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

This double-blind placebo-controlled pre-print 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

“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 Mason, Attila Szabo, Kim Kuypers, Pablo Mallaroni, Rafael de la Torre, Johannes Reckweg, Desmond Tse, Nadia Hutten, Amanda Feilding & Johannes 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.

Study details

Compounds studied
Psilocybin

Topics studied
Immunity

Study characteristics
Placebo-Controlled Double-Blind Randomized Re-analysis

Participants
60 Humans

Authors

Authors associated with this publication with profiles on Blossom

Natasha Mason
Natasha Mason is interested in elucidating the neurobiological and cognitive mechanisms of (psychedelic) drugs by utilizing multimodal study designs, with a particular focus on substances that may hold therapeutic value.

Kim Kuypers
Kim Kuypers is a researcher at Maastricht University. Her work is concerned with understanding the neurobiology underlying flexible cognition, empathy, and well-being. One of the main ways she does is with the use of psychedelics.

Amanda Feilding
Amanda is the Founder and Director of the Beckley Foundation. She's called the 'hidden hand' behind the renaissance of psychedelic science, and her contribution to global drug policy reform has also been pivotal and widely acknowledged.

Johannes Ramaekers
Johannes Ramaekers is a professor at Maastricht University his work focuses on behavioral toxicology of drugs and combines methods from psychopharmacology, forensic toxicology and neuroscience to determine drug-induced changes in human performance. Some of this research is done with DMT.

Institutes

Institutes associated with this publication

Maastricht University
Maastricht University is host to the psychopharmacology department (Psychopharmacology in Maastricht) where various researchers are investigating the effects of psychedelics.

Beckley Foundation
The Beckley Foundation is one of the leading voices that has spurred the scientific renaissance of psychedelics research. Led by Amanda Fielding, the NGO funds research and engages with politicians.

Compound Details

The psychedelics given at which dose and how many times

Psilocybin 11.9 mg | 1x

Linked Research Papers

Notable research papers that build on or are influenced by this paper

Me, myself, bye: regional alterations in glutamate and the experience of ego dissolution with psilocybin
This brain imaging study (n=60) with psilocybin (12mg/70kg) investigated the changes in glutamate levels in various brain areas and found that lower levels in hippocampal glutamate were correlated with positively experienced ego dissolution. Higher levels of medial prefrontal cortical glutamate correlated with negatively experienced ego dissolution.

Spontaneous and deliberate creative cognition during and after psilocybin exposure
This double-blind, placebo-controlled, between-subjects study (n=60) investigated the effects of psilocybin (11.9 mg/70kg) on creativity in healthy participants, with respect to acute and persisting changes in convergent and divergent thinking in relation to restructuralization of Default Mode Network (DMN) connectivity. Although subjects felt more insightful under the acute psychedelic state, their ability to generate ideas and associations in a goal-directed manner was impaired. However, 7 days after psilocybin administration, participants generated a higher quantity of novel ideas for uses of an everyday object. Decreased integrity of the DMN under the acute state was the strongest predictor of subjective insightfulness, acute decrease in scores of originality, and a long-term increase in the generation of novel ideas.

Linked Clinical Trial

Psilocybin as a tool for enhancing cognitive flexibility
The study will assess drug-induced change in performance in divergent thinking and goal-directed behaviour when comparing psilocybin to placebo, before and after an induction of stress. Additional study parameters include frontal-subcortical connectivity alterations and neurotransmission of glutamate and GABA between treatment conditions, as well as subjective questionnaires, pharmacokinetics, and cortisol.

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