Three years ago, when I accepted a position as Director of Clinical and Translational Research at Usona Institute, a non-profit medical research organization pursuing a new drug indication for the psychedelic medicine psilocybin, many of my colleagues in mental health research looked at me like I had two heads. A year later, many of these same colleagues were beginning to ask me how they could become involved in ‘this exciting new field.’ Fast forward to the present and psychedelics are everywhere in the popular press, multiple entities are pursuing therapeutic indications for these agents and the world’s top psychiatric research institutions are beginning to talk about ‘centers for the study of psychedelic medicines.’ In three short years, I have had a front row seat to this amazing transformation, watching psychedelics go from the hippie fringe to the center of psychiatry, from being viewed with suspicion to potentially being over-sold. How is such a thing even possible? The first and deepest answer to this question derives, I believe, from the fact that we are desperate for new and better treatments in psychiatry and have been desperate for a long time. For example, although everyone who does clinical work has seen currently available antidepressants save lives, both literally and figuratively, they leave much to be desired in terms of both efficacy and tolerability; with a shadow side rarely discussed, which is that up to 25% of depressed patients who take these agents may have done better if they’d been given a placebo instead (1). Countering these dark musings is another, and brighter, reason for this explosion of interest in psychedelics. Over the last 3 years, studies have been published suggesting that these medicines have biological and behavioural effects that might make them uniquely valuable therapeutic agents for a range of mood and anxiety disorders. Like ketamine before them, psychedelic agents appear to do things that no one in mental health would have believed in advance, and would not believe now were it not for an increasingly consistent and hopeful database speaking to their efficacy. Psychedelics snuck into modern medicine in the mid-1990s with the pioneering work of Rick Strassman and colleagues, who reported on the biological and behavioural effects of the rapidly acting agent N,N-dimethyltryptamine (DMT) (2, 3) and with the multiple basic science studies conducted by Franz Vollenweider and colleagues at the University of Zurich (4). At the time for many of us this work seemed to come out of nowhere, a testimony to our profound amnesia regarding the central role that psychedelics had played in the development of biological psychiatry decades earlier, before they were made illegal and removed from research (5). Indeed, upwards of a thousand papers were published on classic psychedelics in the 1950s and 1960s. Although none of these studies come close to meeting modern norms for rigor, many of them suggested therapeutic benefits for two conditions in particular: alcoholism and end-of-life depression/anxiety in patients with terminal cancer. Based on these latter findings, as well as on a promising randomized trial in patients with cancer conducted by Charles Grob and colleagues at UCLA (6), when the door of possibilities opened a bit wider at the start of the 21st Century, researchers at Johns Hopkins and New York University (NYU) chose to use modern randomized, placebocontrolled, double-blind designs to examine whether the psychedelic agent psilocybin (the active ingredient in ‘magic mushrooms’) might really help depressed and anxious cancer patients. These studies were done on financial shoe-strings, funded mostly by the Heffter Research Institute. They were conducted against an impressive range of obstacles, and they took a long time to complete. When asked why psilocybin was the chosen agent, several of the researchers ruefully told me, ‘Because it didn’t contain the letters “L, S, D”.’ This honest confession spoke volumes about the

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一切都是新的：迷幻药是否准备好席卷精神健康？

三年前，当我接受了 Usona 研究所临床和转化研究主任的职位时，Usona 研究所是一个非盈利的医学研究组织，致力于为迷幻药裸盖菇素寻找新的药物适应症，我的许多精神健康研究同事看着我我有两个头。一年后，许多同样的同事开始问我他们如何才能参与“这个令人兴奋的新领域”。快进到现在，大众媒体上到处都是迷幻药，多个实体正在为这些药物寻求治疗适应症，世界顶级精神病学研究机构也开始谈论“迷幻药研究中心”。在短短的三年里，我在这个惊人的转变中占据了前排的位置，看着迷幻药从嬉皮士边缘到精神病学的中心，从被怀疑到可能被过度销售。这样的事情怎么可能？我相信，对这个问题的第一个也是最深刻的答案来自这样一个事实：我们迫切需要新的更好的精神病治疗方法，并且已经绝望了很长时间。例如，尽管每个从事临床工作的人都看到目前可用的抗抑郁药可以挽救生命，无论是字面上还是比喻上，但它们在功效和耐受性方面仍有很多不足之处；有一个很少被讨论的阴暗面，那就是服用这些药物的抑郁症患者中，如果服用安慰剂，可能会有更好的表现 (1)。对抗这些黑暗的沉思是另一种更明亮的，对迷幻药的兴趣激增的原因。在过去的 3 年中，已经发表的研究表明，这些药物具有生物学和行为影响，可能使它们成为治疗一系列情绪和焦虑症的独特有价值的治疗剂。就像他们之前的氯胺酮一样，迷幻剂似乎会做一些心理健康领域的人事先不会相信的事情，如果不是因为越来越一致和充满希望的数据库表明它们的功效，他们现在也不会相信。在 1990 年代中期，随着 Rick Strassman 及其同事的开创性工作，迷幻药潜入现代医学，他们报告了速效剂 N,N-二甲基色胺 (DMT) 的生物学和行为影响 (2, 3) 以及由 Franz Vollenweider 及其同事在苏黎世大学 (4) 进行的多项基础科学研究。当时对我们中的许多人来说，这项工作似乎无处不在，这证明了我们对致幻剂在几十年前在生物精神病学的发展中发挥的核心作用的深刻健忘症，然后才被定为非法并从研究中移除（5 ）。事实上，在 1950 年代和 1960 年代发表了超过一千篇关于经典迷幻药的论文。尽管这些研究都没有达到严格的现代规范，但其中许多研究特别表明对两种情况的治疗益处：酒精中毒和晚期癌症患者的临终抑郁/焦虑。根据后面的这些发现，以及由查尔斯·格罗布及其同事在加州大学洛杉矶分校进行的一项有希望的癌症患者随机试验（6），当时可能性的大门在 21 世纪初打开了一点，约翰霍普金斯大学和纽约大学的研究人员（ NYU) 选择使用现代随机、安慰剂对照、双盲设计来检查迷幻剂裸盖菇素（“神奇蘑菇”中的活性成分）是否真的可以帮助抑郁和焦虑的癌症患者。这些研究是在金融鞋带上完成的，主要由赫夫特研究所资助。他们是针对一系列令人印象深刻的障碍进行的，他们花了很长时间才完成。当被问及为什么选择裸盖菇素时，几位研究人员遗憾地告诉我，“因为它不包含字母“L、S、D”。