Psychedelic Mushroom May Help Treat Depression and Anxiety in Parkinson’s

For the first time, researchers have tested the use of psilocybin, a substance found in psychedelic mushrooms, to treat depression and anxiety in people with Parkinson's disease. In a pilot study with 12 participants, the therapy was shown to be safe, well tolerated, and resulted in improvements in mood, motor symptoms, and even some cognitive functions. The positive effects lasted for months, suggesting that psilocybin may be a promising new option for alleviating emotional distress in patients with Parkinson's.

Parkinson's disease (PD) is a progressive neurological condition that affects millions of people worldwide. Traditionally, it is recognized by motor symptoms, such as tremors, muscle stiffness, and slowness of movement, but what many people don't know is that the disease also brings non-motor symptoms, such as depression and anxiety, which profoundly affect patients' quality of life.

These emotional symptoms not only make daily life difficult, but are also associated with a more rapid worsening of the condition. Unfortunately, conventional treatments for dealing with this psychological distress often have limited effectiveness, and little research is looking for innovative alternatives.

It is in this context that psilocybin, a psychedelic substance present in some mushrooms, appears as a potential therapeutic tool.

Studies in other populations, such as people with resistant depression or in palliative care for cancer, already know that psilocybin can provide deep and lasting emotional relief, even after a single dose, when accompanied by psychotherapeutic support.

This is because the substance acts on the brain by stimulating serotonin receptors and promoting a type of “restructuring” of neural connections, a process known as neuroplasticity.

In addition, psilocybin can positively interfere with mechanisms involved in inflammation and synapse function, which makes it especially interesting in the context of Parkinson's, a disease also marked by dysfunctions in these areas.

On the other hand, there are significant concerns regarding the safety of psilocybin use in people with Parkinson's disease. The drug can increase heart rate and blood pressure, which is worrying in a population that is generally elderly and has autonomic problems.

Furthermore, there is a risk that it could trigger or worsen psychotic symptoms, since Parkinson's disease itself already presents a predisposition to psychosis in many patients.

The interaction of psilocybin with the serotonergic system, involved in both mood regulation and the motor and cognitive symptoms of the disease, makes its effects difficult to predict. Another point of uncertainty concerns possible interactions with levodopa, the main medication used to treat the motor symptoms of Parkinson's disease.

To investigate this possibility carefully, researchers conducted a pilot study with a small group of people with mild to moderate Parkinson's disease who also had depression and/or anxiety. In total, 12 participants received two doses of psilocybin (10 mg and 25 mg), always accompanied by psychotherapy sessions.

The main objective was to assess whether the intervention was safe, well tolerated and whether it could bring any emotional benefit.

The results were encouraging: no participant experienced serious adverse effects or required emergency medical intervention. The most common side effects were mild, such as nausea, transient anxiety, and increased blood pressure, all of which were manageable.

Most importantly, there was no worsening of the motor symptoms of Parkinson’s disease or the onset of psychosis. On the contrary, after treatment, participants showed significant improvements not only in mood, but also in motor and cognitive aspects.

The scales used to measure depression and anxiety showed a consistent and clinically relevant reduction in symptoms, and these positive effects were maintained for up to three months after the last dose. This study is the first to report the effects of psilocybin on a neurodegenerative disease such as Parkinson’s.

Although the results are still preliminary and have limited validity due to the small number of participants and the lack of a control group, they provide an important basis for future research.

The idea that a single or small dose of a psychedelic substance, used as therapeutic support, can alleviate the chronic psychological suffering of people with Parkinson's opens up a new and promising front in the treatment of neurological diseases.

Preliminary safety, tolerability, and efficacy results. A) Vital signs during the course of 10 mg (A0) and 25 mg (B0) psilocybin administration sessions; x-axis indicates time since drug administration. B) PD symptom severity scores (MDS-UPDRS) over time, shown for non-motor symptoms (Part I), motor symptoms (Part II), and motor exams (Part III). Follow-up time points were one week after the 10 mg session (A7), one week after the 25 mg session (B7), and one month after the 25 mg session (B30). Lower scores indicate improvement. C) Selected cognitive safety measures. Lower z-scores indicate better performance on the spatial working memory (SWM) and paired associate learning (PAL) tasks. Performance on the PRL task is indexed by the number of reversals achieved; a greater number of reversals reflects better cognitive flexibility. D) Depression (MADRS) and anxiety (HAM-A); both were also assessed three months after the 25 mg (B90) session. Error bars represent 95% confidence intervals. Dotted horizontal lines indicate symptom severity levels for reference, where applicable. MDS-UPDRS Movement Disorders Society review of the Unified Parkinson's Disease Rating Scale, eSAPS-PD Extended Scale for the Assessment of Positive Symptoms in Parkinson's Disease, SWM spatial working memory, PAL paired associates learning, MADRS Montgomery-Åsberg Depression Rating Scale, HAM-A Hamilton Anxiety Rating Scale, PRL Probabilistic Reversal Learning Task

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Psilocybin therapy for mood dysfunction in Parkinson’s disease: an open-label pilot trial

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

Neuropsychopharmacology. 9 April 2025

DOI: 10.1038/s41386-025-02097-0

Abstract:

Mood dysfunction is highly prevalent in Parkinson’s disease (PD), a main predictor of functional decline, and difficult to treat—novel interventions are critically needed. Psilocybin shows early promise for treating depression and anxiety, but its potential in PD is unknown, as safety concerns have excluded people with neurodegenerative disease from previous trials. In this open-label pilot (NCT04932434), we examined the feasibility of psilocybin therapy among people with mild to moderate stage PD plus depression and/or anxiety. 12 participants (mean age 63.2 ± 8.2 years, 5 women) received psilocybin (one 10 mg followed by one 25 mg dose) with psychotherapy. There were no serious adverse events, no medical interventions required to manage effects of psilocybin, and no exacerbation of psychosis. Ten participants experienced treatment-emergent adverse events; the most frequent were anxiety, nausea, and increased blood pressure. We observed no worsening of PD symptomology measured by the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). On the contrary, non-motor (MDS-UPDRS Part I: –13.8 ± 1.3, p < 0.001, Hedges’ g = 3.0) and motor symptoms (Part II: –7.5 ± 0.9, p < 0.001, g = 1.2; Part III: –4.6 ± 1.3, p = 0.001; g = 0.3) as well as performance in select cognitive domains (Paired Associates Learning [-0.44 ± 0.14, p = .003, g = 0.4], Spatial Working Memory [–0.52 ± 0.17, p = 0.003, g = 0.7], and Probabilistic Reversal Learning [2.9 ± 0.9, p = 0.003, g = 1.3]) improved post-treatment, and improvements were sustained until the final safety assessment one month following drug exposure. Baseline Montgomery-Asberg Depression Rating Scale (MADRS) and Hamilton Anxiety Rating Scale (HAM-A) scores were 21.0 ± 8.7 and 17.0 ± 3.7, respectively. Both improved to a clinically meaningful degree post-treatment; these improvements persisted to the final assessment three months following drug exposure (MADRS: -9.3 ± 2.7, p = .001, g = 1.0; HAM-A: –3.8 ± 1.7; p = 0.031, g = 0.7). This study provides the first data on psilocybin’s effects in any neurodegenerative disease. Results suggest that psilocybin therapy in PD warrants further investigation.