UCSD study suggests psilocybin could treat phantom limb pain

State of play: Fadel Zeidan, co-founder and neuroscience director at the Center for Psychedelic Research at UCSD, in 2023 conducted the first randomized controlled trial on the effect of psychedelics on chronic pain.

• Half of the patients took a dose equivalent to 4 or 5 grams of dried mushrooms, while the placebo group took 100 grams of niacin.
• Both underwent three days of preparation with psychologists trained in psychedelic therapy. Following the roughly six-hour psychedelic experience, they underwent a month of ongoing therapy as part of the treatment.

Driving the news: "We just got the results and they're absolutely mind bending, no pun intended," Zeidan told Axios.

• Patients who took psilocybin reported dramatic reductions in the severity of their pain — between 50% and 75% — and the effect of that reduction got stronger the further away they got from the dose.
• The group that took niacin reported a brief reduction immediately after the dose, but their reported pain returned to the previous level two weeks and four weeks after the dose.

Between the lines: Zeidan and fellow researchers theorize that phantom pain is tied to unresolved trauma from the accident that led to the amputation, and the amputation itself.

• The body continues sending pain signals to the brain, indicating that something is wrong and help is needed.
• "What we think is happening is, the large dose is resetting this system," he said. "It's like an Etch-a-Sketch, which can potentially lead to the eradication of the pain.

The intrigue: That system reset, Zeidan said, is analogous to an "aha moment" in psychology, an insight that shifts a person's thinking and leads to relief from depression or anxiety.

• Brain imaging analysis from the study participants showed that when there was a larger reduction in activity within neural networks associated with self-confidence and personal value, there was a greater reduction in pain relief.

What they're saying: "These ego-centric appraisals of their amputation experience were dramatically diminished in the context of the psychedelic experience, which is remarkably consistent with what indigenous populations have been telling us for thousands of years," he said.

• "The brain is rewiring itself after the dosage, and the more the rewiring in certain parts of the brain, the greater the pain relief," he said.

The bottom line: The first phase of the trial was small — just five patients who took mushrooms, and four who took niacin.

• The researchers are now moving to a phase two trial, and are actively seeking patients to experiment with 25 to 30 people in each group, in hopes that a larger sample will allow them to make more confident conclusions.
• They'll also measure pain responses beyond one month after the dose.

What's next: The first study has been submitted for publication and is under peer review.

Flashback: The seeds of the study grew from the experience of Albert Yu-Min Lin, a UCSD researcher and National Geographic explorer whose lower right leg was amputated.

• Suffering from debilitating pain and repeated failed treatments, Lin drove to Joshua Tree, and took mushrooms that eliminated his pain. His case study, published in Neurocase, has been regularly cited and jump started psychedelic research at UCSD.

Context: There had been small studies into the effects of psychedelics on phantom limb pain in the 60s and 70s.

• But that era of research into psychedelics "became taboo when the scientists themselves became zealots, and their subjective biases were contaminating the objectivity of the science," Zeidan said.
• The field effectively disappeared for a few decades, until Roland Griffiths revived it at Johns Hopkins by studying the effects of psychedelics on terminally ill cancer patients, with a landmark 2006 study.
• Michael Pollan's 2018 book on the topic, "How to Change Your Mind," broke through with a mainstream audience and made it easier to pursue serious research, Zeidan said.

Go deeper: Watch Zeidan discuss his study and the implications related research holds for pain management, at a recent Axios event.