Psilocybin ameliorates neuropathic pain-like behaviour in mice and facilitates gabapentin-mediated analgesia
OpenAlex – September 17, 2025
Source: OpenAlex
Summary
A single dose of psilocybin, a psychedelic compound, provided sustained pain relief in a model of chronic nerve injury pain in mice. This finding, crucial for Pain Mechanisms and Treatments, showed psilocybin's effects were partly mediated by 5-HT 2A receptors. Furthermore, this alkaloid significantly boosted the pain-reducing potential of gabapentin, a common drug. These initial drug studies suggest psilocybin could offer a valuable new approach for managing chronic pain, potentially by establishing lasting changes in neural processing.
Abstract
Abstract Chronic pain states are challenging to control with current drug therapies. Here, we demonstrate that a single dose of psilocybin can produce a sustained anti-nociceptive effect in a model of chronic neuropathic pain in male and female mice. Psilocybin anti-nociceptive effects were mediated by 5-HT 2A receptors, although additional mechanisms might also be involved. Furthermore, a single dose of psilocybin caused a significant increase in the anti-nociceptive potential of gabapentin, a widely used treatment for neuropathic pain consistent with the establishment of longer lasting changes in network processing. Overall, these findings present 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.