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

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.

• State of the evidence: LSD and psychedelic-assisted therapy ↕Mixed

  Participant selection and safe environment creation were consistently reported, but other set-and-setting elements such as monitor training, visual distractors, and pleasant environment were not standardized, limiting comparability.

  Synthesized October 22, 2026

Comparable studies

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