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Are psychedelics anti-inflammatory? A systematic review and meta-analysis of studies examining the immunomodulatory effects of serotonergic psychedelics.

Anna Skovgaard Lerche, Dennis Parker Kelley, Michael E Benros, Gerald Billac, Ellen Bradley, Boris D. Heifets, Joshua Woolley, Kristen Nishimi, Aoife O'Donovan

Brain, Behavior, and Immunity September 28, 2026 DOI: 10.1016/j.bbi.2026.107033 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Systematic review and meta-analysis Peer reviewed
Population In vitro studies, non-human in vivo studies, and human trials examining immune markers after serotonergic psychedelic exposure
Intervention Serotonergic psychedelics
Topics Serotonin
Keywords 5-ht2ar Inflammation Meta-analysis Serotonergic psychedelics Systematic review
Key findings Serotonergic psychedelics reduce proinflammatory cytokines in preclinical models with increased baseline inflammation (SMD = -1.23, 95% CI [-1.54, -0.92]) but show no significant effect in healthy murines (SMD = -0.06, 95% CI [-0.54, 0.43]). Human evidence is mixed and too limited for conclusions about translational potential.

Abstract

Serotonergic psychedelics are promising treatments for neuropsychiatric disorders, and their immunomodulatory effects may contribute to their clinical efficacy. However, we lack a systematic review and meta-analysis of these effects across in vitro, in vivo non-human, and human studies. We systematically searched PubMed, EMBASE, Web of Science, PsycINFO, LILACS and ClinicalTrials.gov for all studies, published from database inception through February 9th, 2026, examining changes in immune markers after serotonergic psychedelic exposure, and meta-analyzed eligible studies. Of 9,195 studies screened, 61 studies met eligibility criteria for systematic review including 24 in vitro studies, 30 non-human in vivo studies, and seven human studies including data from 10 separate human trials. Results of the systematic review indicated that most in vitro (19/24) and non-human in vivo (25/30) studies reported anti-inflammatory effects of psychedelics. Human results were mixed with anti-inflammatory effects observed in 3/10 trials. Results of the meta-analysis of 18 eligible in vivo murine studies showed a significant decrease in proinflammatory cytokines in inflammatory models (standardized mean difference (SMD = -1.23, 95% CI [-1.54, -0.92]), but no significant effects in healthy murines (SMD = -0.06, 95% CI [-0.54, 0.43]), following treatment with a serotonergic psychedelic. Four human studies were eligible for meta-analysis; however, the small number of studies resulted in imprecise estimates and limited interpretability. Thus, while serotonergic psychedelics reduce proinflammatory cytokines in preclinical models of increased baseline inflammation, limited human evidence precludes conclusions about their translational potential.

In the evidence

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

  • Serotonergic psychedelics reduced proinflammatory cytokines in inflamed murine models (SMD = -1.23) but not healthy murines, and human evidence was mixed and too limited for conclusions.

    Synthesized

Comparable studies

Other systematic reviews and meta-analyses on serotonin, most cited first.

Study Year Design Participants
Therapeutic effects of classic serotonergic psychedelics: A systematic review of modern‐era clinical studies Patients with cancer- or illness-related anxiety and depression, major depressive... 2020 Systematic review n = 188
Efficacy, tolerability, and safety of serotonergic psychedelics for the management of mood, anxiety, and substance-use disorders: a systematic review of systematic reviews Patients with mood, anxiety, or substance-use disorders, including cancer patients and... 2018 Systematic review of systematic reviews
Adverse events in clinical treatments with serotonergic psychedelics and MDMA: A mixed-methods systematic review Patients in clinical trials with MDMA or serotonergic psychedelics 2022 Systematic review n = 598
Classic serotonergic psychedelics for mood and depressive symptoms: a meta-analysis of mood disorder patients and healthy participants Healthy volunteers and patients with mood disorders 2021 Meta-analysis n = 257
Serotonergic psychedelics and personality: A systematic review of contemporary research 2018 Systematic review

Citations in the library

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