Efforts to understand how classic psychedelics like psilocybin and LSD summon powerful changes in consciousness tend to focus on what's happening inside our head.
That's because these compounds bind tightly to serotonin receptors that densely populate certain structures of the brain, and a growing number of studies demonstrate they can exert long-lasting changes in mental health and well-being for people with a range of psychiatric conditions.
Increasingly researchers have started to probe how these drugs elicit other physiological changes, given that many cells and tissues beyond the brain possess those same receptors, known as 5-HT2A.
Now, new research offers some of the first evidence in humans that psychedelics may also hold potential for treating diseases characterized by inflammation and immune dysregulation throughout the body.
The data, published Wednesday in the medical journal JAMA Psychiatry, draws from a small pool of patients with Parkinson's disease, but it reflects what's been observed in lab studies with animal and cell models for years. For certain diseases, psychedelics appear to combat inflammation and even help restore stressed mitochondria, the energy-producing factories of the cells.
The team at the University of California, San Francisco, who conducted the study, used blood tests to measure five different signaling molecules involved in inflammation in participants, both before and after two sessions with psilocybin.
The participants had significantly lower levels of inflammation following the treatments, compared to baseline, and those changes persisted a month after their final dose of psilocybin. The researchers also tracked a blood marker of mitochondrial stress. Here, too, there were substantial improvements immediately after participants were given psilocybin, though not during the longer-term follow up.
"This gives us an initial biological signal to investigate," says Dr. Ellen Bradley, an associate professor of psychiatry at UCSF who helped lead the analysis.
The findings were based on 12 participants in a pilot study to evaluate the feasibility and safety of giving psilocybin to people with Parkinson's disease. Patients with neurodegenerative conditions are typically excluded from trials on psychedelics and mental health for safety concerns.
The findings of the original study, which were published last year, assuaged researchers' concerns about the risks. Bradley says they found a "really promising safety profile" and that "symptoms even seemed to get a bit better."
The researchers emphasize that the study has limitations: they did not have a control group, and the participants knew they were receiving the drug. So the data on what was happening in their blood needs to be confirmed in follow-up studies before making definitive claims, says Aoife O'Donovan, a professor of psychiatry and behavioral sciences at UCSF and co-author of the paper.
Still, O'Donovan says the findings reflect "objective markers" that changed over time and that gives them confidence to pursue this line of research.
Parkinson's disease is characterized by dysregulated inflammation and mitochondrial dysfunction. This data, Bradley notes, could help explain why the participants appeared to benefit from the drugs during the trial.
Beyond that, the results raise the proposition that psychedelics may help address others diseases that are characterized by troubles with inflammation, says D. Parker Kelley, a research scientist in the Mitochondrial PsychoBiology group at Columbia University who was a first author on the paper with Bradley.
"It's a potential jumping off point for a lot more research in this area," he says, "that may apply not only to Parkinson's, but also neuropsychiatric disorders like depression and anxiety, and even cardio-metabolic and inflammatory disorders."
While previous studies have looked at biomarkers of inflammation after psilocybin, those have generally included healthy volunteers – not people with real disease, says Charles Nichols, a professor of pharmacology, biochemistry and experimental therapeutics at LSU Health Sciences Center in New Orleans.
"I think it's really exciting," says Nichols, who didn't work on the study, but whose lab discovered that certain psychedelics could have powerful anti-inflammatory effects about fifteen years ago.
That insight came from studying lab-grown cell culture that simulated inflammation of blood vessels and hardening of arteries, also known as atherosclerosis.
In that experiment, they found a psychedelic acting on the 5-H2TA receptors functioned as a "potent anti-inflammatory," even at doses well below what would cause a psychoactive trip, he says.
Since then, Nichols' group has run numerous experiments in animal models of disease including asthma, arthritis, and cardiovascular disease, but the field has needed to test whether these protective effects hold up in humans.
He says this new study in Parkinson's patients is a proof of principle.
"We can only draw so much from those conclusions," he says. "But I do think it validates a lot of the pharmacology that we've been doing over the last 15 years on the anti-inflammatory, the mitochondrial protective effects."
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