A clinical trial from UC San Diego has found that psilocybin, the psychoactive compound in magic mushrooms, could provide lasting relief for amputees suffering from phantom limb pain, which affects 60-80% of amputees and has no reliable cure.
Psilocybin mushrooms.
Dr. Fadel Zeidan, co-founder of UCSD’s Center for Psychedelic Research, led the first-ever randomized controlled trial on psychedelics for chronic pain. Participants took either a high dose of psilocybin, equivalent to 4 to 5 grams of dried mushrooms, or a placebo dose of niacin. Both groups underwent three days of psychological preparation before their psychedelic session, followed by a month of integration therapy.
The results were remarkable.
“We just got the results, and they’re absolutely mind-bending,” Zeidan told Axios. Patients who took psilocybin reported a 50-75% reduction in pain severity, which grew stronger over time. The placebo group experienced only brief relief before returning to baseline.
Zeidan and his team believe phantom limb pain is linked to unresolved trauma from the amputation. The nervous system keeps sending distress signals, as if the missing limb were still there.
“What we think is happening is, the large dose is resetting this system,” Zeidan explained. “It’s like an Etch-a-Sketch, potentially leading to the eradication of the pain.”
Brain imaging revealed that greater reductions in activity in self-identity-related neural networks correlated with greater pain relief.
“These ego-centric appraisals of their amputation were dramatically diminished in the psychedelic experience, aligning with what indigenous cultures have long understood,” Zeidan said. “The brain is rewiring itself after the dosage, and the more rewiring we see, the greater the pain relief.”
Though the initial trial was small—five patients received psilocybin, four took niacin—it has paved the way for a larger phase-two trial involving 25-30 participants per group, which is actively seeking participants. Researchers will also study pain responses beyond one month to assess long-term effects. The initial findings are under peer review.
The study was inspired by UCSD researcher and National Geographic explorer Albert Yu-Min Lin, who suffered from severe phantom limb pain after his lower right leg was amputated. After years of failed treatments, Lin took mushrooms in Joshua Tree and found his pain disappeared. His case study, published in Neurocase, helped revive psychedelic research at UCSD.
While psychedelics were studied for phantom limb pain in the 60s and 70s, research stalled when scientists became advocates rather than objective researchers. The field regained legitimacy with Roland Griffiths’ groundbreaking 2006 Johns Hopkins study on psychedelics for terminally ill patients. Michael Pollan’s 2018 book How to Change Your Mind further pushed the conversation into the mainstream.
As the UCSD team prepares for its next trial, Zeidan remains hopeful that psilocybin could revolutionize pain management.
