Psychedelics and Immunomodulation: Novel Approaches and Therapeutic Opportunities
This review (2015) describes the immunomodulatory potential of classical serotonergic psychedelics (DMT, LSD, MDMA, etc) from a perspective of molecular immunology and pharmacology. With a particular focus on functional interaction of serotonin and sigma-1 receptors and cross-talk with toll-like and RIG-I-like pattern-recognition receptor-mediated signalling.
Abstract
Classical psychedelics are psychoactive substances, which, besides their psychopharmacological activity, have also been shown to exert significant modulatory effects on immune responses by altering signaling pathways involved in inflammation, cellular proliferation, and cell survival via activating NF-κB and mitogen-activated protein kinases. Recently, several neurotransmitter receptors involved in the pharmacology of psychedelics, such as serotonin and sigma-1 receptors, have also been shown to play crucial roles in numerous immunological processes. This emerging field also offers promising treatment modalities in the therapy of various diseases including autoimmune and chronic inflammatory conditions, infections, and cancer. However, the scarcity of available review literature renders the topic unclear and obscure, mostly posing psychedelics as illicit drugs of abuse and not as physiologically relevant molecules or as possible agents of future pharmacotherapies. In this paper, the immunomodulatory potential of classical serotonergic psychedelics, including N,N-dimethyltryptamine (DMT), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), lysergic acid diethylamide (LSD), 2,5-dimethoxy-4-iodoamphetamine, and 3,4-methylenedioxy-methamphetamine will be discussed from a perspective of molecular immunology and pharmacology. Special attention will be given to the functional interaction of serotonin and sigma-1 receptors and their cross-talk with toll-like and RIG-I-like pattern-recognition receptor-mediated signaling. Furthermore, novel approaches will be suggested feasible for the treatment of diseases with chronic inflammatory etiology and pathology, such as atherosclerosis, rheumatoid arthritis, multiple sclerosis, schizophrenia, depression, and Alzheimer’s disease.
Research Summary of 'Psychedelics and Immunomodulation: Novel Approaches and Therapeutic Opportunities'
Introduction
Psychedelics are psychoactive compounds that alter perception and cognition primarily via neurotransmitter receptors, most notably serotonergic 5-HT receptor subtypes. Hohlfeld and colleagues frame classical psychedelics (tryptamines, lysergamides, phenethylamines) as agents that, beyond psychopharmacology, may influence immune function because many immune cells express neurotransmitter receptors and participate in neuroimmune communication. The introduction notes that early work on psychedelics and immunity dates from the 1970s, but systematic biomedical interest has only resurged in the past decade, and rigorous evidence on immunomodulatory actions remains limited. The paper sets out to review and synthesise molecular immunology and pharmacology evidence for the immunomodulatory potential of classical serotonergic psychedelics, including DMT, 5-MeO-DMT, LSD, DOI and MDMA, with particular attention to serotonin and sigma-1 receptor biology and their cross-talk with pattern-recognition receptor (PRR) signalling. Hohlfeld and colleagues aim to propose mechanistic models and suggest novel therapeutic approaches for conditions with chronic inflammatory or autoimmune pathology, while highlighting gaps in the literature and translational hurdles.
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Szabo, A. (2015). Psychedelics and Immunomodulation: Novel Approaches and Therapeutic Opportunities. Frontiers in Immunology, 6. https://doi.org/10.3389/fimmu.2015.00358
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