Does Psilocybin Change Synaptic Density in Amnestic Mild Cognitive Impairment
- Conditions
- Amnestic Mild Cognitive Impairment
- Interventions
- Drug: Placebo
- Registration Number
- NCT06041152
- Lead Sponsor
- Centre for Addiction and Mental Health
- Brief Summary
The goal of this clinical trial is to investigate the effects of psilocybin on synaptic vesicular density (SVD) as measured by the positron emission tomography (PET) radiotracer, 18F-SynVesT-1, in participants with amnestic Mild Cognitive Impairment (aMCI) and healthy participants. The investigators hypothesize that SVD levels in the brain will be higher following the ingestion of psilocybin in comparison to placebo, and that increases in SVD will be associated with improvements in cognition.
60 participants (30 with aMCI, and 30 sex and age matched healthy volunteers) will:
* Be randomized to receive either:
1. Two 25 mg macrodoses of psilocybin separated by 1 week.
2. Two placebo doses separated by 1 week.
* Receive a baseline 18F-SynVesT-1 PET scan, clinical, and neuropsychological assessments.
* Receive a 18F-SynVesT-1 PET scan one week after the last dose of treatment.
* Receive a third PET scan at any time within 4 weeks of the screening visit to quantify tauopathy with the \[18F\]T807 radiotracer.
* Receive clinical and neuropsychological testing 1, 4, and 12 weeks after the last treatment.
Researchers will compare placebo vs. experimental groups to see if psilocybin will increase SVD, and if increases in SVD are associated with cognitive improvements.
- Detailed Description
The proposed study will investigate the effects of on synaptic vesicular density (SVD) levels as measured by the positron emission tomography (PET) radiotracer, 18F-SynVesT-1, and cognition (i.e., global cognition, executive function, and memory domains) in amnestic Mild Cognitive Impairment (aMCI) and healthy participants. Participants will be randomized to receive either two 25mg doses of psilocybin separated by one week, or two placebo doses separated by one week. Brain scans, clinical, and cognitive assessments will be conducted one week before, and one week, four weeks, and 12 weeks post dosing.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 60
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Amnestic Mild Cognitive Impairment Participants Receiving Psilocybin Psilocybin Receiving 2 doses of 25mg of psilocybin separated by 1 week. Healthy Participants Receiving Psilocybin Psilocybin Receiving 2 doses of 25mg of psilocybin separated by 1 week. Amnestic Mild Cognitive Impairment Participants Receiving Placebo Placebo Receiving 2 doses of placebo separated by 1 week. Healthy Participants Receiving Placebo Placebo Receiving 2 doses of placebo separated by 1 week.
- Primary Outcome Measures
Name Time Method Synaptic Vesicular Density 3 years Synaptic vesicular density will be assessed with PET imaging by measuring the volume of distribution (i.e., defined as the ratio of the radioligand concentration in tissue target region (CT, kBq·cm-3) to that in plasma (CP, kBq·mL-1) at equilibrium) of the \[18F\]SynVesT-1 radioligand in the cortical and subcortical gray matter regions in the whole brain and more specifically, the hippocampus and dorsolateral prefrontal cortex.
- Secondary Outcome Measures
Name Time Method Global Cognition 3 years The results of the neuropsychological battery will be combined to a global cognition composite score as a Z-score, the change of which will be a secondary outcome measure. Z-scores will be comprised of the Mini-Mental State Examination, Montreal Cognitive Assessment, Boston Naming Test, Category Fluency Test, Letter Fluency Test, Trail Making Test Parts A and B, Wisconsin Card Sorting Test, Stroop Neuropsychological Test, Executive Interview, Block Design Test, Clock Drawing Test, Grooved Pegboard, Digit Symbol Test, Logical Memory Test, California Verbal Learning Test, and Modified Rey-Osterrieth Complex Figure, and will be calculated based on the performance of the equated comparison group. Each domain will contribute equally to the global cognition composite score.
Memory 3 years A memory composite Z-score will be generated using the performance on the following individual tests: Logical Memory Test, California Verbal Learning Test, and Modified Rey-Osterrieth Complex Figure. Z-scores will be calculated based on the performance of the equated comparison group, and each domain will contribute equally to the global cognition composite score.
Executive Function 3 years An executive function composite Z-score will be generated using the performance on the following individual tests: Trail Making Test Part B, Wisconsin Card Sorting Test, Stroop Neuropsychological Screening, and the Executive Interview. Z-scores will be calculated based on the performance of the equated comparison group, and each domain will contribute equally to the global cognition composite score.
Trial Locations
- Locations (1)
Centre for Addiction and Mental Health
🇨🇦Toronto, Ontario, Canada