历史的回响:坏血病与“反果派”的阴影
想象一下,时值1756年,您正身处一艘驶向新大陆的英国海军舰船上。在船舱深处,您与同伴们一同忍受着病痛的折磨:双腿浮肿、牙龈出血、甚至可能因此掉牙。当您向船医求助时,他却将这一切归咎于“内在腐朽与懒惰”。当您提及一种可能有效的柑橘类水果作为药物时,他却断然否定,认为这种“植物性药物”过于简单,并非您病症的疗法,并将您归类为“反果派”。(笑声)最终,他为您开出的处方竟是砷制剂。这并非虚构,而是真实发生过的历史。抵达新大陆时,您的一半同伴已不幸离世。
我的名字是 Nolan Williams,今天我将与大家探讨“反果派”这一群体——他们如何将科学怀疑论武器化,从而阻碍新疗法惠及世人。
(掌声)
坏血病(Scurvy),一种由维生素C(Vitamin C)缺乏引起的疾病,从哥伦布时代直至柑橘疗法被广泛采纳期间,夺去了约两百万人的生命。在漫长的海上航行中,船员们只能依赖脱水肉类等不易腐坏的食物,导致维生素C摄入严重不足。早在16世纪,人们就已观察到食用柑橘类水果与预防或治疗坏血病之间存在关联,并将其视为一种宝贵的药物。这种关联的明确性甚至催生了世界上第一个临床试验(Clinical Trial)。
早期的临床试验通过对比各种人造疗法与柑橘疗法,旨在寻找治愈坏血病的方案。显而易见,摄入柑橘水果的船员在实验结束时,健康状况得到了显著改善。然而,这一发现并未立即被接受。皇家学会(Royal Societies)等权威机构对这一“过于简单”的植物性解决方案表示质疑,认为植物无法解决如此复杂的问题。随之而来的是强烈的反对声音,他们转而推崇砷、汞等人造化学品作为治疗手段。尽管科学最终证明了柑橘的有效性,但从詹姆斯·林德(James Lind)进行研究到柑橘疗法被广泛应用,却耗费了超过一个世纪的时间,期间又有百万人因此丧生。这无疑是一场由“反果派”对医学进步发动的战争。更令人唏mer的是,直到数百年后,我们才真正理解柑橘中究竟是什么成分在治疗坏血病,而那时,坏血病早已被基本根除。
Original English
Alright, it's 1756, you're all aboard a British naval vessel headed to the New World. You're down below deck with your fellow sailors, and you're all sick. Your legs are swollen, your gums are bleeding, you just lost a tooth. You go to the ship's doctor and he tells you this is due to internal decay and laziness. (Laughter) You ask about this foreign fruit medicine, the citrus medicine that you could take, and he tells you that this is not a treatment for what you have, it’s too simple, it’s a plant medicine. And he’s an anti-fruiter. (Laughter) And instead, he prescribes you arsenic tonics. True story. And you get worse. And when you get to the new world, half of your shipmates are deceased. My name is Nolan Williams, and I'm here to talk to you about anti-fruiters. People who weaponize scientific skepticism to thwart new treatments from getting out to the world. (Applause) And so scurvy is an illness that killed two million people from the time of Columbus all the way through to the time of widespread citrus adoption. And scurvy is the result of a lack of vitamin C in the diet. And the reason why these sailors had a lack of vitamin C is because it was a long sea voyage so you need to eat dried meats and that sort of thing. And so we observed early on in the 1500s, this association between eating citrus fruit and the prevention or the treatment of scurvy. And so it was written early on that this was a precious medicine, something that could be used for this problem. So much so that it actually birthed the world's first clinical trial. So the clinical trial, as a scientific tool, is the result of trying to find a solution for scurvy. And so they gave all these man-made treatments, and then they gave citrus. And I don't have to tell you what the answer to this scientific question was. The people that got the citrus fruit were helping everybody else at the end of the experiment. But there was a reaction. The royal societies did not like this idea. There was backlash, and many thought this was too simple to be a solution for such a problem, that a plant could not solve such a complex problem, and instead they prescribed arsenic, mercury, man-made chemicals. Now science eventually prevailed. You know, we were able to see that this was actually helpful. But the problem was that from the time of James Lind's study to the time of widespread implementation was more than 100 years, a million people died. But this was a war waged against progress by these anti-fruiters. And it was another 100 years before we even knew what was in the citrus fruit that was improving scurvy. Right, we'd rid the world of scurvy at that point.
迷幻剂的曙光:应对现代创伤的新希望
现在,我将话题转向另一种植物性药物:迷幻剂(Psychedelics)。迷幻剂已被原住民(Indigenous populations)使用了数千年。例如,中非的依波加树根皮(Tabernanthe iboga root bark)在毕提人(Bwiti)的心理灵性(Psychospiritual)实践中已有数百年历史,他们深知这是一种强大的化合物。在现代医学中,这类药物需要在特定、类似医疗的环境下进行,并且需要对使用者进行严密监控,因为它们确实存在风险,如罕见的心律失常甚至死亡。
如今,水手们面临的现代“瘟疫”已不再是坏血病,而是创伤性脑损伤(Traumatic Brain Injury, TBI)和创伤后应激障碍(Post-Traumatic Stress Disorder, PTSD)。现有的治疗方法,如口服抗抑郁药和谈话疗法,虽然能帮助一部分人,但效果有限。因此,一些退伍军人,在标准治疗效果不佳时,选择尝试迷幻药物。
我曾接触过一位这样的退伍军人,名叫Marcus Capone,还有他的妻子Amber。Marcus曾是一名海军陆战队员(Navy Seal)长达13年,期间遭受了多次脑部创伤,退役后患上了PTSD。他不得不前往美国境外,在一个毒品在美国属于非法的国度,去寻求一种他认为挽救了他生命的化合物。当我与他们交流,听到Marcus和其他人的故事后,起初我有些怀疑。但随着了解的深入,我坚信这确实是值得研究的领域。
接下来,请听听Erick的故事,您将自行判断。
(视频片段) Erick:“我不知道确切的原因,但我感觉自己不再完整。我经历了许多症状,比如我一生中几乎都在酗酒,甚至到了忽视自己的程度,忽视我的孩子。情况糟到我几乎无法控制。我可能已经十年没有一天不喝酒了。这是我的最后机会。我想治愈自己,以便能够完整……为了我的家人。”
Nolan Williams(NW):这是我们在斯坦福大学(Stanford)进行的一项研究。与Erick一样,大多数参与者在接受依波甘(Ibogaine)治疗前,都患有PTSD并伴有脑损伤。但在治疗后,他们的PTSD症状显著减轻,不再符合PTSD的诊断标准。焦虑水平降低了80%以上,抑郁情绪也显著缓解,尤为 remarkable 的是,创伤性脑损伤导致的残疾得到了解决——这是我们前所未见的。
现在,请Erick谈谈治疗效果。
(视频片段) Erick:“大约七个月过去了,几乎一切都变了。前几天,一个朋友来家里。他带着酒,开车来的。“嘿,想喝一杯吗?”“不了,哥们,我没事,我不喝酒了。”他却说……“我给你拿一杯。”我说,“不,我真的不喝了。”他说,“随便你,我给你拿。”他根本不相信我。我们站着聊了大概30分钟。在这段时间里,我以前可能已经抽了五支烟了。他惊讶地问,“等一下,你也戒烟了?”我回答,“是的。”“什么?”一切都改变了。很难向别人解释,就像一个周末,一切就都不同了。好像某种魔法药丸,但它不是。我的意思是,真正的工作是在体验之后才开始的,但正是这次体验给了我进行这项工作的工具。有那么多人可以从中康复。有那么多人本可以活下来。我的朋友们本可以活下来。我的家人本可以活下来。”
NW:现在,请Erick描述一下这次体验的效果。当他接受这种化合物影响时,他感觉如何?许多人会描述他们会回顾早年的记忆,并能以一种超然的、第三方的视角来看待这些记忆,审视它们,并真正地赋予它们新的意义。
(视频片段) Erick:“我记得最清楚的视觉体验,就像在翻阅一本相册,但速度极快,像罗列克斯(Rolodex)一样,你快速翻动,一切都模糊地掠过。里面有我生命中的片段。就像一个局外人在观察。它让我能够面对那些比我意识到的影响更深的创伤。这是我从那个周末获得的最大收获之一,就是……我需要停止毒害自己。在所有可能的方面。”
Original English
And so I'm going to switch to a new plant medicine: psychedelics. Psychedelics have been used for thousands of years by Indigenous populations. The Tabernanthe iboga root bark of central West Africa was used by the Bwiti for psychospiritual purposes for centuries, and they knew that this was a powerful compound. It needed to be done in certain, kind of medical-like or medical settings in modern medicine. And we need to be able to monitor people because it does have risks, like a rare cardiac arrhythmia and death. And so the modern scourge of sailors, Navy Seals, isn't scurvy. It's traumatic brain injury and post-traumatic stress disorder. And the treatments that are out there, oral antidepressants and talk therapy, do help some people, but they're limited. And so these veterans have decided when they don't get, you know, improvement from the standard treatments that some of them have gone out to take psychedelic medicines. And I was approached by one such veteran, Marcus Capone, him and his wife, Amber. Marcus had been a Navy Seal for 13 years and suffered many traumatic brain injuries, had PTSD once he got out. And he went down to Mexico, outside of the US, as a US soldier, outside of the US, down to a foreign country to receive a compound that is illegal in the US, a compound that he believes saved his life. And when I met these folks, I heard the story, at first I was a little bit skeptical. But then once I heard Marcus's story and other stories, I became convinced that this was something worth studying. So now I'm going to let you listen to Erick's story, and you tell me what you think. (Video) Erick: I don't know exactly all the reasons why I'm not whole. I know a lot of the symptoms, like being a basically barely functioning alcoholic my entire life to the point of neglecting myself, neglecting my kids. It's so bad, that I have like, zero control over it. I haven’t gone a day without drinking in probably 10 years. This is my last chance. I want to be able to heal myself so that I can be whole ... For my family. NW: So, this is the study that we conducted at Stanford. Just like Erick, most of these folks had PTSD in addition to traumatic brain injury beforehand. But after, they had a significant reduction and crossed the line to no longer meet PTSD diagnosis after they received ibogaine. Significant reductions in anxiety, 80-plus percent, significant reductions in depression and, remarkably, resolution of disability from traumatic brain injury. Something that we haven't seen before. So now I'm going to let Erick tell you about that. (Video) Erick: It’s been about seven months, and pretty much everything is different. A buddy of mine came by the house the other day. He had a drink with him, he drove there. "Hey, you want a drink?" "Nah, man, I'm good, I don't drink anymore." He's like ... "I'll get you a drink." I'm like, "No, I really don't drink anymore." He's like, "Whatever, I'll go get you a drink." No, he didn't believe me. I mean, we were standing there talking for probably 30 minutes. In that time before I would have smoked five cigarettes, you know. And he was like, "Wait a minute, did you quit smoking, too?" I was like, “Yeah.” "What?" Everything has changed. It's hard to tell somebody like, one weekend and everything's different. Like some kind of magic pill or something, which it's not. I mean, the real work started after the experience, but the experience gave me the tools to be able to do the work in the first place. There are so many people that could heal from this. There are so many people that would still be here. I have friends that would still be here. I have family that would still be here. NW: So now, I'm going to let Erick describe the effect. What did he feel while he was under this compound? And what a lot of people will describe is that they go back and look through earlier-life memories, and they're able to see these memories from a detached third-party perspective and look at them and see them and really reassimilate them into meaning. (Video) Erick: The visuals that I remember the most were like going through like, a photo album, but like a Rolodex and like, you flip it as fast as you can and everything goes by and it's a blur. There's like clips out of my life. Like an outsider looking in. It allowed me to confront traumas that had much more of an impact on me than I realized. That was one of the biggest things I got from the weekend, is just like ... that I need to stop poisoning myself. In every aspect possible.
科学的审判:迷幻剂的合法化之路
正如柑橘之于坏血病,迷幻植物性药物最初也被视为具有积极潜力。甚至在20世纪60年代中期,美国国家精神卫生研究所(National Institute of Mental Health)的主任也认为它们是强大的、具有潜在治疗价值的工具,以及理解大脑行为关系的钥匙。然而,与柑橘不同的是,迷幻植物性药物最终被列为非法。您可以想象一下,如果当初我们禁止了橙子,获取柑橘疗法需要多长时间?
尽管如此,希望依然存在。21世纪初,包括在座的一些科学家在内的一小群研究人员,已经成功地让这些研究重新启动。其中一些项目正接近于提交给美国食品药品监督管理局(FDA)进行评估或重新评估。目前,我们正尝试为依波甘(Ibogaine)提交一项新药临床试验申请(Investigational New Drug application)。
我并非建议大家立刻前往墨西哥服用迷幻剂。不,您需要等待一切研究完成,等待临床试验证明其益处。然而,我确实想说的是,这些数据不应由“反果派”来评估,也不应仅由狂热的支持者来评估。它们应该由思想开放、能够清晰客观地审视数据的人来评估。
我还要告诉大家的是,这些化合物目前被列为第一类管制物质(Schedule I)。这意味着它们与海洛因处于同等严格的管制级别。也就是说,它们被认为没有医疗用途,并且具有高度的滥用风险。有多少人认为Erick的经历中没有获得任何医疗帮助?又有多少人认为有呢?
现在,大家可以回想一下,在18世纪50年代,禁止橙子是多么不可思议。那么,我们的子孙后代会如何看待我们今天的行为呢?我们正站在制度性拒绝与接受的边缘,时间紧迫。我在此提出问题:我们是否也禁止了橙子?只有时间会给出答案。谢谢大家。
(掌声)
Chris Anderson (CA):有几个问题。您刚才没有明确回答Erick是否需要额外的药物帮助,比如。 Nolan Williams (NW):是的,他已经停止使用所有药物。您知道,这些人通常在治疗前就需要心理治疗,并且在治疗后也需要大量的心理治疗,所以这是其中的一部分。 CA:但在药物治疗方面,依波甘就是全部了吗? NW:是的,就是它。 CA:好的。我从您那里学到的一点是,成瘾在许多情况下成为一个大问题的原因是,你服用的物质越多,它在大脑中就会放大你感觉良好所需的多巴胺量。 NW:没错。 CA:而依波甘的一个可能作用是,它基本上重置了那个几乎不可能通过心理手段克服的无情尺度。 NW:是的,这是普遍的看法。其中一部分作用可能是,它实际上促进了大脑中称为胶质细胞源性神经营养因子(Glial-Derived Neurotrophic Factor, GDNF)的生长因子,该因子在调节多巴胺神经元(Dopamine Neurons)方面发挥作用。因此,普遍的观点是,这种作用能够将这些多巴胺神经元重置到成瘾前的功能状态。 CA:而且,我认为,如果您在没有监督的情况下服用依波甘,您确实有心脏病发作的风险。 NW:这是一种心律失常,即心跳不规律。因此,在监督下进行这项工作非常重要。我们认为,通过使用某些风险极低的心律失常药物,如硫酸镁,进行预防性治疗,可以显著降低风险。但这确实需要在医疗和心脏科的监督下进行。 CA:但说清楚一点,在您对不同类型的医疗干预研究中,这种效果有多么显著? NW:是的,我的意思是,我们以前从未见过如此广泛作用的中枢神经系统化合物。在我看来,它是地球上最令人惊叹的药物之一,原因就在于此。它相当于一种广谱抗生素,可以治疗所有感染。它似乎也能治疗这类疾病。当然,现在还处于早期阶段。我们仍需做大量工作来完全证明依波甘的疗效。但是,您知道,对于TBI、PTSD、抑郁症,这是一个非常广泛的效果。 CA:非常感谢您将这个消息带到TED。 (掌声)
Original English
So just like citrus for scurvy, psychedelic plant medicines were initially seen as quite positive, and even the National Institute of Mental Health director in the mid '60s thought that these were powerful, potentially powerful therapeutic tools and tools for understanding the brain-behavior relationships. But unlike citrus for scurvy psychedelic plant medicines, these plant medicines, were made illegal. Can you imagine how much longer it would have taken for us to be able to get citrus out if we made the orange illegal? And so there's hope. A small group of scientists in the early 2000s, including some in the audience, have been able to get these studies back up and running. Some of them all the way through to being evaluated or reevaluated by the FDA very soon. Ibogaine, we're trying to get an investigational new drug application to the FDA right now. Now am I telling you to go and run out and go to Mexico and take psychedelics? No. You need to wait until everything's done, until the trials are done if they are to show us that these are positive. However, what I am saying is that the data shouldn't be evaluated by anti-fruiters. It shouldn't be evaluated by believers either. It should be evaluated by open-minded people that are able to look at the data clear-minded, right? And what I'm also here to tell you is, is that these compounds sit on Schedule I. And what that means is that they're on the same level of control as heroin. Right? It means that there's no medicinal use and they have a high abuse liability. How many of you think that there was no medicinal help for Erick? How many thought that there was? And so you can all sit here and think, in the 1750s, it would have been crazy to make the orange illegal. What will our grandchildren think about us? Right? And so we're on this edge between institutional rejection and acceptance and the time, the clock is ticking. And I'm going to ask you, did we make the orange illegal? Only time will tell. Thank you. (Applause) Chris Anderson: Couple of questions. So you didn't, I think for everyone, clearly answer that question of whether Erick needed additional help with additional drugs, for example. NW: Yeah, he was off of everything. You know, these folks end up needing psychotherapy beforehand, and they need a lot of psychotherapy you know, after, so that is part of it. CA: But in terms of the drug treatment, ibogaine, that was it? NW: That was it. CA: OK. One of the things that I learned from you, and tell me if I've got this right, is that the reason why addiction becomes so much of a problem in so many cases is that the more you take a substance, it dials up in your brain the amount of dopamine that you need to feel OK. NW: Yep. CA: And one possible effect of ibogaine is that it basically resets that relentless scale that is otherwise almost impossible to psychologically do. NW: Yeah, that's the view. Is that part of what is going on is that this actually promotes growth factors called glial-derived neurotrophic factor in the brain, which has a role in regulating dopamine neurons. And so the view is that this kind of resets those dopamine neurons to function pre-addiction-like. CA: And it's also true, I think, that if you take ibogaine unsupervised, you risk like, heart attack. NW: It's an arrhythmia, so an abnormal heart rhythm. And that's why it's important to do this under supervision. We think prophylaxing with certain kind of very low-risk cardiac arrhythmia medications like magnesium sulfate can actually reduce the risk quite a bit. But it is something that needs to be in medical supervision and in cardiac supervision. CA: But to be clear, in your sort of study of different kinds of medical interventions, how dramatic is this? NW: Yeah, I mean, we've never seen such, kind of a broad-acting, CNS compound before, right? I mean, in my view, it's one of the most amazing drugs on the planet because of this. And so, you know, it's the equivalent, like a broad-acting antibiotic that can treat all infections. It seems to be able to treat this kind of, you know. And it's early days. So we still have to do a lot of work to prove this totally in ibogaine. But, you know, TBI, PTSD, depression, that's a really broad effect. CA: Thank you so much for bringing news of this to TED. (Applause)