A single dose of psilocybin produces a sustained anti-nociceptive effect in chronic neuropathic pain models in male and female mice, mediated primarily by 5-HT2A receptors. Psilocybin significantly potentiates the analgesic efficacy of gabapentin, a standard-of-care treatment, representing the first preclinical evidence that a psychedelic can serve as a pain-network primer for existing analgesics. This finding suggests a novel therapeutic strategy, particularly for the 30-50% of neuropathic pain patients who fail gabapentin monotherapy. The data demonstrate that a single psilocybin injection produces sustained month-long changes that enhance gabapentin efficacy in a preclinical model.
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.