Psilocybin induces acute and persisting alterations in immune status in healthy volunteers: An experimental, placebo-controlled study

This double-blind placebo-controlled paper (n=60) explores the effects psilocybin (12mg/70kg) has on a range of inflammatory markers associated with stress-related psychiatric disorders. Blood samples, MRI and questionnaires were used to assess different aspects of the immune response. Psilocybin immediately reduced levels of the inflammation-inducing TNF-α while other markers were unchanged. After seven days, TNF-α returned to baseline while levels of IL-6 and CRP were reduced in the psilocybin group, which were associated with more persisting positive mood and social effects.

Abstract of Psilocybin induces acute and persisting alterations in immune status in healthy volunteers

“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 the 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 behaviour. Psilocybin immediately reduced concentrations of the pro-inflammatory cytokine tumour 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.”

Authors: Natasha L. Mason, Attila Szabo, Kim P. C. Kuypers, Pablo A. Mallaroni, Rafael de la Torre, Johannes T. Reckweg, Desmond H. Y. Tse, Nadia R. P. W. Hutten, Amanda Feilding & Johannes G. Ramaekers

Summary of Psilocybin induces acute and persisting alterations in immune status and the stress response in healthy volunteers

Introduction

Substantial evidence suggests that psychosocial stressors can activate the immune system, resulting in inflammatory processes that may underlie certain psychiatric disorders. Additionally, pharmacological treatments that decrease pro-inflammatory processes may hold therapeutic value in a wide range of neuropsychiatric diseases.

Psychedelic drugs have been found to possess anti-inflammatory properties in preclinical models. Some clinical trials have shown promising results regarding their ability to treat psychiatric disorders characterized by aberrant inflammatory profiles, such as depression, addiction, and PTSD.