The immunomodulatory effects of classical psychedelics: A systematic review of preclinical studies
Zhen Xuen Brandon Low, Wei Shen Ng, Bey Hing Goh, Yatinesh Kumari, Eugene Lim
Progress in Neuro-Psychopharmacology and Biological Psychiatry September 7, 2024 DOI: 10.1016/j.pnpbp.2024.111139 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Peer reviewed |
|---|---|
| Population | Preclinical animal and in vitro studies |
| Interventions | 2 N 5-methoxy-N mescaline |
| Topics | Mescaline Psilocybin |
| Keywords | Hallucinogen Cinahl Medline Web of science Psycinfo Cochrane library Pharmacology Animal studies Meta-analysis |
| Citations | 19 |
| Key findings | Classical psychedelics reduced inflammatory cytokines in most studies but had mixed effects on immune cell activity, alleviating pre-existing inflammation while promoting inflammation under normal conditions. |
Abstract
Emerging evidence suggests that classical psychedelics possess immunomodulatory and anti-inflammatory properties; however, these effects are yet to be well-established. This systematic review aims to provide a timely and comprehensive overview of the immunomodulatory effects of classical psychedelics in preclinical studies. A systematic search was conducted on six databases, including CINAHL, EMBASE, MEDLINE, PsychINFO, Scopus, and Web of Science. Eligible studies targeting classical psychedelics for evaluation of their effects on inflammatory markers and immunomodulation have been included for analysis. Data was extracted from 40 out of 2822 eligible articles, and their risk of bias was assessed using the Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) tool and Quality Assessment Tool for In Vitro Studies (QUIN). Studies examined 2,5-dimethoxy-4-iodoamphetamine (DOI; n = 18); psilocybin (4-PO-DMT; n = 9); N,N-dimethyltryptamine (DMT; n = 8); lysergic acid diethylamide (LSD; n = 6); 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT; n = 3); psilocin (4-HO-DMT; n = 3); and mescaline (n = 2). In 36 studies where inflammatory cytokine levels were measured following psychedelic administration, a decrease in at least one inflammatory cytokine was observed in 29 studies. Immune cell activity was assessed in 10 studies and findings were mixed, with an equal number of studies (n = 5 out of 10) reporting either an increase or decrease in immune cell activity. Classical psychedelics were found to alleviate pre-existing inflammation but promote inflammation when administered under normal physiological conditions. This information is anticipated to inform future clinical trials, exploring classical psychedelics' potential to alleviate inflammation in various pathologies.
Comparable studies
Other systematic reviews and meta-analyses on mescaline, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Risk assessment of ritual use of oral dimethyltryptamine (DMT) and harmala alkaloids Humans (ritual ayahuasca use) | 2006 | Systematic review | |
| Drug–drug interactions involving classic psychedelics: A systematic review | 2023 | Systematic review | |
| Psychedelic‐assisted treatment for substance use disorder: A narrative systematic review Participants in studies of psychedelic-assisted treatment for alcohol, tobacco, and... | 2025 | Systematic review | n = 2,035 |
| Drug-drug interactions between classic psychedelics and psychoactive drugs: a systematic review Humans | 2023 | Systematic review | |
| A Systematic Review of the Neurocognitive Effects of Psychedelics in Healthy Populations: Implications for Depressive Disorders and Post-Traumatic Stress Disorder Healthy individuals and patients with PTSD or MDD | 2024 | Systematic review | n = 43 |
Citations in the library
Cited by 18
- Are we hallucinating or can psychedelic drugs modulate the immune system to control inflammation? British Journal of Pharmacology July 28, 2025
- Examining the potential of psilocybin and 5-MeO-DMT as therapeutics for traumatic brain injury. Progress in Neuro-Psychopharmacology and Biological Psychiatry July 14, 2025
- The Role of Psychedelics in Contemporary Psychological and Interdisciplinary Inquiry. Journal of Personalized Medicine September 28, 2025
- Is there a place for psychedelics in sports practice? Acta Neuropsychiatrica 2025
- Epigenome-wide association study of psilocybin-induced methylome changes in alcohol use disorder. Translational Psychiatry May 26, 2026
and 13 more in the library
Cites 66
- REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics Pharmacological Reviews June 20, 2019
- The Hallucinogen N,N -Dimethyltryptamine (DMT) Is an Endogenous Sigma-1 Receptor Regulator Science February 13, 2009
- Set and setting, psychedelics and the placebo response: An extra-pharmacological perspective on psychopharmacology Journal of Psychopharmacology November 16, 2016
- The Psychedelic State Induced by Ayahuasca Modulates the Activity and Connectivity of the Default Mode Network PLoS One February 18, 2015
- Constructing drug effects: A history of set and setting Drug Science, Policy and Law 2017
and 61 more in the library