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.
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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.
Citations in the library
Cites 62
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder JAMA Psychiatry November 4, 2020
- Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. New England Journal of Medicine November 3, 2022
- The Hallucinogen N,N -Dimethyltryptamine (DMT) Is an Endogenous Sigma-1 Receptor Regulator Science February 13, 2009
- Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels Neuropsychopharmacology January 26, 2019
and 57 more in the library