生物与医学2022nature.com
裸盖菇素蘑菇微剂量：一项双盲安慰剂对照研究
Microdosing with psilocybin mushrooms: a double-blind placebo-controlled study
入门 · 约 30 分钟读完前置知识：安慰剂效应与双盲实验设计、裸盖菇素/迷幻药基本概念
导读
这项双盲安慰剂对照研究检验了裸盖菇素微剂量（microdosing）对情绪、认知等方面的效果。受试者服用含裸盖菇素的蘑菇或安慰剂数周，结果显示微剂量组与安慰剂组之间未观察到显著差异，提示微剂量的主观益处可能主要来自安慰剂效应。
HN 关注点：HN 读者长期关注迷幻物质研究的科学证据，讨论焦点是研究设计（样本量小、个体差异大）是否足以检测出真实效果，以及剂量标准化问题。
HN 评论精选
这几条评论里：质疑 2 亲历 2
质疑质疑研究设计：应分析个体相对基线的变化，低样本量下连 SSRI 也测不出效果
在这类受试者间差异巨大（且许多量表上受试者自身逐日波动也很大）的研究中，更合理的做法是分析各组个体相对基线的变化，而不是只比较组间原始分数。粗看之下本研究大多用的是后者，因此这种低样本量的研究本来就不太可能显示出任何效果——因为个体间差异和自然波动可能大于预期的治疗效应。我几乎可以肯定，那些已获批且疗效确凿的 SSRI 抗抑郁药，在这种设计和类似样本量下也测不出效果。
zosima查看英文原文
In studies such as these with huge intersubject variability, and probably also quite large intrasubject variability from day to day on many scales, it makes sense to look at change from baseline for individuals in the various groups rather than just differences in raw scores between treatment groups. It seems by a cursory glance that most analyses done were of the latter kind, and I think then a study such as this, with low N, is expected to not show very much effect of any kind. (Since the intersubject variability and potentially also the natural intrasubject variability for most measured scales seem higher than any expected treatment effect). I am almost certain that e.g. none of the approved and quite convincingly working SSRI:s would have shown any efficacy in a study with this design and similar N.
质疑指出用蘑菇而非提纯裸盖菇素给药，剂量难以标准化
有点惊讶他们没有直接提取/合成裸盖菇素来给药。几十年前我种过几批古巴光盖菇，即使同一块米糕上的蘑菇，剂量差异也极大——可能一小朵就让你“起飞”，也可能吃一把都毫无感觉。
j_m_b查看英文原文
I'm sort of surprised they didn't extract/synthesize psilocybin directly and administer that. Decades ago, I grew a few batches of P. Cubensis. Even amongst mushrooms from the same rice cake, the dosage wildly varies. You could have a "trip" from a tiny mushroom or eat a handful of duds.
亲历亲历者称小剂量对抑郁有短期效果，但真正起作用的是大剂量，且大剂量无法双盲
（奇怪的是连科学语境都在用“微剂量”这个词——前缀是有含义的，应该叫“十分之一剂量”。）就个人经验而言，小剂量蘑菇对我的抑郁有一定短期效果，但我从未有过坚持微剂量方案所需的持续获取渠道。可惜政府不愿坐到谈判桌前。不过，每次给我带来数月情绪提升的都不是小剂量，而是常让我陷入一夜挣扎的大剂量——这会让双盲测试完全失效。
yarg查看英文原文
(It's strange that we're using the term microdose, even in scientific contexts - prefixes have meanings - it should be called a decidose.) Anecdotally, I've had a degree of short term success treating my depression with smallish doses of mushrooms, but I've never had the continuing access required for a microdosing regiment. It'd be nice if the government were willing to come to the table on this, but alas. That said, every time that I've had a months long lift, it hasn't been a small dose, but an epic dose that often cast me into a night of turmoil. (Which would make the rigours of double-blind testing completely ineffectual.)
亲历亲历者称微剂量有效，尤其帮助程序员跳出思维、连接情绪
断断续续做了几个月，这东西确实有效。不过 0.5 克就足以让我产生幻觉，所以我很少超过 100 毫克。早起、锻炼、冷水澡、冥想，然后服一剂微剂量蘑菇，感觉非常好——微剂量就像冥想的类固醇。对我这种程序员逻辑型的人尤其有帮助，能让你暂时跳出头脑，与情绪和身体建立连接。
EmilyHughes查看英文原文
Been doing it for some months on & off, this shit is legit. Altough 0,5g has me tripping so I rarely dose above 100 milligrams. Get up early, do a workout, take cold shower, meditate and then pop a microdose shrooms, feels great. Microdosing is like steroids for meditation. Especially helpful for the programmer logic types of people like me, gets you out of your head for some time and helps you connect with your emotions and body.
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