Scientists from the University of California, San Francisco (UCSF) recently published the results of a pilot study that opens new doors in understanding and potentially treating Parkinson's disease. The research focused on psilocybin, a psychoactive compound present in certain types of mushrooms known as 'magic mushrooms', examining its safety and potential therapeutic effects in patients suffering from this complex neurodegenerative disease.

Parkinson's disease, a progressive disorder primarily affecting the nervous system, manifests through a wide spectrum of symptoms, the most recognizable being motor problems such as tremors, muscle rigidity, slowness of movement, and balance difficulties. It is estimated that in the United States alone, about one million people live with this diagnosis, while global figures reach up to 10 million. The cause of the disease lies in the gradual death of neurons in a specific part of the brain (substantia nigra) responsible for producing dopamine, a key neurotransmitter for controlling movement.

However, Parkinson's disease is not exclusively a movement disorder. It is often accompanied by numerous non-motor symptoms that significantly affect the quality of life of those affected. Among these, mood disorders, such as depression and anxiety, are particularly pronounced, affecting a significant percentage of patients, sometimes up to 50%. Interestingly, these symptoms can appear years before motor problems become evident. In addition, patients may also face cognitive difficulties, sleep problems, fatigue, and loss of smell.

Challenges in Treatment and the Search for New Approaches

Currently available therapies for Parkinson's disease, such as the drug levodopa which compensates for the lack of dopamine, are primarily aimed at alleviating motor symptoms. Although they can be very effective in the earlier stages of the disease, their effectiveness may decline over time, and side effects such as uncontrolled movements (dyskinesia) may appear. More importantly, existing drugs do not stop or slow down the underlying process of neurodegeneration – the death of brain cells.

A particular challenge is the treatment of non-motor symptoms, especially depression and anxiety. Standard antidepressants often do not show satisfactory efficacy in patients with Parkinson's disease, suggesting that mood changes might be an intrinsic part of the neurodegenerative process itself, not just a psychological reaction to the illness. There is a worrying link between low mood and faster physical decline in these patients, making mood disorders a stronger predictor of quality of life than motor symptoms themselves.

In this context, researchers are constantly searching for new therapeutic strategies that could target not only the symptoms but also the potential causal mechanisms of the disease, including neuroinflammation and reduced neuroplasticity (the brain's ability to change and adapt). It is precisely here that psilocybin has entered the scene as a potential candidate.

The UCSF Pilot Study: Safety and Unexpected Results

Given previous research indicating the potential of psilocybin in treating depression and anxiety in other populations, the UCSF team, assembled within the Translational Psychedelic Research Program (TrPR), decided to investigate its application in Parkinson's disease. The primary goal of the initial pilot study was to assess the safety and tolerability of psilocybin in this specific patient group, as it was the first such trial of a psychedelic in individuals with any neurodegenerative disease.

Twelve patients (seven men and five women) with mild to moderate Parkinson's disease participated in the study. The protocol involved receiving a relatively low dose of psilocybin (10 mg), and two weeks later, a higher dose (25 mg). A key part of the protocol was psychotherapeutic support – patients participated in a total of eight psychotherapy sessions, before and after receiving psilocybin. During and after the intervention, researchers carefully monitored for any side effects and assessed changes in mood, cognitive functions, and motor skills.

The results, published in the journal *Neuropsychopharmacology*, exceeded initial expectations focused primarily on safety. Although almost every participant experienced some transient side effects during the action of psilocybin, such as anxiety, nausea, or elevated blood pressure, they were not serious in nature and did not require medical intervention. Most importantly, no worsening of Parkinson's disease motor symptoms was recorded.

What surprised the researchers were the significant positive effects. Participants showed clinically relevant improvements in mood, cognitive functions, and, unexpectedly, also in motor symptoms. These improvements were visible as early as one week after the psilocybin administration and persisted one month later. It is particularly intriguing that the mood improvements remained statistically significant even three months after the intervention, long after the compound itself had been eliminated from the body.

Possible Explanations and Future Directions

Scientists are considering several hypotheses that could explain these promising, albeit preliminary, findings. One possibility is that the primary effect of psilocybin on improving mood indirectly led to improvements in cognitive and motor functions. When patients feel better, they are more motivated to socialize and engage in physical activity, which are key elements of supportive therapy for Parkinson's disease.

Another, more intriguing theory suggests that psilocybin might have more direct, multiple beneficial effects on the brain affected by Parkinson's disease. There are indications that psilocybin, acting primarily on serotonin receptors (especially 5-HT2A), can influence processes of neuroinflammation (inflammation in the nervous system) and promote neuroplasticity. It is thought that reducing inflammation and stimulating the growth of new neural connections could help restore brain circuits involved not only in mood regulation but also in cognitive processes and motor control. Some research suggests that psychedelics can temporarily 'reset' rigid brain patterns associated with depression and other conditions, allowing for the formation of more flexible and healthier connections.

These results open a completely new chapter in the research of therapies for neurodegenerative diseases. "We are still in the very early stages of this work, but this first study went far beyond what we expected," stated Dr. Ellen Bradley, the study's first author and an assistant professor at UCSF.

Expanding Research: A Larger Study on the Horizon

Encouraged by the results of the pilot study, UCSF researchers have launched a significantly larger, randomized controlled trial (RCT). This new clinical trial will include a larger and more diverse number of patients (the goal is 100 participants) and will use advanced techniques to delve deeper into the mechanisms of psilocybin's action. The plan includes the application of non-invasive brain stimulation, neuroimaging methods (such as fMRI and PET scans), and other tools to monitor the impact of psilocybin on inflammatory processes and neuroplasticity in patients' brains.

The study will be conducted at two locations – alongside UCSF, Yale University is also involved. Funding for this more extensive research has been secured from the same anonymous donor who supported the pilot study, as well as from The Michael J. Fox Foundation for Parkinson's Research, the world's leading organization dedicated to finding a cure for this disease.

"The vast majority of brain diseases still lack disease-modifying interventions," emphasized Dr. Joshua Woolley, the study's senior author and director of the TrPR program at UCSF. "We can often treat symptoms, but we don't change the trajectory or prevent decline. Now that's starting to change. These results raise the exciting possibility that psilocybin could help the brain repair itself."

While further caution and rigorous scientific verification through larger studies are needed, these initial findings raise hope that psychedelic therapy, coupled with appropriate psychotherapeutic support, could one day become a valuable tool in combating the complex challenges posed by Parkinson's disease, potentially improving not only mood but also the cognitive and motor functions of those affected.

Source: University of California