What’s so magical about mushrooms? Could “magic mushrooms,” or psilocybin, help Parkinson’s? What research is happening in this space?
To answer these questions and more, I spoke with Ellen Bradley, MD, a psychiatrist and researcher at the University of California, San Francisco (UCSF). Dr. Bradley is leading a clinical trial to test psilocybin for depression in people with Parkinson’s disease (PD). The Michael J. Fox Foundation recently funded the continued development and expansion of this trial to a second site at Yale University in Connecticut.
Rachel Dolhun, MD, DipABLM (RD): Let’s start big picture. Psilocybin is a “psychedelic.” What does that mean?
Ellen Bradley, MD (EB): People debate this quite a bit! Very broadly, a psychedelic is a compound that alters consciousness — impacting our sensory perception, mood and cognition (memory and thinking). Often the term psychedelic is used more specifically to refer to drugs that produce those consciousness-altering effects primarily by interacting with serotonin receptors in the brain.
What individuals experience when they take a psychedelic can vary widely based on the specific drug, the dose, the person and the setting in which the drug is taken. Some people might have positive — even transformative — experiences, feeling intense euphoria, awe or a sense of unity. Others might feel anxious or like they leave their body, which can, of course, be scary and destabilizing.
RD: Tell us more about psilocybin.
EB: Psilocybin is a psychedelic compound that’s found in hundreds of types of mushrooms. It has been used as part of religious and healing traditions for probably thousands of years and has cultural significance for some Indigenous groups in the Americas. When you consume psilocybin, it starts working in about 20 minutes and the intoxicating effects last about six hours. What’s interesting is that some people can experience benefits from psilocybin therapy that last a lot longer than this “trip” — for weeks or even months.
There’s a lot we don’t know about psilocybin and how it might work. We know that, at a molecular level, psilocybin activates serotonin receptors. The serotonin system is important for regulating mood and many other brain functions. And from pre-clinical (non-human) research, we’ve also learned that psilocybin’s activation of those serotonin receptors kicks off a cascade of other changes in the brain. These include increased expression of genes that support neuron (brain cell) health and decreased inflammation. Other researchers have seen that psilocybin changes the way different regions of the brain connect to one another. We don’t know exactly how all of these effects may lead to improvements in depression and other symptoms. One hypothesis is that psilocybin opens a window where the brain has a turbocharged capacity for change — and that might be why the benefits can last a long time.
RD: Why might psilocybin work for Parkinson’s?
EB: Our current study focuses on using psilocybin to treat depression in Parkinson’s, but it’s possible that one of the reasons so many people with PD experience depression is because mood changes could be related to the neurodegenerative (brain cell loss) process that causes the disease. So we want to find out if psilocybin therapy can improve depression and if it can potentially impact some of the drivers of neurodegeneration. The lab data I mentioned are intriguing — psilocybin has potent anti-inflammatory actions and an ability to boost neuroplasticity, changing the brain’s structure (cells) and function (cell connections and pathways). Could these effects dampen the brain inflammation that contributes to neurodegeneration and strengthen connections between neurons (brain cells) that are weakening? We have a lot of work ahead to figure out if that’s possible.
Clinical research in people without Parkinson’s suggests that psilocybin may ease depression and other symptoms quickly and for some time. After only one dose of psilocybin, people have reported rapid improvement in depression lasting a month or more. Regardless of how psilocybin therapy might work, this is very compelling since available antidepressants typically take at least six to eight weeks to work.
None of the clinical trials to date have enrolled people with Parkinson’s. So that’s where we’re starting — testing psilocybin for depression in people with Parkinson’s. Mood changes affect many in the PD community and these changes can have negative impacts. Depression in PD is linked to faster physical and cognitive decline, and it can lead to isolation and low quality of life. And, unfortunately, our current treatments are somewhat limited.
RD: Tell us about the research on psilocybin for Parkinson’s.
EB: This is uncharted territory, so we want to move forward thoughtfully. We have an incredible team that makes sure participant safety is always front of mind. There’s a lot of excitement and potential but also a deep respect for a complex drug that impacts the brain and nervous system.
Our first step was a small, open label (everyone got drug and knew they were getting drug) pilot study. We tested the safety and tolerability of psilocybin in 12 people with Parkinson’s plus depression and/or anxiety.
With positive results from that study, we’re now running a trial that will enroll 100 people with early to moderate Parkinson’s and depression. Our main goal is to assess the safety and efficacy of psilocybin therapy. But we’ll also look at the potential broader effects on other Parkinson’s symptoms, quality of life, and more. And we’ll explore how the drug works using brain imaging, markers of inflammation and other tests.
The trial and participants’ experiences on psilocybin are carefully thought out and monitored. As I mentioned, the effects of psilocybin can vary widely based on the person, their mindset and the setting in which they take the drug. We work hard to maximize safety in several ways, one of which is to couple psilocybin with psychotherapy, or talk therapy. Participants meet with a therapist before, during and after taking psilocybin to guide them through the whole experience. All participants get synthetically made psilocybin (so we know exactly what the doses are) in a quiet space on our research unit with a therapist and physician on-site. We’ll ideally follow everyone who participates for several years to understand the impact of the treatment on depression and other aspects of PD.
Learn more about this ongoing trial, which is now recruiting participants at UCSF and soon will also begin recruiting volunteers at Yale.
RD: As research moves forward, many are eager to know what they can do now. There’s a lot of buzz around “microdosing,” for example. What should people know about this?
EB: Microdosing is taking very small amounts of psilocybin — much lower than what has been studied in clinical trials — more frequently. The effects of microdosing are not well understood. There hasn’t, to my knowledge, been any research on psilocybin microdosing in people with Parkinson’s. And there isn’t yet even agreement on how much a “microdose” of psilocybin should be.
There has been a lot of positive information about psychedelics in the media. And because psilocybin comes from nature, sometimes people are led to believe it’s always safe or beneficial. But the truth is, it may have downsides, like interactions with other medications, worsening of symptoms like hallucinations, or even negative effects on the heart.
Treatment is never a one-size-fits-all — we want to learn more about psilocybin and other psychedelics so we can offer the right therapy for the right person at the right time.
As always, talk with your doctor about options — or what you are trying on your own — to best control your Parkinson’s symptoms.
The Michael J. Fox Foundation is also funding a trial of ketamine for depression in people with Parkinson’s. Ketamine is another type of psychedelic, which is approved as an anesthetic agent.
