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.
This editorial introduces a themed journal issue on psychedelic and related drugs as potential therapies for a wide range of difficult-to-treat conditions beyond neuropsychiatric disorders. The collection includes reviews and original articles covering the mechanistic basis of how these drugs act, the current status of preclinical research, progress in clinical trials, and insight into regulatory processes for clinical approval. The editorial provides an overview of current controversies and challenges in the field while highlighting the exciting potential these drugs offer.