Psilocybin May Hold Key to Treating Mood, Cognition, and Motor Symptoms in Parkinson’s Disease

A preliminary pilot study has discovered that psilocybin—the primary psychoactive component in magic mushrooms—might enhance both mood as well as cognitive and motor functions in people suffering from Parkinson’s disease. This outcome astonished the researchers, whose initial objective was merely to assess the medication's safety. However, subjects reported significant enhancements that persisted for several weeks after just one high dose administration. These outcomes have been detailed in Neuropsychopharmacology , marking the initial instance of testing a psychedelic substance in individuals diagnosed with any form of neurodegenerative disease.

Parkinson’s disease is most recognized for its motor symptoms like shaking, rigidity, and slow movements. However, numerous individuals affected by this condition also grapple with depression and anxiety, conditions that frequently start several years prior to the emergence of motor signs. These emotional challenges aren’t merely upsetting; they're closely associated with quicker deterioration physically and diminished general well-being. Common therapies for depression and anxiety, including antidepressant medications, tend to be less effective in those who have Parkinson’s, underscoring the critical need to find alternative treatment approaches.

Psilocybin is a natural psychedelic substance that transforms into psilocin within the human body. This process leads to interactions between psilocin and serotonin receptors in the brain. Research involving individuals suffering from severe depression and those experiencing anxiety due to terminal illnesses has demonstrated that just one administration of psilocybin combined with therapy can result in swift and enduring enhancements in emotional well-being. Experts theorize that this medication might facilitate the formation of fresh neural pathways—a characteristic known as neuroplasticity. Such impacts could hold particular significance for patients diagnosed with Parkinson’s disease, characterized by disturbances in serotonin transmission, inflammatory responses, and diminished neural linkages—elements potentially contributing to issues related to mental state and physical movement alike.

The research group at the University of California, San Francisco embarked on studying the safety and tolerability of psilocybin among individuals affected by Parkinson's disease, considering the intricate neurobiological aspects involved as well as worries over potential drug interactions and an increased risk of psychosis. The study included 12 volunteers aged 40 to 75 who suffered from mild to moderate Parkinson’s disease and also exhibited signs of either depression or anxiety according to clinical assessments. Individuals displaying substantial cognitive decline, current psychotic conditions, or additional health hazards were not considered eligible for participation. A majority of these participants were undergoing treatment involving levodopa, which is typically prescribed to control movement-related issues associated with Parkinson’s.

Every participant engaged in two monitored psilocybin sessions conducted within the research facility at UCSF. Initially, they received a smaller, safety-oriented dosage of 10 milligrams, then approximately two weeks later, a larger therapeutic amount of 25 milligrams. Each session included several accompanying psychotherapy appointments both prior to and following the dosing. Throughout these experiences, the therapists offered preparatory guidance, emotional assistance during the process, and post-session integration help.

The investigators employed various evaluations to monitor the impact of psilocybin. This encompassed conventional clinical assessment tools for both motor and non-motor signs of Parkinson’s disease, as well as tests gauging mood, anxiety levels, cognitive abilities, and observations made by caregivers. Throughout the sessions, safety parameters were closely tracked, such as monitoring blood pressure, heart rate, and documenting any unfavorable psychological or physiological reactions.

The research indicated that psilocybin was mostly well-tolerated. During the sessions, typical side effects were minor anxiety, nausea, along with brief spikes in heart rate or blood pressure. Two individuals experienced severe anxiety in one session; for one participant, this also led to a short-term increase in trembling and heightened contemplations about mortality linked to potential future disabilities. Nonetheless, there were no significant negative incidents, and the tendency towards suicidal thinking lessened following the therapy.

In addition to enhancing safety, the study revealed various advancements spanning multiple symptom categories. Individuals noted considerable decreases in depression and anxiety levels just one week following the high-dose session, with these enhancements persisting through the three-month check-in. Improvements were also seen in motor-related issues, assessed via participant feedback and professional evaluations alike. This encompassed less frequent daily motor challenges along with better performance on motor exams. The extent of these positive changes surpassed benchmarks deemed clinically substantial.

Cognitive abilities enhanced across multiple areas as well. The individuals demonstrated superior performance on assessments related to memory, spatial working memory, and cognitive flexibility. These improvements persisted even one month following the psilocybin session. Notably, feedback from caregivers indicated significant alterations too. Close relatives observed that participants experienced reduced distress due to neuropsychiatric symptoms and exhibited decreased behavioral problems. Additionally, they reported considerable contentment with the therapy provided.

The enhancements in mood align with previous studies conducted on depression; however, the positive impacts on motor functions and cognitive abilities came as a surprise. The researchers propose various potential reasons for these findings. They speculate that psilocybin might have an immediate effect on dopamine and serotonin pathways, which could enhance motor skills. Additionally, they consider that alleviating depressive states—often linked to heightened levels of stress and physiological alterations that exacerbate bodily ailments—could lead to better motor outcomes. Lastly, another hypothesis posits that psilocybin could alter the progression of the condition itself via mechanisms such as reducing inflammation, promoting neuroplasticity, or correcting dysfunctions within neurological networks affected by Parkinson’s disease.

We are still in the initial phases of this research, yet our pilot study exceeded all expectations," stated Ellen Bradley, the lead author of the paper and an assistant professor as well as the associate director of UCSF’s Translational Psychedelic Research Program (TrPR). "It often goes unnoticed, but emotional symptoms associated with Parkinson’s disease can accelerate physical deterioration. In fact, these non-motor symptoms have a more significant impact on patients' overall quality of life compared to movement-related issues.

However, this study comes with notable constraints. Given just 12 participants and the absence of a placebo group, the conclusions should be approached carefully. The potential influence of expectancy effects along with the strong psychological setting during therapy sessions might have played a role in the noted enhancements. Additionally, since individuals with more severe conditions or serious health issues were not included, it remains uncertain how broadly applicable these outcomes are. Upcoming studies ought to incorporate broader and bigger groups to gain deeper insights into both the advantages and disadvantages involved.

Motivated by the outcomes of this initial research, scientists have initiated an expanded randomized controlled trial with 100 subjects at two locations: UCSF and Yale University. In this subsequent investigation, they will incorporate brain scans, non-invasive techniques for stimulating the brain, along with blood examinations to better understand the impact of psilocybin on both the brain and the immune system. Their aim is to elucidate the underlying biological processes responsible for these therapeutic advancements and assess if psilocybin might eventually be integrated into treatments for Parkinson’s disease.

The overwhelming number of neurological disorders still do not have treatments that modify their progression," stated the study's lead researcher, Joshua Woolley, who is an associate professor at UCSF and leads the TrPR Program. "While we can manage the symptoms, our ability to halt deterioration or stop disease advancement has been limited. However, this could be shifting now. The findings suggest a promising potential for psilocybin in aiding the brain’s self-repair mechanisms.

The study, “ Psilocybin treatment for mood disorders associated with Parkinson’s disease: an open-label pilot study This work was written by Ellen R. Bradley, Kimberly Sakai, Gisele Fernandes-Osterhold, Balázs Szigeti, Connie Ludwig, Jill L. Ostrem, Caroline M. Tanner, Meredith A. Bock, Katiah Llerena, Patrick R. Finley, Aoife O'Donovan, Jose Rafael P. Zuzuarregui, Zachary Busby, Amber McKernan, Andrew D. Penn, Aliss C.C. Wang, Raymond C. Rosen, and Joshua D. Woolley.