# Psilocybin and Chronic Pain: A New Perspective for Future Pain Therapists?

## TL;DR

Psilocybin, a psychedelic compound, may offer a new approach for treating chronic pain by targeting both physical and emotional aspects.

## Contribution

This review highlights psilocybin's potential as a multidimensional therapy for chronic pain through preclinical and clinical evidence.

## Key findings

- Psilocybin promotes synaptogenesis and reduces neuroinflammation, leading to analgesic and anxiolytic effects in animal models.
- Early clinical trials suggest improvements in mood, resilience, and quality of life for patients with chronic conditions.
- Persistent antinociceptive responses were observed in models of neuropathic and inflammatory pain.

## Abstract

Background: Chronic pain affects nearly one in five adults worldwide and remains a major healthcare burden due to its persistence, multidimensional impact, and resistance to conventional therapies. The opioid crisis has further highlighted the urgent need for safer and more effective alternatives. Psilocybin, a serotonergic psychedelic compound, has re-emerged as a potential therapeutic option for chronic pain given its effects on neuroplasticity, neuroinflammation, and emotional regulation. Methods: This narrative review synthesized evidence from published preclinical and clinical studies. The focus was on the mechanisms of action of psilocybin, animal models of neuropathic and inflammatory pain, and early human trials exploring its effects on pain, mood, and quality of life. Results: Preclinical studies demonstrated that psilocybin promotes synaptogenesis via BDNF-TrkB signalling, modulates 5-HT2A receptor activity, and reduces neuroinflammatory processes, leading to persistent analgesic and anxiolytic effects. Animal models of chemotherapy-induced neuropathy and inflammatory pain showed long-lasting antinociceptive responses. Clinical studies, though limited, reported improvements in depression, anxiety, resilience, and quality of life in patients with advanced cancer and chronic conditions, with preliminary evidence of analgesic benefit. Conclusions: Psilocybin shows promise as a multidimensional therapy for chronic pain, addressing both sensory and affective components. However, ethical issues, safety concerns, and regulatory barriers necessitate careful management, and robust randomized controlled trials are essential to confirm efficacy and guide clinical translation.