Psilocybin induces acute and persisting alterations in immune status and the stress response in healthy volunteers
Natasha L. Mason, Attila Szabo, Kim P. C. Kuypers, Pablo Mallaroni, R. de la Torre Fornell, Johannes T. Reckweg, Desmond H. Y. Tse, Nadia R. P. W. Hutten, Amanda Feilding, Johannes G. Ramaekers
medRxiv November 1, 2022 preprint DOI: 10.1101/2022.10.31.22281688 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Placebo-controlled, parallel group design |
|---|---|
| Sample size | 60 |
| Population | Healthy participants |
| Intervention | Psilocybin |
| Dose | 0.17 mg/kg |
| Duration | 7-day follow-up |
| Topics | Psilocybin |
| Keywords | Placebo Immune system Hallucinogen Cytokine Interleukin 6 Mood Lipopolysaccharide Gastroenterology Immunology |
| Citations | 6 |
| Key points | Psilocybin acutely reduced TNF-α and persistently reduced IL-6 and CRP, and blunted the cortisol stress response, with immune changes linked to hippocampal glutamate and positive mood effects. |
Abstract
Abstract Patients characterized by stress-related disorders such as depression display elevated circulating concentrations of pro-inflammatory cytokines and a hyperactive HPA axis. Psychedelics are demonstrating promising results in treatment of such disorders, however the mechanisms of their therapeutic effects are still unknown. To date the evidence of acute and persisting effects of psychedelics on immune functioning, HPA axis activity in response to stress, and associated psychological outcomes is preliminary. To address this, we conducted a placebo-controlled, parallel group design comprising of 60 healthy participants who received either placebo (n=30) or 0.17 mg/kg psilocybin (n=30). Blood samples were taken to assess acute changes in immune status, and 7 days after drug administration. Seven days’ post-administration, participants in each treatment group were further subdivided: 15 underwent a stress induction protocol, and 15 underwent a control protocol. Ultra-high field magnetic resonance spectroscopy was used to assess whether acute changes in glutamate or glial activity were associated with changes in immune functioning. Finally, questionnaires assessed persisting self-report changes in mood and social behavior. Psilocybin immediately reduced concentrations of the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α), while other inflammatory markers (interleukin (IL)-1α, IL-1β, IL-6, and C-reactive protein (CRP)) remained unchanged. Seven days later, TNF-α concentrations returned to baseline, while IL-6 and CRP concentrations were persistently reduced in the psilocybin group. Changes in the immune profile were related to acute neurometabolic activity as acute reductions in TNF-α were linked to lower concentrations of glutamate in the hippocampus. Additionally, the more of a reduction in IL-6 and CRP seven days after psilocybin, the more persisting positive mood and social effects participants reported. Regarding the stress response, after a psychosocial stressor, psilocybin blunted the cortisol response compared to placebo. Such acute and persisting changes may contribute to the psychological and therapeutic effects of psilocybin demonstrated in ongoing patient trials.
Comparable studies
Other randomized controlled trials on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety | 2016 | Randomized controlled trial | n = 51 |
| Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Patients with cancer-related anxiety and depression | 2016 | Double-blind, placebo-controlled, crossover trial | n = 29 |
| Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance Hallucinogen-naïve adults reporting regular participation in religious or spiritual... | 2006 | Double-blind study | n = 36 |
| Trial of Psilocybin versus Escitalopram for Depression Selected group of patients with depression | 2021 | Randomized controlled trial | |
| Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder Adults aged 21 to 75 years with major depressive disorder, not currently using... | 2020 | Randomized controlled trial | n = 24 |
Citations in the library
Cited by 5
- Psilocybin for dementia prevention? The potential role of psilocybin to alter mechanisms associated with major depression and neurodegenerative diseases Pharmacology & Therapeutics April 6, 2024
- Present and future of metabolic and metabolomics studies focused on classical psychedelics in humans. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie December 31, 2023
- Psychotomimetic compensation versus sensitization. Pharmacology Research & Perspectives August 1, 2024
- Psilocybin in the treatment of eating disorders: a systematic review of the literature and registered clinical trials Eating and Weight Disorders - Studies on Anorexia Bulimia and Obesity July 29, 2025
- MicroRNAs underlying the antidepressant effect of psilocybin – Establishing an nCounter pipeline for microRNA-quantification in the pig brain Research Square January 12, 2024
Cites 33
- Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance Psychopharmacology July 7, 2006
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder JAMA Psychiatry November 4, 2020
- Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects. Psychopharmacology December 1, 2011
- Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial Psychological Medicine June 15, 2018
and 28 more in the library