Serotonin, immune function, and psychedelics as potent anti-inflammatories.

Psychedelics, known for their behavioral effects, also influence the immune system through serotonin 5-HT2A receptors found throughout the body. Serotonin acting at these receptors generally promotes inflammation by increasing cytokine production, eosinophil recruitment, T-cell activation, and mast cell degranulation. However, some psychedelics show powerful anti-inflammatory and immunomodulatory effects via 5-HT2A receptor activation in preclinical models of human inflammatory diseases. Human studies are limited but suggest psychedelics may offer a new strategy for treating inflammatory conditions. This review covers serotonergic modulation of immune function, the role of 5-HT2A receptors, and key findings on psychedelics' anti-inflammatory efficacy.

Study at a glance

Abstract

Psychedelics are primarily recognized for their profound behavioral effects, leading most research on psychedelics and their primary target, the 5-HT2A receptor, to focus on brain activity. However, these receptors are not only found within the brain and are present in nearly every tissue and cell type throughout the body, playing a significant role alongside serotonin in modulating various processes, including immune function. Serotonin acting at 5-HT2A receptors generally promotes inflammation. Levels are elevated at sites of inflammation and through 5-HT2A receptor activation lead to events including increased cytokine production, eosinophil recruitment, T-cell activation, and mast cell degranulation. Some psychedelics, but not all, have been found to have powerful anti-inflammatory and immunomodulatory effects through activation of 5-HT2A receptors in preclinical experimental systems and models of human inflammatory diseases. Human studies examining anti-inflammatory effects of psychedelics are limited but suggestive that psychedelics may represent a new strategy to treat inflammatory diseases. In this review we will present an overview of serotonergic modulation of immune function, the role of 5-HT2A receptors in these processes, and a summary of key findings with psychedelics with regards to anti-inflammatory efficacy.