Neuroplasticity Enhancement From Cognitive Training Reinforced by Psilocybin
2 other identifiers
interventional
200
1 country
1
Brief Summary
Background: Normal aging, as well as dementias such as Alzheimer s disease, can cause changes in the brain that affect memory, attention, and thinking. Researchers want to know if regular mental tasks (cognitive training) can improve brain function in older adults. They also want to know if psilocybin, a compound found in certain mushrooms, can further support improved brain function. Objective: To learn how regular cognitive training, with or without psilocybin, can improve brain health in older adults. Eligibility: People aged 65 years and older with mild cognitive impairment or early-stage Alzheimer s disease. Healthy older adults with normal cognition are also needed. Design: Participants will be screened. They will have a test of their heart function and an imaging scan. They will have mental health screening and tests of their thinking and memory. They will practice brain-training tasks on a tablet. Participants will be divided into 2 groups: 1 will have cognitive training plus psilocybin; 1 will have cognitive training only. Those having cognitive training only will have 5 or 6 clinic visits. They will take the tablet home to practice brain training daily. They will wear a device to measure brain waves as they sleep; they may have 1 overnight stay in the clinic, or they may wear the device at home. Imaging scans and other tests will be repeated at each visit. Those taking psilocybin will have up to 9 clinic visits. In addition to the visits for cognitive training, they will take 1 psilocybin capsule by mouth 2 weeks apart (the second dose is optional). They will remain in the clinic for 24 hours after each dose.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Oct 2026
Typical duration for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 22, 2026
CompletedFirst Posted
Study publicly available on registry
July 23, 2026
CompletedStudy Start
First participant enrolled
October 1, 2026
ExpectedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2030
Study Completion
Last participant's last visit for all outcomes
December 31, 2030
July 24, 2026
July 7, 2026
4.3 years
July 22, 2026
July 23, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Determine whether psilocybin enhances neuroplasticity (Neuroplasticity Composite Score (NPCS))
two doses, 25 mg each, of psilocybin given two weeks apart plus 4 weeks of cognitive training vs. cognitive training alone.
4 weeks
Secondary Outcomes (1)
Assess the safety and tolerability of psilocybin in cognitively healthy older adults and individuals with early-stage AD.
6 weeks
Study Arms (4)
early-stage Alzheimer's Disease (AD) population - cognitive training only
ACTIVE COMPARATORolder adults with early-stage AD, 4 weeks of cognitive training alone
early-stage Alzheimer's Disease (AD) population - cognitive training plus psilocybin
EXPERIMENTALolder adults with early-stage AD, two oral doses of 25mg of psilocybin, administered two weeks apart, plus cognitive training for four weeks
Normal Cognition population - cognitive training only
ACTIVE COMPARATOROlder adults with normal cognition, 4 weeks of cognitive training alone
Normal Cognition population - cognitive training plus psilocybin
EXPERIMENTALOlder adults with normal cognition, two oral doses of 25mg of psilocybin, administered two weeks apart, plus cognitive training for four weeks
Interventions
25 mg orally x 2 (2 weeks apart)
daily for 4 weeks
Eligibility Criteria
You may qualify if:
- In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- Capacity to provide informed consent.
- Stated willingness to comply with all study procedures and availability for the duration of the study.
- Male or female, age \>= 65 years old.
- Cognitive Status:
- Early-stage AD population: Meets the 2024 Alzheimer s Association Workgroup revised criteria for diagnosis and staging of AD (symptomatic cognitive impairment consistent with amnestic MCI or mild AD dementia) with a CDR score of 0.5-1(including 0.5 for the memory box) and a Montreal Cognitive Assessment (MoCA) score of 20-25.5
- Cognitively normal population: No cognitive impairment based on clinical history and examination, with a CDR score of 0 and MoCA score \>= 26.
- For participants with early-stage AD, evidence of underlying AD pathology by the currently only FDA-approved blood-based test, Lumipulse G p217-Tau/Abeta42 ratio \>= 0.00738.123 Alternatively, participants who had previously underwent amyloid PET or CSF testing for diagnosis of AD (to qualify for treatment with anti-amyloid monoclonal antibodies or for any other reason) may provide report of the amyloid PET scan or result of CSF analysis compatible with underlying AD pathophysiology; Lumipulse G p217- Tau/Abeta42 will still be measured to maintain consistency in study assessments, but values \< 0.00738 will not disqualify them.
- Absence of serious neuropsychiatric symptoms, defined as a score of 0 on Delusions and Hallucinations items and a score \<= 2 on Anxiety, Aggression, Irritability, and Disinhibition items of the Neuropsychiatric Inventory Questionnaire (NPI-Q).
- Acetylcholinesterase inhibitors and/or memantine are permitted (alone or in combination) provided the dose(s) have been stable for (Bullet) 6 weeks prior to screening and are expected to remain stable through the psilocybin dosing period and primary outcome assessments, unless a change is medically necessary as determined by the prescribing clinician.
- Concurrent pharmacotherapy with a single selective serotonin reuptake inhibitor (SSRI) other than fluoxetine, serotonin and norepinephrine reuptake inhibitor (SNRI), tricyclic anti-depressant (TCA) or monoamine oxidase inhibitor (MAOI) is allowed only if the participant is willing and able to taper off this medication after Visit 1 (Screening) and have stayed off it for a washout period of at least 7 +/- 2 days prior to Visit 2 (Baseline) and at least 14 +/- 2 days prior to Visit 3 (for the Psilocybin + Cognitive Training group) or Visit 4 (for the Cognitive Training alone group). Bupropion (\<= 300 mg/day) is permitted without taper or washout if the dose has been stable for \>= 6 weeks before screening.
- Absence of active suicidal ideation with plan/intent and no suicidal behavior within the past 6 months, as defined by Columbia-Suicide Severity Rating Scale (C-SSRS) of 0 or 1. Participants with passive ideation (severity 1) may be included only if risk is judged low, a safety plan is documented, and there is no suicidal behavior in the prior 6 months.
- For the early-stage AD population, participation of a study partner who is willing and able to serve as a medical history informant, accompany participants during visits, and provide psychological support following psilocybin sessions. For the cognitively normal population, participation of a study partner will be encouraged, but will not be mandated as eligibility criterion.
- Ability to take oral medication.
- Pregnancy prevention:
- +3 more criteria
You may not qualify if:
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Medical history
- Neurological disorders (besides AD): Clinically significant brain disorders, either previously diagnosed or revealed through the screening exams or baseline neuroimaging, including:
- Stroke (except single asymptomatic old lacune)
- Transient Ischemic Attack (TIA) within the past year, unless full work-up reveals no ongoing risk
- Extensive microvascular pathology or microbleeds
- Multiple sclerosis or related demyelinating disorders
- Parkinson s disease or related movement disorders (e.g., Multiple Systems Atrophy, Progressive Supranuclear Palsy)
- Brain tumors
- History of meningitis or encephalitis
- History of moderate/severe traumatic brain injury (Glasgow Coma Scale \<= 12)
- Other dementias (e.g., vascular dementia, mixed neurodegenerative-vascular dementia, Lewy body disease, frontotemporal dementia, primary progressive aphasia, Huntington s disease, corticobasal degeneration)
- Epilepsy
- Stable, mild neurological conditions (e.g., migraine, essential tremor, peripheral neuropathy) may be allowed at the discretion of the medically responsible investigator.
- Psychiatric disorders:
- +31 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Institute of Aging, Clinical Research Unit
Baltimore, Maryland, 21224, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Dimitrios I Kapogiannis, M.D.
National Institute on Aging (NIA)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- OTHER
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 22, 2026
First Posted
July 23, 2026
Study Start (Estimated)
October 1, 2026
Primary Completion (Estimated)
December 31, 2030
Study Completion (Estimated)
December 31, 2030
Last Updated
July 24, 2026
Record last verified: 2026-07-07
Data Sharing
- IPD Sharing
- Will not share