Classic psychedelics do not affect T cell and monocyte immune responses

Introduction

Psychedelics are psychoactive substances that alter cognition and perception principally via agonism at serotonin (5-HT) receptors, with 5-HT2A activation considered the primary psychedelic trigger. The so-called classic psychedelics include tryptamines (for example N,N-dimethyltryptamine, DMT, and psilocybin/psilocin), lysergamides (such as lysergic acid diethylamide, LSD) and phenethylamines (such as mescaline). Earlier research has reported therapeutic potential of these compounds across several psychiatric and neuropsychiatric indications, and some in vivo and ex vivo studies have suggested immune-modulatory actions linked to 5-HT2A and 5-HT1A receptor activation. However, reports are heterogeneous and direct effects on human immune cells in vitro have been sparsely explored, raising safety questions because T cells and monocytes play central roles in host defence and inflammation. Aday and colleagues set out to test whether four classic psychedelics—LSD, psilocin, DMT and mescaline—directly affect primary human T lymphocyte function and monocyte NF-κB signalling in vitro. The study specifically examined T cell proliferation, early activation marker expression and stimulated cytokine release from CD4+ and CD8+ T cells, and LPS-triggered NF-κB induction in a monocytic reporter cell line, to clarify whether these compounds exert direct immunomodulatory effects that might be relevant to clinical safety in assisted psychotherapy settings.