The Science of MDMA & Its Therapeutic Uses: Benefits & 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 MDMA, sometimes referred to as ecstasy or Molly.

今天，我们讨论的是摇头丸，有时也称为摇头丸或莫莉。

MDMA stands for methylenedioxymethamphetamine.

MDMA 代表亚甲二氧基甲基苯丙胺。

That's right, you heard the word methamphetamine in there.

是的，你在那里听到了甲基苯丙胺这个词。

And MDMA has properties similar to methamphetamine, but also properties that are very distinct from methamphetamine.

MDMA 具有与甲基苯丙胺相似的特性，但也具有与甲基苯丙胺非常不同的特性。

Just as a side note, methamphetamine is a commonly used drug of abuse.

顺便说一句，甲基苯丙胺是一种常用的滥用药物。

It is an illicit drug, and it produces some of the greatest and fastest increases in the neuromodulator dopamine of any available drugs on the street or in the clinic.

它是一种非法药物，在街头或诊所的任何可用药物中，它对神经调节剂多巴胺的增加是最大和最快的。

And believe it or not, methamphetamine is prescribed as a prescription drug in some very limited clinical uses.

不管你相信与否，甲基苯丙胺在一些非常有限的临床用途中被作为处方药开出。

MDMA, methylenedioxymethamphetamine, has properties similar to methamphetamine in that it powerfully promotes the release of dopamine, and it is a stimulant.

MDMA，即亚甲二氧基甲基苯丙胺，具有与甲基苯丙胺类似的性质，能强力促进多巴胺的释放，是一种兴奋剂。

And yet it also powerfully controls the release of serotonin, and in doing so, makes MDMA a distinct category of compound from either classic psychedelics like psilocybin or LSD, which largely work on the serotonin system and tend to produce mystical experiences.

然而，它还能强有力地控制血清素的释放，从而使 MDMA 成为一种与裸盖菇素或 LSD 等经典致幻剂截然不同的化合物，后者主要作用于血清素系统，往往会产生神秘的体验。

And it's also distinct from pure stimulants such as methamphetamine, because MDMA, by producing big increases in both dopamine and serotonin, acts as what's called an empathogen.

它也与甲基苯丙胺等纯粹的兴奋剂不同，因为摇头丸可以大量增加多巴胺和血清素，起到所谓的共情剂的作用。

It actually can increase one sense of social connectedness and empathy, not just for other people, but for oneself.

它实际上可以增加一种社会联系感和同理心，不仅是对其他人，而且是对自己。

And in that way, MDMA is commonly used as a recreational drug, but also is now being tested and is achieving incredible early results in clinical trials for its use as an empathogen for the treatment of PTSD in clinical therapeutic settings.

因此，MDMA 通常被用作娱乐性药物，但现在也正在接受测试，并在临床试验中作为一种治疗 PTSD 的共情剂在临床治疗环境中取得了令人难以置信的早期结果。

I want to be very clear that at this point in time, June 2023, MDMA is still a Schedule I drug.

我想非常清楚地表明，在 2023 年 6 月的这个时间点，MDMA 仍然是一种附表 I 药物。

That is, it is highly illegal to possess or sell in the United States.

也就是说，在美国拥有或出售是高度非法的。

And today we are going to talk about some of the path to legality that's underway.

今天我们将讨论一些正在进行的合法化之路。

We are also going to talk about the history of MDMA and why it became illegal.

我们还将讨论 MDMA 的历史以及它为何成为非法。

And we are going to talk about the key difference between recreational use and therapeutic use, and the important components of the studies exploring MDMA in the clinical setting for the treatment of PTSD.

我们将讨论娱乐用途和治疗用途之间的主要区别，以及探索 MDMA 在临床环境中治疗 PTSD 的研究的重要组成部分。

So during today's discussion, we will talk about what MDMA really is, how it works at the level of neurons, which brain circuits it activates and deactivates.

因此，在今天的讨论中，我们将讨论 MDMA 到底是什么、它如何在神经元层面发挥作用、它激活和停用哪些大脑回路。

And in doing so, you will come to understand why it is so exciting as a treatment for PTSD.

在这样做的过程中，您将会明白为什么它作为创伤后应激障碍的治疗方法如此令人兴奋。

We will also, of course, talk about the results of these clinical trials using MDMA for the treatment of PTSD.

当然，我们还将讨论这些使用 MDMA 治疗 PTSD 的临床试验的结果。

They are incredibly exciting.

他们非常令人兴奋。

In fact, the field of psychiatry has never before seen the kind of success in treatment of PTSD with any other compound that they are seeing and achieving with the appropriate safe use of MDMA.

事实上，精神病学领域以前从未见过用任何其他化合物治疗创伤后应激障碍（PTSD）所取得的成功，并通过适当安全地使用 MDMA 来实现。

And when I say appropriate, that means in conjunction with nine therapy sessions.

当我说适当时，这意味着需要结合九次治疗课程。

So this is an area that really deserves some time for us to discuss because, again, there is a distinct difference between the recreational and the therapeutic use of MDMA.

因此，这是一个确实值得我们花一些时间讨论的领域，因为 MDMA 的娱乐用途和治疗用途之间存在明显的区别。

We will also talk about the toxicity of MDMA.

我们还将讨论 MDMA 的毒性。

This is a very important issue because many of you have perhaps heard that MDMA, quote, unquote, "puts holes in your brain" or kills serotonin neurons or kills dopamine neurons.

这是一个非常重要的问题，因为你们中的许多人可能听说过 MDMA，引用或取消引用，“在你的大脑中留下漏洞”或杀死血清素神经元或多巴胺神经元。

And indeed, MDMA, because of its similarity to methamphetamine, which is highly neurotoxic, MDMA can be neurotoxic.

事实上，MDMA 与具有高度神经毒性的甲基苯丙胺相似，因此 MDMA 可能具有神经毒性。

However, there are ways to use MDMA therapeutically that avoid its toxicity, and yet there are still questions about its toxicity and its long-term effects, both after acute use, meaning just one to three times, as well as chronic use, meaning people who have taken it many, many times.

然而，在治疗上使用MDMA有一些方法可以避免其毒性，但其毒性和长期影响仍然存在疑问，无论是在急性使用（即仅一到三次）还是慢性使用（即人们服用了很多次）之后。

We'll talk about the spacing between sessions of MDMA.

我们将讨论 MDMA 疗程之间的间隔。

We will talk about dosages.

我们将讨论剂量。

We will also talk about things that people do and that can be done to offset some of the potential toxicity of MDMA.

我们还将讨论人们所做的事情以及可以做的事情来抵消 MDMA 的一些潜在毒性。

So by the end of today's discussion, you will have a thorough understanding of what MDMA is, what it isn't, what is known about what it does, what is known about what it doesn't do, as well as some of the still outstanding questions about MDMA that remain to be resolved.

因此，在今天的讨论结束时，您将彻底了解 MDMA 是什么、它不是什么、它的作用和不作用的已知情况，以及有关 MDMA 的一些仍悬而未决的问题有待解决。

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 MDMA.

我们来谈谈摇头丸。

MDMA or ecstasy is a fascinating compound.

MDMA 或摇头丸是一种令人着迷的化合物。

And I say fascinating from the perspective of its chemical structure, which is highly unusual.

我说的是从其化学结构的角度来看令人着迷，这是非常不寻常的。

I say fascinating because it has an incredible set of subjective effects in terms of how it makes people feel, and it has a fascinating history.

我说令人着迷是因为它在给人的感觉方面具有一系列令人难以置信的主观效果，并且它有一段令人着迷的历史。

So let's just briefly start with the history of MDMA.

让我们简单地从 MDMA 的历史开始吧。

MDMA was synthesized by the drug company Merck in the early 1900s, but it actually was never applied to any particular clinical use, and it wasn't really explored much in any laboratories at all.

MDMA 是由制药公司默克 (Merck) 在 1900 年代初合成的，但实际上从未应用于任何特定的临床用途，并且在任何实验室中都没有进行过真正的探索。

And then it was later rediscovered by a guy named Alexander Shulgin, who was a bit of a renegade drug chemist who was designing different drugs for the purpose of understanding their subjective effects on humans.

后来它被一个名叫亚历山大·舒尔金（Alexander Shulgin）的人重新发现，他是一位叛逆的药物化学家，他正在设计不同的药物，以了解它们对人类的主观影响。

So there's a long history of Shulgin designing drugs, he was, after all, a chemist, and then taking those drugs himself.

所以舒尔金设计药物的历史很长，毕竟他是一名化学家，然后自己服用这些药物。

And then if he liked the effects of a particular drug, or rather if he thought that it had potential clinical utility, he would give it to his wife.

然后，如果他喜欢某种药物的效果，或者更确切地说，如果他认为它具有潜在的临床用途，他就会把它送给他的妻子。

Then she would give him her notes about those drugs, and then they would share them with their friends.

然后她会给他关于这些药物的笔记，然后他们会与朋友分享。

And it was a small group of friends who consisted of therapists and physicians.

这是一小群由治疗师和医生组成的朋友。

So this was a really underground kind of operation.

所以这是一次真正的地下行动。

It was technically not illegal when it started because MDMA wasn't illegal when it started.

从技术上讲，它在出现时并不违法，因为摇头丸在出现时并不违法。

But over the several decades that Shulgin and his wife and this group were doing this kind of exploration, MDMA did become illegal, and he fell under, let's just say, scrutiny by the DEA.

但在舒尔金和他的妻子以及这个小组进行这种探索的几十年里，摇头丸确实变得非法，他受到了缉毒局的审查。

Now, here's the important thing to understand about MDMA and its history.

现在，了解 MDMA 及其历史的重要事项如下。

First of all, MDMA is a synthetic compound.

首先，MDMA是一种合成化合物。

As far as we know, it does not exist anywhere in nature.

据我们所知，它在自然界中不存在。

So unlike similar compounds such as mescaline, because MDMA and mescaline are very similar in their chemical properties and to some extent, their subjective properties.

因此，与麦斯卡林等类似化合物不同，因为 MDMA 和麦斯卡林的化学性质非常相似，在某种程度上，它们的主观性质也非常相似。

Unlike mescaline, which can be found in the plant kingdom, or LSD, which comes from ergot, or psilocybin, which of course can be found in magic mushrooms, MDMA is a unique chemical in that, again, as far as we know, only exists in its synthetic form.

与植物界中存在的麦斯卡林、来自麦角的迷幻剂、或迷幻蘑菇中存在的裸盖菇素不同，MDMA 是一种独特的化学物质，据我们所知，它只以合成形式存在。

It is human-made.

它是人造的。

And as we get into the chemical effects and the subjective effects of MDMA a little bit later in the episode, I think you'll understand why it is such a unique and to some extent, exciting compound from the perspective of clinical treatment.

当我们在本集中稍后讨论 MDMA 的化学作用和主观作用时，我想您会理解为什么从临床治疗的角度来看，它是一种如此独特且在某种程度上令人兴奋的化合物。

Put differently, there's really no other compound that we know of in nature or in the pharmaceutical industry shelf, or options of drugs that are prescription drugs that produce the kinds of effects that MDMA does.

换句话说，我们所知道的自然界中或制药行业货架上确实没有其他化合物，也没有处方药可以产生 MDMA 那样的效果。

And by the way, if you're interested in the story of Alexander Shulgin and the drugs he synthesized, and the group that he built up to take these drugs and try them, and actually had several members of this group using these drugs in therapy with their patients for a long period of time, both before and after MDMA became illegal.

顺便说一句，如果您对亚历山大·舒尔金和他合成的药物的故事感兴趣，以及他建立的服用这些药物并尝试它们的小组，实际上这个小组的几名成员在摇头丸成为非法之前和之后都在很长一段时间内使用这些药物治疗患者。

There's a wonderful book called "PIKHAL." That stands for P-I-K-H-A-L.

有一本很棒的书，名叫《PIKHAL》。这代表 P-I-K-H-A-L。

"PIKHAL" is the title of the book which Shulgin wrote, which describes his discovery of MDMA.

“PIKHAL”是舒尔金所写的书的标题，书中描述了他对摇头丸的发现。

I confess it also describes the synthesis of MDMA, and for that reason, was a book that for a long time was not available, but is now available again in audible form and in printed form.

我承认它还描述了 MDMA 的合成，因此，这本书很长一段时间都没有出版，但现在又以可听形式和印刷形式提供。

PIKHAL stands for Phenethylamines I Have Known And Loved.

PIKHAL 代表我所了解并喜爱的苯乙胺。

Phenethylamines is the category of drug for which MDMA belongs to.

苯乙胺是 MDMA 所属的一类药物。

And it's a long book, but a very interesting one, both from the perspective of understanding the history of MDMA and what MDMA is and the effects that it produces.

这是一本很长的书，但从理解 MDMA 的历史、MDMA 是什么及其产生的影响的角度来看，都是一本非常有趣的书。

But it's also an interesting book because it will teach you a lot about the history of the pharmaceutical industry, the war on drugs in the United States, and the interaction between illegal drug exploration and drugs for clinical treatment of psychiatric challenges.

但这也是一本有趣的书，因为它会教你很多关于制药业的历史、美国的​​禁毒战争，以及非法药物探索和临床治疗精神疾病药物之间的相互作用。

So right now, this is a very important issue because MDMA is currently granted breakthrough status, which means it's now something that scientists and clinicians can study if they have authorization to do that.

所以现在，这是一个非常重要的问题，因为 MDMA 目前已被授予突破性地位，这意味着如果科学家和临床医生获得授权，他们现在可以研究它。

It is, as I mentioned earlier, still a Schedule I drug, so it's illegal to possess unless you are one of these scientists who has been granted permission to study it in the clinical setting or the laboratory setting.

正如我之前提到的，它仍然是一种附表一药物，因此拥有它是非法的，除非您是已获准在临床环境或实验室环境中研究它的科学家之一。

And right now, we are on the cusp of MDMA becoming legal, but again, it is not yet legal.

现在，我们正处于 MDMA 合法化的风口浪尖，但它仍然不合法。

And this is something I'm going to touch back on a few times during today's episode.

这是我将在今天的节目中多次提及的内容。

Later, for instance, when we talk about the potential toxicity of MDMA, its ability potentially to kill neurons, and the neurons it has been hypothesized to kill are neurons of the serotonin and dopamine type, so this is something you would not want.

例如，稍后，当我们谈论 MDMA 的潜在毒性时，它有可能杀死神经元的能力，而它被假设杀死的神经元是血清素和多巴胺类型的神经元，所以这是你不想要的。

Let's just recall that killing off of or death of dopamine neurons is the underlying basis for Parkinson's disease, which is a movement disorder where people have difficulty generating smooth movements, and in very severe form, they can't move at all.

让我们回想一下，多巴胺神经元的杀死或死亡是帕金森病的根本原因，帕金森病是一种运动障碍，人们很难产生平稳的运动，在非常严重的情况下，他们根本无法运动。

They sort of become locked in to some extent, and it also has cognitive effects, so you don't want to lose dopamine neurons.

它们在某种程度上被锁定，而且它也有认知作用，所以你不想失去多巴胺神经元。

And loss of serotonergic neurons is known to impact mood negatively, mood regulation negatively, et cetera.

众所周知，血清素能神经元的丧失会对情绪、情绪调节等产生负面影响。

The story of MDMA and its potential neurotoxicity comes slam right up against this issue of legality, and what we'll get into a little bit later is that there has been a sort of race in the scientific community consisting of two groups.

MDMA 的故事及其潜在的神经毒性直接与合法性问题发生了冲突，稍后我们将讨论的是，科学界中存在着由两个群体组成的某种竞赛。

One set of groups trying to establish the toxicity of MDMA so that it does not become legal again, and another group trying to establish the utility and the lack of toxicity in MDMA so that it does become legal again for the treatment of PTSD.

一组小组试图确定 MDMA 的毒性，以使其不再合法化，另一组则试图确定 MDMA 的效用和无毒性，以便其在治疗 PTSD 方面再次合法化。

So even though the story, PIKHAL, relates to events that took place largely in the 1970s, '80s, and '90s, right now, MDMA and its toxicity or lack of toxicity, its legality or lack of legality, are really key issues.

因此，尽管《PIKHAL》这个故事主要涉及 20 世纪 70 年代、80 年代和 90 年代发生的事件，但现在，MDMA 及其毒性或无毒性、其合法性或不合法性，才是真正的关键问题。

So as you're listening to this, I'm giving you a real-time blow-by-blow of what led up to where we are now, but we will also want to think about how what's happening right now, including the description of these data on MDMA, may or may not impact the potential legal status of MDMA.

因此，当您收听此内容时，我将向您实时详细介绍导致我们现在所处位置的原因，但我们也会想一下现在发生的事情，包括对 MDMA 的这些数据的描述，可能会或可能不会影响 MDMA 的潜在法律地位。

Okay, so what is MDMA?

好的，那么什么是 MDMA？

MDMA is 3,4-methylenedioxymethamphetamine, but unless you're a chemist, that's not going to mean much to you, nor should it.

MDMA 是 3,4-亚甲二氧基甲基苯丙胺，但除非您是化学家，否则这对您来说意义不大，也不应该。

MDMA has some very interesting properties.

MDMA 有一些非常有趣的特性。

The first of which is that methamphetamine component, which because it's a methamphetamine and acts like other amphetamines, what it does is it blocks the reuptake of dopamine from neurons after dopamine is released.

第一个是甲基苯丙胺成分，因为它是一种甲基苯丙胺，作用与其他苯丙胺类似，它的作用是在多巴胺释放后阻止神经元对多巴胺的再摄取。

So for those of you that heard the episode that I did on drugs to treat ADHD, I discussed the biology and mechanisms of drugs like Adderall and Vyvanse, which basically are either combinations of amphetamines or single types of amphetamines that have either a quick release or a long release.

因此，对于那些听过我关于治疗 ADHD 药物的报道的人，我讨论了 Adderall 和 Vyvanse 等药物的生物学和机制，这些药物基本上要么是安非他明的组合，要么是具有快速释放或长期释放的单一类型的安非他明。

Now MDMA, because it has this methamphetamine component, prevents the reuptake of dopamine, and in doing so, creates net increases in dopamine.

现在，摇头丸由于含有甲基苯丙胺成分，可以防止多巴胺的再摄取，从而导致多巴胺的净增加。

So for those of you that don't have a background in neurobiology, let me just briefly explain.

因此，对于那些没有神经生物学背景的人，让我简单解释一下。

I'll make this very simple.

我会让这变得非常简单。

Neurons or nerve cells release chemicals at their sites of communication, which are called synapses.

神经元或神经细胞在其通讯部位（称为突触）释放化学物质。

Synapses are little gaps between neurons, and what happens is the neurons spit out these little spherical balls, which we call vesicles or vesicles, depending on where in the world you live.

突触是神经元之间的小间隙，神经元会吐出这些小球，我们将其称为囊泡或囊泡，具体取决于您生活在世界的哪个地方。

They'll either be called vesicles or vesicles.

它们要么被称为囊泡，要么被称为囊泡。

And those little vesicles contain neurotransmitter, or what's technically referred to as a neuromodulator.

这些小囊泡含有神经递质，或者技术上称为神经调节剂。

Dopamine is a neuromodulator.

多巴胺是一种神经调节剂。

It can modulate the activity of other neurons.

它可以调节其他神经元的活动。

It can either increase or decrease the activity of other neurons.

它可以增加或减少其他神经元的活动。

Now, at the end of the neuron, what we call the axonal bouton, okay, axon is the wire component of the neuron that can reach to another site in the brain and then release the neurotransmitter and neuromodulator there.

现在，在神经元的末端，我们所说的轴突，好吧，轴突是神经元的导线组件，可以到达大脑的另一个部位，然后在那里释放神经递质和神经调节剂。

At those axonal boutons, which are the sites of release, the vesicles literally fuse with the edge of the neuron and vomit their neuromodulator out into the synapse, and then the neuromodulator, in this case, dopamine, will bind to receptors on the postsynaptic side.

在这些轴突按钮上，也就是释放的部位，囊泡实际上与神经元的边缘融合，并将它们的神经调节剂吐到突触中，然后神经调节剂，在这种情况下是多巴胺，将与突触后侧的受体结合。

That means to another neuron.

这意味着另一个神经元。

And then depending on how much binds and depending on what else is going on in that local neighborhood of neuronal connections, the neuron will either increase its neural activity and itself release neuromodulator or neurotransmitter someplace else, so sort of a chain reaction, or else it will suppress its activity and the flow of communication from one neuron to the next will be stopped.

然后，根据结合的程度以及神经元连接的局部邻域中发生的其他情况，神经元要么会增加其神经活动，并在其他地方释放神经调节剂或神经递质，这样一种连锁反应，要么会抑制其活动，并且从一个神经元到下一个神经元的通信流将停止。

Okay?

好的？

So MDMA doesn't prevent the release of dopamine at the synapse.

因此，MDMA 不会阻止突触释放多巴胺。

It does quite the opposite.

它的作用恰恰相反。

It actually prevents the sucking up of the dopamine that's been released and that does not bind to the receptors.

它实际上阻止了已释放且不与受体结合的多巴胺的吸收。

So basically what it does is it blocks these things called dopamine transporters, and the transporters are the things that suck back up the dopamine that's been released that has not bound to receptors.

所以基本上它的作用是阻止这些被称为多巴胺转运蛋白的东西，而转运蛋白是吸回已释放的未与受体结合的多巴胺的东西。

So because it blocks that sucking up process, there's more dopamine around in the synapse to hang out and then bind to receptors once some become available.

因此，因为它阻止了吸收过程，所以突触周围有更多的多巴胺悬挂，然后一旦有一些受体可用，就会与受体结合。

Okay?

好的？

The other thing that the methamphetamine component of MDMA does, just like methamphetamine, is that it actually gets into what we call the presynaptic neuron, the neuron that releases the dopamine, and it interferes with the repackaging of dopamine into those vesicles.

MDMA 中的甲基苯丙胺成分的另一件事，就像甲基苯丙胺一样，它实际上进入我们所说的突触前神经元，即释放多巴胺的神经元，并干扰多巴胺重新包装到这些囊泡中。

Now, you might think, oh, it interferes with the repackaging of dopamine into vesicles, and therefore less will be released.

现在，您可能会想，哦，它会干扰多巴胺重新包装到囊泡中，因此释放的量会减少。

But actually what happens is, as a consequence of that, a bunch of dopamine builds up in the presynaptic neuron, so that when an electrical impulse comes down that neuron and dopamine is released, a huge amount of dopamine is released.

但实际上发生的情况是，结果是，突触前神经元中积聚了一堆多巴胺，因此，当电脉冲传到神经元时，多巴胺被释放，大量的多巴胺被释放。

And this is one of the characteristic properties of methamphetamine and of MDMA, which is that it leads to enormous increases in the amount of dopamine released and the amount of dopamine that hangs around in the synapse, and therefore it increases what we call dopaminergic tone or dopaminergic drive.

这是甲基苯丙胺和摇头丸的特征之一，它会导致释放的多巴胺量和突触中徘徊的多巴胺量大幅增加，因此它会增加我们所说的多巴胺能音或多巴胺能驱动力。

That's just a bunch of different ways to describe increases in dopamine.

这只是描述多巴胺增加的多种不同方式。

Okay, so that's the main way that MDMA, and by extension, methamphetamine, increase dopamine.

好的，这就是摇头丸（MDMA）以及甲基苯丙胺增加多巴胺的主要方式。

However, MDMA is not just methamphetamine, it's methylenedioxymethamphetamine, and it has another incredible property, which is that it doesn't just lead to huge increases in dopamine, it also leads to huge increases in serotonin.

然而，MDMA不仅仅是甲基苯丙胺，它是亚甲二氧基甲基苯丙胺，它还有另一个令人难以置信的特性，那就是它不仅会导致多巴胺大量增加，还会导致血清素大量增加。

And that's because there are other neurons that release serotonin, and they have serotonin transporters, which are sometimes called SERTs, S-E-R-T-Ss, serotonin transporters, and they work very much in the same way that dopamine transporters do.

这是因为还有其他释放血清素的神经元，它们有血清素转运蛋白，有时被称为 SERT、S-E-R-T-S、血清素转运蛋白，它们的工作方式与多巴胺转运蛋白非常相似。

Right?

正确的？

They basically control the sucking back up of serotonin that's been released into the synapse and that has not bound to serotonin receptors on the other neurons yet, and in doing so, allow more serotonin to hang out and have its effects as those receptors become available for serotonin to bind to them.

它们基本上控制了释放到突触中且尚未与其他神经元上的血清素受体结合的血清素的吸回，这样做时，允许更多的血清素悬停并发挥其作用，因为这些受体可供血清素与其结合。

The other thing MDMA does is it also gets into the presynaptic neuron to impact the packaging of serotonin into something called the vesicle monoamine transporter for serotonin.

MDMA 的另一件事是，它还会进入突触前神经元，影响将血清素包装成称为血清素囊泡单胺转运蛋白的物质。

And in doing so, it leads to a big buildup of serotonin in the presynaptic terminals and then massive increases in serotonin release.

这样做会导致突触前末梢血清素大量积聚，然后血清素释放大量增加。

Okay?

好的？

So what we've got with MDMA is a really interesting compound.

所以我们用 MDMA 得到了一种非常有趣的化合物。

Unlike methamphetamine or other amphetamines such as Adderall, Vyvanse, et cetera, that cause increases in dopamine by blocking reuptake and increasing release of dopamine, MDMA does that, but it also does the same thing for serotonin, and here's a really key point.

甲基苯丙胺或其他安非他明（如 Adderall、Vyvanse 等）通过阻止再摄取和增加多巴胺的释放来增加多巴胺，而 MDMA 则不同，MDMA 可以做到这一点，但它对血清素也有同样的作用，这是一个非常关键的点。

The increases in serotonin that MDMA creates are at least three times and maybe as much as eight times greater than the amount of dopamine release that MDMA causes.

MDMA 产生的血清素增加量至少是 MDMA 引起的多巴胺释放量的三倍，甚至可能高达八倍。

But when you put those two things together, what you basically have is a drug that causes huge increases in dopamine and even bigger increases in serotonin.

但当你把这两件事放在一起时，你基本上得到的是一种药物，它会导致多巴胺大幅增加，甚至血清素更大程度增加。

And remember earlier when I said that MDMA is a purely synthetic compound?

还记得我之前说过 MDMA 是一种纯合成化合物吗？

As far as we know, it does not exist in any plants or fungus or anything else in nature.

据我们所知，它不存在于任何植物、真菌或自然界的任何其他东西中。

Well, this is a very unusual circumstance of having big increases in dopamine and big increases in serotonin caused by the same compound.

嗯，这是一种非常不寻常的情况，由同一化合物引起多巴胺大幅增加和血清素大幅增加。

And that combination of big increases in dopamine and big increases in serotonin are what lead to these highly unusual and yet what seem to be potentially clinically very beneficial effects of having people feel a lot of mood elevation and a lot of stimulation from the stimulant properties of the methamphetamine component.

多巴胺的大幅增加和血清素的大幅增加相结合，导致了这些极不寻常的现象，但在临床上似乎可能产生非常有益的效果，让人们感受到大量的情绪提升和甲基苯丙胺成分的兴奋特性的大量刺激。

So that's the dopamine effect.

这就是多巴胺效应。

The dopaminergic tone goes way up, so it's a stimulant.

多巴胺能的音调升高，所以它是一种兴奋剂。

People feel really alert.

人们感到非常警觉。

They feel like talking a lot.

他们感觉想说很多话。

They feel very excited.

他们感到非常兴奋。

They feel a lot of Positive motivation.

他们感受到很多积极的动力。

These are classic effects of drugs that promote the release of dopamine, including amphetamine, cocaine, et cetera.

这些是促进多巴胺释放的药物的典型作用，包括安非他明、可卡因等。

But ordinarily, that's not such a good thing, because what happens is there's then a crash in the dopamine levels, and then people feel depressed, they feel lethargic.

但通常情况下，这并不是一件好事，因为多巴胺水平会急剧下降，然后人们会感到沮丧，感到昏昏欲睡。

They don't feel good at all.

他们感觉一点都不好。

MDMA seems to cause these increases in dopamine and all the accompanying effects I just described.

MDMA 似乎会导致多巴胺的增加以及我刚才描述的所有伴随效应。

But by also causing big increases in serotonin, it activates neural networks that are associated with feeling more socially connected.

但它也会导致血清素大幅增加，从而激活与社交联系感更强相关的神经网络。

In fact, we'll talk about data in a little bit where people have had their brains imaged while under the influence of MDMA, and it's very clear that people who have taken MDMA look at faces that ordinarily they would rate as fearful and rate them as less fearful.

事实上，我们稍后会讨论一些数据，这些数据是人们在服用摇头丸的影响下进行大脑成像的结果，很明显，服用摇头丸的人会看到那些通常被他们认为是恐惧的面孔，以及认为他们不那么恐惧的面孔。

They see faces that are smiling, and they rate those smiling, happy faces as more positive than they would off the drug.

他们看到微笑的面孔，并且认为这些微笑、快乐的面孔比戒毒后更积极。

The big increases in serotonin create what we call a prosocial effect, and that, combined with the dopaminergic increase in mood and the stimulation effect, creates this thing that we call an empathogen, where, and this is very important, the empathy isn't just for other people, it's also for oneself and one's own experiences happening in the moment, as well as empathy for experiences from the past.

血清素的大幅增加会产生我们所说的亲社会效应，再加上情绪中多巴胺能的增加和刺激效应，就会产生我们所说的同理心，这一点非常重要，同理心不仅针对其他人，也针对自己和自己当下发生的经历，以及对过去经历的同理心。

Which, as you can imagine, could be very beneficial for the treatment of PTSD.

正如你可以想象的那样，这对于治疗创伤后应激障碍非常有益。

Okay?

好的？

So hopefully, the way I describe the biology of MDMA makes some sense.

所以希望我描述 MDMA 生物学的方式是有意义的。

If you didn't get anything out of the description I provided except the understanding that MDMA is unusual in that it causes big increases in dopamine and even bigger increases in serotonin, then you have more in your knowledge base now about MDMA than you need in order to understand the rest of our discussion.

如果您没有从我提供的描述中得到任何信息，除了了解 MDMA 是不寻常的，因为它会导致多巴胺大幅增加，甚至血清素大幅增加，那么您现在关于 MDMA 的知识库比您理解我们讨论的其余部分所需的更多。

Before we go any further, I do want to separate MDMA out from some other compounds which are referred to as psychedelics.

在我们进一步讨论之前，我确实想将摇头丸与其他一些被称为致幻剂的化合物分开。

And I recently did a podcast episode all about psilocybin and its therapeutic exploration and its chemical basis, et cetera.

我最近做了一个播客节目，内容是关于裸盖菇素及其治疗探索及其化学基础等。

You can find that, like all episodes, at hubermanlab.com.

与所有剧集一样，您可以在 hubermanlab.com 上找到该内容。

I also did an episode with expert guest, Dr. Robin Carhart-Harris, who's at University of California, San Francisco, who's pioneering a lot of the studies on the clinical application of psilocybin.

我还与专家嘉宾 Robin Carhart-Harris 博士一起做了一集，他来自旧金山加利福尼亚大学，他开创了许多有关裸盖菇素临床应用的研究。

Psilocybin and LSD are mainly going to increase serotonin activation in the brain.

裸盖菇素和LSD主要会增加大脑中血清素的激活。

In fact, they very closely resemble serotonin itself, and they activate what's called the 5-HT2A, or serotonin, 5-HT just stands for serotonin, the 5-HT2A receptor to create very mystical type experiences.

事实上，它们与血清素本身非常相似，它们会激活所谓的 5-HT2A 或血清素，5-HT 只是代表血清素，即 5-HT2A 受体，可创造非常神秘的体验。

They are considered classic psychedelics and are very introspective.

他们被认为是经典的迷幻剂并且非常内省。

And, as I described in those episodes, are being explored extensively now for the treatment of major depression.

而且，正如我在这些剧集中所描述的那样，现在正在广泛探索治疗重度抑郁症的方法。

A different compound that's being used for the treatment of depression is ketamine.

另一种用于治疗抑郁症的化合物是氯胺酮。

I will do an entire episode all about ketamine.

我会做一整集都是关于氯胺酮的。

Ketamine is actually a N-methyl-D-aspartate receptor blocker, NMDA receptor blocker.

氯胺酮实际上是一种N-甲基-D-天冬氨酸受体阻滞剂，NMDA受体阻滞剂。

That shouldn't mean anything to most of you, but it is a dissociative anesthetic, not unlike PCP, what used to be called angel dust on the street.

这对你们大多数人来说应该没有任何意义，但它是一种解离麻醉剂，与 PCP 不同，PCP 过去被称为街上的天使尘。

Ketamine is being used as a treatment for depression.

氯胺酮被用来治疗抑郁症。

It is currently legal.

目前这是合法的。

So unlike psilocybin and LSD, which are granted breakthrough status for the study of depression but are not yet legal, they are still illegal.

因此，与裸盖菇素和LSD不同，它们在抑郁症研究中被授予突破性地位，但尚未合法，它们仍然是非法的。

And of course, as I mentioned earlier, MDMA has breakthrough status but is still illegal.

当然，正如我之前提到的，摇头丸具有突破性的地位，但仍然是非法的。

Ketamine is being used for the treatment of depression, and it does so, as its name suggests, a dissociative anesthetic, by creating a sense of dissociation from emotions.

氯胺酮被用于治疗抑郁症，顾名思义，它是一种分离性麻醉剂，通过产生一种与情绪分离的感觉。

Okay?

好的？

Now, I raise this distinction between psilocybin and LSD, which are mystical in their effects, ketamine, which is dissociative in its effects, with MDMA, which is an empathogen, or sometimes called an enactogen.

现在，我提出裸盖菇素和LSD之间的区别，它们的作用是神秘的，氯胺酮的作用是解离的，MDMA是一种共情剂，有时也称为促生剂。

But as an empathogen or an enactogen, it's creating more affiliation.

但作为一种共情剂或刺激剂，它正在创造更多的归属感。

It's affiliative.

是有隶属关系的。

Okay?

好的？

So it's a very distinct compound.

所以它是一种非常独特的化合物。

And this is important to understand because when we hear the word psychedelic, a lot of people tend to lump together LSD, psilocybin, and MDMA.

理解这一点很重要，因为当我们听到迷幻这个词时，很多人倾向于将LSD、裸盖菇素和MDMA混为一谈。

If you talk to researchers in these areas, they will tell you that MDMA really isn't that much of a psychedelic.

如果您与这些领域的研究人员交谈，他们会告诉您，摇头丸实际上并不是那么迷幻。

It's an empathogen with stimulant properties, and it also has this serotonergic component that makes it an empathogen or an enactogen.

它是一种具有刺激特性的移情剂，并且还具有血清素能成分，使其成为移情剂或促刺激剂。

So MDMA is very different than the other psychedelics, and my hunch is that over the next few years, we will stop talking about MDMA as a psychedelic because it does not tend to produce visual hallucinations or auditory hallucinations of the sort that classic psychedelics do.

因此，MDMA 与其他迷幻药有很大不同，我的预感是，在接下来的几年里，我们将不再谈论 MDMA 作为迷幻药，因为它不会产生经典迷幻药那样的幻视或幻听。

And in general, it is more of a mood-impacting drug than it is mystical.

总的来说，它更像是一种影响情绪的药物，而不是神秘的。

Okay?

好的？

So we'll get into some of the brain networks and which ones are activated while under the influence of MDMA.

因此，我们将了解一些大脑网络，以及哪些网络在 MDMA 的影响下被激活。

But I do think it's very important to segment out MDMA from the other so-called classic psychedelics and also segment it out from ketamine.

但我确实认为将摇头丸与其他所谓的经典致幻剂区分开来，并将其与氯胺酮区分开来，这一点非常重要。

Thanks to some really terrific studies, both in animal models and in humans, we now understand a lot of what makes MDMA produce these incredibly unique effects.

得益于一些非常出色的动物模型和人类研究，我们现在了解了摇头丸产生这些令人难以置信的独特作用的很多原因。

And when I say unique, I mean unique from drugs like psilocybin and LSD and ketamine, and from methamphetamine, for that matter.

当我说独特时，我的意思是与裸盖菇素、迷幻剂和氯胺酮等药物以及甲基苯丙胺等药物相比是独特的。

And it's really the combination of big increases in dopamine and even bigger increases in serotonin that create a situation where people have more energy, and yet, despite having more energy, they don't feel irritated.

事实上，正是多巴胺的大幅增加和血清素的大幅增加相结合，创造了一种人们拥有更多能量的情况，然而，尽管有更多的能量，他们却不会感到恼怒。

They feel a lot of pleasure.

他们感到非常高兴。

They seem to want to be in the state of having a lot of energy.

他们似乎想要处于一种精力充沛的状态。

This will become important as we talk about anxiety and the anxiety symptoms of PTSD.

当我们谈论焦虑和创伤后应激障碍（PTSD）的焦虑症状时，这一点将变得很重要。

It also, because of the big increases in serotonin, produces a sense of emotional warmth Towards others and towards oneself.

它还由于血清素的大量增加，产生一种对他人和对自己的情感温暖感。

That's the empathogen component.

这就是共情原成分。

And for reasons that we still don't understand, it seems to increase trust.

由于我们仍然不明白的原因，它似乎增加了信任。

And the increases in trust turn out to be vital because, as you will also learn later when we look at the clinical trials exploring MDMA for the treatment of PTSD, the major effect of MDMA for the treatment of PTSD is not to cure PTSD, but rather to make the talk therapy for PTSD much more effective.

信任的增加被证明是至关重要的，因为，正如您稍后在研究探索 MDMA 治疗 PTSD 的临床试验时所了解到的那样，MDMA 对于治疗 PTSD 的主要作用不是治愈 PTSD，而是使 PTSD 的谈话疗法更加有效。

This is a very important point.

这是非常重要的一点。

In fact, so important, I'm going to repeat it at least three times during today's episode.

事实上，这非常重要，我将在今天的节目中至少重复三遍。

MDMA taken on its own does not cure PTSD.

单独服用 MDMA 并不能治愈 PTSD。

MDMA can augment or boost the effects of talk therapy for PTSD, and it does that through the engagement of specific neural circuits.

MDMA 可以增强或增强谈话疗法治疗 PTSD 的效果，它是通过特定神经回路的参与来实现的。

But before we talk about what those neural circuits are, I want to emphasize that the increases in serotonin that MDMA produces seem to act on different receptors than the big increases in serotonin that LSD and psilocybin produce.

但在我们讨论这些神经回路之前，我想强调的是，MDMA 产生的血清素增加似乎与 LSD 和裸盖菇素产生的血清素大幅增加作用于不同的受体。

So if you listen to the episode that I did on psilocybin, and we haven't done yet one on LSD, but the mechanisms are very similar for psilocybin and LSD, whereby psilocybin and LSD very closely mimic the molecule serotonin itself, but seem to have a more selective activation of just the so-called serotonin 2A receptor, abbreviated 5-HT2A.

所以，如果你听过我关于裸盖菇素的那一集，我们还没有关于LSD的，但是裸盖菇素和LSD的机制非常相似，其中裸盖菇素和LSD非常接近地模仿分子血清素本身，但似乎对所谓的血清素2A受体（缩写为5-HT2A）具有更高的选择性激活。

And that leads to more interconnectedness between different brain areas, more consideration of new possibilities about events from the past, present, and future.

这导致不同大脑区域之间的联系更加紧密，更多地考虑过去、现在和未来事件的新可能性。

And also the opening of so-called neuroplasticity, of rewiring of neural connections that persist long after the psilocybin or LSD effects have worn off.

还有所谓的神经可塑性的开启，即神经连接的重新布线，这种重新连接在裸盖菇素或LSD效应消失后仍持续很长时间。

Now, MDMA can activate the serotonin 2A receptor, but it seems that it largely activates the serotonin 1B receptor.

现在，MDMA可以激活血清素2A受体，但它似乎主要激活血清素1B受体。

Now, what does that mean?

现在，这意味着什么？

Activation of the serotonin 1B receptor seems to be what gives MDMA its very strong impact on the neural circuits of the brain that relate to trust and to social engagement.

血清素 1B 受体的激活似乎使 MDMA 对与信任和社交参与相关的大脑神经回路产生了非常强烈的影响。

Not just the willingness to engage socially and to confide in a therapist or another person, but the intense desire to do so.

不仅仅是参与社交活动以及向治疗师或其他人倾诉的意愿，而且是这样做的强烈愿望。

And when I say intense desire, that takes us back to the dopamine system.

当我说强烈的欲望时，这让我们回到了多巴胺系统。

Remember, dopamine, even though when increased in the brain can increase our mood, it is largely responsible for increasing our sense of motivation and desire for something and to do something.

请记住，多巴胺在大脑中的增加可以改善我们的情绪，但它在很大程度上负责增加我们对某事和做某事的动力和渴望。

So the increase in dopamine that's created by MDMA seems to make people what I call forward center of mass.

因此，MDMA 产生的多巴胺增加似乎使人们成为我所说的前向质心。

They want to do something.

他们想做点什么。

They're very motivated to do something.

他们非常有动力去做某事。

And the increases in serotonin acting on the serotonin 1B receptor seems to be what creates this desire to bond or create trust, or to have a discussion of real things, both things that are positive, but also to explore things that are difficult.

作用于血清素 1B 受体的血清素增加似乎是产生这种渴望的原因，这种渴望是建立联系或建立信任，或者讨论真实的事物，这两种事物都是积极的，但也都是探索困难的事物。

And this I realize is going to be a little bit of a mind bend for people to understand, but one of the key things that quality MDMA therapy consists of is not just having a very good rapport and communication with the therapist that's guiding the PTSD treatment, but also rapport and a willingness to engage in conversations with oneself.

我意识到这对人们来说有点难以理解，但优质 MDMA 治疗的关键之一不仅是与指导 PTSD 治疗的治疗师建立良好的融洽关系和沟通，而且还包括融洽的关系以及与自己对话的意愿。

I think that most of us can relate to the fact that we have experiences, some of which are hard, some of which are great, and everything in between.

我认为我们大多数人都能体会到这样一个事实：我们都有过经历，其中有些是艰难的，有些是伟大的，以及介于两者之间的一切。

Trauma is, I believe, best defined by the words that a former guest on this podcast who's a world expert in trauma, Paul Conti, explained as trauma is an event that fundamentally changes the way that our brain works for the worse.

我相信，对创伤的最好定义是用这个播客的前嘉宾、世界创伤专家保罗·康蒂（Paul Conti）的话来解释的，创伤是一种从根本上改变我们大脑工作方式的事件，使我们的大脑变得更糟。

Okay, so not every bad event of our past is trauma, but events that change the way that we think, our emotional tone, or our behavior in ways going forward that are not adaptive for us.

好吧，并不是我们过去发生的每一件坏事都是创伤，而是那些改变了我们的思维方式、我们的情绪基调或我们的行为方式的事件，这些事件改变了我们不适合我们的未来方式。

They don't serve us well, either because they are highly distracting or because they create anxiety, or because they disrupt sleep, or any number of different things that are maladaptive consequences.

它们不能很好地为我们服务，要么因为它们高度分散注意力，要么因为它们产生焦虑，或者因为它们扰乱睡眠，或者因为许多不同的事情会导致适应不良的后果。

That's what really defines trauma.

这才是创伤的真正定义。

And when under the influence of MDMA, because of those parallel increases in dopamine and serotonin, people seem far more willing to both trust the therapist that they're talking about that trauma with, but also to trust their own ability to, quote, unquote, "Go internal" and think about the challenging thing or things, because oftentimes trauma can consist of many events, not just one event, and the thought patterns around that and the context around that, and therein, to be able to explore new possibilities to essentially rewire their relationship to that trauma.

当在摇头丸的影响下，由于多巴胺和血清素的平行增加，人们似乎更愿意相信与他们谈论创伤的治疗师，而且也相信自己的能力，引用，取消引用，“深入内心”并思考具有挑战性的事情或事情，因为创伤通常可以由许多事件组成，而不仅仅是一个事件，以及围绕该事件的思维模式和围绕该事件的背景，并且在其中，能够探索新的可能性，从本质上重新布线他们与那个创伤的关系。

So I promise that a little bit later we'll talk about the direct application of MDMA for the treatment of PTSD.

所以我保证稍后我们会讨论直接应用 MDMA 治疗 PTSD。

But now I'd like to shift off of the chemical changes that MDMA produces and some of the subjective changes, these increases in trust and pleasure and energy and emotional warmth, to some of the brain circuits that are activated and modified by MDMA use.

但现在我想把 MDMA 产生的化学变化和一些主观变化（这些增加信任、愉悦、能量和情感温暖）转移到使用 MDMA 激活和修改的一些大脑回路上。

And then we will explore the toxicity issue.

然后我们将探讨毒性问题。

And then we will explore the clinical studies, of which I can promise you are extremely exciting.

然后我们将探索临床研究，我可以保证您会非常兴奋。

But until we understand the neural circuit phenomena, and of course, until we consider the neurotoxicity issues, I don't think those clinical findings can be appreciated in their full value.

但在我们了解神经回路现象之前，当然，在我们考虑神经毒性问题之前，我认为这些临床发现不能充分发挥其价值。

But now I'd like to talk about what MDMA really does in the brain, both in the short term while someone is under the influence of the drug, and in the long term.

但现在我想谈谈 MDMA 对大脑的真正作用，无论是在某人受到药物影响的短期内，还是长期内。

What sorts of neuroplastic or rewiring changes does MDMA produce, and how can those be beneficial or perhaps not beneficial?

MDMA 会产生什么样的神经塑性或重新布线变化，这些变化如何可能有益或可能无益？

So in order to understand what MDMA does to the human brain, we need to take a step back and really define the sorts of experiments that one could do.

因此，为了了解 MDMA 对人脑的作用，我们需要退后一步，真正定义可以进行的实验类型。

So for instance, you could take a person who's never ingested MDMA and put them into an fMRI machine, which is functional magnetic resonance imaging.

举例来说，您可以将一个从未摄入过摇头丸的人放入功能磁共振成像仪中，这就是功能性磁共振成像。

Put them into the fMRI machine and just have them sit there with their eyes closed, what we would call resting functional connectivity Or resting state functional connectivity, and simply look at how interconnected certain brain areas are, which brain areas are active, which brain areas are less active at rest.

将它们放入功能磁共振成像机器中，让它们闭上眼睛坐在那里，我们称之为静息功能连接或静息状态功能连接，然后简单地观察某些大脑区域的相互连接程度，哪些大脑区域活跃，哪些大脑区域在休息时不太活跃。

This is an important thing to do, not just to provide a baseline for understanding what the drug MDMA will subsequently do, but also because it addresses what's called the default mode network.

这是一件重要的事情，不仅为了解 MDMA 药物随后的作用提供基线，而且还因为它解决了所谓的默认模式网络问题。

The default mode network, or DMN, is the network that is active in our brains when we aren't really attending to anything specific outside us, and we're not trying to think about anything specific or accomplish anything specific.

默认模式网络（DMN）是当我们没有真正关注外部的任何特定事物，并且我们没有尝试思考任何特定事物或完成任何特定事物时，我们大脑中活跃的网络。

It actually relates to our sense of imagination and daydreaming.

它实际上与我们的想象力和白日梦有关。

It has a lot to do with our self-referencing, what we're thinking about ourselves.

这与我们的自我参照、我们对自己的看法有很大关系。

This may come as no surprise, but if you're just sitting there on the bus or around the dinner table and you're not paying attention to what's going on, in large part, your brain is in this default mode network, and you're thinking about yourself.

这可能并不奇怪，但如果你只是坐在公共汽车上或餐桌旁，而你没有注意正在发生的事情，那么在很大程度上，你的大脑就处于这种默认模式网络中，而你正在考虑自己。

Okay, so we can get a sense of what the default mode network activation is, we can get a sense of which brain areas are more or less active simply by putting somebody into an fMRI machine.

好的，我们可以了解默认模式的网络激活是什么，只需将某人放入功能磁共振成像机器中，我们就可以了解哪些大脑区域或多或少活跃。

Then, of course, you could give somebody MDMA while they are in the fMRI machine and see how the activation of different brain networks changes.

然后，当然，你可以在某人在功能磁共振成像机器中时给他们服用摇头丸，看看不同大脑网络的激活如何变化。

And then, of course, you could analyze how the default mode networks and other brain networks change in the days and weeks and even years after the drug has worn off, so-called neuroplasticity effects.

当然，你可以分析默认模式网络和其他大脑网络在药物失效后的几天、几周甚至几年内如何变化，即所谓的神经可塑性效应。

What changed in a permanent or pervasive way?

是什么发生了永久性或普遍性的改变？

Okay, so that's one basic paradigm for exploring the effects of drugs like MDMA on the brain.

好的，这就是探索 MDMA 等药物对大脑影响的一个基本范例。

The other way that you can explore the effects of MDMA on the brain is to ask people in the general population, "Hey, who out there has taken MDMA?

探索 MDMA 对大脑影响的另一种方法是询问普通人群，“嘿，谁服用了 MDMA？

How many times have you taken it?

你拿过几次了？

And come on into the laboratory and we will image your brain" and compare people who have, for instance, taken MDMA zero times to people who have taken MDMA one time or five times, or believe it or not, there are some studies sitting right here in front of me on my desk of people who have taken MDMA more than 200 times and asked the same sorts of questions.

来实验室吧，我们会对你的大脑进行成像”，并将服用过 0 次 MDMA 的人与服用过 1 次或 5 次 MDMA 的人进行比较，不管你信不信，在我面前的桌子上有一些研究，研究对象是服用过 200 次以上 MDMA 的人，并提出了同样的问题。

Which brain areas are more or less active?

哪些大脑区域比较活跃或不太活跃？

Those studies have been done as well.

这些研究也已经完成。

And of course, one can do studies where you give people different dosages of MDMA, as well as giving people MDMA and then giving them specific stimuli, meaning not just asking them to sit there in the fMRI scanner with eyes closed, looking at the resting state functional connectivity, but also how the brain responds to the presentation of happy faces or sad faces, or images of oneself, or even images that recall memories of traumatic events and so on.

当然，人们可以进行研究，给人们不同剂量的摇头丸，以及给人们摇头丸，然后给他们特定的刺激，这意味着不仅仅是要求他们闭上眼睛坐在功能磁共振成像扫描仪中，观察静息状态的功能连接，还可以研究大脑如何对快乐的面孔或悲伤的面孔，或自己的图像，甚至是回忆创伤事件记忆的图像等做出反应。

So fortunately, all of those sorts of studies have been done in humans, and there are also a large number of studies in animal models exploring how the social activity of laboratory mice changes when they are under the effects of MDMA.

幸运的是，所有这些类型的研究都是在人类身上进行的，而且还有大量的动物模型研究探索实验小鼠的社交活动在受到 MDMA 影响时如何变化。

There are even studies, believe it or not, on the effects of MDMA in cephalopods.

不管你信不信，甚至还有关于 MDMA 对头足类动物的影响的研究。

Cephalopods include octopuses as well as cuttlefish and other aquatic animals that are known for having complex behavior.

头足类动物包括章鱼、墨鱼和其他以行为复杂而闻名的水生动物。

Some people believe that the cephalopods are extremely intelligent.

有些人认为头足类动物非常聪明。

The obsession with cephalopods is something that really intrigues me.

对头足类动物的痴迷确实引起了我的兴趣。

I actually used to have cuttlefish in my laboratory.

事实上，我的实验室里曾经有过墨鱼。

We did not put them on MDMA.

我们没有给它们服用摇头丸。

But there is a study that's been published in the journal Current Biology.

但《当代生物学》杂志上发表了一项研究。

It's a Cell Press journal, excellent journal.

这是一份 Cell Press 期刊，优秀的期刊。

This is from Gül Dölen's laboratory at Johns Hopkins School of Medicine, showing that if you give octopuses MDMA, they like to spend more time with other octopuses than they do if they are not on MDMA.

这是来自约翰·霍普金斯大学医学院 Gül Dölen 实验室的研究结果，表明如果给章鱼服用 MDMA，它们会比不服用 MDMA 时更喜欢与其他章鱼待在一起。

And that might sound like a playful experiment just done in order to entertain oneself and the octopuses, perhaps, but actually, in that study, they identified the serotonin transporter in octopuses and showed that it has a lot of homology similarity to human serotonin transporter receptors.

这听起来像是一个有趣的实验，只是为了娱乐自己和章鱼，但实际上，在这项研究中，他们鉴定了章鱼中的血清素转运蛋白，并表明它与人类血清素转运蛋白受体有很多同源相似性。

And so what that really speaks to is the fact that the prosocial effects of MDMA that are observed in mice and in humans and in octopuses all have a common basis, which is the activation of more serotonin release in particular brain networks.

因此，这真正说明了这样一个事实：在小鼠、人类和章鱼中观察到的摇头丸的亲社会效应都有一个共同的基础，那就是激活特定大脑网络中更多的血清素释放。

Okay, so that interesting study on octopuses aside, I think what most of us are interested in is how MDMA impacts the brain.

好吧，除了对章鱼的有趣研究之外，我想我们大多数人感兴趣的是 MDMA 如何影响大脑。

And so I'm going to spell out the three major ways in which MDMA changes the activation of the brain in the short and long term.

因此，我将详细说明 MDMA 在短期和长期内改变大脑激活的三种主要方式。

And here I'm pooling across a number of different studies.

在这里，我汇集了许多不同的研究。

But one of the key sets of studies in this area comes from the, what I consider, very beautiful work of Harriet de Wit.

但我认为，这一领域的一组关键研究来自 Harriet de Wit 非常漂亮的作品。

Harriet de Wit runs the Human Behavioral Pharmacology Laboratory in the Department of Psychiatry and Behavioral Neuroscience at the University of Chicago.

Harriet de Wit 负责芝加哥大学精神病学和行为神经科学系的人类行为药理学实验室。

And her laboratory has a long history of giving people certain drugs in very specific dosages and then measuring their effects on the brain using different types of imaging, including fMRI.

她的实验室长期以来一直以非常特定的剂量向人们提供某些药物，然后使用不同类型的成像（包括功能磁共振成像）测量它们对大脑的影响。

And one particular study that I'll highlight is entitled "Effects of MDMA on Sociability and Neural Responses to Social Threat and Social Reward." So what this study looked at is how MDMA impacts people's perceptions of others' emotional expressions on their face.

我要强调的一项特别研究的标题是“摇头丸对社交性以及对社会威胁和社会奖励的神经反应的影响”。因此，这项研究着眼于 MDMA 如何影响人们对其他人面部情绪表达的感知。

What they found is that when people are on MDMA, their response to threatening faces or other threatening stimuli is reduced, and it's reduced in a very specific way, which is reductions in activity of the amygdala.

他们发现，当人们服用摇头丸时，他们对威胁性面孔或其他威胁性刺激的反应会减弱，而且以一种非常具体的方式减弱，即杏仁核活动的减少。

The amygdala is a structure that some of you may be familiar with.

杏仁核是你们中有些人可能熟悉的结构。

It is known to be involved in the threat detection systems or networks of the brain.

众所周知，它参与威胁检测系统或大脑网络。

It is sometimes called the fear area of the brain, although I want to caution people against assigning any one particular subjective experience to any one particular brain area.

它有时被称为大脑的恐惧区域，尽管我想提醒人们不要将任何一种特定的主观体验分配给任何一个特定的大脑区域。

The amygdala is actually a complex.

杏仁核实际上是一个复合体。

It's actually called the amygdaloid complex and has a lot of different sub-areas, and it's involved in a lot of things besides fear and threat detection.

它实际上被称为杏仁核复合体，有很多不同的子区域，除了恐惧和威胁检测之外，它还涉及很多事情。

Nonetheless, when people are under the influence of MDMA and you show them a face that is grimacing or would otherwise be rated as quite threatening, they tend to rate it as less threatening.

尽管如此，当人们受到摇头丸的影响时，如果你向他们展示一张做鬼脸或被认为具有相当威胁性的面孔，他们往往会认为其威胁性较小。

In addition, they tend to respond to happy faces or even slightly happy faces as more kind or more generous or happier than they would when they are not on MDMA.

此外，他们对笑脸甚至轻微笑脸的反应往往比不服用摇头丸时更友善、更慷慨或更快乐。

Again, the faces that are being shown are not of people on MDMA.

再次强调，所显示的面孔并不是服用摇头丸的人。

That would be an interesting experiment, but that's not what they did here.

这将是一个有趣的实验，但这不是他们在这里所做的。

What's happening here is people are being given MDMA, and then they are rating, in a subjective way, the friendliness or the level of threat that they detect in these facial expressions.

这里发生的事情是，人们被给予摇头丸，然后他们以主观的方式对他们在这些面部表情中检测到的友善程度或威胁程度进行评级。

And of course, they have extremes of friendly and threatening, but then they also grade them.

当然，他们也有友好和威胁的极端，但他们也会对他们进行评分。

They titrate them so that they also have mildly threatening and mildly happy faces, et cetera.

他们对它们进行滴定，使它们也有轻微威胁和轻微快乐的面孔，等等。

So everything from a grin to a smirk to a giant smile, everything from somebody looking a little bit askance at somebody to really wide-eyed and looking angry like they're going to attack you and things of that sort.

所以一切，从咧嘴笑到傻笑，再到大笑，从某人斜视某人到睁大眼睛，看起来很生气，好像他们要攻击你之类的。

So what's discovered in this study is that MDMA has a bidirectional effect on our perception of others' emotions, making people more likely to rate something as positive if it's initially positive or even a little bit positive, and less likely to rate a threatening face as more threatening.

这项研究发现，摇头丸对我们对其他人情绪的感知有双向影响，如果某件事最初是积极的，甚至有点积极，那么人们更有可能将其评价为积极，而不太可能将威胁性的面孔评价为更具威胁性。

Now, one thing I have not mentioned thus far are the dosages of MDMA used in this and in other studies.

现在，到目前为止我还没有提到的一件事是本研究和其他研究中使用的 MDMA 剂量。

And fortunately, despite the studies that we're going to talk about using a lot of different types of people, different ages, different sexes, so male and female, located in different parts of the world even, some with PTSD, some not with PTSD, et cetera, there's been fairly tight dosage control of MDMA in these studies.

幸运的是，尽管我们将要讨论的研究使用了许多不同类型的人，不同年龄，不同性别，甚至是男性和女性，甚至位于世界不同地区，有些患有创伤后应激障碍，有些没有创伤后应激障碍，等等，但这些研究中对摇头丸的剂量控制相当严格。

It's not perfectly matched from study to study, but it's pretty darn close, which makes interpreting results across studies a lot easier for me, and therefore for you.

各项研究之间并不完全匹配，但非常接近，这使得解释不同研究的结果对我来说更加容易，对你来说也是如此。

The typical dosages of MDMA used in these neuroimaging studies and in the clinical studies of PTSD that we're going to talk about later range anywhere from 0.75 milligrams per kilogram of body weight to 1.5 milligrams per kilogram of body weight.

这些神经影像学研究和我们稍后要讨论的 PTSD 临床研究中使用的 MDMA 典型剂量范围为每公斤体重 0.75 毫克到每公斤体重 1.5 毫克。

So for somebody like me, I weigh 220 pounds, that's 100 milligrams.

所以对于像我这样的人来说，我的体重是 220 磅，也就是 100 毫克。

1.5 milligrams per kilogram of body weight would therefore be 150 milligrams in a single dose.

因此，每公斤体重 1.5 毫克，单剂量为 150 毫克。

Okay?

好的？

A dosage of one milligram per kilogram of body weight would mean 100 milligrams for my 100 kilograms.

每公斤体重一毫克的剂量就意味着我的 100 公斤体重需要 100 毫克。

Okay?

好的？

Somebody lighter than 100 kilograms would obviously take less MDMA in one of these studies.

在其中一项研究中，体重低于 100 公斤的人显然会服用更少的 MDMA。

But in general, the range of MDMA that's been explored is 0.75 to 1.5 milligrams per kilogram of body weight.

但总的来说，MDMA 的探索范围是每公斤体重 0.75 至 1.5 毫克。

The exception being in the clinical studies that we'll talk about a little bit later, there's a tendency to explore both an initial dose of 1.5 milligrams per kilogram of body weight.

例外的是我们稍后会讨论的临床研究，有一种倾向是探索每公斤体重 1.5 毫克的初始剂量。

So again, for a 100-kilogram person, that would be 150 milligrams or so, and then a so-called booster of half that amount, about 90 minutes to two and a half hours into the session, so another 75 milligrams later.

同样，对于一个 100 公斤的人来说，这将是 150 毫克左右，然后是所谓的一半量的加强剂，大约 90 分钟到两个半小时开始，所以之后又是 75 毫克。

And I should point out that there is not always the inclusion of the so-called booster, and in some cases, lower doses of MDMA, such as the 0.75 milligrams per kilogram dosages, are used.

我应该指出，并不总是包含所谓的加强剂，在某些情况下，会使用较低剂量的 MDMA，例如每公斤 0.75 毫克的剂量。

Why am I getting so into the details of dosages?

为什么我要如此详细地了解剂量？

Well, if we are going to talk about toxicity of MDMA, we absolutely have to talk about dosages.

好吧，如果我们要谈论 MDMA 的毒性，我们绝对必须谈论剂量。

Because like any drug, the toxicity of MDMA does scale with the dosage that's applied, not just the frequency of MDMA use.

因为与任何药物一样，摇头丸的毒性确实与所使用的剂量有关，而不仅仅是摇头丸的使用频率。

And we hear a lot about that.

我们听到了很多这样的事情。

Someone has taken MDMA one time or four times or 200 times.

有人服用过一次、四次或 200 次 MDMA。

We hear about frequency of use, but rarely do we hear about the specific dosages that are taken in any one particular session.

我们听说过使用频率，但很少听说过在任何一次特定疗程中服用的具体剂量。

So when we talk about the subjective effects or the brain networks that are activated when people take MDMA, in general, we're talking about dosages somewhere between 0.75 milligrams per kilogram of body weight and 1.5 milligrams per kilogram of body weight.

因此，当我们谈论人们服用 MDMA 时被激活的主观效应或大脑网络时，一般来说，我们谈论的剂量介于每公斤体重 0.75 毫克到每公斤体重 1.5 毫克之间。

Although typically, you're going to see studies, both clinical and more research explorative, using anywhere from one to 1.5 milligrams of MDMA per kilogram of body weight.

尽管通常情况下，您会看到临床研究和探索性研究，每公斤体重使用 1 到 1.5 毫克 MDMA。

So that's important to highlight.

所以强调这一点很重要。

I told you about the subjective effects of MDMA engaging the responses of people's faces, but I didn't tell you about the brain areas that are responsible, except for the reduction in amygdala activity.

我告诉过你 MDMA 对人们面部反应的主观影响，但除了杏仁核活动减少之外，我没有告诉你负责的大脑区域。

Now, one of the key features of PTSD seems to be that there is a heightened connectivity between the amygdala and a brain area called the insula.

现在，创伤后应激障碍的主要特征之一似乎是杏仁核和称为岛叶的大脑区域之间的连接性增强。

The insula is a brain area that's very important for something that's called interoception.

岛叶是一个大脑区域，对于内感受非常重要。

Interoception is one's perception of our feelings, both pure sensations, but also our emotional states and our feelings of wellbeing or lack of wellbeing for everything from our skin inward.

内感受是一个人对我们的感受的感知，既包括纯粹的感觉，也包括我们的情绪状态以及我们对皮肤内部一切事物的幸福感或缺乏幸福感。

Okay?

好的？

So that's interoception.

这就是内感。

You actually can interocept now, even though you're always interocepting a little bit.

你现在实际上可以进行交互，尽管你总是进行一点交互。

You can interocept now to a great degree if you were to, for instance, close your eyes or simply focus on the contact points between your body and any surface that you happen to be contacting.

例如，如果您闭上眼睛或只是专注于身体与您碰巧接触的任何表面之间的接触点，您现在可以在很大程度上进行交互感知。

So maybe the backs of your legs against a chair or your feet against the floor or the bottoms of your shoes or sandals.

因此，也许你的腿背靠着椅子，你的脚靠着地板，或者鞋底或凉鞋。

Your nervous system is constantly sensing those contact points, but normally they're not under your conscious awareness unless you direct your interoceptive capacity to them, which is just fancy nerd speak for saying you normally don't notice what's going on from your skin inward unless you focus on it.

你的神经系统不断地感知这些接触点，但通常它们并不在你的意识之下，除非你将你的内感受能力引导到它们，这只是花哨的书呆子的说法，说你通常不会注意到你的皮肤内部发生了什么，除非你集中注意力。

That focus is interoception.

这个焦点是内感受。

It can be about the fullness of your gut.

这可能与你的肠道是否饱满有关。

It can be about how happy or sad you are.

它可以是关于你有多高兴或多悲伤。

It can be about how tired or alert you happen to feel.

这可能与您碰巧感到的疲倦或警觉程度有关。

But that's interoception, and it is distinctly different from exteroception, which is your ability and tendency to focus on things beyond the confines of your skin.

但这是内感受，它与外感受明显不同，外感受是你关注皮肤范围之外的事物的能力和倾向。

So this could be visual attention, auditory attention It could be paying attention to events like birds flying by, whether or not your Uber is showing up, these kinds of things.

所以这可能是视觉注意力，听觉注意力，也可能是关注鸟儿飞过的事件，无论你的优步是否出现，诸如此类的事情。

And we are always in a balance, a push-pull of interoception and exteroception.

我们总是处于内感受和外感受的推拉平衡之中。

The insula is a brain area that is absolutely critical for interoception, so much so that it has a map of the complete body surface, including our internal organs.

岛叶是一个对于内感受绝对至关重要的大脑区域，以至于它拥有整个身体表面的地图，包括我们的内脏器官。

In other words, if you put somebody into an fMRI machine, or you were to record from the insula with electrodes, as has been done in humans many times now during the course of neurosurgery for other purposes, what you would find is that if you stimulate neurons in one end of the insula, the person will say, "Oh, I feel something going on in my gut and on my left side."

换句话说，如果你把某人放入功能磁共振成像机器中，或者你用电极从岛叶进行记录，就像现在在出于其他目的的神经外科手术过程中在人类身上多次所做的那样，你会发现，如果你刺激岛叶一端的神经元，这个人会说，“哦，我感觉到我的肠道和左侧正在发生一些事情。”

And then as you were to march that stimulation across the insula, you would find that they would now be paying attention to their legs, or just to one leg, or to their whole body, or to the sensations in their face or their head.

然后，当你将刺激穿过脑岛时，你会发现他们现在会注意自己的腿，或者只注意一条腿，或者注意他们的整个身体，或者注意他们脸上或头部的感觉。

So there's a systematic map of interoception in the insula.

所以岛叶有一个系统的内感受图。

And there are direct connections between the amygdala and the insula.

杏仁核和岛叶之间有直接的联系。

And the amygdala, despite getting this reputation as just being a fear center or a threat detection center, is actually part of a much larger set of networks that include inputs from the hippocampus, an area of the brain that's involved in memory formation and storage.

尽管杏仁核被认为只是恐惧中心或威胁检测中心，但它实际上是一个更大的网络的一部分，其中包括来自海马体的输入，海马体是大脑中参与记忆形成和存储的区域。

And what is observed is that people who have PTSD tend to have greater, or rather stronger connections between the amygdala and the insula than is normally observed in people who do not have PTSD.

我们观察到，与没有患有创伤后应激障碍的人相比，患有创伤后应激障碍的人杏仁核和岛叶之间的联系往往更大，或者说更强。

Okay?

好的？

So there seems to be heightened input from the threat detection centers of the brain to this area of the brain, the insula, that is responsible for our sense of interoception.

因此，大脑的威胁检测中心似乎对负责我们内感受的脑岛区域进行了更高的输入。

Which provides a logical explanation for why people with PTSD often will feel the memory, or sense the discomfort, or just feel agitation, or even other types of bodily sensations like back pain or perhaps just a sense within their body that's more generalized.

这为为什么患有创伤后应激障碍的人经常会感受到记忆、或感到不适、或只是感到烦躁，甚至其他类型的身体感觉，如背痛或可能只是身体内更普遍的感觉，提供了一个合乎逻辑的解释。

It doesn't even have to be pain, doesn't even have to be negative, but that's associated with the negative memory of some traumatic event or series of events.

它甚至不一定是痛苦，甚至不一定是消极的，但这与某些创伤事件或一系列事件的消极记忆有关。

Okay?

好的？

So this is a really interesting brain network that I should mention exists in everybody, but that in people with PTSD seems to have heightened connectivity.

所以这是一个非常有趣的大脑网络，我应该提到它存在于每个人身上，但患有创伤后应激障碍的人似乎具有更高的连接性。

And those brain networks can be revealed by putting people with PTSD into functional imaging machines, getting them to recall a traumatic event, or even looking at the resting state of connectivity between the amygdala and the insula.

这些大脑网络可以通过将患有创伤后应激障碍的人放入功能成像机器中，让他们回忆创伤事件，甚至观察杏仁核和岛叶之间连接的静息状态来揭示。

So those experiments have been done, and what's also been done is to give people 1.5 milligrams per kilogram of MDMA and to look at the connectivity between the amygdala and the insula, and between the hippocampus, the amygdala, and the insula.

所以这些实验已经完成了，还给人们注射了每公斤 1.5 毫克的 MDMA，并观察杏仁核和岛叶之间以及海马体、杏仁核和岛叶之间的连接性。

And so what's observed over time in people that have been given MDMA and, this is very important and, and have done therapy for PTSD both before, during, and after the drug, there's a weakening of connections between the amygdala and the insula.

因此，随着时间的推移，在服用 MDMA 的人中观察到，杏仁核和岛叶之间的联系减弱，这一点非常重要，而且在用药前、用药期间和用药后都接受过 PTSD 治疗。

And that scales very directly with the relief of symptoms from PTSD.

这与创伤后应激障碍 (PTSD) 症状的缓解有非常直接的关系。

So this is really exciting because it's one thing to see a brain network get activated or inactivated, or you say, okay, in one person, a certain connection between threat centers and the interoceptive centers of the brain was, let's say, arbitrary units.

所以这真的很令人兴奋，因为看到大脑网络被激活或失活是一回事，或者你说，好吧，在一个人中，威胁中心和大脑内感受中心之间的某种联系是任意单位。

Let's say it was level eight out of 10 for that person.

假设那个人的等级是 8 级（满分 10 级）。

These things are normalized for a particular person.

这些事情对于特定的人来说是正常的。

And then after taking MDMA and doing PTSD therapy, it was five out of 10 or four out of 10.

然后服用 MDMA 并进行 PTSD 治疗后，这一比例为十分之五或十分之四。

That's a good experiment, but what's far more powerful is to observe that in that patient or that person, and then to see a change that's perhaps less dramatic.

这是一个很好的实验，但更有效的是观察那个病人或那个人的情况，然后看到可能不那么引人注目的变化。

So a shift from eight out of 10 to seven out of 10 in another person, and to see less shift in brain connectivity in the same network.

因此，在另一个人身上，从十分之八转变为十分之七，并且在同一网络中看到大脑连接性的变化较小。

And then perhaps in the person that went from full-blown PTSD to full remission of PTSD, something that, believe it or not, has been observed in single sessions with MDMA.

然后，也许在从全面的 PTSD 到 PTSD 完全缓解的人身上，无论你相信与否，在使用 MDMA 的单次治疗中都观察到了这一点。

If that person demonstrates an even greater reduction in the connections between the amygdala and the insula, well, then that gives even more confidence that this connection between the amygdala and the insula is actually perhaps causally related to the reduction in symptoms of PTSD.

如果这个人表现出杏仁核和岛叶之间的联系更加减少，那么这就更加有信心杏仁核和岛叶之间的这种联系实际上可能与 PTSD 症状的减少存在因果关系。

Or even if it's just correlated with a reduction in symptoms of PTSD, the fact that the degree of reduction of connection of this circuit scales with the reduction in clinically relevant symptoms, that's a very powerful finding because it moves things away from pure correlation of, oh, this brain area is active or less active over time, and this person has more or fewer symptoms of PTSD, to something that starts to look like a mechanistic and logical framework for understanding PTSD, as well as the effects of MDMA, and for understanding how changes in the brain underlie relief from PTSD.

或者，即使它只是与 PTSD 症状的减轻相关，事实上，该回路连接的减少程度与临床相关症状的减少成正比，这是一个非常有力的发现，因为它使事情从纯粹的相关性，哦，随着时间的推移，这个大脑区域活跃或不活跃，以及这个人或多或少的 PTSD 症状，到一些开始看起来像是理解 PTSD 的机械和逻辑框架，以及 MDMA 的影响，以及了解大脑的变化是如何缓解创伤后应激障碍的。

Okay, so again, even if you just could grasp the idea that you have a brain area, the amygdala, that's involved in threat detection, and it provides inputs to another brain area called the insula, which is involved in this thing called interoception, and that reductions in those connections between the amygdala and the insula scale with or correlate with reductions in PTSD symptoms as a consequence of people taking MDMA.

好吧，再说一遍，即使你能理解这样的想法：你有一个大脑区域，杏仁核，它参与威胁检测，它向另一个称为岛叶的大脑区域提供输入，岛叶参与称为内感受的东西，并且杏仁核和岛叶之间的连接减少与服用 MDMA 导致的 PTSD 症状的减少相关。

So if you have that under your mental belt, I promise you, you understand far more about how MDMA impacts the brain in the short and long term than 99.9% of people out there.

因此，如果您有这一点，我向您保证，您比 99.9% 的人更了解 MDMA 如何在短期和长期影响大脑。

However, it's also important that you understand a few other things that MDMA does to the brain, as well as what it doesn't do to the brain.

然而，了解 MDMA 对大脑的其他一些作用以及它不会对大脑产生的作用也很重要。

First of all, classic psychedelics like psilocybin and LSD, as I mentioned earlier, are known to create more lateral connectivity between different areas of the so-called neocortex.

首先，正如我之前提到的，裸盖菇素和LSD等经典迷幻药可以在所谓的新皮质不同区域之间建立更多的横向连接。

And these are long-lasting changes that are thought to underlie both some of the relief from major depression, but also some of the enhanced creativity and some of the other things that have been observed with psilocybin treatment.

这些持久的变化被认为是重度抑郁症缓解的基础，也是创造力增强和裸盖菇素治疗观察到的其他一些效果的基础。

And again, if you're interested in psilocybin treatments and psilocybin itself, please check out the episode that I did on psilocybin and the guest episode with Dr. Robin Carhart-Harris.

再说一遍，如果您对裸盖菇素治疗和裸盖菇素本身感兴趣，请查看我关于裸盖菇素的剧集以及罗宾·卡哈特-哈里斯博士的客座剧集。

Those episodes, like all other episodes of the Huberman Lab podcast, can be found at hubermanlab.com.

这些剧集与 Huberman Lab 播客的所有其他剧集一样，可以在 hubermanlab.com 上找到。

It's a fully searchable site.

这是一个完全可搜索的网站。

You can put keywords into the search function.

您可以在搜索功能中输入关键字。

It will take you to specific timestamps.

它将带您到特定的时间戳。

Every episode is timestamped, so you can navigate to topics of particular interest to you.

每集都有时间戳，因此您可以导航到您特别感兴趣的主题。

Feel free to go there and listen to those episodes about psilocybin.

请随意去那里听一下有关裸盖菇素的节目。

MDMA, by contrast, does not seem to produce long-lasting increases in lateral connectivity between those same brain networks, probably because it impacts different serotonin receptors.

相比之下，MDMA 似乎不会持久增加这些相同大脑网络之间的横向连接，可能是因为它影响不同的血清素受体。

It does, however, seem to change resting state functional connectivity within these limbic structures like the amygdala and related structures that are associated with threat detection.

然而，它似乎确实改变了这些边缘结构（如杏仁核和与威胁检测相关的结构）内的静息状态功能连接。

Now, this is interesting, and it actually was highlighted very nicely in a study I'll provide a link to in our show note caption, which actually has Dr. Robin Carhart-Harris as the first author.

现在，这很有趣，实际上在一项研究中很好地强调了这一点，我将在我们的节目注释标题中提供一个链接，该研究实际上以罗宾·卡哈特-哈里斯博士为第一作者。

So not only has he done incredible work on psilocybin and LSD and DMT and ayahuasca in his laboratory, but also on MDMA.

因此，他不仅在实验室中对裸盖菇素、LSD、DMT 和死藤水进行了令人难以置信的研究，而且还在 MDMA 方面进行了令人难以置信的研究。

And the particular study that I have in mind here showed that people who take MDMA at more or less the dosages that we talked about earlier report marked increases in positive mood, as well as decreased blood flow to the amygdala and hippocampus.

我在这里想到的一项具体研究表明，服用 MDMA 剂量或多或少的人，我们之前提到的报告显示，积极情绪显着增加，杏仁核和海马体的血流量减少。

So again, these threat detection centers of the brain and brain areas associated with memory.

再次强调，这些威胁检测中心位于大脑和与记忆相关的大脑区域。

And those changes are seen both while under the influence of MDMA and afterwards when the brain is simply at rest.

这些变化在 MDMA 的影响下以及之后大脑完全休息时都会出现。

So it really does appear that MDMA creates neuroplasticity that changes the overall level of activation of these threat detection networks and their connections to memory systems in a way that's pervasive over time, and that doesn't require any particular probe with a negative stimulus.

因此，摇头丸确实产生了神经可塑性，改变了这些威胁检测网络的总体激活水平及其与记忆系统的连接，这种方式随着时间的推移而普遍存在，并且不需要任何带有负面刺激的特定探针。

Now, translated to English, what that means is that during the MDMA session, people report feeling less threatened, more prosocial towards others, more empathic towards others and themselves, and then after the session, they have less of a threat response to memories that before the session were more troubling, and those changes in the brain do seem to be pervasive.

现在，翻译成英语，这意味着在MDMA治疗期间，人们报告感觉更少的威胁，对他人更加亲社会，对他人和自己更有同理心，然后在治疗后，他们对治疗前更令人不安的记忆的威胁反应减少，大脑中的这些变化似乎确实普遍存在。

So there are both short-term and long-term effects of MDMA, all of which point in the direction of lowered levels of threat detection, heightened levels of positivity, prosocial components of the brain, more active threat detection centers of the brain, less active.

因此，摇头丸既有短期影响，也有长期影响，所有这些影响都表明威胁检测水平降低、积极性水平提高、大脑的亲社会成分、大脑威胁检测中心更加活跃、不那么活跃。

Now, earlier we talked about MDMA as a drug that potently increases dopamine and even more potently increases serotonin, largely acting through this serotonin 1B receptor.

现在，前面我们谈到 MDMA 作为一种药物，可以有效增加多巴胺，甚至更有效地增加血清素，主要通过血清素 1B 受体发挥作用。

Now, without getting into too many more details before moving on to issues of toxicity around MDMA, I do want to touch on what I think is perhaps the finest of the animal model studies of MDMA that explored which brain networks and which chemical, that is serotonin or dopamine, is responsible for, say, the motivational components of MDMA versus the prosocial effects of MDMA.

现在，在继续讨论 MDMA 的毒性问题之前，我确实想谈谈我认为可能是最好的 MDMA 动物模型研究，该研究探讨了哪种大脑网络和哪种化学物质（即血清素或多巴胺）负责 MDMA 的动机成分与 MDMA 的亲社会效应。

And then it also raises a really important point, which I haven't mentioned yet in this episode, which is the role of oxytocin, something that many of you have perhaps heard of.

然后它还提出了一个非常重要的点，我在这一集里还没有提到，那就是催产素的作用，你们很多人可能都听说过。

The paper that I'm going to describe is from the laboratory of Dr. Robert Malenka.

我要描述的这篇论文来自 Robert Malenka 博士的实验室。

He's a colleague of mine at Stanford University School of Medicine, Psychiatry, and Behavioral Sciences.

他是我在斯坦福大学医学院、精神病学和行为科学学院的同事。

He is both a pioneer and luminary in the field of neuroplasticity, of how the brain wires and forms memories and can change itself over time in response to experience, as well as the study of drugs of abuse, as well as the study of drugs like MDMA and now additional compounds that can provide therapeutic support in certain conditions.

他是神经可塑性领域的先驱和杰出人物，该领域涉及大脑如何连接和形成记忆，以及如何随着时间的推移根据经验而改变自身，以及滥用药物的研究，以及对 MDMA 等药物和现在可以在某些条件下提供治疗支持的其他化合物的研究。

The study, which I will provide a link to in the show note caption, is entitled 'Distinct Neural Mechanisms for the Prosocial and Rewarding Properties of MDMA.' And I'm just going to summarize the major results of this study.

我将在节目注释标题中提供该研究的链接，该研究的标题是“MDMA 的亲社会和奖励特性的独特神经机制”。我将总结这项研究的主要结果。

It's a study that was done on mice, and I realize that a lot of people will hear that and think, "Ah, what relevance does that have to humans?" But when thinking about the effects of dopamine and serotonin in the types of circuits that we've been talking about thus far, these circuits that are subcortical, as we refer to them, so these are limbic circuits, these are hypothalamic circuits, these are what are called mesolimbic circuits.

这是一项针对老鼠的研究，我意识到很多人听到这个后会想，“啊，这与人类有什么关系？”但是，当考虑多巴胺和血清素对我们迄今为止所讨论的回路类型的影响时，这些回路是皮质下的，正如我们所说的那样，这些是边缘回路，这些是下丘脑回路，这些是所谓的中边缘回路。

These are all names for circuits that are highly conserved between mice and humans, and so results in mice really do translate quite well to results in humans, at least insofar as the effects of MDMA and which neurochemicals are involved is concerned.

这些都是在小鼠和人类之间高度保守的电路的名称，因此小鼠的结果确实可以很好地转化为人类的结果，至少就 MDMA 的影响以及涉及的神经化学物质而言是如此。

So what they found in this study, using a huge array of beautiful techniques, such as inactivation of specific brain areas, activation of specific brain areas, drug antagonists to prevent oxytocin function, or drug antagonists to prevent specific receptors involved in the serotonin pathway.

所以他们在这项研究中发现了这一点，使用了大量漂亮的技术，例如特定大脑区域的失活、特定大脑区域的激活、药物拮抗剂来阻止催产素功能，或者药物拮抗剂来阻止参与血清素途径的特定受体。

Lots and lots of tools in their toolkit.

他们的工具箱中有很多很多工具。

What they found is that MDMA causing the release of dopamine is what really establishes the rewarding effects of an experience.

他们发现，MDMA 会导致多巴胺的释放，这才是真正建立体验的奖励效果的原因。

This isn't really a surprise.

这其实并不奇怪。

We've known that MDMA, just like cocaine or methamphetamine or Adderall for that matter, or Vyvanse for that matter, creates big increases in dopamine that tend to couple an experience with a sense of reward and lead to changes in the neural circuitry that make the animal or human more likely to seek out that same experience again.

我们知道，MDMA，就像可卡因、甲基苯丙胺、阿得拉或 Vyvanse 一样，会大幅增加多巴胺，从而将体验与奖励感结合起来，并导致神经回路发生变化，使动物或人类更有可能再次寻求相同的体验。

Okay, these are the rewarding or sometimes called reinforcing properties of dopamine that take place in the so-called mesolimbic reward pathway.

好的，这些是多巴胺的奖励特性，有时也称为增强特性，发生在所谓的中脑边缘奖励通路中。

If you want to learn about mesolimbic reward pathways and dopamine and how they control everything from your level of motivation to your tendency to procrastinate or overcome procrastination, I've done two episodes about dopamine.

如果你想了解中脑边缘奖励通路和多巴胺，以及它们如何控制一切，从你的动机水平到你的拖延倾向或克服拖延，我已经做了两集关于多巴胺的内容。

You can simply go to hubermanlab.com, put dopamine into the search function, and you'll find at least two episodes on that topic.

您只需访问 hubermanlab.com，将多巴胺输入搜索功能，您就会找到至少两集有关该主题的内容。

And you'll also find a number of different tools related to how one can better regulate their own patterns of dopamine release for sake of motivation, et cetera.

您还会发现许多不同的工具，这些工具与人们如何更好地调节自己的多巴胺释放模式以获取动力等相关。

So MDMA is increasing dopamine to increase reward to a particular experience.

因此，MDMA 会增加多巴胺，以增加对特定体验的奖励。

What's the experience?

什么体验？

Well, this paper beautifully parses the fact that it is serotonin release within a structure called the nucleus accumbens, which is part of the reward pathway, which is rewarding the experience of social interaction.

这篇论文很好地解析了这样一个事实：伏隔核结构中血清素的释放，伏隔核是奖励途径的一部分，奖励社交互动的体验。

Now they do this by putting mice in arenas where they have the option of either spending time with other mice or not spending time with other mice, and blocking the activation of certain brain areas, and again, using drug antagonists, et cetera.

现在，他们通过将小鼠放入竞技场，让它们可以选择与其他小鼠共度时光或不与其他小鼠共度时光，并阻断某些大脑区域的激活，并再次使用药物拮抗剂等。

And what they find is that it really is the activation of the serotonin 1B receptor in the nucleus accumbens by MDMA that leads to this prosocial effect of MDMA.

他们发现，MDMA 确实激活了伏隔核中的血清素 1B 受体，从而导致了 MDMA 的这种亲社会效应。

So that's really nice to know because there's always been this conundrum of, okay, psilocybin and LSD are basically like serotonin.

所以很高兴知道这一点，因为一直存在这样的难题：裸盖菇素和迷幻药基本上就像血清素。

They activate the serotonin 2A receptor.

它们激活血清素 2A 受体。

MDMA has this huge serotonergic component, tons of serotonin released when one takes MDMA, but very different effects in the short and long term.

MDMA 具有巨大的血清素能成分，服用 MDMA 时会释放大量血清素，但短期和长期的效果却截然不同。

Very different subjective effects, very different patterns of change of activity in the brain in the short and long term.

短期和长期的主观影响截然不同，大脑活动变化模式也截然不同。

Well, that's because MDMA is activating the serotonin 1B receptor, not the serotonin 2A receptor, and it's doing so in a completely different set of brain networks, as is LSD and psilocybin.

嗯，那是因为 MDMA 激活的是血清素 1B 受体，而不是血清素 2A 受体，而且它是在一组完全不同的大脑网络中进行激活的，LSD 和裸盖菇素也是如此。

So what happens when an animal or a person takes MDMA is that social connection is strongly rewarded and reinforced, making social connection more likely after the drug wears off.

因此，当动物或人服用 MDMA 时，社会联系会得到强烈的奖励和加强，从而在药物失效后更有可能建立社会联系。

Now, that's one component of social connection, but in addition, people who take MDMA in the clinical therapeutic setting for the treatment of PTSD often report feeling more empathy and compassion for themselves during the session, but also for long periods of time, maybe even indefinitely after the session.

现在，这是社会联系的一个组成部分，但除此之外，在临床治疗环境中服用摇头丸来治疗创伤后应激障碍的人经常报告说，在治疗期间，而且在很长一段时间内，甚至可能在治疗后无限期地对自己感到更多的同理心和同情心。

So it really seems that the addition of this huge release of serotonin by MDMA on top of the release of dopamine sets in motion two parallel circuits, one for rewarding something, anything.

因此，在多巴胺释放的基础上，MDMA 释放的大量血清素似乎确实启动了两个并行电路，一个用于奖励某些东西，任何东西。

That's the dopamine component.

这就是多巴胺成分。

And then fortunately, because the increase in serotonin caused by MDMA increases empathy and sociability for and with others, but also for oneself, the motivation that's reinforced, that's wired into the brain, seems to be a motivation to perceive others as more kind, but also to be kinder to oneself.

幸运的是，由于 MDMA 引起的血清素增加，增加了对他人以及与他人的同理心和社交能力，同时也增加了对自己的同情心和社交能力，因此强化的动机，连接到大脑中的动机，似乎是一种认为他人更友善的动机，同时也是对自己更友善的动机。

Now, I realize that for some of you who are listening to this, you're probably saying, "Well, of course," right?

现在，我意识到对于你们中的一些人来说，您可能会说，“嗯，当然，”对吧？

Serotonin is prosocial and dopamine is motivation, so you put the two together and people become more motivated to be social and kinder to themselves.

血清素是亲社会的，多巴胺是动力，所以你把两者放在一起，人们就会变得更有动力去社交，对自己更友善。

Ah, but it didn't necessarily have to be that way, right?

啊，但不一定非得这样，对吧？

It is very hard to go from a statement like, drug A produces effects B, C, and D, to neurochemicals B, C, and D cause motivation and sociability, and therefore, when you take that drug, you're going to get all of that stuff.

很难从药物 A 产生效果 B、C 和 D 到神经化学物质 B、C 和 D 引起动机和社交性这样的说法非常困难，因此，当你服用该药物时，你会得到所有这些东西。

In fact, we have to go back to our understanding that MDMA, despite causing a big increase in serotonin, also causes huge increases in dopamine, and it does so with this molecule that is methamphetamine.

事实上，我们必须回到我们的理解，MDMA 尽管会导致血清素大幅增加，但也会导致多巴胺大幅增加，而且它是通过甲基苯丙胺这种分子来实现的。

Now, methamphetamine is not known to be a prosocial drug.

目前，甲基苯丙胺并不被认为是一种亲社会药物。

In fact, the study I just referred to, as well as some human studies, have explored how the application of methamphetamine, so not MDMA, but pure methamphetamine, impacts social interactions.

事实上，我刚才提到的研究以及一些人类研究都探讨了甲基苯丙胺（不是摇头丸，而是纯甲基苯丙胺）的应用如何影响社交互动。

And what it does to social interactions is very profound.

它对社交互动的影响是非常深远的。

It dramatically reduces one's tendency to engage in social interaction.

它极大地降低了一个人参与社交互动的倾向。

So this really speaks to the polypharmacology, as it's called, of MDMA.

所以这确实说明了 MDMA 的多重药理学。

The fact that serotonin and dopamine are released together has distinctly different effects than if just dopamine or just serotonin is increased.

血清素和多巴胺同时释放的事实与仅增加多巴胺或仅增加血清素具有明显不同的效果。

So much so that it's worth taking a step back and talking about another class of drugs which dramatically increases serotonin, which are the SSRIs, the selective serotonin reuptake inhibitors.

如此之多，以至于有必要退一步讨论另一类可显着增加血清素的药物，即 SSRIs，选择性血清素再摄取抑制剂。

SSRIs such as fluoxetine, Prozac, as well as Zoloft, and of course, there are many other SSRIs out there, citalopram, et cetera.

SSRIs，如氟西汀、百忧解、左洛复，当然，还有许多其他 SSRIs，如西酞普兰等。

They block the reuptake of serotonin and thereby lead to net increases in the amount of serotonin.

它们阻止血清素的再摄取，从而导致血清素量的净增加。

And yet those drugs are not known to create even close to the same sorts of effects as MDMA.

然而，这些药物是否会产生与 MDMA 相同的效果尚不清楚。

In fact, there have been human and animal studies showing that if you give somebody an SSRI prior to them taking MDMA, you actually block the prosocial and empathogenic effects of MDMA.

事实上，人类和动物研究表明，如果您在服用 MDMA 之前给某人服用 SSRI，您实际上可以阻止 MDMA 的亲社会和共情作用。

Now, you might say, why in the world would that be?

现在，你可能会说，到底为什么会这样呢？

Aren't these drugs just increasing serotonin and the increase in serotonin is prosocial, et cetera?

这些药物不只是增加血清素吗？血清素的增加是有利于社会的，等等？

Ah.

啊。

Well, that speaks to the complexity of all this polypharmacology and the fact that it's really the activation of serotonin at particular receptors, in this case, the serotonin 1B receptor, in particular brain areas.

嗯，这说明了所有这些多药理学的复杂性，以及它实际上是特定受体（在本例中为血清素 1B 受体）（特别是大脑区域）处血清素激活的事实。

In this case, the nucleus accumbens, a brain area associated with motivation and reward that largely explains the effects of MDMA in making people and animals, and octopuses included for that matter, more prosocial and more empathic towards themselves.

在这种情况下，伏隔核是一个与动机和奖励相关的大脑区域，它在很大程度上解释了摇头丸对人类和动物（包括章鱼）的影响，使他们变得更加亲社会，对自己更有同理心。

It's not just an issue of raising the levels of one neurochemical.

这不仅仅是提高一种神经化学物质水平的问题。

It's really about raising levels of a particular neurochemical acting at particular receptors in particular brain areas.

这实际上是为了提高作用于特定大脑区域的特定受体的特定神经化学物质的水平。

And in the case of MDMA, the fact that there's also dopamine increased in those very same brain areas, right?

就 MDMA 而言，事实上，那些相同的大脑区域中的多巴胺也有所增加，对吗？

I don't think I mentioned this before, but the nucleus accumbens is part of that mesolimbic reward pathway that is essentially establishing a reward for whatever is happening at the moment.

我想我之前没有提到过这一点，但伏隔核是中脑边缘奖励通路的一部分，该通路本质上是为当前发生的任何事情建立奖励。

So the way to conceptualize MDMA and its effects on the brain, both subjectively and mechanistically Is that it's an empathogen for which empathy and social connection is very strongly reinforced while under the influence of the drug, and in a way so intense and powerful that those neural networks get stronger and persist in being more active for long periods of time after the drug has worn off.

因此，从主观上和机械上来概念化 MDMA 及其对大脑的影响的方法是，它是一种共情剂，在药物的影响下，同理心和社会联系会得到非常强烈的强化，并且以一种如此强烈和强大的方式，以至于这些神经网络变得更强，并在药物失效后的很长一段时间内持续更加活跃。

Now, one of the things that's been explored in both the animal literature and the human literature is that MDMA doesn't just increase dopamine and doesn't just increase serotonin, but it also profoundly increases levels of oxytocin release in the brain.

现在，动物文献和人类文献中探索的一件事是，MDMA 不仅会增加多巴胺和血清素，而且还会大大增加大脑中催产素的释放水平。

Now, oxytocin is considered what's called a neurohormone because it acts as both a neurotransmitter, or I guess if we were going to be really specific, we'd say a neuromodulator because it tends to modulate the activity of a bunch of other circuits, and a hormone.

现在，催产素被认为是所谓的神经激素，因为它既充当神经递质，或者我想如果我们要真正具体的话，我们会说它是神经调节剂，因为它倾向于调节一堆其他回路的活动，并且是一种激素。

How can we say it's a hormone or a modulator or a transmitter?

我们怎么能说它是一种激素、调节剂或递质呢？

Well, hormonal effects tend to be effects that act not just locally, but on many sites within the brain and body as well.

嗯，荷尔蒙效应往往不仅作用于局部，而且作用于大脑和身体内的许多部位。

And oxytocin is known to do that as well as to work locally.

众所周知，催产素可以做到这一点，并且可以在局部发挥作用。

So that's what we call a neurohormone.

这就是我们所说的神经激素。

It activates neurons and is associated with neural networks related to pair bonding, both between parent and child, both mother and child, and father and child, or caretaker and child, not just biological parent, as well as bonding between friends, bonding between lovers, and it's thought to actually be involved in the process, that is the painful process, of breaking of bonds when people are no longer available to us as caretakers or as partners, either by way of breakup, death, departure, et cetera.

它激活神经元，并与配对关系相关的神经网络相关，包括父母和孩子之间、母亲和孩子之间、父亲和孩子之间、看护者和孩子之间，不仅仅是亲生父母之间，还有朋友之间的联系、恋人之间的联系，并且它被认为实际上参与了这个过程，即当人们不再作为看护者或伴侣时，无论是通过分手、死亡、离开等方式，打破联系的痛苦过程。

In fact, there are even data suggesting that humans can have strong oxytocin responses to their pets, in particular dogs, and their dogs can have strong oxytocin patterns of release in response to their owners.

事实上，甚至有数据表明，人类会对他们的宠物（尤其是狗）产生强烈的催产素反应，而他们的狗也会对其主人产生强烈的催产素释放模式。

I think for any dog lovers or dog owners, certainly includes me, I'm raising my hand, that comes as no surprise.

我想对于任何爱狗人士或狗主人来说，当然包括我，我举手，这并不奇怪。

Anyone that's ever had to put down a dog or has lost a dog, and here, no disrespect to the cat owners, but I'm just referring to the studies that have been done on humans and dogs, you can certainly relate to the incredible pain of that loss.

任何曾经不得不杀死一只狗或失去了一只狗的人，在这里，并不是对猫主人的不尊重，但我只是指对人类和狗所做的研究，你当然可以体会到失去狗所带来的难以置信的痛苦。

Oxytocin is thought to be involved in bonding between people and other creatures, as well as the breaking of those bonds.

催产素被认为与人与其他生物之间的联系以及这些联系的破坏有关。

MDMA is known to powerfully increase oxytocin release.

众所周知，MDMA 可以强力增加催产素的释放。

In fact, there's a really nice study on this done in humans.

事实上，有一项针对人类的非常好的研究。

This is a study I'll provide a link to in the show note captions entitled Plasma Oxytocin Concentrations Following MDMA or Intranasal Oxytocin in Humans.

这是一项研究，我将在标题为人类 MDMA 或鼻内催产素后血浆催产素浓度的显示注释标题中提供链接。

Nowadays, oxytocin is available by nasal inhaler.

如今，催产素可以通过鼻吸入器获得。

To be honest, I don't know the legality around it.

老实说，我不知道它的合法性。

I don't know if it's gray market or, but what I'm about to tell you will basically discourage you from wanting to take it because what they found in this study was people given either 0.75 or 1.5 milligrams per kilogram of body weight of MDMA experienced increases in oxytocin.

我不知道这是否是灰色市场，但我要告诉你的基本上会让你打消服用它的念头，因为他们在这项研究中发现，服用每公斤体重 0.75 或 1.5 毫克 MDMA 的人会出现催产素增加的情况。

However, it was only the group that took 1.5 milligrams per kilogram of body weight of MDMA that experienced the really big significant changes in oxytocin.

然而，只有每公斤体重服用 1.5 毫克 MDMA 的那组人的催产素发生了真正显着的变化。

And when I say really big, really highly statistically significant, what they observed is that in the placebo group, because of course they include a placebo group, the amount of circulating oxytocin was 18.6 picograms per milliliter, which to you probably means nothing, and to me also sort of means nothing because those units of oxytocin can't be directly related to any kind of direct experience of feeling bonded or not bonded.

当我说非常大，非常具有统计显着性时，他们观察到的是，在安慰剂组中，因为当然他们包括安慰剂组，循环催产素的量为每毫升 18.6 皮克，这对你来说可能没有任何意义，对我来说也没有任何意义，因为这些单位的催产素不能与任何类型的束缚或不束缚的直接体验直接相关。

That's just a number.

这只是一个数字。

But nonetheless, it provides a baseline to compare to the average levels of oxytocin in the bloodstream of people that were given 1.5 milligrams per kilogram of MDMA, which is 83.7 picograms per milliliter.

但尽管如此，它还是提供了一个基线，用于与服用每公斤 1.5 毫克 MDMA（即每毫升 83.7 皮克）的人血液中催产素的平均水平进行比较。

That equates to nearly a fivefold increase in the amount of circulating oxytocin when people are under the influence of MDMA.

这相当于当人们受到 MDMA 的影响时，循环催产素的量增加了近五倍。

Now, this study had a bunch of different conditions, not just MDMA of different doses, not just placebo.

现在，这项研究有很多不同的条件，不仅仅是不同剂量的 MDMA，不仅仅是安慰剂。

They also had people take oxytocin by nasal spray, which we know can change levels of circulating oxytocin.

他们还让人们通过鼻喷雾剂服用催产素，我们知道这可以改变循环催产素的水平。

And indeed, when measured in the study, it did change levels of circulating oxytocin.

事实上，在研究中测量时，它确实改变了循环催产素的水平。

And the endpoint in the study was to have people give subjective ratings of their feelings of connectedness to one another, as well as rate, and here I'm just drawing directly from the paper of how much they like the feeling, how much they felt high.

这项研究的终点是让人们对彼此之间的联系感以及评分进行主观评分，在这里我只是直接从纸上得出他们对这种感觉的喜欢程度，以及他们感觉有多高。

They measure their heart rate, their systolic pressure, their diastolic blood pressure, et cetera.

他们测量心率、收缩压、舒张压等。

And they looked at how social people felt.

他们观察了社会人士的感受。

They looked at how insightful people felt.

他们观察人们的感受有多有洞察力。

And the key takeaway from this study, for sake of our discussion here today, is that it does not, again, it does not appear that the increases in oxytocin produced by taking MDMA are the source of the prosocial effects of MDMA.

为了我们今天在这里讨论，这项研究的关键结论是，服用 MDMA 产生的催产素增加似乎并不是 MDMA 亲社会效应的根源。

And that's also what was found in the animal studies of MDMA, where in those studies, mice were given MDMA at comparable doses.

这也是 MDMA 动物研究中发现的结果，在这些研究中，小鼠被给予相当剂量的 MDMA。

The doses were a little bit higher than used in the human studies.

这些剂量比人体研究中使用的剂量稍高一些。

But at comparable doses, big increases in oxytocin were observed, increases in sociability of those mice were observed, just as they are in humans that take MDMA.

但在相当的剂量下，观察到催产素大幅增加，这些小鼠的社交能力也有所增加，就像服用 MDMA 的人类一样。

But in those mice, they were also given a drug to block the oxytocin receptor, and lo and behold, no changes in sociability were observed.

但在这些小鼠中，他们还服用了一种药物来阻断催产素受体，结果发现，没有观察到社交能力的变化。

In humans that take oxytocin by nasal spray, you can see big increases in oxytocin.

在通过鼻喷雾剂服用催产素的人中，您可以看到催产素的大幅增加。

That's not surprising.

这并不奇怪。

Gets across the blood-brain barrier, oxytocin goes up, and levels of sociability do not increase.

穿过血脑屏障后，催产素会上升，而社交能力不会增加。

So what this points to is a situation where MDMA is increasing dopamine to increase motivation and to reward something.

所以这表明 MDMA 正在增加多巴胺以增加动力并奖励某些东西。

What gets rewarded?

得到什么奖励？

Well, what gets rewarded is the serotonin activation of particular brain networks associated with sociability, and the dramatic increases in oxytocin that are very, very real when people take MDMA do not appear to underlie any of the known short or long-term subjective effects of MDMA.

嗯，得到回报的是与社交相关的特定大脑网络的血清素激活，以及当人们服用 MDMA 时催产素的急剧增加，这似乎并不是 MDMA 任何已知的短期或长期主观影响的基础。

Now, a conclusion like that needs to have a caveat, and the caveat is that as far as we know, the big increases in oxytocin that are produced by MDMA aren't doing anything for the sorts of effects that we've been talking about here, sociability, empathy, et cetera.

现在，这样的结论需要有一个警告，而且警告是，据我们所知，MDMA 产生的催产素的大幅增加对于我们在这里讨论的各种影响（社交性、同理心等）没有任何作用。

But there could be other effects of oxytocin that we're just not aware of.

但催产素可能还有其他我们不知道的作用。

That said, the data from both animal models and in humans really point to the fact that the increases in oxytocin that are produced by MDMA are not directly related to any of the short and long-term effects of MDMA that we are most familiar with, namely motivation, sociability, increased empathy, or the longstanding changes in neural circuitry that underlie, for instance, reduced threat detection or reduced connectivity between threat detection centers of the brain and interoception.

也就是说，来自动物模型和人类的数据确实表明，MDMA 产生的催产素的增加与我们最熟悉的 MDMA 的任何短期和长期影响（即动机、社交能力、同理心增加）或神经回路的长期变化（例如威胁检测减少或大脑威胁检测中心与内感受之间的连接减少）没有直接关系。

So is the big increase in oxytocin produced by MDMA completely irrelevant in the context of this discussion?

那么 MDMA 产生的催产素的大幅增加与本次讨论的背景完全无关吗？

We don't know.

我们不知道。

It appears that it's not very relevant.

看来这并不是很相关。

Is oxytocin a meaningless molecule?

催产素是一个无意义的分子吗？

Right after all, they gave these people nasal infusions of oxytocin.

毕竟，他们给这些人鼻腔注射了催产素。

Oxytocin went way up.

催产素大幅上升。

They didn't observe anything very interesting or significant in the context of sociability.

他们没有观察到任何在社交方面非常有趣或重要的事情。

But we do know that oxytocin can play a powerful role in pair bonding and in human-human, human-animal bonding of various kinds from other experiments that have been done.

但我们确实从其他实验中知道，催产素可以在配对纽带以及人与人、人与动物的各种纽带中发挥强大的作用。

So I don't want to diminish the incredible power that oxytocin has in our brains and bodies, but it doesn't appear that the MDMA-induced increases in oxytocin, which are enormous, have much to do with anything related to the value of MDMA as a treatment for PTSD, or for its subjective effects on empathy, sociability, or any of those other factors either.

所以我不想削弱催产素在我们大脑和身体中所具有的令人难以置信的力量，但摇头丸引起的催产素的巨大增加似乎与摇头丸作为治疗创伤后应激障碍（PTSD）的价值或其对同理心、社交能力或任何其他因素的主观影响有很大关系。

Now, perhaps the one caveat to that is that Harriet de Wit's laboratory, which I referred to earlier, has looked at how variations in oxytocin receptor genes vary between people.

现在，也许需要注意的是，我之前提到的 Harriet de Wit 实验室已经研究了催产素受体基因的变异如何在人与人之间发生变化。

So it turns out that some people have an allele, basically a version of the oxytocin receptor that is different from other people that makes oxytocin work differently and actually less effectively in activating certain brain networks.

事实证明，有些人有一个等位基因，基本上是催产素受体的一个版本，它与其他人不同，使得催产素的作用不同，实际上在激活某些大脑网络方面效率较低。

And it does appear that when those people take MDMA, they actually experience less of a prosocial effect of the drug.

确实，当这些人服用 MDMA 时，他们实际上感受到的药物亲社会效应较少。

Now, that spits in the face of everything I just said about oxytocin not being involved in the effects of MDMA on prosociability and empathy.

现在，这与我刚才所说的关于催产素不参与摇头丸对社交能力和同理心的影响的一切都嗤之以鼻。

I think the bulk of the data really point to the fact that it's the serotonin increases combined with the dopamine increases caused by MDMA that lead to most of the understood effects, and that oxytocin, if it's playing a role, is going to play a more minor role.

我认为大量数据确实表明了这样一个事实：正是 MDMA 引起的血清素增加和多巴胺增加导致了大多数已知的影响，而催产素，如果它发挥了作用，将发挥更次要的作用。

Let's talk about the safety and potential neurotoxicity of MDMA.

我们来谈谈 MDMA 的安全性和潜在的神经毒性。

And here I really want to highlight that our discussion today is couched in a discussion about the application of pure MDMA to animals or humans in the context of laboratory or clinical studies.

在这里，我真的想强调，我们今天的讨论是在实验室或临床研究的背景下讨论纯 MDMA 对动物或人类的应用。

This is really important to point out because I would be remiss if I didn't note that there is a lot of recreational use of MDMA.

指出这一点非常重要，因为如果我没有注意到摇头丸有很多娱乐用途，那就是我的失职。

In fact, it was the recreational use of MDMA in the 1980s, but really that took off, even exploded in the 1990s with so-called rave culture that created the massive attention on illegality of MDMA and put the drug enforcement agencies onto MDMA as a drug that they wanted to, and indeed do restrict.

事实上，MDMA 在 20 世纪 80 年代只是用于娱乐性用途，但真正开始流行，甚至在 1990 年代爆发，所谓的狂欢文化引起了人们对 MDMA 非法性的广泛关注，并让缉毒机构将 MDMA 作为一种他们想要并确实限制的药物。

In fact, just today, in anticipation of this episode, I put MDMA into the search function on Google and clicked News, and there were at least two reports of major MDMA seizures and busts.

事实上，就在今天，为了期待这一事件，我将摇头丸放入谷歌的搜索功能中，然后点击新闻，至少有两则关于缉获和查获重大摇头丸的报道。

So again, I want to highlight the fact that MDMA is still illegal to possess or sell and certainly to traffic.

因此，我想再次强调这样一个事实：拥有或出售 MDMA 仍然是非法的，当然贩运也是非法的。

I also want to highlight the fact that nowadays, all recreational drugs, but certainly MDMA included, are often, in fact, very often contaminated with fentanyl.

我还想强调这样一个事实：如今，所有消遣性药物（当然也包括摇头丸）实际上经常受到芬太尼的污染。

And while fentanyl has certain clinical uses, fentanyl is highly deadly.

虽然芬太尼具有一定的临床用途，但芬太尼具有高度致命性。

The current estimates are as much as 60%, maybe even 80% of drugs that are sold on the gray market are being repackaged or reformulated with fentanyl, and there have been a lot of fentanyl-related deaths, both in kids and adults.

目前估计，灰色市场上出售的药物中有多达 60%、甚至 80% 是用芬太尼重新包装或重新配制的，并且已经发生了大量与芬太尼相关的死亡，包括儿童和成人。

So the sourcing of MDMA is extremely important, and the safety issues simply cannot be overlooked.

因此，MDMA的来源极其重要，安全问题也不容忽视。

And I say that not to protect me, I say that to protect you.

我这样说不是为了保护我，我这样说是为了保护你。

Right?

正确的？

The last thing any of us want is for someone to take a compound thinking it's one compound and it contains another compound, and them getting hurt or even dying.

我们最不希望发生的事情就是有人服用一种化合物，认为它是一种化合物，但其中含有另一种化合物，而他们会受伤甚至死亡。

And that is happening a lot, a lot, and it is certainly happening a lot for people that think that they're buying MDMA.

这种情况发生了很多很多，对于那些认为自己正在购买 MDMA 的人来说，这种情况肯定发生了很多。

The use of MDMA in the laboratory or in the clinical setting with pure MDMA has also been explored for the potential neurotoxicity of MDMA.

还探讨了在实验室或临床环境中使用纯 MDMA 的 MDMA 的潜在神经毒性。

So how would methamphetamine and MDMA be neurotoxic?

那么甲基苯丙胺和摇头丸如何具有神经毒性呢？

Well, that's because they increase dopamine in the case of methamphetamine, and dopamine and serotonin in the case of MDMA, and they do so to a very high degree.

嗯，那是因为它们会增加甲基苯丙胺的多巴胺，以及摇头丸的多巴胺和血清素，而且程度非常高。

The big increases in dopamine and serotonin, but in particular, the big increases in dopamine tend to promote electrical activity of other neurons.

多巴胺和血清素的大幅增加，特别是多巴胺的大幅增加往往会促进其他神经元的电活动。

Remember, these are, after all, neuromodulators.

请记住，这些毕竟是神经调节剂。

They modulate up or down the activity of other neurons, and dopamine tends to modulate the activity of other neurons up.

它们调节其他神经元的活动，而多巴胺往往会调节其他神经元的活动。

So dopamine itself is not neurotoxic, but when a lot of dopamine is released, it is neurotoxic, and it's well known that even a single dose of methamphetamine can be neurotoxic, not just for dopamine neurons, but for other types of neurons as well, including serotonergic neurons.

所以多巴胺本身并没有神经毒性，但当大量多巴胺释放时，它就具有神经毒性，众所周知，即使是单剂量的甲基苯丙胺也可能具有神经毒性，不仅对多巴胺神经元，而且对其他类型的神经元，包括血清素能神经元。

Put differently, we know that the brains of people that take methamphetamine degenerate to a small or to a large degree, depending on how often they take the drug, how potent the drug is, and whether or not they combine it with other drugs.

换句话说，我们知道服用甲基苯丙胺的人的大脑会或多或少地退化，这取决于他们服用药物的频率、药物的效力以及他们是否将其与其他药物结合使用。

And yes If you heard that combining caffeine with amphetamines can increase the neurotoxicity of amphetamines such as methamphetamine, that is true.

是的，如果您听说咖啡因与安非他明混合会增加安非他明（如甲基安非他明）的神经毒性，那是真的。

If you've heard that taking caffeine within the hours or same day as MDMA can increase the toxicity of MDMA, that does appear to be true based on animal studies.

如果您听说在服用摇头丸的几小时内或同一天服用咖啡因会增加摇头丸的毒性，根据动物研究，这似乎是正确的。

Now, there are not a lot of studies looking at the toxicity of MDMA in humans, but there are a few.

现在，关于 MDMA 对人体毒性的研究并不多，但也有一些。

There are also studies looking at the toxicity of MDMA in animal models, including non-human primate models.

还有研究在动物模型（包括非人类灵长类动物模型）中观察 MDMA 的毒性。

Now, this is a very complex literature, a lot of results, not all over the place, but they're scattered in a number of ways.

现在，这是一个非常复杂的文献，有很多结果，虽然不是到处都是，但它们分散在很多方面。

First of all, some of the animal studies have used dosages of MDMA as high as two milligrams per kilogram of body weight, as high as three milligrams per kilogram of body weight, and even in upwards of that.

首先，一些动物研究使用的MDMA剂量高达每公斤体重2毫克，高达每公斤体重3毫克，甚至更高。

But even for the animal studies that used a range of dosages from 0.75 to 1.5 milligrams per kilogram of body weight, there is some evidence that in laboratory mice or rats, there can be some loss of serotonergic tone in the brains of animals that have been administered MDMA.

但即使对于使用每公斤体重 0.75 至 1.5 毫克剂量的动物研究，也有一些证据表明，在实验室小鼠或大鼠中，服用 MDMA 的动物大脑中的血清素张力可能会有所损失。

Now, notice I said serotonergic tone, I didn't say serotonin neurons.

现在，请注意我说的是血清素能基调，我没有说血清素神经元。

Because of the way that MDMA works in encouraging or promoting big releases in dopamine, big releases in serotonin, it's not surprising that if the animals that were given MDMA are subsequently sacrificed, say, later that day or the next day, or maybe even a week or two weeks later, and those brains are stained for proteins that are related to the synthesis or release of serotonin, it's not surprising that there would be reductions in those sorts of proteins.

由于 MDMA 的作用方式是鼓励或促进多巴胺大量释放、血清素大量释放，因此如果随后将给予 MDMA 的动物处死（例如，当天晚些时候或第二天，甚至一周或两周后），并且这些大脑被与血清素合成或释放相关的蛋白质染色，那么这些蛋白质的减少也就不足为奇了。

Right?

正确的？

After all, a lot of dopamine and serotonin is released, and it can be depleted.

毕竟，大量的多巴胺和血清素被释放，并且可能会被耗尽。

But I should point out, depletion of a neuromodulator in the short term is not the same thing as depletion of that neuromodulator in the long term, nor is it the same as loss of the neurons that release dopamine and serotonin itself.

但我应该指出，短期内神经调节剂的消耗与长期内神经调节剂的消耗不同，也与释放多巴胺和血清素本身的神经元的损失不同。

So there are data pointing to the fact that repeated administration of MDMA at dosages that are very much within lines with what we're talking about today, 1.5 milligrams per kilogram of body weight, can lower total amounts of serotonin or other proteins in the serotonin synthesis pathway, or dopamine or proteins that are in the dopamine synthesis pathway in specific areas of the brain related to reinforcement, related to mood, related to motivation, et cetera.

因此，有数据表明，重复服用 MDMA 的剂量与我们今天讨论的剂量非常一致，即每公斤体重 1.5 毫克，可以降低血清素或血清素合成途径中其他蛋白质的总量，或者大脑中与强化、情绪、动机等相关的特定区域中多巴胺或多巴胺合成途径中蛋白质的总量。

However, the primate studies, or I should say the non-human primate studies, which are the sorts of animal studies that most closely mimic what one expects to see in the human brain, because after all, mice and the effects of these drugs in mice do translate to humans, but it's thought that non-human primates provide a model that's far more similar to humans.

然而，灵长类动物研究，或者我应该说非人类灵长类动物研究，是最接近地模仿人们期望在人类大脑中看到的东西的动物研究，因为毕竟，小鼠和这些药物在小鼠身上的效果确实会转化为人类，但人们认为非人类灵长类动物提供了一种与人类更相似的模型。

There, the data start to get kind of complicated in a way that suggests that MDMA might not be as neurotoxic as is thought based on the rodent studies.

在那里，数据开始变得有点复杂，表明 MDMA 可能不像啮齿动物研究中认为的那样具有神经毒性。

And this gets into a whole history of back and forth between different laboratories and governing bodies who are trying to keep MDMA illegal, as well as people such as the Sasha Shulgins of the world and people in the therapy community that are excited about the potential for MDMA becoming legal for the treatment of PTSD.

这涉及到不同实验室和管理机构之间的来回历史，这些实验室和管理机构试图将 MDMA 定为非法，而世界各地的 Sasha Shulgins 等人以及治疗界的人们对 MDMA 成为合法治疗 PTSD 的潜力感到兴奋。

And it really centers around one or two studies, both of which were published in very high-profile journals.

它实际上围绕一两项研究展开，这两项研究都发表在非常知名的期刊上。

And the one that I'll highlight, because the results are now very clear and conclusive, is a study that was published back in 2002, which was entitled "Severe Dopaminergic Neurotoxicity in Primates after a Common Recreational Dose Regimen of MDMA or Ecstasy." This paper was published in the journal, "Science," which is one of the three apex journals for publishing scientific research.

我要强调的一项研究是 2002 年发表的，因为现在的结果非常明确和结论性的，该研究的标题是“服用 MDMA 或摇头丸的常见休闲剂量方案后灵长类动物的严重多巴胺能神经毒性”。这篇论文发表在发表科学研究的三大顶级期刊之一的《Science》杂志上。

So there's "Science," "Nature," and "Cell." Those are the top, top journals, the most stringent journals to get scientific manuscripts into.

所以就有了“科学”、“自然”和“细胞”。这些都是顶级期刊，对科学稿件投稿要求最严格的期刊。

The paper received a lot of attention because, as you can imagine based on the title, it suggested that even recreational doses of ecstasy, even if it's pure ecstasy and it doesn't have contamination from additional methamphetamine or other things in it, is neurotoxic to serotonergic and/or dopaminergic neurons.

这篇论文受到了很多关注，因为正如你根据标题可以想象的那样，它表明即使是娱乐剂量的摇头丸，即使它是纯粹的摇头丸并且没有受到额外的甲基苯丙胺或其他物质的污染，对血清素能和/或多巴胺能神经元也具有神经毒性。

This is largely where MDMA got the reputation for, quote, unquote, putting holes in your brain.

这很大程度上就是 MDMA 获得“引用、取消引用、让你的大脑出洞”的名声的原因。

However, this study came under a lot of scrutiny for a couple of reasons.

然而，由于多种原因，这项研究受到了广泛的关注。

First of all, and I'm certainly not saying this, but it was argued that the authors of the study were perhaps trying to prevent the legalization of MDMA for the treatment of PTSD.

首先，我当然不是这么说的，但有人认为，该研究的作者可能试图阻止 MDMA 用于治疗 PTSD 的合法化。

As far as I know, there's no direct evidence that that statement is true, but you will actually find that in some of the scientific journals.

据我所知，没有直接证据表明该说法是正确的，但实际上您会在一些科学期刊中找到这一点。

In fact, I was able to find an editorial that was published in the biomedical journal in 2003, which argued somehow that Dr.

事实上，我找到了 2003 年生物医学杂志上发表的一篇社论，其中以某种方式认为 Dr.

Ricaurte was accused of, quote, rushing his results into print because of legislation designed to curb ecstasy use before US Congress.

引用里考特的话，他被指控因美国国会旨在遏制摇头丸使用的立法而仓促发表他的研究结果。

So there were some connotations, or rather there were some strong suggestions that there was a political backing to trying to get this study done quickly and into print and so forth.

因此，有一些含义，或者更确切地说，有一些强烈的建议，表明有政治支持来试图快速完成这项研究并付诸印刷等等。

I don't think that ever really got resolved.

我认为这个问题还没有真正得到解决。

What did get resolved, however, is that the very study in question was retracted.

然而，最终解决的是相关研究被撤回。

Okay?

好的？

So the authors themselves published a letter of retraction that unfortunately is not as well-recognized as the paper that stimulated this idea that MDMA is neurotoxic in primates.

因此，作者自己发表了一封撤回信，不幸的是，这封撤回信没有像激发 MDMA 对灵长类动物具有神经毒性这一观点的论文那样得到广泛认可。

And keep in mind that we are human primates, non-human primates being the closest model to human primates that we are aware of.

请记住，我们是人类灵长类动物，非人类灵长类动物是我们所知道的最接近人类灵长类动物的模型。

But to make a long story short, there were some issues of labeling of MDMA versus other drugs in the laboratory.

但长话短说，与实验室中的其他药物相比，MDMA 的标签存在一些问题。

There were some issues of mislabeling, all of which were eventually acknowledged by the authors of the study.

存在一些标签错误的问题，所有这些问题最终都被该研究的作者所承认。

And they concluded, in fact, they verified, based on some very detailed analysis, that what these monkeys were injected with was not actually MDMA, but rather was methamphetamine itself.

他们得出的结论是，事实上，他们根据一些非常详细的分析证实，这些猴子注射的实际上并不是摇头丸，而是甲基苯丙胺本身。

So what's not often acknowledged is the retraction of the paper on neurotoxicity And unfortunately, the neurotoxicity issue is often what's mentioned.

因此，不常被承认的是有关神经毒性的论文被撤回。不幸的是，神经毒性问题经常被提及。

Now, keep in mind, there are studies in rodents showing neurotoxicity of MDMA, perhaps even at recreational doses.

现在，请记住，对啮齿动物的研究显示摇头丸具有神经毒性，甚至在娱乐剂量下也是如此。

But to date, at least to my knowledge, there don't seem to be any data in either non-human primates or in humans showing toxicity of MDMA at clinically relevant doses, provided it is pure MDMA.

但迄今为止，至少据我所知，似乎没有任何数据在非人类灵长类动物或人类中显示临床相关剂量的 MDMA 的毒性，前提是它是纯 MDMA。

Now, I want to be very clear, I'm not saying that if you can get pure MDMA that you should take it or that it won't be neurotoxic.

现在，我想澄清的是，我并不是说如果你能得到纯 MDMA，你就应该服用它，或者它不会具有神经毒性。

Certainly, we can expect that because of the huge known variation in dopamine receptors, in serotonin receptors, and of course, because of the known interactions between MDMA and other compounds, in particular caffeine, but also drugs such as cocaine or other stimulants, that some people might experience more toxicity to a given dose of MDMA compared to somebody else.

当然，我们可以预期，由于多巴胺受体、血清素受体存在巨大的已知差异，当然，由于 MDMA 与其他化合物（特别是咖啡因）以及可卡因或其他兴奋剂等药物之间已知的相互作用，某些人可能会比其他人对给定剂量的 MDMA 产生更多的毒性。

And there's really no way to detect that susceptibility to neurotoxicity.

而且确实没有办法检测对神经毒性的敏感性。

Now, what we do know is that there are people in the general population that have taken a lot of MDMA, anywhere from one to 200, or sometimes even in excess of 400 doses of MDMA.

现在，我们所知道的是，普通人群中有人服用了大量 MDMA，剂量从 1 到 200 剂不等，有时甚至超过 400 剂 MDMA。

And there now are studies that have explored the neurotoxicity and perhaps even more importantly, the neurocognitive and behavioral effects of taking MDMA either zero times, one time, five times, 40 times, 200 times, et cetera.

现在有研究探索了神经毒性，也许更重要的是，服用 MDMA 零次、一次、五次、40 次、200 次等对神经认知和行为的影响。

And one of the, what I would consider landmark studies in this area is a study entitled "Residual Neurocognitive Features of Long-Term Ecstasy Users with Minimal Exposure to Other Drugs." And those words, "with minimal exposure to other drugs," is really key in the context of this conversation.

我认为该领域具有里程碑意义的研究之一是一项题为“长期服用摇头丸的人在接触其他药物最少的情况下的残留神经认知特征”的研究。 “尽量减少接触其他药物”这句话在本次对话中非常关键。

Because as I mentioned before, interactions between drugs, what's called polypharmacology, can create neurotoxicity.

因为正如我之前提到的，药物之间的相互作用，即所谓的多重药理学，会产生神经毒性。

It's unclear if MDMA is neurotoxic, but we know methamphetamine on its own is neurotoxic.

目前尚不清楚 MDMA 是否具有神经毒性，但我们知道甲基苯丙胺本身具有神经毒性。

We also know that people often will combine MDMA and methamphetamine.

我们还知道，人们经常会将 MDMA 和甲基苯丙胺结合起来。

We also know that a lot of so-called MDMA out there is mostly methamphetamine with only a little bit of MDMA.

我们还知道，很多所谓的摇头丸主要是甲基苯丙胺，只有一点点摇头丸。

So a study of the sort that I'm about to describe, where it is essentially confirmed that people were taking pure MDMA and not taking any other drugs, is of immense value.

因此，我将要描述的此类研究具有巨大的价值，该研究基本上证实了人们服用纯 MDMA 而没有服用任何其他药物。

This study has been a little bit controversial.

这项研究存在一些争议。

In fact, I've talked about it before.

其实我之前也谈过。

I talked about it on the Joe Rogan podcast.

我在乔·罗根播客上谈到过它。

I've talked about it briefly with a guest on this podcast, Dr. Nolan Williams, who's a triple board-certified physician, psychiatrist, and neurologist at Stanford School of Medicine.

我在这个播客上与诺兰·威廉姆斯博士简短地讨论过这个问题，他是斯坦福大学医学院三重委员会认证的医生、精神病学家和神经学家。

And it's an interesting study and a little bit controversial because it relied on a population of people who have taken MDMA anywhere from one to 200 times and who've not taken any other drugs, including caffeine.

这是一项有趣的研究，但也有一点争议，因为它依赖于服用过 1 到 200 次 MDMA 且未服用任何其他药物（包括咖啡因）的人群。

And the population in mind here is a population of people living in Utah who self-identify as members of the Church of Latter-day Saints, sometimes referred to as Mormons, sometimes referred to as LDS or of the Church of Latter-day Saints.

这里所指的人口是居住在犹他州的人口，他们自认为是后期圣徒教会的成员，有时被称为摩门教徒，有时被称为 LDS 或后期圣徒教会。

The Church of Latter-day Saints, as I understand, does not allow for taking of certain compounds, certain drugs, certainly most recreational drugs, alcohol, even caffeine.

据我了解，后期圣徒教会不允许服用某些化合物、某些药物，当然是大多数娱乐性药物、酒精，甚至咖啡因。

And I'm sure there's some variation on some of those themes, depending on where people live and the certain communities that they happen to be in.

我确信其中一些主题会有所不同，具体取决于人们居住的地方以及他们碰巧所在的某些社区。

I am in no way, shape, or form declaring that I'm an expert on Latter-day Saints.

我绝不以任何方式、形式或形式宣称我是后期圣徒方面的专家。

I have a couple of friends who are LDS, happen to be very nice people.

我有几个朋友是摩门教，碰巧他们都是很好的人。

As far as I know, they were not the people in this study.

据我所知，他们不是这项研究的对象。

But this study really emphasized ecstasy users, as they're called, who have not taken other drugs, who self-identify as LDS.

但这项研究确实强调了摇头丸使用者（他们被称为“摇头丸使用者”），他们没有服用其他药物，自认为是摩门教徒。

And the major takeaway of this study was that for moderate, meaning people who have taken ecstasy anywhere from 22 to 50 times in their lifetime, as well as heavy users of MDMA, so these are people who have taken MDMA anywhere from 60, 6-0, to 450 times in their lifetime, there was little evidence of decreased cognitive performance in standard assays for cognitive performance.

这项研究的主要结论是，对于中度人群（即一生中服用摇头丸 22 至 50 次的人）以及 MDMA 的重度使用者（即一生中服用 60、6-0 到 450 次 MDMA 的人）来说，在认知能力的标准检测中几乎没有证据表明认知能力下降。

Now, there were some effects showing poor, here I'm quoting from the findings, poor strategic self-regulation, quote, "possibly reflecting increased impulsivity." However, when you see a conclusion like that, you should immediately be thinking chicken versus egg.

现在，有一些效果显示不佳，在这里我引用调查结果，不良的战略自我调节，引用，“可能反映了冲动性的增加”。然而，当你看到这样的结论时，你应该立即思考先有鸡还是先有蛋。

Right?

正确的？

It could be that people that are more impulsive and that have less strategic self-regulation are more likely to take ecstasy 450 times.

比较冲动、缺乏策略性自我调节的人可能更容易服用 450 倍的摇头丸。

You could conclude that, or you could conclude that people who have taken ecstasy 75 times or 25 times, et cetera, are degrading their levels of self-control and thereby increasing impulsivity.

你可以得出这样的结论，或者你可以得出这样的结论：服用摇头丸 75 次或 25 次等等的人正在降低他们的自我控制水平，从而增加冲动。

The direction of the effect is not known.

影响的方向尚不清楚。

These are purely correlations.

这些纯粹是相关性。

Nonetheless, this study and a few others like it really stand as our best evidence, believe it or not, as to how ecstasy taken many times, because after all, these people are taking anywhere from 22 to 450 doses of ecstasy in their lifetime, is producing severe detriments in cognitive performance, and that simply does not appear to be the case.

尽管如此，不管你信不信，这项研究和其他一些类似的研究确实是我们关于多次服用摇头丸的最佳证据，因为毕竟，这些人一生中服用了 22 到 450 剂摇头丸，对认知能力产生了严重损害，但事实似乎并非如此。

Now, unfortunately, there are no data looking at the brains of these individuals, looking at, for instance, which brain structures are active or less active, or perhaps even looking at levels of serotonin or dopamine, all things that can be done with positron emission tomography imaging, functional MRI, et cetera.

不幸的是，现在没有数据观察这些人的大脑，例如观察哪些大脑结构活跃或不活跃，甚至可能观察血清素或多巴胺的水平，所有这些都可以通过正电子发射断层扫描成像、功能性核磁共振成像等来完成。

Hopefully, those studies will be done in the not-too-distant future.

希望这些研究能够在不久的将来完成。

But if we were to just take a step back from all the data, the data in mice, in rats, in non-human primates, the retraction of the study in non-human primates, which showed that the primates that showed neurodegeneration were not given MDMA as was thought by the researchers, but rather, as later was acknowledged, were actually given methamphetamine, and we take into account these moderate and heavy users of MDMA, who, as far as we know, are being honest and haven't taken any other drugs And we look at the clinical studies where people who have never taken MDMA are given one or two or three defined doses of pure MDMA.

但如果我们从所有数据中退一步，小鼠、大鼠、非人类灵长类动物的数据，撤回非人类灵长类动物的研究，该研究表明，表现出神经退行性变的灵长类动物并没有像研究人员所认为的那样服用摇头丸，而是，正如后来所承认的那样，实际上服用了甲基苯丙胺，而且我们考虑到了这些中度和重度摇头丸使用者，据我们所知，他们是诚实的，没有服用过任何药物。其他药物 我们还研究了一些临床研究，其中从未服用过 MDMA 的人被给予一、两或三种规定剂量的纯 MDMA。

We'll talk about those studies in a moment.

我们稍后将讨论这些研究。

I think the gestalt, the top contour, the overall view of those studies is that provided it is pure MDMA and provided the individual is not consuming other drugs which have the potential to be neurotoxic, and provided that it's being done in a controlled clinical setting, the risk for toxicity seems quite a bit lower than the popular press has promoted.

我认为格式塔，顶部轮廓，这些研究的总体观点是，只要它是纯摇头丸，并且个人没有服用其他可能具有神经毒性的药物，并且如果它是在受控的临床环境中进行的，那么毒性风险似乎比大众媒体宣传的要低得多。

And yet there is still the risk of neurotoxicity if people are taking high doses of MDMA or taking it very frequently, or certainly if they are taking it in conjunction with other drugs or, or I should say and/or taking MDMA in settings that can promote neurotoxicity.

然而，如果人们服用高剂量的 MDMA 或非常频繁地服用，或者当然如果他们与其他药物一起服用，或者，或者我应该说和/或在可能促进神经毒性的环境中服用 MDMA，仍然存在神经毒性的风险。

And the settings I'm referring to are any settings in which blood pressure or body temperature have the propensity to be greatly increased.

我所指的环境是指血压或体温有大幅升高倾向的任何环境。

Every study in mice, in non-human primates, and in humans in which MDMA is administered has observed significant increases in blood pressure and heart rate.

每一项针对小鼠、非人类灵长类动物和人类的研究都发现，服用 MDMA 后血压和心率显着升高。

MDMA is, after all, a psychostimulant.

毕竟，摇头丸是一种精神兴奋剂。

It's a sympathomimetic.

这是一种拟交感神经药。

Talked about sympathomimetics and what that means in the episode on Adderall and Vyvanse and ADHD.

在关于 Adderall 和 Vyvanse 和 ADHD 的剧集中谈论了拟交感神经药及其含义。

But basically it's ramping up the activity of the sympathetic nervous system, which is your fight or flight system.

但基本上它会增强交感神经系统的活动，也就是你的战斗或逃跑系统。

Okay?

好的？

This is why people who take these drugs get big pupils, big pupils of the eyes.

这就是为什么服用这些药物的人的瞳孔会变大，眼睛的瞳孔变大。

This is why they feel agitated.

这就是他们感到焦躁的原因。

They want to talk a lot.

他们想聊很多。

They feel like they want to move a lot.

他们觉得自己很想搬家。

This is why people take it to dance at raves, et cetera.

这就是为什么人们带着它在狂欢派对等场合跳舞。

But when people take sympathomimetics, whether or not it's MDMA or amphetamine or cocaine or even caffeine, there's an increase in blood pressure and heart rate, but also body temperature.

但当人们服用拟交感神经药时，无论是摇头丸、安非他明、可卡因，甚至是咖啡因，血压和心率都会升高，体温也会升高。

And if that's done in an environment in which there's very little temperature regulation, so people aren't, for instance, drinking enough fluids and electrolytes, it's very hot in the room, you can get neurotoxicity based on temperature effects.

如果这是在温度调节很少的环境中进行的，例如，人们没有喝足够的液体和电解质，房间里很热，你可能会因温度影响而产生神经毒性。

And that's because serotonin and dopamine also act on the so-called medial preoptic area of the hypothalamus, which is involved in temperature regulation.

这是因为血清素和多巴胺也作用于下丘脑的所谓内侧视前区，该区域参与温度调节。

If you're curious about temperature regulation, I covered a lot of that in the episodes of the Huberman Lab podcast on deliberate cold exposure and deliberate heat exposure.

如果您对温度调节感到好奇，我在 Huberman 实验室播客的有关故意冷暴露和故意热暴露的剧集中介绍了很多内容。

This is an area I used to work on many years ago as a research scientist before moving on to other topics to research in my laboratory.

这是我多年前作为一名研究科学家从事的一个领域，然后才在我的实验室转向其他主题进行研究。

Big increases in body temperature are not good.

体温大幅升高并不好。

The body, and in particular your brain, can tolerate decreases in body temperature that are pretty robust and you can still stay safe.

身体，特别是您的大脑，可以承受相当强劲的体温下降，并且您仍然可以保持安全。

You're not going to kill neurons.

你不会杀死神经元。

But even an increase of three or four degrees in body temperature can start to kill off neurons.

但即使体温升高三四度也会开始杀死神经元。

So when thinking about the potential neurotoxicity of MDMA, the conditions, that is the environmental conditions, the behavioral conditions under which somebody takes MDMA are vitally important.

因此，当考虑 MDMA 的潜在神经毒性时，服用 MDMA 的条件，即环境条件和行为条件至关重要。

At least important, I would argue, as any other compounds they might be ingesting with MDMA.

我认为，至少重要的是，就像他们可能与 MDMA 一起摄入的任何其他化合物一样。

So that's something really serious to consider.

所以这是需要认真考虑的事情。

So if somebody says MDMA puts holes in your brain, you would be correct in being skeptical or at least giving them some counterarguments for that statement.

因此，如果有人说摇头丸会让你的大脑出现漏洞，你应该持怀疑态度，或者至少为他们的说法提供一些反驳。

But if somebody says MDMA is not toxic, well, then you would be equally valid in saying, "Ah, wait, but we need to think about the conditions under which MDMA is being taken.

但如果有人说 MDMA 无毒，那么你同样可以说：“啊，等等，但我们需要考虑服用 MDMA 的条件。

Is it pure MDMA or is it mostly methamphetamine?" In which case it would be very toxic.

是纯粹的摇头丸还是主要是甲基苯丙胺？”在这种情况下，它的毒性会很大。

Is it MDMA alone or in conjunction with caffeine within that same 24 hour period?

在同一 24 小时内，MDMA 是单独服用还是与咖啡因同时服用？

Is it MDMA while moving around a lot or being outdoors or being in an environment, perhaps a rave or dance type environment where temperature is going up?

是否是在经常走动或在户外或在温度升高的环境中（也许是狂欢或舞蹈类型的环境）时使用摇头丸？

Well, in that case it could be very neurotoxic.

好吧，在这种情况下，它可能具有很强的神经毒性。

So pharmacology of MDMA counts, but so does polypharmacology, the ingestion of other compounds, not just during the MDMA session, but also in the 24 hours before and after that MDMA session.

因此，MDMA 的药理学很重要，但复合药理学（即摄入其他化合物）也很重要，不仅在 MDMA 服用期间，而且在 MDMA 服用前后的 24 小时内也如此。

And behaviors will certainly impact temperature, which will impact whether or not MDMA is neurotoxic or not.

行为肯定会影响温度，从而影响 MDMA 是否具有神经毒性。

And despite my efforts, I couldn't find out whether or not the LDS community has officially sanctioned the use of MDMA.

尽管我付出了努力，我还是无法查明 LDS 社区是否正式批准使用 MDMA。

Certainly that's one possibility, but I have no evidence for that, or rather whether or not certain people within the LDS community have allowed themselves, given themselves permission to use MDMA and they are not using other drugs.

当然这是一种可能性，但我没有证据证明这一点，或者更确切地说，摩门教社区中的某些人是否允许自己使用 MDMA 并且他们没有使用其他药物。

What I do understand to be the case is that people within the LDS community are discouraged from using drugs like caffeine or cocaine or alcohol.

据我所知，摩门教社区内的人们不鼓励使用咖啡因、可卡因或酒精等药物。

And this particular population of people that was explored in this study self-identify as LDS and self-identify as having taken MDMA anywhere from 22 to 450 times.

本研究中探讨的这一特定人群自认为是 LDS，并自认为服用过 MDMA 22 至 450 次。

But where they got permission for that, whether or not it was from someone else or from themselves, I do not know.

但我不知道他们是从哪里获得许可的，无论是来自别人还是他们自己。

What I do know is that within the acknowledgments of the paper, there's actually a thank you to the person that identified this, quote, unique population for our study.

我所知道的是，在论文的致谢中，实际上是对为我们的研究识别出这一独特人群的人表示感谢。

So I welcome you to, uh, take a look at the paper and if any of you know more about if and how a particular subgroup within the LDS community is allowed to take MDMA, perhaps you want to put those in the comment section on YouTube.

因此，我欢迎您，呃，看一下这篇论文，如果你们中的任何人知道更多关于 LDS 社区中的特定小组是否以及如何允许服用 MDMA 的更多信息，也许您想将它们放在 YouTube 上的评论部分。

Before moving to our discussion about what MDMA is doing and the effects that people are seeing in the clinical studies for the treatment of PTSD, which by the way are extremely exciting, I can't wait to share these data with you.

在我们开始讨论 MDMA 的作用以及人们在治疗 PTSD 的临床研究中所看到的效果之前（顺便说一下，这些效果非常令人兴奋），我迫不及待地想与您分享这些数据。

I do want to touch on something that anyone who's heard about MDMA or perhaps used MDMA is familiar with, and that's the so-called crash that people experience after MDMA.

我确实想谈一谈任何听说过 MDMA 或可能使用过 MDMA 的人都熟悉的事情，这就是人们在 MDMA 后经历的所谓崩溃。

There are a lot of myths about the post MDMA crash and there's a lot of lore out there on the internet about how to offset the crash and a lot of lore about how to prevent the potential neurotoxicity of MDMA.

关于 MDMA 崩溃后有很多神话，互联网上有很多关于如何抵消崩溃的传说，以及很多关于如何预防 MDMA 潜在神经毒性的传说。

Earlier we talked about some of the major points around offsetting neurotoxicity, so certainly Making sure that any MDMA that one takes is in the legal clinical setting, that it's therefore pure MDMA, that it's not cut with other things, which certainly can increase toxicity.

早些时候我们讨论了有关抵消神经毒性的一些要点，所以当然要确保人们服用的任何 MDMA 都处于合法的临床环境中，因此它是纯 MDMA，它不会与其他物质混合，这肯定会增加毒性。

Controlling the temperature of one's environment, restricting caffeine intake, at least on the day of MDMA ingestion, but certainly the day before and the day after would be advantageous as well, simply because of the way that caffeine and activation of the adenosine receptor, as well as caffeine's effects on dopamine receptors, can interact with the potential, again, potential neurotoxicity of MDMA.

控制环境温度，限制咖啡因摄入量，至少在摄入 MDMA 当天，但当然前一天和后一天也是有利的，因为咖啡因和腺苷受体的激活，以及咖啡因对多巴胺受体的影响，可以与 MDMA 的潜在神经毒性相互作用。

But the crash that one experiences after MDMA is actually a phenomenon very common to the crash that one experiences after ingestion of any type of stimulant, cocaine, amphetamine, et cetera.

但吸食 MDMA 后出现的崩溃实际上是一种与摄入任何类型的兴奋剂、可卡因、安非他明等后出现的崩溃一样常见的现象。

And the crash that we're referring to is a drop in mood, increase in lethargy, feelings of lack of motivation.

我们所说的崩溃是指情绪低落、昏昏欲睡、缺乏动力的感觉。

Many people have wrongly assumed that the crash was due to "depletion of serotonin" or depletion of dopamine, or maybe even death of serotonergic and dopaminergic neurons.

许多人错误地认为崩溃是由于“血清素耗尽”或多巴胺耗尽，甚至可能是血清素能和多巴胺能神经元死亡所致。

And while certainly that could be the case, it's very unlikely that that would be the case in the immediate 24 or 48 hours after MDMA ingestion.

虽然确实可能是这种情况，但在摄入 MDMA 后 24 或 48 小时内不太可能出现这种情况。

That said, you will see protocols that people have put out on the internet, such as, after taking MDMA, you should take a bunch of 5-HTP or other precursors to serotonin or dopamine, which come in amino acid form.

也就是说，您会看到人们在互联网上发布的协议，例如，服用 MDMA 后，您应该服用一堆 5-HTP 或其他血清素或多巴胺的前体，它们以氨基酸形式存在。

So L-tryptophan, for instance, is the amino acid precursor to serotonin.

例如，L-色氨酸是血清素的氨基酸前体。

It's in the serotonin synthesis pathway.

它位于血清素合成途径中。

You'll hear that people will take L-tyrosine, which is the amino acid precursor to dopamine, as a way to try and buffer or increase dopamine during the so-called period of the crash.

您会听说人们会服用 L-酪氨酸（多巴胺的氨基酸前体）作为在所谓的崩溃期间尝试缓冲或增加多巴胺的一种方法。

There's really no evidence that any of those things can be beneficial, and there is actually some reason to believe that it might be detrimental, because if anything, taking L-tryptophan and taking L-tyrosine would actually further deplete serotonin and dopamine.

确实没有证据表明这些东西可能是有益的，而且实际上有一些理由相信它可能是有害的，因为如果有的话，服用 L-色氨酸和服用 L-酪氨酸实际上会进一步消耗血清素和多巴胺。

So the logic there is simply not very good.

所以那里的逻辑根本就不是很好。

What is clear, however, is that MDMA can cause not just profound increases in dopamine, serotonin, and oxytocin, but that any time there's a big increase in dopamine, there is going to be a post-dopaminergic increase in prolactin release.

然而，显而易见的是，摇头丸不仅会导致多巴胺、血清素和催产素的大幅增加，而且每当多巴胺大幅增加时，多巴胺能后催乳素的释放就会增加。

And prolactin is a hormone, sometimes considered a neurohormone, but it's really a hormone that's involved in a lot of things, milk letdown in lactating women.

催乳素是一种激素，有时被认为是一种神经激素，但​​它实际上是一种与很多事情有关的激素，例如哺乳期妇女的乳汁分泌不足。

It's involved in setting the refractory period to sexual arousal, and erection and ejaculation in males after ejaculation.

它涉及设定性唤起的不应期以及射精后男性的勃起和射精。

It's involved in lots of different functions in the brain and body, including the laying down of body fat stores.

它涉及大脑和身体的许多不同功能，包括体内脂肪储存的沉积。

And it's also associated with increases in lethargy, decreases in dopamine.

它还与嗜睡的增加和多巴胺的减少有关。

This is why drugs that increase dopamine are known to decrease prolactin, at least in the short term.

这就是为什么增加多巴胺的药物会降低催乳素，至少在短期内是这样。

This is why drugs like cabergoline, for instance, that increase dopamine, are used as ways to suppress prolactin.

这就是为什么像卡麦角林这样增加多巴胺的药物被用作抑制催乳素的方法。

Now, MDMA ingestion is known to dramatically increase prolactin, and people are starting to realize that it perhaps is the increase in prolactin that occurs both during and for some period of time, probably hours or days after ingestion of MDMA, that leads to at least some components of the so-called crash, that feeling of lethargy and lack of motivation, maybe diminished mood, et cetera.

现在，已知摄入 MDMA 会显着增加催乳素，人们开始意识到，可能是摄入 MDMA 期间和一段时间内（可能是摄入 MDMA 后数小时或数天）催乳素的增加，导致了所谓崩溃的至少某些组成部分，即昏昏欲睡和缺乏动力的感觉，可能情绪低落等。

And for that reason, some people have started to explore the use of things like P5P, which is essentially a metabolite of vitamin B6, which is known to suppress prolactin as a way to try and buffer some of that crash.

出于这个原因，一些人开始探索使用 P5P 等物质，它本质上是维生素 B6 的代谢产物，众所周知，维生素 B6 可以抑制催乳素，以此来尝试缓冲一些崩溃。

To my knowledge, there are no human data yet exploring the use of P5P or other vitamin B6 derivatives or cabergoline or things of that sort to reduce prolactin in a controlled, standardized clinical trial kind of manner.

据我所知，目前还没有人类数据探索使用 P5P 或其他维生素 B6 衍生物或卡麦角林或类似物质以受控、标准化临床试验的方式降低催乳素。

But I've spoken to some of the clinicians that are using MDMA legally within the context of the treatment of PTSD, and this is an area that's starting to receive some additional attention.

但我已经与一些在治疗创伤后应激障碍（PTSD）的情况下合法使用摇头丸的临床医生进行了交谈，这是一个开始受到更多关注的领域。

So I just mention it briefly here because, for instance, there's a lot of ideas out there that people should be taking L-tryptophan, they should be taking L-tyrosine, they should be taking magnesium, other things, et cetera, after taking MDMA in order to recover from the post-MDMA crash more quickly.

所以我在这里简单提一下，因为，例如，有很多想法认为人们在服用 MDMA 后应该服用 L-色氨酸、L-酪氨酸、镁等，以便更快地从 MDMA 后的崩溃中恢复过来。

But it's really the increase in prolactin which speaks most directly to the subjective effects of the so-called crash.

但实际上，催乳素的增加最直接地说明了所谓崩溃的主观影响。

So by my read of the mechanisms of MDMA, the neurochemicals it releases, the neurohormones that it promotes the release of, prolactin in particular, this P5P suppression of prolactin is perhaps the one that's most intriguing and that really has any kind of mechanistic basis.

因此，根据我对 MDMA 机制、它释放的神经化学物质、它促进释放的神经激素（尤其是催乳素）的了解，这种 P5P 对催乳素的抑制可能是最有趣的，并且确实具有某种机制基础。

So I promise that going forward, as the scientists and clinicians that are using MDMA for the treatment of PTSD and other conditions such as alcohol use disorder, et cetera, start to explore the use of post-MDMA session P5P and other modes of suppressing prolactin for the hours and days after MDMA, promise to update you on those findings.

因此，我保证，随着使用 MDMA 治疗 PTSD 和其他疾病（如酒精使用障碍等）的科学家和临床医生开始探索使用 MDMA 后的 P5P 和其他在 MDMA 后数小时和数天内抑制催乳素的模式，我承诺向您通报这些发现的最新情况。

Throughout today's episode, I've been referring to clinical studies, that is clinical trials, exploring the use of MDMA in order to augment treatment for PTSD.

在今天的节目中，我一直在提到临床研究，即临床试验，探索使用 MDMA 来增强 PTSD 的治疗。

So let's just take a moment and talk about what PTSD is.

让我们花点时间谈谈什么是创伤后应激障碍。

PTSD is post-traumatic stress disorder.

PTSD 是创伤后应激障碍。

Trauma is anything that modifies the brain to function less well going forward.

创伤是指任何改变大脑功能从而使其未来功能较差的事情。

You can have physical trauma, you can have emotional trauma.

你可能会受到身体上的创伤，也可能会受到情感上的创伤。

Typically, PTSD is used to refer to emotional trauma caused by either single events, so you can imagine car accident, sexual assault.

通常，创伤后应激障碍（PTSD）是指由单一事件造成的情感创伤，所以你可以想象车祸、性侵犯。

These could be first-person experiences, so things that happen to somebody that leads to trauma and then PTSD.

这些可能是第一人称经历，所以发​​生在某人身上的事情会导致创伤，然后导致创伤后应激障碍。

These can also be third-person events where someone observes something that is traumatic to them Maybe somebody being killed, dismembered, any number of different things that could be very traumatic in the immediate and long term.

这些也可以是第三人称事件，其中有人观察到对他们造成创伤的事情，也许有人被杀，肢解，任何数量的不同的事情都可能在短期和长期造成非常严重的创伤。

And of course, PTSD need not be caused only by single event traumas, but by multiple event traumas, entire relationships, entire childhoods, wartime experiences, combinations of different traumas, and on and on.

当然，创伤后应激障碍不一定是由单一事件创伤引起的，而是由多重事件创伤、整个关系、整个童年、战时经历、不同创伤的组合等等引起的。

There are so many different forms of trauma.

创伤有很多种不同形式。

If any of you are interested in trauma and its treatment, I highly recommend the book, "Trauma" by Dr. Paul Conti.

如果你们中有人对创伤及其治疗感兴趣，我强烈推荐保罗·康蒂博士的《创伤》一书。

He's an MD, medical doctor, psychiatrist.

他是医学博士、医生、精神病学家。

He was featured as a guest on this podcast.

他作为嘉宾出现在这个播客中。

He's been on a number of other prominent podcasts.

他还参加过许多其他著名的播客。

We will provide a link in our show note captions to the book, "Trauma." I consider that book to be the best book in terms of describing what trauma is and isn't, and how it leads to PTSD.

我们将在节目注释标题中提供“创伤”一书的链接。我认为这本书是描述创伤是什么、不是创伤以及创伤如何导致创伤后应激障碍（PTSD）的最好的书。

It also describes some of Dr. Paul Conti's own experiences with trauma and his own treatment of trauma in his patient population, which is quite wide-ranging.

它还描述了保罗·孔蒂医生自己的一些创伤经历以及他自己对患者群体的创伤的治疗，范围相当广泛。

Men, women, young people, older people, and a variety of traumatic experiences.

男人、女人、年轻人、老年人，以及各种创伤经历。

So excellent book for those of you interested in trauma.

对于那些对创伤感兴趣的人来说，这是一本非常棒的书。

Now, the treatment of trauma has been met with some degree of success through quality talk therapy.

现在，通过高质量的谈话疗法，创伤治疗已经取得了一定程度的成功。

Let's define quality talk therapy in the way that Dr. Paul Conti did on this episode.

让我们按照保罗·康蒂博士在这一集中所做的方式来定义高质量的谈话疗法。

That's talk therapy for which the patient, sometimes referred to as the client, but more traditionally referred to as the patient, and the therapist, so a psychologist or psychiatrist, has good rapport.

这就是谈话疗法，患者（有时被称为客户，但更传统地称为患者）和治疗师（即心理学家或精神病学家）有着良好的融洽关系。

And as a consequence of that rapport, there is the feeling of support, that there is a safe place in which to explore the trauma and what's happening in one's current life in order to understand how that trauma is fitting into adaptive and maladaptive behaviors and emotional states.

这种融洽关系的结果是，有一种支持的感觉，有一个安全的地方可以探索创伤和当前生活中发生的事情，以便了解创伤如何适应适应性和适应不良的行为和情绪状态。

Now, in addition to rapport and support being critical, there's a third component of effective talk therapy for trauma, which is insight, or one's ability to come to an understanding of why one feels the way they do, and to link that to some larger context that brings about some degree of relief.

现在，除了至关重要的融洽和支持之外，有效的创伤谈话疗法还有第三个组成部分，那就是洞察力，或者说一个人能够理解为什么一个人会有这样的感受，并将其与一些更大的背景联系起来，从而带来一定程度的缓解。

And that's where things start to get a little bit abstract, and that's also where we start to see that while trauma therapy in the form of talk therapy can be very effective, about half of people that undergo talk therapy and talk therapy alone for the treatment of PTSD achieve no long-lasting relief of symptoms, and an even smaller number of them undergo complete remittance of their PTSD.

这就是事情开始变得有点抽象的地方，也是我们开始看到的地方，虽然以谈话治疗形式进行的创伤治疗可能非常有效，但大约一半接受谈话治疗和单独谈话治疗来治疗 PTSD 的人并没有实现症状的持久缓解，而且只有更少的人经历了 PTSD 的完全缓解。

Okay, so their symptoms can lessen, they can get some improvement, but that improvement is often slight or is transient, and for those that do achieve relief, it's often not complete remission of the PTSD itself.

好的，所以他们的症状可以减轻，他们可以得到一些改善，但这种改善通常是轻微的或短暂的，对于那些确实得到缓解的人来说，创伤后应激障碍本身通常并没有完全缓解。

Now, in addition to talk therapy for PTSD, there is of course prescription drug therapies, and most often these fall under the category of SSRIs, selective serotonin reuptake inhibitors.

现在，除了针对 PTSD 的谈话疗法之外，当然还有处方药疗法，而且最常见的是这些疗法属于 SSRIs（选择性血清素再摄取抑制剂）类别。

And it's well known that SSRIs can be, in limited circumstances, effective for the treatment of PTSD.

众所周知，SSRIs 在有限的情况下可以有效治疗 PTSD。

It has been shown, for instance, that as many as 40, maybe as many as 60% of people that take SSRIs for the treatment of PTSD get some symptom relief.

例如，研究表明，在服用 SSRI 治疗 PTSD 的人中，多达 40%（也许多达 60%）的症状得到了一定程度的缓解。

Now, that is not to say that SSRIs don't have side effects.

但这并不是说 SSRI 没有副作用。

They can have side effects.

它们可能有副作用。

Some of you are probably familiar with these side effects.

你们中的一些人可能熟悉这些副作用。

Things like blunting of libido, blunting of appetite, or increases in appetite in some cases, disruption of sleep-wake rhythms, motivation, et cetera.

诸如性欲减弱、食欲减弱或在某些情况下食欲增加、睡眠-觉醒节律、动机紊乱等。

So there's often an exploration for the so-called minimal effective dose that provides some symptom relief to PTSD, but that doesn't introduce unwanted side effects.

因此，人们经常探索所谓的最小有效剂量，该剂量可以缓解 PTSD 的一些症状，但不会带来不必要的副作用。

And of course, there's a third situation where people are taking SSRIs and doing talk therapy for PTSD, and what's very clear is that any time you add quality talk therapy to a drug treatment, you're going to improve the outcomes for that drug treatment.

当然，还有第三种情况，人们服用 SSRIs 并进行谈话治疗来治疗 PTSD，很明显，任何时候你在药物治疗中添加高质量的谈话治疗，你都会改善药物治疗的结果。

The reverse is not always true.

反之亦然。

It's not always the case that adding prescription drug treatment to talk therapy improves outcomes for talk therapy, although that has been observed in a number of studies.

尽管许多研究已经观察到这一点，但在谈话治疗中添加处方药治疗并不总是可以改善谈话治疗的结果。

Now, the whole idea of exploring the use of MDMA for the treatment of PTSD stemmed from the fact that even in people who are getting quality talk therapy, and again, we can define quality talk therapy as good rapport between patient and clinician, as well as feelings of support, as well as potential insight.

现在，探索使用 MDMA 治疗 PTSD 的整个想法源于这样一个事实：即使是在接受高质量谈话治疗的人中，我们也可以将高质量谈话治疗定义为患者和临床医生之间的良好关系、支持感以及潜在的洞察力。

And even when SSRIs are combined with that quality talk therapy, there's still a large number of people who simply do not achieve significant or long-lasting relief from their PTSD, and an even fewer number who go into full remittance of their PTSD.

即使当 SSRIs 与高质量的谈话疗法相结合时，仍然有很多人根本无法从 PTSD 中获得显着或持久的缓解，而完全缓解 PTSD 的人则更少。

That is despite being diligent and hardworking in their talk therapy, despite the therapist being very committed, despite the use of SSRIs in conjunction with that talk therapy, those people often still qualify as having PTSD.

尽管他们在谈话治疗中勤奋努力，尽管治疗师非常投入，尽管将 SSRI 与谈话治疗结合使用，但这些人通常仍然有资格患有 PTSD。

And the goal, of course, is for somebody to receive treatment that allows them to no longer meet the criteria for having PTSD.

当然，我们的目标是让某人接受治疗，使他们不再符合患有创伤后应激障碍的标准。

Not just in terms of a clinical evaluation, but that they themselves report feeling much better, not feeling overwhelmed with the symptomology of PTSD.

不仅是在临床评估方面，而且他们自己也报告说感觉好多了，没有因创伤后应激障碍的症状而感到不知所措。

Now, the symptomology for PTSD is vast, and it's far too vast to go into a lot of detail right now.

现在，创伤后应激障碍（PTSD）的症状非常广泛，而且现在无法详细讨论。

I think most people are familiar with the stereotyped example of PTSD.

我想大多数人都熟悉创伤后应激障碍（PTSD）这个刻板印象的例子。

This is the soldier that comes back from overseas, that has been in gunfights or in battles of different kinds, has likely seen casualties and severe injuries, and that upon return to a safe environment, is still experiencing a lot of anxiety and sometimes panic attacks that occur seemingly at random or that can be sparked by, the classic stereotyped example is a car backfires and then the person suddenly feels as if they're back in battle.

这是从海外回来的士兵，经历过枪战或不同类型的战斗，可能已经看到人员伤亡和重伤，并且在返回安全环境后，仍然经历着很多焦虑，有时会出现看似随机发生或可能引发的恐慌发作，典型的刻板例子是汽车回火，然后这个人突然感觉好像回到了战斗中。

That sort of thing does happen, certainly.

当然，这种事情确实会发生。

But there are a whole other category of symptoms of PTSD Which include dissociative symptoms of PTSD.

但 PTSD 的症状还有一类，其中包括 PTSD 的分离症状。

People who have PTSD from very intensely traumatic experiences that are checked out.

因遭受过严重创伤经历而患有创伤后应激障碍（PTSD）的人经过检查。

They don't feel like they can engage, they have brain fog, they are distracted, they go from feeling anxious to feeling exhausted.

他们觉得自己无法参与，他们有脑雾，他们分心，他们从感到焦虑到感到疲惫。

They have sleep issues.

他们有睡眠问题。

Not surprisingly then, people with PTSD of either the dissociative type or other symptomology of PTSD, and keep in mind that one can have both dissociative and non-dissociative symptoms of PTSD, such as anxiety and panic, are at a far greater risk of substance abuse.

因此，毫不奇怪，患有分离型或其他 PTSD 症状的 PTSD 患者，并记住，一个人可能同时患有 PTSD 的分离和非分离症状，例如焦虑和恐慌，他们滥用药物的风险要大得多。

So the current estimates are that people with PTSD, no matter what type of PTSD, dissociative symptoms or otherwise, panic attacks or both, are at a much greater risk of having addictions to either illicit drugs or prescription drugs, or both.

因此，目前的估计是，患有创伤后应激障碍的人，无论是何种类型的创伤后应激障碍、解离症状或其他症状、惊恐发作或两者兼而有之，对非法药物或处方药或两者都上瘾的风险要大得多。

So things like alcohol use disorder is very common in people with PTSD, opioid use disorder is very common, stimulant use disorder, and on and on.

因此，酒精使用障碍在创伤后应激障碍患者中很常见，阿片类药物使用障碍很常见，兴奋剂使用障碍等等。

So people with PTSD suffer at a number of different levels, and there are all these, what are called comorbidities with PTSD, including addiction, but also depression, anxiety.

因此，患有 PTSD 的人会遭受多种不同程度的痛苦，所有这些都是所谓的 PTSD 合并症，包括成瘾，但也包括抑郁、焦虑。

And so you can start to see how PTSD sets up a whole cascade of things that make living life extremely problematic at the level of basic relationships, functioning in the workplace, and even when mental health appears to be in check, oftentimes people are holding a lot in, so they have cardiovascular and cerebrovascular deficits that cause a lot of problems in their immediate and long-term physical health.

因此，你可以开始了解创伤后应激障碍如何引发一连串的事情，使生活在基本人际关系、工作场所运作等方面变得极其成问题，即使心理健康似乎得到了控制，人们通常也会压抑自己，因此他们会出现心血管和脑血管缺陷，从而导致他们的近期和长期身体健康出现很多问题。

So PTSD is a very serious issue.

所以PTSD是一个非常严重的问题。

The current estimates are that as many as 8% of people in the United States have PTSD, and again, the estimates around comorbidities range anywhere from 17 to 46, or as high as 65% of people with PTSD having comorbidities for other mental health issues, and addiction in particular.

目前估计，美国有多达 8% 的人患有 PTSD，而且，有关合并症的估计范围在 17 到 46 之间，即高达 65% 的 PTSD 患者患有其他心理健康问题，尤其是成瘾问题。

So finding lasting relief to PTSD is extremely important and made even more important by the fact that many people with PTSD sadly end up committing suicide.

因此，找到持久的创伤后应激障碍缓解方法极其重要，而且由于许多患有创伤后应激障碍的人最终以自杀告终，这一事实变得更加重要。

So suicide rates are far greater in people with PTSD.

因此，患有创伤后应激障碍的人的自杀率要高得多。

The exact rates of increase in suicidality in people with PTSD are a little bit hard to arrive at in the statistics because of all the comorbidities.

由于所有合并症，创伤后应激障碍患者自杀率的确切增加率很难在统计数据中得出。

But suffice to say that suicide is far more likely in people with PTSD, along with all the other issues that PTSD brings about.

但我只想说，患有创伤后应激障碍的人自杀的可能性要大得多，还有创伤后应激障碍带来的所有其他问题。

Now, PTSD creates all the problems that it does, largely through changes in brain circuitry, as well as neural communication between the brain and body.

现在，创伤后应激障碍造成了它所造成的所有问题，主要是通过大脑回路以及大脑和身体之间的神经通讯的变化。

Many people have perhaps heard of the book, "The Body Keeps the Score," which is a very successful and popular book about the idea that trauma can be, quote, unquote, "stored in the body." To be clear, traumas can't actually be stored in the body.

许多人可能听说过《身体记录分数》这本书，这是一本非常成功且受欢迎的书，它讲述了创伤可以“存储在身体中”的想法。需要明确的是，创伤实际上无法储存在体内。

You don't actually store memories in the body.

你实际上并没有在体内储存记忆。

What you store are activation of neural circuits that include brain and body, and they all seem to center back into the insula, that structure that we talked about earlier, this structure in our brain that has a map of our body surface.

你储存的是包括大脑和身体在内的神经回路的激活，它们似乎都集中在脑岛，我们之前讨论过的那个结构，我们大脑中的这个结构，有我们身体表面的地图。

So contrary to popular belief, we don't store memories in the body or trauma in the body in a way that, for instance, working out a knot or a pain in one's lower back will relieve the trauma.

因此，与普遍的看法相反，我们不会以某种方式将记忆或创伤存储在身体中，例如，通过解决腰部的结或疼痛来缓解创伤。

It sometimes can activate a memory of the trauma, but when one is doing that, what you're really doing is activating neural circuits that reside within the brain, within the insula, that correspond to sensations within the body.

它有时可以激活对创伤的记忆，但当你这样做时，你真正做的是激活大脑内、岛叶内的神经回路，这些神经回路与体内的感觉相对应。

Now, I don't want to diminish the role of the body in the formation and the persistence of PTSD, and I certainly think the book, "The Body Keeps the Score," is a pioneering book.

现在，我不想削弱身体在创伤后应激障碍的形成和持续中所扮演的角色，我当然认为《身体记录分数》这本书是一本开创性的书。

It's, in fact, an important book.

事实上，这是一本重要的书。

But I want to emphasize that the modern neuroscience really points to the fact that PTSD is caused by the exact sorts of brain network activations that we were discussing earlier.

但我想强调的是，现代神经科学确实指出了这样一个事实：创伤后应激障碍是由我们之前讨论过的大脑网络激活引起的。

Things like heightened levels of activation in the amygdala to insula pathway, which of course would exacerbate bodily sensations related to the trauma, or heightened activation of the hippocampus, this memory center in the brain to amygdala, to insula circuitry.

比如杏仁核到岛叶通路的激活水平升高，这当然会加剧与创伤相关的身体感觉，或者海马体的激活增强，海马体是大脑中的记忆中心到杏仁核、岛叶回路。

Now, therefore, it should come as no surprise that if MDMA can reduce the levels of activity in the hippocampal to amygdala, to insula circuitry, and can do so both while someone is under the effects of MDMA, but then lead to persistent, long-lasting reductions in the activation of those brain networks, well, then it stands to reason that MDMA could be a valid therapeutic for the treatment of PTSD.

因此，如果 MDMA 可以降低海马、杏仁核、岛叶回路的活动水平，并且在某人受到 MDMA 影响时也能做到这一点，但随后会导致这些大脑网络的激活持续、持久地减少，那么，MDMA 理所当然地可能成为治疗 PTSD 的有效疗法。

And of course, this has been explored.

当然，这已经被探索过。

And here we can really give a nod and a large debt of gratitude to the so-called MAPS group.

在这里，我们确实可以向所谓的 MAPS 组织表示敬意和感激。

The MAPS group is a group that's operating mainly out of Santa Cruz, California, but they have a number of different satellite laboratories and clinical groups, both in the US, in Canada, and abroad, where they've worked with government organizations to get legal authorization to give MDMA to patients who have PTSD, to also give them talk therapy, and then to compare the effects of talk therapy with MDMA to talk therapy with placebo alone.

MAPS 小组主要在加利福尼亚州圣克鲁斯开展业务，但他们在美国、加拿大和国外拥有许多不同的卫星实验室和临床小组，他们与政府组织合作，获得法律授权，向患有 PTSD 的患者提供 MDMA，同时给予他们谈话治疗，然后比较 MDMA 谈话治疗与单独安慰剂谈话治疗的效果。

And there are about three to five studies in this area now that stand as large-scale clinical trials that are showing what can only be described as remarkable results for the treatment of PTSD.

目前该领域大约有三到五项研究作为大规模临床试验，显示出治疗 PTSD 的显着效果。

So rather than going to any one of those studies in immense detail, I'm going to summarize across those studies.

因此，我不会详细讨论其中任何一项研究，而是对这些研究进行总结。

I will provide links to those in the show note captions.

我将提供节目注释标题中的链接。

The two that I think are most interesting are the study entitled, "MDMA-Assisted Therapy for Severe PTSD, a Randomized, Double-blind, Placebo-controlled, Phase 3 Study," as well as the study entitled, "The Effects of MDMA-Assisted Therapy on Alcohol and Substance Use in a Phase 3 Trial for the Treatment of Severe PTSD." So as the title suggests, both clinical trials involve giving people talk therapy and MDMA, or talk therapy and placebo.

我认为最有趣的两项研究是题为“重度 PTSD 的 MDMA 辅助治疗，一项随机、双盲、安慰剂对照的第 3 期研究”的研究，以及题为“治疗严重 PTSD 的第 3 期试验中 MDMA 辅助治疗对酒精和药物使用的影响”的研究。正如标题所示，这两项临床试验都涉及给予人们谈话疗法和 MDMA，或者谈话疗法和安慰剂。

I'll talk about exactly how that was done in a moment.

稍后我将详细讨论这是如何完成的。

And then to look at relief of PTSD symptoms, but also relief of some of the addictive symptoms that are commonly associated With PTSD.

然后看看 PTSD 症状的缓解，以及一些通常与 PTSD 相关的成瘾症状的缓解。

So just to give you an overview of what's happening with these trials and why there's so much excitement and why we really are on the cusp of legalization of MDMA for the treatment of PTSD in the sorts of clinical contexts I described.

因此，我只是想向您概述一下这些试验的进展情况，以及为什么如此令人兴奋，以及为什么我们真正处于 MDMA 合法化的风口浪尖，用于在我所描述的各种临床背景下治疗 PTSD。

When people are given just talk therapy alone or talk therapy with SSRIs, they will often, as I mentioned earlier, experience reductions in their severity of PTSD symptoms, and rarely they will experience complete remittance of their PTSD.

正如我之前提到的，当人们仅接受谈话治疗或联合 SSRI 进行谈话治疗时，他们通常会经历 PTSD 症状严重程度的减轻，而且很少会经历 PTSD 的完全缓解。

That is, they will no longer qualify for PTSD after receiving a number of talk therapy sessions.

也就是说，在接受多次谈话治疗后，他们将不再符合创伤后应激障碍的资格。

So let's compare that to what happens when people do talk therapy in conjunction with MDMA, and I'll explain exactly what that means in a moment, but it essentially means taking MDMA while doing talk therapy.

因此，让我们将其与人们在进行谈话治疗与 MDMA 结合时发生的情况进行比较，我稍后将准确解释这意味着什么，但这本质上意味着在进行谈话治疗的同时服用 MDMA。

However, this is a very important however, the people who are taking MDMA in these trials have already done talk therapy without MDMA.

然而，这是非常重要的，在这些试验中服用 MDMA 的人已经接受了不含 MDMA 的谈话治疗。

Then they're doing talk therapy under the influence of MDMA, and then they are doing sessions of talk therapy, not under the influence of MDMA, and the entire time they're doing that with the same two therapists.

然后他们在 MDMA 的影响下进行谈话治疗，然后他们在不受 MDMA 影响的情况下进行谈话治疗，并且在整个过程中他们都是与同样的两位治疗师一起进行。

Okay?

好的？

In the placebo group, people are doing talk therapy with two therapists, but they're not taking MDMA.

在安慰剂组中，人们与两名治疗师进行谈话治疗，但他们不服用摇头丸。

Okay?

好的？

So they're doing the same number of therapy sessions, but they're not taking MDMA.

因此，他们进行了相同次数的治疗，但他们没有服用摇头丸。

So to just get to the key numbers first, the overall rate for clinically effective response to MDMA-assisted therapy is 88%.

因此，首先来看关键数据，MDMA 辅助治疗的临床有效反应率为 88%。

That's what's emerging from these trials, versus 60% for the placebo and therapy alone.

这就是这些试验得出的结果，而安慰剂和单独治疗的结果为 60%。

So on the face of it, you might say, okay, wow, 88% of people who do talk therapy-- and here I might as well just finally explain how this is done.

所以从表面上看，你可能会说，好吧，哇，88% 的人都接受谈话治疗——在这里我不妨最后解释一下这是如何完成的。

Patients are selected because they have PTSD.

选择患者是因为他们患有创伤后应激障碍（PTSD）。

They meet the clinical criteria for PTSD.

他们符合 PTSD 的临床标准。

They do three 90-minute therapy sessions with two therapists, talking about their PTSD symptoms, talking about, to the extent that they can, the incident or incidents, the life events that led to that PTSD.

他们与两名治疗师一起进行三个 90 分钟的治疗疗程，谈论他们的 PTSD 症状，尽可能谈论导致 PTSD 的事件或事件，生活事件。

None of that is done under the influence of any drug.

这些都不是在任何药物的影响下完成的。

Okay?

好的？

So everyone in the experiment does that.

所以实验中的每个人都这样做。

Then the group divides into two, where half are taking MDMA.

然后小组分成两部分，其中一半正在服用摇头丸。

They take that three times.

他们这样做了三次。

During those three times, they are also receiving therapy sessions with the same therapists that they were working with before they took MDMA.

在这三次期间，他们还接受了与服用 MDMA 之前相同的治疗师的治疗。

The first session, they're taking 80 milligrams of MDMA and then a 40-milligram booster about an hour and a half to two hours in.

第一个疗程中，他们服用 80 毫克 MDMA，然后在大约一个半小时到两个小时后服用 40 毫克加强剂。

The second session, they are taking a higher dose of MDMA.

第二次治疗时，他们服用了更高剂量的摇头丸。

It's 120 milligrams, and then if they elect to, they can take a 60-milligram booster about an hour and a half to two hours into the session.

剂量为 120 毫克，如果他们愿意，可以在疗程开始大约一个半小时到两个小时后服用 60 毫克加强剂。

And then there's a third session where they take, again, 120 milligrams of MDMA and have the option to take a 60-milligram booster about an hour and a half to two hours into the session.

然后是第三次疗程，他们再次服用 120 毫克 MDMA，并可以选择在疗程开始大约一个半小时到两个小时后服用 60 毫克加强剂。

Again, anytime they're on MDMA, they have therapists there that they're talking to about their trauma.

再说一次，每当他们服用摇头丸时，他们都会有治疗师在那里与他们谈论他们的创伤。

They are either spending time with their eyes closed, lying down, sometimes in an eye mask, and thinking about the trauma, thinking about their current state and experience, also thinking about what happened before.

他们要么闭上眼睛，躺着，有时戴着眼罩，思考创伤，思考他们当前的状态和经历，也思考之前发生的事情。

Then they're exiting the eye mask or talking to the therapist.

然后他们离开眼罩或与治疗师交谈。

The therapist is taking notes, asking questions.

治疗师正在做笔记，提出问题。

Remember, they've established a strong rapport, supportive relationship with these therapists prior to taking MDMA in the therapy session.

请记住，在治疗过程中服用摇头丸之前，他们已经与这些治疗师建立了牢固的融洽和支持关系。

And then they also undergo three 90-minute therapy sessions with the two therapists spaced one week apart after the final MDMA session.

然后，他们还在最后一次 MDMA 疗程后，与两位治疗师相隔一周，进行 3 次 90 分钟的治疗疗程。

Now, those that were placed into the placebo condition do everything exactly the same as I just described.

现在，那些被置于安慰剂条件下的人所做的一切都与我刚才描述的完全相同。

So three 90-minute sessions as prep, then three eight-hour sessions with those two therapists, and then three 90-minute follow-up sessions one week apart.

因此，三个 90 分钟的课程作为准备，然后是与这两位治疗师一起进行的三个 8 小时的课程，然后是间隔一周的三个 90 分钟的后续课程。

But they take a placebo, not MDMA.

但他们服用的是安慰剂，而不是摇头丸。

So you can see that in these so-called MAPS studies, these clinical trials for PTSD, the conditions are very similar except for the inclusion of the drug MDMA.

所以你可以看到，在这些所谓的 MAPS 研究中，这些针对 PTSD 的临床试验，除了包含 MDMA 药物外，条件非常相似。

So those rates of success with talk therapy and MDMA, again, overall rate for clinically effective response to MDMA-assisted therapy was 88% compared to 60% for therapy and placebo.

因此，谈话疗法和 MDMA 的成功率再次表明，MDMA 辅助治疗的临床有效反应总体率为 88%，而治疗和安慰剂的临床有效反应率为 60%。

What's even more impressive, however, is that 67% of the people in the MDMA plus therapy treatment group no longer met the criteria for PTSD by the end of the treatment.

然而，更令人印象深刻的是，MDMA 加疗法治疗组中有 67% 的人在治疗结束时不再符合 PTSD 的标准。

So in other words, their PTSD went into remittance.

换句话说，他们的创伤后应激障碍（PTSD）进入了汇款状态。

Now, we could say they are, quote, unquote, "cured," but typically, for things like PTSD, that's not the language that's used.

现在，我们可以说它们是，引用，不引用，“治愈”，但通常，对于像创伤后应激障碍这样的事情，这不是使用的语言。

Rather, what's used is statistical evaluation of how the different symptoms like dissociation or anxiety or sleep disorders are explored.

相反，所使用的是对如何探索解离、焦虑或睡眠障碍等不同症状的统计评估。

So while to some of you, a difference between 60% success with talk therapy and placebo versus 88% success with talk therapy plus MDMA might not seem like that big of a difference, it is indeed quite an enormous difference.

因此，虽然对你们中的一些人来说，谈话治疗加安慰剂的成功率 60% 与谈话治疗加 MDMA 的成功率 88% 之间的差异可能看起来没有那么大，但它确实是一个巨大的差异。

In fact, to my knowledge, there's no other example of a treatment for a psychiatric disorder that is successful to the same magnitude.

事实上，据我所知，没有其他治疗精神疾病的例子能够达到同样的成功程度。

I could be wrong about that.

我可能是错的。

I'm sure some psychiatrists out there are going to jump on me about this, and please do.

我确信一些精神科医生会因为这件事攻击我，请这样做。

I would encourage you if you are aware of any therapy plus drug treatment that is effective at rates of greater than 88% for the treatment of a major psychiatric disorder, please do put that information in the comments on YouTube, and perhaps a reference to a study would be even better.

如果您知道任何疗法加药物治疗对于治疗主要精神疾病的有效率超过 88%，我鼓励您，请务必将该信息放在 YouTube 上的评论中，也许引用一项研究会更好。

But even if not, just put a reference to that.

但即使没有，也只需引用它即可。

That would be great for sake of future episodes, et cetera.

这对于未来的剧集等等来说都是非常好的。

But nonetheless, an 88% Success rate, and here I'm referring to success rate as a significant reduction in clinical symptoms for PTSD, and 67% of those people going into full remittance for PTSD by the end of the treatment is pretty spectacular.

但尽管如此，88% 的成功率，在这里我指的是 PTSD 临床症状显着减少的成功率，其中 67% 的人在治疗结束时全额缓解 PTSD，这是相当惊人的。

Which is why you're hearing so much these days about the potential transition of MDMA from a Schedule 1 drug for which there are "no clinical applications" to potentially a legal within the context of clinical use application of MDMA, which it does appear the legislature is at least considering for as early as 2024, maybe even later in 2023.

这就是为什么你最近听到很多关于 MDMA 可能从“没有临床应用”的附表 1 药物转变为 MDMA 临床使用应用范围内的潜在合法药物的原因，立法机关似乎至少在 2024 年（甚至可能在 2023 年晚些时候）考虑这样做。

It remains to be seen.

这还有待观察。

Now, a number of other important results have emerged from this and other clinical trials.

现在，这项临床试验和其他临床试验已经得出了许多其他重要结果。

For instance, remember earlier I talked about how many people with PTSD also suffer from alcohol use disorder.

例如，记得之前我谈到有多少患有创伤后应激障碍的人也患有酒精使用障碍。

What's interesting is that for people that were in the MDMA plus talk therapy group in this and other studies who also had patterns of alcohol use disorder and even some other substance use disorders, the MDMA plus talk therapy treatment in many cases resolved their addiction to alcohol or other symptoms as well.

有趣的是，对于本研究和其他研究中 MDMA 加谈话治疗组中也有酒精使用障碍甚至其他物质使用障碍模式的人来说，MDMA 加谈话治疗在许多情况下也解决了他们的酒精成瘾或其他症状。

And perhaps that shouldn't be surprising if we think about the addictions as stemming directly from their PTSD.

如果我们认为成瘾直接源于他们的创伤后应激障碍，也许这并不奇怪。

But it is surprising if you think about the fact that alcohol use disorder and some other addictive disorders oftentimes will stem from disruptions in neural circuitry that are the same disruptions in neural circuitry that occur in PTSD, but often are the consequence of entirely other brain wiring phenomenon.

但如果你想到酒精使用障碍和其他一些成瘾性疾病常常源于神经回路破坏，这与 PTSD 中发生的神经回路破坏相同，但往往是完全其他大脑接线现象的结果，你就会感到惊讶。

What I'm saying here is that just because addiction and PTSD are often comorbid with one another, it is not necessarily the case that treating and resolving PTSD would resolve the alcohol or substance abuse disorder, and yet that seems to be the case often, not always, but often in these successful treatments of PTSD.

我在这里想说的是，仅仅因为成瘾和 PTSD 经常同时存在，治疗和解决 PTSD 并不一定能解决酒精或药物滥用障碍，但在这些成功的 PTSD 治疗中，这种情况似乎经常发生，并非总是如此，但经常发生。

So that's very exciting.

所以这非常令人兴奋。

Some of the other particularly exciting results from these clinical trials on MDMA plus talk therapy is that the dissociative form of PTSD has traditionally proved to be especially hard to treat.

这些关于摇头丸加谈话疗法的临床试验的其他一些特别令人兴奋的结果是，传统上证明分离形式的创伤后应激障碍（PTSD）特别难以治疗。

And that's thought to stem from the fact that successful treatment of PTSD, whether or not it's by talk therapy or talk therapy combined with SSRIs or talk therapy combined with any drug treatment or behavioral treatment like EMDR, eye movement desensitization reprogramming, or other forms of treatments that are designed to rewire neural circuitry, almost always involve the patient getting very close to or at least reporting the traumatic experiences in a lot of detail.

人们认为，成功治疗 PTSD 的事实是，无论是谈话疗法、谈话疗法与 SSRI 相结合，还是谈话疗法与任何药物治疗或行为治疗（如 EMDR、眼动脱敏重编程或其他旨在重新连接神经回路的治疗形式）相结合，几乎总是让患者非常接近或至少详细地报告创伤经历。

And you can imagine why for somebody who's dissociating from that very experience, who's "checked out" and can't really seem to access the emotional states and the memories because they're blocked off from them or because they're unwilling to access those memories and really think about the full emotional capacity of those memories, that it would be particularly hard to bring them through any kind of treatment for PTSD.

你可以想象，为什么对于那些与这种经历分离的人，那些被“检查出来”并且似乎无法真正接触情绪状态和记忆的人，因为他们与情绪状态和记忆被封锁，或者因为他们不愿意接触这些记忆并真正思考这些记忆的全部情感能力，那么让他们接受任何类型的创伤后应激障碍治疗都会特别困难。

So it appears that MDMA, in providing this prosocial, empathic, again, empathic for others and empathic for self, chemical and mental environment, as well as the presence of two trusted therapists, which one has a really good rapport, allows patients with PTSD to really get close to those experiences that were traumatic, to talk about them and to think about them, and in many ways to reframe them in a context that often involves empathy for others and empathy for self.

因此，MDMA 似乎通过提供这种亲社会的、同理心的、对他人的同理心、对自我的同理心、化学和心理环境，以及两位值得信赖的治疗师（其中一位关系非常融洽）的存在，让 PTSD 患者能够真正接近那些创伤性的经历，谈论它们并思考它们，并以多种方式在经常涉及对他人的同理心和对自我的同理心的背景下重新构建它们。

Now, here we're not necessarily talking about forgiveness of perpetrators, although that's sometimes the case, that people will forgive the person that inflicted the trauma on them.

现在，我们不一定要谈论对肇事者的宽恕，尽管有时会出现这种情况，人们会原谅给他们造成创伤的人。

But more often than not, it's about tying their feelings of trauma and their feelings of depression, anxiety, dissociation, et cetera, to some sort of larger context that allows them to see themselves in the role of agency.

但通常情况下，这是将他们的创伤感以及抑郁、焦虑、分离等感觉与某种更大的背景联系起来，使他们能够看到自己扮演的角色。

To be in the role of knowing that, yes, these things happened, and yet by getting close to the emotional load of those things and really being, in many ways, unafraid to get close to the emotional load of that and having support around that, that the emotional load seems diminished.

知道，是的，这些事情发生了，但通过接近这些事情的情感负担，并且在很多方面真正不害怕接近这些事情的情感负担并获得周围的支持，情感负担似乎减轻了。

And that they experience the emotional load of those experiences as diminished both within the MDMA treatment session and afterwards for long periods of time.

而且他们在 MDMA 治疗过程中以及治疗后很长一段时间内感受到这些经历的情绪负担都减轻了。

So essentially what happens is these people feel that what once burdened them, they can still remember, but it no longer burdens them.

所以本质上发生的事情是这些人觉得曾经给他们带来负担的事情他们仍然记得，但它不再给他们带来负担。

It no longer feels like it's in their body and in their mind or on loop or on repeat in a way that's invasive, in a way that interferes with other aspects of normal functioning.

它不再感觉像是在他们的身体和头脑中，或者以一种侵入性的方式循环或重复，以一种干扰正常功能的其他方面的方式。

So when one hears about these kinds of results and when you hear about some of the patient reports, and I invite you to do that, you can go to the MAPS site, which by the way is recruiting subjects for these clinical trials, and you'll also find reports of individuals who participated in these clinical trials.

因此，当人们听到这些结果，当您听到一些患者报告时，我邀请您这样做，您可以访问 MAPS 网站，顺便说一下，该网站正在招募这些临床试验的受试者，您还会找到参与这些临床试验的个人的报告。

And of course, we will provide links to these incredible clinical trials that MAPS has spearheaded.

当然，我们将提供 MAPS 牵头的这些令人难以置信的临床试验的链接。

What you find is that the combination of MDMA and talk therapy in many ways is not about the drug having a particular effect.

您会发现，摇头丸和谈话疗法的结合在很多方面并不是药物具有特定的效果。

It's really about the drug having a particular effect that allows the motivations and the results of talk therapy to really be heightened.

这实际上是一种具有特殊效果的药物，可以真正提高谈话治疗的动机和结果。

And I think that's a really key point to make, because up until now, we've really been talking about the neurochemistry of MDMA, the potential toxicity or lack thereof of MDMA.

我认为这是一个非常关键的观点，因为到目前为止，我们一直在讨论 MDMA 的神经化学、MDMA 的潜在毒性或缺乏毒性。

We've been talking about the brain networks, et cetera.

我们一直在谈论大脑网络等等。

But when one thinks about the valid clinical use of MDMA for the treatment of PTSD, and I should mention, it also had some success in dealing with not only alcohol use disorders and other use disorders associated with PTSD, but also relieving the depression associated with PTSD.

但是，当人们想到 MDMA 治疗 PTSD 的有效临床用途时，我应该提到的是，它不仅在处理酒精使用障碍和与 PTSD 相关的其他使用障碍方面取得了一些成功，而且在缓解与 PTSD 相关的抑郁症方面也取得了一些成功。

So now MDMA is being explored for treatment of not just PTSD, but also for depression, for alcohol use disorder, and for eating disorders as well.

因此，现在人们正在探索 MDMA 不仅可以治疗创伤后应激障碍 (PTSD)，还可以治疗抑郁症、酒精使用障碍和饮食失调。

MDMA seems to be a compound that produces the right kind of subjective and neurochemical milieu in the brain that allows therapy to be that much more potent within a limited number of sessions.

MDMA 似乎是一种化合物，可以在大脑中产生正确的主观和神经化学环境，从而使治疗在有限次数的疗程中更加有效。

And when one thinks about the cost of mental health care, how expensive it is to get therapy over and over and over again, which in ideal circumstances, people are able to do that either by way of insurance or by their own finances.

当人们想到精神卫生保健的费用时，一次又一次接受治疗的费用是多少，在理想的情况下，人们可以通过保险或自己的财务来做到这一点。

I don't want to say that the cost of therapy should be reduced, because of course, therapists have to survive also.

我并不是说治疗费用应该降低，因为治疗师当然也必须生存。

But the idea here is that people who are suffering would be able to achieve relief from their PTSD, their depression, their addiction, and to be able to do so by hopefully persisting in their therapy over whatever period of time is required, but also to assume a circumstance in which somebody only has 10 or 15 or maybe even just three opportunities to undergo treatment for PTSD, and nonetheless is able to achieve tremendous relief during the session and after the session.

但这里的想法是，遭受痛苦的人将能够从 PTSD、抑郁、成瘾中获得缓解，并且能够通过在需要的任何时间段内坚持治疗来实现这一点，但也假设一个人只有 10 或 15 甚至可能只有 3 次接受 PTSD 治疗的机会，但仍然能够在治疗期间和治疗后获得巨大的缓解。

And it really does seem to be the case that for reasons that you now understand, the activation of particular brain networks, the suppression of other brain networks, in particular this amygdala to insula pathway, that when people are under the influence of MDMA in these very safe and therapeutic supportive settings, they are able to look at traumatic events and the ways that those traumatic events impact them in ways that really allow them to cognitively reframe those events and somatically reframe those events, to really change the way that it lives in their body and mind so that it's no longer invasive, and then they can go on and lead productive, adaptive lives.

事实似乎确实如此，由于您现在了解的原因，特定大脑网络的激活，其他大脑网络的抑制，特别是杏仁核到岛叶的通路，当人们在这些非常安全和治疗性支持环境中受到 MDMA 的影响时，他们能够以真正允许他们认知地重新构建这些事件并在躯体上重新构建这些事件的方式来看待创伤性事件以及这些创伤性事件影响他们的方式，从而真正改变它在他们体内的生活方式，并且使其不再具有侵入性，然后他们就可以继续过上富有成效、适应性强的生活。

And as a final point related to these clinical studies, I, of course, would be remiss if I didn't touch on some of the so-called adverse effects, because anytime there's a drug or talk therapy for a mental health issue, adverse events have to be considered.

作为与这些临床研究相关的最后一点，如果我没有提到一些所谓的不良反应，那我当然是失职的，因为任何时候有针对心理健康问题的药物或谈话疗法，都必须考虑不良事件。

And I think it's quite reassuring that in the case of MDMA therapy, there were no increases in the number of suicide attempts or suicidality or obsession with suicide.

我认为令人欣慰的是，在 MDMA 治疗的情况下，自杀未遂、自杀倾向或对自杀的痴迷的数量没有增加。

Contrast that with the group that received placebo, where there were a certain number of baseline and predicted obsessions with suicide.

与接受安慰剂的组相比，该组有一定数量的基线和预测的自杀倾向。

Fortunately, at least to my knowledge, there was no actual suicide attempt or successful suicide, thankfully.

幸运的是，至少据我所知，没有真正的自杀企图或成功自杀，谢天谢地。

But the point being that the addition of MDMA drug therapy to PTSD talk therapy does not seem to increase the quote, unquote, "side effects" that are sometimes associated with PTSD talk therapy, because indeed, there can be side effects to exploring PTSD and trauma as one would expect.

但重点是，在 PTSD 谈话治疗中添加 MDMA 药物治疗似乎并没有增加有时与 PTSD 谈话治疗相关的“副作用”，因为事实上，正如人们所期望的那样，探索 PTSD 和创伤可能会产生副作用。

So overall, I would say it's very exciting times for the exploration of MDMA as an augmented talk therapy for the treatment of PTSD and these other conditions.

总的来说，我想说，探索 MDMA 作为治疗 PTSD 和其他疾病的增强谈话疗法是非常令人兴奋的时刻。

Again, I think the MAPS group has done a remarkable job of keeping this within the realm of legal and trying to move things forward in terms of legislation to make sure that MDMA isn't simply made legal and then abused recreationally.

再次强调，我认为 MAPS 小组在将其保持在合法范围内方面做得非常出色，并试图在立法方面取得进展，以确保 MDMA 不只是简单地合法化然后被娱乐性地滥用。

I know people out there have different views on whether or not drugs like MDMA should be legal or not.

我知道人们对于摇头丸等药物是否合法有不同的看法。

That's not what this episode is about.

这不是本集的主题。

What I am very excited about, as you can probably tell, and what I think a lot of people in the psychology and psychiatry community are very excited about, you say the mental health community at large, is that these compounds that for many years were only associated with their recreational uses and therefore were not well understood because they were often contaminated or taken in combination with other things or by people that never should have been taking them in the first place.

正如你可能会说的那样，我感到非常兴奋的是，我认为心理学和精神病学界的很多人，你说整个心理健康界，都非常兴奋的是，这些化合物多年来只与它们的娱乐用途有关，因此没有得到很好的理解，因为它们经常被污染或与其他东西结合使用，或者被那些本来就不应该服用它们的人服用。

Taken by young kids, which is a whole other matter.

由小孩子拍摄，这完全是另一回事。

A lot of issues and problems associated with these compounds, and yet we're now seeing from these clinical trials, when used, let's say properly, because really when safety protocols are obeyed, when there's clinical support, it is very clear that when MDMA is combined with quality talk therapy, that the outcomes are looking tremendously positive.

与这些化合物相关的很多问题和问题，但我们现在从这些临床试验中看到，当使用时，可以说正确使用，因为实际上，当遵守安全协议时，当有临床支持时，很明显，当 MDMA 与高质量的谈话疗法相结合时，结果看起来非常积极。

It's by no means a miracle cure.

这绝不是一种灵丹妙药。

It is by no means perfect, and time will tell what problems, if any, arise from the short or long-term use of MDMA in this context.

它绝不是完美的，时间会告诉我们在这种情况下短期或长期使用 MDMA 会产生什么问题（如果有的话）。

But I think it's remarkable that anywhere from two to three sessions with MDMA and talk therapy have been shown to significantly reduce PTSD symptoms, and in some cases, completely eliminate PTSD symptoms in such a wide range of patients and in patients that have experienced both PTSD and these other comorbid disorders.

但我认为值得注意的是，两到三次摇头丸和谈话疗法已被证明可以显着减轻 PTSD 症状，并且在某些情况下，可以完全消除如此广泛的患者以及同时经历过 PTSD 和其他共病疾病的患者的 PTSD 症状。

I think it's really remarkable.

我认为这真的很了不起。

It's very exciting, and I look forward to seeing what the next round of data produce.

这非常令人兴奋，我期待看到下一轮数据产生什么。

So as is often the case on this podcast, today we went into a lot of detail about a subject.

正如本播客中经常发生的情况一样，今天我们详细介绍了一个主题。

MDMA is this incredible compound synthesized, as far as we know, first by humans, not by plants, not by aliens, but by humans, and that produces big increases in dopamine and serotonin to create these highly motivated, prosocial, empathic states, meaning both empathy for others and for self, and that when applied in the context of psychiatric challenges like PTSD and addiction, is proving to create a lot of relief for a lot of people where other forms of drug therapy or combination drug and talk therapy had failed before.

据我们所知，MDMA 是一种令人难以置信的化合物，首先是由人类合成的，不是由植物合成的，不是由外星人合成的，而是由人类合成的，它会产生大量增加的多巴胺和血清素，从而创造出这些高度积极的、亲社会的、同理心的状态，这意味着对他人和自我的同理心，并且当应用于 PTSD 和成瘾等精神挑战时，事实证明，它可以为许多人带来很大的缓解，而其他形式的药物治疗或药物和谈话的组合之前治疗失败过。

We talked about some of the potential neurotoxicity issues.

我们讨论了一些潜在的神经毒性问题。

I don't think that is a resolved issue just yet, although the bulk of data in humans and non-human primates point to the fact that at reasonable doses, and we talked earlier about what those are, at reasonable doses, when not combined with other drugs, it does not appear that MDMA is exceedingly neurotoxic, and it may not be neurotoxic at all.

我认为这还不是一个已解决的问题，尽管人类和非人类灵长类动物的大量数据表明，在合理的剂量下，我们之前讨论过这些是什么，在合理的剂量下，当不与其他药物联合使用时，MDMA 似乎并没有极度的神经毒性，而且可能根本没有神经毒性。

Of course, one needs to be exceedingly cautious when thinking about the use of any sympathomimetic.

当然，在考虑使用任何拟交感神经药时都需要极其谨慎。

They, of course, can be neurotoxic.

当然，它们可能具有神经毒性。

Anything with methamphetamine in it has the potential to be neurotoxic.

任何含有甲基苯丙胺的物质都可能具有神经毒性。

But of course, dosage matters, context matters.

但当然，剂量很重要，背景也很重要。

We talked about that.

我们讨论过这个。

And of course The purity of drug matters.

当然，药物的纯度也很重要。

And again, I just want to reemphasize the fentanyl contamination of MDMA that's sold on the street and that is being used recreational is of very serious, potentially lethal concern.

再次，我想再次强调街头出售的、用于娱乐的 MDMA 的芬太尼污染是非常严重的、可能致命的问题。

I also expect that there will be a lot of interest in these clinical trials that MAPS is doing.

我还预计人们会对 MAPS 正在进行的这些临床试验产生很大的兴趣。

So again, you can find links to that in the show note captions.

同样，您可以在显示注释标题中找到该链接。

And I think in general, we should acknowledge that we are at a very interesting and important time in human history for the treatment of psychiatric disorders and for neuroscience generally.

我认为总的来说，我们应该承认，对于精神疾病的治疗和神经科学来说，我们正处于人类历史上非常有趣和重要的时刻。

Because whether or not we're talking about psilocybin or LSD or ayahuasca or ketamine or today's topic of MDMA, regardless of what drug and neurotransmitter and neuromodulator systems are involved, what we're really talking about are ways to access neuroplasticity, the nervous system's incredible ability to modify itself in response to experience, ideally to be modified in adaptive ways that make it function better.

因为无论我们谈论的是裸盖菇素、LSD、死藤水、氯胺酮还是今天的摇头丸，也无论涉及什么药物、神经递质和神经调节系统，我们真正谈论的是获得神经可塑性的方法，即神经系统根据经验进行自我修改的令人难以置信的能力，理想情况下以适应性方式进行修改，使其更好地发挥作用。

So that's really the crux of what talk therapy and drug therapies are about.

所以这确实是谈话疗法和药物疗法的关键所在。

That's what the goal of using MDMA as a clinical tool is all about.

这就是使用 MDMA 作为临床工具的目标。

And in that sense, I find MDMA to be an incredibly interesting and important topic, and I hope you did as well.

从这个意义上说，我发现摇头丸是一个非常有趣和重要的话题，我希望你也这么认为。

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 a terrific zero-cost way to support us.

这是支持我们的绝佳零成本方式。

In addition, please subscribe to the podcast on both Spotify and Apple.

此外，请在 Spotify 和 Apple 上订阅该播客。

And on both Spotify and Apple, you can leave us up to a five-star review.

在 Spotify 和 Apple 上，您都可以给我们五星级的评价。

If you have questions for me or comments about the podcast or guests that you'd like me to interview on the Huberman Lab podcast, please put those in the comments section on YouTube.

如果您对我有疑问或对您希望我在 Huberman Lab 播客上采访的播客或嘉宾有意见，请在 YouTube 的评论部分中提出。

I do read all the comments.

我确实阅读了所有评论。

Please also check out the sponsors mentioned at the beginning and throughout today's episode.

另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 discuss supplements.

在今天的节目中，我们讨论的不是很多，而是在 Huberman Lab 播客的许多之前的节目中，我们讨论了补充剂。

While supplements aren't necessary for everybody, many people derive tremendous benefit from them for things like improving sleep, for hormone support, and for focus.

虽然补充剂并不是每个人都需要的，但许多人从它们中获得了巨大的好处，例如改善睡眠、激素支持和注意力集中。

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 see the supplements discussed on the Huberman Lab podcast, you can go to Live Momentous, spelled O-U-S, so that's livemomentous.com/huberman.

如果您想查看 Huberman Lab 播客上讨论的补充内容，您可以访问 Live Momentous，拼写为 O-U-S，即 livemomentous.com/huberman。

If you're not already following me on social media, I am hubermanlab on Instagram, Twitter, Facebook, and LinkedIn.

如果您还没有在社交媒体上关注我，我是 Instagram、Twitter、Facebook 和 LinkedIn 上的 hubermanlab。

And at all those places, I discuss science and science-related tools for mental health, physical health, and performance.

在所有这些地方，我都会讨论有关心理健康、身体健康和表现的科学和与科学相关的工具。

Some of which overlap with the science and tools that are discussed on the Huberman Lab podcast, but much of which is distinct from the information covered on the Huberman Lab podcast.

其中一些与胡伯曼实验室播客中讨论的科学和工具重叠，但其中大部分与胡伯曼实验室播客中涵盖的信息不同。

So again, it's hubermanlab on all social media platforms.

再说一遍，所有社交媒体平台上都是 hubermanlab。

If you haven't already subscribed to our Neural Network Newsletter, the Neural Network Newsletter is a monthly newsletter, it's completely zero cost, where we provide podcast summaries as well as toolkits.

如果您还没有订阅我们的神经网络通讯，神经网络通讯是每月通讯，完全零成本，我们提供播客摘要和工具包。

The toolkits are short lists in PDF form of things that you can do to improve, for instance, sleep or neuroplasticity or dopamine regulation or deliberate cold exposure or fitness, and on and on.

这些工具包是 PDF 形式的简短列表，列出了您可以采取的改善措施，例如睡眠、神经可塑性、多巴胺调节、有意的寒冷暴露或健身等等。

Again, all of that is available at zero cost.

同样，所有这些都是零成本可用的。

You simply go to hubermanlab.com, go to the menu, scroll down to Newsletter, and provide your email.

您只需访问 hubermanlab.com，进入菜单，向下滚动到时事通讯，然后提供您的电子邮件即可。

We do not share your email with anybody.

我们不会与任何人分享您的电子邮件。

So if you're interested in those toolkits and the Neural Network Newsletter, again, that's available at hubermanlab.com.

因此，如果您对这些工具包和神经网络通讯感兴趣，请再次访问 hubermanlab.com。

Thank you again for joining me for today's discussion all about MDMA.

再次感谢您参加今天有关 MDMA 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。