Parkinson’s disease is becoming increasingly prevalent in the United States and around the world and is now the second leading neurodegenerative disease second only to Alzheimer’s disease. Besides the characteristic motor symptoms, depression and anxiety are the most common non-movement symptoms and are highly associated with accelerated decline and poor quality of life. Although medications such as Carbidopa, Levodopa, Sinemet, and Requip are current treatment options, they all have side effects ranging from unpleasant to life-threatening. A safer, natural remedy for Parkinson’s mood dysregulation is warranted.
Parkinson’s Disease: A Brief Review
Parkinson’s disease is primarily a movement disorder affecting the nervous system and becomes worse over time. Symptoms begin slowly and at times unnoticeably, like a minor tremor of the hand and muscle stiffness. Symptoms may show up only on one side of the body and then eventually affect both sides. Physical symptoms include tremor, slowed movement (bradykinesia), poor posture and balance, rigid muscles, changes in speech and handwriting. Non-movement symptoms include anxiety, depression, sleep difficulties, nightmares, fatigue and cognitive impairment.
Psilocybin
Psilocybin is the psychedelic compound found in “magic mushrooms” and can be obtained from natural mushrooms or lab-created forms. There has been much interest lately for the use of psychedelics, including psilocybin as a potential treatment for addiction, depression and other mental disorders, due to its ability to stimulate particular areas of the brain which may reduce or eliminate negative symptoms. An attractive characteristic of psilocybin is its quick action as opposed to the weeks or months it takes traditional antidepressants to work. Some negative side effects include confusion, hallucinations, headache, nausea and increased blood pressure, which tend to subside within hours.
How It Works
Symptoms of anxiety and depression in Parkinson’s disease are associated with serotonin and dopamine dysfunction, deficits in synapses, and elevated inflammation. Psilocybin converts into its active metabolite, psilocin, which acts upon serotonin receptors, affecting mood. Psilocybin is said to have “psychoplastogen” qualities, meaning the ability to cause neuron growth, glutamatergic signaling which regulates neuroinflammation, and the ability to target anxiety and depression. Psilocybin has also shown to interact with serotonin receptors linked to tremor and dyskinesia, and modulate activity between serotonin and dopamine-regulated neural networks.
Final Thoughts on Psilocybin, Depression and Parkinson’s Disease
The prevalence of Parkinson’s disease is increasing worldwide and while many pharmacological treatments are available, they all come with negative side effects. It is imperative to find a safer and effective natural treatment for mood disorders that accompany Parkinson’s. Psilocybin has been found to impact the pathophysiology of Parkinson’s disease itself by modulating glutamatergic activity, reducing inflammatory activity, promoting neural growth and inducing neuroplasticity. It has also shown promising results in reducing anxiety and improving overall mood, which may lead to improved motor function and better quality of life.
Reference
- Bradely E.R. et al. 2025. Psilocybin therapy for mood dysfunction in Parkinson’s disease: An open-label pilot trial. American College of Neuropsychopharmacology, https://doi.org/10.1038/s41386-025-02097-0.