盖菇素，谈论它是什么。

In fact, you may be surprised to learn that psilocybin basically is serotonin.

事实上，您可能会惊讶地发现裸盖菇素基本上就是血清素。

Now, for those of you that are familiar with psilocybin and serotonin, you might think, "Wait, that's not true." But in fact, psilocybin's main effect is to mimic serotonin, but it does it in a very specific way because it activates a subset of serotonin receptors in a very strong fashion, leading to neuroplasticity at the level of the neural circuits, that is the brain areas and connections that serve things like memory and perception.

现在，对于那些熟悉裸盖菇素和血清素的人来说，您可能会想，“等等，这不是真的。”但事实上，裸盖菇素的主要作用是模仿血清素，但它以一种非常特殊的方式发挥作用，因为它以非常强烈的方式激活血清素受体的子集，导致神经回路水平的神经可塑性，即服务于记忆和感知等的大脑区域和连接。

So if any of that is confusing at this point, I promise to make it all clear in just a few minutes.

因此，如果目前有任何令人困惑的地方，我保证在几分钟内全部弄清楚。

Psilocybin is one of many psychedelics, of course.

当然，赛洛西宾是众多致幻剂中的一种。

There are things like LSD, DMT, 5-MeO-DMT.

有 LSD、DMT、5-MeO-DMT 之类的东西。

Even MDMA, while not considered a classic psychedelic, is considered a psychedelic in the general sense.

即使是摇头丸，虽然不被认为是经典的迷幻药，但在一般意义上也被认为是迷幻药。

Today's episode is going to focus on psilocybin in particular.

今天的节目将特别关注裸盖菇素。

I will tell you what psilocybin is, how it works at the molecular and cellular level.

我将告诉您裸盖菇素是什么，它如何在分子和细胞水平上发挥作用。

I'll talk about how it changes brain circuitry.

我将讨论它如何改变大脑回路。

I'll talk about the clinical effects, what's been demonstrated in controlled laboratory studies.

我将讨论临床效果，以及在对照实验室研究中所证明的内容。

I'll talk about dosages and translating from psilocybin mushrooms to actual psilocybin, and the compound that actually exerts the effects of psilocybin, which it turns out is not psilocybin, but something called psilocin.

我将讨论剂量以及从裸盖菇素蘑菇到实际裸盖菇素的翻译，以及实际发挥裸盖菇素作用的化合物，事实证明它不是裸盖菇素，而是一种叫做裸盖菇素的东西。

Psilocin is the actual compound that goes into the brain to create all the changes in consciousness and all the rewiring effects that we associate with psilocybin.

裸盖菇素是一种真正的化合物，它进入大脑，产生意识的所有变化以及我们与裸盖菇素相关的所有重新布线效应。

So understanding how psilocybin is converted to psilocin has tremendous impact on the duration of a psilocybin journey, whether or not that psilocybin journey is going to lead to a short or longer window for neuroplasticity.

因此，了解裸盖菇素如何转化为裸盖菇素对裸盖菇素旅程的持续时间具有巨大影响，无论裸盖菇素旅程是否会导致神经可塑性的短期或较长窗口。

In fact, many people don't realize this, but much of the positive changes that are possible with proper, and I do want to underscore proper psilocybin therapeutic approaches, takes place after the session in which one feels all the typical or typically associated effects of psilocybin, like hallucinations and changes in thought patterns, et cetera.

事实上，许多人没有意识到这一点，但正确的裸盖菇素治疗方法可能会带来许多积极的变化，我确实想强调适当的裸盖菇素治疗方法，在疗程结束后发生，在疗程中人们会感受到裸盖菇素的所有典型或通常相关的效果，例如幻觉和思维模式的改变等。

So today, we are going to talk a little bit about chemistry, but I promise to make it accessible to anyone and everyone, regardless of whether or not you have a background in chemistry or biology.

所以今天，我们要谈谈化学，但我保证让任何人都能接触到它，无论你是否有化学或生物学背景。

We're going to talk about some cell biology, the actual neuronal changes that occur when one takes psilocybin, and we're going to talk about how neural circuits change over time and how all of that impacts the changes that most people are interested in when they go on a psilocybin journey.

我们将讨论一些细胞生物学，即服用裸盖菇素时发生的实际神经元变化，我们将讨论神经回路如何随着时间的推移而变化，以及所有这些如何影响大多数人在进行裸盖菇素之旅时感兴趣的变化。

Things such as longstanding improvements in mood.

比如情绪的长期改善。

Things such as tremendous insight into themselves, into others, into their past, their present, and their future.

比如对自己、他人、他们的过去、现在和未来的深刻洞察。

And even changes in their levels of creativity or their ability to experience joy from music or their ability to dissociate in a positive way from things that formerly were depressing or triggers for depression.

甚至他们的创造力水平或从音乐中体验快乐的能力或以积极的方式摆脱以前令人沮丧或引发抑郁的事物的能力也发生了变化。

In fact, we're going to talk quite a lot about the conditions inside of a psilocybin journey that make it actually positive and therapeutic.

事实上，我们将大量讨论裸盖菇素之旅中的条件，这些条件使其实际上具有积极性和治疗性。

This is a very important point that I'll make several times throughout today's episode, which is that just because something invokes neuroplasticity, changes in brain circuitry, does not mean that it's therapeutic, or I should say, does not necessarily mean that it's therapeutic.

这是一个非常重要的观点，我将在今天的节目中多次强调，即仅仅因为某些东西会引起神经可塑性、大脑回路的变化，并不意味着它具有治疗作用，或者我应该说，并不一定意味着它具有治疗作用。

For neuroplasticity to be therapeutic, it has to be adaptive.

为了使神经可塑性具有治疗作用，它必须具有适应性。

It has to allow someone to function better in life than they did previously.

它必须让某人的生活比以前更好。

So today, we will talk about how the conditions of a psilocybin journey, including whether or not it's done with eyes closed or eyes open, or whether or not people alternate between eyes closed and eyes open phases of that journey, as well as whether or not music is played during that journey, and even what types of music are played, will dictate whether or not somebody will feel better or worse in the days and weeks and years following that psilocybin journey, as well as the dosage level.

因此，今天，我们将讨论裸盖菇素旅程的条件，包括是否在闭眼或睁眼的情况下完成，或者人们是否在该旅程的闭眼和睁眼阶段之间交替，以及在该旅程中是否播放音乐，甚至播放什么类型的音乐，将决定一个人在裸盖菇素旅程后的几天、几周和几年内是否会感觉更好或更差，以及剂量水平。

Because, as you'll soon learn as well, there are clinical studies showing that just one psilocybin journey can improve mood in a longstanding way, but most clinical trials involve two dosages spaced in very precise ways from one another with appropriate follow-up.

因为，正如您很快就会了解到的那样，临床研究表明，仅一次裸盖菇素之旅就可以长期改善情绪，但大多数临床试验都涉及以非常精确的方式间隔的两种剂量，并进行适当的后续治疗。

But in both of those particular journeys, the structure of the journey, who's present, who's not present, eyes open or eyes closed, the particular music that's played, all of those features make up part of a larger neuroplasticity trigger of which psilocybin is critical, but psilocybin is not the only variable.

但在这两个特定的旅程中，旅程的结构、谁在场、谁不在场、睁眼或闭眼、播放的特定音乐，所有这些特征构成了更大的神经可塑性触发器的一部分，其中裸盖菇素至关重要，但裸盖菇素并不是唯一的变量。

So whether or not you're interested in participating in a clinical study or whether or not you're interested in psilocybin for other reasons, this is critical information to understand.

因此，无论您是否有兴趣参加临床研究，或者您是否因其他原因对裸盖菇素感兴趣，这都是需要理解的关键信息。

So today, we're going to talk about nearly every feature of psilocybin possible, including what psilocybin is, how it works at the level of chemistry, cell biology, and neural networks, and neuroplasticity.

所以今天，我们将讨论裸盖菇素几乎所有可能的特征，包括裸盖菇素是什么，它在化学、细胞生物学、神经网络和神经可塑性层面上如何发挥作用。

We'll talk about the clinical studies.

我们将讨论临床研究。

We'll talk about dosages.

我们将讨论剂量。

We will talk about conditions of clinical studies, and we will talk about the post-psilocybin journey period in which neuroplasticity and the various activities, including therapy or perhaps not therapy Can contribute to positive therapeutic changes from psilocybin.

我们将讨论临床研究的条件，我们将讨论裸盖菇素后的旅程，其中神经可塑性和各种活动（包括治疗或可能不治疗）可以有助于裸盖菇素的积极治疗变化。

Now, as we go into this discussion, I do want to underscore the fact that at the time of recording this episode, meaning now, May 2023, psilocybin is still a Schedule I drug.

现在，当我们进入讨论时，我确实想强调这样一个事实：在录制本集时，即现在，即 2023 年 5 月，裸盖菇素仍然是一种附表 I 药物。

It is considered illegal in the United States.

这在美国被认为是非法的。

There's perhaps just one exception to that, maybe a few others, but the main exception is in the state of Oregon, psilocybin has been approved in particular therapeutic settings for use in particular conditions, namely depression and some forms of addiction.

也许只有一个例外，也许还有其他一些例外，但主要的例外是在俄勒冈州，裸盖菇素已被批准在特定的治疗环境中用于特定的情况，即抑郁症和某些形式的成瘾。

So in Oregon, it's more or less in the domain of decriminalized as opposed to actually legal.

因此，在俄勒冈州，它或多或少属于非刑事化领域，而不是真正合法的领域。

In other areas of the country, including Oakland, California, there's some areas in which it has been decriminalized, and perhaps there are a few others that I'm not aware of.

在美国的其他地区，包括加利福尼亚州奥克兰，有些地区已经将其合法化，也许还有其他一些我不知道的地区。

But in general, psilocybin and other psychedelics are still considered illegal.

但总的来说，裸盖菇素和其他迷幻药仍然被认为是非法的。

And this is very important.

这非常重要。

I'm not just saying this to protect me, I'm saying this to protect you.

我这么说不仅是为了保护我，也是为了保护你。

Possessing or certainly selling psilocybin, except for rare instances such as clinical studies and these decriminalized areas that I talked about a moment ago, is still very much not allowed under the law.

拥有或肯定出售裸盖菇素，除了临床研究和我刚才谈到的这些非刑事化领域等极少数情况外，法律仍然非常不允许。

Today, I'll also discuss safety issues.

今天我还要讨论一下安全问题。

I'll talk about whether or not young people, meaning people 25 or younger, should consider psilocybin, given that their brain is still in a rampant period of naturally occurring neuroplasticity.

我将讨论年轻人（即 25 岁或以下的人）是否应该考虑裸盖菇素，因为他们的大脑仍处于自然发生的神经可塑性的猖獗时期。

I will also talk about dosages as it relates to people who have formerly been on or may currently be on different forms of antidepressants.

我还将讨论剂量，因为它与以前服用或目前可能服用不同形式的抗抑郁药的人有关。

And I will talk about people who are at risk for psychotic episodes, either because they know they themselves have a propensity for psychosis, or they have close family members who have psychosis, which includes things like schizophrenia, bipolar depression, as well as things like borderline personality and some related psychiatric conditions.

我会谈论那些有精神病发作风险的人，要么因为他们知道自己有精神病倾向，要么因为他们的亲密家庭成员患有精神病，其中包括精神分裂症、双相抑郁症，以及边缘人格和一些相关的精神疾病。

So today's episode really will be a deep dive into psilocybin.

所以今天的节目将深入探讨裸盖菇素。

So whether or not you think you're already familiar with psilocybin and its effects or whether or not you're just curious about them, I do encourage, if you're willing, to try and ratchet through some of the understanding of how psilocybin works and what it is, leading up to some of the therapeutic applications and different patterns of dosing, spacing of different sessions, et cetera.

因此，无论您是否认为自己已经熟悉裸盖菇素及其作用，或者您是否只是对它们感到好奇，如果您愿意，我确实鼓励您尝试逐步了解裸盖菇素的作用原理及其含义，从而了解一些治疗应用和不同的给药模式、不同疗程的间隔等。

Because I do believe that with that knowledge in hand, you will be able to make far better, much more informed decisions about whether or not psilocybin is right for you.

因为我确实相信，掌握了这些知识，您将能够就裸盖菇素是否适合您做出更好、更明智的决定。

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。

Let's talk about psilocybin.

我们来谈谈裸盖菇素。

And again, today we're going to focus specifically on psilocybin, and we're going to set aside all the other psychedelics for future episodes.

再说一遍，今天我们将特别关注裸盖菇素，并且我们将把所有其他致幻剂放在未来的剧集中。

Psilocybin is what's called a tryptamine.

裸盖菇素就是所谓的色胺。

That refers to its chemical composition, not to the so-called psychedelic trip.

那指的是它的化学成分，而不是所谓的迷幻之旅。

In fact, it's spelled differently.

事实上，它的拼写不同。

Tryptamine is T-R-Y-P, trip, T-R-I-P, of course.

色胺是T-R-Y-P，旅行，T-R-I-P，当然。

Tryptamines include psilocybin, but also things like DMT and 5-MeO-DMT.

色胺包括裸盖菇素，还包括 DMT 和 5-MeO-DMT 等物质。

The tryptamine psychedelics very closely resemble serotonin itself.

色胺迷幻药与血清素本身非常相似。

That's right.

这是正确的。

Most of you have probably heard of the chemical serotonin, and serotonin is what's called a neuromodulator, which means your brain and body naturally make it, and that it modifies or changes the activity of other neurons and neural circuits.

你们中的大多数人可能听说过化学血清素，血清素是所谓的神经调节剂，这意味着您的大脑和身体会自然产生它，并且它会修改或改变其他神经元和神经回路的活动。

And it does that generally by either increasing or decreasing the activity of those neural circuits.

它通常通过增加或减少这些神经回路的活动来实现这一点。

If I were to show you a picture of the chemical structure of psilocybin or its active derivative, psilocin, and I were to also put right alongside it an image of the chemical structure of serotonin, provided that you weren't a chemist who really likes to focus on the detailed differences between things, you would say, "Those look very similar."

如果我向你展示裸盖菇素或其活性衍生物裸盖菇素的化学结构图片，并在其旁边放一张血清素的化学结构图片，只要你不是真正喜欢关注事物之间细节差异的化学家，你会说，“那些看起来非常相似。”

And indeed, psilocybin and its active form, psilocin, are very similar structurally and chemically to serotonin itself.

事实上，裸盖菇素及其活性形式裸盖菇素在结构和化学上与血清素本身非常相似。

Now, as I mentioned before, serotonin is something that you naturally make.

现在，正如我之前提到的，血清素是您自然产生的。

And yes, it's true that about 90% of the serotonin in your brain and body is manufactured in your gut.

是的，大脑和身体中大约 90% 的血清素确实是在肠道中产生的。

However, contrary to popular belief, the serotonin in your brain is not manufactured from the serotonin in your gut.

然而，与普遍看法相反，大脑中的血清素并不是由肠道中的血清素产生的。

You have separate independent sources of serotonin.

您有不同独立的血清素来源。

That is, you have particular neurons that make serotonin in your brain.

也就是说，您的大脑中具有产生血清素的特殊神经元。

You also have serotonin in your gut, and those work more or less in parallel separately.

你的肠道里也有血清素，它们或多或少是并行工作的。

Now, what does serotonin do?

现在，血清素有什么作用？

This is really important to understand because of the similarity between psilocybin and its active form, psilocin, and serotonin.

由于裸盖菇素及其活性形式裸盖菇素和血清素之间的相似性，理解这一点非常重要。

Serotonin, in that it's a neuromodulator, changes the activity of other neurons, and the net effects of those changes are things that you're familiar with.

血清素是一种神经调节剂，可以改变其他神经元的活动，这些变化的净效应是您所熟悉的。

For instance, satiety or the feeling that we've had enough of various things, such as food, or a social interaction, or sex, or pleasure of any kind.

例如，饱腹感或我们已经受够了各种事物的感觉，例如食物、社交互动、性或任何形式的快乐。

Serotonin is involved in all of that and an enormous number of other things, such as mood regulation, such as our sense of pleasure itself or lack of pleasure, such as whether or not we feel motivated or not motivated.

血清素参与所有这些以及大量其他事情，例如情绪调节，例如我们的快乐感本身或缺乏快乐，例如我们是否感到有动力或没有动力。

It works in concert with other neuromodulators such as dopamine and epinephrine and norepinephrine.

它与其他神经调节剂（如多巴胺、肾上腺素和去甲肾上腺素）协同作用。

In fact, if this were an episode about serotonin, which it is not, you would soon realize that serotonin is involved in so many different functions that impact our daily life.

事实上，如果这是关于血清素的一集（事实并非如此），您很快就会意识到血清素涉及影响我们日常生活的许多不同功能。

And that is one reason why certain antidepressant medications, which Alter, either increase or decrease, the amount of serotonin transmission in the brain will often have a lot of side effects related to things like mood, libido, appetite, sleep, et cetera.

这就是为什么某些抗抑郁药物会改变、增加或减少大脑中血清素的传输量，通常会产生许多与情绪、性欲、食欲、睡眠等相关的副作用。

It's because serotonin is involved in so many different things.

这是因为血清素涉及很多不同的事情。

And serotonin is involved in so many different things because there are a lot of different so-called serotonin receptors.

血清素参与了许多不同的事情，因为有很多不同的所谓的血清素受体。

Serotonin is a chemical that we call a ligand, and the chemical ligand is simply the thing that plugs into the receptor for that chemical or ligand.

血清素是一种我们称为配体的化学物质，化学配体只是插入该化学物质或配体受体的物质。

The receptors, in this case serotonin receptors, have the opportunity to do all sorts of different things.

这些受体，在这种情况下是血清素受体，有机会做各种不同的事情。

They can change the activity of neurons, making them more active or less active.

它们可以改变神经元的活动，使它们更活跃或更不活跃。

They can cause growth factors to be released, making sure that those neurons reinforce or even build up stronger connections so that they're more likely to be active in the future.

它们可以导致生长因子释放，确保这些神经元加强甚至建立更牢固的连接，以便它们在未来更有可能活跃。

Serotonin binding to particular receptors can even change the gene expression in particular cells, making those cells proliferate, so make more of them, making those cells more robust, making those cells interact with new elements of the brain and body.

血清素与特定受体的结合甚至可以改变特定细胞中的基因表达，使这些细胞增殖，从而产生更多的细胞，使这些细胞更加强大，使这些细胞与大脑和身体的新元素相互作用。

Basically, serotonin and all these different receptors that it binds to has dozens if not hundreds and maybe even thousands of different functions.

基本上，血清素和它所结合的所有这些不同的受体具有数十种甚至数百种甚至数千种不同的功能。

So the fact that psilocybin so closely resembles serotonin leads to a very important question that we should all be asking ourselves, which is, why is it that psilocybin, which looks so much like serotonin, when one takes it in the form of magic mushrooms or some other form, maybe the synthetic form of psilocybin itself, which nowadays is manufactured in laboratories and placed in different psilocybin-containing foods and pills, et cetera, why that leads to complex yet fairly circumscribed sets of experience like visual and auditory hallucinations, changes in particular thought patterns, and neuroplasticity that, in many cases in the clinical setting, provided things are done correctly, improvements in mood, relief from depression, relief from various compulsive disorders, et cetera.

因此，裸盖菇素与血清素非常相似这一事实导致了一个非常重要的问题，我们都应该问自己，那就是，为什么裸盖菇素看起来如此像血清素，当人们以迷幻蘑菇或其他形式（可能是裸盖菇素本身的合成形式）服用它时，裸盖菇素本身是在实验室中制造的，并放置在不同的含裸盖菇素的食物和药丸中，等等，为什么这会导致复杂的结果相当有限的一系列体验，如幻视和幻听、特定思维模式的变化以及神经可塑性，在临床环境中的许多情况下，只要事情做得正确，情绪就会改善，抑郁症的缓解，各种强迫症的缓解等等。

This is really what you need to understand if you want to understand psilocybin and how it works, and how to make it work optimally for a given condition or goal.

如果您想了解裸盖菇素及其工作原理，以及如何使其针对给定条件或目标以最佳方式发挥作用，这确实是您需要了解的内容。

You have to understand what it's actually doing.

你必须了解它实际上在做什么。

And what allows psilocybin to do fairly specific things in comparison to serotonin, even though psilocybin and serotonin are so similar, is that psilocybin mainly binds to and activates the so-called serotonin 2A receptor.

尽管裸盖菇素和血清素非常相似，但与血清素相比，裸盖菇素能够发挥相当特殊的作用，因为裸盖菇素主要结合并激活所谓的血清素 2A 受体。

The serotonin 2A receptor is one of, again, many different serotonin receptors, but serotonin 2A is expressed in particular areas of the brain, and even on particular areas of neurons in the brain that allow for very specific types of changes in neural circuitry to take place, not just when one is under the influence of psilocybin, but afterwards as well.

血清素 2A 受体是许多不同的血清素受体之一，但血清素 2A 在大脑的特定区域表达，甚至在大脑的神经元的特定区域表达，这些区域允许神经回路发生非常特定类型的变化，不仅在一个人受到裸盖菇素的影响时，而且在之后也是如此。

So really, in order to have a useful discussion about psilocybin, we need to talk a lot about the serotonin 2A receptor.

因此，实际上，为了对裸盖菇素进行有用的讨论，我们需要详细讨论 5-羟色胺 2A 受体。

But fortunately for you, unless you're somebody really interested in structural biology or cell biology, that discussion is not going to be about the binding pocket for serotonin on serotonin 2A receptor, or a lot of the downstream signaling of the serotonin 2A receptor.

但幸运的是，除非您真的对结构生物学或细胞生物学感兴趣，否则讨论不会涉及血清素 2A 受体上的血清素结合袋，或血清素 2A 受体的许多下游信号传导。

We'll talk a little bit about that where it's relevant, but more importantly, at least for sake of today's discussion, we're going to talk about how the serotonin 2A receptor is really the one responsible for triggering all the changes in neural circuitry that lead to the changes, that is the improvements in mood, the relief from compulsive disorders in many case.

我们将在相关的地方讨论一下，但更重要的是，至少为了今天的讨论，我们将讨论血清素 2A 受体如何真正负责触发神经回路的所有变化，从而导致变化，即情绪的改善，在许多情况下缓解强迫症。

But really, it's the serotonin 2A receptor selectivity of psilocybin that is leading to all the excitement that you hear about in terms of psilocybin as a therapeutic tool.

但事实上，正是裸盖菇素对血清素 2A 受体的选择性导致了您所听到的关于裸盖菇素作为治疗工具的所有兴奋。

Let me say that from a slightly different angle.

让我从稍微不同的角度来说。

There are data that I'll talk about today which show that one, although in most cases, two psilocybin journeys done with particular dosages of psilocybin lead to maximal binding or occupancy of those serotonin 2A receptors in ways that lead to significant and unprecedented relief for major depression.

我今天要讨论的数据表明，尽管在大多数情况下，使用特定剂量的裸盖菇素进行两次裸盖菇素之旅会导致这些血清素 2A 受体的最大结合或占据，从而导致重度抑郁症得到显着且前所未有的缓解。

In fact, you'll soon learn that the clinical trials for psilocybin are outperforming standard therapy and outperforming so-called SSRIs and various other antidepressants in terms of providing depression relief in ways that are frankly staggering, not just to me, but to the psychiatric community at large, and this is where so much of the excitement is coming from.

事实上，您很快就会了解到，裸盖菇素的临床试验在缓解抑郁方面的表现优于标准疗法，也优于所谓的 SSRI 和其他各种抗抑郁药，坦率地说，这不仅对我来说是令人震惊的，对整个精神病学界也是如此，这就是如此令人兴奋的地方。

Now, that statement could be taken one way, which is to just say, okay, well, here's a compound, psilocybin, that outperforms SSRIs, and therefore all the attention should be on psilocybin.

现在，这种说法可以用一种方式来理解，也就是说，好吧，好吧，这是一种化合物，裸盖菇素，它的效果优于 SSRI，因此所有的注意力都应该集中在裸盖菇素上。

But SSRI stands for selective serotonin reuptake inhibitor.

但 SSRI 代表选择性血清素再摄取抑制剂。

In other words, the SSRIs of which there's now a lot of controversy, things like Prozac, Zoloft, et cetera.

换句话说，现在有很多争议的SSRIs，比如百忧解、左洛复等等。

I'm sure you've heard some of this controversy.

我相信你已经听过一些这样的争议。

There are people who are very pro SSRIs, although there are a growing number of people who really feel that the SSRIs are probably most appropriate for things like obsessive compulsive disorder, where they, in fact, can be very beneficial.

有些人非常支持 SSRIs，尽管越来越多的人确实认为 SSRIs 可能最适合治疗强迫症等疾病，事实上，它们可能非常有益。

But there's a lot of leaning back from SSRIs as the be-all end-all for the treatment of depression nowadays because of the side effect profiles, and the fact that it's not even really clear that serotonin deficiencies are the major cause of depression in the first place.

但由于其副作用，目前人们对 SSRI 类药物作为治疗抑郁症的最终手段的态度有所转变，而且事实上，人们甚至还不清楚血清素缺乏是否是抑郁症的主要原因。

Now, again, we're talking about psilocybin, not about SSRIs, but you should be thinking, wait, how is it that two molecules Psilocybin and some particular SSRI, both of which look like and/or increase serotonin transmission in the brain, are leading to either incredibly positive and interesting outcomes or to kind of troubling side effect riddled outcomes.

现在，我们再次讨论的是裸盖菇素，而不是 SSRI，但你应该思考，等等，裸盖菇素和某些特定的 SSRI 两种分子，两者看起来都像和/或增加大脑中血清素的传输，是如何导致令人难以置信的积极和有趣的结果，或导致某种令人不安的副作用的结果。

And again, it all boils back down to the selectivity of psilocybin to bind that serotonin 2A receptor.

再说一次，这一切都归结为裸盖菇素与血清素 2A 受体结合的选择性。

And so in order to understand how psilocybin works and in order to understand proper dosing profiles and spacing of sessions, AKA journeys, we really need to talk a little bit more about the serotonin 2A receptor, where it is in the brain, what sorts of things happen when psilocybin binds the serotonin 2A receptor, and how those things set in motion the various changes, the neuroplasticity, that allows people to feel better in terms of their mood, and as you'll soon learn, can experience more pleasure and joy from things like music and enhanced creativity.

因此，为了了解裸盖菇素如何发挥作用，并了解正确的剂量配置和疗程间隔（又称为旅程），我们确实需要更多地讨论血清素 2A 受体，它在大脑中的位置，当裸盖菇素与血清素 2A 受体结合时会发生什么事情，以及这些事情如何引发各种变化，即神经可塑性，使人们在情绪方面感觉更好，并且你很快就会学到，可以从音乐和增强的创造力等事物中体验到更多的乐趣和快乐。

All the things that I do believe, whether or not people are thinking about or maybe even exploring psilocybin for recreational or therapeutic purposes, all the things that people want and are really talking about and perhaps even doing psilocybin in order to obtain.

我确实相信的所有事情，无论人们是否正在考虑或什至出于娱乐或治疗目的而探索裸盖菇素，所有人们想要并真正谈论的事情，甚至可能为了获得而使用裸盖菇素。

So before going any further, I just want to place an image in your mind.

因此，在进一步讨论之前，我只想在您的脑海中放置一个图像。

You can place an image in your mind whereby when serotonin is released in the brain naturally, not having taken any compound, any drug, anything, it's getting released at a lot of different sites, binding to a lot of different serotonin receptors, doing a lot of different things.

你可以在脑海中想象出这样一个画面：当血清素在大脑中自然释放时，没有服用任何化合物、任何药物或任何东西，它就会在很多不同的部位释放，与很多不同的血清素受体结合，做很多不同的事情。

When somebody takes an SSRI, the net effect of that selective serotonin reuptake inhibitor is that there's more serotonin around to exert its effects.

当有人服用 SSRI 时，选择性血清素再摄取抑制剂的净效应是周围有更多的血清素来发挥其作用。

Because it's a reuptake inhibitor at the synapse, the connections between neurons, the serotonin can do its thing more extensively and for longer periods of time, but it's doing it kind of non-specifically.

因为它是突触（神经元之间的连接）的再摄取抑制剂，所以血清素可以更广泛、更长时间地发挥作用，但它的作用是非特异性的。

So when you think about standard antidepressant treatments, at least for sake of this discussion, you kind of think of a sprinkling or a kind of spraying of serotonin at different locations in the brain and binding to lots of different receptors.

因此，当您考虑标准的抗抑郁治疗时，至少为了讨论，您会想到在大脑的不同位置喷洒或喷洒血清素，并与许多不同的受体结合。

Whereas when you think about psilocybin, even though the subjective effects are pretty diverse, we'll talk about those in a few moments, what you're really talking about is a molecule, psilocybin, that looks a lot like serotonin, that is selectively and very strongly binding to and activating that serotonin 2A receptor.

然而，当你想到裸盖菇素时，尽管主观效果相当不同，但我们稍后会讨论这些，你真正谈论的是一种分子，裸盖菇素，它看起来很像血清素，它选择性地、非常强烈地结合并激活血清素 2A 受体。

So that's the image I'd like you to embed in your mind.

这就是我希望你铭记在心的形象。

And then the next image I'd like you to embed in your mind is where these serotonin 2A receptors are located in the brain.

然后我希望您牢记在心的下一个图像是这些 5-羟色胺 2A 受体在大脑中的位置。

Now, the serotonin 2A receptors are located in multiple brain regions, but they have a tremendous amount of expression in the so-called neocortex, the outside of the brain that includes things like our prefrontal cortex, which is involved in understanding context, right?

现在，5-羟色胺 2A 受体位于多个大脑区域，但它们在所谓的新皮质（大脑的外部，包括我们的前额皮质等）有大量表达，它参与理解上下文，对吗？

Which behaviors, thoughts, and speech patterns are appropriate for certain circumstances, how to switch context and category switch when you go from playing sports to hanging out with friends to being in a professional setting.

哪些行为、想法和言语模式适合某些情况，当你从参加运动到与朋友闲逛再到进入专业环境时如何切换环境和类别。

You change your behavior and the way that you speak and perhaps even the way that you think.

你改变了你的行为和说话的方式，甚至可能改变了你的思维方式。

You might think some things that are out of context, but you probably keep those to yourself, and your ability to keep those to yourself are dependent on a functional prefrontal cortex.

你可能会认为一些断章取义的事情，但你可能会把这些事情留给自己，而你把这些事情留给自己的能力取决于功能性的前额叶皮层。

There are a lot of 5-HT2A, and by the way, 5-HT is the abbreviation for serotonin.

5-HT2A有很多，顺便说一下，5-HT是血清素的缩写。

So there are a lot of serotonin 2A receptors in the prefrontal cortex, also in other areas of the cortex that are associated with sensation and perception.

因此，前额叶皮层以及与感觉和知觉相关的其他皮层区域中存在大量血清素 2A 受体。

That is hearing of sounds, that is seeing of particular things, and in particular, there is a very, very, very high expression of serotonin 2A receptors in the visual cortex.

那就是听到声音，那是看到特定的事物，特别是，视觉皮层中血清素 2A 受体的表达非常非常高。

And that is one of the reasons why psilocybin triggers visual hallucinations.

这就是裸盖菇素引发幻视的原因之一。

And provided psilocybin is present at sufficient enough concentration, that is taken at a sufficient dosage, one will experience profound visual hallucinations, regardless of whether or not their eyes are open or their eyes are closed.

如果裸盖菇素以足够的浓度存在，即以足够的剂量服用，那么无论他们的眼睛是睁着还是闭着，都会经历深刻的幻视。

Now, that's an important fact because it explains one of the major effects of psilocybin that people experience while they are on the drug.

现在，这是一个重要的事实，因为它解释了人们在服用该药物时所经历的裸盖菇素的主要作用之一。

Now, as I'll talk about a little bit later in terms of what constitutes a useful psilocybin session, useful meaning that it's leading to adaptive improvements in mood, adaptive improvements in creativity and cognition, et cetera, is that people not have their eyes open for at least the majority of the psilocybin session.

现在，正如我稍后将讨论的什么构成了有用的裸盖菇素疗程，有用的意思是它导致情绪的适应性改善、创造力和认知的适应性改善等等，是人们至少在裸盖菇素疗程的大部分时间里没有睁开眼睛。

This is something I've discussed with several experts who are running clinical studies on psilocybin in their laboratories, some of whom are going to be guests on the Huberman Lab podcast in upcoming episodes.

这是我与几位在实验室进行裸盖菇素临床研究的专家讨论过的问题，其中一些专家将在即将播出的节目中担任休伯曼实验室播客的嘉宾。

And I can't underscore this enough.

我无法充分强调这一点。

Because your visual cortex contains so many of these serotonin 2A receptors, and because psilocybin binds so strongly to that serotonin 2A receptor, you're going to experience a lot of visual hallucinations when you are under the influence of psilocybin.

因为您的视觉皮层含有如此多的血清素 2A 受体，并且裸盖菇素与该血清素 2A 受体的结合非常牢固，所以当您受到裸盖菇素的影响时，您会出现很多幻视。

There's no surprise there.

这并不奇怪。

This has been known for hundreds, if not thousands of years.

这一点即使不是几千年，也已经为人所知数百年了。

It's one of the main reasons why people take psilocybin.

这是人们服用裸盖菇素的主要原因之一。

However, as I mentioned earlier, these hallucinations occur even when the eyes are closed, and it's now fairly well established that if people are to take psilocybin and have their eyes open, much of their cognition, much of their thinking, much of the time spent in that psilocybin journey is focused on the altered perceptions of things in the outside environment.

然而，正如我之前提到的，即使闭上眼睛，这些幻觉也会发生，而且现在已经相当确定，如果人们服用裸盖菇素并睁开眼睛，他们的大部分认知、大部分思考、在裸盖菇素旅程中花费的大部分时间都集中在对外部环境中事物的看法改变上。

Sometimes this looks like a sort of a fracturing of the outside world into kind of geometric shapes.

有时，这看起来像是外部世界破碎成某种几何形状。

Sometimes it appears as a kind of melting of things in the visual environment, including people's faces, or a morphing of people's faces.

有时它表现为一种视觉环境中事物的融化，包括人脸，或者人脸的变形。

All of that has a strong, let's just call it a draw for a lot of people who are looking for a highly unusual experience inside of the psilocybin journey.

所有这些对于许多正在寻找裸盖菇素之旅中非常不寻常的体验的人来说都具有很强的吸引力。

But I think if one's goal is to derive long-lasting benefit from the psilocybin Experience.

但我认为，如果一个人的目标是从裸盖菇素体验中获得持久的益处。

It's very clear that having an eye mask or some other eye covering or something that ensures that one's eyes are closed for the majority, if not the entire psilocybin session, is going to be very useful because it's going to limit the extent to which one is focused on those outside changes in visual perception, AKA hallucinations, and rather will allow the person to go inward to combine whatever it is that they happen to be seeing in their mind's eye with the different thoughts and memories and changes in their emotions that are occurring.

很明显，使用眼罩或其他眼罩或其他东西来确保一个人在大多数时间（如果不是整个裸盖菇素治疗期间）闭上眼睛，将会非常有用，因为它将限制一个人对视觉感知的外部变化（又名幻觉）的关注程度，并且会让人们向内将他们碰巧在脑海中看到的任何东西与不同的想法、记忆和情绪变化结合起来。发生。

And that going inward by staying in the eye mask, at least for the majority of the time, seems to be a very, if not the critical feature of making the psilocybin journey effective in the therapeutic sense.

至少在大部分时间里，通过留在眼罩中向内走，似乎是使裸盖菇素之旅在治疗意义上有效的一个非常关键的特征。

Now, once again, I want to cue to some of the safety precautions here.

现在，我想再次提示一些安全预防措施。

I'm going to say this at least three times throughout today's episode.

在今天的节目中，我将至少说三遍。

As I'm talking now and various other times throughout today's episode, you may get the impression that I'm all for everybody doing psilocybin, and that is simply not the case.

正如我现在和今天这一集其他时候所说的那样，你可能会觉得我完全支持每个人服用裸盖菇素，但事实并非如此。

In order for a psilocybin journey to be therapeutically useful, it does require certain conditions and supports, and there are certain people for which psilocybin use is going to be contraindicated, meaning they should not do psilocybin.

为了使裸盖菇素之旅具有治疗作用，它确实需要一定的条件和支持，并且某些人将禁忌使用裸盖菇素，这意味着他们不应该使用裸盖菇素。

In particular, people who have existing or have a predisposition to psychotic episodes or bipolar episodes.

特别是已经患有或有精神病发作或双相情感障碍倾向的人。

Even having a first relative who has bipolar or schizophrenic or schizotypal issues can be a rule-out condition, that is, can get someone eliminated from a clinical study on psilocybin for fear of triggering psychotic episodes, not just during the psilocybin journey, but potentially in a longstanding way.

即使有一个患有双相情感障碍或精神分裂症或精神分裂症问题的第一个亲戚也可能是一种排除条件，也就是说，可能会使某人被排除在裸盖菇素的临床研究之外，因为担心引发精神病发作，不仅是在裸盖菇素治疗过程中，而且可能是长期的。

So again, that's really critical.

再说一遍，这真的很关键。

The other thing is that everything I'm talking about today, unless I say otherwise, is really focused on adults, meaning people who are 25 years old or older.

另一件事是，除非我另有说明，否则我今天谈论的一切实际上都是针对成年人，即 25 岁或以上的人。

That is, their basic wiring and rewiring of the brain that we call developmental neuroplasticity is completed.

也就是说，我们称之为发育性神经可塑性的大脑基本接线和重新接线已经完成。

All right?

好的？

Most of the studies today that I'll talk about involve subjects ranging from 25 years of age out to about 70 years of age, but no one younger.

我今天要讨论的大多数研究都涉及 25 岁到 70 岁左右的受试者，但没有一个更年轻的。

So again, psilocybin and its use is certainly not for everybody.

再说一次，裸盖菇素及其用途肯定不适合所有人。

It's still illegal.

这仍然是非法的。

It's being used in the clinical setting and research setting.

它被用于临床环境和研究环境。

There are these pockets of decriminalized areas and potentially soon legalization of psilocybin, but again, only in the proper clinical setting.

有这些非刑事化领域，裸盖菇素可能很快就会合法化，但同样，只有在适当的临床环境下。

Okay?

好的？

Again, I say that not just to protect myself, but I say that also to protect all of you.

再说一遍，我这么说不仅仅是为了保护我自己，也是为了保护你们所有人。

Psilocybin is a powerful drug, not just to be under the influence of, but also in terms of its longstanding changes after the effects of psilocybin have worn off.

裸盖菇素是一种强效药物，不仅是在其影响下，而且是在裸盖菇素的作用消失后，其长期存在的变化。

Let's talk a little bit about dosing of psilocybin and also about microdosing of psilocybin.

我们来谈谈裸盖菇素的剂量以及裸盖菇素的微剂量。

Now, this is an area that I wouldn't say is controversial, but that there's...

现在，我不会说这是一个有争议的领域，但是……

How should we say this?

这句话该怎么说呢？

There's a lot of loose thinking around this in the non-clinical, non-research communities.

非临床、非研究界对此有很多松散的想法。

But within the clinical and research communities, there's a lot of data that's come out indicating what effective and safe doses, provided all other things are considered safe, of psilocybin actually are.

但在临床和研究界，有大量数据表明，只要所有其他因素都被认为是安全的，裸盖菇素的有效和安全剂量实际上是多少。

And here we really can go back to our discussion of psilocybin as "magic mushrooms" or mushrooms.

在这里，我们真的可以回到我们对裸盖菇素作为“神奇蘑菇”或蘑菇的讨论。

And if one were to translate from the mushroom form of psilocybin to the psilocybin that's actually used in various studies, because frankly, in these studies, people aren't eating mushrooms, they're typically taking synthetic psilocybin, either intravenously injected into a vein or orally, and that's how the researchers are able to tightly control the amount of psilocybin.

如果要将蘑菇形式的裸盖菇素转化为实际用于各种研究的裸盖菇素，因为坦率地说，在这些研究中，人们不吃蘑菇，他们通常服用合成的裸盖菇素，要么静脉注射，要么口服，这就是研究人员能够严格控制裸盖菇素含量的方式。

And the typical dosage that's used in clinical studies ranges from one milligram, often given repeatedly from day to day over long periods of time, so-called microdosing.

临床研究中使用的典型剂量范围为一毫克，通常在很长一段时间内每天重复给药，即所谓的微剂量。

And really that one milligram per day or even up to three milligrams per day repeatedly over time is what people generally think of as microdosing, as compared to, say, a 10-milligram dose given once, maybe twice in two separate sessions, or a 25 to 30-milligram dosage that's given once or twice.

实际上，随着时间的推移，每天重复服用一毫克，甚至每天重复服用三毫克，这就是人们通常认为的微剂量，相比之下，例如，一次服用 10 毫克，可能分两次服用两次，或者一次或两次服用 25 至 30 毫克剂量。

Now, those amounts of one to three milligrams or 10 milligrams or 25 to 30 milligrams might not mean much to those of you that don't think about these things in the research terms.

现在，一到三毫克或 10 毫克或 25 到 30 毫克的含量对于那些不从研究角度考虑这些事情的人来说可能没有多大意义。

Perhaps you've heard of microdosing, and you've also heard of macro or "heroic dosing." Okay?

也许您听说过微剂量，也听说过宏观剂量或“英雄剂量”。好的？

That's sort of a common, or I should say, popular nomenclature for psychedelics, and I'll circle back to that in a few minutes.

这是一种常见的，或者我应该说，迷幻药的流行术语，几分钟后我将回到这个术语。

But I think one of the questions that I hear a lot is how much psilocybin is present in a given amount of mushrooms.

但我认为我经常听到的问题之一是一定数量的蘑菇中含有多少裸盖菇素。

And so the way this typically works is that mushrooms are often discussed in terms of grams or ounces.

因此，通常的工作方式是，蘑菇通常以克或盎司为单位进行讨论。

So an eighth of mushrooms refers to an eighth of an ounce of mushrooms or X number of grams of mushrooms.

因此，八分之一的蘑菇是指八分之一盎司的蘑菇或 X 克的蘑菇。

The breakdown is actually quite simple.

分解其实很简单。

1,000 milligrams equals one gram.

1,000 毫克等于一克。

And the concentration of psilocybin in most so-called magic mushrooms is about 1%.

大多数所谓的迷幻蘑菇中裸盖菇素的浓度约为 1%。

So one gram of mushrooms being 1,000 milligrams means that it contains approximately, and again, it's approximately 10 milligrams of psilocybin.

因此，一克蘑菇等于 1,000 毫克，意味着它大约含有 10 毫克裸盖菇素。

And in most of the clinical studies, it's been shown that the dosage of 25 to 30 milligrams given, or I should say, taken once or twice, we'll talk about the spacing of sessions a little bit later, taken once or twice is what's leading to the most pronounced therapeutic outcomes.

大多数临床研究表明，给予 25 至 30 毫克的剂量，或者我应该说，服用一次或两次，我们稍后会讨论疗程的间隔，服用一次或两次，可以带来最明显的治疗效果。

But of course, with enhanced therapeutic outcomes, one also observes enhanced side effect profiles or what are called adverse events.

当然，随着治疗效果的增强，人们也会观察到副作用或所谓的不良事件的增强。

So there's an important nuanced conversation that has to take place, but right now we're talking about the conversion of grams of mushrooms to psilocybin.

因此，必须进行一次重要的、细致入微的对话，但现在我们正在讨论将蘑菇克数转化为裸盖菇素的过程。

So one gram of mushrooms being 1,000 milligrams Containing 1% psilocybin means that it contains 10 milligrams of psilocybin.

因此，一克蘑菇含有 1000 毫克裸盖菇素，即含有 1% 裸盖菇素，意味着它含有 10 毫克裸盖菇素。

Now, the so-called heroic doses that you've heard about, and this is something that's discussed more with the, let's call them traditional or classic psychonauts.

现在，你听说过所谓的英雄剂量，这是与传统或经典的心理飞行员更多讨论的事情。

These are people that may have an advanced degree, but typically are not running laboratories exploring the effects of psilocybin in controlled clinical trials.

这些人可能拥有高级学位，但通常不会在对照临床试验中运行实验室来探索裸盖菇素的作用。

These are people who have been longtime explorers and often writers, and people who have been spokespeople for psilocybin and other psychedelics, and they will often refer to the so-called heroic doses.

这些人都是长期的探险家，通常是作家，也是裸盖菇素和其他致幻剂的代言人，他们经常会提到所谓的英雄剂量。

It's a little bit hard to translate from that informal community to the scientific data, but in discussing that topic with various researchers who run laboratories at major universities focused on psychedelic therapies, what I was told is that the "heroic dose" that's often discussed really refers to a five-gram or so dose of mushrooms.

从非正式社区转化为科学数据有点困难，但在与在主要大学经营迷幻疗法实验室的各种研究人员讨论这个话题时，我被告知经常讨论的“英雄剂量”实际上是指五克左右剂量的蘑菇。

So what that translates to is 50 milligrams of psilocybin.

那么这意味着 50 毫克裸盖菇素。

So when you hear someone talk about a "heroic dose," they're probably referring to ingestion of 50 milligrams or so of psilocybin, but in its mushroom form.

因此，当您听到有人谈论“英雄剂量”时，他们可能指的是摄入 50 毫克左右的裸盖菇素，但以蘑菇形式存在。

So about five grams of mushrooms.

大约五克蘑菇。

And again, it's important to point out that the concentration of psilocybin in different strains of mushrooms and in different batches, and depending on the age of those mushrooms and how they've been stored, et cetera, can vary tremendously from batch to batch.

再次需要指出的是，不同品种和不同批次的蘑菇中裸盖菇素的浓度，以及根据这些蘑菇的年龄和储存方式等，不同批次的裸盖菇素浓度可能存在巨大差异。

In fact, there are some laboratories that have explored the range of psilocybin concentration in different mushroom strains and different so-called magic mushrooms, and that range is pretty broad.

事实上，有一些实验室已经探索了不同蘑菇品种和不同所谓迷幻蘑菇中裸盖菇素浓度的范围，而且这个范围相当广泛。

It's anywhere from a half percent all the way up to 2%.

其范围从 0.5% 一直到 2%。

What that means is that someone might get a hold of one gram of mushrooms thinking that they're taking 10 milligrams of psilocybin in those mushrooms, when in fact, they're actually taking 20.

这意味着，有人拿到一克蘑菇时可能会认为他们在这些蘑菇中摄入了 10 毫克裸盖菇素，而事实上，他们实际上摄入了 20 毫克。

Or somebody could take three grams of mushrooms thinking they're taking 30 grams of psilocybin, and in fact, they're only taking 10 or 15 milligrams of psilocybin.

或者有人服用 3 克蘑菇，认为自己服用了 30 克裸盖菇素，但事实上，他们只服用了 10 或 15 毫克裸盖菇素。

So the sourcing is really key.

所以说货源真的很关键。

Obviously, as things become more legal and more regulated and more used in the therapeutic setting, or, and this is what's happening more and more, or as people start to rely on synthetically made psilocybin as opposed to using mushrooms to ingest psilocybin, then certainly the dosaging is going to be more consistent from batch to batch because we're not talking about batches of mushrooms, we're talking about batches of psilocybin itself.

显然，随着事情变得更加合法，更加规范，并且更多地用于治疗环境，或者，这就是越来越多的情况，或者随着人们开始依赖合成的裸盖菇素而不是使用蘑菇来摄入裸盖菇素，那么批次之间的剂量肯定会更加一致，因为我们不是在谈论蘑菇批次，我们谈论的是裸盖菇素本身批次。

So now I'd like to take a step back from all this chemistry and cell biology and talk a little bit about the structure of a psilocybin journey itself and relate that to what we now know about what's happening in the brain during the psilocybin journey.

所以现在我想从所有这些化学和细胞生物学中退一步，谈谈裸盖菇素旅程本身的结构，并将其与我们现在所知道的裸盖菇素旅程期间大脑中发生的情况联系起来。

And then a little bit later, we will return to that serotonin 2A receptor when we talk about some of the more lasting changes in brain chemistry and brain wiring that occur after the psilocybin journey is over.

稍后，当我们谈论裸盖菇素之旅结束后大脑化学和大脑接线发生的一些更持久的变化时，我们将回到血清素 2A 受体。

So let's take a couple of minutes and just discuss the various components of an effective therapeutic psilocybin journey.

因此，让我们花几分钟时间讨论有效的裸盖菇素治疗过程的各个组成部分。

And here I'm not detailing a menu of things that people should do in order to pretend that they are a psilocybin-assisted therapy coach, or to do self-administered psilocybin therapy.

在这里，我不会详细列出人们应该做的一系列事情，以便假装自己是裸盖菇素辅助治疗教练，或进行自我管理的裸盖菇素治疗。

That is not what I'm doing.

那不是我正在做的事情。

What I am trying to do is to share with you the consistent components that are present in the clinical trials that have demonstrated the effectiveness of psilocybin for the treatment of depression and for other compulsive and addictive disorders.

我想做的是与您分享临床试验中存在的一致成分，这些临床试验已证明裸盖菇素对于治疗抑郁症和其他强迫性和成瘾性疾病的有效性。

And those data, meaning the specific data related to those trials and the references themselves, we'll get into a little bit later.

这些数据，意味着与这些试验相关的具体数据以及参考文献本身，我们稍后会讨论。

But we can't really have a conversation about psilocybin and what it does without talking about the so-called set and setting, as it's often referred to, that is known to at least bias the probability of the journey being beneficial and not a so-called bad trip.

但我们不能真正谈论裸盖菇素及其作用，而不谈论所谓的设置和设置，正如人们经常提到的那样，众所周知，这至少会影响旅程有益的概率，而不是所谓的糟糕旅行。

So what are the variables that make up an effective and safe psilocybin journey?

那么，构成有效且安全的裸盖菇素之旅的变量有哪些呢？

And again, when we say safe, we're referring to people who are not prone to psychotic episodes, that don't even have a first relative that's prone to psychotic episodes.

再说一次，当我们说安全时，我们指的是那些不易患精神病发作的人，甚至没有一个容易患精神病发作的第一亲属。

We're talking about people that are 25 years or older.

我们谈论的是 25 岁或以上的人。

We're talking about people that, for instance, are not taking antidepressants that impact the serotonin system.

例如，我们谈论的是那些没有服用影响血清素系统的抗抑郁药的人。

This is very important to understand.

理解这一点非常重要。

I think a lot of people don't know this, but as far as I know, all of the studies that have explored psilocybin for its ability to positively impact brain chemistry and mood and function have required that people either not be on or abstain from antidepressants in the weeks leading up to the psilocybin journey.

我认为很多人不知道这一点，但据我所知，所有探索裸盖菇素对大脑化学物质、情绪和功能产生积极影响的能力的研究都要求人们在裸盖菇素之旅前的几周内不要服用或放弃抗抑郁药物。

Now, that is not to say that if you are currently taking SSRIs or something similar that you should cease taking them and do psilocybin.

现在，这并不是说，如果您目前正在服用 SSRI 或类似药物，您应该停止服用它们并服用裸盖菇素。

I am absolutely not saying that.

我绝对不是这么说的。

That could be very dangerous, if not catastrophic.

这即使不是灾难性的，也是非常危险的。

Anytime you're going to take anything or stop taking anything for that matter, you do need to consult with your physician.

任何时候您要服用任何药物或停止服用任何药物，都需要咨询您的医生。

This case, a psychiatrist as well.

这个案例，也是一位心理医生。

So let's talk about psilocybin journeys from the subjective side and from the structural side.

那么让我们从主观方面和结构方面来谈谈裸盖菇素的旅程。

And when I say the structural side, what I mean is, what does a psychedelic journey actually include?

当我说结构方面时，我的意思是，迷幻之旅实际上包括什么？

And here the words set and setting become extremely important.

而这里的用词设置和背景就变得极其重要。

Some of you may have heard that set and setting are the foundation of a well-done or even therapeutically beneficial psychedelic journey.

你们中的一些人可能听说过布景和环境是成功甚至有益于治疗的迷幻之旅的基础。

And all of that really hinges on safety and outcomes.

所有这一切实际上都取决于安全和结果。

So set refers to mindset, the mindset of the person taking the psychedelic, and setting refers to, as the name suggests, the setting in which they're taking it in and the people that are present there.

因此，设定指的是心态，即服用迷幻剂的人的心态，而环境，顾名思义，是指他们接受迷幻剂的环境以及在场的人。

So let's talk about setting first.

那么我们先来谈谈设置。

The setting for a psychedelic journey needs to be one in which the person under the influence of the psilocybin or other psychedelic is safe.

迷幻之旅的环境必须是受裸盖菇素或其他迷幻剂影响的人是安全的。

That means no windows they can jump out of.

这意味着它们没有窗户可以跳出去。

That means no streets of moving cars they can run out into.

这意味着他们不能冲进满是行驶车辆的街道。

That means no opportunity for getting lost.

这意味着没有迷路的机会。

That means no opportunity for getting into bodies of water.

这意味着没有机会进入水体。

In other words, it requires that there be at least one, and perhaps even two or more other individuals who are not also taking psychedelics, right?

换句话说，它要求至少有一个，甚至两个或更多其他人不服用迷幻药，对吗？

Who are not also taking psychedelics present in that setting to ensure that the person taking the psilocybin is not going to harm themselves or others.

他们不会在该环境中服用迷幻药，以确保服用裸盖菇素的人不会伤害自己或他人。

I say this not to sound like a school teacher, even though technically I'm a school teacher, but because, of course, I don't want anyone to get harmed.

我这么说并不是为了听起来像一个学校老师，尽管从技术上讲我是一名学校老师，但当然，因为我不想让任何人受到伤害。

And I'm also aware that there's a lot of interest nowadays in psychedelics such as psilocybin becoming legal or decriminalized for their therapeutic applications.

我还知道，现在人们对迷幻药（例如裸盖菇素）的治疗应用合法化或非刑事化非常感兴趣。

And if we look back to the late 1960s and early 1970s, when the Controlled Substances Act was invoked to make psychedelics like psilocybin illegal, one of the bases for that was not just the geopolitical unrest at the time and things like the Vietnam War, but also some highlighted instances in which people did not take set and setting into consideration.

如果我们回顾 20 世纪 60 年代末和 1970 年代初，当时援引《管制物质法》将裸盖菇素等致幻剂定为非法，其根源之一不仅是当时的地缘政治动荡和越南战争等事件，还包括一些人们没有考虑到设定和背景的突出例子。

Took things like LSD, stared at the sun, went blind, or took psilocybin, went out and harmed somebody else.

服用LSD之类的东西，盯着太阳看，失明，或者服用裸盖菇素，出去伤害别人。

Again, these are very, very isolated instances, but these are the exact sort of instances that lead to criminalization, or the fact that things like psilocybin and LSD, and MDMA for that matter, are considered illegal.

同样，这些都是非常非常孤立的实例，但这些实例正是导致刑事定罪的实例，或者导致裸盖菇素和LSD以及MDMA等物质被视为非法的事实。

Again, I completely acknowledge that there are a number of different factors making them illegal.

再次，我完全承认有许多不同的因素导致它们非法。

We could have a whole discussion about that.

我们可以对此进行全面的讨论。

We talk about the drug trade, the war on drugs.

我们谈论毒品贸易、毒品战争。

But right now is such a critical time in the history and the use of psychedelics for therapeutic and other reasons, and getting setting correct, meaning making it absolutely as safe as possible for the person taking the psychedelic, is absolutely key.

但现在是历史上的一个关键时刻，迷幻药用于治疗和其他原因，正确设置，意味着使服用迷幻药的人尽可能安全，绝对是关键。

And one of the best ways to ensure that it's safe is to have responsible individuals who are not under the influence of psychedelics present in that environment.

确保安全的最佳方法之一是让不受迷幻剂影响的负责任的人员出现在该环境中。

So that's one component of setting.

这是设置的一个组成部分。

The other component of setting that we talked about earlier, which turns out to be very important, is the opportunity and perhaps even the bias toward the person on the psychedelic being seated or ideally lying down and being in the eye mask, or at least having their eyes covered, so that they can combine any spontaneous visual hallucinations that occur with the various thought processes that are occurring while under the influence of psychedelics.

我们之前讨论过的设置的另一个组成部分非常重要，那就是机会，甚至可能是对迷幻剂的人坐着或理想地躺着并戴在眼罩中，或者至少遮住眼睛的偏见，这样他们就可以将在迷幻剂影响下发生的任何自发的幻视与各种思维过程结合起来。

This is far and away different than, quote, unquote, "taking mushrooms and going into the woods or taking mushrooms and going to the beach." What we're talking about today is the use of psychedelics for particular brain rewiring outcomes that, yes, can involve things like changing one's relationship to nature or changing one's relationship to somebody else by interacting with nature or somebody else.

这与“带着蘑菇走进树林，或者带着蘑菇去海滩”截然不同。我们今天讨论的是使用致幻剂来实现特定的大脑重新布线结果，是的，这可能涉及到改变一个人与自然的关系，或者通过与自然或其他人互动来改变一个人与其他人的关系。

And while I'm not trying to diminish the potential value of those sorts of psychedelic journeys, if we look at the scientific data, the vast majority of it, not just in the clinical setting, but in terms of understanding the safety and efficacy and positive rewiring of brain circuitry that allows people to feel better, to understand themselves better, and to interact with life in more adaptive ways going forward out of the psychedelic journey, involve these very, let's say subdued settings that are typically in one room, a closed environment, with one or two other individuals acting as sort of guides or helping the individual by talking to them from time to time if they feel like they have to sort through a particular aspect of the psychedelic journey that's creating anxiety.

虽然我并不是想削弱这类迷幻之旅的潜在价值，但如果我们看一下科学数据，绝大多数科学数据不仅在临床环境中，而且在理解大脑回路的安全性和有效性以及积极的重新布线方面，使人们感觉更好，更好地了解自己，并在迷幻之旅中以更适应性的方式与生活互动，涉及这些非常，比方说，通常在一个房间、一个封闭的环境中的柔和环境。一个或两个其他人充当向导，或者如果他们觉得必须解决迷幻之旅中造成焦虑的特定方面，则通过不时与他们交谈来帮助他们。

And we'll talk about the contour of the psychedelic journey that almost everyone who takes psilocybin at somewhere between 20 and 30 milligram dosages tends to experience.

我们将讨论几乎每个服用 20 至 30 毫克剂量的裸盖菇素的人都会经历的迷幻之旅的轮廓。

But the setting that I'm describing is not just a list of things to make sure you're safe, but they're really the list of things that also ensure that one can get the maximum benefit out of the psilocybin journey.

但我所描述的设置不仅仅是确保您安全的一系列事项，而且实际上也是确保人们能够从裸盖菇素之旅中获得最大利益的一系列事项。

Now, other things included in setting that are known, again, from scientific literature, to be very influential in terms of the experience that one has and to bias things towards a positive experience are, again, safety, eye mask, but also the presence of music.

现在，科学文献中已知的环境中包含的其他因素对人们的体验非常有影响力，并且使事物偏向于积极的体验，这些因素再次是安全、眼罩，还有音乐的存在。

Now, when I first heard about this from one of the premier researchers on psilocybin and other psychedelics, which is Robin Carhart-Harris, he's a professor at University of California, San Francisco, who's one of the major pioneers in the studies of psychedelics.

现在，当我第一次从裸盖菇素和其他迷幻药的主要研究人员罗宾·卡哈特-哈里斯那里听说这一点时，他是加州大学旧金山分校的教授，也是迷幻药研究的主要先驱之一。

And when he first started telling me about the critical role that music plays, I thought, "Okay, that makes sense.

当他第一次开始告诉我音乐所扮演的关键角色时，我想，“好吧，这是有道理的。

Music can impact our emotion, impact the way that we think, and could therefore impact what one experiences during the psychedelic journey." But he really underscored for me the extent to which music is not just a sort of incidental feature of the setting in psychedelic set and setting, but that it is one of the major drivers of the actual cognitive and emotional experience that somebody has on something like psilocybin that allows the psilocybin journey to be looked at or viewed, not just as beneficial, but, and this is quoted in the scientific literature, as one of the most profound and important positive experiences that one ever experienced in their life.

音乐可以影响我们的情感，影响我们的思维方式，从而影响人们在迷幻之旅中的体验。”但他确实向我强调了音乐在某种程度上不仅仅是迷幻场景和环境中的一种偶然特征，而且是人们对裸盖菇素之类的东西所拥有的实际认知和情感体验的主要驱动力之一，它允许裸盖菇素之旅被视为有益的，而且，这在科学文献中被引用为人们一生中经历过的最深刻和最重要的积极体验之一。

So let's talk about the sorts of music that have been used in these clinical studies.

那么让我们来谈谈这些临床研究中使用的音乐类型。

Well, first of all, we need to think about how long the psilocybin journey itself is going to be.

好吧，首先，我们需要考虑裸盖菇素的旅程本身需要多长时间。

And the typical duration of the psilocybin journey is anywhere from four to six hours.

裸盖菇素旅程的典型持续时间为四到六个小时。

It's going to depend somewhat on dose.

这在一定程度上取决于剂量。

It's going to depend somewhat on variability in people's liver metabolism, and it's also going to depend somewhat on how much food people have in their gut.

这在一定程度上取决于人们肝脏代谢的变化，而且在一定程度上也取决于人们肠道内有多少食物。

In all the clinical studies that I read, it was advised that people not have any food in their gut at the time at which they ingest or are injected with the psilocybin.

在我读到的所有临床研究中，建议人们在摄入或注射裸盖菇素时肠道内不要有任何食物。

It's particularly true if people are going to be taking psilocybin mushrooms in order to get their psilocybin, and that has been done in a few studies.

如果人们为了获取裸盖菇素而服用裸盖菇素，这一点尤其正确，一些研究已经做到了这一点。

Most studies, however, use synthetic psilocybin taken orally.

然而，大多数研究使用口服合成裸盖菇素。

Again, that's converted to psilocin in the gut by the acidity of the gut, and the acidity of the gut is going to be impacted by the various foods that people eat.

同样，它在肠道中通过肠道酸度转化为裸头菌素，而肠道酸度将受到人们所吃的各种食物的影响。

And so that's one of the major reasons why people are advised to not eat for at least four hours prior to the psilocybin journey.

因此，这就是为什么建议人们在服用裸盖菇素之前至少四个小时不要进食的主要原因之一。

So here we've got this six-hour, what we're calling journey, because that's what everyone calls it, or trip.

所以这里我们有这个六个小时，我们称之为旅程，因为这就是每个人所说的，或旅行。

That people start experiencing about 30 to 45 minutes after ingesting psilocybin or taking psilocybin.

人们在摄入裸盖菇素或服用裸盖菇素约 30 至 45 分钟后开始出现这种症状。

There's a peak component in which there's a maximal intensity of emotion, and often that's also associated with anxiety.

有一个峰值部分，其中情绪强度最大，而且通常也与焦虑有关。

And this is very important to understand.

理解这一点非常重要。

The anxiety component is part of what, in the therapeutic setting, they refer to as ego dissolution, and that anxiety around the peak.

在治疗环境中，焦虑成分是他们所说的自我消解和高峰期焦虑的一部分。

And I think most people would probably hear peak experience and think, "Oh, we're talking about a peak positive experience." But no, we're referring to a peak experience and anxiety that people stay with and then come down from gradually as one goes from the second or third hour after taking psilocybin, and that tapers off slowly toward the six-hour mark, what sometimes people refer to as parachuting back in.

我认为大多数人可能会听到高峰体验并想，“哦，我们正在谈论高峰积极体验。”但事实并非如此，我们指的是一种高峰体验和焦虑，人们在服用裸盖菇素后的第二或第三个小时后会持续经历这种高峰体验和焦虑，然后逐渐下降，并在接近六个小时时逐渐减弱，有时人们将其称为“跳伞回归”。

Of course, hopefully, I would very much hope people aren't actually parachuting back in while on psilocybin.

当然，我非常希望人们在服用裸盖菇素时不会真的跳伞回来。

But I think you get the idea.

但我想你明白了。

The music that's typically played in the clinical studies using psilocybin for the treatment of depression or for compulsive disorders or addiction tends to have a particular contour that matches with and can also drive that contour of the psilocybin journey that I just described.

在使用裸盖菇素治疗抑郁症或强迫症或成瘾的临床研究中通常播放的音乐往往具有与我刚才描述的裸盖菇素旅程的轮廓相匹配的特定轮廓，并且也可以驱动该轮廓。

Again, we're talking about people wearing an eye mask with guides present, so people who are not taking psilocybin there as well to ensure that the person feels supported and is safe.

再说一遍，我们谈论的是戴着眼罩并有引导者在场的人，因此那些没有服用裸盖菇素的人也在那里，以确保该人感到受到支持并且安全。

The person is typically lying down, sometimes sitting down, but more often than not lying down, wearing an eye mask.

该人通常是躺着的，有时是坐着的，但更多时候不是躺着，戴着眼罩。

And the music that's played at the beginning of the psilocybin session tends to be music that doesn't have a lot of vocalizations.

在裸盖菇素疗程开始时播放的音乐往往是没有太多发声的音乐。

It tends to be things like classical music.

它往往是古典音乐之类的东西。

It tends to be fairly low volume, but that then transitions into music that has a lot of percussion, so often drums, that tends to be higher volume, that has a lot of intensity at about the time that one would be experiencing the peak in emotion and in perception, the so-called peak of the journey.

它的音量往往相当低，但随后会转变为有大量打击乐的音乐，通常是鼓，音量往往较高，在人们体验情感和感知的高峰时有很大的强度，即所谓的旅程高峰。

That intense music tends to be played for about 45 minutes to 90 minutes, depending on the study one looks at, and then tends to transition into softer music again, sometimes choral type or more melodic music, often female voices in particular, and then transition into nature sounds and things that more or less mimic the outside natural world and less so synthetic things like drums or instruments and vocalizations and things of that sort.

这种激烈的音乐往往会播放大约 45 分钟到 90 分钟，具体取决于人们所关注的研究，然后往往会再次过渡到较柔和的音乐，有时是合唱类型或更旋律化的音乐，尤其是女性声音，然后过渡到自然声音和或多或少模仿外部自然世界的东西，而不是合成的东西，如鼓或乐器和发声之类的东西。

So why would it be so important that music match and even contribute to the subjective experience that people have on psychedelics?

那么，为什么音乐与人们对迷幻剂的主观体验相匹配甚至有所贡献如此重要呢？

And here we should probably take a couple of moments and just talk about what those subjective experiences are like.

在这里，我们也许应该花一些时间来谈谈这些主观体验是什么样的。

So for people that haven't done psilocybin or any psychedelics, it's a little hard to describe, but one way to describe it is that there's a lot of so-called perceptual blending.

因此，对于没有服用过裸盖菇素或任何致幻剂的人来说，这有点难以描述，但描述它的一种方法是，有很多所谓的感知混合。

So for instance, people in the eye mask will report seeing some geometric shapes and colors, but perhaps the music they're listening to will then start to change the intensity or the movement of whatever it is that they're seeing, hallucinating inside of the eye mask in ways that are linked.

例如，戴着眼罩的人会报告看到一些几何形状和颜色，但也许他们正在听的音乐会开始改变他们所看到的任何东西的强度或运动，以相关的方式在眼罩内部产生幻觉。

This is referred to as synesthesia, or the merging of different senses that are not ordinarily merged.

这被称为联觉，或通常不合并的不同感觉的合并。

In addition, people under the influence of psilocybin, or other psychedelics for that matter, often will report that their pattern of breathing becomes linked to the perceptions of things that they are hearing or seeing or feeling.

此外，受到裸盖菇素或其他迷幻药影响的人经常会报告说，他们的呼吸模式与他们听到、看到或感觉到的事物的感知有关。

So for instance, if they take a big deep breath in and then a long exhale out, they may find that during the long exhale out, that the notes of music that they're hearing in those moments are also drawn out for the duration of the breath.

例如，如果他们深吸一口气，然后长长地呼气，他们可能会发现在长长的呼气过程中，他们在这些时刻听到的音乐音符也在呼吸期间被拉长。

Then they'll inhale, and that they're getting at least what they perceive as control over the music, which of course they are not actually controlling, by using their breath.

然后他们会吸气，并且他们至少获得了他们认为的对音乐的控制，当然他们实际上并没有通过呼吸来控制音乐。

And that perhaps their visual perceptions are also being merged with that.

也许他们的视觉感知也正在与之融合。

So those are just a couple of examples of how perceptual blending, AKA synesthesia, can occur while under the influence of psilocybin.

这些只是在裸盖菇素的影响下如何发生知觉混合（又名联觉）的几个例子。

And this really is highly individual from one person to the next.

从一个人到另一个人，这确实是非常个体化的。

Some people, for instance, will find that if they take their fingertips and rub them across the couch or the chair that they happen to be lying down or sitting on, that they will experience a change in the music.

例如，有些人会发现，如果他们用指尖在他们碰巧躺着或坐着的沙发或椅子上摩擦，他们会感受到音乐的变化。

Maybe even if they move their hand up, they hear an increase in frequency of sound.

也许即使他们抬起手，他们也会听到声音频率的增加。

They move their hand down, they hear a decrease in frequency of sound, and that all of this is linked to their emotional state at the same time and vice versa.

他们将手向下移动，听到声音频率的降低，所有这些都同时与他们的情绪状态相关，反之亦然。

Okay, so we're talking about a lot of perceptual and emotional blending and some sense of control over one's perceptions and emotions in a way that's very unordinary, even extraordinary.

好吧，我们谈论的是很多感知和情感的混合，以及以一种非常不寻常、甚至非凡的方式对一个人的感知和情感进行控制的感觉。

Now we can step back from all of this very subjective description of the psychedelic journey and ask, what is going on that would allow these sorts of things to occur?

现在我们可以从所有这些对迷幻之旅的非常主观的描述中退一步，问一下，到底发生了什么才会让这些事情发生？

And there you are already equipped with an understanding of the cell biology and the chemistry that makes all of this possible.

在那里，您已经了解了使这一切成为可能的细胞生物学和化学。

And that is that when psilocybin is ingested and then converted to psilocin, and it's the psilocin that crosses the blood-brain barrier, and then even though psilocin looks a lot like serotonin, psilocin has this incredible ability to predominantly activate the serotonin 2A receptor.

也就是说，当裸盖菇素被摄入后转化为裸盖菇素，裸盖菇素会穿过血脑屏障，尽管裸盖菇素看起来很像血清素，但裸盖菇素具有这种令人难以置信的能力，主要激活血清素 2A 受体。

Well, we can understand much of what's happening at a subjective level during the psychedelic journey, even right down to the sorts of emotions and perceptual blending, the synesthesia.

好吧，我们可以理解在迷幻之旅中主观层面上发生的很多事情，甚至可以深入到各种情感和知觉混合，即联觉。

We can understand a lot of that by understanding where the serotonin 2A receptors are expressed on neurons and what those particular neurons are doing.

通过了解 5-羟色胺 2A 受体在神经元上的表达位置以及这些特定神经元的作用，我们可以了解很多内容。

And the simplest way to describe this is that there's a category of neurons that we call pyramidal neurons.

描述这一点的最简单方法是有一类神经元，我们称之为锥体神经元。

Pyramidal neurons are found lots of places in the brain, but they're called pyramidal neurons because they're sort of shaped like a pyramid.

大脑中很多地方都有锥体神经元，但它们之所以被称为锥体神经元，是因为它们的形状有点像金字塔。

They have a cell body, which is the part of the cell that has the DNA in it and a lot of other important The things like the organelles, mitochondria, et cetera.

它们有一个细胞体，这是细胞的一部分，里面有 DNA 和许多其他重要的东西，如细胞器、线粒体等。

And then they also have what are called dendrites.

然后它们也有所谓的树突。

Dendrites are the little branches or processes that reach out both from the bottom of these cells, and then these pyramidal cells are interesting because they also grow a branch up into layers of neural tissue above them, and they have what's called an apical branch.

树突是从这些细胞底部伸出的小分支或突起，这些锥体细胞很有趣，因为它们也长出一个分支，进入它们上方的神经组织层，并且它们有所谓的顶端分支。

That's the part that grows up.

这就是成长的部分。

And then they fan out at the top, and that fanning out at the top allows them to communicate with other neurons in their environment.

然后它们在顶部呈扇形散开，而顶部的扇形散开使它们能够与环境中的其他神经元进行交流。

Okay, so if you're not getting a good picture of this in your mind from my description, I apologize, but simply think about putting your arms out to the side, and by doing that, you're able to interact with things that are some distance from your body.

好吧，如果你没有从我的描述中清楚地了解这一点，我很抱歉，但只要想一下将你的手臂伸到一边，通过这样做，你就可以与距离你身体有一定距离的事物进行互动。

Sort of an obvious thing in that case.

在这种情况下这是显而易见的事情。

These cells are effectively doing the same thing by extending little processes out into layers above them and to the sides.

这些细胞通过将小过程延伸到它们上方和侧面的层中，有效地做同样的事情。

And this is really important because much of the serotonin 2A receptors that are present on neurons in the brain are present in those apical dendrites, those branches of these pyramidal neurons that are above and that extend out to the side of those neurons.

这非常重要，因为大脑神经元上存在的大部分血清素 2A 受体都存在于顶端树突中，即这些锥体神经元的分支，这些分支位于这些神经元的上方并延伸到这些神经元的侧面。

And so when somebody is under the influence of psilocybin, that means that psilocin has bound to the receptors on those apical dendrites, and it's increasing lateral communication across brain areas.

因此，当某人受到裸盖菇素的影响时，这意味着裸盖菇素已与顶端树突上的受体结合，并且它增加了大脑区域之间的横向通讯。

In fact, this is perhaps one of the most well-documented effects of psilocybin and other psychedelics, which is that there's a shift from the brain being more modular, meaning more segmented.

事实上，这可能是裸盖菇素和其他迷幻药最有据可查的作用之一，即大脑变得更加模块化，意味着更加分段。

Like auditory neurons are communicating electrically and chemically largely with other auditory neurons.

就像听觉神经元主要与其他听觉神经元进行电和化学通信一样。

Of course, they'll communicate with other types of neurons, too, right?

当然，它们也会与其他类型的神经元进行交流，对吗？

When I hear something off to my right, like a snap of fingers off to the right, I'll turn my head, and my ability to do that depends on my auditory neurons being linked up with things like my motor system and my visual system.

当我听到右边有什么声音时，比如向右打响指，我会转过头，而我这样做的能力取决于我的听觉神经元与我的运动系统和视觉系统等东西的连接。

But the key thing to understand is that when there is psilocybin present in one system, that the communication of any of these pyramidal neurons, the ones involved in hearing, the ones involved in thinking, the ones involved in memory, the ones involved in visual perception or in the generation of visual hallucinations with eyes closed, those are all talking to many, many more other neurons more extensively.

但要理解的关键是，当一个系统中存在裸盖菇素时，任何这些锥体神经元的通讯，涉及听觉的神经元、涉及思维的神经元、涉及记忆的神经元、涉及视觉感知或闭眼产生幻视的神经元，都在与许多、更多的其他神经元进行更广泛的通信。

So what happens effectively is that there's a reduction in the modularity, the separateness of function in the brain, and an increase in what's called integration of communication across what would otherwise be disparate brain regions.

因此，有效发生的情况是，大脑中的模块化和功能的独立性有所减少，而所谓的跨不同大脑区域的通信整合则有所增加。

We can say that really simply by saying psilocybin increases communication across the brain.

我们可以简单地说，裸盖菇素可以增强大脑之间的交流。

Now, in addition to that, there's a reduction in what's called the hierarchical organization of the brain.

现在，除此之外，大脑的等级组织也减少了。

Typically, sensory information comes in from the outside environment.

通常，感官信息来自外部环境。

So we hear something, we see something, we taste something, we smell something.

所以我们听到一些东西，看到一些东西，尝到一些东西，闻到一些东西。

And in what's called a bottom-up fashion, meaning bottom from the periphery, up meaning it propagates up through the eyes, through the nose, through the ears, through the skin, or the senses in those regions, I should say, up into areas of the brain that sit deep to the cortex, like the thalamus.

以所谓的自下而上的方式，意思是从外围向下，向上意思是它通过眼睛、鼻子、耳朵、皮肤或这些区域的感觉向上传播，我应该说，到达大脑皮层深处的区域，比如丘脑。

And then the thalamus is sort of a way station.

丘脑就像一个中转站。

It's like a switchboard that sends visual stuff to the visual centers, and auditory stuff to the auditory centers, and touch stuff to the touch centers, and things that maybe trigger a memory off to the memory centers of the brain, et cetera.

它就像一个总机，将视觉信息发送到视觉中心，将听觉信息发送到听觉中心，将触摸信息发送到触摸中心，将可能触发记忆的信息发送到大脑的记忆中心，等等。

That's the typical organization.

这就是典型的组织。

It's hierarchical because it goes from the periphery up to the more complex processing regions of the brain that make decisions, that link all of that stuff to prior experience, maybe plans about the future.

它是分层的，因为它从外围一直到大脑中做出决策的更复杂的处理区域，将所有这些东西与之前的经验（也许是关于未来的计划）联系起来。

When psilocybin is present in the system, there's a broadening of the flow of that information from the bottom up as well.

当系统中存在裸盖菇素时，信息流也会自下而上扩大。

Okay?

好的？

And that has to do with what's called thalamic gating.

这与所谓的丘脑门控有关。

The thalamus is a very interesting structure.

丘脑是一个非常有趣的结构。

We probably don't want to go into it in too much detail right now, but it really is like a switchboard and a way station saying, "Hey, pay attention to the visual stuff.

我们现在可能不想详细讨论它，但它确实就像一个总机和一个中转站，说：“嘿，注意视觉上的东西。

Pay attention to the auditory stuff, or just to the visual and auditory stuff, and ignore touch sensation for the time being, or vice versa." When psilocybin is present in the system, and when serotonin 2A receptors are activated very strongly, there's a tremendous broadening of the flow of information up and through the thalamus.

注意听觉的东西，或者只注意视觉和听觉的东西，暂时忽略触觉，反之亦然。”当裸盖菇素存在于系统中时，并且当血清素 2A 受体被非常强烈地激活时，向上并通过丘脑的信息流就会极大地拓宽。

So not only is there more communication of so-called higher order brain centers, and we refer to them as higher order because they're involved in thinking, and decision-making, and emotion, et cetera, but there's also a shift in the flow of sensory information into the brain that can generally be described as broader and including more blending of the different senses.

因此，不仅所谓的高阶大脑中心之间存在更多的交流，我们将它们称为高阶，因为它们涉及思考、决策和情感等，而且进入大脑的感觉信息流也发生了变化，通常可以描述为更广泛，包括不同感官的更多混合。

And when I say blending of the senses, I'm also referring to blending of the sense of interoception, of our sense of our body and what's happening inside of our body.

当我说感官的混合时，我也指的是内感受的混合，我们对身体的感觉以及身体内部发生的事情的混合。

And this, without question, at least partially explains why when under the influence of psilocybin, one's breathing can be linked to a sound, and then suddenly the sound one thinks is being controlled by one's breathing, or that the sound itself can be linked to something that we see in our mind's eye while in the eye mask.

毫无疑问，这至少部分解释了为什么在裸盖菇素的影响下，一个人的呼吸可以与声音联系起来，然后突然一个人认为声音是由一个人的呼吸控制的，或者声音本身可以与我们戴着眼罩时在心灵之眼中看到的东西联系起来。

Essentially what I'm describing here is that serotonin 2A receptor activation allows for more broad, less precise, and less hierarchical activation of brain circuitry.

本质上，我在这里描述的是，5-羟色胺 2A 受体激活可以实现更广泛、更不精确、更少层级的大脑回路激活。

And when I say hierarchical, what I mean is that normally things go from periphery, from eyes to thalamus to visual cortex.

当我说分层时，我的意思是通常事物从外围开始，从眼睛到丘脑再到视觉皮层。

However, when under the influence of psilocybin, as I mentioned before, even in the eye mask, the visual cortex is going to be very activated, even in the absence of any visual input.

然而，正如我之前提到的，在裸盖菇素的影响下，即使在眼罩中，即使没有任何视觉输入，视觉皮层也会非常活跃。

So then if one hears a sound, perhaps from music, a particular motif or voice, and that's linked to a particular emotional state, that is now being blended with visual phenomenon occurring within the brain that have no external stimulus.

因此，如果一个人听到一种声音，可能来自音乐、特定的主题或声音，并且与特定的情绪状态相关，那么它现在就会与大脑内发生的没有外部刺激的视觉现象混合在一起。

And so while the patterns of activation in the brain while under the influence of psilocybin aren't random, they are far less channeled, far less modular, and far less hierarchical than would ever be the case when not under the influence of psilocybin.

因此，虽然在裸盖菇素影响下大脑中的激活模式不是随机的，但与未受到裸盖菇素影响时的情况相比，它们的通道性、模块化程度和层次性要低得多。

Now, in all fairness to the scientific literature, there are not one, not two, not three, but four prominent theories of which brain networks are most activated during a psilocybin or other psychedelic journey.

现在，公平地说，科学文献中，在裸盖菇素或其他迷幻旅程中大脑网络最活跃的著名理论不是一种、不是两种、不是三种，而是四种。

And so for those of you that are interested in those different models, first of all, please know that they are not competing models.

因此，对于那些对这些不同型号感兴趣的人，首先请知道它们不是竞争型号。

While some of them disagree about some of the details, it's very likely that all of these models are true.

虽然其中一些人对某些细节存在分歧，但所有这些模型很可能都是真实的。

They include things like changes in the so-called default mode network.

其中包括所谓的默认模式网络的更改等。

There's a lot of interest in this.

人们对此很感兴趣。

I've talked about it before on this podcast.

我之前在这个播客上谈过这个问题。

The default mode network is the network in the brain that's thought to be responsible for spontaneous imagination, for daydreaming, and that reflects sort of the base activation state of the brain when there's no drugs in our system.

默认模式网络是大脑中负责自发想象力和白日梦的网络，它反映了当我们的系统中没有药物时大脑的基本激活状态。

And the default mode network is one of the systems, or networks rather, that is thought to be rewired under conditions of psilocybin or other psychedelics.

默认模式网络是系统之一，或者更确切地说是网络，被认为在裸盖菇素或其他迷幻药的条件下会重新布线。

Again, if you're interested in these models and comparing and contrasting them, there's a very nice review from Brian Roth's lab at Duke, entitled "The Neural Basis of Psychedelic Action." We'll provide a link to this in the show note captions.

再说一遍，如果您对这些模型感兴趣并比较它们，可以阅读杜克大学 Brian Roth 实验室的一篇非常好的评论，题为“迷幻作用的神经基础”。我们将在节目注释标题中提供指向此内容的链接。

And again, I just want to emphasize that all of these models have been shown to be true in different studies.

再次，我想强调的是，所有这些模型都在不同的研究中被证明是正确的。

And what they all point to is more extensive communication between areas of the brain that normally are not as active at the same time, while under the influence of psychedelics such as psilocybin.

他们都指出，在裸盖菇素等致幻剂的影响下，通常不那么活跃的大脑区域之间会进行更广泛的交流。

The controversy in the field relates to which of these networks is the one that changes the most to explain the therapeutic outcomes that have been discovered in recent years.

该领域的争议在于，这些网络中哪一个网络在解释近年来发现的治疗结果方面变化最大。

So again, check out that review if you're interested in that sort of thing.

所以，如果您对此类事情感兴趣，请再次查看该评论。

In the meantime, we can cut a broad swath through all of those models and just say that psilocybin expands the functional connectivity of the brain while one is under the influence of psilocybin, and it does seem that some of that expanded functional connectivity persists after the effects of psilocybin have worn off.

与此同时，我们可以对所有这些模型进行大范围的剖析，只是说，当一个人受到裸盖菇素的影响时，裸盖菇素会扩大大脑的功能连接，而且在裸盖菇素的作用消失后，某些扩大的功能连接似乎仍然存在。

And that statement about the functional connectivity of the brain being more expanded, not just during the psilocybin session, but after as well, has been substantiated in a number of papers.

关于大脑功能连接得到进一步扩展的说法，不仅在裸盖菇素治疗期间，而且在裸盖菇素治疗之后，都得到了许多论文的证实。

But one of the key papers in this area is one that I recommend people check out if they're interested in this sort of thing, is entitled "The Effects of Psilocybin and MDMA on Between-Network Resting-State Functional Connectivity in Healthy Volunteers." And I like this paper for a number of reasons.

但这个领域的一篇关键论文是我建议人们如果对这类事情感兴趣的话可以看看，题为“裸盖菇素和 MDMA 对健康志愿者网络间静息状态功能连接的影响”。我喜欢这篇论文有很多原因。

First of all, it's a very high-quality paper carried out in the laboratory of Robin Carhart-Harris at UCSF, again, one of the premier researchers in this area of psychedelics and their function, what they do in the brain, and also their therapeutic applications, but also because it focused on healthy volunteers.

首先，这是一篇在加州大学旧金山分校 Robin Carhart-Harris 实验室发表的高质量论文，他也是迷幻药及其功能、它们在大脑中的作用以及它们的治疗应用领域的顶尖研究人员之一，而且还因为它关注的是健康志愿者。

They explored, using brain imaging, what brain areas are active in a resting state, so things like default mode network.

他们利用大脑成像技术探索了哪些大脑区域在静息状态下是活跃的，例如默认模式网络等。

Then they had people take psilocybin or MDMA, and then they looked at the connectivity between those brain areas in those same individuals when they were not under the influence of these drugs and found more extensive connectivity.

然后他们让人们服用裸盖菇素或摇头丸，然后他们观察了这些人在不受这些药物影响时大脑区域之间的连接，发现了更广泛的连接。

All of which pointed to an enhanced lateral connectivity, less hierarchical organization, effectively more interconnection and communication between different brain areas.

所有这些都表明横向连接性增强，层级组织减少，不同大脑区域之间有效地加强了互连和沟通。

I think not only is the fact that they looked at healthy volunteers very interesting and important, but also that they looked at this resting state of the brain.

我认为他们不仅对健康志愿者进行了非常有趣和重要的观察，而且还对大脑的这种静息状态进行了观察。

They weren't providing a particular auditory or visual stimulus for people to hear or look at while they were in the brain imaging scanner, as it's called.

他们并没有提供特定的听觉或视觉刺激，让人们在大脑成像扫描仪中听到或看到。

Rather, they were simply looking at how the brain was behaving at rest.

相反，他们只是观察大脑在休息时的表现。

And so it's very clear that for people that do two or even just one of these psilocybin journeys at a particular dose, that the brain is actually getting rewired.

因此，很明显，对于以特定剂量进行两次甚至仅一次裸盖菇素旅程的人来说，大脑实际上正在重新布线。

We hear this a lot.

我们经常听到这样的说法。

Psilocybin or other psychedelics lead to plasticity.

裸盖菇素或其他迷幻药会导致可塑性。

They rewire your brain.

他们重新连接你的大脑。

Well, let's go back to what we said at the beginning.

好吧，让我们回到一开始所说的。

Rewiring of the brain is not the goal.

大脑的重新布线不是目标。

Adaptive rewiring of the brain is the goal, right?

大脑的适应性重新布线是我们的目标，对吗？

Rewiring that leads to new ideas that are interesting, that are accessible after the psychedelic journey.

重新布线会带来有趣的新想法，这些想法在迷幻之旅之后是可以实现的。

New ideas and new ways of thinking or feeling that allow people to function better in their lives.

新的想法和新的思维或感受方式可以让人们在生活中更好地发挥作用。

That's the goal of effective psychedelic therapies, not simply rewiring of the brain.

这是有效迷幻疗法的目标，而不仅仅是大脑的重新布线。

A brain injury, for that matter, will lead to rewiring of the brain, but that's maladaptive rewiring.

就此而言，脑损伤会导致大脑重新布线，但这是适应不良的重新布线。

The use of things like amphetamines or methamphetamines in particular will lead to rewiring of the brain, but that is strongly maladaptive rewiring.

特别是使用安非他明或甲基苯丙胺等药物会导致大脑重新布线，但这是一种强烈的适应不良重新布线。

So now there are really dozens of studies conducted in humans using brain imaging and other techniques, have evaluated how things like psilocybin change connectivity in the brain.

因此，现在确实有数十项研究使用大脑成像和其他技术在人类身上进行，评估了裸盖菇素等物质如何改变大脑的连接性。

And I think the take-home message is, it expands that connectivity.

我认为最重要的信息是，它扩展了这种连通性。

However, it seems to do so in ways that still allow people to function in their daily lives.

然而，它的实现方式似乎仍然允许人们在日常生活中发挥作用。

And one of the key things that I gleaned from the literature on the therapeutic use of psilocybin for the treatment of depression is that very seldom do people who take psilocybin experience long-term issues with memory.

我从有关裸盖菇素治疗抑郁症的文献中收集到的关键信息之一是，服用裸盖菇素的人很少会出现长期记忆问题。

Why is that so critical?

为什么如此重要？

Well, you could imagine that increasing connectivity in the brain, reducing modularity, reducing hierarchical organization in the brain, would lead to disruptions in memory, right?

好吧，你可以想象，增加大脑的连通性、减少模块化、减少大脑的层次结构，会导致记忆中断，对吗？

It's as if you're shuffling books on the bookshelf, so to speak.

可以这么说，就像你在书架上翻阅书籍一样。

But that doesn't seem to be the case.

但事实似乎并非如此。

Rather, it seems that the increase in connectivity is leading, provided set and setting are correct, provided safety protocols are followed, to positive rewiring or adaptive rewiring of neural tissue.

相反，如果设定和设置正确，如果遵循安全协议，连接性的增加似乎会导致神经组织的积极重新布线或适应性重新布线。

So that's one of the things that makes psychedelics, and psilocybin in particular, very exciting from the therapeutic standpoint.

因此，从治疗的角度来看，这就是迷幻药（尤其是裸盖菇素）非常令人兴奋的原因之一。

And of course, we have to acknowledge it's also what has a lot of people excited about psychedelics, not just for the treatment of depression, but for expanding the brain's capabilities more generally.

当然，我们必须承认，这也是很多人对迷幻药感到兴奋的原因，不仅是为了治疗抑郁症，而且是为了更广泛地扩展大脑的能力。

So along those lines, I want to touch on the issues of creativity and the experience of life outside of psychedelic journeys is impacted by psychedelic journeys.

因此，沿着这些思路，我想谈谈创造力的问题，以及迷幻旅程之外的生活体验受到迷幻旅程的影响。

And here, this relates to a question that I heard a lot when I put the call out on social media that I was going to do this episode, and I asked people, "What do you want to know about psilocybin?" And one of the more common questions that I got was, does it increase creativity?

在这里，这与我在社交媒体上呼吁制作这一集时经常听到的一个问题有关，我问人们，“关于裸盖菇素，你们想了解什么？”我收到的最常见的问题之一是，它会增加创造力吗？

Does it increase our experience of life in ways that are beneficial, aside from its now documented positive effects in treating depression and compulsive disorders and addiction?

除了目前已记录在治疗抑郁症、强迫症和成瘾方面的积极作用之外，它是否还能以有益的方式增加我们的生活体验？

And the short answer to this is yes, but that the positive effects of psychedelics, psilocybin in particular, on creativity and our experience of life have only been explored in a fairly narrow set of dimensions.

对此问题的简短回答是肯定的，但迷幻药（尤其是裸盖菇素）对创造力和我们的生活体验的积极影响仅在相当狭窄的范围内进行了探索。

However, where it's been explored, there's some really interesting findings.

然而，在对其进行探索的地方，有一些非常有趣的发现。

So one of the more interesting findings, I think, is a paper entitled "Increased Low-Frequency Brain Responses to Music after Psilocybin Therapy for Depression." I think this is a really interesting paper because what the authors did is they took advantage of the fact that in these therapeutic psilocybin sessions that are carried out for the treatment of depression, music is being played, and there are prior studies showing that when music is played, you activate different brain areas depending on what sort of music is being played.

因此，我认为更有趣的发现之一是一篇题为“使用赛洛西宾治疗抑郁症后大脑对音乐的低频反应增加”的论文。我认为这是一篇非常有趣的论文，因为作者所做的是他们利用了这样一个事实：在这些用于治疗抑郁症的裸盖菇素治疗疗程中，正在播放音乐，并且之前的研究表明，当播放音乐时，您会根据播放的音乐类型激活不同的大脑区域。

That's somewhat obvious, perhaps.

也许这有点明显。

Sad music versus intense.

悲伤的音乐与激烈的音乐。

You could think about heavy metal versus choir music versus Gregorian chants versus punk rock music, and on and on.

你可以考虑重金属音乐、合唱音乐、格里高利圣歌、朋克摇滚音乐，等等。

It makes sense that different brain areas would be activated when different patterns of music are played.

当播放不同模式的音乐时，不同的大脑区域会被激活，这是有道理的。

However, there do seem to be some universal features of brain activation in response to music.

然而，大脑对音乐的激活似乎确实存在一些普遍特征。

This should probably be the topic of an entire episode of the Huberman Lab podcast, and indeed it will be.

这可能应该是休伯曼实验室播客整集的主题，而且确实如此。

For instance, there are areas of the auditory cortex that are activated, no surprise there, and areas of the brain's reward circuitry, the so-called ventral striatum, and the so-called mesolimbic reward pathway.

例如，听觉皮层的某些区域被激活，这并不奇怪，还有大脑奖励回路的区域，即所谓的腹侧纹状体和所谓的中边缘奖励通路。

Talked a lot about these in the episodes about dopamine that I've done previously.

在我之前做过的关于多巴胺的剧集中谈论了很多这些。

These are brain areas that lead to the release of dopamine in other brain areas and that reinforce certain experiences and that tend to give us the subjective feeling of, "Yes, I like this.

这些大脑区域会导致其他大脑区域释放多巴胺，并强化某些体验，并且往往会给我们这样的主观感觉：“是的，我喜欢这个。

I want more." So in this particular paper, what the authors did is they took advantage of the fact that people are in the clinic, they're on psilocybin, they're listening to music, and as you recall, the music played at different stages of the psilocybin journey are different.

我想要更多。”因此，在这篇特别的论文中，作者所做的是，他们利用了这样一个事实：人们在诊所，服用裸盖菇素，他们正在听音乐，正如你所记得的，在裸盖菇素旅程的不同阶段播放的音乐是不同的。

They have a different emotional component, and music is a really nice stimulus in the laboratory, as we say, because like with visual stimuli, you can break it down into high frequency, low frequency.

他们有不同的情感成分，正如我们所说，音乐在实验室中是一种非常好的刺激，因为就像视觉刺激一样，你可以将其分解为高频和低频。

Right?

正确的？

Sounds like dun dun or ah ah.

听起来像顿顿或者啊啊。

These kinds of things.

诸如此类的事情。

That was my attempt at low frequency versus high frequency auditory stimuli.

这是我对低频与高频听觉刺激的尝试。

Or at the spatial frequency, or what in the auditory domain would be called the temporal frequency.

或者在空间频率上，或者在听觉领域中称为时间频率。

Is it boom, boom, boom, or is it boom, boom, boom, boom?

是繁荣、繁荣、繁荣，还是繁荣、繁荣、繁荣、繁荣？

All we've changed there is the temporal frequency.

我们改变的只是时间频率。

The sound was somewhat the same, but the distance between those sounds was different.

声音有些相似，但声音之间的距离却不同。

You get the idea.

你明白了。

So they have access to these people and these different conditions, and they can put them in the brain scanner, and they can do that before and after having taken psilocybin.

因此，他们可以接触到这些人以及这些不同的条件，他们可以将他们放入脑部扫描仪中，他们可以在服用裸盖菇素之前和之后进行。

And the long and short of this study is that psilocybin changes one's experience of music not just during the psilocybin journey itself, but thereafter.

这项研究的长处和短处是，裸盖菇素不仅在裸盖菇素之旅本身，而且在之后改变了一个人的音乐体验。

And in fact, it changes one's emotional response to music in very interesting ways.

事实上，它以非常有趣的方式改变了一个人对音乐的情感反应。

For instance, one of the more common features of major depression is that people don't derive as much pleasure from different types of experiences, whether or not it's food or sex or social experiences, to the point where sometimes they just stop trying to seek out those experiences.

例如，重度抑郁症的一个更常见的特征是，人们无法从不同类型的经历中获得尽可能多的快乐，无论是食物、性还是社交经历，以至于有时他们不再试图寻找这些经历。

People with depression often feel as if music no longer has the same impact.

抑郁症患者常常感觉音乐不再具有同样的影响力。

It just doesn't really lift them up very much.

它只是并没有真正让他们振作起来。

This study found that people who have taken psilocybin, according to the parameters we talked about earlier, can get a return of the elevated emotionality, the positive emotions associated with music that formerly made them feel good.

这项研究发现，根据我们之前讨论的参数，服用裸盖菇素的人可以恢复高涨的情绪，即以前让他们感觉良好的与音乐相关的积极情绪。

In other words, they can feel music again.

换句话说，他们可以再次感受到音乐。

They can feel good in response to music again.

他们可以再次对音乐产生良好的反应。

Now, this is interesting because in theory, it could be that psilocybin simply allowed them to access the emotions around music again more generally, but that's actually not what this paper and some other papers that have been published report.

现在，这很有趣，因为从理论上讲，裸盖菇素可能只是让他们更普遍地再次接触到音乐周围的情感，但实际上这并不是这篇论文和其他一些已发表论文的报告。

Rather, it seems that taking psilocybin can increase one's positive perception of music that one likes and can tone down or reduce the depressiveness or the sadness of music that tends to make one sad even after the psilocybin has worn off and for a long period of time afterwards, maybe even forever.

相反，服用裸盖菇素似乎可以增加一个人对自己喜欢的音乐的积极感知，并且可以淡化或减少音乐的抑郁或悲伤感，即使在裸盖菇素药效消失后，甚至在之后很长一段时间内，甚至可能永远，音乐都会让人感到悲伤。

Although no study, of course, can be carried out forever because forever is forever.

当然，虽然没有任何研究可以永远进行，因为永远就是永远。

What we do know, however, is that psilocybin can rewire the connections between the emotion centers in the brain and the networks that control auditory perception of music and leads to this condition in which people who felt like, "Ugh, I was depressed," or, "I couldn't feel the music.

然而，我们所知道的是，裸盖菇素可以重新连接大脑中的情感中心和控制音乐听觉感知的网络之间的连接，并导致人们感觉“呃，我很沮丧”或“我感觉不到音乐。

I just wasn't getting the same lift and joy from it again," they can start to experience more joy from that music again, and that music that made them feel sad and depressed has a diminished capacity to make them feel sad and depressed.

我只是不再从中得到同样的提升和快乐，”他们可以再次从音乐中体验到更多的快乐，而那些让他们感到悲伤和沮丧的音乐让他们感到悲伤和沮丧的能力减弱了。

And there's a lot of neuroimaging data in this paper that point to the specific brain areas that include areas like the ventral tegmental area that can explain why these sorts of effects would occur.

本文中有大量神经影像数据指出了特定的大脑区域，包括腹侧被盖区等区域，可以解释为什么会发生这些效应。

So this isn't just subjective reports of people saying, "Oh, yeah, I was depressed, and then music didn't feel really good, now it feels great," or, "That used to make me feel so sad, and now I feel like I have a capacity to listen to that without being crushed by feelings of sadness."

因此，这不仅仅是人们的主观报告，他们说：“哦，是的，我很沮丧，然后音乐感觉不太好，现在感觉很棒，”或者，“这曾经让我感到如此悲伤，现在我觉得我有能力聆听音乐，而不会被悲伤的感觉压垮。”

The paper included some subjective reports of that sort, but then was able to link those to changes in brain circuitry and brain activation in response to music using neuroimaging.

该论文包含了一些此类主观报告，但随后能够使用神经影像学将这些报告与大脑回路的变化以及对音乐做出反应的大脑激活联系起来。

So in that way, it really points to both the subjective and structural and functional changes that psilocybin can bring about through that expanded connectivity between brain areas.

因此，通过这种方式，它确实表明了裸盖菇素可以通过扩大大脑区域之间的连接来带来主观、结构和功能的变化。

Because remember, during the psilocybin session, it's not as if music or the perception of music is specifically being looked at or focused on in these studies.

因为请记住，在裸盖菇素治疗期间，这些研究并不是特别关注或关注音乐或音乐感知。

Rather, music is playing.

相反，音乐正在播放。

People are in the eye mask.

人们都在眼罩里。

They're feeling all sorts of things.

他们感受到各种各样的事情。

They're breathing.

他们在呼吸。

They're hearing.

他们正在听。

They're touch.

他们有触摸。

It's all happening all at once.

这一切都是同时发生的。

There's a peak.

有一个高峰。

It's long.

很长。

There's a long taper.

有一个长锥度。

The music's changing.

音乐正在改变。

Okay, all of that took place in this study as well.

好吧，所有这些也都发生在这项研究中。

But it is after the session when comparing brain activation states to music of a particular type, sad or happy, and comparing that to the patterns of brain activation that occurred before the psilocybin journey, that they discover that people's brains have rewired during the psilocybin session in a way that allows them to experience joy in response to music again.

但在疗程结束后，当将大脑激活状态与特定类型的音乐（悲伤或快乐）进行比较，并将其与裸盖菇素之旅之前发生的大脑激活模式进行比较时，他们发现人们的大脑在裸盖菇素疗程期间进行了重新连接，使他们能够再次体验到对音乐做出反应的快乐。

So that's one of the more rigorous studies I was able to find that addresses this question of whether or not psilocybin really does rewire the brain in ways that allows us to be more creative and experience life differently after the psilocybin session.

因此，这是我能够找到的更严格的研究之一，它解决了裸盖菇素是否真的能够以某种方式重新连接大脑的问题，使我们在裸盖菇素疗程后更具创造力并以不同的方式体验生活。

Now, that paper didn't focus specifically on creativity.

现在，那篇论文并没有专门关注创造力。

I did an entire episode on creativity that talked about different types of meditation, like open monitoring meditation.

我做了一整集关于创造力的节目，讨论了不同类型的冥想，比如开放监控冥想。

It talked about different patterns of thinking that one can actually practice to increase creativity.

它讨论了人们可以实际练习以提高创造力的不同思维模式。

We had arguably one of the most creative people on the planet, Rick Rubin, came on this podcast, talked about the creative process from the perspective of music and his role in producing music.

我们可以说是地球上最具创造力的人之一，里克·鲁宾 (Rick Rubin) 来到这个播客，从音乐的角度谈论了创作过程以及他在制作音乐中的作用。

So you can check out those episodes if you're interested in the neural circuitry related to creativity.

因此，如果您对与创造力相关的神经回路感兴趣，可以查看这些剧集。

At least at the time of recording this episode, there haven't been a lot of studies looking specifically at the brain networks that we think are involved in creativity and how those change in response to psilocybin and other psychedelics.

至少在录制本集时，还没有大量研究专门研究我们认为与创造力有关的大脑网络，以及这些网络如何响应裸盖菇素和其他迷幻药而发生变化。

I imagine those studies are either happening now or will happen in the future.

我想这些研究要么现在正在发生，要么将来会发生。

But the studies I just described, referring to the changes in emotionality and responses to music, I think provide a nice template for what's likely happening both during psilocybin journeys and after those psilocybin journeys.

但我刚才描述的研究，涉及情绪和对音乐的反应的变化，我认为为裸盖菇素之旅期间和裸盖菇素之旅之后可能发生的情况提供了一个很好的模板。

When we talk about less hierarchical organization, more connectivity between brain areas, what it's pointing to is the fact that during the psilocybin journey, people have the opportunity to learn new relationships between different sensory and emotional states.

当我们谈论更少的等级组织、更多的大脑区域之间的连接时，它所指的是这样一个事实：在裸盖菇素之旅中，人们有机会学习不同感官和情绪状态之间的新关系。

And those new relationships seem to persist long after the psychedelic journey has been finished.

在迷幻之旅结束后，这些新的关系似乎仍会持续很长时间。

And a lot of people researching psilocybin in the clinical setting think that that's one of the major reasons why psilocybin and other psychedelics can rewire our relationship to things more broadly.

许多在临床环境中研究裸盖菇素的人认为，这是裸盖菇素和其他迷幻药可以更广泛地重新连接我们与事物的关系的主要原因之一。

It allows for new learning, new contingencies.

它允许新的学习、新的突发事件。

And when we look at depression, we often think diminished mood, people don't have an appetite, they're not interested in social relationships or romantic relationships.

当我们看待抑郁症时，我们经常会想到情绪低落，人们没有胃口，他们对社交关系或浪漫关系不感兴趣。

They're really struggling.

他们真的很挣扎。

And all of that, of course, is true.

当然，所有这些都是真的。

But another lens to look at depression through is that a lot of that thinking and a lot of those emotional states that are negative are somewhat habitual.

但看待抑郁症的另一个视角是，很多消极的想法和情绪状态在某种程度上都是习惯性的。

They relate to a sort of implicit understanding and living out of the idea that A leads to B leads to C.

它们与一种隐含的理解有关，并遵循“A导致B导致C”的想法。

Okay?

好吧？

You seek out a relationship, it doesn't work out.

你寻求一段关系，但没有成功。

You try a new job, you don't get the job.

你尝试一份新工作，但你没有得到这份工作。

You get the job, it's no good.

你得到了这份工作，这并不好。

All these negative outcomes of if A, then B, then C.

如果 A，然后 B，然后 C，所有这些负面结果。

And it does seem that psilocybin can have this effect of invoking new patterns of learning, new considerations about what might be possible, and indeed may even lead to actual rewiring of the emotion centers in the brain with these other brain areas and vice versa, in ways that eject people from the psilocybin session thinking, "Oh, yeah, I used to feel this way about something, work, relationships, myself, et cetera, but I'm willing to consider this other possibility," or, "This other possibility seems at least partially true to the extent that I'm willing to go out and evaluate that."

裸盖菇素似乎确实可以产生这样的效果，激发新的学习模式，对可能发生的事情进行新的思考，甚至可能导致大脑中的情感中心与其他大脑区域的实际重新连接，反之亦然，以一种将人们从裸盖菇素会话中驱逐出来的方式，认为“哦，是的，我曾经对某些事情，工作，人际关系，我自己等等有这种感觉，但我愿意考虑另一种可能性”，或者，“另一种可能性似乎在至少部分正确的是我愿意出去评估这一点。”

Now, here I'm speaking very subjectively, but remember, we have to tie back the subjective experiences and changes of things like music and emotion and our relationship to life and jobs and relationships back to the cell biology and chemistry of psilocybin, because ultimately, it really is just a chemical activating receptors, those receptors changing networks in the brain.

现在，我在这里说的是非常主观的，但请记住，我们必须将诸如音乐和情感之类的主观体验和变化，以及我们与生活、工作和关系的关系，与裸盖菇素的细胞生物学和化学联系起来，因为最终，它实际上只是一种化学激活受体，这些受体改变了大脑中的网络。

And the journey itself seems to be the time when all of those changes are put in motion.

而旅程本身似乎就是所有这些变化开始运转的时刻。

It's like a boulder that gets rolling.

它就像一块滚滚的巨石。

In fact, I think the best way to think about psilocybin and other psychedelics is that they initiate the neuroplasticity process, but they are not the neuroplasticity process itself, and the journey itself is not where all the neuroplasticity occurs.

事实上，我认为思考裸盖菇素和其他迷幻药的最佳方式是它们启动了神经可塑性过程，但它们不是神经可塑性过程本身，旅程本身也不是所有神经可塑性发生的地方。

We know that for sure.

我们肯定知道这一点。

In fact, if you want to imagine how psilocybin and other psychedelics work to change the brain, think about them as a wedge that gets underneath the boulder that is the neuroplasticity that gets rolling forward.

事实上，如果你想想象裸盖菇素和其他致幻剂如何改变大脑，请将它们想象成一个楔子，位于巨石下方，这就是向前滚动的神经可塑性。

And then think about whether or not the plasticity is adaptive or maladaptive, whether or not it actually serves you in your life on a daily basis or not, depending on whether or not you're using your conscious brain to move that boulder in a particular direction, right?

然后想想可塑性是适应性的还是适应不良的，它是否真的在你的日常生活中为你服务，这取决于你是否使用你的有意识的大脑将巨石移向特定的方向，对吧？

Not just bulldozing through things and destroying them, but clearing a path through old, ineffective, maybe even destructive patterns of thoughts or emotions, et cetera.

不仅仅是用推土机推倒并摧毁它们，而是为旧的、无效的、甚至可能具有破坏性的思想或情感模式等扫清道路。

I give you that analogy because I think it more accurately captures what psychedelics like psilocybin are doing, rather than the typical discussion around psychedelics that we tend to hear, which is that, oh, it creates plasticity, and plasticity is what you want.

我给你这个类比是因为我认为它更准确地捕捉了像裸盖菇素这样的迷幻药正在做的事情，而不是我们经常听到的关于迷幻药的典型讨论，那就是，哦，它创造了可塑性，而可塑性就是你想要的。

For the next couple of minutes, I'd like to focus on some of the key and stereotype that is characteristic experiences that people tend to have during a psilocybin journey, because there's some really interesting research on this.

在接下来的几分钟里，我想重点讨论人们在裸盖菇素之旅中往往会经历的一些关键和刻板印象，因为对此有一些非常有趣的研究。

These are phrases that perhaps you've heard before, things like letting go, ego dissolution, feelings of connectedness.

这些短语也许你以前听过，比如放手、自我消解、联系感。

While all of that is very subjective on the one hand, those words are heard often enough and repeatedly enough in psilocybin sessions and after psilocybin sessions, along with this description of the psilocybin experience as one of the most profound of one's life, or one of the most positive, in the ideal case, of one's life, that they are worth exploring.

虽然所有这些一方面都是非常主观的，但这些话在裸盖菇素疗程中和裸盖菇素疗程后经常被听到，并且被多次重复，同时将裸盖菇素体验描述为一个人一生中最深刻的经历之一，或者在理想情况下，一生中最积极的体验之一，值得探索。

We should also, of course, explore the so-called bad trip, the possibility that someone will have a not good time or even very frightening time while under the influence of psilocybin.

当然，我们也应该探索所谓的糟糕旅行，即某人在裸盖菇素的影响下度过一段不愉快甚至非常可怕的时光的可能性。

So there have been some scientific studies that have explored what sorts of subjective experiences, that is thoughts and feelings insights that people have that relate to positive therapeutic outcomes, and more generally, with the sense that the psilocybin journey was positive or maybe even tremendously positive in one's life.

因此，已经有一些科学研究探索了什么样的主观体验，即人们的想法和感受洞察力与积极的治疗结果相关，更一般地说，是与裸盖菇素之旅对一个人的生活是积极的，甚至可能是非常积极的感觉有关。

So while there's a century or more of writings about psychedelics that describe things like enhanced feelings of connectedness or dissolution of the ego, the loss of one sense of self, and then the regaining of one sense of self, and so on, there's a particular paper that describes some of those things in terms of rating scales.

因此，尽管有一个多世纪的关于迷幻药的著作描述了诸如增强联系感或自我消解、失去一种自我意识，然后重新获得一种自我意识等事情，但有一篇特定的论文用评级量表描述了其中一些事情。

That is, the sorts of tests that people can take in which they answer particular questions and that link back to things like feelings of connectedness and ego dissolution that allows us to put some numbers to those experiences and to look at some of the statistics associated with those experiences.

也就是说，人们可以进行一些测试，在这些测试中，他们回答特定的问题，并与联系感和自我消解等事物联系起来，使我们能够对这些经历进行一些统计，并查看与这些经历相关的一些统计数据。

And this is really what's important about scientific studies, whether or not a measure is subjective, so if someone's self-reporting how they felt or feel, or whether or not it's a measure of blood pressure or of a chemical in the bloodstream, et cetera.

这确实是科学研究的重要之处，无论测量是否是主观的，所以如果有人自我报告他们的感受或感受，或者它是否是血压或血液中化学物质的测量，等等。

It's the use of numbers and statistics that allows comparison between different groups and that can be compared between studies that allows us to make some firm conclusions about what sorts of things psilocybin may or may not be doing when it's effective or not.

正是使用数字和统计数据，可以在不同组之间进行比较，并且可以在研究之间进行比较，使我们能够就裸盖菇素在有效或无效时可能会或可能不会做哪些事情做出一些明确的结论。

So the paper I'd like to highlight is entitled "Quality of Acute Psychedelic Experience Predicts Therapeutic Efficacy of Psilocybin for Treatment-Resistant Depression." I'll put a link to this paper in the show note captions.

因此，我想强调的论文标题为“急性迷幻体验的质量预测裸盖菇素治疗难治性抑郁症的治疗效果”。我将在节目注释标题中放置这篇论文的链接。

But the basic contour of this paper is that they looked at subjects that underwent two different psilocybin sessions.

但这篇论文的基本轮廓是，他们研究了接受两次不同裸盖菇素治疗的受试者。

One at a relatively low-ish dose of 10 milligrams of psilocybin.

其中一种剂量相对较低，为 10 毫克裸盖菇素。

Again, that would be equivalent to about one gram of psychedelic mushrooms, more or less.

同样，这或多或少相当于大约一克迷幻蘑菇。

And a second session involving subjects taking 25 milligrams of psilocybin, or what's roughly equivalent to somebody taking two and a half grams of psilocybin mushrooms.

第二次测试涉及受试者服用 25 毫克裸盖菇素，或者大约相当于某人服用两克半裸盖菇素。

Those people then answered what's called the Altered States of Consciousness Questionnaire, which allowed them to address, and here I'm paraphrasing, the quality of experiences in the 25-milligram psilocybin session.

然后，这些人回答了所谓的意识状态改变问卷，这使他们能够解决（我在这里解释一下）25 毫克裸盖菇素疗程中的体验质量。

So without going into too much detail, it's often the case in these sorts of two-session studies that subjects will take a slightly lower dose of psilocybin to familiarize themselves with the experience, and then the higher dose that leads to the more intense experience.

因此，在不涉及太多细节的情况下，在此类两次会话的研究中，通常情况下，受试者会服用稍低剂量的裸盖菇素来熟悉这种体验，然后使用较高剂量来获得更强烈的体验。

Intense meaning a bigger, more intense peak, a longer session overall, greater distortions in emotionality and perceptual experience, all the stuff we talked about before.

强烈意味着更大、更强烈的峰值，整体时间更长，情绪和知觉体验更大的扭曲，所有我们之前讨论过的东西。

So what this study found is that one of the key features, if not the key feature of a positive, quote-unquote, psychedelic experience is this sense of oceanic boundlessness occurring at some point during the psychedelic journey.

因此，这项研究发现，积极的、引述不引述的迷幻体验的关键特征之一（如果不是关键特征的话）就是在迷幻之旅的某个时刻发生的这种海洋无边无际的感觉。

Now, oceanic boundlessness doesn't necessarily mean anything to any of us.

现在，海洋的无边无际对我们任何人来说都不一定意味着什么。

It probably means different things to different people.

对于不同的人来说，它可能意味着不同的事情。

It's this idea that one is experiencing something extremely unusual, even mystical, beyond this world and one's normal experience, but that it's not aligned with any specific outcome in the moment.

这种想法认为，一个人正在经历一些极其不寻常的事情，甚至是神秘的事情，超出了这个世界和一个人的正常经历，但它与当前的任何具体结果都不相符。

It's not directly attached to any one feeling or memory or thought process.

它不直接依附于任何一种感觉、记忆或思维过程。

It's a little bit tough to describe because I can guarantee you, I'm not on psilocybin or any psychedelics right now, and I can only imagine that you're not, although some of you might be.

这有点难以描述，因为我可以向你保证，我现在没有服用裸盖菇素或任何迷幻药，我只能想象你没有服用，尽管你们中的一些人可能会服用。

I can't even imagine what this podcast would be like for somebody on psilocybin at this moment.

我什至无法想象这个播客对于此时服用裸盖菇素的人来说会是什么样子。

But in any case, oceanic boundlessness, a feeling of the experience being mystical and not really heading in any one particular direction, just a feeling of massive connectedness with one's environment, both in the room and session, perhaps with the guides, with one's self, with one's past, with one's present, people outside the room, with the entire world, maybe even the universe, that sort of thing.

但无论如何，海洋般的无边无际，一种体验的感觉是神秘的，并不是真正走向任何一个特定的方向，只是一种与环境的巨大联系的感觉，无论是在房间里还是在会议中，也许与导游，与一个人的自我，与一个人的过去，与一个人的现在，与房间外的人，与整个世界，甚至宇宙，诸如此类的东西。

The intensity of that experience of oceanic boundlessness, the mystical experience, seems to be positively correlated with positive therapeutic outcomes.

那种海洋无边无际的体验的强度，即神秘的体验，似乎与积极的治疗结果呈正相关。

That is, relief from major depression.

也就是说，重度抑郁症的缓解。

Now, during the psychedelic journey, as we talked about before, there are a number of steps that one typically goes through.

现在，在迷幻之旅中，正如我们之前谈到的，人们通常会经历许多步骤。

So there's the build-up to first experiencing the effects of the drug, about maybe 20 to 45 minutes into the journey or trip, then the peak, and it is during that peak that people often feel the sense of oceanic boundlessness.

因此，在旅程或旅程开始后大约 20 到 45 分钟，第一次体验到药物的效果需要一段时间，然后是高峰期，正是在高峰期，人们经常感受到海洋无边无际的感觉。

However, it's also often the case that it is during the peak or the maximum intensity of emotion, and we know based on direct measurements, also increases in blood pressure and heart rate, often very significant increases in anxiety and fear as well, that people will experience things like ego dissolution.

然而，通常情况下，在情绪的高峰或最大强度期间，我们根据直接测量知道，血压和心率也会增加，焦虑和恐惧通常也会显着增加，人们会经历诸如自我消解之类的事情。

And the guide's role at that point is, of course, to keep the person safe, make sure they don't run out of the room, jump out of a window, run into traffic.

当然，此时导游的作用是保证人员安全，确保他们不会跑出房间、跳出窗户、撞上车流。

Sadly, these are things that have happened outside of a strong, healthy, safe set and setting.

可悲的是，这些事情发生在一个强大、健康、安全的环境和环境之外。

But the guide's role is to keep the person safe, but also to encourage them to let go and move through that experience, to experience the anxiety, allow it to peak, allow them to see that they're not going to die from that anxiety.

但向导的作用是保证人的安全，同时也鼓励他们放手并经历这种经历，体验焦虑，让它达到顶峰，让他们看到自己不会死于这种焦虑。

They're not going to dissolve.

他们不会溶解。

They won't lose their sense of self completely, or they may temporarily feel as if they lose their sense of self, but then they feel it restored at various intervals during the peak or as they exit that peak and move toward the, say, second, third, fourth, fifth hour of the session.

他们不会完全失去自我意识，或者他们可能会暂时感觉好像失去了自我意识，但随后他们会在高峰期间的不同时间间隔或当他们离开高峰并进入训练的第二、第三、第四、第五个小时时感觉自我意识恢复了。

So when exactly these feelings of oceanic boundlessness and ego dissolution occur varies from person to person, but typically it's during the peak that the ego dissolution, the fear, and the need to, quote-unquote, "let go" is most typical.

因此，这些海洋无边无际和自我消解的感觉何时发生，因人而异，但通常在自我消解的高峰期，恐惧和“放手”的需要是最典型的。

I think perhaps the best way to describe the data in this paper in a way that's meaningful to everybody is to refer you to Figure 2, which if you're not looking at the paper, won't mean anything to you, but I'll describe it, and if you do want to take a look at Figure 2, again, you can access the paper in the show note captions.

我认为，以对每个人都有意义的方式描述本文中的数据的最佳方式也许是让您参考图 2，如果您不看本文，图 2 对您来说没有任何意义，但我会对其进行描述，如果您确实想再次查看图 2，您可以在显示注释标题中访问该论文。

What they did is they looked at a number of different subjective measures, things like Experience of unity, the feeling that one is connected to others and to the world.

他们所做的是研究了许多不同的主观衡量标准，比如团结的体验，一个人与他人和世界相连的感觉。

Things like spirituality, whether or not the whole thing felt like a spiritual experience, whether or not it was a blissful state, whether or not there were insights, whether or not somebody felt disembodied, out of body, whether or not somebody had a lot of anxiety, whether or not they had these synesthesias, these blending of visual, auditory touch and breathing and things of that sort.

比如灵性，无论整个事情是否感觉像是一种精神体验，是否是一种幸福的状态，是否有洞察力，是否有人感到脱离身体，脱离身体，是否有人有很多焦虑，他们是否有这些联觉，这些视觉、听觉触摸和呼吸的混合以及诸如此类的东西。

And they addressed which of those measures related to the positive clinical outcomes that were observed later after the psilocybin wore off.

他们还讨论了哪些措施与裸盖菇素失效后观察到的积极临床结果相关。

And while I'm not going to go point by point through each one of these measures, there's a general feature to emerge from this study, which is that the experience of unity, the sense that the psilocybin journey was spiritual, an experience of bliss at some point inside of the psilocybin journey.

虽然我不打算逐一讨论这些措施中的每一项，但这项研究有一个普遍特征，那就是团结的体验，裸盖菇素之旅是精神性的感觉，裸盖菇素之旅中某个时刻的幸福体验。

The sense that there were insights, that there were learnings about one's life and oneself.

感觉有洞察力，有关于自己的生活和自我的学习。

When those things were experienced very strongly, that correlated with the person being what was called a responder to the psilocybin treatment, meaning they got relief from their depression.

当这些事情经历得非常强烈时，这与这个人对裸盖菇素治疗有反应有关，这意味着他们从抑郁中得到了缓解。

Whereas people who felt less of that, okay, so the non-responders, as they're called, the people who do not benefit so much in the long run from the psilocybin treatment, tended to report less of an experience of unity, less of a spiritual experience, less of a blissful state, less insightfulness, and so on.

而那些感觉较少的人，好吧，所以所谓的无反应者，从长远来看，从裸盖菇素治疗中获益不多的人，往往报告较少的团结体验，较少的精神体验，较少的幸福状态，较少的洞察力，等等。

Whereas there were very few differences between the people that derived benefit from the psilocybin treatment and those did not, along the dimensions of synesthesia, this blending of different perceptions that ordinarily doesn't occur for most people, or complex imagery, right?

然而，从裸盖菇素治疗中受益的人和没有从裸盖菇素治疗中受益的人之间几乎没有什么区别，但在联觉方面，这种不同感知的混合通常不会发生在大多数人身上，或者复杂的意象，对吗？

Put simply, everyone who took psilocybin in this study at 25 milligrams saw complex imagery.

简而言之，在这项研究中服用 25 毫克裸盖菇素的每个人都看到了复杂的图像。

They saw a lot of hallucinations.

他们看到了很多幻觉。

But just seeing hallucinations did not lead to the positive clinical outcomes in terms of mood.

但仅仅看到幻觉并不会在情绪方面带来积极的临床结果。

Anxiety was a very interesting measure here because ordinarily we think of the ego dissolution, the letting go as such a key component of the psychedelic journey in terms of the positive therapeutic outcomes.

焦虑在这里是一个非常有趣的衡量标准，因为通常我们认为自我消解、放手是迷幻之旅的关键组成部分，可以带来积极的治疗结果。

This has been discussed quite a lot.

这已经被讨论了很多。

And in full disclosure, Robin Carhart-Harris has already come on to record an episode of the Huberman Lab podcast.

完全公开的是，罗宾·卡哈特-哈里斯已经开始录制胡伯曼实验室播客的一集。

That episode hasn't been released yet, but it will be released soon.

该集尚未发布，但很快就会发布。

And he talks about the importance of this letting go in terms of the positive clinical outcomes of the psilocybin journey.

他谈到了这种放手对于裸盖菇素之旅的积极临床结果的重要性。

And indeed, that is true.

确实如此。

And I should also mention that Dr. Matthew Johnson from Johns Hopkins, who also runs a laboratory exploring psychedelics and their role in treating things like eating disorders and depression, et cetera, also doing incredible work, also talked about the importance of letting go during the psilocybin journey, this ego dissolution, this ability to move through the anxiety.

我还应该提到约翰·霍普金斯大学的马修·约翰逊博士，他也经营着一个实验室，探索致幻剂及其在治疗饮食失调和抑郁症等疾病中的作用，他也做了令人难以置信的工作，他也谈到了在裸盖菇素之旅中放手的重要性，这种自我溶解，这种克服焦虑的能力。

And again, I can't underscore this enough because it's been told to me over and over again by the top researchers in this area that people head into that peaking phase of the psilocybin journey, and oftentimes it is not pleasant for them.

再说一次，我无法充分强调这一点，因为该领域的顶尖研究人员一遍又一遍地告诉我，人们正进入裸盖菇素之旅的高峰阶段，而且通常这对他们来说并不愉快。

They're feeling like it's uncomfortable, it's scary, and their heart rate is up, and their blood pressure is up, and they're having a hard time calming down than they want to calm down.

他们感觉不舒服，很害怕，心率加快，血压升高，他们很难平静下来，而不是他们想要平静的地方。

But it does seem that while the guides should not ramp them up and get them more stressed, that the ability to move through that stressful period, to somewhat guide oneself or to be encouraged to guide oneself through that peak and that anxiety and the fear of losing oneself and the so-called ego dissolution that occurs, is an important feature for an effective therapeutic session.

但看起来，虽然引导者不应该让他们增加压力，让他们承受更大的压力，但能够度过那个充满压力的时期，在某种程度上引导自己或被鼓励引导自己度过那个高峰，以及那种焦虑和对迷失自我的恐惧以及发生的所谓的自我消解，是有效治疗过程的一个重要特征。

In this study, anxiety itself was inversely correlated with a positive therapeutic outcome.

在这项研究中，焦虑本身与积极的治疗结果呈负相关。

Okay, so this is important and somewhat nuanced.

好的，这很重要，而且有些微妙。

On the one hand, I'm telling you that the letting go, the ego dissolution does seem to be important in terms of reporting a psychedelic experience as effective as having accomplished something, and perhaps even explaining some of the long-term positive effects to emerge from that psychedelic journey, in this case, psilocybin journey.

一方面，我告诉你，放手、自我消解似乎对于报告迷幻体验和完成某件事一样有效很重要，甚至可能解释迷幻之旅（在本例中为裸盖菇素之旅）中产生的一些长期积极影响。

However, non-responders, that is people who did psilocybin but did not have a positive therapeutic outcome in comparison to the responders, those non-responders tended to have higher subjective ratings of anxiety than did the responders.

然而，无反应者，即服用裸盖菇素但与反应者相比没有获得积极治疗结果的人，这些无反应者往往比反应者有更高的主观焦虑评级。

So this is important, and what it speaks to is the fact that, while yes, letting go during the session, experiencing some anxiety, perhaps even ego dissolution and the dissolving of self and then the return of self is important.

所以这很重要，它所说明的事实是，虽然是的，在治疗期间放手，经历一些焦虑，甚至可能是自我消解和自我消解，然后自我回归是重要的。

It is also important, it seems, that anxiety not be so, so high or subjectively experienced as so high that one does not experience the positive neuronal rewiring that leads to a more pervasive elevated mood.

同样重要的是，焦虑不要太高，或者主观体验太高，以至于人们不会经历积极的神经元重新布线，而这种积极的神经元重新布线会导致更普遍的情绪升高。

Okay, so I'm definitely saying two things at once because I'm trying to capture the data accurately.

好的，所以我肯定会同时说两件事，因为我正在努力准确地捕获数据。

It would not be fair for me to say, "Just let go, experience as much anxiety as is possible, and that's part of the process." Yes, letting go, again, in air quotes, seems to be important for one's experience of the psychedelic journey, in particular around the peak that occurs about two hours in or so.

对我来说，“放手，体验尽可能多的焦虑，这就是这个过程的一部分”是不公平的。是的，放手，再次，在空中引用中，似乎对于一个人的迷幻之旅体验很重要，特别是在大约两个小时左右发生的高峰期。

However, extreme levels of anxiety seem inversely correlated or negatively correlated, would be the better way to put it, with the positive therapeutic outcome or relief from depression.

然而，极端的焦虑水平似乎与积极的治疗结果或抑郁症的缓解呈负相关或负相关，这是更好的说法。

So this takes us back to all of the things we've been talking about thus far, not just the chemistry and biological action of psilocybin, but the key importance of getting dosage right, the key importance of making sure that you're in a safe environment, but also one in which the guides really know what they're doing.

因此，这让我们回到了迄今为​​止我们一直在讨论的所有事情，不仅仅是裸盖菇素的化学和生物作用，还有正确剂量的关键重要性，确保您处于安全环境的关键重要性，而且导游真正知道他们在做什么。

I think this is one of the biggest and most important reasons for having well-trained guides who really understand the contour of the psychedelic journey, but are also trained in how to help somebody with their anxiety in real-time while they're under the effects of psilocybin.

我认为这是拥有训练有素的导游的最大和最重要的原因之一，他们真正了解迷幻之旅的轮廓，但也接受过如何在人们受到裸盖菇素影响时实时帮助他们缓解焦虑的培训。

And of course, to help people integrate those feelings of high anxiety and maybe guide them back down to a calmer state during the psychedelic session itself.

当然，帮助人们整合那些高度焦虑的感觉，并可能在迷幻治疗期间引导他们回到更平静的状态。

And here I can just mention some unpublished data and studies, and again, these are very preliminary, but through discussions with Dr.

在这里我只能提到一些未发表的数据和研究，再说一次，这些都是非常初步的，但是通过与博士的讨论。

Matthew Johnson, who's running these psilocybin and other sorts of psychedelic trials at Johns Hopkins He and I discussed the importance of having a real-time tool to adjust anxiety while under the influence of psychedelics like psilocybin, and there he asked, and they've started to incorporate, is my understanding, some of the real-time respiration tools, that is breathing tools, that we know based on work in my laboratory, Dr. David Spiegel's laboratory, can reduce anxiety very quickly in real time, and that involves the use of the so-called physiological sigh.

马修·约翰逊（Matthew Johnson）在约翰·霍普金斯大学进行了这些迷幻药和其他类型的迷幻药试验，他和我讨论了在迷幻药（如裸盖菇素）的影响下拥有一个实时工具来调整焦虑的重要性，他问，他们已经开始整合，我的理解是，一些实时呼吸工具，即呼吸工具，我们根据我的实验室（大卫·斯皮格尔博士的实验室）的工作知道，可以实时快速减少焦虑，这涉及使用所谓的生理叹息。

I've talked a lot about this before on previous podcasts, so rather than explain it to you again here now, we'll put a link to the physiological sigh.

我之前在之前的播客中已经讨论过很多这个问题，所以我们不再在这里再次向您解释，而是添加一个指向生理叹息的链接。

I do a demonstration of it in the show note captions.

我在节目注释标题中对其进行了演示。

I'll also link to a recent paper that we published in the Cell Reports Medicine.

我还将链接到我们最近在《细胞报告医学》上发表的一篇论文。

This was a collaborative work that my laboratory did with Dr.

这是我的实验室与 Dr. 的合作工作。

David Spiegel's laboratory at Stanford School of Medicine, showing that the physiological sigh is, among the different deliberate respiration techniques, one of the fastest and most effective ways to reduce levels of autonomic arousal, AKA anxiety or stress.

斯坦福大学医学院的大卫·斯皮格尔实验室表明，在不同的深思熟虑的呼吸技术中，生理叹息是降低自主神经唤醒（又名焦虑或压力）水平最快、最有效的方法之一。

And Dr. Matthew Johnson's laboratory has started to incorporate physiological sighs within these psychedelic sessions as a tool that the guides can refer people to before the session begins, teaching it to them so they realize they can calm themselves down if necessary in real time.

马修·约翰逊博士的实验室已经开始将生理叹息纳入这些迷幻课程中，作为引导者可以在课程开始前向人们推荐的工具，向他们教授它，以便他们意识到如果有必要，他们可以实时让自己平静下来。

It works the first time.

第一次就可以了。

It works every time.

每次都有效。

This is not because it's some magic breathing technique that I created.

这并不是因为这是我创造的某种神奇的呼吸技巧。

It certainly is not.

当然不是。

This is a naturally occurring pattern of breathing that occurs in sleep and in waking, but that when done deliberately, leads to very rapid and quite significant decreases in stress and anxiety.

这是一种自然发生的呼吸模式，发生在睡眠和清醒时，但如果有意识地进行，会导致压力和焦虑非常快速且显着地减少。

And then when people are inside of the psychedelic session, if they feel their anxiety levels are going too high, they're heading toward what might be called a quote, unquote, "bad trip," they're starting to panic or really think they're going to have a panic attack or die.

然后，当人们处于迷幻状态时，如果他们觉得自己的焦虑水平太高，他们就会走向所谓的引用、不引用、“糟糕的旅行”，他们开始恐慌，或者真的认为自己会惊恐发作或死亡。

Again, the subjective experience is going to be layered on top of the physiological experience of one's heart rate being really elevated, so stress and agitation.

同样，主观体验将叠加在心率真正升高的生理体验之上，因此压力和焦虑。

By using the physiological sigh inside of the psychedelic session, Dr. Johnson's laboratory, and I believe at least one other laboratory, are starting to use breathing techniques such as the physiological sigh as a way for these people who are under the influence of psilocybin to self-direct their own calm and to bring that level of anxiety down so that they can continue to move through the peak and move through the other phases of the psychedelic journey in ways that could be most beneficial for them.

通过在迷幻过程中使用生理叹息，约翰逊博士的实验室，我相信至少还有一个其他实验室，正在开始使用呼吸技术，例如生理叹息，作为这些受裸盖菇素影响的人自我引导自己平静并降低焦虑程度的一种方式，以便他们能够继续度过高峰，并以对他们最有利的方式度过迷幻之旅的其他阶段。

So to close out the description of this really wonderful study, and by the way, it's another one from the Cardhardt-Harris Laboratory, about the subjective experience of ego dissolution or oceanic boundlessness, this mystical state, as so key as a component of a positive psilocybin journey.

因此，为了结束这项非常精彩的研究的描述，顺便说一句，这是卡哈特-哈里斯实验室的另一项研究，关于自我消解或海洋无边无际的主观体验，这种神秘的状态，作为积极的裸盖菇素之旅的一个组成部分非常关键。

I'll just read for you the final sentence of this paper because it captures it so well.

我将为您朗读本文的最后一句话，因为它很好地表达了这一点。

Quote, "It seems vital that appropriate consideration is paid to the importance of promoting a certain kind of experience, as the quality of that experience may be the critical determinant of therapeutic success." Now, before we move into what will be a very brief description of some of the other rewiring phenomena that psilocybin can induce, and then into some of the therapeutic applications of psilocybin as they relate to these recent, really exciting clinical trials for depression and addictive disorders and things of that sort.

引用：“适当考虑促进某种体验的重要性似乎至关重要，因为这种体验的质量可能是治疗成功的关键决定因素。”现在，在我们简要描述裸盖菇素可以诱导的其他一些重新布线现象之前，然后介绍裸盖菇素的一些治疗应用，因为它们与最近的抑郁症和成瘾性疾病等令人兴奋的临床试验有关。

I just want to cue everybody to a paper that I think many people will want to take a look at in thinking about psilocybin, and I'll provide a link to this paper as well in the show note captions.

我只是想提醒大家看一篇论文，我认为很多人在思考裸盖菇素时都会想看一下这篇论文，我也会在节目注释标题中提供这篇论文的链接。

This paper is entitled "Therapeutic Use of Psilocybin: Practical Considerations for Dosing and Administration."

本文的标题是“裸盖菇素的治疗用途：剂量和给药的实际考虑因素”。

And this is a wonderful paper because it really goes step by step through the pharmacology of psilocybin, of which you now understand a bit, but it goes into a bit more detail.

这是一篇很棒的论文，因为它确实一步一步地介绍了裸盖菇素的药理学，您现在已经了解了一点，但它更详细。

But then it also really nicely describes the contour of a psilocybin session and what's happening at the level of chemistry, early, middle, peak, and toward the end of the psilocybin session.

但它也很好地描述了裸盖菇素治疗的轮廓，以及裸盖菇素治疗的早期、中期、高峰和接近尾声时化学水平上发生的情况。

And then also importantly, gets into issues of dosage and translating from mushrooms to psilocybin itself to psilocyn.

然后同样重要的是，涉及剂量问题以及从蘑菇到裸盖菇素本身到裸盖菇素的转化问题。

Things I talked about earlier, but in a bit more detail, if you'd like to see that detail.

我之前谈过的事情，但如果你想了解细节的话，可以讲得更详细一些。

And then perhaps most importantly, there's a section on contraindications where it points out that, of course, women who are pregnant or breastfeeding, people who have a predisposition to psychosis, those people should really avoid the use of psilocybin and other psychedelics entirely.

也许最重要的是，有一个关于禁忌症的部分指出，当然，怀孕或哺乳的女性，有精神病倾向的人，这些人应该完全避免使用裸盖菇素和其他迷幻药。

It also talks about where the evidence is strong, moderate, and weak for the use of psilocybin for treatment of various disorders.

它还讨论了使用裸盖菇素治疗各种疾病的证据强、中、弱的情况。

And I can just summarize that very quickly because it's where we're going to head in a few minutes, which is that the most evidence for positive therapeutic outcomes in response to psilocybin taken and conducted in the manner that we've been describing today in terms of dosage and journey, set and setting, is for cancer-related depression, cancer-related anxiety, and treatment-resistant depression.

我可以很快地总结这一点，因为这是我们几分钟后要讨论的地方，即按照我们今天在剂量和旅程、设置和设置方面描述的方式服用裸盖菇素，取得积极治疗结果的最证据是针对癌症相关抑郁症、癌症相关焦虑症和难治性抑郁症。

That's where most of the evidence resides.

那是大部分证据所在。

There's also some evidence for the use of psilocybin journeys, and again, this is typically one or two psilocybin journeys spaced, in the cases of two journeys, anywhere from one to two weeks apart.

还有一些证据表明使用裸盖菇素旅行，而且，这通常是一两次裸盖菇素旅行，在两次旅行的情况下，间隔一到两周不等。

And again, with all of the same contour of supports and set and setting that we've been talking about today.

再说一次，我们今天讨论的支撑、设置和设置都具有相同的轮廓。

And there, there's some evidence for improvement in terms of outcomes in alcohol use disorder and dependence and tobacco addiction.

有一些证据表明酒精使用障碍、依赖性和烟草成瘾的结果有所改善。

And then finally, there's the least amount of evidence, although there is clinical trial support for relief or partial relief for obsessive compulsive disorder, cluster headaches and migraines, and demoralization due to AIDS diagnosis.

最后，尽管有临床试验支持缓解或部分缓解强迫症、丛集性头痛和偏头痛，以及因艾滋病诊断而导致的士气低落，但证据却是最少的。

Okay, so this paper has a lot of really interesting information in terms of different conditions, in terms of dosage, and again, contraindications and what's called adverse events.

好的，这篇论文有很多非常有趣的信息，涉及不同的条件、剂量、禁忌症和所谓的不良事件。

What sorts of bad things can and do happen as a consequence of psilocybin and other types of psychedelic journeys, both during and after those psilocybin or psychedelic sessions.

在裸盖菇素或其他类型的迷幻旅程期间和之后，裸盖菇素和其他类型的迷幻之旅可能会并且确实会发生什么样的坏事。

And we'll talk a bit more about this when we go into some of those clinical studies, because adverse reactions is always a key measure in any clinical study.

当我们进行一些临床研究时，我们会更多地讨论这一点，因为不良反应始终是任何临床研究中的关键指标。

So very soon, we'll get into the more recent clinical studies related to Psilocybin for the use of treating depression and some other conditions.

因此，很快，我们将进入与裸盖菇素相关的最新临床研究，用于治疗抑郁症和其他一些疾病。

But before we do that, I'd be remiss if I didn't talk about how psilocybin does and does not change the brain.

但在此之前，如果我不谈谈裸盖菇素如何改变大脑以及不改变大脑，那就是我的失职。

What is and what is not known about that.

关于这一点，什么是已知的，什么是未知的。

In fact, when I put out the call for questions about psilocybin, many of the questions related to these issues.

事实上，当我发出有关裸盖菇素的问题征集时，许多问题都与这些问题有关。

The first thing to understand is that a psilocybin journey is really a way to try and put that wedge under the boulder, as I described it, to try and invoke neuroplasticity of a particular kind.

首先要理解的是，裸盖菇素之旅实际上是一种尝试将楔子放在巨石下的方法，正如我所描述的那样，尝试调用特定类型的神经可塑性。

And in that way, it's kind of remarkable if you think about it, that everyone has different lives, different experiences.

从这个角度来看，如果你仔细想想，每个人都有不同的生活、不同的经历，这真是太了不起了。

Psychedelics, in this case psilocybin, are activating these brain networks that each of us has more broadly than they would normally be activated.

迷幻药，在这种情况下是裸盖菇素，正在激活我们每个人的大脑网络，这些网络比正常情况下激活的范围更广泛。

These are very abnormal patterns of thinking and perceiving and experiencing our emotional and physical life, et cetera.

这些是非常不正常的思维、感知和体验我们的情感和身体生活的模式，等等。

And yet, so often the outcomes are positive.

然而，结果往往是积极的。

Not always, but the outcomes are positive.

并非总是如此，但结果是积极的。

The experience is positive, even though it might have these anxiety moments or components within them.

这种体验是积极的，尽管它可能有这些焦虑时刻或其中的成分。

It's very important to understand that psilocybin and the journey, while important, are not really what all of this is about.

重要的是要了解裸盖菇素和旅程虽然很重要，但并不是这一切的真正含义。

It's really about neuroplasticity.

这确实与神经可塑性有关。

So researchers, in particular neuroscientists, are very intensely interested in understanding what sorts of neuroplasticity psilocybin creates.

因此，研究人员，特别是神经科学家，对了解裸盖菇素会产生什么样的神经可塑性非常感兴趣。

Because it turns out there are lots of different types or processes involved with neuroplasticity.

因为事实证明，神经可塑性涉及许多不同的类型或过程。

For instance, brain networks, behavior, thinking, emotion, et cetera, can change because of the addition of new neurons.

例如，大脑网络、行为、思维、情感等都会因为新神经元的添加而改变。

That's one form of neuroplasticity that's referred to as neurogenesis, the production of new neurons, most typically in the so-called dentate gyrus or other subregions of the hippocampus, a brain area involved in learning and memory.

这是神经可塑性的一种形式，被称为神经发生，即新神经元的产生，最常见的是所谓的齿状回或海马体的其他亚区域，海马体是涉及学习和记忆的大脑区域。

Neurogenesis in other regions of the adult human brain are exceedingly rare and, to be honest, may not occur at all.

成年人大脑其他区域的神经发生极其罕见，说实话，可能根本不会发生。

This is a debated area.

这是一个有争议的领域。

We could do an entire episode about this, but for the most part, neuroscientists don't really believe that your neocortex, your striatum, your cerebellum has that much neurogenesis that's related to learning and memory of new things or new experiences.

我们可以用一整集来讨论这个问题，但在大多数情况下，神经科学家并不真正相信你的新皮质、纹状体、小脑有那么多与学习和记忆新事物或新经历相关的神经发生。

And we don't actually think that occurs as a consequence of taking psilocybin either.

我们实际上也不认为这种情况是服用裸盖菇素的结果。

Now, some of you who are familiar with, for instance, the cerebellum might be saying, "Wait, what about granular cell proliferation in the cerebellum?" Or, "What about the rostral migratory stream from the subventricular zone where there are neuroblasts spitting out little new neurons that migrate into the nose to replenish the olfactory neuron population?" Yes, that's all true.

现在，你们中一些熟悉小脑的人可能会说，“等等，小脑中的颗粒细胞增殖怎么样？”或者，“来自脑室下区的喙部迁移流怎么样？那里的神经母细胞吐出一些新的神经元，这些神经元迁移到鼻子中以补充嗅觉神经元群？”是的，这都是真的。

That does occur.

这种情况确实发生了。

It's been observed in mice, it's been observed in monkeys, and to some extent it's been observed in humans.

人们在老鼠身上观察到了这种现象，在猴子身上也观察到了这种现象，在某种程度上也在人类身上观察到了这种现象。

But it's not, again, I repeat, it is not a prominent feature of learning and acquisition of new skills, new ideas, or new emotional states.

但我再说一遍，这并不是学习和获取新技能、新想法或新情绪状态的一个突出特征。

Perhaps the best-supported evidence for neurogenesis underlying new thoughts, experiences, abilities, emotions, et cetera, is the production of new neurons in that dentate gyrus subregion of the hippocampus, and that probably does occur in humans.

也许新思想、经验、能力、情感等背后的神经发生最有力的证据是海马齿状回亚区域新神经元的产生，而这可能确实发生在人类身上。

But neurogenesis is not really the dominant mode of changing neural circuitry in adult humans.

但神经发生并不是改变成年人神经回路的真正主要模式。

It might be a player in adolescence, in young childhood.

它可能是青春期、童年时期的玩家。

It is certainly a player before we are born when we are still in utero.

当我们还在子宫里的时候，它肯定是我们出生之前的一个玩家。

But then the brain is being wired up in many different ways, including the addition of new neurons and changing of connections.

但随后大脑会以多种不同的方式连接起来，包括添加新的神经元和改变连接。

All this is to say that while neurogenesis is a really sticky idea and it makes great headlines, the addition of new neurons is not really the way that the brain changes under psilocybin, other psychedelics, or just generally.

所有这一切都表明，虽然神经发生是一个非常棘手的想法，而且它经常成为头条新闻，但新神经元的添加并不是裸盖菇素、其他迷幻药或一般情况下大脑发生变化的方式。

It's perhaps responsible for maybe 1% to 2%, and I'm being generous there, of the rewiring events that are going to be most important for all of us.

对于我们所有人来说最重要的重新布线事件，它可能负责 1% 到 2%（我很慷慨）。

So we need to set that down and cement that there until further evidence comes out to the contrary.

因此，我们需要把这一点写下来并巩固下来，直到有更多相反的证据出现。

That's certainly where I, and here I feel comfortable speaking for the majority of neuroscientists out there, professional neuroscientists that is.

这当然是我的立场，在这里我很乐意为大多数神经科学家，即专业神经科学家发言。

The papers showing adult neurogenesis are interesting, but they don't really explain most of the plasticity that occurs in the adult human brain.

显示成人神经发生的论文很有趣，但它们并没有真正解释成人大脑中发生的大部分可塑性。

So if neurogenesis ain't it, what is?

那么，如果不是神经发生，那什么才是呢？

Well, it's very clear that psilocybin, other psychedelics, and any sort of behavioral or drug intervention that can induce neuroplasticity does so largely through the addition or strengthening of new neural connections or through the elimination or weakening of other neural connections.

很明显，裸盖菇素、其他致幻剂以及任何可以诱导神经可塑性的行为或药物干预在很大程度上是通过添加或加强新的神经连接或通过消除或削弱其他神经连接来实现的。

And if you look at the data exploring the mechanistic basis for psilocybin-induced neuroplasticity, it's mostly focused on animal brains, animal models, mice and rats in particular.

如果你看一下探索裸盖菇素诱导的神经可塑性机制基础的数据，你会发现它主要集中在动物大脑、动物模型、尤其是小鼠和大鼠上。

A little bit on primates, but mostly mice and rats, because that's where the interventions can be done of knockout animals, of imaging the brain in real time.

灵长类动物有一点，但主要是小鼠和大鼠，因为这是可以对基因敲除动物进行干预的地方，对大脑进行实时成像。

Of course, there are the beautiful studies of Robin Carhart-Harris and others exploring neuroplasticity at the level of brain imaging, at the level of ultrasound measurements, of how active are certain brain areas in humans, how extensive is the modularity or not extensive is the modularity, et cetera.

当然，罗宾·卡哈特-哈里斯（Robin Carhart-Harris）和其他人在大脑成像水平、超声测量水平上探索了神经可塑性，研究了人类某些大脑区域的活跃程度、模块性的广泛程度或不广泛程度等。

The stuff we talked about earlier.

我们之前讨论过的事情。

So in other words, there are neuroplasticity studies of the effects of psilocybin in humans.

换句话说，有关于裸盖菇素对人类影响的神经可塑性研究。

But in terms of underlying mechanisms of neuroplasticity, I think the predominant theory is that psilocybin induces neuroplasticity through the addition of novel connections in those pyramidal neurons of the frontal cortex, elsewhere in the cortex, and certainly also in the visual cortex.

但就神经可塑性的潜在机制而言，我认为主要的理论是裸盖菇素通过在额叶皮层的锥体神经元、皮层其他地方以及视觉皮层中添加新的连接来诱导神经可塑性。

Probably also subcortically as well below the cerebral cortex in areas like the thalamus, maybe even in the brain stem as well.

可能也在皮质下以及大脑皮层下方的丘脑等区域，甚至可能在脑干中。

And that those neuroplasticity events are structural and functional, and they involve a couple of basic events, the most prominent of which is the growth of dendrites.

这些神经可塑性事件是结构性和功能性的，它们涉及几个基本事件，其中最突出的是树突的生长。

Dendrites are those little branches or processes that come out of the neurons, not just the pyramidal neurons, but other neurons as well.

树突是从神经元发出的小分支或突起，不仅是锥体神经元，还包括其他神经元。

But since we're talking mainly about pyramidal neurons today, both the apical, those ones, the top, they're called the apical tufts.

但由于我们今天主要讨论锥体神经元，无论是顶端，那些顶部，它们都被称为顶端簇。

They're the ones that reach laterally to connect with other neurons, communicate with other neurons that we talked about before, as well as the dendrites that come out of the base of those pyramidal neurons.

它们横向延伸以与其他神经元连接，与我们之前讨论过的其他神经元以及从这些锥体神经元底部伸出的树突进行通信。

Those processes grow in response to psilocybin As well as the addition of what are called dendritic spines.

这些过程会响应裸盖菇素以及所谓的树突棘的添加而生长。

So the dendrites are the branches, the spines are these little protrusions that grow out.

所以树突就是树枝，刺就是长出来的小突起。

They actually, in here, I don't know if this is coincidence or not, again, I always say I wasn't consulted at the design phase, but these little protrusions actually look like little mushrooms.

他们其实在这里，我不知道这是不是巧合，再说一次，我总是说在设计阶段没有征求我的意见，但是这些小突起实际上看起来像小蘑菇。

They have a little stalk, and they have a little head, a little spine head, and those little spines.

它们有一个小茎，还有一个小头，一个小刺头，还有那些小刺。

So think of these as like little tiny mushroom-appearing, okay?

所以把它们想象成像小蘑菇一样，好吗？

They aren't actual mushrooms.

它们不是真正的蘑菇。

Okay?

好的？

The first person that puts in the comments, "Oh my goodness, I learned today that mushrooms grow out of our neurons when we take magic mushrooms," that is not what I'm saying.

第一个发表评论的人“天哪，我今天了解到，当我们服用迷幻蘑菇时，蘑菇会从我们的神经元中长出来”，这不是我所说的。

What I'm saying is that these little mushroom-shaped protrusions that we're calling dendritic spines do in fact grow out of dendritic branches of neurons when animals ingest psilocybin or are injected with psilocybin, and that those little mushroom-shaped protrusions are the sites of new excitatory connections, new locations for input from other neurons to activate those neurons that have those little mushroom shape protrusions.

我的意思是，当动物摄入裸盖菇素或注射裸盖菇素时，这些我们称之为树突棘的小蘑菇状突起实际上确实是从神经元的树突分支中生长出来的，并且这些小蘑菇状突起是新的兴奋性连接的位点，是来自其他神经元的输入的新位置，以激活具有这些小蘑菇状突起的神经元。

If you'd like to see examples of this, both movies and still shots, it's pretty remarkable.

如果你想看这方面的例子，无论是电影还是静态照片，这都是非常了不起的。

There's a paper that I'll provide a link to in the show note captions.

我将在节目注释标题中提供一篇论文的链接。

This was published in the journal Neuron, Cell Press journal, excellent journal, entitled "Psilocybin Induces Rapid and Persistent Growth of Dendritic Spines in the Frontal Cortex In Vivo." So these measurements were done in the mouse equivalent, more or less, of the prefrontal cortex.

这篇文章发表在《Neuron》杂志、《Cell Press》杂志上，优秀杂志，题为“Psilocybin Induces Rapid and Persistent Growth of Dendritic Spines in the Frontal Cortex In Vivo”。因此，这些测量或多或少是在相当于小鼠的前额叶皮层中进行的。

There's some interesting details in this paper, for instance, that those new connections persist.

本文中有一些有趣的细节，例如，这些新连接仍然存在。

So they don't just grow out during the psilocybin being active in the bloodstream and brain of the animal, they persist.

因此，当裸盖菇素在动物的血液和大脑中活跃时，它们不仅会生长，而且会持续存在。

Okay?

好的？

So this may, again, may explain some of the persistent changes that occur in people after psilocybin journeys.

因此，这可能再次解释了人们在裸盖菇素之旅后发生的一些持续变化。

They may too grow new spines.

它们也可能长出新的刺。

I should also mention that a reduction in the number of dendritic spines, these little mushroom-shaped protrusions, in the frontal cortex neurons of humans occurs in depressed patients.

我还应该提到，抑郁症患者的人类额叶皮层神经元中的树突棘（这些蘑菇状的小突起）数量减少。

We know that from postmortem tissue.

我们从死后组织中得知这一点。

And that drugs that relieve depression or that treatments, including behavioral treatments, that provide some relief from depression do seem to be correlated with increases in spine growth in frontal cortex neurons as well.

缓解抑郁症的药物或可以在一定程度上缓解抑郁症的治疗方法（包括行为治疗）似乎也与额叶皮层神经元脊柱生长的增加有关。

So this raises a very interesting idea, which is perhaps it's the growth of new connections, these new dendritic spines, in particular neurons, that's created by administration of psilocybin that explains the relief from depression that people experience.

因此，这提出了一个非常有趣的想法，这也许是新连接的生长，这些新的树突棘，特别是神经元，是通过服用裸盖菇素而产生的，这解释了人们经历抑郁症的缓解。

So this is just one paper, but it's one paper of a growing body of work showing that, yes, indeed, psilocybin induces both structural and functional plasticity in the human and animal brain.

所以这只是一篇论文，但它是越来越多的研究工作中的一篇论文，表明裸盖菇素确实会诱导人类和动物大脑的结构和功能可塑性。

It does that in the human brain at therapeutic doses of anywhere from 10 to 25, perhaps even 30 milligrams per session, one or two sessions.

它在人脑中发挥作用，治疗剂量为每次 10 至 25 毫克，甚至可能 30 毫克，一次或两次。

I should mention that the mouse studies tended to use quite high doses of psilocybin.

我应该提到的是，小鼠研究倾向于使用相当高剂量的裸盖菇素。

I was actually, I wasn't shocked, but I was somewhat wide-eyed for a moment to realize that most of the studies looking at changes in plasticity in the mouse brain in response to psilocybin use the equivalent of one milligram per kilogram of body weight, which is, if you do the math and you translate what we were talking about before in terms of dosages, I'll just spare you all the time, it's about double the sorts of dosages that are typically used in humans, maybe even triple in some cases.

事实上，我并不感到震惊，但我有点睁大了眼睛，意识到大多数针对裸盖菇素对小鼠大脑可塑性变化的研究都使用了相当于每公斤体重一毫克的剂量，也就是说，如果你计算一下，并用剂量来翻译我们之前谈论的内容，我就一直不打扰你了，它大约是人类通常使用的剂量的两倍，在某些情况下甚至可能是三倍。案例。

Now, it's often the case in animal studies because of the metabolism of animals being different, but also because seeing effects of drugs in animal studies can be difficult.

现在，在动物研究中经常出现这种情况，因为动物的新陈代谢不同，而且还因为在动物研究中观察药物的效果可能很困难。

They did use a dose response anywhere from zero to 0.25 to half to one to two milligrams per kilogram of psilocybin in the study, so they had a dose response curve, but focused mainly on this one milligram per kilogram dosage.

他们在研究中确实使用了每公斤裸盖菇素零到0.25到半到一到两毫克的剂量反应，因此他们有一条剂量反应曲线，但主要集中在每公斤一毫克的剂量上。

In any event, the point is that many of the studies that describe these pretty dramatic structural changes in the animal brain, most typically the mouse brain, in response to psilocybin, use dosages of psilocybin that, if translated to humans, would be about double the human therapeutic dose.

无论如何，要点是，许多研究描述了动物大脑（最典型的是小鼠大脑）对裸盖菇素的反应，所使用的裸盖菇素剂量，如果换算到人类身上，将是人类治疗剂量的两倍左右。

So that is something that we need to take into consideration.

所以这是我们需要考虑的事情。

Nonetheless, it's very clear that in both animal studies and humans, psilocybin is inducing both structural and functional changes in brain circuitry, and that in humans, the network connectivity is being changed dramatically.

尽管如此，很明显，在动物研究和人类研究中，裸盖菇素都会引起大脑回路的结构和功能变化，并且在人类中，网络连接性正在发生巨大变化。

We talked about those data earlier.

我们之前讨论过这些数据。

And that the underlying basis for that might be, again, might be, we don't know for sure, the addition of new dendritic spines on these pyramidal neurons that we've been talking about repeatedly throughout today's episode.

我们不确定，其根本基础可能是在这些锥体神经元上添加新的树突棘，我们在今天的节目中一直在反复讨论这一点。

Although neurogenesis, perhaps, and other modes of neuroplasticity, such as the elimination of certain connections, perhaps related to unhealthy maladaptive thoughts or feeling that a particular sad song is overwhelmingly sad.

尽管神经发生和神经可塑性的其他模式，例如某些联系的消除，可能与不健康的适应不良想法或感觉一首特定的悲伤歌曲非常悲伤有关。

It could be the case that those sorts of things change subjectively because of the removal of neural connections.

由于神经连接的消除，这些事情可能会主观地发生变化。

If you're going to think like a neurobiologist, or scientist for that matter, you don't ever want to think that one mechanism can explain all the effects of a given drug or a given experience.

如果你想像神经生物学家或科学家那样思考，你就不会想认为一种机制可以解释给定药物或给定经历的所有影响。

It's almost certainly likely to be the consequence of multiple mechanisms acting in parallel.

几乎可以肯定，这很可能是多种机制并行作用的结果。

And because I know there are people out there who would like to know even more about the neuroplasticity induced by psychedelics, including psilocybin, there's a wonderful review that I provide a link to in the show note captions entitled "Psychedelics and Neuroplasticity: A Systematic Review Unraveling the Biological Underpinnings of Psychedelics."

因为我知道有人想更多地了解迷幻药（包括裸盖菇素）引起的神经可塑性，所以我在节目笔记标题中提供了一篇精彩的评论链接，题为“迷幻药和神经可塑性：揭示迷幻药生物学基础的系统评论”。

This review is great because it goes a step beyond just psilocybin, psilocyn binding to the serotonin 2A receptor, and things like brain-derived neurotrophic factor.

这篇评论很棒，因为它超越了裸盖菇素、裸盖菇素与血清素 2A 受体结合以及脑源性神经营养因子等物质。

It actually talks a lot about the intracellular signaling and exactly how neurons change their excitability patterns based on this activation of the serotonin 2A receptor.

它实际上讨论了很多关于细胞内信号传导以及神经元如何根据血清素 2A 受体的激活改变其兴奋性模式。

It's probably more detail than most of you out there are interested in, but if you are interested in that level of detail, this is a wonderful open access review.

它可能比你们大多数人感兴趣的更详细，但如果您对这种程度的细节感兴趣，这是一篇精彩的开放获取评论。

So a few minutes ago, I talked about where there is strong, modest, and somewhat weak, or rather I should say minimal evidence for the therapeutic use of psilocybin to treat various disorders.

因此，几分钟前，我谈到了裸盖菇素治疗各种疾病的证据，其中有强的、适度的和有些弱的，或者更确切地说，我应该说的是最小的证据。

And across the board, it really appears that major depression and so-called intractable depression, in some cases Is where we're seeing the most exciting research to date.

总的来说，在某些情况下，重度抑郁症和所谓的顽固性抑郁症确实是我们迄今为止看到的最令人兴奋的研究。

Now, keep in mind that because of the Controlled Substances Act being invoked in 1970 in the United States, and because it was only just a few years ago, really, only about five years ago, that psychedelics, including psilocybin, received what's called breakthrough status at the FDA, that there are now a lot of clinical trials exploring how psilocybin can impact various things like mood disorders, addictive disorders, and so on.

现在，请记住，由于美国于 1970 年启动了《管制物质法案》，而且就在几年前，实际上，大约五年前，迷幻药（包括裸盖菇素）在 FDA 获得了所谓的突破性地位，因此现在有很多临床试验正在探索裸盖菇素如何影响情绪障碍、成瘾性疾病等各种疾病。

Prior to 2018, when that therapeutic breakthrough potential was established in the United States, I think a lot of people in the so-called psychedelics community had the sense and really the belief that these drugs had enormous potential, but they just weren't being explored that extensively.

2018 年之前，当这种治疗突破潜力在美国确立时，我认为所谓迷幻药界的很多人都有感觉并相信这些药物具有巨大的潜力，但只是没有得到广泛的探索。

So I do want to give a nod to the incredible researchers, such as Robin Carhart-Harris, but also Matthew Johnson, Roland Griffiths, Nolan Williams, and many others.

因此，我确实想向那些令人难以置信的研究人员致敬，例如罗宾·卡哈特-哈里斯，还有马修·约翰逊、罗兰·格里菲斯、诺兰·威廉姆斯和其他许多人。

Okay, I'm certainly not listing off everybody.

好吧，我当然不会列出所有人。

That would take hours.

那需要几个小时。

But those researchers have really pioneered both the legal efforts and the funding efforts and, most importantly, the research efforts defining the clinical data that I'm about to describe.

但这些研究人员确实开创了法律工作和资助工作，最重要的是，定义了我将要描述的临床数据的研究工作。

And here I'm going to summarize the clinical data in a bit of a top-contour fashion, just giving you the kind of highlights.

在这里，我将以一种顶部轮廓的方式总结临床数据，只是给你一些亮点。

We will, of course, provide links to the papers if you'd like to look into it further.

当然，如果您想进一步研究，我们会提供论文的链接。

But I'm only giving you the top contour because I've had the great fortune of having Matthew Johnson on this podcast before.

但我只给你提供了顶部轮廓，因为我之前很幸运地让马修·约翰逊（Matthew Johnson）参与过这个播客。

You can find that episode at hubermanlab.com.

您可以在 hubermanlab.com 上找到该剧集。

Just simply put Matt's name or psychedelics into the search function.

只需将马特的名字或迷幻药输入搜索功能即可。

It'll take you to that episode in all formats or links to all formats, rather.

它会带您转到所有格式的该剧集或所有格式的链接。

I've also had the great fortune of sitting down recently with Dr. Robin Carhart-Harris to talk about his work at University of California, San Francisco, on psilocybin, LSD, ayahuasca, and DMT as it relates to depression and other disorders.

最近，我也有幸与罗宾·卡哈特-哈里斯 (Robin Carhart-Harris) 博士坐下来谈论他在旧金山加利福尼亚大学关于裸盖菇素、LSD、死藤水和 DMT 的研究，因为它们与抑郁症和其他疾病有关。

And that episode, which also will be released at hubermanlab.com and on all platforms, YouTube, Apple, Spotify, really goes in-depth into these clinical studies and what those studies really look like.

该集也将在 hubermanlab.com 以及 YouTube、Apple、Spotify 等所有平台上发布，真正深入探讨了这些临床研究以及这些研究的真实情况。

Who's in the room, whether or not people just get one dose or two doses, how far apart those are separated.

谁在房间里，人们是否只接种了一剂或两剂，它们之间的距离有多远。

All of that is covered in extensive detail in that, what I found to be wonderful discussion with Dr.

所有这些都在其中进行了广泛的详细介绍，我发现与 Dr. 的讨论非常精彩。

Robin Carhart-Harris.

罗宾·卡哈特-哈里斯。

So if you're interested in all of the details as it relates to clinical application of psychedelics, stay tuned for that episode soon.

因此，如果您对与迷幻药临床应用相关的所有细节感兴趣，请尽快关注该集。

Again, you can find that at hubermanlab.com and on all platforms.

同样，您可以在 hubermanlab.com 和所有平台上找到它。

In the meantime, I would be remiss if I didn't include a bit of discussion about what has been observed in terms of using psilocybin journeys as a way to treat depression, because the data are just oh, so exciting.

与此同时，如果我没有对使用裸盖菇素旅程作为治疗抑郁症的方法所观察到的情况进行一些讨论，那就是我的失职了，因为这些数据实在是太令人兴奋了。

Again, these data really started to surface as the consequence of studies that were initiated around 2006 in just a few select laboratories, and then really picked up in terms of the number of laboratories and number of studies between 2018 and now.

同样，这些数据真正开始浮出水面，是 2006 年左右在少数选定的实验室中启动的研究的结果，然后从 2018 年至今，实验室数量和研究数量确实有所增加。

So what you'll notice is that most of the papers I'm about to describe were published in, for instance, phenomenal journals, "New England Journal of Medicine" in 2021, "New England Journal of Medicine," November 2022, "Journal of the American Medical Association Psychiatry," just very recently, 2021.

所以你会注意到，我即将描述的大多数论文都发表在一些杰出期刊上，例如 2021 年的《新英格兰医学杂志》、2022 年 11 月的《新英格兰医学杂志》、2021 年最近的《美国医学会精神病学杂志》。

So these are very recent papers.

所以这些都是最近的论文。

Essentially, all of these clinical studies involve either one or two psilocybin sessions.

本质上，所有这些临床研究都涉及一次或两次裸盖菇素疗程。

The dosages that were explored range from zero milligrams, so placebo, if you will, 10 milligrams, some cases 25 milligrams, in some cases, 30 milligrams.

探索的剂量范围从零毫克开始，所以安慰剂，如果你愿意的话，可以是 10 毫克，有些情况下是 25 毫克，有些情况下是 30 毫克。

And most typically, people received the same dosage for both sessions, if indeed they did both sessions.

最典型的是，如果人们确实进行了两次治疗，那么他们在两次治疗中都接受了相同的剂量。

However, there's at least one study looking at just one single episode of psilocybin administration.

然而，至少有一项研究只关注裸盖菇素的单次给药。

So this is the paper entitled, no surprise, "Single-Dose Psilocybin for Treatment-Resistant Episode of Major Depression." This was published in the "New England Journal of Medicine" in November of 2022.

毫不奇怪，这篇论文的标题是“单剂量裸盖菇素治疗难治性重度抑郁症”。该文章于2022年11月发表在《新英格兰医学杂志》上。

I'll just summarize the results of this single application study.

我将总结这个单一应用研究的结果。

They randomly assigned subjects who had treatment-resistant depression, so they'd resisted treatment to other things, to receive a single dose of a synthetic formulation of psilocybin.

他们随机分配患有难治性抑郁症（因此他们拒绝接受其他治疗）的受试者接受单剂量的裸盖菇素合成制剂。

So they're not eating mushrooms.

所以他们不吃蘑菇。

They're getting a synthetic dose of psilocybin, but the dose is known of either 25 milligrams, 10 milligrams, or 1 milligram, which was the control.

他们获得了合成剂量的裸盖菇素，但已知剂量为 25 毫克、10 毫克或 1 毫克（对照）。

And they received psychological support.

他们还得到了心理支持。

There were a number of different tests, subjective tests of depression, taken before and after the psilocybin journey.

在裸盖菇素之旅之前和之后进行了许多不同的测试，即抑郁症的主观测试。

They had about 75 to 79 participants in each group, again, at the three different doses, 25, 10, or 1 milligram.

每组约有 75 至 79 名参与者，剂量分别为 25、10 或 1 毫克三种不同剂量。

And they looked at the changes in these scores, these depression-related scores on these tests.

他们观察了这些分数的变化，这些测试中与抑郁症相关的分数。

There are many results from this paper one could summarize, but among the most important results I can summarize from the discussion, and here I'm paraphrasing, that the change in baseline levels of depression, that is, at week three following the psilocybin session, was significantly better.

这篇论文有很多结果可以总结，但我可以从讨论中总结出最重要的结果，在这里我解释一下，抑郁症基线水平的变化，即在裸盖菇素治疗后的第三周，明显更好。

That is, people experienced more relief, or more people experienced more relief from the 25-milligram dose than from the 1-milligram dose.

也就是说，25 毫克剂量的患者比 1 毫克剂量的患者经历了更多的缓解，或者更多的人经历了更多的缓解。

And this is important, there was no significant difference between the 10-milligram dose and the 1-milligram dose.

这很重要，10毫克剂量和1毫克剂量之间没有显着差异。

This really points to the fact that the 25 to 30-milligram dose that's used in the largest numbers of studies exploring treatment-resistant depression really seems to be, I don't want to say the best dose, but the most effective dose, at least in this clinical context, in this set and setting, and with this particular patient population.

这确实指出了这样一个事实：在探索难治性抑郁症的大量研究中使用的 25 至 30 毫克剂量似乎确实是，我不想说最好的剂量，而是最有效的剂量，至少在这个临床背景下，在这个组和环境中，以及对于这个特定的患者群体。

So we want to be careful to say that so that one doesn't just translate that 25 milligrams is better than 10 milligrams, although in this study, it was for sake of treatment-resistant depression relief.

因此，我们要小心地说，这样人们就不会简单地理解为 25 毫克比 10 毫克更好，尽管在这项研究中，这是为了缓解难治性抑郁症。

There were a number of other key aspects of this paper, in particular, the exploration of so-called adverse events, so things like headaches, propensity for self-harm, actual self-harm, anxiety, and so on.

这篇论文还有许多其他关键方面，特别是对所谓不良事件的探索，例如头痛、自残倾向、实际自残、焦虑等。

It's worth mentioning that there were adverse events in essentially every group.

值得一提的是，基本上每个组都出现了不良事件。

The number of adverse events was highest in the 25-milligram dose group, and this is observed in other studies as well.

25 毫克剂量组的不良事件数量最多，这在其他研究中也观察到。

With higher dosages, there tends to be greater relief from depressive symptoms, but also a greater chance for adverse events.

剂量越高，抑郁症状往往能得到更大的缓解，但发生不良事件的机会也越大。

Some of those adverse events can be quite severe, so feelings of suicidal ideation, et cetera.

其中一些不良事件可能非常严重，例如自杀意念等。

Some of them one could consider a little less severe, mild headache, or severe headache that was transient, or anxiety that was transient.

其中一些可以认为是不太严重的轻微头痛，或短暂的严重头痛，或短暂的焦虑。

Again, highly individual responses.

再次，高度个性化的反应。

We could go line by line and table by table through this paper, which we won't because there's a lot of data.

我们可以逐行、逐表地阅读本文，但我们不会这么做，因为数据量很大。

Again, we'll provide a link to this paper if you'd like to peruse it yourself.

同样，如果您想自己仔细阅读，我们将提供本文的链接。

It's fairly straightforward to read.

阅读起来相当简单。

That's one thing that's nice about these clinical trials, is they tend to be written in fairly non-technical language, although there's a little bit of technical language.

这些临床试验的好处之一是，它们往往是用相当非技术性的语言编写的，尽管有一点技术性的语言。

The important point is that a single dose of 25 milligrams of psilocybin provided significant relief from treatment-resistant depression in this particular patient population.

重要的一点是，单剂量 25 毫克的裸盖菇素可以显着缓解这一特定患者群体的难治性抑郁症。

But it is not the case that 100% of the people who took 25 milligrams of psilocybin experienced that relief.

但服用 25 毫克裸盖菇素的人并非 100% 都能感受到这种缓解。

However, the majority of them did.

然而，他们中的大多数人都这么做了。

Now, when you say majority in science, you really need to look to numbers.

现在，当你说科学占多数时，你确实需要看看数字。

And the reason I'm not telling you, "Oh, it was 75% or 60% or 50%," is because it depends on which time point people were analyzed.

我之所以没有告诉你，“哦，是 75%、60% 或 50%”，是因为这取决于对人们进行分析的时间点。

People were asked about their level of depression relief immediately after, one week after, two weeks after, three weeks after, and the degree of relief tended to change over time.

人们被问及抑郁症立即缓解、一周后、两周后、三周后的缓解程度，缓解程度往往会随着时间的推移而变化。

In fact, it tended to diminish over time, but it was also stable, or remarkably stable, I should say, at least by my read, in the 25-milligram dose group.

事实上，随着时间的推移，它往往会减少，但我应该说，在 25 毫克剂量组中，它也是稳定的，或者非常稳定，至少根据我的解读。

And that is summarized nicely in figure two of the paper, because they explored these people's levels of depression out to week 12, and they still saw a significant degree of depression relief 12 weeks after the single 25-milligram psilocybin dose session.

论文的图二很好地总结了这一点，因为他们研究了这些人直到第 12 周的抑郁程度，并且在单次 25 毫克裸盖菇素剂量疗程后 12 周后，他们仍然看到了显着程度的抑郁缓解。

So as I mentioned earlier, there are now about a dozen or so excellent studies, clinical trials exploring the use of single or two-session psilocybin treatment in that 25 to 30-milligram range, which seems to be the most effective dose for long-lasting relief from depression.

正如我之前提到的，现在有大约十几项优秀的研究和临床试验，探索使用 25 至 30 毫克范围内的单次或两次裸盖菇素治疗，这似乎是长期缓解抑郁症的最有效剂量。

Each one of those studies explored something different, as is important.

每一项研究都探索了不同的东西，这一点很重要。

Replication is also important, of course, in order to validate previous studies.

当然，为了验证以前的研究，重复也很重要。

But for instance, there have been comparisons of psilocybin versus SSRIs or other antidepressants.

例如，有人对裸盖菇素与 SSRIs 或其他抗抑郁药进行了比较。

There have been comparisons of psilocybin plus psychoanalysis or cognitive behavioral therapy versus cognitive behavioral therapy alone or psychoanalysis alone.

对裸盖菇素加精神分析或认知行为疗法与单独认知行为疗法或单独精神分析进行了比较。

And so there's a lot of evaluation now of the clinical outcomes and the statistical outcomes of these subjective measures and even some objective measures of neurochemistry where that's possible in terms of trying to understand if and how psilocybin is effective for the treatment of depression.

因此，现在对这些主观测量的临床结果和统计结果进行了大量评估，甚至对神经化学的一些客观测量进行了很多评估，试图了解裸盖菇素是否以及如何有效治疗抑郁症。

And the major takeaway is that indeed it does seem to be the case, and the numbers that I feel comfortable not throwing out there, but putting out to you reflect my conversation with Robyn Cardar Harris, again, that will be released soon at hubermanlab.com, as well as takeaways from what I would say are the six broadest studies, meaning they had the widest range of age groups, the broadest demographic in terms of the subjects, their backgrounds, their levels of education, men, women, ethnicity, et cetera.

主要的结论是，情况似乎确实如此，我觉得不把这些数字扔在那里，而是向你们展示，反映了我与 Robyn Cardar Harris 的对话，该对话很快将在 hubermanlab.com 上发布，以及我所说的六项最广泛的研究的结论，这意味着它们拥有最广泛的年龄组，在受试者、背景、教育水平、男性、女性、种族等方面有最广泛的人口统计数据等等。

And a lot of that can be summarized in the paper entitled "Effects of Psilocybin Assisted Therapy on Major Depressive Disorder." This was a particular randomized clinical trial, but in the discussion, I think they summarize it quite well, which is that if you look at the number of people who take this 25-milligram dose twice in sessions spaced about a week apart, what you will find is that anywhere from 60% to 75% of the people who have major depressive disorder, who do these psilocybin sessions in the proper setting, report a good experience with it, have minimal adverse events coming out of those sessions and in the weeks following.

其中很多内容可以在题为“裸盖菇素辅助治疗对重度抑郁症的影响”的论文中进行总结。这是一项特殊的随机临床试验，但在讨论中，我认为他们总结得很好，那就是，如果你观察一下两次服用这种 25 毫克剂量的人数，每次间隔大约一周，你会发现，60% 到 75% 的重度抑郁症患者，在适当的环境下进行裸盖菇素治疗，报告了良好的体验，在这些治疗中以及接下来的几周内出现了最少的不良事件。

Those people experience substantial positive relief from major depression in ways that other treatments that they'd explored, including antidepressant drugs, cognitive behavioral therapy, and other types of therapy alone could not provide.

这些人从重度抑郁症中获得了实质性的积极缓解，这是他们探索过的其他治疗方法（包括抗抑郁药物、认知行为疗法和其他类型的疗法）无法单独提供的。

Now, it's a general feature of these clinical trials focusing on psilocybin that people are asked to stop taking their antidepressants prior to participating in the trial.

现在，这些针对裸盖菇素的临床试验的一个普遍特征是要求人们在参加试验之前停止服用抗抑郁药。

It's also a general feature of these trials that people are encouraged to not suddenly start their antidepressant treatment immediately afterwards, because of course, that could confound the results of the psilocybin treatment.

这些试验的一个普遍特征是，鼓励人们不要在事后立即开始抗抑郁治疗，因为这当然可能会混淆裸盖菇素治疗的结果。

However, and this is a very important thing to note, all subjects were encouraged not to avoid taking those antidepressant medications if in fact their clinician felt that it was important for their immediate and long-term survival.

然而，值得注意的是，如果临床医生认为这对他们的近期和长期生存很重要，那么所有受试者都被鼓励不要避免服用这些抗抑郁药物。

So, no one should be reckless in thinking about what to add or delete from their drug protocol when dealing with depression.

因此，在治疗抑郁症时，任何人都不应该鲁莽地考虑在药物方案中添加或删除哪些内容。

All right?

好的？

The outcomes could be very severe in that case.

在这种情况下，后果可能会非常严重。

Nonetheless, we can paraphrase from the discussion of the paper I just mentioned, because it really highlights the incredible results that psilocybin applied in these particular therapeutic settings are providing.

尽管如此，我们可以解释一下我刚才提到的论文的讨论，因为它确实强调了裸盖菇素在这些特定治疗环境中应用所提供的令人难以置信的结果。

And here again, I'm paraphrasing.

在这里，我再次解释一下。

The present trial showed that psilocybin administered in the context of supportive psychotherapy consisting of approximately 11 hours of psychotherapy, so this is going to be two sessions of the psilocybin with proper therapeutic support, produced large, rapid, and sustained antidepressant effects.

目前的试验表明，裸盖菇素在支持性心理治疗的背景下施用，包括大约 11 小时的心理治疗，因此这将是两个疗程的裸盖菇素在适当的治疗支持下，产生了巨大、快速和持续的抗抑郁作用。

The effect sizes reported in the study were approximately 2.5 times greater than the effect sizes found in psychotherapy And more than four times greater than the effect sizes found in psychopharmacologic depression treatment studies.

该研究报告的效应大小大约是心理治疗中发现的效应大小的 2.5 倍，比精神药物抑郁症治疗研究中发现的效应大小高出四倍多。

In other words, four times the positive effect observed with typical SSRIs or other pharmacology of that sort.

换句话说，是典型 SSRI 或其他同类药理学观察到的积极效果的四倍。

These findings are consistent with the literature that showed that combined pharmacotherapy and psychotherapy were more efficacious in the treatment of major depressive disorder than either intervention alone.

这些发现与文献一致，文献表明药物治疗和心理治疗相结合在治疗重度抑郁症方面比单独使用任何一种干预措施更有效。

So again, this points to the fact that combining drug therapy with talk therapy, as it's often called, is going to be more effective than either treatment alone.

这再次表明，将药物疗法与通常所说的谈话疗法相结合，比单独使用任何一种疗法都更有效。

Here, the drug therapy is psilocybin therapy.

这里，药物疗法是裸盖菇素疗法。

And again, please don't take the fact that in these studies they tended to ask people to not take their antidepressant medication heading into the study as a sign that one should stop taking their antidepressant medication.

再次强调，请不要将这些研究中他们倾向于要求人们在研究中不要服用抗抑郁药物的事实视为人们应该停止服用抗抑郁药物的标志。

Rather, I think this study and other studies like it, again, which we'll provide links to in the show note captions that are discussed extensively in the episode with Dr. Carter Harris soon to come, really point to the incredible role that psilocybin can have in creating an experience inside of the session, the journey or the trip as it's called, as well as initiating neuroplastic events.

相反，我认为这项研究和其他类似的研究，我们将在即将到来的卡特·哈里斯博士的节目中广泛讨论的节目说明文字中提供链接，真正指出了裸盖菇素在创造会议、旅程或所谓的旅行中的体验以及引发神经可塑性事件方面所发挥的令人难以置信的作用。

Perhaps the addition of dendritic spines, maybe even some new neurons, maybe, although I don't think that's the predominant mode.

也许会增加树突棘，甚至可能会增加一些新的神经元，尽管我不认为这是主要模式。

But that leads to these more extensive connectivities in the brain, the so-called reduction in modular networks, enhanced activity in brain areas that normally wouldn't be talking to one another, but not doing that in any kind of haphazard way.

但这会导致大脑中更广泛的连接，即所谓的模块化网络的减少，增强大脑区域的活动，这些区域通常不会相互交谈，但不会以任何一种随意的方式进行交谈。

It really does seem that the one or two sessions of psilocybin that induce these feelings of ego dissolution, that induce these feelings of oceanic boundlessness, right?

看起来确实是一两次裸盖菇素会引发这些自我消解的感觉，引发这些海洋无边无际的感觉，对吗？

So mystical, right?

太神秘了，对吧？

And in many ways, it's what I find so incredible about psilocybin and other psychedelics is that despite the highly mystical, highly subjective, and still at this time, somewhat top contour understanding of how they might exert their effects.

从很多方面来说，我对裸盖菇素和其他迷幻药如此难以置信的地方在于，尽管人们对它们如何发挥作用的方式具有高度神秘性、高度主观性，而且目前仍然处于某种高度的了解。

You can highlight boldface and underline might there, right?

您可以突出显示粗体和下划线，对吗？

Because it hasn't really been firmly established what the exact cell biological rewiring events are.

因为还没有真正确定确切的细胞生物重连事件是什么。

But there is now what I would refer to as a center of mass of data that point to the fact that psilocybin, when taken in the appropriate set and setting, at the appropriate dosages, can invoke the sorts of neuroplasticity and changes in emotionality, in perceptual experience, not just during the psychedelic session, but for long periods of time after the psychedelic session that can provide really remarkable relief from things like major depression and perhaps other psychiatric issues as well.

但现在我所说的大量数据表明，裸盖菇素在适当的组合和环境下以适当的剂量服用时，可以在知觉体验中引发神经可塑性和情绪变化，不仅在迷幻治疗期间，而且在迷幻治疗后的很长一段时间内，可以真正显着缓解重度抑郁症和其他精神问题等问题。

And of course, I realize that many of you are listening to and/or watching this episode, and you're not necessarily depressed or thinking about psychedelics like psilocybin in the context of depression.

当然，我意识到你们中的许多人正在收听和/或观看这一集，并且您不一定感到沮丧或在抑郁的背景下思考诸如裸盖菇素之类的迷幻药。

I hope today's discussion allowed you to better understand how psychedelics and psilocybin in particular, because that's what we've been talking about, are able to exert these incredible effects that they seem to exert.

我希望今天的讨论能让您更好地了解迷幻药和裸盖菇素（尤其是裸盖菇素）如何发挥它们似乎发挥的令人难以置信的作用，因为这就是我们一直在谈论的内容。

This is not a call for everyone to run out and do psilocybin.

这并不是呼吁每个人都跑出去服用裸盖菇素。

It is absolutely not that.

绝对不是那样的。

It is, however, my attempt to really put a magnifying lens on this incredible area of research that's happening, not just in the context of clinical trials, but in the context of trying to understand how serotonin and how drugs like psilocybin, which in many ways mimic serotonin, and more particularly, the activation of particular receptors in the brain, like the serotonin 2A receptor.

然而，我试图真正把放大镜放在这个令人难以置信的研究领域上，不仅仅是在临床试验的背景下，而是在试图了解血清素和裸盖菇素等药物如何在许多方面模仿血清素，更具体地说，激活大脑中特定受体（如血清素 2A 受体）的过程中。

I mean, just sit back and think about that.

我的意思是，坐下来想一想。

The selective activation of this receptor, which is, by the way, associated with the expansion of the neocortex across evolution, didn't mention that before, but indeed it is.

顺便说一下，这种受体的选择性激活与新皮质在进化过程中的扩张有关，之前没有提到过，但确实如此。

How that can lead to enhanced ways of thinking, changed ways of thinking, actual learning inside of this short four-hour or six-hour session that we call the psilocybin journey.

这如何能够在这个短暂的四小时或六小时课程（我们称之为裸盖菇素之旅）中增强思维方式、改变思维方式和实际学习。

So as is often the case, perhaps as is always the case here on the Huberman Lab podcast, we did a deep dive into a topic.

因此，就像经常发生的情况一样，也许就像胡伯曼实验室播客上总是发生的情况一样，我们深入探讨了一个主题。

Today, into the topic of psilocybin, what it is, how it works, the different ways in which it changes brain circuitry, how it creates the experiences that we think of as the psilocybin journey, what the safety issues are, what the so-called set and setting are that can lend themselves to positive therapeutic outcomes.

今天，我们来谈谈裸盖菇素的主题，它是什么，它是如何工作的，它改变大脑回路的不同方式，它如何创造我们所认为的裸盖菇素之旅的体验，安全问题是什么，所谓的可以带来积极治疗结果的设置和环境是什么。

And in doing so, my goal was really to highlight several things.

这样做的目的是为了强调几件事。

First of all, I am very excited about the potential for psychedelics such as psilocybin to provide relief for mental health issues that to date have been very hard for people to access.

首先，我对迷幻药（如裸盖菇素）缓解心理健康问题的潜力感到非常兴奋，而迄今为止，人们很难获得这些药物。

In addition to that, I'm just fundamentally interested in the brain and how it works and how it can change this thing we call neuroplasticity.

除此之外，我只是对大脑及其工作原理以及它如何改变我们所说的神经可塑性感兴趣。

To me, neuroplasticity is the holy grail of the human nervous system.

对我来说，神经可塑性是人类神经系统的圣杯。

As far as we know, we are the animal that can have long-lasting neuroplasticity throughout the lifespan, and if it requires the use of compounds in a safe and controlled way, such as psilocybin, in order to achieve maximal plasticity in a short amount of time, that's exciting.

据我们所知，我们是一种在整个生命周期中都可以具有持久的神经可塑性的动物，如果需要以安全可控的方式使用裸盖菇素等化合物，以便在短时间内实现最大的可塑性，那就令人兴奋。

But of course, that also needs to be considered with all of the safety precautions in mind that we talked about earlier, including the fact that people who have a predisposition or who have psychosis or bipolar disorder or a relative that has psychosis or bipolar disorder, younger people, meaning people 25 years of age and younger, and really anyone who's not working with a dedicated and highly trained physician needs to be very cautious about these compounds as well.

当然，这还需要考虑到我们之前讨论过的所有安全预防措施，包括有倾向的人、患有精神病或双相情感障碍的人或患有精神病或双相情感障碍的亲戚、年轻人，即 25 岁及以下的人，以及任何没有与专门且训练有素的医生一起工作的人，也需要对这些化合物非常谨慎。

They're very exciting.

他们非常令人兴奋。

I think psilocybin is an exciting and super interesting compound for basic and clinical reasons, and for other reasons as well.

我认为出于基本和临床原因以及其他原因，裸盖菇素是一种令人兴奋且超级有趣的化合物。

But they are sharp blades, as we say, and with sharp blades, you can do incredible things, but you can also cut yourself very badly.

但正如我们所说，它们是锋利的刀片，有了锋利的刀片，你可以做出令人难以置信的事情，但你也可能会严重割伤自己。

So all those considerations need to be taken to mind.

因此，所有这些考虑因素都需要考虑在内。

So I consider the science and use of psilocybin to be an exciting but still preliminary area that I certainly am paying a lot of attention to, and I know there's a lot of excitement about, so stay tuned for the episode with Dr. Robin Carhart-Harris, and we will probably revisit psilocybin, and we will certainly revisit the other psychedelics and non-classical psychedelics, including LSD, DMT, 5-MeO-DMT, ketamine, MDMA, mescaline, and all the rest in future episodes as well.

因此，我认为裸盖菇素的科学和使用是一个令人兴奋但仍处于初步阶段的领域，我当然对此非常关注，而且我知道有很多令人兴奋的地方，所以请继续关注罗宾·卡哈特-哈里斯博士的这一集，我们可能会重新审视裸盖菇素，我们肯定会重新审视其他迷幻药和非经典迷幻药，包括LSD、DMT、5-MeO-DMT、氯胺酮、摇头丸、麦司卡林以及未来剧集中的所有其他药物。

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。

That's the best zero-cost way to support us.

这是支持我们的最佳零成本方式。

In addition, please subscribe to the podcast on both Apple and Spotify.

此外，请订阅 Apple 和 Spotify 上的播客。

And on both Apple and Spotify, you can also leave us up to a five-star review.

在 Apple 和 Spotify 上，您还可以给我们留下五星级的评价。

If you have questions for me or comments about this or any other podcasts or topics that you'd like me to cover or guests you would like me to interview on the "Huberman Lab" podcast, please put those in the comment section on YouTube.

如果您对本播客或您希望我报道的任何其他播客或主题或您希望我在“Huberman Lab”播客上采访的嘉宾有疑问或评论，请将这些内容放入 YouTube 的评论部分。

I do read all the comments.

我确实阅读了所有评论。

In addition, please check out the sponsors mentioned at the beginning and throughout today's episode.

此外，请查看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。

Not so much during today's episode, but on many previous episodes of the "Huberman Lab" podcast, we talk about supplements.

在今天的节目中，我们谈论的不是补充剂，而是在“Huberman Lab”播客的许多之前的节目中，我们谈论了补充剂。

While supplements aren't necessary for everybody, many people do derive tremendous benefit from them for things like enhancing the quality and duration of their sleep, for things like improving focus, and for hormone augmentation and much more.

虽然补充剂并不是每个人都需要的，但许多人确实从它们中获得了巨大的好处，例如提高睡眠质量和持续时间、提高注意力、增强荷尔蒙等等。

The "Huberman Lab" podcast is proud to have partnered with Momentous Supplements.

“Huberman Lab”播客很荣幸与 Momentous Supplements 合作。

If you'd like to learn more about the supplements discussed on the "Huberman Lab" podcast, you can go to livemomentous, spelled O-U-S, so livemomentous.com/huberman.

如果您想了解有关“Huberman Lab”播客中讨论的补充剂的更多信息，您可以访问 livemomentous，拼写为 O-U-S，即 livemomentous.com/huberman。

If you haven't already subscribed to our "Huberman Lab" Podcast Neural Network Newsletter, the Neural Network Newsletter is a completely zero-cost newsletter that includes summaries of podcast episodes and summaries of protocols, things like a toolkit for improving your sleep, a toolkit for improving focus, toolkit for neuroplasticity, toolkit related to deliberate cold or deliberate heat exposure, to fitness, to flexibility, and much more.

如果您还没有订阅我们的“Huberman Lab”播客神经网络时事通讯，神经网络时事通讯是完全零成本的时事通讯，其中包括播客剧集摘要和协议摘要、改善睡眠的工具包、改善注意力的工具包、神经可塑性工具包、与有意冷或有意热暴露、健身、灵活性相关的工具包等等。

Again, all zero cost.

再次强调，一切都是零成本。

Simply go to hubermanlab.com, go to the menu, scroll down to Newsletter, and provide your email.

只需访问 hubermanlab.com，进入菜单，向下滚动到新闻通讯，然后提供您的电子邮件即可。

We do not share your email with anybody, and again, the newsletter is completely zero cost.

我们不会与任何人分享您的电子邮件，而且，时事通讯完全是零成本。

And to see previous newsletters, you can simply scroll down a bit further on that Neural Network Newsletter page at hubermanlab.com, and you'll find downloadable PDFs, and you can just click on any of those PDFs, no signup required.

要查看以前的时事通讯，您只需在 hubermanlab.com 的神经网络时事通讯页面上进一步向下滚动，您就会找到可下载的 PDF，并且只需单击任何 PDF，无需注册。

And if you're not already following me on social media, it's hubermanlab on Instagram, Twitter, Facebook, and LinkedIn.

如果您还没有在社交媒体上关注我，请关注 Instagram、Twitter、Facebook 和 LinkedIn 上的 hubermanlab。

And on all those places, I discuss science and science-related tools, some of which overlaps with the content of the "Huberman Lab" podcast, but much of which is distinct from the content covered here on the "Huberman Lab" podcast.

在所有这些地方，我讨论了科学和科学相关的工具，其中一些与“Huberman Lab”播客的内容重叠，但其中大部分与“Huberman Lab”播客中涵盖的内容不同。

So again, it's hubermanlab on Instagram, Facebook, Twitter, and LinkedIn.

再说一遍，Instagram、Facebook、Twitter 和 LinkedIn 上都是 hubermanlab。

Thank you once again for joining me for today's discussion all about psilocybin.

再次感谢您参加今天有关裸盖菇素的讨论。

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。