Psilocybin Tied to Lower Inflammation in Parkinson’s Trial

Markers of systemic inflammation and mitochondrial stress were reduced after psilocybin therapy in Parkinson’s disease patients with mood dysfunction, a small nonrandomized trial showed.

Relative to baseline, an inflammatory index was significantly lower at all follow-up time points after psilocybin was administered, reported Ellen Bradley, MD, of the University of California San Francisco (UCSF), and co-authors.

The standard mean difference (SMD) was -0.72 (adjusted P=0.003) 1 day after 10 mg of psilocybin, Bradley and colleagues wrote in a JAMA Psychiatry research letter.

One day after 25 mg of psilocybin, the SMD was -0.60 (adjusted P=0.02), and 30 days after 25 mg, the SMD was -0.62 (adjusted P=.047).

The results support the researchers’ parent trial, which showed an association between psilocybin therapy and reduced depression, anxiety, and motor symptoms in Parkinson’s patients.

“To our knowledge, this is the first report of changes in these types of markers after psychedelic treatment in people with a neurodegenerative disease,” Bradley told MedPage Today. “That gives us and other researchers super-interesting biological questions to pursue: What could be producing these changes, are they consistent in larger groups of people, and do they have anything to do with clinical benefits people with Parkinson’s might experience with psilocybin?”

This research comes as part of a series of studies examining the biological effects of psychedelics as potential therapeutics for non-psychiatric conditions, said Albert Garcia-Romeu, PhD, of the Johns Hopkins University School of Medicine in Baltimore, who wasn’t involved with the study. It also comes on the heels of work showing that psilocybin appeared to block nerve damage related to chemotherapy in mice, he pointed out.

Much of the work looking at psilocybin or LSD has focused squarely on mental health conditions like depression, anxiety, or addiction, Garcia-Romeu noted. “However, this study is in patients with a neurological condition — Parkinson’s disease — and shows evidence that psilocybin may have impacted biological markers of inflammation and mitochondrial stress,” he told MedPage Today.

“These new data suggest biological effects of psychedelics could be driving potential benefits in patients and pave the way for more work to better understand how psilocybin might be a useful therapeutic both in psychiatric and non-psychiatric conditions,” he added.

In their open-label trial, Bradley and colleagues studied 12 people with mild-to-moderate Parkinson’s disease ages 40 to 75. Participants received 10-mg and 25-mg doses of oral synthetic psilocybin approximately 2 weeks apart.

The researchers collected plasma samples from nine participants at four time points: baseline, 1 day after each psilocybin administration, and 30 days after the 25-mg dose.

The primary outcome to assess systemic inflammation was a proinflammatory index calculated as the mean z score of interleukin (IL)-6, IL-8, tumor necrosis factor alpha, interferon gamma, and high-sensitivity C-reactive protein concentrations. Mitochondrial stress was evaluated with growth differentiation factor 15 (GDF-15) and fibroblast growth factor 21 (FGF-21) measurements.

Components of the index, including IL-6, were significantly lower 1 day after the 10-mg dose but at no other time points. IL-10 was significantly higher 1 day after the 10-mg dose but not at other times.

GDF-15 was significantly lower relative to baseline 1 day after each psilocybin administration, but not from baseline 30 days after the 25-mg dose. FGF-21 was higher 1 day after each psilocybin administration, but this finding was not significant.

This was a small study of psilocybin therapy and results must be interpreted cautiously, noted co-author Aoife O’Donovan, PhD, also of UCSF. “However, the results are highly promising and suggest that more research in this area is warranted,” she told MedPage Today. “We are already following this study up with more in-depth analyses of the effects of psilocybin therapy on inflammation and mitochondrial stress in a randomized controlled trial in patients with Parkinson’s disease.”

Work from Garcia-Romeu’s lab also is studying psilocybin in a trial of people with mild cognitive impairment or early-stage Alzheimer’s disease and depression. “To date, we’ve treated 18 individuals in that study, and enrolled 19 of a targeted 20 patients,” he said. “We plan to complete the trial and publish our findings next year.”