Human Data Hint at Psilocybin's Potential Against Inflammation

Classic psychedelics such as psilocybin and LSD bind tightly to serotonin receptors known as 5-HT2A, which are dense in some brain structures but also present on many cells and tissues outside the brain. The findings come from a small pilot study led by researchers at the University of California, San Francisco, to evaluate the feasibility and safety of giving psilocybin to people with Parkinson's disease. The study included 12 participants. People with neurodegenerative disease and inflammatory conditions are typically excluded from trials of psychedelics for mental health because of safety concerns.

The UCSF team used blood tests to measure five signaling molecules involved in inflammation before and after two psilocybin sessions. Participants had significantly lower inflammation levels after treatment than at baseline, and the changes persisted a month after their final dose. The researchers also tracked a blood marker of mitochondrial stress; it showed substantial improvement immediately after psilocybin, though not during longer-term follow-up.

"This gives us an initial biological signal to investigate," said Dr. Ellen Bradley, an associate professor of psychiatry at UCSF who helped lead the analysis. The original study, published last year, assuaged researchers' concerns about risks, Bradley said; they found a "really promising safety profile" and that "symptoms even seemed to get a bit better."

The researchers emphasized that the study has limitations: there was no control group, and participants knew they were receiving the drug. Aoife O'Donovan, a professor of psychiatry and behavioral sciences at UCSF and co-author of the paper, said the blood data still needs to be confirmed in follow-up studies before definitive claims. Still, O'Donovan said the findings reflect "objective markers" that changed over time and give the team confidence to pursue this line of research.

Parkinson's disease is characterized by dysregulated inflammation and mitochondrial dysfunction. Bradley said the data suggest these improvements in inflammation and cellular stress could be why participants appeared to benefit from the drugs during the trial. D. Parker Kelley, a research scientist in the Mitochondrial PsychoBiology group at Columbia University and a first author on the paper with Bradley, said the results raise the proposition that psychedelics may help address problems with inflammation and the immune system seen in many diseases. "It's a potential jumping off point for a lot more research in this area," he said, "that may apply not only to Parkinson's, but also neuropsychiatric disorders like depression and anxiety, and even cardio-metabolic and inflammatory disorders."

Charles Nichols, a professor of pharmacology, biochemistry and experimental therapeutics at LSU Health Sciences Center in New Orleans, did not work on the study. He said previous studies that looked at biomarkers of inflammation after psilocybin generally included healthy volunteers, not people with real disease. "I think it's really exciting," Nichols said. His lab discovered about 15 years ago that certain psychedelics could have powerful anti-inflammatory effects, based on lab-grown cell culture that simulated inflammation of blood vessels and hardening of arteries, or atherosclerosis. In that experiment, a psychedelic acting on 5-HT2A receptors functioned as a "potent anti-inflammatory" even at doses well below what would cause a psychoactive trip, he said. Since then, Nichols' group has run numerous experiments in animal models of disease including asthma, arthritis and cardiovascular disease.