Psilocybin therapy for mood dysfunction in Parkinson's disease: an open-label pilot trial.
Study Goal
The researchers aimed to assess the feasibility and effects of psilocybin therapy in individuals with mild to moderate Parkinson's disease (PD) who also had depression and/or anxiety.
Results Summary
The study found that psilocybin therapy was feasible and safe, with no serious adverse events or worsening of PD symptoms. Participants showed significant improvements in non-motor and motor symptoms, cognitive domains, and sustained reductions in depression and anxiety scores.
Population
Individuals with mild to moderate Parkinson's disease (PD) plus depression and/or anxiety (mean age 63.2 ± 8.2 years, 5 women).
Effective Dosage
One 10 mg dose followed by one 25 mg dose, administered with psychotherapy.
Duration
The intervention lasted until the final safety assessment one month post-treatment, with some outcomes tracked for three months.
Interactions
None mentioned
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
psilocybin therapy | no change | serious adverse events | people with mild to moderate stage PD plus depression and/or anxiety | no serious adverse events | no serious adverse events | #1 |
psilocybin therapy | no change | medical interventions required to manage effects of psilocybin | people with mild to moderate stage PD plus depression and/or anxiety | no medical interventions required | no medical interventions required to manage effects | #2 |
psilocybin therapy | no change | psychosis | people with mild to moderate stage PD plus depression and/or anxiety | no exacerbation | no exacerbation of psychosis | #3 |
psilocybin therapy | increase | treatment-emergent adverse events | people with mild to moderate stage PD plus depression and/or anxiety | Ten participants | experienced treatment-emergent adverse events | #4 |
psilocybin therapy | no change | PD symptomology measured by the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) | people with mild to moderate stage PD plus depression and/or anxiety | no worsening | no worsening of PD symptomology | #5 |
psilocybin therapy | decrease | non-motor symptoms (MDS-UPDRS Part I) | people with mild to moderate stage PD plus depression and/or anxiety | -13.8 ± 1.3, p < 0.001, Hedges' g = 3.0 | improved | #6 |
psilocybin therapy | decrease | motor symptoms (MDS-UPDRS Part II) | people with mild to moderate stage PD plus depression and/or anxiety | -7.5 ± 0.9, p < 0.001, g = 1.2 | improved | #7 |
psilocybin therapy | decrease | motor symptoms (MDS-UPDRS Part III) | people with mild to moderate stage PD plus depression and/or anxiety | -4.6 ± 1.3, p = 0.001; g = 0.3 | improved | #8 |
psilocybin therapy | decrease | performance in Paired Associates Learning | people with mild to moderate stage PD plus depression and/or anxiety | -0.44 ± 0.14, p = .003, g = 0.4 | improved | #9 |
psilocybin therapy | decrease | performance in Spatial Working Memory | people with mild to moderate stage PD plus depression and/or anxiety | -0.52 ± 0.17, p = 0.003, g = 0.7 | improved | #10 |
psilocybin therapy | increase | performance in Probabilistic Reversal Learning | people with mild to moderate stage PD plus depression and/or anxiety | 2.9 ± 0.9, p = 0.003, g = 1.3 | improved | #11 |
psilocybin therapy | decrease | Montgomery-Asberg Depression Rating Scale (MADRS) scores | people with mild to moderate stage PD plus depression and/or anxiety | -9.3 ± 2.7, p = .001, g = 1.0 | improved to a clinically meaningful degree | #12 |
psilocybin therapy | decrease | Hamilton Anxiety Rating Scale (HAM-A) scores | people with mild to moderate stage PD plus depression and/or anxiety | -3.8 ± 1.7; p = 0.031, g = 0.7 | improved to a clinically meaningful degree | #13 |
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.