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

Psychedelics are primarily recognized for their profound behavioral effects, leading most research on psychedelics and their primary target, the 5-HT_2A 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-HT_2A receptors generally promotes inflammation. Levels are elevated at sites of inflammation and through 5-HT_2A 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.