神经科学与心理学2020sciencedirect.com
低剂量LSD后的情绪与认知：一项安慰剂对照的剂量效应研究
Mood and cognition after low LSD doses: A placebo controlled dose-effect study
入门 · 约 45 分钟读完前置知识：实验设计与安慰剂对照、基础统计学
导读
这项安慰剂对照的剂量-效应研究考察了低剂量 LSD（微剂量）对情绪和认知的影响。结果显示总体情绪效应偏正面，但焦虑和困惑评分也有所升高，且不同剂量（5/10/20 微克）的效果并不一致。
HN 关注点：微剂量 LSD 是 HN 上长期热门话题，这篇对照研究提供了少见的实证数据，讨论焦点集中在效果是否真实以及研究设计的局限。
HN 评论精选
这几条评论里：质疑 2 补充 1 亲历 1
质疑研究忽略了焦虑和困惑升高的负面结果，亲历者观察到微剂量带来虚假的成就感
作者得出总体效果偏正面的结论，却轻描淡写地忽略了焦虑和困惑评分升高这一事实。就我的观察：几位同事曾热衷于 LSD 微剂量，这项研究恰好印证了我看到的情形——情绪似乎变好，但困惑增加。他们更投入工作，部分原因是连简单任务在微剂量日都变得更难了。最令人担忧的是药物扭曲了他们的自我判断：解决琐碎问题后会觉得获得了重大顿悟，坚信微剂量日充满突破，实际上只是小任务被放大成了巨大胜利。当他们开会跟不上时，我们才委婉劝停。Gwern 的自试也显示出类似的负面趋势（https://www.gwern.net/LSD-microdosing）。
PragmaticPulp查看英文原文
The author’s conclusion that the overall effect was generally positive seems strangely dismissive of the fact that anxiety and confusion scores were increased. Anecdotally, I had a few coworkers go through a phase of LSD microdosing enthusiasm. From my outside perspective, this study matches what I observed: Vaguely better moods associated with increased confusion. They were more immersed in their tasks, but that was partially because even easy tasks were more difficult on their microdosing days. The most concerning part of their experiment was how it distorted their own perceptions and judgment. They’d feel like they had arrived at great epiphanies or accomplished something impressive after solving trivial or obvious problems. They were convinced that their LSD days were full of breakthroughs and leaps forward, when in reality the drug was just making even small tasks feel like great victories. We politely hinted that they should stop when they struggled to keep up in meetings and conversations. For another perspective, Gwern has some self trials with LSD that also showed some worrisome negative trends: https://www.gwern.net/LSD-microdosing
补充纳入/排除标准和戒药期设计使样本偏向不会出现负面反应的人，结论外推性有限
研究有趣，但评估时需注意标题之外的细节：1) 纳入标准要求此前使用过致幻剂；2) 排除标准筛掉了曾有恐慌发作/焦虑等不良体验的人。仅这两条就造成偏差——样本只包含已知不会对该药产生负面反应的人。如果你从未用过药，不能用这项研究预测自己的体验。3) 受试者在研究前戒药三个月，因此对持续微剂量者（存在耐受性积累）的参考价值有限。
vikramkr查看英文原文
Overall interesting research, but as with any preliminary research, there are a lot of little details that aren't in the headline that are important to know when evaluating it. A couple points: 1) the inclusion criteria include prior use of psychedelic substances 2) the exclusion criteria filters out people with a previous bad experience of having panic attacks/anxiety/etc Those two factors alone are going to create a bias by including only people who are known to not have a negative reaction to the drug anyway, so if you've never dosed before, you cannot use this study to determine what your likely experience is. The study group is not reflective of you, and you might after dosing find yourself meeting the exclusion criteria. Another point: 3) participants stayed drug free for 3 months before the study This means that these results are less reflective of you if you continually microdose, as they do not account for tolerance etc over time.
亲历亲历者称微剂量帮助其走出抑郁的博士困境，如同跳出思维局部最优的化学冲击
我的亲身经历：我曾深陷一个糟糕的博士项目（美国知名物理系），导师极其恶劣，多年被因小错吼叫、几乎没有反馈、疯狂加班，我彻底失去自信，变得抑郁、超重、不敢与人交流。我本对药物很谨慎，但微剂量帮我找回了一些方向感和前进的信心。就像 Gwern 说的模拟退火——我的思维困在局部极小值，需要一次化学冲击跳出去。顺带一提，我已博士毕业正在找工作，现在快乐多了，也已停用，因为不再需要。
throwaway967查看英文原文
My anecdotal experience: I felt trapped in an awful PhD program (a well-known physics dept in the US) with an extremely toxic advisor. After years of getting yelled at for small mistakes with little or no feedback, insane hours (weekend/holiday meetings and deadlines) and zero growth I had completely lost any confidence. I became depressed, overweight, afraid to talk to people, etc. I'm weary of drugs, even caffeine, but microdosing helped me regain some sense of direction and a bit of confidence to move forward. It is like simulated annealing as gwern describes. My mind was trapped in a minima and I needed a chemical shock to move it elsewhere. As a side-note, I finished my PhD and am job hunting. Now, I'm exponentially happier around friends and family. I'm still rebuilding my confidence but I've stopped microdosing because I don't feel the need.
质疑质疑剂量-效应曲线出现双峰是否真实，还是多重比较下的偶然显著
在专注度和焦虑上，5 和 20 微克剂量相对安慰剂有统计显著性，但 10 微克没有。我该相信剂量-效应曲线真的在 5 和 20 附近有两个峰、中间是谷，还是该怀疑 5/20 微克的显著结果是碰巧得到的（p 值 <1%）？其他药物中是否已知存在多峰响应曲线？
throwaway287391查看英文原文
So for attentiveness and anxiety, the 5 and 20 mcg doses both had a statistically significant effect vs. placebo, but the 10 mcg dose didn't. Should that lead me to believe that there's really a dose-response curve with two peaks near 5 and 20 and a valley in between, or should I be wondering whether they got "lucky" finding a significant result with either the 5/20mcg doses? (P-value was <1% for the significant results.) Is the former (multiple peaks in the response curve) known to happen in other drugs?
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