致幻剂用于心理健康的科学 | Robin Carhart-Harris 博士

安德鲁·休伯曼：欢迎收听 Huberman Lab 播客。在这里，我们讨论科学，以及以科学为基础的日常生活工具。

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我是安德鲁·休伯曼，是斯坦福医学院神经生物学和眼科学教授。今天的嘉宾是 Robin Carhart-Harris 博士。Carhart-Harris 博士是加州大学旧金山分校神经病学和精神病学杰出教授，是研究致幻剂以及致幻剂如何改变大脑神经回路领域的顶尖研究者之一。

例如，他的实验室负责研究裸盖菇素（有时也称为神奇蘑菇）如何改变大脑神经回路，从而促成新的想法和新的学习形式。他的实验室还负责开展各种临床试验，其中一些试验显示，适当剂量的裸盖菇素可以缓解服用者的重度抑郁，比例超过 67%。

这并不是说每个人都应该服用裸盖菇素。今天的讨论会介绍临床试验，也会解释为什么致幻剂治疗在某些情况下能够、在另一些情况下却不能治疗重度抑郁。我们还会讨论裸盖菇素、麦角酸二乙胺（有时也称为 LSD）以及 DMT。

我们会讨论这些物质如何改变大脑，以及这些脑部变化如何与心理健康变化相关，包括抑郁和其他精神疾病方面的挑战；也会讨论如何利用致幻剂改变神经回路，以扩展人类心智的不同方面，包括创造力、智力以及更多能力。

在今天的讨论中，Carhart-Harris 博士会向我们介绍致幻剂研究的历史，以及美国和其他地方围绕致幻剂的法律如何变化，尤其是将致幻剂用于治疗精神疾病挑战的法规。听完今天的讨论，你将全面了解致幻剂如何发挥作用，包括在实际体验或“旅程”的短期内如何作用。

事实上，我今天与 Carhart-Harris 博士的大部分讨论都围绕致幻体验的不同方面，以及这些方面如何与治疗结果相关。当然，听完今天的讨论，你也会了解致幻剂的长期影响，也就是它们如何真正重塑大脑。

开始之前，我想强调，这档播客与我在斯坦福的教学和研究工作彼此独立。不过，这档播客确实是我向公众免费提供科学及科学相关工具信息的愿望和努力的一部分。秉持这一主题，我要感谢今天播客的赞助商。

第一位赞助商是 Eight Sleep。Eight Sleep 制造配备制冷、加热和睡眠追踪功能的智能床垫罩。我以前在这档播客中多次谈到，睡眠是心理健康、身体健康和表现的基础。要获得高质量睡眠，一个绝对关键的变量就是睡眠环境的温度。

也就是说，为了在夜间入睡并保持深度睡眠，你的体温实际上需要下降约 1 到 3 度；而为了在早晨醒来时感到精神饱满、警觉，体温需要上升约 1 到 3 度。控制睡眠环境温度有很多方法，其中最好的方法之一就是控制实际床垫的温度，也就是你睡在上面的表面。

使用 Eight Sleep，你可以非常容易地做到这一点。它有一个易于使用的应用，你可以设定床垫在整晚不同时间的温度。你可以让它在刚入睡时略微凉一些，之后逐渐变得更凉，帮助你进入深度睡眠，再进入快速眼动睡眠。所有这些对睡眠的影响，都可以在同一个应用中追踪。

我使用 Eight Sleep 床垫罩已经两年多了，它彻底改变了我的睡眠。如果你想试试 Eight Sleep，现在可以访问 eightsleep.com/huberman，享受截至 2023 年 6 月 5 日的专属阵亡将士纪念日优惠。Eight Sleep 目前向美国、加拿大、英国、欧盟部分国家和澳大利亚发货。再说一次，网址是 eightsleep.com/huberman。

今天的节目还由 Levels 赞助。Levels 是一个通过连续血糖监测仪提供饮食实时反馈，让你了解不同食物如何影响健康的项目。影响能量水平以及即时和长期健康的最重要因素之一，就是血糖，也就是通常所说的血糖水平。

使用 Levels，你可以评估不同食物和活动如何影响血糖水平。我使用时学到了几件事。首先，我发现某些食物确实会让我的血糖大幅升高。血糖升高并不总是坏事，但我能够发现某些食物让血糖升得过高，以至于吃完后我的能量水平会下降。

去掉这些食物，换成其他食物后，我的能量水平变得平稳多了。如果你想进一步了解 Levels 并亲自尝试连续血糖监测仪，请访问 levels.link/huberman。目前，Levels 还额外提供两个月的免费会员期。再说一次，网址是 levels.link/huberman。

今天的节目还由 HVMN Ketone-IQ 赞助。Ketone-IQ 是一种能够提高血酮水平的酮补充剂。现在，大多数人都听说过所谓的生酮饮食。但包括我在内的大多数人并不采用生酮饮食。也就是说，我和大多数人除了优质蛋白质等食物外，还会吃复合碳水化合物、水果以及类似食物。

事实证明，即使你不遵循生酮饮食，提高血酮水平仍然可能有益。例如，每当我想进行长时间的专注工作时，我都会使用 Ketone-IQ，比如准备播客、做研究、写基金申请；如果我想锻炼却没有时间进食，或者不想让胃里装满食物时，也会使用它。服用 Ketone-IQ 并由此提高血酮水平，可以让我在不感到饥饿的情况下进行认知工作或身体训练，同时保持充足的能量和认知专注。

如果你想试试 Ketone-IQ，可以访问 hvmn.com/huberman，享受八折优惠。再说一次，网址是 hvmn.com/huberman。我很高兴地宣布，2023 年 9 月我将主持两场现场活动。第一场将于 9 月 12 日在多伦多举行，第二场将于 9 月 28 日在芝加哥举行。

两场现场活动都包括讲座和问答环节，主题名为“脑—身契约”。届时我会讨论与心理健康、身体健康和表现有关的工具与科学。我还要说明，其中许多内容与此前在 Huberman Lab 播客或其他地方介绍过的内容完全不重叠。

如果你想参加其中一场或两场活动，请访问 hubermanlab.com/tour，并输入代码“Huberman”以提前购票。再说一次，访问 hubermanlab.com/tour，并使用代码“Huberman”获取购票资格。希望在那里见到你们。现在开始我与 Robin Carhart-Harris 博士的谈话。

Carhart-Harris 博士，欢迎你。我很久以来一直想和你交流。当然，我已经了解你很长时间了，因为我把你看作一小群非常特殊且重要的研究者之一：你们率先将致幻剂用于治疗特定临床疾病，实际上几乎是在为整个领域传承火炬。

所以我想先表达感谢，谢谢你开展这项极其重要的工作。你能否先介绍一下致幻剂是什么？事实上，我很好奇，“致幻剂”这个名称最初是怎么来的？

Robin Carhart-Harris：嗯。

安德鲁·休伯曼：以及你认为它们可能揭示了哪些关于大脑运作的内容。然后我们再谈临床应用。

Robin Carhart-Harris：当然。光是这个问题就有点敏感，因为人们对如何定义致幻剂存在不同看法。但也许，一个好的起点是先从词源讲起：这个词从哪里来？当时有一位被逐出教会、生活在加拿大的英国人 Humphry Osmond，他原本要在美国国家科学院的一次会议上发表论文，主题是“拟精神病药”，也就是作用上模仿精神病某些方面的药物。

像麦司卡林——让我想想，是 1956 年左右——以及 LSD 这样的药物都在议程上。他对把它们归入“拟精神病药”这一类别感到不满，认为这些化合物具有标志性的心理效应，不只是模仿精神病症状。

因此，他想找一个更恰当的术语，来表达这些化合物作用的核心成分。他写下了大约十几个不同的可能词语。我记得其中一个最初是 psychodelic，后来变成了 psychedelic。他还与另一位同样生活在美国的英国人 Aldous Huxley 保持通信，两人一起琢磨用哪些词来指代这些化合物。

最后，Osmond 采用了 psychedelic，还写了一句短诗：“要探究地狱或翱翔天使，只需一撮 psychedelic。”这就是需要加免责声明的地方。那么它是什么意思？它由两个古希腊词组成：psyche，指人类的心智；如果严格按照古希腊语，也可以理解为灵魂。

另一个词根的意思是使之清晰、使之可见、使之显现，或者揭示。这些解释都成立。它是一个新造词，是人为创造出来的词，但确实源自古希腊语。它表达了这样一个原则：这些化合物会揭示心灵、人类心智或灵魂的某些方面，而这些方面在通常情况下并不完全可见。

这就是它的词源，也非常有诗意。但我认为它也非常准确。这是一个有用的词，因为可以说它不预设体验的情感方向。它没有说你会获得一段美好时光，也没有说你会发疯；它只是揭示心灵，而心灵可能通向地狱，也可能通向天堂。

这既是词源，也涉及一点心理学，并指向现象学，也就是主观体验。不过，这里还涉及药理学。最近有人发表了一份关于致幻剂的共识声明，主要讨论所谓的经典致幻剂：这些化合物都作用于大脑中的一种特定受体，即 5-羟色胺 2A 受体。这也是定义这些化合物的一种方式。

我说这个问题有点敏感，是因为我认为，虽然药理学，也就是药物如何在化学层面发挥作用，非常有用，但你无法绕开现象学。如果我们忠于这个术语的词源，就必须承认并且不能忽视主观体验。

安德鲁·休伯曼：谢谢你对“致幻剂”这个词如何带我们走到今天所作的精彩解释。如今这个词被到处使用。

Robin Carhart-Harris：是的，使用得太多了。

安德鲁·休伯曼：是的，太多了。我猜——不，我不是猜，我确定这个词也被用来描述许多并不作用于 5-HT2A，也就是 5-羟色胺 2A 受体的化合物。所以大多数人采用的是更宽泛的分类。未来这些术语和名称会如何发展，很值得关注。眼下，我希望你能进一步解释这样一个观点：无论如何定义致幻剂，它们都能揭示某些通常无法以其他方式揭示的心智内容。

你说的是潜意识吗？我的意思是，心理学家，最著名的是 Freud，也包括 Jung，还有神经科学家，我想他们都会思考潜意识加工。对我而言，一个最突出的、但不属于致幻领域的例子是盲视。

这种现象是：你找来一些失明但大脑中仍保留部分连接的人，在他们面前放一块板，或者一块电脑屏幕，屏幕两侧有不同数量的点，然后问他们每一侧有多少个点。他们会说，你是什么意思？我看不见屏幕，我是盲人。你于是说，那就猜猜看。他们猜中的比例远远高于随机概率所能预测的水平。

Robin Carhart-Harris：嗯。

安德鲁·休伯曼：所以他们有所谓的盲视。有人说，这就是潜意识显现出来了。这里没有致幻药物参与。但你描述的是一种由药理学诱导的状态，它揭示了某些平常应该被遮蔽、或者我们没有意识到的内容——尽管这些内容正在表现出来。对这些药物揭示心智运作中原本不会明显呈现的部分，这到底意味着什么？

Robin Carhart-Harris：是的。盲视这个例子很有意思，但情况不同。盲视指的是无意识加工，也许是内隐加工。也就是说，心智在感知中进行着某种低于意识觉察阈值的活动，但这些活动仍然会影响你。

So it's sort-- it's kind of related, 但 it's 不同的. So in depth, psychology, psychoanalysis, psychodynamic, psychology, Sigmund Freud, Carl Jung, 和 so on. 我们 talk 关于 the unconscious. 和 there, it's 更多 关于 the kind of 血液 和 guts of the human condition, the human nature-- both the personal unconscious. So things 那 你 可能 not want to necessarily be conscious of, 因为 it's painful. So 那's the repression aspect pushing it out of conscious awareness.

ANDREW HUBERMAN: Repressed memories in particular?

ROBIN CARHART-HARRIS: Yeah. Like traumatic memories, difficult relationships. It could be complex trauma, not necessarily just a 具体的 index trauma, 但 a series of trauma. 和 then 你 have the collective unconscious, which was 确实 Carl Jung's contribution to say 那 there's a transpersonal quality to the unconscious.

There's aspects 关于 humans, not just 这 individual human. There's aspects to 我们的 minds, 我们的 psyches 那 are not fully available to conscious awareness, 但 可以 come up in certain states. Psychoanalysis went crazy 对于 dreaming as their royal road to a knowledge of the unconscious. 那 was Freud. 但 我们 now 与 psychedelics, 和 这 was what drew me 进入 the area. Was discovering literature 那 was speaking to 这 particular action, the psychedelic action.

和 was saying 那 when 这些 drugs-- like LSD, psilocybin found in magic mushrooms, when they're used in psychotherapy, material comes up 那 may be may have been repressed 那 is of therapeutic value 和 awareness 和 insight of 这 material seems to catalyze the therapeutic process 与 strong emotional 释放. 这些 cathartic experiences 和 insights. Whether they're insights 那 are personal 或 whether they're transpersonal.

但 对于 me, 这 is 确实 where the meat of it is 与 psychedelics 和 classic psychedelics, in particular. The likes of compounds like LSD 和 psilocybin. I 会 say 那 if it wasn't 对于 这 action by classic psychedelics, 我们 wouldn't be so interested in psychedelics. I think, if 我们 only had compounds like ketamine, MDMA cannabis, 那 could be said, broadly speaking, to be psychedelic-like.

I don't think it necessarily 会 have captured the world's 注意力 as psychedelics are right now. I actually think it's a major gap to fill. Is 这 principal action of the classic psychedelics. What does 这 mean 那 I'm referring to? Psyche-revealing. What is 那? 和 I suppose where I'm going 与 这 is, what is 那 in terms of the biology as well? What's going on in the 大脑 和 the 身体 when 人们 become aware of things 那 previously they weren't fully aware of.

ANDREW HUBERMAN: I'd like to talk 关于 some of the clinical trials 那 你've been involved 与. In particular, looking at psilocybin. As 你 mentioned, the principal hallucinatory psychedelic agent in magic mushrooms. I'd like to start 与 a kind of nuts 和 bolts question just so 那 everyone's on the same page.

I've read the papers 那 你've published 和 那 others have published in 这 area. 和 通常, the dosages used in 这些 trials are 25 milligrams of psilocybin. 和 我们 talk 关于 一 recent trial, in particular, 那 compared 25 to 10 milligrams to 更多 frequent use of 非常 small amounts. 1 milligram over 3 周, 对于 instance.

然而, when 人们 talk 关于 magic mushrooms, they 经常 talk 关于 gram doses of the mushroom, 因为 I'm assuming 那 they contain milligram dosages of psilocybin. Here, 我们're not encouraging use of any kind. 这些 are clinical trials. 但 对于 clarity of understanding, what is the conversion, 通常? Like 1 gram of magic mushrooms 会 contain how many milligrams of psilocybin on average.

因为 what I'm trying to do here is calibrate 人们 to 这 idea of microdosing versus macrodosing. 和 那's fairly straightforward to do 与 respect to the clinical trials. 但 then in a lot of the lay discussion 大约 这, 你 hear 关于 heroic doses versus microdoses. 和 so I think there's a lot of confusion. So if 你 会, educate us on 这 idea of what's a microdose. 和 perhaps, also how many milligrams of psilocybin are contained in a gram of quote unquote, "magic mushrooms?"

ROBIN CARHART-HARRIS: Sure. Well, a microdose is neither of 这些 are 那. Simple. 但 they're fun. It's a fun challenge. 但 microdose, 一 definition is 那 it's a dose of 通常 a classic psychedelic like LSD 或 psilocybin 那 has some perceptible psychedelic effects. It doesn't put 你 进入 a noticeable altered state of consciousness 那 feels like 你're tripping. 和 if 那 was LSD, it looks as though the threshold is 大约 关于, let's see, 10, 11, 12 micrograms.

ANDREW HUBERMAN: Micrograms.

ROBIN CARHART-HARRIS: Micrograms.

ANDREW HUBERMAN: Want to be 非常 clear here. Micrograms.

ROBIN CARHART-HARRIS: Yeah.

ANDREW HUBERMAN: So 10 micrograms of LSD, are 你 saying 会 not induce visual hallucinations in most 人们?

ROBIN CARHART-HARRIS: So 那's threshold 水平. 那's 关于 the 水平 那 some 人们 who are sensitive could feel it. 但 if 你 were to talk to the microdosing gurus, they 可能 say 那 那's the ballpark 对于 an LSD dose 那 你 会 consider a micro dose, 和 then 你 会 take semi-regularly. It's 通常 something like 一 天 on, 一 天 off 或 一 天 on, 二 天 off. 这 kind of thing.

There's 不同的 方案. 和 yeah. So some like Jim Fadiman-- 一 of the popularizers of microdosing, I think 会 say 那 a true microdose 应该 be sub-perceptible. 你 shouldn't feel it, yet the assumption is it's going to change 你 in some way on a kind of trait 水平 更多 than a state 水平, 和 maybe behaviorally.

和 the typical story goes, it 会 改善 well-being. 和 maybe, maybe, it could 改善 certain aspects of cognition, say, related to creative thinking. I emphasize the maybe there 因为 那's another angle 与 microdosing. 我们're waiting 对于 some compelling 证据. As things stand right now, I'd say, 我们 lack 那 compelling 证据.

There's some suggestive stuff, 但 经常 the 研究 designs aren't 那 strong. It's 确实 hard to do a 研究 与 microdosing, 因为 你 need to have permission to give 人们 a microdose 那 对于 practical reasons, they 会 go home 与, otherwise, 你're requiring them to be in the lab, say 三 times a 周 对于 x number of 周 to meet the criteria of a course of microdosing, which 可能 be 二 或 三 times a 周 对于 say, a month.

和 那's a hard thing to do in a lab 研究. It's expensive. 你'd need to do 那 against a suitable control, so a placebo control. 和 there is a 研究 那's been done in New Zealand 那 has some interesting preliminary 数据 那 did-- I think did the design right. 但 it hasn't been published yet. I've seen some positive findings presented 大约 improvements in 情绪. 但 it's a bit early to get too excited 关于 那. It needs to go 通过 peer review 和 all 那.

但 as things stand, the 证据 is pretty thin. 和 我们 have to be honest 关于 那. 我们 did quite a creative 研究 与 my colleagues at Imperial. The guy leading 那, Balazs Szigeti, a Hungarian chap, did a 确实 creative design. 非常 much his brainchild. He instructed 人们 to do their own blinding, their own placebo-controlled blinding of their own microdosing.

So 这 was a classic citizen science 研究 like do it yourself science where they 会 get their LSD tabs 和 chop them up, put them 进入 gel capsules, opaque, 和 have other capsules 那 are the placebos 那 they just close empty capsule. 和 then there was a whole barcode scan technique so 那 你 kind of shuffle them up. 但 they've got the barcode in, the QR code. So 你 可以 break the code later on, 但 once 你've shuffled them up, 你 no longer know which ones had the microdosing 和 which ones are empty.

ANDREW HUBERMAN: Was 这 LSD?

ROBIN CARHART-HARRIS: 这 was LSD. Also tried it 与 mushrooms, 但 the issues 与 the mushrooms was 人们 会 burp sometimes. They'd belch. 和 then they'd have 这 mushroom taste. So then he instructed 人们 to get some non-psychoactive mushroom material to put in. So it's 确实--

ANDREW HUBERMAN: Not an easy 研究.

ROBIN CARHART-HARRIS: --not an easy 研究. 和 it was-- I love 那 kind of science. Real creative 首先 mover kind of science. 和 the 结果 were fascinating, 因为 the short story is 那 the microdosing didn't compellingly beat the placebo.

ANDREW HUBERMAN: It did not.

ROBIN CARHART-HARRIS: It didn't. 和 he controlled, 因为 he asked. He controlled 对于 expectancy. So 人们's positive expectancy, which is, in a sense, the vehicle 那 carries the placebo response. It's why 你 have a placebo. Is 那 positive expectancy 可以 drive a therapeutic effect to a large extent.

So 你 measured 那 pre-trial 和 then used it to correct 对于 the response. 和 how did it work? 那些 who got a placebo 但 thought they got a microdose did as well as 那些 who thought they got a microdose 和 did get a microdose. So it was the bigger effect-- the majority of the effect was in thinking 那 你 got a microdose.

So in a sense, it was a victory 对于 the power of the placebo response. 和 it's created all sorts of controversy. 人们 don't want to believe it, 那 kind of thing. 但 那's the beauty of science, isn't it? 那 science is not 关于 what 你 want to believe. 那 right there is the beauty of science.

ANDREW HUBERMAN: I love 那 experiment. Kudos to them. I'm not going to attempt to say his last name correctly.

ROBIN CARHART-HARRIS: I tried. Yeah. Probably 你 made a mess of it--

ANDREW HUBERMAN: No. No. I think 你 got it. 你 were involved in a clinical trial 那 was published last year comparing 25 milligrams of psilocybin to 10 milligrams of psilocybin to a drug called escitalopram.

ROBIN CARHART-HARRIS: Yeah.

ANDREW HUBERMAN: Yeah.

ROBIN CARHART-HARRIS: Lexapro. Yeah.

ANDREW HUBERMAN: Lexapro?

ROBIN CARHART-HARRIS: Mhm.

ANDREW HUBERMAN: 和 这 1 milligram over a 3-周 dosage. I'm wanting to discuss the 结果 of 那 研究 a bit 和 some of the other trials 那 你've done involving psilocybin 对于 depression, the treatment of depression. Could 我们 calibrate ourselves? 25 milligrams of psilocybin, is 那 what-- it's going to be a perceptible dose presumably. Hallucinations 和 all 那.

和 is 那 what 一 会 find in-- I'm guessing here, if I'm accurate, 这 does not mean 那 I have experience here. 但 2 grams of mushrooms?

ROBIN CARHART-HARRIS: It's 更多 than 那 我们 think. Yeah. Sorry. I missed 那--

ANDREW HUBERMAN: No, no.

ROBIN CARHART-HARRIS: I missed 那 一. Went off on a tangent. 但 yeah. 25 milligrams of psilocybin 会 be-- 我们 don't know, 和 it's 重要 那 I say 那 因为 I wouldn't want 人们 to hear my answer here, 和 then use it to calibrate their own dosing of mushrooms 和 get it way off.

So it's guesswork. 和 I 会 love to see someone do a proper 研究 on it. 和 look at the psilocybin content in a given mass of psilocybin mushrooms, magic mushrooms. 但 to my knowledge, 那 hasn't 确实 been done. Someone like Paul Stamets 会 give a better answer here.

但 I think the percentage within the mushroom mass is-- of psilocybin in the mushroom mass 和 psilocin which is the metabolite of psilocybin is something in the 1%, a little bit higher, maybe, range.

ANDREW HUBERMAN: OK. So 1 gram, 1000 milligrams of magic mushroom 会 contain 关于 10 milligrams of psilocybin. Is 那 right?

ROBIN CARHART-HARRIS: Broadly speaking, yeah.

ANDREW HUBERMAN: OK. Great. 那 helps calibrate. 和 I think, again, just allows the layperson to understand a bit 更多 of where 我们're headed 与 这些 psilocybin trials 和 the 结果. So 我们 don't have to restrict 我们的 discussion to just 那 I clinical trial. 但 if 我们 include 那 一 和 compare it to some of the other trials 那 你've done, I mean, 你的 laboratory is seeing phenomenal-- in my opinion, phenomenal 结果 in the treatment of, otherwise, intractable depression, major depression, which so many 人们 suffer 从.

从 二-- I suppose there 二 sessions of using psilocybin in 这些 ranges of 10 to 25 milligrams. Do I have 那 correct?

ROBIN CARHART-HARRIS: Yes.

ANDREW HUBERMAN: OK. Could 我们 talk a little bit 关于 what 人们 通常 experience 期间 那些 sessions 那 allows 这 phenomenal transformation of 情绪 和 state 和 trait as well? 和 I'm 尤其是 interested in whether 或 not it is the experience 期间 那些 sessions 那 is the trigger 那's necessary 对于 the transformation 从 a depressed to a non-depressed state.

因为 the impulse is to think it is. 那 what 一 thinks 和 sees 和 hallucinates is-- 和 hears is so vital. 但 of course, 这些 drugs 可以 create neuroplasticity changes in 我们的 neural wiring, presumably 对于 long periods of time. So what are 你的 thoughts on the experience itself? 和 maybe 对于 那些 who have not done 这些 compounds 之前, 你 could explain a little bit 关于 what's typical 对于 人们, 和 what 你 think is leading to 那 incredible positive 和 pervasive change in 情绪, state, 和 trait.

ROBIN CARHART-HARRIS: I 会 say 那 it's 更多 than impulse 那 is leading us to think 那 the experience is 重要. It's 确实 数据 和 converging 证据 now. So independent teams, independent 研究 are converging on the magnitude of certain kinds of experience rated, yes, 与 subjective rating scales is predicting therapeutic outcomes. Pretty strongly 和 非常 reliably.

和 so 那's guiding us. Now, could 你 say, well, maybe 那些 experiences are some kind of epiphenomenon of say, a central 大脑 action? Well, absolutely. 但 then all experience are epiphenomenon by 那 principle. 和 yet 我们 care 关于 it, 你 know? 和 it matters to us 和 in 我们的 human relations 与 each other.

So I think it does matter to a human being when they're in say, a psilocybin therapy session, 和 as the drug effects begin to come on 和 the 身体 starts to feel a little strange 和 tingly 和 there's some initial anxiety. 和 then in their 心智's eye, they start to notice patterns 和 maybe colors 和 then, maybe, 那些 patterns deepen 和 they're dynamic 和 they have 这 fascinating organic quality.

ANDREW HUBERMAN: Are they-- patients in 你的 研究 通常 using an eye mask?

ROBIN CARHART-HARRIS: Yes.

ANDREW HUBERMAN: So they're in the eye mask? So eyes closed?

ROBIN CARHART-HARRIS: Yeah.

ANDREW HUBERMAN: 那's why 你 said 心智's eye as opposed to looking out 进入 the clinical setting.

ROBIN CARHART-HARRIS: Yes. 和 那's 一 of the major differences to psychedelic therapy versus taking a psychedelic. Is 你 shut 你的 eyes. 和 it's a world away 从 taking a psychedelic. Yeah. A rave 或 something. In a sense, good luck 与 那. 但 in psychedelic therapy, yeah. It's settled conditions. There's music playing. 和 what I'm describing here is 非常 much the default.

There's actually 非常 little variability between the 不同的 sites 那 have done 这 work on 这些 conditions. 通常, it's 二 人们. Ideally, 心理健康 professionals, at least 一 who's a psychiatrist 或 a clinical psychologist 或 some other kind of psychotherapist 或 psychiatric nurse. 但 ideally, 二 who meet 那些 criteria 与 a individual who's ingested the drug 和 music playing throughout. A kind of runway 进入 taking the drug 和 then throughout, so there's continuity.

ANDREW HUBERMAN: They're music 与 lyrics 或 没有 lyrics?

ROBIN CARHART-HARRIS: 没有 lyrics, to begin 与, 和 the music 通常 is spacious to begin 与. 和 then builds 和 becomes atmospheric. There 可能 be, I don't know, some tribal drums in the distance 或 something as it develops 或 like the sound of a bird in the distance. A call.

和 then as it gets 进入 更多 stronger drug effects, the music starts to coax emotion, 和 非常 intentionally, strings, 对于 example, 会 come in 和 it 会 be an interesting experiment 和 一 那 我们'd love to do actually to see whether if 你 were to pull 那 out, whether the psychedelic experience 会 be as emotionally intense as it is in psychedelic therapy when 你 have music there as a default.

和 across the board, 人们 应该 find 这 remarkable, 因为 it kind of is. All of the published 研究 那 are now having such an impact on psychiatry 和 beyond have music there as a staple component. 和 我们 just take it as assumption 那 it needs to be. I tend to share 那 assumption. 但 it's remarkable 那 it hasn't been tested properly. 但 it's there.

和 if 你 were to run 与 那, 和 if 你 had a critical agenda, 你 会 say, well, 这 is music therapy. Why are 你 making all 这 fuss 关于 psychedelics when it's music 那's there in all of 这些 trials 与 all 这些 fantastic findings. So there is something to 那. 和 这 会 tee me up probably to talk 关于 psychedelic-therapy being a combination treatment.

我们 have a hyphen between the 二, 因为 I share the hypothesis. The assumption 那 应该 be tested better. There is a positive interaction between the 二. 那 there's a synergy between the 二.

ANDREW HUBERMAN: 那's why it's psychedelic-therapy 与 a hyphen, just like Carhart-Harris.

ROBIN CARHART-HARRIS: OK. Yeah.

ANDREW HUBERMAN: I'd like to take a quick break, 和 acknowledge 一 of 我们的 sponsors, Athletic Greens. Athletic Greens, now called AG1, is a vitamin mineral probiotic drink 那 covers all of 你的 foundational nutritional needs. I've been taking Athletic Greens since 2012. So I'm delighted 那 they're sponsoring the podcast.

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和 那些 probiotics in Athletic Greens are optimal 和 vital 对于 microbiotic health. In addition, Athletic Greens contains a number of adaptogens, vitamins, 和 minerals 那 make sure 那 all of my foundational nutritional needs are met. 和 it tastes great. If 你'd like to try Athletic Greens, 你 可以 go to athleticgreens.com/huberman, 和 they'll give 你 five free travel packs 那 make it 确实 easy to mix up Athletic Greens while 你're on the road, in the car, on the plane, et cetera.

和 they'll give 你 a year's supply of vitamin D3 K2. Again, 那's athleticgreens.com/huberman to get the five free travel packs 和 the year supply of vitamin D3 K2. 这 is extremely useful to hear 因为 I think most 人们 think, OK. Psychedelic. Whether 或 not they have experience 与 psychedelics 或 not, get some visual hallucinations, some auditory hallucinations, some synesthesia, some visual auditory blending, somatosensation, 你 know? Rubbing a surface 和 being able to elicit the sounds in 一's 心智. Of course, et cetera.

但 so seldom do 我们 actually hear 关于 the specifics of 这些 clinical trials in a way 那, 对于 instance, points to music as 一 of the, perhaps, key variables. Now, 你 mentioned 那 as 人们 enter 这些 psychedelic states, 那 there's a little bit of initial anxiety. 关于 a year 和 a half ago, I had a discussion 与 Dr. Matthew Johnson who's running some psilocybin trials at Johns Hopkins, as 你 know.

和 he mentioned the critical importance, at least in his 心智, to 这 idea of the patient, quote unquote, "letting go" 或 allowing the experience to take them someplace mentally as opposed to trying to constrain their sensory 和 cognitive experience. I'm curious what 你的 reflections are on 那 idea. 和 why it 可能 be so valuable clinically.

和 这 ties back to 这 earlier discussion 我们 were having 关于 the unconscious 或 关于 psychedelics revealing something 那's there all the time 但 那 我们 don't have access to. 和 again, I'm struggling to find the right language 对于 这, 因为 我们 don't 确实 have a neural mechanism like top-down inhibition 或 something like 那 to explain how 这 unconscious 可能 be uncorked in the psychedelic experience.

但 to make it quite simple 和 direct, how 重要 do 你 think it 确实 is 对于 the patient to feel like they are, quote unquote, "letting go" 和 what in the world is "letting go" in biological terms?

ROBIN CARHART-HARRIS: Yeah. Yeah. Well, I think 我们'll get there in terms of having the neural correlates of the 心智 revealing itself to itself. The emergence of the unconscious 进入 consciousness 或 unconscious material 进入 conscious awareness. It's a wonderful challenge. It's a huge challenge, 但 it's a challenge to embrace.

和 letting go 非常 much is, again, a staple component of how the 不同的 teams do 这 work in terms of encouraging a willingness to let go. 和 when 我们 started out doing 我们的 depression work 和 did 那 首先 trial, it was the 首先 trial of psychedelic in a formally diagnosed depression, 你 know? Where 那 was the target population. A depressed population. It was the 首先 modern 研究 to do 那.

和 我们 visited Hopkins, friends there 和 were mentored on how to do the guiding Bill Richards, Mary Cusumano. They were just so brilliant 和 wise in their guidance to us as how to do the guiding in 我们的 trial. 和 so 这 phrase of trust, let go, be open, 你'll hear a lot.

I don't know who fairly it 应该 be attributed to, 但 I 会 attribute it to Bill Richards. Yeah. Everything's borrowed. 你 probably got it 从 someone else. 但 it's such a key principle. 和 it's almost like a mantra 那 你're trying to instill in 人们. Trust, let go, be open. 和 那些 不同的 components where the trust is 关于 the therapeutic rapport 那, again, 这 goes beyond just intuition now.

我们 formerly measured therapeutic rapport. 我们 do it even 与 just a single item, a visual analog scale item, a subjective rating scale item on the 早晨 of dosing, 和 我们 find 那 it's a significant predictor of the quality of the experience 那 你 have under the drug in the psychedelic therapy, 和 then the therapeutic outcomes x 周 或 months later.

So 非常 powerful chain of predictive components there, 但 trust, 本质上, 重要. 和 again, not just to intuition 但 the 数据 pointing to 那. Let go, there's a readiness to surrender, to let go, to not resist. 和 我们 do measure 那 too 和 see 那 it's predictive of response.

和 then the being open is 关于 a willingness to go there, to confront, to be inquisitive. Something 那's easier said than done. 可以 be terrifying. When 你're dealing 与 a 非常 vulnerable population, it's probably 更多-- the rule then, the exception 那 they're carrying some significant adversity, life adversity 或 frank trauma 那 they've suffered.

和 so 那 message of be open, be willing to confront 和 to go there is 确实 powerful. 和 那's how it plays out. 和 经常, there is struggle. There's something going on 那 is I don't want to be feeling 这. Make it stop. 那 可以 be nightmarish at times, 但 it's 非常, 非常 strong. 和 与 这些 big doses 那 我们 give, it's 非常 strong.

和 actually, a student 那 I've worked 与, I think now doing a PhD, at Harry Brouwer is working on a fantastic project characterizing the 不同的 phases of the psychedelic experience where the early phase is dominated by negative emotions 和 negatively-valenced feelings of anxiety 和 struggle. 和 then it's a 不同的 story in the latter half.

ANDREW HUBERMAN: Could I ask 关于 那? 首先 of all, I think 那's fascinating 和 重要 to analyze the 不同的 phases 和, again, I'm delighted here 因为 人们 通常 hear 关于 a psychedelic journey 但 我们 从不 确实 hear 关于 the stereotypic components of the beginning, middle, 和 end of 那 journey. 我们 know 那 there's a peak 和 那 there's a parachuting down 和 et cetera.

但 when 你 say 那 通常 there's an anxiety, maybe some negative valence in the early stage, do 你 mean 关于 the sensations 人们 are experiencing 或 关于 some prior event 那's being called to 心智 那 they're remembering? Likewise, 对于 the positive phase of the psychedelic journey 或 trip are 人们-- do they still call it a trip?

ROBIN CARHART-HARRIS: Yeah.

ANDREW HUBERMAN: All right. 对于 the-- I guess, 我们'll use trip. 对于 the psychedelic trip. Are 人们 feeling positive 关于 the experience like, uh. Like there's been some sort of breakthrough 或 they're in a calmer state, 或 is it 那 they tend to be focusing on prior events 那 were positive.

So in other words, is there a threading 通过 of some concept 那 comes to 心智 对于 人们? Maybe 关于 an earlier trauma 或 maybe 关于 a sense of self 或 a sense of other forgiveness. It could be any of 这些 things. 但 what do 我们 know 关于 the finer details of all 那?

ROBIN CARHART-HARRIS: Mhm. I 会 say, the initial struggle is 更多 against the general drug effects than pinning it on something 具体的. It's 更多 那 normal waking consciousness. 我们 have a sense, generally speaking, if 我们're well 或 well enough, a sense of assuredness 关于 what is a table here 和 so on.

和 我们 have 那 assuredness to an extent 关于 ourselves as well. It 可能 be illusory, 但 我们 have it. 和 what the drug's doing is it's breaking down all of 那. 和 it's scary as hell. 和 if it's a big dose, it's just like human nature to rage against 那 a bit 和 a bit like dying. I don't want 这. It feels like I could be dying.

ANDREW HUBERMAN: I 可能 lose my 心智.

ROBIN CARHART-HARRIS: Yeah. 那 too.

ANDREW HUBERMAN: I'd 从不 come back.

ROBIN CARHART-HARRIS: 那些 二 are the classics. Is oh, 但 I 可能 know 那 I've taken a psychedelic 和 I 可能 even know a bit 关于 psychedelics, 但 I still fear 那 I'm going to go mad 或 I know 那 generally speaking, 这些 drugs don't have a high fertility risk. I still think I'm going to die.

和 it's 非常 palpable 和 那 comes up. So yeah. I mean, 那些 are the core fears. 那 那些 二 和 非常 reliably, 那 comes up. 和 it's 确实 like a basic drug action. It's dose-dependent 但 it's a basic drug action 那 is forcing something 关于 the nature of the 心智 和 the way it's made up 那 makes it feel 那 way, 但 it feels like I'm losing my 心智 或 it feels like I could lose my 心智 或 那 I could go insane 或 那 maybe I'm dying here 和 这 is bad. Yeah.

ANDREW HUBERMAN: 你've talked many times 之前 和 have done 确实 wonderful work looking at the changes in communication between 不同的 大脑 areas while 人们 are under the influence of psychedelics. 和 I think the gestalt of 那些 数据, correct me if I'm wrong, is 那 compared to the non-psychedelic state, 那 under psychedelic influence. There is far 更多-- let's just call it interconnectivity 或 communication between 大脑 areas 那 通常 aren't communicating, which probably is not surprising to 人们 given the subjective effects of 这些 drugs.

What is the 证据 那 之后 the psychedelic journey is over, 那 some 或 perhaps all of 那 enhanced communication across 大脑 areas is maintained? 和 if so, what role do 你 feel 那 could play in 这些 incredible positive therapeutic outcomes?

ROBIN CARHART-HARRIS: Yeah. So 我们've had some recent findings in 那 direction where, yes, it's true. 和 picture says a thousand words 那 some 人们 可能 be familiar 与 are 这些 二 circles project 那 我们 did in collaboration 与 some researchers where ordinarily, the communication is going on within 系统 like other regions of the visual 系统 会 be speaking mostly within the visual 系统. There'll be a kind of cliquishness 或 a modularity to the quality of the communication in the 大脑.

和 then the cool finding 与 psilocybin was the 首先 paper, is 那 the communication, yes. It transcends 这些 modules 和 becomes much 更多 inter-modular crossing 不同的 modalities 和 那 effect correlated 与 the magnitude of the subjective effects 和 then 我们 replicated it 与 LSD using 不同的 methods. 和 a new paper 会 come out soon 与 DMT showing a 相似的 effect.

It's a bit of a debate 关于 what regions are most implicated. 但 the general effect of an 增加 in global functional connectivity is what 我们 call it 或 global communication in the 大脑.

ANDREW HUBERMAN: 和 这 is while under the influence of 这些 drugs.

ROBIN CARHART-HARRIS: 这 is under the--

ANDREW HUBERMAN: So putting 人们 进入 a 大脑 scanner while they are under the influence of the drug. Is 那 right?

ROBIN CARHART-HARRIS: Yes.

ANDREW HUBERMAN: 那 itself must be quite an experience, given 那 这些 scanners are small tubes. 你're in a bite bar, 你've got a bite bar in 你的 mouth. 那's quite a 研究.

ROBIN CARHART-HARRIS: 你 don't 总是 have a bite bar, at least 与 the psychedelics. 但 yeah. 你've got to keep 你的 head still. 和 你 have the loud MR scanner noise going. 但 因为 it's regular, there aren't too many surprises. So it's actually surprisingly tolerable.

ANDREW HUBERMAN: 你're in a hospital setting. So 你're not worried 关于 what 会 happen if 你 had a cardiac event 或 something.

ROBIN CARHART-HARRIS: Yeah. 你 got professionals 大约, 和 most 人们 generally tolerate 那 setting quite well, surprisingly well. 但 yeah. 我们 do all 那. 和 yes, 我们 do see the opening up of the communication across 系统 in the 大脑. 和 it does speak to intuition 关于 the subjective experience. The 不同的 modalities 可能 be blending 与 each other.

ANDREW HUBERMAN: Sorry 对于 interrupting, 但 I have to ask, is it thought 那 the activation of the serotonin 2A 受体 what's responsible 对于 the 增加了 communication between 大脑 areas 那 under normal circumstances 会 not be communicated?

ROBIN CARHART-HARRIS: Yes. So there's a few reasons why some modeling work 那-- computational modeling work 那 首先 identifies where the 2A 受体 is 和 then looks at-- models its basic effect on neural activity. 会 recapitulate the-- 或 recreate the effect 那 我们 see actually in the 数据 与 the scanning. So doing the computational modeling. 你 可以 see the same effect by knowing where the key 受体 are 和 then making them do a certain thing 那 我们 know psychedelics do.

ANDREW HUBERMAN: I 可以 imagine 二 possibilities. 和 I think it's 重要 to distinguish between 这些 二. 一 possibility is 那 the activation of 这 serotonin 2A 受体 leads to 增加了 connectivity 和 thereby auditory 和 visual hallucinations emerge, changed patterns of thinking emerge, et cetera. 那's the obvious interpretation.

但 the scientist in me has to ask, is it 可能 那 all of 那 增加了 connectivity is occurring, 和 yet 那 is a distinct phenomenon layered on top of some other effect of the psychedelic drugs impacting access to the unconscious, hallucinations? In other words, is it the 增加了 connectivity 那's leading to the subjective experience, 或 are 那些 二 things happening in parallel?

ROBIN CARHART-HARRIS: Well, they happen in parallel 和 they map to each other. 但 the question of causality, what causes what, is the tricky thing where I 会 suggest 那 the causality is circular. 那 they influence each other. 和 这 gets a bit philosophical. 但 it matters, 因为 otherwise, there's a trap 那 it's easy to fall 进入 where 你're thinking 那 it's all 关于 the 大脑 action causing the subjective experience.

和 那's 通常 what 我们 do in cognitive neuroscience. It's like the 首先 port of call materialist approach. 但 一 可以 be a materialist, 本质上, 但 still appreciate 那 circular causality 那 心智 also interacts 与 大脑. 和 it's so hard to pick the 二 apart. 和 there is a kind of essential dualism where subjective experience is a thing in 和 of itself. 但 那's not to divorce it 从 what's going on the biological 水平.

ANDREW HUBERMAN: The reason I ask is 因为 as I understand it, nowadays, there's a bit of a movement within the scientific community 那 研究 psychedelics to develop drugs 那 可以, 本质上, cure 或 alleviate many of the symptoms of depression 或 trauma 那 are built off 我们的 understanding of how psychedelics like psilocybin 和 here I'll throw MDMA in there, 尽管 classically not a psychedelic, it gets lumped in. 我们 可以 get back to 那 later.

但 那 do not produce hallucinations 或 massive changes in subjective experience. Actually, I think 这 is what initially got us 进入 conversation on Twitter as I had learned 关于 这 paper published out of a group at UC Davis. 那 本质上 modifying psychedelics so 那 they have potential therapeutic application 对于 the treatment of depression 但 zero hallucinogenic properties.

和 I thought, wow. 这 is going to be a 非常 controversial thing in the world, right? 因为 the history of psychedelics, as 你 pointed out, has been 一 of 人们 accessing 不同的 modes of thinking, feeling. Seeing things 和 letting go. Trust, et cetera. A therapeutic relationship. 和 here 我们 have-- I don't want to say pharma 因为 it's not 确实 pharma, 但 我们 have laboratories who are trying to tease apart the activation of 受体 independent of all 那 subjective experience in order to, 本质上, treat the same conditions.

I'd love 对于 你 to comment on 这, where 你 think it 可能 be going. 和 whether 或 not 你 think 那's the right 或 the wrong approach, if it has any validity at all.

ROBIN CARHART-HARRIS: It is pharmas, just smaller pharma, sort of startup pharma. 但--

ANDREW HUBERMAN: OK. So 因为 pharma 会 like to have drugs 那 可以 cure depression 但 don't make 人们 hallucinate. Is 那 correct?

ROBIN CARHART-HARRIS: Oh, they 会. 和 patients 可能 和 the 系统 会 love it, 因为 the 系统 is used to it. It's medicine.

ANDREW HUBERMAN: Right. 和 it doesn't give 这 mental imagery of the Summer of Love in San Francisco 或 of kaleidoscope eyes, right? It's 更多 of--

ROBIN CARHART-HARRIS: Yeah.

ANDREW HUBERMAN: 你 可以 imagine, the 更多-- I have to be careful 与 my wording here. 那些 who 会 not be inclined toward 那 可能 embrace a therapeutic 那 is strictly effective at treating depression 与 no hallucinations.

ROBIN CARHART-HARRIS: Yeah. 和 it doesn't look like an individual lying on a sofa crying their eyes out 关于 the life 那 they've lived. 和 那 deep catharsis being life-transforming. Is 非常 不同的 从 那 model. I'm skeptical of it 对于 a few reasons. 和 一 is 那 I 可以't see the logic-- I 可以't see the pieces fit in a way 那's compelling.

和 I'm also skeptical, 因为 I think it could easily be wishful thinking, 因为 of 那 point 那 patients 会 like it 和 the 系统 会 like it. 和 你 got to bear 那 in 心智 as well. So wouldn't it be convenient if it were true 和 你 could get the therapeutic action 没有 the psychedelic effects?

ANDREW HUBERMAN: Well, in a way, 那's a little bit of what microdosing seems to be designed to do. Like 你 said, take dosages 那 are below 那 perceptual 或 awareness of some effect threshold over a longer period of time in an attempt to ping the 回路 或 alter the 回路 但 not hallucinate. Not have a catharsis.

ROBIN CARHART-HARRIS: So if microdosing 可以 do 那, 和 it's sub-perceptible, then microdosing isn't a psychedelic action, 因为 whereas the psychedelic action. When psychedelic, when defined, means psyche revealing. 你're not getting 那 effect. 你 可能 be getting the pharmacology, 你 可能 be getting some direct serotonin to a 受体 agonism 那 could be driving a therapeutic response, 但 你 可以 get 那 与 SSRIs as well.

和 so my point is, what's new? OK. Maybe it's a bit new 和 人们 are now developing direct 2A agonists rather than indirect 通过 a serotonin releaser like the selective serotonin reuptake inhibitors, the SSRIs like Lexapro.

ANDREW HUBERMAN: Are there any SSRIs 那 selectively agonize, which folks by the way means, activate, in a good way. Agony sounds terrible. 那些 not informed 可能 think 那 mean 那 disrupt. 但 那 可以 activate the serotonin 2A 受体. Are there any drugs 那 会 do 那 are not psychedelic? I'm not aware of any, 但 then again I'm not a psychopharmacologist.

ROBIN CARHART-HARRIS: Well, there are. I mean, are there any 那 are licensed 和 used as medicines in psychiatry? I actually had 这 debate recently on social media, 和 I couldn't see a compelling example. I saw 2A agonists 那 were used 对于 other things. 你 have a compound like Lesuride used in treating Parkinson's, 但 actually it's 更多 of a 多巴胺 agonist.

ANDREW HUBERMAN: Right. So they're 总是 hitting other things, right?

ROBIN CARHART-HARRIS: Yeah. Yeah.

ANDREW HUBERMAN: They're 总是 tapping other 神经递质--

ROBIN CARHART-HARRIS: All 那 being used 对于 other things. So is there a selective serotonin 2A 受体 stimulator, an agonist, 那 isn't psychedelic, 那 is therapeutic in psychiatry 和 the answer firmly is, no. I haven't seen it yet. 会 they develop 一? Well, 对于 patients sake, I hope so. 因为 it 会 be great. Let's wait 和 see. If they do, I doubt it'll be psychedelic 和 I doubt it 会 have much to do 与 psychedelic therapy.

和 it 会 be much 更多 like the 系统 我们're used to of chronic pharmacotherapy. Take 你的 drug every 天. Let's hope they find it 和 it works 对于 patients sake. 但 as things stand right now, I'm a little skeptical. Now, some of the findings 那 are being seen 那 are 确实 exciting, fantastic work being done, showing things like 增加 in the communication components of neurons, dendritic growth, spine growth, synaptic spine growth.

ANDREW HUBERMAN: Yeah, by the way, folks, just I'll interrupt 对于 not necessarily spine-- not the cerebral column 但 spines are 这些 little tiny twigs 与 bulbs on the end of neurons 那 allow 对于 communication points between neurons. So neuroplasticity is 经常 associated 与 growth of dendrites 和 spines 和 so forth, which is what Robin's referring to.

那 reminds me, 和 I just want to make sure 那 我们 close the hatch on the earlier answer, 因为 I interrupted 你. Is the 增加了 connectivity between-- 或 communication between 大脑 areas 那's observed while 人们 are under the influence of the psychedelic also observed later 之后 the effects of the drug wear off?

ROBIN CARHART-HARRIS: Yeah.

ANDREW HUBERMAN: 和 then I'll just throw in another question there, 因为 我们're on to 这 topic now. To what extent do 我们 think 那 neuroplasticity, structural changes in neurons, functional changes in neurons are responsible 对于 那? 和 how long does 那 last?

Let's say I come 进入 你的 clinic, I'm a subject in 你的 experiment, I take-- come in the 早晨, I do my psychedelic journey five 或 six 小时 later. I'm parachuting back to reality, as 我们 call it, 和 then I go home. 增加 connectivity lasts 对于 how long, 和 how long are the structural 大脑 changes occurring?

ROBIN CARHART-HARRIS: Well, 你're asking fantastic questions, 和 partly 因为 我们 don't have the answer yet. 但 我们 do have some 数据. 和 so 我们 have looked at, 首先 of all, in a sense, the functional plasticity of what 我们 assume it to be 或 at least the functional changes, the 增加 in communication across 系统 那 增加 in global connectivity, functional connectivity. Do 我们 see it 之后 the trip? 我们 know 我们 see it 期间 the trip pretty well replicated correlating 与 intense drug effects. Do 我们 see it 之后 the trip?

Well the answer is, 我们've seen it in 二 不同的 depression cohorts, psilocybin therapy 对于 depression. In 一 研究 where 我们 looked the next 天, 我们 saw it. A kind of residual effect 相似的 to what 你 see acutely being seen the next 天. 和 then in a subsequent 研究, 我们 saw it also 三 周 later.

So 我们've seen it in 二 independent 数据 sets. 这 降低 in modularity is how 我们 measure it. It's the same thing, 本质上. Broadly speaking, it's the same thing. An 增加 in global connectivity, functional connectivity. 和 actually, unpublished 我们've seen it in healthy volunteers on a correlational 水平.

Not on an absolute change 水平, 但 if 你 look at its relationship to a 心理健康 outcome, 和 这 is an 重要 thing to 压力 与 the depression work, 我们 saw a relationship between the magnitude of 那 change, the 降低 in modularity 或 增加 in global connectivity, 和 the improvement in symptom severity.

ANDREW HUBERMAN: So interesting.

ROBIN CARHART-HARRIS: Yeah.

ANDREW HUBERMAN: 和 just to state it a 不同的 way, so what Robin is referring to is when 你 say modularity, as neuroscientists, 我们 think of the 不同的 modular networks of the 大脑. The eye talks to a region of the thalamus involved in vision, which talks to the visual cortex, which eventually converges 与 auditory information, of course.

但 there's a separation 或 modularity of function. 这 增加了 connectivity is cross-modular in 期间 the trip, 但 afterwards as well. 和 你're saying 那 那 correlates 非常 strongly 与 the 力量 of the therapeutic outcome 对于 depression. I mean, the logical extension of 那 is 那 extreme modularity of 大脑 function is depressive in some way. Now, 我们 don't want to go too far, 但 what does 那 mean 那 increasing crosstalk between 不同的 modules of the 大脑 is so strongly correlated 与 a positive therapeutic outcome?

ROBIN CARHART-HARRIS: 我们 don't other than there's a relationship. I mean, 这 is the thing. 我们 need to be a little careful not to run 与 it too far. I mean, there's some things 那 it suggests. I think it suggests a 更多 flexible mode of 大脑 functioning, if 你're not getting stuck in modules 或 the modules aren't excessively cut off 从 each other.

但 你 see 不同的 things 与 不同的 presentations if 你 were to look at cognition. Sharper cognition is actually associated 与 更多 modularity. So it's a rule 那's a little slippery. 和 我们 need to be careful 与 it.

ANDREW HUBERMAN: Again, forgive me 对于 interrupting, 但 I think I have friends who are-- I 会 say, are on the spectrum. Who are 非常 linear in their thinking 和 extremely intelligent in the kind of classic sense of being able to ratchet 通过 hard problems to arrive at a solution.

和 then I have friends who are-- let's just call them what they are. 从 the creative communities outside of science 那 are 非常 expansive, they see connections between many 不同的 things, 但 sometimes, 你 have to-- not all of them, 但 你 have to catch their ideas 与 a butterfly net. 和 oftentimes, what they're saying sometimes it just doesn't make any sense.

Now, they also produce incredible creative works. 但 to have a conversation 与 them is anything 但 a linear experience. They are not random thought generators, 但 there's a non-linearity 或 randomness to their processing 那's distinct 从 这些 other folks 那 I'm describing on the spectrum. 和 of course, it's a spectrum. There's a whole range in between. It sounds to me like there is some therapeutic value to being able to move along 这 continuum 从 the 更多 linear to the nonlinear. Is 那 correct?

ROBIN CARHART-HARRIS: Well, I think so. Yeah. It's resonating what 你're saying. It's speaking to my intuition. 那 你 could be 非常 passy, passing things up, chopping things up like an analytical scientist like I'm doing a bit.

ANDREW HUBERMAN: A splitter as 我们 say in science. 你're either a lumper 或 a splitter. Yeah.

ROBIN CARHART-HARRIS: The way I'm being 非常 particular 关于 when to call something psychedelic. 那 kind of passy analytical way of thinking 你 可能 associate 与 a 更多 modular 系统. Whereas the 系统 那's 更多 globally, interconnected, 和 open, yeah. 可能 be 更多 flexible 和 creative 和 divergent in the associations 和 so on so.

Yes. 那's speaking to my intuition to how 你're describing it. 和 I imagine, if 你 take severe psychopathology, severe mental illness like a depression, I've 总是 thought 那 there's something intuitive 关于 the term itself. Like a depression in a landscape, which is a halt.

ANDREW HUBERMAN: Physical depression.

ROBIN CARHART-HARRIS: A physical depression 那 is easy to fall 进入. 和 if 你 do, it's hard to get out of.

ANDREW HUBERMAN: So almost-- if I understand what 你're saying correctly, almost like getting stuck at 一 location on 这 continuum. 因为 most 人们 don't reside at 一 extreme 或 the other full time. They 可以 kind of migrate back 和 forth between expansive states 和 更多 linear states.

ROBIN CARHART-HARRIS: Like 你 do 与 low 情绪. If 你're "healthy" in inverted commas, 你 可以 feel 你的 low 情绪, 你的 disappointment. 但 你 可以 spring back. 但 someone 与--

ANDREW HUBERMAN: 和 你 know 你 可以 spring back.

ROBIN CARHART-HARRIS: Yeah.

ANDREW HUBERMAN: Right. Whereas the suicidal depressive person 或 suicidally depressed person, somehow, at least in my understanding, there's something 关于 那 extreme depressive states 和 extreme anxiety states, something my laboratory is a bit 更多 familiar 与 anxiety, which alters the perception of time such 那 人们 feel like 那 negative state is going to go on forever 或 那 if it goes away, 那 it's going to return at random.

ROBIN CARHART-HARRIS: Yeah.

ANDREW HUBERMAN: Kind of a vulnerability to the time domain.

ROBIN CARHART-HARRIS: Yeah. Yeah. 和 it's so tragic, 那 cognitive bias in depression 那 everything's hopeless 和 那 there is no light at the end of the tunnel. Yeah. Yes. So if 你 were to get stuck in 那 rut 和 have 那 bias, then 你're cut off 从 other things, other sensory modalities 或 modules, cut off 从 the world, cut off 从 other 人们. Stuck in 你的 inner rut.

So yes. I think 我们're sharing 这 intuition 那 a 降低 in modularity 或 an opening up of the 系统, the 大脑 could relate to an opening up of the 心智 那 is enduring 之后 the psychedelic dosing session. 和 yeah. 和 the third replication was to see in healthies an improvement in well-being. 因为 they're healthy, 我们 don't look at depression.

ANDREW HUBERMAN: So 这些 are 人们 那 are healthy walking 进入 the trial?

ROBIN CARHART-HARRIS: Yeah.

ANDREW HUBERMAN: Take psilocybin twice?

ROBIN CARHART-HARRIS: Well, actually they do. 但 the 首先 dose is 1 milligram, which they don't feel it's a placebo dose.

ANDREW HUBERMAN: Quote unquote, "micro dose." Yeah.

ROBIN CARHART-HARRIS: Yeah. 我们 stick EGG on their heads to measure their brainwaves 期间 each dose. 和 1 milligram, 你 see no change.

ANDREW HUBERMAN: I think 那, 你 microdosers. No, I'm just kidding. I mean, nothing against the micro doses. I've 总是 just been a little bit skeptical based on my conversations 与 the scientists actually doing the work 与 psychedelics. It seems like the answer keeps coming back. 1 或 2, maybe 3 macro doses in a controlled safe setting.

ROBIN CARHART-HARRIS: Well, 那's compelling. The 证据 对于 那 is compelling. 和 那's what's making all the difference right now. Microdosing is just appealing, 但 again, science isn't 关于 what 我们 want to believe, it's 关于 what's actually coming 通过 和 what seems to hold up to testing.

ANDREW HUBERMAN: I'd like to just take a brief break 和 thank 一 of 我们的 sponsors, which is LMNT. LMNT is an electrolyte drink 那 has everything 你 need 和 nothing 你 don't. 那 means, plenty of salt-- sodium, magnesium, 和 potassium, the so-called electrolytes 和 no sugar. Now, salt, magnesium, 和 potassium are critical to the function of all the cells in 你的 身体, in particular, to the function of 你的 nerve cells, also called neurons.

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I 通常 drink LMNT 首先 thing in the 早晨 when I wake up in order to hydrate my 身体 和 make sure I have enough electrolytes. 和 while I do any kind of physical 训练 和 之后 physical 训练 as well, 尤其是, if I've been 出汗 a lot 和 certainly, I drink LMNT in my 水 when I'm in the sauna 和 之后 going in the sauna, 因为 那 causes quite a lot of 出汗.

If 你'd like to try LMNT 你 可以 go to drinklmnt-- 那's L-M-N-T.com/huberman to claim a free LMNT sample pack 与 你的 purchase. Again, 那's drinklmnt-- L-M-N-T.com/huberman. 会 你 say 那's right? 那 一 或 二 或 三 sessions, 和 how far apart are 那些 通常 spaced in time?

ROBIN CARHART-HARRIS: Yeah. 通常, 一 to 三 周 across the sites is the way 人们 are doing the psychedelic therapy dosing sessions. 二 sessions, 你 know, Hopkins, Imperial, NYU. 那's been a kind of default to-- 我们 actually use 三 in a current anorexia trial, psilocybin therapy 对于 anorexia. 二 patients left to see 之后 19 who've gone 通过 the trial. 非常 exciting 结果 there.

ANDREW HUBERMAN: 你're seeing an alleviation of the obsessive thought 关于 food 和 a willingness to consume healthier amounts of food.

ROBIN CARHART-HARRIS: Yeah. Even 改善了 weight at the long follow-up.

ANDREW HUBERMAN: So critical. When 我们 did an episode on eating disorders, I learned 那 anorexia nervosa, which by the way folks, the rates are not increasing. It's been pretty stable 通过 time despite what's said 关于 social media, 和 et cetera. 但 anorexia nervosa being the most deadly of all psychiatric illnesses, which is a big statement, 因为 manic depression, so-called bipolar depression, has a 20 to 30 times the typical suicide rate.

Basically, many 人们 与 anorexia, I think is how it's-- is what 一 says, not anorexics. 但 人们 与 anorexia 经常 die. Many of them die.

ROBIN CARHART-HARRIS: Yeah. So tragic. So 经常 young 人们 as well. 和 similarly, 与 suicide in terms of premature death. So the tragedy 与 psychiatry is so strong. It's so rewarding to be doing 那 trial 和 to be seeing good 结果. I have to check myself a little bit 那 I'm reporting on it in 这 确实 promisory way 和 the trial isn't yet publicly 释放了 和 published. So it's still ongoing as well.

ANDREW HUBERMAN: 但 那 was 三 sessions.

ROBIN CARHART-HARRIS: It is 三 sessions. 和 I 可以't say what the dosage is, 因为 我们 still have-- there is a blinding component. 但 there are 三 dosing sessions in there. Let's see now. I think they're 二 周 apart 和 我们 do the follow-up. Yes.

ANDREW HUBERMAN: I'd like to close out 这 description of the journey 和 the trip by extending past the 天 when 人们 actually take the drug 进入 这-- what I've described as the integration phase. 你 have to re-integrate. All 这 增加了 connectivity 期间 the session. Hallucinations, insights, anxiety, letting go. Maybe revelation, maybe epiphany. OK. Great.

At what point is 那 consolidated? Meaning, are 这些 patients 或 受试者 in 研究 having daily conversation 与 their therapist? Are they journaling every 天? 和 I want to keep in 心智 那 most 人们 are not going to be part of a clinical trial. 和 of course, here 我们're not suggesting what 人们 do 或 not do.

但 let's just put it 这 way. Were 人们 to use psychedelics, what is the way 那 人们 可以 maximize on the neuroplasticity 和 the 大脑 changes in a positive way in the 天 和 周 afterwards? In other words, how long does 这 so-called integration last? 和 how far 可以 我们 take 这? I mean, I could imagine 那 how 经常 一 chooses to think 关于 the insights could also have an impact.

ROBIN CARHART-HARRIS: Yeah.

ANDREW HUBERMAN: Right? 因为 clearly 人们 went to raves, clearly 人们 did psychedelics in the '60s. 我们 don't know if clearly 人们 do psychedelics now. 但 我们 don't have 数据 on 那些 人们. 你 have access to the understanding of how they're spending their time 和 the therapeutic outcomes, which 我们 haven't gotten to the numbers yet, 但 again, are incredibly impressive. In upwards of, as I understand it, 60% 或 更多 人们 getting relief 从 depression.

ROBIN CARHART-HARRIS: Yeah. 70%, yeah.

ANDREW HUBERMAN: 70%. Incredible, 尤其是 when compared to the typical antidepressant treatments 和 so on. So what is 这 business of integration? How is it done properly?

ROBIN CARHART-HARRIS: Yeah. Yeah. Gosh. Well, how long does it last as well? A lifetime? 你 know? Life is a journey like a trip is a journey. 和 there's 总是 work to do. As Jack Kornfield says, 之后 the, ecstasy the laundry. 和 你 know?

ANDREW HUBERMAN: I love 那.

ROBIN CARHART-HARRIS: Yeah. Yeah. There'll be other good ones as well, 但 forget them. 但 yeah. So the work is ongoing, 和 yeah. 但 这 gives 你 a foot up. It enables 人们 to do the work 更多 easily, 和 那's true. The classic psychedelics is also true. 非常 true of MDMA therapy 对于 post-traumatic 压力 disorder.

It's 确实 giving 你 a leg up, making it easier to do 非常, 非常 difficult work going back to a trauma. Trying to digest it, process it, integrate it. So it's such an essential component of the treatment model. 但 一 has to be realistic as well by saying, oh, integration lasts a lifetime.

Well, 人们 delivering a service 可以't be there 对于 a lifetime. So what's the answer there? 和 人们 are wrestling 与 那 issue right now. 和 I think 一 of the solutions 可能 be 那 it's, in a sense, on 你 to appoint. The therapeutic team 可以 treat 你 to a point 和 then it becomes what 你 可能 call practice. In a 相似的 way, 那 meditation is a practice.

It's something 那 你 have to keep up. 和 if it slips, then things could slip. 和 那's the way it is. 或 你 have another psychedelic treatment. So 人们 have even used 这 term of practice in relation to psychedelics, where there's a psychedelic practice like there's a meditation practice.

但 I'm using meditation intentionally here 因为 they actually think 那 meditative practice, elements of spiritual practice could be a 非常 重要 complement to psychedelic therapy. 和 I think it's probably doing something 相似的 in terms of promoting an ability to sit 与-- a former colleague of mine said it quite well. In relation to psychedelic therapy versus chronic pharmacotherapy 或 like SSRIs being on them all the time.

Says psychedelic therapy allows 你 to sit 与 rather than sit on. 和 so 那's quite good. Yeah. So the meditation, the mindfulness, the ability to, yes, be present-centered 但 also present-centered 和 accepting so if things come up, 你 可以 watch 和 process 和 then let go.

ANDREW HUBERMAN: 那 Holy Grail of mindfulness.

ROBIN CARHART-HARRIS: Yeah.

ANDREW HUBERMAN: Awareness 没有 reactivity, respond. I grew up in the Bay Area 和 你'd hear 这 language, right? 和 I'm not being disparaging 这. I have friends 那 are on the board of Esalen 和 work down there. 和 I've gone there. 和 yet 你 hear 这些 terms, right? Be responsive, not reactive, which to a neuroscientist is like grates on me, which probably just means I have issues. 和 surely, I do.

但 what does 那 mean? It's saying like, oh, to be the observer 但 not be drawn 进入 the experience. 和 again, I don't want to be overly reductionist, 但 what I find so compelling 关于 the emerging 数据, 因为 it 确实 is 数据, on psychedelics as treatments 对于 depression 和 trauma, namely psilocybin 和 MDMA is 那 it 确实 seems to allow 人们 这 space 那 is so commonly thrown 大约. Giving space between stimulus 和 reaction.

Viktor Frankl talked 关于 这. 但 I've been reading a wonderful book called The Prince of Medicine. Dates back to the origins of medicine. 非常 dense book. 人们 have been talking 关于 这 stuff 和 thinking 关于 这 stuff 对于 thousands of years. Psychedelics seem to give 人们 access to 那 better version of self, which is remarkable. What's also remarkable, it's, perhaps, worth pointing out is 那, five years ago, I 从不 会 have been comfortable having 这 conversation. I 会 have been afraid to lose my job.

Stanford Magazine, 这 周, just published an entire issue 关于 psychedelics 与 how ketamine works, MDMA, psilocybin 与 the appropriate cautionary notes in there. 但 clearly, times are changing. Speaking of which, I know 你're doing a trial on 首先-time use of psychedelics. What inspired 那? 和 what are 你 observing? 和 as 你 tell us 那, please give us a few of the key contours.

What's the dose, how old are 这些 受试者? I'm assuming it's men, women. Are they suffering 从 depression 或 not? What's the landscape of 那 研究? 和 I realize 这 is still early 天 of the 研究 或 maybe it's close to completion. It's not yet published, 然而, correct?

ROBIN CARHART-HARRIS: It's not published, it's not submitted, it is completed. So 这 was another 一 of 我们的 COVID 研究, in a sense, meaning COVID hit 和 我们 had to finish the 研究. 和 it was hard to finish the 研究 因为 of COVID. 那 was true of 我们的 psilocybin therapy versus escitalopram. Lexapro trial, which is published in The New England Journal of Medicine. 但 the--

ANDREW HUBERMAN: 这 was '20-- 那 paper, by the way, folks, 我们'll provide a link to in the show note captions as well as some of Robin's other papers. I think the 2022 New England Journal paper is 确实 fabulous given the 不同的 dosages 和 the comparison to, 本质上, what is microdosing 和 the comparison to citalopram.

ROBIN CARHART-HARRIS: Mhm. Yeah. 那's interesting 那 你 link the way 我们 gave small doses of psilocybin to microdosing. 我们 didn't think of it 那 way. 我们 thought it was just a necessary placebo 对于 the big dose, the 25 milligrams. Yeah. So 那 我们 could say to everyone 我们're giving 你 psilocybin 和 not be lying.

Yeah. 对于 那些 who got escitalopram, Lexapro 对于 six 周, they got a 非常, 非常 low dose of psilocybin. 但 it allowed us to standardize all the psychotherapy 和 so on. 但 the other 研究 那 你're referring to was in healthy volunteers. Middle-aged. Average age, I think, was 40. So not 你的 typical student 研究 那 is so 经常 the case in psychology 研究. All the undergrads end up volunteering 对于 你的 研究.

So 这 is 更多 of an age range 和 also-- I think it was an equal proportion of male 和 female. All the staff actually were female, which the staff were 非常 proud of them.

ANDREW HUBERMAN: 尽管, it produces its own potential confound, right? To become all 一 sex of staff.

ROBIN CARHART-HARRIS: Possibly.

ANDREW HUBERMAN: Yeah.

ROBIN CARHART-HARRIS: They did a good job in the sense 那 我们 saw significant improvements in well-being at the end of the trial. So let me describe the design. It was a repeated measures design, meaning 人们 come in, 你 collect 你的 baseline 数据 和 do a 大脑 scan, 和 你 give 人们 a placebo. 我们 gave 人们 a placebo. 和 actually let me rewind a little bit.

Everyone's healthy volunteers, middle-aged 从不 taken a psychedelic in their life. None of them. Entirely fresh, virgin 人们 coming in. 和 the plan is to give them their 首先 ever psychedelic experience. So 那's what 我们 did in 这 研究. 但 to do it, 我们 have 这 repeated measures design where they'll 首先 get a placebo.

和 我们 have the placebo so 那 我们 可以 do all the procedures, all the therapy, all the music listening 但 not give a whopping dose of psilocybin. Again, 我们 gave them a placebo dose of psilocybin. 1 milligram. 我们 stick EEG headsets on 期间 the experience to record the 大脑 activity 从 the scalp, the oscillating electrical activity.

和 我们 do the MRI scanning 之前 和 之后 to see deeper 进入 the 大脑, 和 我们 可以 look at the functional connectivity 那 我们 were referring to earlier, 和 also properties of 大脑 anatomy, which 我们 did in 这 研究. So the short story is 那 all of the changes 那 我们 saw both psychologically 和 neurobiologically were seen 与 the 25 milligrams. It all happened 与 那 big whopping dose.

和 what did 我们 see? Well, 我们 did see significant improvements in psychological well-being. 我们 saw what I call the entropic 大脑 effect, which is actually formerly quite accurate. 我们 see an 增加 in the informational complexity of ongoing 大脑 activity recorded 与 the EEG on the dose of psilocybin.

The activity becomes 更多 complex. It's harder to predict across time. It's 更多 informationally rich. 和 那 effect correlates as it does 非常 reliably 与 the magnitude of the subjective effect. So the bigger the trip, the bigger 这 entropic 大脑 effect. Now, pretty well replicated finding. 但 then the MRI, seeing deep 进入 the 大脑 was probably 我们的 most exciting result where 我们 didn't just see some functional 大脑 changes, 但 我们've seen some anatomical 大脑 changes as well.

和 我们 used a technique called diffusion tensor imaging 那 looks at the cabling of the 大脑, the white matter tracts. 和 我们 saw a change in major tracts. So 我们 limited 我们的 search space to 确实 thick tracts. 确实 thick fibers. 和 the fibers 那 came 通过 as changing were ones 那 traveled between the prefrontal cortex 和 the thalamus 和 the striatum.

There were 二 tracks, 二 prefrontal tracks 那 changed. 和 they changed in the direction of a 降低 in axial diffusivity, which could be interpreted as tract integrity where a 降低 会 be an 增加 in tract integrity. It is something 那 你 see in the developing 大脑. The axial diffusivity 降低 as the 大脑 goes 从 being a baby to being an adult. Axial diffusivity goes down. 和 then in aging 和 pathologies of aging, axial diffusivity goes up.

ANDREW HUBERMAN: 这 is in the opposite direction of the 结果 你 talked 关于 earlier in terms of 大脑 connectivity of 增加了 communication across areas. If I understand correctly, 和 I'm perfectly happy to be wrong, by the way, 那 这 降低 in axial diffusivity translates to a higher fidelity of communication between the prefrontal cortex 和 the thalamus 和 striatum as opposed to 更少.

和 你的 description of 这 as somewhat like the transition 从 babyhood 和 childhood to adulthood. Speaks to the same where 我们 know 那 there's a massive culling of connections as opposed to growth of connections. So in other words, as 我们 get older, 我们 get better at doing certain things 和 更少 good at doing potentially most everything else. Is 那 right?

ROBIN CARHART-HARRIS: Ish. 因为 the change was anatomical 和 not functional. So the other stuff was is 确实 measuring communication in the 大脑 by looking at how the activity fluctuates across time 和 whether 那些 fluctuations in activity are synchronous between regions.

和 if they are, 我们 say they're functionally connected. 和 我们 infer 那 they're talking to each other, 因为 they go up 和 down in synchrony. 但 when it comes to the anatomy, 我们're talking 关于 the just static material stuff. 和 so 我们're seeing the fibers 和 a property of the fibers change. At least 那's what 我们 think.

和 recently, 我们 had an independent person come in 和 reanalyze the 数据, 因为 一 of 那些 things, incredible finding requires credible 证据, 确实 strong 证据. 和 I 会 say, the 证据 at the moment is 一 研究. So 我们 need to be cautious on 那. 但 我们 did re-analyze it 和 use 这 correction procedure-free 水 correction to be 更多 sure 那 it was a change in the actual microstructure rather than something to do 与 the extracellular space. The 水 surrounding the fibers.

和 it came 通过. In fact, the change was strengthened by doing 这 correction step.

ANDREW HUBERMAN: So 这 is neuroplasticity as the consequence of 一 首先 time session 与 25 milligrams of psilocybin.

ROBIN CARHART-HARRIS: Yeah. Yeah. So 我们're excited 和 the 二--

ANDREW HUBERMAN: Understandably so.

ROBIN CARHART-HARRIS: --the 二 不同的-- the 秒 analyst coming in wasn't sure she believed it 和 then she thought 这 correction technique 可能 kill the result 和 then it came 通过, 和 she's like, OK. Now, I'm excited too. So 我们'll see. 我们 don't know what it means. What does it mean functionally? 我们 don't know. How did the 人们 change? Well, psychologically, as I said, well-being 改善了.

我们 did look at their cognition, 和 我们 used a cognitive flexibility paradigm 那 looks at 人们's ability to notice a rule change 和 then flexibly adapt their behavior based on noticing 这 rule change 和 人们 改善了 之后 the 25 milligrams 和 didn't significantly 改善 之后 the placebo dose.

There weren't correlations 与 the DTI change, the cabling change 和 这些 psychological outcomes. 但 与 这些 研究 和 smaller sample sizes, 你 don't 总是 see 那些 correlations come 通过. So it's something. 我们 don't know what it means. 但 it's a change in 大脑 anatomy 那's in the opposite direction to what 你 see in an aging 大脑 或 与 pathology of aging. 和 it's what 你 see in a healthy 大脑 as it goes 从 normal neurodevelopment 进入 adulthood.

ANDREW HUBERMAN: 非常, 非常 exciting 和 intriguing. 和 I appreciate 那 你 highlighted 那 it's just 一 研究, 尽管 从 everything 你've said, it sounds like it's been done 与 immense rigor. So 我们 会 eagerly await the publication of 那 研究 so 我们 可以 peruse all the 数据 和 the subsequent 研究.

I want to hear a bit 关于 the 研究 那 你 have been carrying out on the use of psilocybin 对于 the treatment of fibromyalgia. I'm intrigued by fibromyalgia, 因为 I have a good friend who also-- I won't reveal who it is. No. It's not me. 这 isn't the "I have a friend thing." Who also is a scientist who sits at a fairly high position in the National Institutes of Health who quietly has expressed to me 那 they are incredibly frustrated 与 the fact 那 the standard medical community has largely ignored fibromyalgia.

和 那 对于 many years, it was lumped 与 things like chronic fatigue syndrome 和 other so-called-- again, so-called. I'm not saying 这. 但 人们 经常 refer to 这些 as, oh. It's psychosomatic. 那's all in 你的 head. Which, as a neuroscientist, is a ridiculous statement to hear, 因为 it's all in 你的 head. 你的 大脑 is in 你的 head 之后 all.

你的 physiology 和 你的 psychology are influencing each other. Of course. 和 the world is starting to appreciate 那 更多. 但 首先 of all, maybe 你 could tell 人们 what fibromyalgia is, what inspired 你 to do a 研究 on fibromyalgia using psilocybin of all things 因为 那's surprising to me. 和 if 你 are allowed to 或 if 你 have access to the 数据 in 心智, share 与 us a little bit 关于 what 你're discovering in 那 研究.

ROBIN CARHART-HARRIS: Sure. Yeah. Happy to. So again, it's psilocybin therapy 和 the population is fibromyalgia syndrome. So 这 is 人们 presenting 与 a generalized chronic pain. So unlike some other pain disorders where the pain is focused. 你 可以 say, it's my lower back, which is 非常 common. Chronic lower back pain. 这 is 更多 generalized.

和 对于 那 reason, it's hard to know what it is. 和 那's why it's been a controversial space in medicine 和 it's been-- yeah. It's had 那 charge thrown at it 那 maybe it's psychosomatic, 和 just to 你的 point, is anything ever independent of the 心智, anyway. 但 这 is actually a fascinating space 对于 how subjective experience, the lived experience, 和 the 心智 可以 influence the 身体.

因为 there's some 确实 interesting literature 大约 the etiology. How the pain has come 关于. In a sense like what caused the pain. What's the story there? 和 the head of the trial, I 会 say to my colleagues, let's just be careful. 因为 there is some fascinating literature 大约 things like a background of trauma 和 how 那 可以 relate to issues related to 炎症 和 how 那 可以 express 进入 things like fibromyalgia syndrome.

I just said, be 非常 careful there, 因为 if 你 go in 与 an assumption 那 there's some buried trauma, 对于 example, then there's 那 whole other side of psychoanalysis 那 massively tripped it up 大约 false memory 和 so on. 和 so please don't hold prior assumptions 那 你're going to uncover buried trauma in every case.

Now, the team of treated, I think, eight 人们 和 it is going 非常 well. Again, I just want to be careful 与 how I describe it to manage expectations 和 not get too carried away. 但 I check in 与 the team every 周, 和 they're still based in London doing the work.

和 it's remarkable what I hear 关于 the profound experiences 那 人们 have under the drug. In 这 研究, 我们 only give 一 dose. It's a 非常 mechanistic 研究. 我们 actually have the EEG cap on in the sessions like in the healthy volunteer 研究, 但 这 time now taking it 进入 a clinical population. 和--

ANDREW HUBERMAN: So they are wearing an eye mask under the influence of 25 milligrams of psilocybin. Most of them probably have not done psilocybin 之前. So it's a little bit like the 首先 time 研究 in some sense. They have fibromyalgia 那's debilitating in some way. They don't want it, obviously. 和 期间 the session, are they thinking 关于 their pain? Are they being told to think 关于 their pain?

ROBIN CARHART-HARRIS: They're not being told to think 关于 the pain. In fact, as I understand it, while there is a therapeutic model 大约 acceptance of the pain, it isn't-- unlike some of the PTSD work, 你 aren't encouraging them to 专注 on the index trauma 和 then work 通过 it 和 try 和 digest it. 我们 don't do 那 与 the pain.

So the pain is there, 但 there isn't an invitation to 专注 on it. 和 那's probably 一 of the differences 与 classic psychedelic therapy versus MDMA therapy. Arguably, MDMA therapy is 更多 like it's a bit closer to traditional talk therapy where there is 更多 dialogue. 人们 are able to talk on MDMA.

ANDREW HUBERMAN: In the MDMA trials, do 你 know whether 或 not they used eye masks 或-- 因为 这 seems to be an 重要 distinction between, as 你 described, the therapeutic trip versus the trip 那 一 does going 进入 the woods 和 taking psilocybin in the woods 或 at a party 或 while staring at a poster 或 a leaf.

Again, I'm not trying to trivialize 那些 experiences. I mean, obviously, they 可以 be profound. So I'm told. 但 the MDMA trials seem to involve, as 你 said, 更多 directed dialogue. 和 sometimes, even empathic connection between 人们 by they're actually looking at 一 another, the eyes 和 eye contact being such a key part of the human social cognitive connective networks. So do 你 know if they put eye masks on 人们 期间 the therapeutic session?

ROBIN CARHART-HARRIS: I'm pretty sure 那 they have the eye masks there.

ANDREW HUBERMAN: Right. 因为 a lot of the MDMA work, 和 I was part of an MDMA trial. Was, as I understand geared toward developing, 因为 it's an empathogen empathy toward the self.

ROBIN CARHART-HARRIS: Yeah. I'm pretty sure they have the eye masks there, 但 they probably-- 和 it's a great question, 因为 你 could formally test 这. It probably don't use them as much.

ANDREW HUBERMAN: Mhm.

ROBIN CARHART-HARRIS: The thing is 与 the classic psychedelics, if 你're looking at 你的 guides 或 你的 facilitators 和 their faces are melting 或--

ANDREW HUBERMAN: On MDMA, 你 just 可能 确实 start to feel 更多 connected to 你.

ROBIN CARHART-HARRIS: Yeah. They 可能 look 尤其是 beautiful 和 你 know--

ANDREW HUBERMAN: sure. Yeah.

ROBIN CARHART-HARRIS: 和 yeah. There's 那 fascinating effect of loving the 人们 那 你're 与. 和 so yeah. I imagine they talk 更多 和 use the eye shades 更少. 和 it is 更多 interpersonal rather than like intrapersonal 或 going inside. They do use a fascinating terminology 那 some 人们 have critiqued, 但 it is a 非常 interesting phenomenon.

和 it's 这 notion of the inner healer. They use 那 language a lot. It's been critiqued 因为 it sounds 非常 suggestive. 你 know? 和 那's probably 一 of the vehicles here. Driving the therapeutic process is suggestion. I think 我们 have to be honest 关于 那. So when they go inside, 那's another term 那 我们 use 非常 much in the classic psychedelic therapy work. 你 go inside. 你 put the eyeshades on, 和 人们 are encouraged to go inside.

但 when they do 那 in the MDMA work, 尤其是, they 可能 be told explicitly 和 listen to the inner healer 和 那 language. So 你 could see how a cynic 或 a skeptic could come in 和 see 那 as some kind of like suggestive priming 或 biasing. I think they have a point. Skeptics 经常 do, 但 I don't think it's all of the story.

和 just briefly, 因为 it's an interesting point, speaking to 那 point a bit in 我们的 psilocybin therapy versus escitalopram trial, 我们 measured pre-trial expectancy. 和 我们 did it 对于 both conditions. So what kind of improvement do 你 expect 与 the Lexapro, the escitalopram at the end of the trial? 和 what kind of improvement if 你 go 进入 the psilocybin arm 和 get 二 big doses of psilocybin. What kind of improvement do 你 think 你'll see in 那 arm?

和 of course, it was a coin flip as to what arm 人们 went 进入 和 there was no crossover. What 我们 found was 那 it was true 那 我们 had a sample bias, so most 人们 had higher expectation stations. On average, there were higher expectations 对于 psilocybin 和 its efficacy 或 effectiveness versus the SSRI, the Lexapro.

然而, when 我们 looked at the correlation 或 the predictive relationship between pre-trial expectancy 和 response, 我们 saw 那 pre-trial expectancy 对于 the escitalopram predicted response to escitalopram across virtually every single measure, all 这些 不同的 measures of depression 和 anxiety 和 well-being, 和 I think none of the scales.

I'm pretty sure it was none of 关于 12 或 so 心理健康 rating scales. Was there a relationship between pre-trial expectancy? Even though it was high, it didn't predict-- pre-trial expectancy didn't predict response to the psilocybin therapy. So 那 was a bit of a smash on the head 对于 the idea 那 the classic psychedelic therapy is some kind of placebo response.

和 I think it's so 重要 to address 那 question. 因为 if it doesn't come 通过 as it didn't come 通过, then it opens up even 更多 intrigue 关于, well, what is it then? If it's not just a placebo response 或 a super placebo response like an amplification of the placebo response, then it must be something else. 和 how intriguing? It has a direct therapeutic action. It must be something.

和 我们 don't yet know what it is. I talked 关于 the residual 增加 in global connectivity. 那's 一 possibility. 但 the truth is, 我们're just scratching the surface.

ANDREW HUBERMAN: 和 yet the therapeutic outcomes are, again, just so marvelously impressive. I'm curious as to why as-- well, there are 那 many labs. 但 the laboratories 那 are focused on classic psychedelics 对于 the treatment of depression 和 now as 你 mentioned, promising 结果 对于 anorexia 和 fibromyalgia as well. 尽管 preliminary 非常 promising.

Why the lack of 注意力 toward LSD? Is it 那 the LSD trips are just too long? Is it 那 they are qualitatively 不同的? Are there any 数据 on non-microdoses of LSD? 和 here I want to be 非常 careful, 因为 I learned 通过 my interactions on social media 那 这 term microdose is 非常 misleading.

和 in some cases, 可以 be dangerously misleading, 因为, as 你 mentioned earlier, the effective psychedelic dose 或 the-- effective meaning 那 可以 induce a real trip 与 hallucinations, et cetera, of LSD is actually in the microgram range. So some 人们 hear microdose, 和 they think microgram of LSD is a-- micrograms is a microdose when, in fact, a macrodose of LSD 可以 be measured in micrograms, right?

So 这 is where in the absence of scientific 训练, 人们 可以 确实 go astray. 或 even just in lack of understanding of the metric 系统. 和 since now 你're a recent arrival to the US, fortunate 对于 us. Sorry. England's loss is the US's gain by-- Robbins Lab moved 从 England to the United States recently. So score 1 对于 us. 但 why isn't there 更多 use of LSD in 这些 trials?

ROBIN CARHART-HARRIS: I think it probably is the duration of the trip. It used to be stigma 和 it was easier to get 你的 psilocybin 研究 通过, 因为 others were, they were getting 那 通过. So there was the likes of Franz Vollenweider in Zurich in Switzerland 和 then Roland Griffiths coming along 和 doing the psilocybin work at Hopkins.

So 你 could appeal to 那 precedence 和 say, well, they're doing it over there. 可以 我们 not do it in little England? So 那's how it worked 对于 us. 我们 did actually go on 和 do an LSD 研究 once 我们'd laid the foundations 对于 doing 这 kind of work. 和 it was a 大脑 imaging 研究. It was a 确实 extensive 一 actually where 我们 used both MRI 和 another modality called MEG, sort of super EEG in a sense.

但 你 know, why didn't 那 turn 我们的 heads to think, oh, 应该 我们 not be doing 我们的 trials 与 LSD? It does have something to do 与 the pragmatics like a 研究 天 与 psilocybin is long enough.

ANDREW HUBERMAN: So four to six-小时 trip?

ROBIN CARHART-HARRIS: Yeah. 和 the FDA asked us to have the 人们 in the lab until eight 小时 post-dose, which personally I think could be quite excessive, 尤其是 if it's a low dose. 和 if 你 have 那 in the placebo condition as well, it becomes impractical.

ANDREW HUBERMAN: Yeah. Scientists are not paid nearly enough to warrant the-- there's no such thing as overtime 对于 the graduate students 和 postdocs.

ROBIN CARHART-HARRIS: Yeah. It's 经常 那些 更多 junior members 那 are doing 那 确实 hard work.

ANDREW HUBERMAN: It was described 非常 well to me by a student when I was-- a graduate student said to me, they 确实 可以't afford to pay us by the 小时. 因为 我们 used to work. He was a electrophysiologist, so he 会 run experiments. No joke, folks. 三 to five-天 experiments. Sleeping in bouts of 二 小时 here 或 there in a dark room 与 a bunch of equipment 和 recordings.

So 这些 are long, long acute electrophysiological recordings. So yeah. No scientist does it 对于 the money, I promise 你. There is money in pharma, there is not money in personal income. It's not lucrative 对于 the basic scientist. So yes. LSD is what? Anywhere 从 8 to 15 小时, something like 那.

ROBIN CARHART-HARRIS: Yeah. 15 会 be a little long. 你'd be a bit worried if 你 were still tripping at 那 time, maybe 与 a 确实 big dose.

ANDREW HUBERMAN: Oops. No. Just kidding.

ROBIN CARHART-HARRIS: Yeah. Eight 小时 plus-- 和 dose dependent, yeah. If it's a bigger dose, it's a longer experience. 但 if 你're going to dose say, 10:00 AM in the 早晨, which is 更多 或 更少 how it 经常 goes, then 那's 6:00 PM still feeling the effects. 和 then how long do 你 wait now to close things out 之前 they 可以 go home.

Even 与 psilocybin, 你 have 人们 still at work 进入 the 晚上. 和 the staff are 总是 there later, of course, 因为 they've got to pack up 和 yeah. So 这些 are long 天. 和 it's too much, 你 know?

ANDREW HUBERMAN: 那 makes sense. Practical constraints. I learned 从 a recent guest on 这 podcast 那 我们 recorded 与, Dr. Satchin Panda who is a colleague of mine when I was down at the Salk Institute. Pioneered a lot of the 研究 on so-called intermittent fasting.

那 the reason 那 the eating period in 这些 研究-- in animals 和 now on humans is 8 小时, the feeding window in 这些 研究 is 因为 the graduate student was going to, otherwise, lose their relationship. 因为 their significant other says, listen, 你 可以 be in the lab 对于 12 小时, 那 meant some 小时 之前 the experiment, then 8 小时, 和 then some 小时 afterwards. 但 你 可以't stay in there longer. 和 many 人们 use the eight-小时 feeding window as a consequence. So the scientist has to exist 和 be carried out in real-world frame.

ROBIN CARHART-HARRIS: It does.

ANDREW HUBERMAN: Yeah.

ROBIN CARHART-HARRIS: It does.

ANDREW HUBERMAN: MDMA is a little bit shorter, right? It's 关于 a four to-- it's also 关于 four to six 小时, correct?

ROBIN CARHART-HARRIS: Yeah. It's kind of 相似的 to psilocybin. Yeah. It is. 和 actually, in the maps work, they redose 之后 a certain point.

ANDREW HUBERMAN: The booster.

ROBIN CARHART-HARRIS: They have a booster 或 optional booster, yeah. So there is 那. 和 now, 人们 are thinking, well, even the psilocybin sessions are long 和 expensive. 和 if 你 have to have 二 staff members there all the time, 那's expensive. 那's where most of the expense is. Is in the staffing. So 可以 我们 abridge the experience, make it shorter, 和 get away 与 it, 和 get 相似的 therapeutic outcomes? So there's a lot of interest in 那 direction.

ANDREW HUBERMAN: May I ask 关于-- sorry to interrupt, 但 I want to make sure I don't forget to ask 关于 combination psilocybin MDMA therapies. The reason I ask 关于 这 is-- 和 here, truly not me, 但 I know 人们 who do self-administered combination psilocybin 和 MDMA. I think I heard 这 right. I think it's called a hippy flip.

There's another 一 那 involves LSD too. Again, I'm not suggesting 人们 do 这些 drug combinations. 但 the way it was described to me was 那 the psilocybin, 因为 it's so serotonergic, sometimes 可以 be not a downer 但 可以 have a bit of kind of a murky feel to it. Some real deep introspection, sometimes in the darker realms of 一's psyche depressive thoughts, et cetera.

Not 那 it necessarily stays 那 way throughout the trip, 但 那 the MDMA, 因为 it has a 非常 strongly serotonergic 但 also 多巴胺能的-- I mean, it has an amphetamine component. Cocaine-like, in fact. If 你've ever seen someone on MDMA, their pupils are 关于 the size of a quarters. 对于 a reason, they're extreme autonomic arousal compared to a sedative, which by the way, 会 constrict the pupils.

So they describe the use of MDMA to balance out the affect component of it. What are 你的 thoughts on combination psilocybin MDMA? Does 这 hold any therapeutic potential? 这 is, obviously, backyard chemistry in the sense 那 人们 are cowboying 这 stuff on their own, which again, I don't 确实 recommend. I'd like to see the science go 首先, 但 I understand 这 is how it works in the real world. Yeah. What are 你的 thoughts on combining compounds?

ROBIN CARHART-HARRIS: Yeah. Well, I guess, they're cowboying it in recreational context, 但 also underground therapists do work 与 这 combo.

ANDREW HUBERMAN: 那's what I'm referring to. So I'm not talking 关于 人们 partying 与 这 stuff. I'm talking 关于 there are thousands now of therapists 那 offer psychedelic therapies illegally, 确实, 因为 it's not legal at least, not in the US, to possess 或 sell. 但 那 are doing 这.

ROBIN CARHART-HARRIS: Yeah.

ANDREW HUBERMAN: So 那's 确实 why I'm asking.

ROBIN CARHART-HARRIS: Yeah. 和 I think there's something to be said 对于-- 一 has to be careful 与 这 as a scientist. 但 if they're doing it, are they using some kind of trial 和 error? The same is true, of course, 与 longer history of psychedelic plant medicine use if by plants, 我们 include the fungi as well. So in the extended sense plants.

There 会 have been trial 和 error there. It 可能 not be as systematic as the science 我们 do today, 但 maybe there's been a learning process. 和 maybe what they do, they've come to 因为 they found it works. So by 那 principle, I'm interested in 那 combination 和 whether it does offer some advantages, maybe, in certain patients.

一 of the buzz terms in medicine 这些 天 is precision medicine. A precision medicine 和 personalized medicine. So maybe there are certain cases where introducing say, psilocybin 之后 the MDMA 或 the other way 大约 could offer some advantages. 和 the differences are interesting.

Psilocybin 可以 get 你 to deep places. Maybe the kernel of 你的 suffering 和 major life experiences 和 complexes 那 are causally linked to whatever the pathology 那 你're presenting 与. 但 it 可以 do it, sometimes, quite aggressively. 和 if it say, post-traumatic 压力 disorder, it 可以 be overwhelming. 和 你 可以 fight it. 和 确实, it's 那. The resistance is 确实 challenged, 和 they fight back.

和 the therapeutic breakthrough 和 the progress isn't happening 因为 你've agitated the defense mechanisms. Whereas what MDMA offers is something arguably 更多 directionally reliable in terms of the valence. It's 更多 directionally positive generally, an MDMA experience.

ANDREW HUBERMAN: Hard to have a bad time on MDMA.

ROBIN CARHART-HARRIS: Yeah.

ANDREW HUBERMAN: To be quite blunt, I mean. 但 一 of the concerns I had 与 MDMA, I've 从不 done it recreationally. I have had not 和 have not ever done it recreationally. 但 when it was done in 这 therapeutic setting, I realized, 因为 there was a music on at the beginning, I actually asked them to turn it off, 因为 I realized 那 the music was becoming such an attractor to my 注意力 那 I suddenly was starting to think 关于 music 和 my love of music, which was not the 专注 of the session 那 was there 对于.

和 I'm glad 那 they did turn the music off, 因为 the moment they did, I was able to drop in within the eye mask to 这 sort of go inward 和 address some certain issues 那 at least to me felt key 和 productive. So 那 seems to be the kind of hazard 与 MDMA. Is 那 it's such an empathogen 那 一 could start to-- 你 could go down any number of 不同的 rabbit holes.

ROBIN CARHART-HARRIS: Yeah. 但 it's also-- it's a 力量, 因为 你 well, the classics like psilocybin 可以 take 你 there 非常 reliably 但 maybe a bit aggressively. MDMA makes it easier to go there. 和 那's its 力量. 和 那's why 那 marriage of MDMA therapy 对于 PTSD, in particular, is a good combo. It works, 因为 你 are going to go there. In a sense, 你 have to 确实 make the therapeutic progress. 你're going to have to go back there.

但 我们're going to set it up so 那 你 可以 go back there 和 feel safer 和 更多 trusting 和 be able to go back there whereas 你've 从不, otherwise, been able to go back there 没有 dissociating 或 having horrible flashbacks 和 so on. So 那's the 力量 那 it offers. I guess the limitation 会 be 那, maybe, it doesn't take 你 as deep as the classic psychedelics.

和 I tend to think I'm biased on 这 一, 那 there's a kind of honesty to the classics in 那 it is hell as well as heaven. 和 那's the psyche. It isn't all roses.

ANDREW HUBERMAN: I 确实 appreciate 那 你 bring 那 up. 因为 I think 那 there's such a fear of so-called bad trips. There's such a fear in non-psychedelic states to avoid the painful 和 everything 我们 know 从 trauma 和 the treatment of trauma. 和 我们've had several guests on here.

和 my close colleague, close, close colleague at Stanford, Dr. David Spiegel, 我们的 Associate Chair of Psychiatries, Clinical Hypnotist. Amazing human being 和 scientist 和 clinician, has 确实 just embedded 这 in my 心智. 那 the only way to deal 与 trauma is to get right up next to 那 trauma to the point where some relief is experienced.

There is no other real way. 和 so, I 确实 appreciate 那 你're saying 那 the classic psychedelics may offer 与 a 非常 strong nudge, perhaps, the opportunity to get 进入 the uncomfortable in a way 那 MDMA 或 some non-classical psychedelics, perhaps, do not. 我们 were talking 关于 time frames 或 duration of trips 和 这些 不同的 compounds 和 how they differ 和 how they're 相似的.

I'd love 对于 你 to educate me on DMT 和 some of the work 那 你're doing 与 DMT. My understanding is 那 it's a 非常 brief trip 分钟. 人们 I know who have done 这. Again, therapeutically, actually, I'll just point to 一 非常 exciting, I think, group 和 initiative which is the Veterans Solutions Initiative, which is a group-- 这 is carried out in Mexico, 但 in conjunction 与 laboratories at Stanford 和 elsewhere who are evaluating the neural changes.

和 这 involves ibogaine, which is iboga, which is a 非常 long duration psychedelic. 22 小时 或 更多, followed by I think 一 或 二 doses of DMT. 这 is 对于 veterans to deal 与 any number of issues. Appears to be working 与 great success. 和 I've spoken to several 人们 who've gone 通过 这.

和 the way 那 they described DMT, almost across the board, was quote, here I'm just pulling quotes, right? Anecdata. The most profound experience of my entire life, even greater than the birth of my children, quote, "like being attached to the shockwave of an atom bomb." Quote. "There's no way I 会 do another dose, 因为 the 首先 一 was so unbelievable." Interesting, by the way.

I think most of us, including me, 会 think, why wouldn't 你 want to do it again then? 但 这 idea 那 那 was just beyond anything. So 这些 are significant-- excuse me 这些 are significant statements coming 从 个体 who have existed at the extremes of human experience to begin 与. 这些 are so-called tier 1 operators within special operations who exit 和 may 或 may not have trauma. 但 DMT sounds like a big deal.

ROBIN CARHART-HARRIS: Yeah.

ANDREW HUBERMAN: Short duration, 确实 big deal. What do 我们 know 关于 its chemistry? What do 我们 know 关于 how it's impacting 大脑 networks? 和 what in the world is going on 那 人们 are describing it as the ways I just mentioned a few moments ago?

ROBIN CARHART-HARRIS: Yeah. It's a rocket ship. If the psilocybin is like a ship leaving port, then yeah. 这 is a rocket ship 进入 craziness.

ANDREW HUBERMAN: Is it serotonin 2A?

ROBIN CARHART-HARRIS: It is. Yeah. So it is a classic psychedelic. It's a direct agonist, a direct stimulator of the serotonin 2A 受体. It's an order of magnitude 更少 potent than psilocybin. 但 potency is a funny thing, 因为 it's dose-dependent. So 那 doesn't mean 那 the experience 与 DMT is 更少 than 那 of psilocybin. It's just 那 你 give 更多 of the drug.

但 那's matched by it's stickiness 对于 the serotonin 2A 受体, which is 这 kind of golden rule in psychedelic sciences 那 it was discovered in the mid 1980s. 这 tight relationship between the affinity 或 the stickiness 或 the binding potential of a psychedelic 对于 2A 受体, in particular. Serotonin 2A 和 its potency. 和 the stickier the drug, the 更多 potent. So LSD 确实 sticky. 非常, 非常 potent. 你 only need 那些 tiny microgram doses.

So DMT, by its affinity, is a little 更少 potent, 但 by its effects when 你 give a standard dose, it's just wild. 和 DMT, 因为 there's another compound called 5-methoxy DMT, which is a bit 不同的 pharmacologically 和 subjectively, it's 相似的 in terms of its kinetics. It's another rocket ship.

Both compounds in the wild, so to speak, are smoked 经常. DMT 和 5-MeO. 人们 are vaping both actually now. There are vape pens 那 are being developed 对于 人们 to administer 这, 但 更多 traditionally, it's been a smoking thing.

ANDREW HUBERMAN: 这 is clinically not recreationally 或 both.

ROBIN CARHART-HARRIS: Both no. I mean, underground practitioners are using the vape pens. They like them 因为 人们 titrate the dosage. They get a feel 对于 what it is to be going 进入 这 state so 那 they feel they 可以 let go 和 go 进入 it. 和 actually, I think some of the veterans work 可能 be giving 5-MeO 之后 the ibogaine.

Phenomenologically, if there's a difference between DMT 和 5-MeO, 人们 可能 put it on 5-MeO being 更多 of a reliable ego dissolution experience. 更少 visual 和 更多 all round immersion in the greater whole loss of self-identity 和 just immersion in everything.

ANDREW HUBERMAN: Yeah. Maybe 我们 could just talk 关于 ego dissolution 对于 a 秒, 因为 it's such a sticky, interesting idea. I 可以 take a step back as a neuroscientist 和 say, OK. Ego dissolution. 这 idea 那-- 从 a 非常 early age, 我们 have a concept of self 和 那 I wake up every 早晨 和 I know I'm me 和 not somebody else. 和 presumably, 你 do the same. 和 most 人们 do the same, I 会 hope.

和 那 there are objects in the world 和 人们 in the world beyond us. 但 every time I hear 关于 ego dissolution, it sounds like it's kind of a temporary elimination of the idea 那 things start 和 stop between us 和 everything else. Almost like in a kind of a-- here I'm not trying to sound philosophical 或 metaphysical, 但 there's the molecular continuity of life, right? 我们're all just little bits--

ROBIN CARHART-HARRIS: Which is true.

ANDREW HUBERMAN: --which is true, right? Not a functional way to go 通过 the 天, right? 因为 你 want to make a cup of coffee, 你 don't 确实 want to get lost in 那 if 你的 goal is to make a cup of coffee. 但 what is the power of ego dissolution? Is it the idea 那 我们 belong, is it a sense of meaning? Is it the sense 那 我们're not as 重要 as 我们 think, which, of course, could be a wonderfully useful way to go 通过 life? To think 那 我们're not as-- like 我们 are vitally 重要, 但 我们're not the only thing, right? 因为 I do believe connection is vital as most 人们 do.

What is ego dissolution? 和 why 会 这 serotonin 2A activation cause 那? 那's remarkable.

ROBIN CARHART-HARRIS: Yeah. Great questions. I mean, what is it? 你 alluded to it 与 the start/stop, I think. 因为 你 could define it by boundaries. In a sense what isn't me is as valid here as the a developing sense of what is me 那 a child develops at whatever age.

和 so a major characteristic of the ego dissolution experience rather than just a negative, a thing going away. My sense of self going away is the positive. Oh. Now, I feel interconnected 与 other 人们 和 the world at large. 和 I realize 那 there is 那 molecular continuity. 和 actually, 那's a ground truth. 和 oh, maybe the ego thing is somewhat illusory 或 at least a construction of my 心智.

ANDREW HUBERMAN: 和 indeed it is, right?

ROBIN CARHART-HARRIS: Well, it is. Yeah. I mean, there's no transcendentalism 关于 那. It's just not like logic.

ANDREW HUBERMAN: I think 我们 are 关于 it a little bit like family. I mean, 我们 all know what immediate family is, 但 it's like-- forgive me 对于 interrupting myself. I do it all the time, anyway. When I teach neuroanatomy, some clever student 总是 figures out, OK. Well, 那's connected to 那 和 那's connected. 但 ultimately, everything in the 大脑 is connected to everything else.

ROBIN CARHART-HARRIS: Yeah.

ANDREW HUBERMAN: There's just no way 大约 那. 那's a true statement.

ROBIN CARHART-HARRIS: Yeah.

ANDREW HUBERMAN: 和 so 你 确实 just have to decide where 你 draw the boundaries between--

ROBIN CARHART-HARRIS: Yeah. Where do 你 draw the line?

ANDREW HUBERMAN: Where are the modules? What are the modules? 你 could say, the 大脑 is just 一 big macro module.

ROBIN CARHART-HARRIS: Yeah.

ANDREW HUBERMAN: 和 then 你 also want to include the 身体. 和 now fortunately, 人们 are starting to embrace 这 idea 那 it's not 心智-身体, it's both. 因为 the 神经系统 extends 通过 both, of course. So the same could be said of family. 我们're related, right? Not just by virtue of the fact 那 我们're human beings. If 我们 did 我们的 genealogical charts, 我们 会 find a convergence at some point.

ROBIN CARHART-HARRIS: Yeah.

ANDREW HUBERMAN: 和 of course, 这 becomes a bit of a game. 但 then 一 realizes 那 where 你 draw the boundaries 和 if 你 draw them at brother, sister, parents, biological parents, et cetera, 那's a game too. 和 so it is just a construct.

ROBIN CARHART-HARRIS: Yeah. I mean, it is a fun game. Where do 你 draw the line 和 when to pass 和 when to collapse. It's also a classic consideration in science when to pass 和 when--

ANDREW HUBERMAN: 那 lumper versus the splitter.

ROBIN CARHART-HARRIS: There 你 go. It's brilliant. Yeah. 但 你 asked 这 question, like, well, why does psychedelics do it? 和 there, 我们 think psychedelics do it, 因为 the target 受体, at least, classic psychedelics do it. 和 那's 重要 to 压力. So MDMA doesn't 确实 do it in the same way, 可能 soften the ego a bit. 但 yeah. 那's debatable.

ANDREW HUBERMAN: My experience 与 MDMA is 那 it's such a strong empathogen.

ROBIN CARHART-HARRIS: Yeah.

ANDREW HUBERMAN: 和 那 it 可以 cause empathy 对于 others. Certainly, 你 could imagine situations where 一 in MDMA journey 和 afterwards says, oh, my oppressors are the 人们 那 harmed me. 和 here I'm not referring to my experience. 但 they did the best 与 what they have. Actually have empathy 对于 them. Forgiveness. 但 also 对于 oneself. 那 there's an empathy 对于 self, I know I said 这 earlier, 那 is 非常 hard 对于 most 人们 to access.

Perhaps, not the narcissists out there listening. They'll be like, of course, empathy 对于 self. 但 everyone else, I think, all the other healthy 人们 或 the healthy 人们 other than narcissists 和 not picking on narcissists. I have to imagine they suffer too. In fact, I think 那's the root of their narcissism.

那 empathy 对于 self is not something 那 comes reflexively 对于 most 人们. 和 here I'm not talking 关于 self love 或 self respect. 但 这 notion of being able to see the self as not just deserving of love 和 care 但 actually holding 那 in place while in confrontation 与 something challenging in a way 那 allows a 更多, not 更少 access to adaptive responses to 那 challenge. I think 那's the way I conceptualize it.

ROBIN CARHART-HARRIS: Yeah. Yeah. I mean, drugs offer a great-- they offer great-- they are great scientific tools 对于 tackling 这 question. What is ego dissolution, 和 why do drugs modulate it? 和 what does 那 tell 你 关于 the 大脑? 因为 other drugs like cocaine releasing 更多 of a 不同的 神经递质, 多巴胺 更多 than serotonin. The opposite is the case 与 MDMA. Is 更多 of an ego inflator, right?

ANDREW HUBERMAN: Oh, absolutely. 人们 会 become hyper-linear, hyper-linked to their own desires 和 wishes, 和 future outcomes become an obsession. It's the stuff of American Psycho 和 the cliches 和 stereotypes of the '80s cocaine culture.

ROBIN CARHART-HARRIS: Yeah. Yeah. 我们 did a 研究 once actually looking at dose-dependent relationship 与 ego inflation on 一 axis 和 ego dissolution on the other 和 saw 那 it just massively passed 或 differentiated between cocaine 和 psychedelics. It's quite a neat 研究.

ANDREW HUBERMAN: So cocaine makes 人们's egos super inflated?

ROBIN CARHART-HARRIS: Yeah. 和 doesn't touch dissolution 和 the opposite is the case 与 psychedelics.

ANDREW HUBERMAN: Is there any neuroimaging to explain how cocaine does 那?

ROBIN CARHART-HARRIS: 那 会 be a great 研究. Yeah. Great idea.

ANDREW HUBERMAN: 我们 应该 do 那. I have a sabbatical coming up. I've got 12 months of sabbatical coming up.

ROBIN CARHART-HARRIS: Yeah. 那's--

ANDREW HUBERMAN: I'm going to show up in 你的 lab.

ROBIN CARHART-HARRIS: Yeah. 那's a 确实 good 一. If it's all right to finish the thread on why psychedelics 和 ego dissolution, 我们 do know some things 或 我们 have some hypotheses. 和 it's 那 the target 受体, the serotonin 2A 受体 那 classic psychedelics hit, are heavily expressed in what 这些 天 I like to call recent 大脑. 因为 evolutionarily, it's recent 大脑. It's cortex 那 humans have 更多 than any other species.

If 你 look at a mapping of cortical expansion 从 say, macaque 或 chimp to human, it's the 非常 same map 那 你'll find the 2A 受体 in. So 那's the target. 和 it's just easy to think 那-- oh, well, 那 could be the egoic 大脑 和 the classic psychedelics come in. They scramble up the activity. 那's the entropic 大脑 action. 和 in terms of the start/stop, the boundaries, 那 entropic action spreads out the 系统. It doesn't shut it off. It spreads it out.

ANDREW HUBERMAN: Dissolution?

ROBIN CARHART-HARRIS: Yeah. 和 你 were talking 关于 the headspace as well. So 那 fits. If it's 更多 capacious, it fits. The big qualifier 与 psychedelic therapy 那 人们 rightly bring up is it doesn't last. 那's the paradox of it. The paradox of ego dissolution.

So the ego 可能 go away 期间 the trip, 和 你 have 这些 profound insights 关于 the molecular continuity 和 how 我们're all 一 和 interconnected. 和 then 你 come down, 和 然而 long later, the ego comes back, 但 maybe 与 a vengeance. 和 sadly, things 可以 go awry when 人们 haven't done the work. Perhaps haven't done the integration work 和 maybe ego defenses come back 和 it's not a pretty picture.

ANDREW HUBERMAN: How 经常 do 你 see 那 in the trials 那 你 do? What percentage of 人们 coming 通过 do 你 think end up 与 worse than they were 之前 the trial?

ROBIN CARHART-HARRIS: It's 非常 rare in the trials 那 我们've done. Yeah. 但 你 see defenses come back. So 你 do see 人们 relapse. 那's 更多-- if 你're pushing out to like 三 months plus in something like treatment resistant depression, 那's 更多 the rule than the exception sadly. 人们 relapse.

If their histories are histories of chronic depression, then while 你 可能 give them a window of wellness, sadly, it doesn't last. 那's not to say 那 it doesn't ever last. It does. 和 我们 have 人们 who are in 我们的 首先 treatment resistant depression trial who are well to my knowledge today, back at work doing fantastically well. 但 sadly, the majority have relapsed, to my knowledge.

ANDREW HUBERMAN: 和 need to do 更多 psychedelic journeys.

ROBIN CARHART-HARRIS: Well, they 可以't, 因为 it's illegal. 那's been the 确实 difficult situation 那 我们've been up against. Is 那 我们 do a trial where all of a sudden 这 schedule 1 drug becomes a medicine in the trial, 或 at least an experimental medicine. 我们 give the treatment, it works fantastically well, gives 人们 a remission 那 they've 从不 确实 had 对于 然而 long, 和 then the trial ends 和 they're denied 那 treatment.

和 worse still, if they were to have 那 treatment, they 会 be committing a crime. It's a sick joke in a way. 但 那's the situation 那 我们've been in.

ANDREW HUBERMAN: 和 那's a perfect segue 对于 what I want to talk 关于 now, which is, what is the current state of legality in terms of-- 或 the progression towards legality. I'd also like to touch on the role of, let's just say, incoming big pharma. There are a lot of start up companies now trying to capitalize on 这些 discoveries 那 你 和 others have made.

The landscape out there is 非常 unclear to me. Maybe I'll just call out some silos as I see them 和 maybe 我们 可以 draw some bridges between them, if they exist. At the ground 水平, not the grassroots, 但 at the ground 水平, I look to laboratories like yours, Matthew Johnson's, Roland Griffith's some laboratories at Stanford. Nolan Williams.

Laboratories studying the effects of psychedelics in human beings, so not animal models, in terms of their clinical application 对于 the treatment of depression, anorexia. I now know fibromyalgia, trauma. Let's lump MDMA in there as well, assuming 那 it all works in equivalent way at the 水平 of where the legislature is taking things.

OK. So labs using government money, philanthropy, et cetera. Then there are the therapists out there 那 are accessing what 我们 believe are clean sources of MDMA. Psilocybin, LSD to do 这. They are doing it illegally. 这 is in the US 或 other Western European countries, 因为, obviously, it's going to differ by country. Who are administering 这些 things on the basis of what they're reading in 这些 研究 那 你 all are publishing.

但 also expanding on 和 experimenting hippie flips 和 combination drugs 和 ketamine 和 et cetera. 但 let's leave ketamine out right now 因为 it's legal. 但 there's 那. Then there's the-- I don't want to say recreational/open market, black market. 和 here I want to raise a flag to the fact 那 Dr. Peter Attia did a terrific podcast on 这 recently in his own podcast, The Drive.

The fact 那 fentanyl-- lacing 与 fentanyl is now showing up in MDMA 和 psychedelics 那 are purchased on the street. So serious caution to 那些 getting it 从 uncertain sources. 和 then 你've got pharma. 和 then as an umbrella 对于 all of 这, 你've got the FDA 和 law enforcement agencies, which currently say, 这 stuff is illegal unless it's being used in a clinical trial.

Selling it 或 possessing it 可以 get 你 charged 与 a crime ranging 从-- I don't want to say 因为 I don't know. 但 up to felonies. Right years in prison. So 可以't take it 通过 airports, don't get caught 与 it, don't buy it, don't sell it kind of thing. So where are 我们 going 从 那 picture of the silos?

I know things are in clinical trials now. Most 人们, including myself, are not familiar 与 how the 不同的 phases relate to the proximity to legality. Could 你 just give us the landscape 和 touch on how long 你 think it 会 be 之前 the 人们 那 come 通过 你的 trials could then go get a prescription 对于 psilocybin 或 potentially buy it 没有 the risk 从 a reliable source, 一 会 hope, 但 没有 the risk of getting thrown in jail.

I used to live in Oakland, California. My understanding-- 和 please correct me if I'm wrong, folks. Don't trust 这 information 和 get in trouble. My understanding is 那 psilocybin is decriminalized in Oakland, 但 那's not the same as being legal. So what is going on out there?

ROBIN CARHART-HARRIS: Mhm. Wow. Well, so much.

ANDREW HUBERMAN: Yeah. I just asked 55 questions.

ROBIN CARHART-HARRIS: I know.

ANDREW HUBERMAN: 但 feel free to answer just a subset of them if 你 like.

ROBIN CARHART-HARRIS: Yeah. Well, Oakland's a funny 一. I live close to Oakland. There are head shops in Oakland 那 可能 be selling cannabis 和 cannabis-related paraphernalia 那 are selling mushrooms as well. Psilocybin, mushrooms--

ANDREW HUBERMAN: 那's a fact.

ROBIN CARHART-HARRIS: --openly. Yeah.

ANDREW HUBERMAN: 那's a fact. I 可以 verify 那.

ROBIN CARHART-HARRIS: OK.

ANDREW HUBERMAN: I haven't purchased them, 但 I've gone in 和 checked it out, what's going on here.

ROBIN CARHART-HARRIS: Yeah.

ANDREW HUBERMAN: Yeah.

ROBIN CARHART-HARRIS: Yeah. So the police aren't going to prioritize 那 activity, the purchasing of 那些 mushrooms as a crime now in Oakland 因为 of the decriminalization. So 那些 head shops shouldn't strictly be selling. Well, they shouldn't be selling. They won't have a license to be selling. Licenses don't exist yet 对于 那 here.

但 let's see whether they get shut down. They probably 会, I don't know. 但 there's a church in Oakland sort of say 那 they're selling 和 it's part of religious rights. They're using 那 church model as a loophole, the way 那 Native Americans 可以 use peyote 和 they have a 更多 genuine case, I think. 因为 there is a history there. 但 they're trying to kind of piggyback on 那.

Anyway, 那's close to where 我们 are right now. 但 federally, which is 确实 the major inflection point, is the FDA 和 the licensing of psychedelics as medicines to be legally prescribed across the country, across the US 和 beyond, 那 is close 因为 the key phase-- so there are 不同的 phases of clinical trials, 和 the key 一 to know 关于 is phase III.

Phase III trials are licensing trials. If they're successful, 和 通常 你 have to do at least 二 successful ones, show the 结果 to the regulators who are the FDA, the medicine regulators, 和 say, is 这 good enough now 对于 你 to give me a license so 那 I 可以 sell 和 provide 这 medicine 那 我们've demonstrated is a medicine.

So 那 work has been done 与 MDMA therapy 对于 post-traumatic 压力 disorder. MAPS have led 那 work 和 done 二 phase III trials. I think they've already publicly announced 那 the 秒 trial had 结果 consistent 与 the 首先. 我们 know the 结果 of the 首先, 因为 they're published 和 they were remarkably good. Something like 67% remission rates.

ANDREW HUBERMAN: 和 long term. My understanding is some of 那些 remission rates 对于 trauma were years, which is 不同的 than what 你're describing 对于 psilocybin, where 人们 可能 need ongoing dosing.

ROBIN CARHART-HARRIS: Yeah. 那's true. Yeah. Yeah.

ANDREW HUBERMAN: 但 of course, just 对于 trauma in 那些 trials. My understanding is 那些 MDMA trials were not focused on depression.

ROBIN CARHART-HARRIS: Yes. Yes. Focused on the trauma. So 那's something, 因为 那 数据 is being filed now, to my knowledge, like as 我们 speak. 和 they're anticipating a decision maybe 这 year 与 rollout happening as early as next year. I mean, 那's best case, I think.

ANDREW HUBERMAN: Could I ask 你 when 你, when 你 say rollout, 和 it's the appropriate term 对于 MDMA, 因为 of so-called rolling. 关于 20% of my audience, maybe 50 会 understand 那 not funny joke 那 I made. Who's going to roll it out? Where 会 一 get the clean source of MDMA, meaning not laced 与 fentanyl, not laced 与 methamphetamine, not undergone any chemical conversion to some other drug which 可以 happen 与 extended shelf life, et cetera.

Are 人们 going to go to their psychiatrist to get MDMA? 和 who's going to be providing it? Is it going to be some big major pharma? 这 seems like a serious set of issues.

ROBIN CARHART-HARRIS: Mhm. It is. 和 I don't have all the answers. I do know 那 MAPS 会 be providing, 因为 they've done the work 和 they have set themselves up in a sense to potentially become the provider, whether as a pharma company, which is the big question they're wrestling 与 at the moment. It's 非常 expensive to become a pharma company.

ANDREW HUBERMAN: 和 yet they probably deserve to make the choice, 因为 they've put in so many years of hard work when all of 这 stuff was considered like raver culture party drug, they were the ones 那 spotted the therapeutic potential. I mean, 我们 knew there was therapeutic potential based on work going back many decades, 但 points to them, 和 I think in my opinion, they 应该 have the agency to make 那些 decisions.

ROBIN CARHART-HARRIS: Yeah. 和 it's such a remarkable thing 那's been achieved. 和 I think they've done it all on philanthropic donations. I think so. Yeah. So there is 这 big question mark. 和 the FDA are also asking questions 关于, to 你的 question, who 可以 provide 这, 因为 in the phase III work 和 up until 这 point, there's been a MAPS 训练, a MAPS therapist 训练.

和 你 have to do 这 formal 训练 in order to be a practitioner within the trials. 但 now, there's a question 从 the FDA whether 那 MAPS 训练 可以 be the 训练 那 a clinician has to have to now be a provider. 和 when I say rollout, it's like offering 这 as a service, 本质上.

和 so where 会 the referral come 从? 那's a good question. 那 I'm not 100% on the answer. Whether it 会 have to come 从 a psychiatrist 或 whether someone's-- sort of general physician could do 那 referral. 但 they 会 be going to a provider who is licensed 和 certified 和 会 have done some 训练. 和 there 会 be a consensus on what constitutes good enough 训练 to provide.

There 会 also be some stipulations on the basic underlying professionalism of the clinician who provides. So I imagine, they'll have to be a 心理健康 professional. I don't think they 会 have to necessarily be a psychiatrist, they could be, I think, a clinical psychologist. 对于 all the dosings, I think 没有 question, there 会 have to be a physician present 或 at least within ready access in case of an emergency.

ANDREW HUBERMAN: Yeah, 尤其是, 与 MDMA 因为 of the propensity 对于 cardiac issues.

ROBIN CARHART-HARRIS: Yeah.

ANDREW HUBERMAN: 因为 of the amphetamine properties. 和 where is psilocybin in terms of the phase trials? Is it in phase II, phase III?

ROBIN CARHART-HARRIS: It's in phase III. There's psilocybin therapy work being done 对于 treatment resistant depression by a company called Compass. 那些 trials which are 总是 multi-site. So there's 总是 a bunch of teams 或 labs in a sense. Geographically spread out 那 are each contributing to 数据 那 then gets matched together 和 is then submitted as part of the phase III trial 结果.

So 那's happening 与 Compass right now. It's psilocybin therapy 对于 treatment-resistant depression. 那些 trials have just started 和 I think the earliest estimate 那 I heard in a journalistic article was 因为 I don't think Compass 会 say 或 they wouldn't say publicly something like 2026.

ANDREW HUBERMAN: '26. Wow. So MDMA is ahead of psilocybin.

ROBIN CARHART-HARRIS: Oh, yeah. Yeah. It's quite a few years ahead. 和 it's 更多 of, not a certainty 但 it's 非常, 非常 strong position 与 MDMA. Whereas the work's only just begun 与 psilocybin in terms of the phase III trials. 但 then 你 have 这 other situation of 然而 many psychedelic 研究 centers there are now across the globe, 我们 had the 首先 一 in London in 2019.

The 首先 一 in 2019, it's 2023 now, 和 I don't know how many there are. 但 so much has happened in such a small space of time. Yes. 但 all 这些 不同的 indications I've been able to tell 你 关于-- anorexia 和 fibromyalgia syndrome. Trying to do a trial 与 a colleague of mine at UCSF in methamphetamine use disorder.

He's got a trial going on in Parkinson's disease 和 chronic lower back pain 和 bipolar disorder. I mean, there's so much going on. OCD. Almost the full gamut of psychiatric disorders. Not schizophrenia, to my knowledge, are being looked at. So there's so much groundswell of activity.

和 I think 这些 small investigator-led 研究, 通常, they're small 因为 trials are expensive, are going to be reporting positive 结果. I know what 我们're seeing. 和 it 会 be four-- let's see now, at least four trials all 与 确实 positive 结果 in 非常 difficult-to-treat disorders. 和 那's just us. 和 I know there's so much elsewhere. Addiction disorders as well.

Mike Johnson's work, obviously, Michael Bogenschutz. So all 这 compelling groundswell, it's 确实 something. 和 yet the 系统 to 确实 make a big breakthrough in terms of licensing is, of course, slow. 和 那 可以 frustrate 人们, 但 it has to be done properly.

ANDREW HUBERMAN: Yeah. Else 我们 revert back to what happened in the '70s where there was a lot of interest in psychedelics. It's interesting to me. There was a close juxtaposition of meditation 和 behavioral approaches to self-directed state change 和 psychedelics. Meditation made it 通过 the hatch.

I mean, there were some years where it was considered counterculture woo magic carpet weirdo stuff by Western science. 但 now, I mean, there are-- probably tens of thousands is not an overstatement of quality 研究 exploring how meditation 可以 provide advantages 对于 the 心智 和 even 对于 心理健康.

和 psychedelics are now catching up, 但 they used to be close cousins in the cultural framework. 但 the problem was, I think, psychedelics were viewed as making 人们 crazy. 和 university professors lost their jobs 对于 having discussions like the 一 那 你 和 I are having right now.

和 some 人们 went to jail, 但 mostly 人们 either left academic institutions 或 lost their jobs, whereas now 这些 are some of-- 这些 研究 of the sort 那 你 are doing 和 那 are taking place at Stanford 和 Hopkins 和 elsewhere are some of the greatest magnetic pull 对于 philanthropy 对于 universities.

Donors are 非常 interested in supporting 这些 sorts of 研究, 因为 they 和 their family members 和 人们 they know suffer 从 psychiatric illness 对于 which the current big pharma approaches simply have not worked. So it's interesting to me 那 what once was seen as poison is now being viewed as a potential therapeutic. It's not just interesting, hopefully, it speaks to the evolution of the human species. 人们 seem to be coming 更多 open-minded 关于 becoming 更多 open-minded.

ROBIN CARHART-HARRIS: Right. Yeah. 那's a good 一. Yeah. 和 yet-- yeah. There's so much 那's happening so fast. 和 there are elements of-- it's complexifying the space. There is critique, there's been some bad practice in psychedelic therapy, boundary crossing issues 那 have caused some scandals.

ANDREW HUBERMAN: 那's too bad.

ROBIN CARHART-HARRIS: Isn't it?

ANDREW HUBERMAN: Yeah. Well, I think too the gene therapy, right? It just takes 一 bad incident. Gene therapy was on a fast track 三 decades ago 和 then sadly, a child died in a gene therapy trial. 和 it's like shut down gene therapy practically 对于 half a decade 和 then it slowly started ratcheting up again.

Gene therapy broadly defined, 和 now 我们're in the age of potential directed gene therapy using CRISPR 和 things of 那 sort, which makes some 人们 cringe 和 other 人们 非常 excited. If 你 have Huntington's in 你的 family, CRISPR is like the most exciting technology ever, 因为 你 could potentially eliminate it 从 你的 family line going forward, of course.

ROBIN CARHART-HARRIS: So I just 确实 hope 那 我们 可以 be balanced as 这 all plays out. 因为 it could go 相似的 way given the stigma, given the history 那 人们 会 be 非常 twitchy 与 some isolated incidents. 和 overgeneralize them, perhaps, in a sense, shining a light on them, I think, is 重要 那 has happened recently is 重要, 因为 it 确实 drills home how 重要 it is 那 这 work be done right 和 what the necessary safeguards 和 standards 应该 be.

Yeah. 和 it won't be an easy road forwards. 但 let's hope-- 我们've got to hope 那 it succeeds, 因为 current treatments-- 人们 talk 关于 the 心理健康 crisis 和 to 你的 point earlier 关于 anorexia rates, it's not 总是 actually the case when 你 look at the epidemiology. When 你 look at the 数据 那 你 see a big inflection in diagnoses 或 cases of psychiatric illness.

I 会 say, it's 更多-- the treatments haven't moved. They haven't 确实 progressed. They haven't got any better since the 1950s 更多 或 更少. 和 new drugs have been 更多 of the same. So there haven't been any paradigm shifts. 和 那's why I get a little impassioned when I talk 关于 psychedelic therapy 和 那 point 那 这 is something 不同的. It's not a drug every 天.

那 系统, it's not cutting it. Do 我们 确实 want to keep on 与 那 系统? Sure. Not everyone 会 want to trip. 和 那 会 terrify some 人们 so much 那 they'll just want to be on their Lexapro 或 a non-psychedelic, psychedelic, 或 whatever. 和 of course, it 应该 be allowed to have 那些 options. Of course. 和 the 更多 options, the better.

但 I think there is great value in 确实 understanding what psychedelic therapy is. 和 I think when 你 do, 你 realize 那 it is a major paradigm challenge on many 水平. 和 the fact 那 it's 不同的 可能 be its greatest appeal at the moment, I think.

ANDREW HUBERMAN: Well, I am certainly grateful 对于 你的 passion 对于 the potential 对于 psychedelics to be added to the array of potential treatments. 和 I 确实 also appreciate how much 你 put it in there alongside the other treatments. Maybe even in combination 与 other treatments as opposed to saying, 这 is the thing 那's going to cure everything. 和 yet the passion 那 你 have 对于 这 potential paradigm shift, the 一 那 确实 appears to be happening at the 水平 of clinical 数据 now is so 重要.

So I want to extend a voice of gratitude 对于 那 和 对于 the work 那 你're doing. I mean, I've been outside of 这 field, 但 as a neuroscientist, I've been paying careful 注意力 to it 确实 对于 the last five, seven years 或 so. 和 it's abundantly clear 那 it is a small group of 个体 who are 确实 thinking in terms of how the 系统 works now 和 what needs to be done in order to change the 系统 对于 the better like yourself 那 are 确实 the driving force behind 这 new movement 或 paradigm shift.

那 没有 question, is going to lead to improvements in 心理健康 和 身体健康 outcomes. So I just want to say thank 你 对于 那. Also thank 你 so much 对于 joining us today to share 这 immense knowledge set 关于 the history of psychedelics. What they are, what they aren't. Their clinical applications as seen in 你的 laboratory 和 other laboratories.

I'm sure 人们 already notice 这, 但 你're incredibly generous in terms of attribution 和 also in 你的 caution 关于 explaining how some of the 结果 in particular, on anorexia, fibromyalgia, are perhaps preliminary 但 非常 exciting. They're not published yet, anyway. 我们 wouldn't call them preliminary.

和 also 对于 touching on mechanism. 那 is not just 关于 人们 feel better, 但 pointed to some potential underlying mechanisms in terms of connectivity changes 和 on 和 on. So thank 你 so much 对于 你的 time today. Thank 你 对于 the work 那 你're doing. 和 thank 你 对于 the work 那 is sure to continue. 我们 会 provide links to 研究 in 你的 laboratory, links to 你的 laboratory so 人们 可以 learn 更多 和 support in the ways 那 they deem appropriate 对于 them. 但 just thank 你, thank 你, thank 你. Such 重要 work 你're doing, Robin.

ROBIN CARHART-HARRIS: Thank 你, Andrew. It's been a pleasure.

ANDREW HUBERMAN: Thank 你 对于 joining me today 对于 my discussion 与 Dr. Robin Carhart-Harris. I hope 你 found it to be as informative 关于 the science 和 clinical uses of psychedelics as I did. If 你'd like to learn 更多 关于 Dr. Carhart-Harris's 研究 或 support 那 研究 或 inquire 进入 being a 研究 subject in 一 of his laboratory 研究, please see the links in the show note captions.

In addition, please see the links to his Twitter account 和 other social media accounts also in the show note captions. Also in the show note captions 你'll find a link to Dr. Carhart-Harris's Twitter account where he regularly posts 关于 new advances in the field of psychedelic science. If 你're learning 从 和/或 enjoying 这 podcast, please subscribe to 我们的 YouTube channel. 那's a terrific zero cost way to support us.

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