Chronic pain affects about 1.5 billion people worldwide. Current treatments like opioids and non-opioid drugs can cause side effects, addiction, or fail to relieve pain. Psychedelics such as LSD and psilocybin may alter pain perception through serotonin receptor activation, anti-inflammatory effects, and synaptic remodeling. This scoping review identified 21 human studies on psychedelics for pain. Few clinical trials exist, and sample sizes are small, limiting clinical use. Overall, psychedelics show promise for analgesia in certain headache disorders and cancer pain. Future research should examine combining psychotherapy with psychedelics for chronic pain.
A proposed clinical trial design for psilocybin as a treatment for neuropathic pain, called the PEACE-PAIN trial, is supported by patient survey responses but could be improved by adding detailed discussions of the existing evidence on efficacy, safety, tolerability, and management of adverse effects. The finding that individuals with prior psychedelic use are interested in participating has important implications for the trial's inclusion and exclusion criteria.
Chronic pain affects about 8 million Canadians (20%) and costs the healthcare system over US $60 billion yearly. This paper describes the planned protocol for a pilot randomized controlled trial testing three treatments: intravenous ketamine alone, cognitive behavioral therapy with mindfulness meditation (CBT/MM), or a combination of both. The primary goal is to assess feasibility—recruitment, consent, withdrawal, adherence, missing data, and adverse events—in 30 participants over 20 weeks. Secondary outcomes include changes in pain intensity and pain interference at week 20. Recruitment had not started as of November 2023; the study is expected to complete by December 2025. Results will inform a larger trial.
All participants reported decreased pain with ketamine infusions, though pain experiences varied. To improve ketamine's benefit for chronic neuropathic pain, it is important to address stigma, research ways to extend the duration of its effects, and provide a safe treatment environment. Understanding barriers and facilitators, along with implementing participant suggestions, can inform ketamine programs, improve access to pain management, and guide future research.