MDMA俗称摇头丸，是一种著名的酒吧夜店药物，但它也显示出了治疗顽固性创伤后应激障碍（PTSD）的潜能，包括闪回现象（flashback）、抑郁和其他在创伤性事件后长期复发的症状，它还可能有助于其他疾病的治疗。作为一种药物，MDMA可能很快就会被美国食品药品管理局（FDA）批准。免责声明：MDMA目前仍是一种非法药物。本文讨论的是其潜在的治疗应用，并非纵容或提倡任何人使用它。20世纪80年代，MDMA开始在美国的酒吧夜店流行，它会使人们感到兴奋和眩晕，在那时它就已经有了“摇头丸”（Ecstasy）“和莫莉”（Molly）的俗称。但在那之前，一些精神病学家在谈话治疗中使用它，他们认为这有助于病人在治疗中敞开心扉。MDMA是一种精神活性药物，具有刺激和增强情绪的作用。它可能是通过让大脑充斥着神经递质5-羟色胺来发挥作用，产生狂喜和爱意。但这些绝对不是它一开始研发出来的目的。1912年，制药巨头默克公司试图开发一种凝血剂，他们想出了3,4-亚甲二氧甲基苯丙胺（3,4-Methylenedioxymethamphetamine）。默克公司早期在动物身上做了一些关于MDMA的实验，但最终被搁置，因为合成它所需的原料太昂贵了。多年之后，当它用在人类身上时，人们发现这种药物具有某些......其他特性。这就是为什么它成为了一种酒吧夜店药物。但事实上，早在1970年代，它就被用于治疗目的。1968年，迷幻化学家亚历山大·舒尔金（Alexander Shulgin）在美国旧金山湾区重新合成了MDMA。舒尔金在1976年亲自尝试过它，并把它介绍给了他的一些治疗师朋友，MDMA因此在湾区的治疗师中传播开来，而这些治疗师又把它传播到了美国其他地区甚至是其他国家。它成了一群专业人士最喜欢使用的治疗催化剂，但它同时也是一种让人感觉良好的药物，因而不可避免地，它从治疗师的办公室流出，在20世纪80年代初进入了夜店。美国政府曾宣布MDMA为I类管制药物，这意味着它没有公认的医疗用途，而且有很大的滥用可能性。MDMA的相关研究也因此更难开展或获得资金。而在一开始，MDMA是一种治疗性药物，总是与心理疗法搭配使用。早在70年代末和80年代初，科学家们就开始对它进行过一些研究，他们发现有证据表明，它可以帮助解决从夫妻咨询到药物使用障碍到创伤的各种问题。与治疗创伤性疾病和其他用途相比，夫妻咨询似乎是一种奇怪的用途，但确实有一些婚姻即将走到尽头的夫妇，在尝试了所有其他方法仍没有任何效果时，他们通过MDMA重新获得了情感上的连接。不过，支持这些例子的研究也不是很多。关于使用MDMA治疗严重PTSD的研究则要多得多。有一个致力于推动MDMA研究的非营利组织，名为多学科迷幻药研究协会（Multidisciplinary Association for Psychedelic Studies，MAPS），到目前为止，他们已经资助了几个大型的后期临床试验，使用MDMA来治疗PTSD，其中一项试验已于2021年5月完成，相关成果发表在《自然-医学》（Nature Medicine）杂志上。试验中，90名患有严重PTSD的患者被随机分配到接受MDMA或安慰剂的实验组和对照组，两组患者在接受训练有素的治疗师的治疗之前和之后，还进行了几次谈话治疗。领导这项试验的研究人员之一、精神病学家迈克尔·米索弗（Michael Mithoefer）说：“接受MDMA加治疗的人中，88%的人PTSD症状得到了有意义的改善，而单独接受治疗的人中有60%得到了改善。”米索弗从事MDMA辅助治疗PTSD的临床研究已超过20年。米索弗说：“对于被诊断不再患有PTSD方面，治疗加MDMA的受试者中有67%不再符合PTSD诊断标准，而只接受治疗的受试者这一数据只有32%。”这些结果相当震撼，特别是对于那些与PTSD斗争多年且没能被其他治疗方法治愈的人。MDMA为何会有这么好的效果？一些科学家认为……[查看全文]
MDMA Moves from Club Drug to Real Therapy
Josh Fischman: Today, we’re talking about MDMA. It’s a well-known party drug. But it is also showing real promise for treating intractable PTSD —flashbacks, depression, and other symptoms that recur long after a traumatic event. And it might help other conditions too. The medication could soon be headed for FDA approval.Tanya Lewis: Just a quick disclaimer: MDMA is currently an illegal drug. Although we’ll be talking about its potential therapeutic applications, we are not condoning or advocating its use.Lewis: Josh, what do you know about MDMA?
Fischman: Well, I know it got a reputation as a party drug in the 1980s, making people feel excited and giddy. That’s when it got the nicknames Ecstasy and Molly. But before that, some psychiatrists were using it during talk therapy. They thought it helped patients open up in sessions.Lewis: Yeah, that’s the gist of it. MDMA is a psychoactive drug with both stimulant and mood-enhancing effects. It appears to act by flooding the brain with the neurotransmitter serotonin, producing feelings of euphoria and affection.
But that’s definitely not what it was invented for. In 1912 the pharmaceutical giant Merck was trying to develop a blood-clotting agent.They came up with [three-four METHUH-LEEN-DIOXY-METHAMPHETAMINE] 3,4-Methylenedioxymethamphetamine.Fischman: No wonder they called it MDMA.Lewis: Right? And thank you so much to our show’s producer, Jeff DelViscio, for forcing me to say it…Merck did some early experiments with MDMA in animals, but ended up shelving it because the chemicals needed to synthesize it were too expensive.But years later, when it was given to humans, the drug was found to have certain…other properties. That’s why it became a party drug.[CLIP “This is your brain on drugs”]But in fact it was used for therapy purposes as early as the 1970s.Rachel Nuwer: MDMA was resynthesized in 1968 by the psychedelic chemist Alexander Shulgin, in the Bay Area. Shulgin tried it himself in 1976, for sure. He introduced it to some therapist friends of his who spread it among all these Bay Area therapists, who in turn spread it broader outside into the United States and even other countries.Lewis: That’s Rachel Nuwer, a science journalist, author and frequent Scientific American contributor. She recently wrote a book on MDMA called “I FEEL LOVE: MDMA and the Quest for Connection in a Fractured World.”Nuwer: And it really became this favorite therapeutic catalyst that a bunch of professionals were using, but it's also a drug that makes you feel good. And inevitably, it escaped from the therapist's office, as people like to say, onto the dance floor in the early 1980s.Lewis: The U.S. government declared MDMA a Schedule I drug, meaning it has no accepted medical use and a high potential for abuse. And that made it a lot harder to do research on or get funding for.Nuwer: It is, like, really worth emphasizing that this started as a therapeutic drug, always paired with psychotherapy. And you know, back in the late 70s, and early 80s, scientists were starting to do some studies about it. And they were finding evidence that it could help with everything from couples counseling to substance use disorders to trauma.Fischman: Couples counseling is kind of a weird use, compared with trauma disorders and other stuff, isn’t it?Lewis: Yeah it is strange—but there are stories about couples on the brink of divorce who had tried everything else and nothing worked, yet MDMA helped them reconnect. But there’s not a lot of research to back up the anecdotes.There’s much more research on using MDMA to treat severe PTSD.So, there's this one group that has been a real mover in the MDMA research space. It's called the Multidisciplinary Association for Psychedelic Studies, or MAPS.It's a nonprofit, and so far, they've funded a couple of large, late-stage clinical trials using MDMA to treat PTSD. One of these trials finished in May 2021.Fischman: How were these tests designed?Lewis: 90 patients with severe PTSD were randomly assigned to receive either MDMA or a placebo. Both groups also had several talk therapy sessions before and afterward with a trained therapist.Fischman: What did they find out? Did the drug work?Lewis: So I talked to one of the researchers who led the trial.Michael Mithoefer: … 88 percent of people receiving MDMA plus the therapy had meaningful improvement in their PTSD symptoms, versus 60 percent who had improvement with the therapy alone.Lewis: That’s Michael Mithoefer, a psychiatrist. He’s been doing clinical research on MDMA-assisted therapy for PTSD for more than two decades.Mithoefer: And then in terms of losing the PTSD diagnosis, the therapy plus MDMA was 67 percent of people no longer meeting the criteria for a PTSD diagnosis versus 32 percent in the therapy-only group.Fischman: Those are pretty impressive results, especially for people who’ve struggled with PTSD for years while other treatments have failed them. It makes me wonder why this drug worked so well. What do the researchers think?
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论文信息Mitchell, J.M., Bogenschutz, M., Lilienstein, A. et al. MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nat Med 27, 1025–1033 (2021).
DOI: 10.1038/s41591-021-01336-3
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