Safety, feasibility, and tolerability of psilocybin in older adults with amnestic MCI: Preliminary data from a SV2a PET imaging study
Bibliographic record
Abstract
BACKGROUND: Amnestic mild cognitive impairment (aMCI) is characterized by synaptic loss and cognitive decline and is considered a precursor to Alzheimer's Disease. Currently, there are no effective treatments for aMCI, and available treatments (i.e., cholinesterase inhibitors) do not appear to improve cognitive or functional outcomes. Psychedelics, including psilocybin, have regained interest for treatment of treatment-resistant neuropsychiatric disorders. Research suggests psilocybin's psychedelic and clinical effects may be due to interaction with the 5HT2A serotonin receptor (5HTA-R) in the brain. Cognitive impairments, such as memory decline, have been associated with lower 5HT2A-R density in the brain. Encouragingly, preclinical animal studies suggest that psilocybin may promote synaptogenesis in the brain, particularly in areas associated with learning and memory, likely through its interaction with the 5HT2A-R. Psilocybin may represent a novel treatment to counter neurodegenerative progression and consequently improve cognitive outcomes in patients with aMCI. METHOD: F]SynVesT to assess psilocybin's effect on synaptic density in the hippocampus and prefrontal cortex of patients with aMCI, and whether these changes are associated with improved cognitive outcomes. aMCI participants and sex-matched healthy controls will be randomized to receive either two doses of 25mg psilocybin or placebo one week apart. Participants will be monitored by a study physician and qualified therapist. PET scans are conducted pre- and one-week post-treatment. Clinical, safety, and neuropsychological assessments are done at baseline and 1-, 4-, and 12-weeks post-treatment. Safety measures include monitoring vital signs, suicidal ideation, and adverse events (AEs). RESULT: Pilot data from two aMCI participants (Male% = 50%, mean age = 71.0(±3.0), mean baseline MOCA = 22(±3.0)) and three healthy controls (Male% = 67%, mean age = 66.3(±5.1); mean baseline MOCA = 27.7(±1.5)) is available. All participants completed study procedures without issue. Psilocybin was well tolerated, with no unexpected or serious AEs. All expected AEs resolved without sequelae. Expected AEs included dizziness (n=4) and altered perception (n=3). Blinding remains in effect. CONCLUSION: The preliminary data suggest psilocybin is safe, well-tolerated, and can be feasibly investigated in a supervised medical setting in older adults as a prospective treatment for aMCI.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".