School of Pharmacy, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand.
School of Pharmacy, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand.
Biol Psychiatry. 2023 Sep 15;94(6):511-521. doi: 10.1016/j.biopsych.2023.03.013. Epub 2023 Mar 28.
Microdosing psychedelic drugs is a widespread social phenomenon with diverse benefits claimed for mood and cognition. Randomized controlled trials have failed to support these claims, but the laboratory-based dosing in trials conducted to date may have limited ecological validity.
Healthy male volunteers were randomized into lysergic acid diethylamide (LSD) (n = 40) and placebo (n = 40) groups and received 14 doses of either 10 μg LSD or an inactive placebo every 3 days for 6 weeks. First doses were given in a supervised laboratory setting, with other doses self-administered in a naturalistic setting. Results of safety data, blinding, daily questionnaires, expectancy, and pre-/postintervention psychometrics and cognitive tasks are presented here.
The most notable reported adverse event was treatment-related anxiety, which prompted the withdrawal of 4 participants from the LSD group. Daily questionnaires showed credible evidence (>99% posterior probability) of improved ratings of creativity, connectedness, energy, happiness, irritability, and wellness on dose days compared with nondose days, and these effects remained when controlling for preintervention expectancy. No questionnaire or cognitive task showed a credible change between baseline and 6-week assessment time points.
Microdosing LSD appears to be relatively safe in healthy adult men, notwithstanding a risk of anxiety. While microdosing elicited transient increases in scales associated with mood-elevating effects, it was not sufficient to promote enduring changes to overall mood or cognition in healthy adults. Future microdosing trials in clinical populations will require the use of active placebos to control for placebo effects and dose titration to adjust for interindividual variability in drug response.
微剂量使用迷幻药物是一种广泛存在的社会现象，据称其对情绪和认知有多种益处。随机对照试验未能支持这些说法，但迄今为止进行的试验中的基于实验室的剂量可能具有有限的生态有效性。
健康男性志愿者随机分为 LSD（n=40）和安慰剂组（n=40），并在 6 周内每隔 3 天接受 14 次 10μg LSD 或无效安慰剂。首次剂量在监督下的实验室环境中给予，其他剂量在自然环境中自我管理。这里介绍了安全性数据、盲法、每日问卷、预期以及干预前后心理测量和认知任务的结果。
最值得注意的不良事件是与治疗相关的焦虑，这促使 4 名 LSD 组的参与者退出。每日问卷显示，与非剂量日相比，在剂量日有可信证据（>99%的后验概率）改善了创造力、联系感、能量、幸福感、易怒和健康状况的评分，并且在控制干预前预期后仍然如此。没有问卷或认知任务显示出在基线和 6 周评估时间点之间有可信的变化。
在健康成年男性中，LSD 微剂量似乎相对安全，尽管存在焦虑风险。虽然微剂量会引起与情绪提升作用相关的量表短暂增加，但不足以促进健康成年人整体情绪或认知的持久变化。未来在临床人群中进行的微剂量试验将需要使用活性安慰剂来控制安慰剂效应，并进行剂量滴定以调整个体对药物反应的变异性。
