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
Frederick S. Barrett, David Wolinsky, Zach Daily, Joseph Ciancio, Kristy Arthur, Ryan Vandrey
Psychopharmacology August 27, 2026 DOI: 10.1007/s00213-026-07138-0 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Pilot human laboratory study, double-blind, placebo-controlled, within-subject crossover Pilot study Peer reviewed |
|---|---|
| Sample size | 4 |
| Population | Healthy adults aged 31-47, 3 female |
| Interventions | Delta-9-tetrahydrocannabinol Psilocybin Placebo |
| Dose | 25 mg and 50 mg THC; 25 mg psilocybin |
| Topics | Cannabis Psilocybin Psychedelic-assisted therapy |
| Registration | NCT06772753 |
| Key points | A 25 mg oral dose of THC produced subjective experiences similar to 25 mg psilocybin, and dronabinol was mistaken for a classic hallucinogen by both a psychedelic-naive and a psychedelic-experienced participant. The authors suggest that set and setting conditions of a psychedelic trial can influence THC's subjective effects. |
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.
In the evidence
This study is part of the evidence base for 3 syntheses in the library. Here is how each one recorded it.
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A 25 mg oral dose of THC produced subjective experiences similar to 25 mg psilocybin, and dronabinol was mistaken for a classic hallucinogen, suggesting set and setting can influence THC's subjective effects.
Synthesized
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State of the evidence: Cannabis Supports
This pilot study found that a 25 mg oral dose of THC produced subjective experiences similar to 25 mg psilocybin, and dronabinol was mistaken for a classic hallucinogen by both a psychedelic-naive and a psychedelic-experienced participant.
Synthesized
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A 25 mg oral dose of THC produced subjective experiences similar to 25 mg psilocybin, and dronabinol was mistaken for a classic hallucinogen by both a psychedelic-naive and a psychedelic-experienced participant.
Synthesized
Comparable studies
Other randomized controlled trials on psilocybin and psychedelic-assisted therapy, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects. Healthy adults, mostly hallucinogen-naïve | 2011 | Randomized controlled trial | n = 18 |
| Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder Adults aged 25–65 with DSM-IV alcohol dependence and at least 4 heavy drinking days in... | 2022 | Randomized controlled trial | n = 95 |
| Increased global integration in the brain after psilocybin therapy for depression. Patients with treatment-resistant depression and patients with major depressive disorder | 2022 | Open-label trial and double-blind phase II randomized controlled trial | |
| Single-dose psilocybin-assisted therapy in major depressive disorder: A placebo-controlled, double-blind, randomised clinical trial. Adults diagnosed with major depressive disorder and no unstable somatic conditions | 2023 | Double-blind, randomised clinical trial | n = 52 |
| Implications for psychedelic-assisted psychotherapy: functional magnetic resonance imaging study with psilocybin Healthy participants | 2012 | Randomized controlled trial | n = 10 |