Post-acute psychological effects of classical serotonergic psychedelics: a systematic review and meta-analysis

Classical psychedelics such as psilocybin, ayahuasca, and LSD produce significant psychological effects lasting at least 24 hours after administration, according to a systematic review and meta-analysis of 34 experimental studies involving 549 participants. Large effects were observed for reducing targeted symptoms in psychiatric samples, improving negative and positive affect, social outcomes, and existential or spiritual well-being, with between-group effect sizes ranging from Hedges' g = 0.84 to 1.08. Effects may be larger in clinical samples. Evidence for changes in personality traits or mindfulness was weak. No post-acute adverse effects were found, but high risk of bias, heterogeneity, and possible publication bias underscore the need for larger, placebo-controlled trials.

Study at a glance

Abstract

Abstract Background Scientific interest in the therapeutic effects of classical psychedelics has increased in the past two decades. The psychological effects of these substances outside the period of acute intoxication have not been fully characterized. This study aimed to: (1) quantify the effects of psilocybin, ayahuasca, and lysergic acid diethylamide (LSD) on psychological outcomes in the post-acute period; (2) test moderators of these effects; and (3) evaluate adverse effects and risk of bias. Methods We conducted a systematic review and meta-analysis of experimental studies (single-group pre-post or randomized controlled trials) that involved administration of psilocybin, ayahuasca, or LSD to clinical or non-clinical samples and assessed psychological outcomes ⩾24 h post-administration. Effects were summarized by study design, timepoint, and outcome domain. Results A total of 34 studies (24 unique samples, n = 549, mean longest follow-up = 55.34 weeks) were included. Classical psychedelics showed significant within-group pre-post and between-group placebo-controlled effects on a range of outcomes including targeted symptoms within psychiatric samples, negative and positive affect-related measures, social outcomes, and existential/spiritual outcomes, with large between-group effect in these domains (Hedges' g s = 0.84 to 1.08). Moderator tests suggest some effects may be larger in clinical samples. Evidence of effects on big five personality traits and mindfulness was weak. There was no evidence of post-acute adverse effects. Conclusions High risk of bias in several domains, heterogeneity across studies, and indications of publication bias for some models highlight the need for careful, large-scale, placebo-controlled randomized trials.