Psilocybin has anti-inflammatory effects in Parkinson’s disease patients; Should 2 million veterans get psychedeli…
Psilocybin has anti-inflammatory effects in Parkinson’s disease patients; Should 2 million veterans get psychedelic treatment?
Plus: 5-MeO-DMT nasal spray shows promise for depression; And is the media overly positive about psilocybin?
Happy Friday and welcome back to The Microdose, an independent journalism newsletter brought to you by the U.C. Berkeley Center for the Science of Psychedelics.
Psilocybin has anti-inflammatory effects in Parkinson’s disease patients
Scientists know that psilocybin acts on 5-HT2A serotonin receptors in the brain, but what about elsewhere in the body? Animal and cellular studies suggest serotonergic psychedelics can reduce inflammation, and some researchers even posit that their anti-inflammatory effects contribute to their clinical efficacy. Now, results from a study published this month in JAMA Psychiatry reveal some of the first evidence in humans of psilocybin’s anti-inflammatory action.
The study stemmed from a trial, published in 2025, looking at safety and feasibility of administering psilocybin therapy to 12 patients with Parkinson’s disease and depression or anxiety. (Inflammation is typical in Parkinson’s disease.) In a secondary analysis, researchers in the present study measured levels of inflammatory markers in blood tests from nine participants, before and after two doses of psilocybin (10 mg and 25 mg, about two weeks apart). They collected blood plasma samples at four time points: before the first dose, one day after each dose, and 30 days after the final dose.
To assess inflammation, the authors measured five biomarkers in the blood that play key roles in the body’s inflammatory response: interleukin (IL)-6, IL-8, tumor necrosis factor α (TNF-α), interferon γ (IFN-γ), and high-sensitivity C-reactive protein (CRP). The researchers found that levels of the inflammation markers in this panel were significantly lower after psilocybin treatment, compared to baseline.
“These participants were relatively healthy for having Parkinson’s,” said Columbia University research scientist Parker Kelley,co-first author on the study, in an interview with The Microdose on Wednesday. “So I was a little surprised that we saw anti-inflammatory effects.”
Perhaps the most critical finding was that the reduction in markers of inflammation persisted 30 days after the last dose of psilocybin, added senior author Aoife O’Donovan,professor of psychiatry and behavioral sciences at the University of California, San Francisco. Moving forward, her team plans to look at inflammatory markers in psychedelics studies of conditions such as chronic pain, bipolar II disorder, and major depression.
“Will this apply to patients with psychiatric disorders who don’t have medical comorbidities, or will this be an effect that we really just see in patients with chronic medical diseases with an inflammatory etiology?” O’Donovan said.
The researchers found improvement in not only inflammation measures, but also in a marker of mitochondrial stress. Mitochondria are responsible for converting nutrients into cellular energy. Mitochondrial stress, which can cause symptoms including fatigue and cognitive issues, can be elevated in Parkinson’s. In the study, one blood protein marker of mitochondrial stress, growth differentiation factor 15 (GDF-15), was significantly lower after both psilocybin doses, but the effect didn’t persist to 30 days post-treatment, the authors found. The trial had a small sample size and no control group, making causal inference limited overall.
Next, the researchers are collecting inflammation data from trial participants with a range of conditions, and they are also recruiting for a larger, follow-up, trial of the Parkinson’s study. “It’ll just be really exciting in the next few years to see what holds in larger samples and with control groups, and what else we learn,” said physician and co-first author Ellen Bradley, an associate professor at UCSF.
SubscribedPsychedelic treatments for more than 2 million veterans?
U.S. Department of Veterans Affairs senior advisor Andrew Gradison caused quite a stir by suggesting up to 2.1 million veterans could benefit from psychedelic treatments. The statement, reported in Politico this week, concerned some, who worry about unchecked hype around psychedelic therapies that have not yet been deemed safe and effective by federal regulators.
At the October ‘Horizons: Perspectives on Psychedelics’ conference in New York City, Gradison told attendees that about one third of the 6.4 million veterans who receive regular care at the VA have conditions such as PTSD and major depression, which psychedelic therapies have shown promise in treating. “So the need is immense,” Gradison said. He said his agency is working to be able to quickly implement the treatments, pending Food and Drug Administration approval.
Gradison’s comments prompted a flurry of pushback. Policy researcher Carolyn D. Gorman, a fellow at the conservative think tank Manhattan Institute wrote on X.
“There is no miracle pill and psychedelics will not be one either. By bowing the government to industry, investor, and drug-using enthusiasts, this work will imperil veterans who are once again being used in a bait-and-switch to legalize drugs,” co-founder of the Foundation for Drug Policy Solutions, Luke Niforatos, wrote on X. The foundation is a national drug policy think tank and advocacy organization. Niforatos’ comments sparked an online argument with Calley Means, who resigned last week as senior adviser at the Department of Health and Human Services. “Nobody said it was a magic pill and it is laughably ignorant for you to say this policy is a cave to industry,” Means wrote.
5-MeO-DMT nasal spray shows promise for depression
A nasal spray delivery of the psychedelic 5-MeO-DMT produces rapid and durable reduction in symptoms of treatment-resistant depression, according to results of a large Phase 2 clinical trial published in JAMA this week. The drug, called ‘mebufotenin’ in the study, has been packaged into a formulation that was recently acquired by pharmaceutical giant Eli Lilly, in their purchase of the psychedelic biopharmaceutical company AtaiBeckley Inc. The drug was previously called BPL-003, a synthetic nasal form of 5-MeO-DMT that received the Food and Drug Administration’s Breakthrough Therapy Designation (which expedites a drug’s review).
BPL-003 is fast acting, with its psychedelic effects fitting into a two-hour clinic session. Thus, the JAMA study authors posit, this mebufotenin nasal spray “may improve treatment access and convenience, requiring a shorter monitoring period and fewer clinic visits compared with psilocybin and esketamine, respectively.”
The trial included 193 participants with treatment-resistant depression, at 38 sites across Australia, Europe, and the US. The researchers examined changes in participants’ total score on the Montgomery-Åsberg Depression Rating Scale after they were randomly assigned to one of three groups, each of which received a dose of 8 mg, 12 mg, or 0.3 mg (essentially a placebo) of the mebufotenin nasal spray. The researchers found a statistically significant difference in depression scores from baseline between both of the higher dose groups and the placebo group, starting the day after dosing, and lasting eight weeks. “These findings suggest that a prolonged psychedelic effect is not required for durable antidepressant efficacy,” the authors write.
Of note, over 70% of participants in all three treatment groups reported adverse events related to the treatment, such as headache and nausea. The vast majority of events were mild to moderate, the authors write.
The trial’s results overall were promising, psychiatrist Chittaranjan Andrade of India’s Manipal Academy of Higher Education writes in an editorial for JAMA, commenting on this study.(Andrade was not an author on the study). However, the patients’ therapeutic response and remission rates were below those seen with treatments like ketamine and electroconvulsive therapy, Andrade writes.
Is the media overly positive about psilocybin?
Scientists recently publisheda sweeping review of psilocybin clinical research and how it was presented in media from 2014 to 2025, in JAMA Network Open. Their assessment of 70 clinical trials and 172 media articles concluded that outlets should be clearer about communicating the limitations of psilocybin trials. (Of note, some of the articles included were from university press offices, which are likely to be biased towards the institution’s research interests.)The authors found the annual amount of both published trials and media articles increased after 2018.
They found depression was the most common condition in both psilocybin trials and media articles, but media articles tended to reference PTSD and anxiety as well, despite limited clinical evidence of the drug showing promise for these conditions. They also found 71% of the media articles had a “favorable tone,” and only 30% mentioned safety. Indeed, 70% of the trials they analysed also showed positive effects, while most also included references to small sample sizes and methodological limitations, and 44% included safety outcomes. Thus, the authors concluded, media and trial reporting of positive indications following psilocybin treatment occurred with similar frequency. Researchers tend to be more cautious in presenting their findings than journalists, who often presented psilocybin’s clinical benefits as established.
“Media coverage can also contribute constructively by avoiding sensationalism and grounding reporting in the best available evidence, including study limitations and remaining uncertainties,” the authors conclude.
Many leaders in Silicon Valley no longer see psychedelics as a threat to American capitalism, but as its savior, writes Loughborough University law professor Kojo Koram in a piece called “Psychedelic Muskism,” for Dissent Magazine.
Voters in Idaho will weigh in on a proposed amendment to their state constitution next week. If passed, House Joint Resolution 4, or HJR 4, will give the Idaho Legislature the sole authority to legalize drugs including marijuana and other psychoactive substances. In doing so, voters would forfeit the chance to legalize such drugs via ballot initiatives in the future, the Idaho Capital Sun reports.
Psychedelic Alpha founder and analyst Josh Hardman published an AI-assisted analysis of over 600 public comments submitted to the FDA in response to their public hearing in September. He concludes they were mostly supportive but divided on subjects like whether psychotherapy should be optional in psychedelic treatments.
Compass Pathways CEO Kabir Nath spoke with Business Insider about the company’s recent hiring spree ahead of the anticipated Food and Drug Administration approval of their COMP360 psilocybin treatment.
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