Department of Psychiatry and Behavioral Sciences, San Francisco VA Medical Center, University of California, 401 Parnassus Ave., San Francisco, CA, 94143, USA.
Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, CA, USA.
Psychopharmacology (Berl). 2022 Jun;239(6):1989-2010. doi: 10.1007/s00213-022-06123-7. Epub 2022 Apr 1.
Psychedelic research continues to garner significant public and scientific interest with a growing number of clinical studies examining a wide range of conditions and disorders. However, expectancy effects and effective condition masking have been raised as critical limitations to the interpretability of the research.
In this article, we review the many methodological challenges of conducting psychedelic clinical trials and provide recommendations for improving the rigor of future research.
Although some challenges are shared with psychotherapy and pharmacology trials more broadly, psychedelic clinical trials have to contend with several unique sources of potential bias. The subjective effects of a high-dose psychedelic are often so pronounced that it is difficult to mask participants to their treatment condition; the significant hype from positive media coverage on the clinical potential of psychedelics influences participants' expectations for treatment benefit; and participant unmasking and treatment expectations can interact in such a way that makes psychedelic therapy highly susceptible to large placebo and nocebo effects. Specific recommendations to increase the success of masking procedures and reduce the influence of participant expectancies are discussed in the context of study development, participant recruitment and selection, incomplete disclosure of the study design, choice of active placebo condition, as well as the measurement of participant expectations and masking efficacy.
Incorporating the recommended design elements is intended to reduce the risk of bias in psychedelic clinical trials and thereby increases the ability to discern treatment-specific effects of psychedelic therapy.
迷幻药研究继续引起公众和科学界的浓厚兴趣，越来越多的临床研究正在检查广泛的病症和障碍。然而，预期效应和有效的条件掩盖已被提出作为研究解释的关键限制。
在本文中，我们回顾了进行迷幻药临床试验的许多方法学挑战，并为提高未来研究的严谨性提供了建议。
尽管一些挑战与更广泛的心理治疗和药理学试验共享，但迷幻药临床试验必须应对几个潜在偏见的独特来源。高剂量迷幻剂的主观影响通常非常明显，以至于很难掩盖参与者的治疗状况；积极的媒体报道对迷幻剂临床潜力的大量炒作影响了参与者对治疗益处的期望；参与者的揭示和治疗期望可以以一种使迷幻治疗非常容易受到大的安慰剂和反安慰剂效应影响的方式相互作用。在研究开发、参与者招募和选择、研究设计的不完全披露、选择活性安慰剂条件以及参与者期望和掩盖效果的测量等方面，讨论了增加掩盖程序成功和降低参与者期望影响的具体建议。
纳入建议的设计要素旨在降低迷幻药临床试验中的偏差风险，从而提高辨别迷幻治疗特定效果的能力。
