IUPHAR Article: Psilocybin induces long-lasting effects via 5-HT2A receptors in mouse models of chronic pain.
Pharmacological research – May 01, 2025
Source: PubMed
Summary
A single dose of psilocybin, the active compound in magic mushrooms, provides lasting pain relief in mice suffering from chronic pain conditions. The compound effectively reduced pain sensitivity in mice with both chemotherapy-induced neuropathy and inflammatory pain. Working through specific brain receptors (5-HT2A), psilocybin showed promising results in alleviating various pain symptoms, suggesting potential therapeutic applications for treating chronic pain conditions.
Abstract
Chronic pain is a debilitating disease with current treatments lacking efficacy and safety, therefore discovery of new treatments is crucial. Initial studies suggest that psychedelics may be feasible for targeting pain, however clinical and preclinical controlled studies are necessary to further investigate that possibility. In this study we assessed the effects of two classical psychedelics psilocybin and 2,5-Dimethoxy-4-iodoamphetamine (DOI) in two models of chronic pain after systemic administration in male and female mice. Psilocybin and DOI dose-dependently reversed mechanical and cold hypersensitivity in the chemotherapy-induced peripheral neuropathy (CIPN) mouse model with different time-course of action. Similarly, psilocybin and DOI dose-dependently reversed thermal hypersensitivity in the chronic inflammatory mouse model of Complete Freud's Adjuvant (CFA). The effects of Psilocybin and DOI in both models were mediated by activation of 5-HT2A receptors (5-HT2AR). Overall, the present study suggests that classical psychedelics psilocybin and DOI are effective in reducing pain-like behaviors via 5-HT2AR activation in two mouse models of chronic pain.