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

被引：37

作者：

Mason, N. L. ^{[1
]}

Szabo, A. ^{[2
,3
,4
]}

Kuypers, K. P. C. ^{[1
]}

Mallaroni, P. A. ^{[1
]}

Fornell, R. de la Torre ^{[5
]}

Reckweg, J. T. ^{[1
]}

Tse, D. H. Y. ^{[1
]}

Hutten, N. R. P. W. ^{[1
]}

Feilding, A. ^{[6
]}

Ramaekers, J. G. ^{[1
]}

机构：

[1] Maastricht Univ, Fac Psychol & Neurosci, Dept Neuropsychol & Psychopharmacol, POB 616, NL-6200 MD Maastricht, Netherlands

[2] Univ Oslo, Inst Clin Med, Norwegian Ctr Mental Disorders Res NORMENT, Oslo, Norway

[3] Oslo Univ Hosp, Div Mental Hlth & Addict, Oslo, Norway

[4] Univ Oslo, KG Jebsen Ctr Neurodev Disorders, Oslo, Norway

[5] Univ Pompeu Fabra, Hosp Mar, Med Res Inst, Integrat Pharmacol & Syst Neurosci Res Grp,Neurosc, Dr Aiguader 88, Barcelona 08003, Spain

[6] Beckley Fdn, Beckley Pk, Oxford OX3 9SY, England

来源：

BRAIN BEHAVIOR AND IMMUNITY | 2023年 / 114卷

关键词：

Cytokines; Psilocybin; Stress; Psychedelics; Glutamate; Magnetic resonance spectroscopy; Hypothalamic-pituitary-adrenocortical axis; C-REACTIVE PROTEIN; INNATE IMMUNITY; ACUTE STRESS; DEPRESSION; INFLAMMATION; INTERLEUKIN-6; CYTOKINES; GLUTAMATE; RECEPTOR; SCHIZOPHRENIA;

D O I：

10.1016/j.bbi.2023.09.004

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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 and persisting (7 day) changes in immune status. 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 (7-Tesla) 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-alpha (TNF-alpha), while other inflammatory markers (interleukin (IL)-10, IL-6, and C-reactive protein (CRP)) remained unchanged. Seven days later, TNF-alpha 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-alpha 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 did not significantly alter the stress response. Results are discussed in regards to the psychological and therapeutic effects of psilocybin demonstrated in ongoing patient trials.

引用

页码：299 / 310

页数：12

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[1] Decreased IL-1β-induced CCL20 response in human iPSC-astrocytes in schizophrenia: Potential attenuating effects on recruitment of regulatory T cells [J].