Two psychedelic compounds, (R)-DOI and (R)-DOTFM, both activate the serotonin 2A receptor with comparable in vitro activity and behavioral potency, yet only (R)-DOI prevents inflammation and airway hyperresponsiveness in a mouse model of asthma. The compounds produce distinct differences in protein expression and inflammatory-related gene expression in lung tissue. The anti-inflammatory effects of certain psychedelics involve suppression of arginase 1 expression, revealing key mechanistic components of their anti-inflammatory action.
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.