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Set and setting of psychedelics for therapeutic use in psychiatry: A systematic review

Clémentine Estric, Thomas Duron, Sarah Kabani, Jorge Lopez-Castroman

Journal of Psychopharmacology May 12, 2025 DOI: 10.1177/02698811251338214 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Systematic review Randomized Open-label Peer reviewed
Sample size 763
Population Participants in clinical trials of psychedelics for psychiatric disorders
Topics Ayahuasca DMT LSD Psilocybin Psychedelic-assisted therapy
Keywords Context Pap Therapeutic procedures Medical standards Therapeutic space Environment Treatment conditions
Citations 10
Key findings Participant selection and safe environment creation were consistently reported across psychedelic clinical trials, but other aspects of set and setting like monitor training, visual distractors, and pleasant environment were not standardized, limiting comparability and reproducibility.

Abstract

Psychedelics offer promising outcomes in psychiatry. However, the preparation of participants (set) and the environmental conditions of taking a psychedelic (setting) are not standardized. We describe the set and setting for therapeutic use of psychedelic drugs in people with psychiatric disorders. In this systematic review, articles were identified in the PubMed and Web of Science databases until 12 December 2023. Only clinical trials published in English or French were eligible, and studies using psychedelics for withdrawal were excluded. Sixteen domains of set and setting were assessed covering participant selection, pre- and post-session interventions, monitor presence, environmental management, and end-of-session procedure. Of 4912 articles screened, 27 articles were retained reporting on 25 studies. Thirteen of the included studies reported randomized trials, while 12 were open-label studies, on a total of 763 participants. Studies considered features of set and setting to different extents. Participant selection and the creation of a safe environment were consistently present, but articles were more heterogeneous about reporting monitor training (52%), controlling visual distractors (64%) and creating a pleasant environment (68%). Psilocybin was over-represented (47%). Many key elements were described in each study, but differences in set and setting limit comparability and reproducibility. Harmonizing these aspects would aid the interpretation of future studies and help understand the effect of psychedelics in psychiatry.

In the evidence

This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.

  • Participant selection and safe environment creation were consistently reported across psychedelic clinical trials, but other aspects of set and setting like monitor training, visual distractors, and pleasant environment were not standardized, limiting comparability and reproducibility.

    Synthesized

Comparable studies

Other systematic reviews and meta-analyses on LSD and psychedelic-assisted therapy, most cited first.

Study Year Design Participants
Psychedelic therapy for depressive symptoms: A systematic review and meta-analysis. Participants in studies of psychedelic therapy for depressive symptoms (Major... 2023 Systematic review with meta-analysis n = 14
United States National Institutes of Health grant funding for psychedelic-assisted therapy clinical trials from 2006-2020. 2022 Systematic review
Safety and risk assessment of psychedelic psychotherapy: A meta-analysis and systematic review. Human subjects in studies of psychedelic-assisted psychotherapy 2024 Systematic review and meta-analysis n = 30
The impact of psychedelics on patients with alcohol use disorder: a systematic review with meta-analysis. Patients with alcohol use disorder 2024 Systematic review and meta-analysis

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