Psilocybin as a novel treatment for chronic pain

Psychedelic drugs are being considered for clinical use, particularly as anti-nociceptive treatments for chronic pain and co-morbid depression. This review examines preclinical animal models used to study psilocybin's potential as an anti-nociceptive agent. Initial studies in animal models of neuropathic and inflammatory pain are summarized, highlighting areas needing further research. Potential mechanisms include activation of 5-HT2A receptors in serotonergic pathways at spinal and central levels, and neuroplastic actions that improve functional connectivity in brain regions involved in chronic pain. Current clinical aspects and the translational potential of psilocybin from animal models to chronic pain patients are reviewed. Psilocybin is discussed as an ideal anti-nociceptive agent with broad effects against chronic pain and its inflammatory or emotional components.

Study at a glance

Abstract

Abstract Psychedelic drugs are under active consideration for clinical use and have generated significant interest for their potential as anti‐nociceptive treatments for chronic pain, and for addressing conditions like depression, frequently co‐morbid with pain. This review primarily explores the utility of preclinical animal models in investigating the potential of psilocybin as an anti‐nociceptive agent. Initial studies involving psilocybin in animal models of neuropathic and inflammatory pain are summarised, alongside areas where further research is needed. The potential mechanisms of action, including targeting serotonergic pathways through the activation of 5‐HT 2A receptors at both spinal and central levels, as well as neuroplastic actions that improve functional connectivity in brain regions involved in chronic pain, are considered. Current clinical aspects and the translational potential of psilocybin from animal models to chronic pain patients are reviewed. Also discussed is psilocybin's profile as an ideal anti‐nociceptive agent, with a wide range of effects against chronic pain and its associated inflammatory or emotional components.