ArticlePsychopharmacology2026
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.
Article in Psychopharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06772753 (Investigation of Psychedelic Effects in Psychoactive Substances), which is not on this map. Not yet cited in PubMed.
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Investigation of Psychedelic Effects in Psychoactive Substances
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6 authors.
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Abstract
rationaleDelta-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.
objectivesThis 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.
methodsFour 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.
results25 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.
conclusionsThese 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 registrationThis trial was registered at ClinicalTrials.gov (NCT06772753) on January 13, 2025.
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