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.
A single dose of psilocybin produced a sustained reduction in pain sensitivity in a mouse model of chronic neuropathic pain. Additionally, this single dose dramatically increased the pain-relieving effect of gabapentin, a common neuropathic pain medication. These findings suggest that psilocybin may induce lasting changes in neural network processing that enhance the effectiveness of existing treatments.
A single dose of psilocybin produced a sustained anti-nociceptive effect in a mouse model of chronic neuropathic pain, in both male and female mice. This effect was mediated by 5-HT2A receptors, though other mechanisms may also contribute. Psilocybin also significantly increased the anti-nociceptive potential of gabapentin, a common neuropathic pain treatment, suggesting longer-lasting changes in network processing. These findings provide the first preclinical evidence that psilocybin could be a valuable approach for treating chronic pain from nerve injury and serve as a new therapeutic addition for pain management.