Pilot study comparing the effects of high dose THC to high dose psilocybin and placebo in the set and setting of a classic psychedelic therapy session.

IF 3.3 3区医学 Q2 NEUROSCIENCES

Psychopharmacology Pub Date : 2026-08-27 DOI:10.1007/s00213-026-07138-0

Frederick S Barrett, David Wolinsky, Zach Daily, Joseph Ciancio, Kristy Arthur, Ryan Vandrey

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引用次数: 0

Abstract

Rationale: Delta-9-tetrahydrocannabinol (Δ9-THC) has been reported to evoke psychedelic-like experiences at high doses in some individuals. However, the doses of Δ9-THC that occasion such effects and the phenomenology of these experiences are poorly understood.

Objectives: This brief report presents preliminary findings from a pilot human laboratory study that directly compared the acute effects of Δ9-THC and psilocybin under set (expectancy) and setting (context) conditions of a typical psychedelic clinical trial.

Methods: Four healthy adults (ages 31-47, 3 F) received oral administration of placebo, psilocybin (25 mg), and 25 mg Δ9-THC, and two of these participants also received 50 mg Δ9-THC, in a double-blind, placebo-controlled, within-subject crossover study. Δ9-THC was administered as either synthetic Δ9-THC (dronabinol) or a whole-plant cannabis distillate extract (89.9% Δ9-THC). Subjective effects, cardiovascular measures, and safety were monitored throughout each session. Participants were asked after each session what drug they thought they had received.

Results: 25 mg Δ9-THC in both forms yielded a subjective experience similar to 25 mg psilocybin. Dronabinol was mistaken for a classic hallucinogen by both a psychedelic-naïve and a psychedelic-experienced participant.

Conclusions: These preliminary data suggest that a 25 mg oral dose of pure, synthetic Δ9-THC can be mistaken for a classic hallucinogen, and that oral Δ9-THC can elicit a psychedelic-like experience under set and setting conditions of a typical psychedelic clinical trial. While limited by sample size, these initial results provide insights into the comparative psychopharmacology of Δ9-THC and psilocybin as well as the potentially substantial impact of set and setting on subjective effects of psychoactive drugs.

Trial registration: This trial was registered at ClinicalTrials.gov (NCT06772753) on January 13, 2025.

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比较高剂量四氢大麻酚与高剂量裸盖菇素和安慰剂在经典迷幻治疗过程中的作用的初步研究。

理由：据报道，delta -9-四氢大麻酚（Δ9-THC）在高剂量下会引起一些人的迷幻样体验。然而，引起这种效果的Δ9-THC剂量和这些体验的现象学却知之甚少。目的：这篇简短的报告介绍了一项实验性人体实验室研究的初步结果，该研究直接比较了Δ9-THC和裸盖菇素在典型迷幻药临床试验的设定（预期）和设定（背景）条件下的急性效应。方法：在一项双盲、安慰剂对照、受试者内交叉研究中，4名健康成年人（31-47岁，3岁）口服安慰剂、裸盖菇素（25 mg）和25 mg Δ9-THC，其中2名参与者还口服50 mg Δ9-THC。Δ9-THC作为合成Δ9-THC（曲大麻酚）或整株大麻蒸馏提取物（89.9% Δ9-THC）进行管理。主观影响、心血管测量和安全性在每个疗程中都被监测。每次疗程结束后，参与者都会被问及他们认为自己服用了什么药物。结果：25毫克Δ9-THC两种形式产生的主观体验类似于25毫克裸盖菇素。psychedelic-naïve和有过迷幻经历的参与者都把屈大麻酚误认为是一种经典的致幻剂。结论：这些初步数据表明，口服25毫克纯合成Δ9-THC可能被误认为是一种经典的致幻剂，并且在典型致幻剂临床试验的设定条件下，口服Δ9-THC可以引起类似致幻剂的体验。虽然受样本量的限制，这些初步结果提供了Δ9-THC和裸盖菇素的比较精神药理学的见解，以及设置和设置对精神活性药物主观效应的潜在实质性影响。试验注册：该试验于2025年1月13日在ClinicalTrials.gov （NCT06772753）注册。

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来源期刊

Psychopharmacology 医学-精神病学

CiteScore

7.10

自引率

5.90%

发文量

257

审稿时长

2-4 weeks

期刊介绍： Official Journal of the European Behavioural Pharmacology Society (EBPS) Psychopharmacology is an international journal that covers the broad topic of elucidating mechanisms by which drugs affect behavior. The scope of the journal encompasses the following fields: Human Psychopharmacology: Experimental This section includes manuscripts describing the effects of drugs on mood, behavior, cognition and physiology in humans. The journal encourages submissions that involve brain imaging, genetics, neuroendocrinology, and developmental topics. Usually manuscripts in this section describe studies conducted under controlled conditions, but occasionally descriptive or observational studies are also considered. Human Psychopharmacology: Clinical and Translational This section comprises studies addressing the broad intersection of drugs and psychiatric illness. This includes not only clinical trials and studies of drug usage and metabolism, drug surveillance, and pharmacoepidemiology, but also work utilizing the entire range of clinically relevant methodologies, including neuroimaging, pharmacogenetics, cognitive science, biomarkers, and others. Work directed toward the translation of preclinical to clinical knowledge is especially encouraged. The key feature of submissions to this section is that they involve a focus on clinical aspects. Preclinical psychopharmacology: Behavioral and Neural This section considers reports on the effects of compounds with defined chemical structures on any aspect of behavior, in particular when correlated with neurochemical effects, in species other than humans. Manuscripts containing neuroscientific techniques in combination with behavior are welcome. We encourage reports of studies that provide insight into the mechanisms of drug action, at the behavioral and molecular levels. Preclinical Psychopharmacology: Translational This section considers manuscripts that enhance the confidence in a central mechanism that could be of therapeutic value for psychiatric or neurological patients, using disease-relevant preclinical models and tests, or that report on preclinical manipulations and challenges that have the potential to be translated to the clinic. Studies aiming at the refinement of preclinical models based upon clinical findings (back-translation) will also be considered. The journal particularly encourages submissions that integrate measures of target tissue exposure, activity on the molecular target and/or modulation of the targeted biochemical pathways. Preclinical Psychopharmacology: Molecular, Genetic and Epigenetic This section focuses on the molecular and cellular actions of neuropharmacological agents / drugs, and the identification / validation of drug targets affecting the CNS in health and disease. We particularly encourage studies that provide insight into the mechanisms of drug action at the molecular level. Manuscripts containing evidence for genetic or epigenetic effects on neurochemistry or behavior are welcome.