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RecruitingNCT07721467Updated Nov 10, 2026

Neuroplasticity Enhancement From Cognitive Training Reinforced by Psilocybin

A Phase 2 interventional study of Psilocybin and Cognitive Training in Alzheimer's Disease, sponsored by National Institute on Aging (NIA). Recruiting at 1 site in United States. Open to participants aged 65 Years to 120 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-11-10.

Sponsored by National Institute on Aging (NIA) · Phase 2, Interventional, and Other

Updated Nov 10, 2026Now RecruitingStart date moved+2 moreGo to Updates ↓
Phase
Phase 2
Study type
Interventional
Enrollment
200
Allocation
Randomized
Ages
65 Years to 120 Years
Sex
All
01

Study 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.

Read the detailed description

Study Description:

A randomized, open-label, parallel-group clinical trial with two arms aimed at evaluating whether psilocybin enhances the neuroplastic and cognitive benefits of cognitive training in two populations: older adults with normal cognition and individuals with early-stage Alzheimer s disease (AD). Participants in both populations will be randomized to receive either two oral doses of 25 mg of psilocybin, administered two weeks apart, plus cognitive training for four weeks or cognitive training alone for four weeks. The primary outcome will be the change from baseline in a novel Neuroplasticity Composite Score (NPCS) assessed four weeks after the first psilocybin session or the onset of cognitive training. Secondary outcomes include the assessment of safety and tolerability, cognitive performance on TabCAT, RBANS, and autobiographical memory; psychological well-being; quality of life; and sleep. Additional outcomes will include MRI/fMRI/MRS measures of neuroplasticity, brain network connectivity and neurochemistry; EEG during sleep; and plasma and plasma extracellular vesicle (EV)-associated biomarkers of synaptic integrity, serotonergic transmission, neurodegeneration, mitochondrial function, and inflammation. Screening will include clinical and cognitive assessments, assessment of suicidal ideation and behavior, biomarker confirmation of AD pathology, neuroimaging eligibility screening, and laboratory tests for metabolic, hepatic, and renal function. A urine drug screen will confirm the absence of illicit substances, and a urine pregnancy test will be required for female participants of childbearing potential. By simultaneously assessing cognitive and brain function and structure at multiple levels, this study will provide proof-ofconcept for psilocybin s potential to promote neuroplasticity, enhance cognition, improve emotional well-being, and mitigate neurodegenerative processes in aging and AD. Additionally, the inclusion of understudied geriatric populations will address critical gaps in psilocybin s safety and efficacy profile in older adults.

Objectives:

Primary Objective:

-Determine whether psilocybin enhances neuroplasticity four weeks after the first psilocybin session compared to cognitive training alone.

Secondary Objectives:

  • Assess the safety and tolerability of psilocybin in cognitively healthy older adults and individuals with early-stage AD.
  • Assess whether psilocybin enhances cognitive performance on TabCAT, RBANS and autobiographical memory, compared to cognitive training alone.
  • Evaluate whether psilocybin enhances neuroplasticity-related changes on MRI, resting state fMRI, and MRS (i.e., changes in microanatomy, structural \& functional connectivity, neurotransmitter levels) compared to cognitive training alone.
  • Evaluate whether psilocybin enhances neuroplasticity-related changes on EEG during sleep (sleep architecture, spectral power) compared to cognitive training alone.
  • Investigate whether psilocybin followed by cognitive training changes plasma and plasma EV-associated biomarkers, compared to cognitive training alone, focusing on synaptic, neurodegenerative, mitochondrial, and inflammatory markers.
  • Characterize salivary stress-related biomarkers (e.g., cortisol and related hormones) and explore their association with acute psilocybin response and longer-term outcomes, and their longitudinal changes.
  • Evaluate changes in psychological well-being (anxiety, depressive symptoms, trauma-related symptoms, alcohol craving/misuse, broader dimensions of well-being such as autonomy, purpose in life, personal growth); overall quality of life; and sleep with psilocybin followed by cognitive training compared to cognitive training alone.
  • Assess differences between the first and second psilocybin session.

Endpoints:

Primary Endpoint:

-Change in NPCS four weeks after the first psilocybin session and initiation of cognitive training compared to cognitive training alone.

Secondary Endpoints:

  • Safety \& Tolerability: Incidence of adverse events.
  • Change in NPCS, four days after the first psilocybin session and initiation of cognitive training, compared to cognitive training alone.
  • Cognitive Outcomes: Change in TabCAT Brain Health Assessment (TabCAT-BHA) global composite score and individual task scores, RBANS total score, autobiographical memory performance (Reminiscence Functions Scale, Autobiographical Event Recall Test, DRM Paradigm), and performance in individual cognitive tests with psilocybin followed by cognitive training, in the short- (i.e., four days) and mid-term (i.e., four weeks), compared to cognitive training alone.
  • Neuroimaging Outcomes: Changes in MRI, resting state fMRI, and MRS measures, including changes in microstructure and myelin and axonal integrity, BrainAGE, brain network connectivity, and neurotransmitter concentrations with psilocybin followed by cognitive training, compared to cognitive training alone.
  • EEG Outcomes: Changes in sleep architecture and quantitative EEG spectral power with psilocybin and cognitive training, compared to cognitive training alone.
  • Biomarkers: Changes in plasma and plasma EV-associated markers of synaptic function and neuroplasticity, neurodegeneration, mitochondrial function, and inflammation, with psilocybin and cognitive training, compared to cognitive training alone.
  • Salivary Stress Biomarkers: Association of salivary cortisol and related hormones with acute psilocybin response and longer-term outcomes, and their longitudinal changes.
  • Psychological and Quality of Life Outcomes: Changes in State- Trait Anxiety Inventory-State (STAI-State), Montgomery(SqrRoot) sberg Depression Rating Scale Self report (MADRS-S), PTSD Checklist for DSM-5 (PCL-5), Penn Alcohol Craving Scale (PACS), National Institutes of Health-Healing Experience of All Life Stressors (NIH-HEALS), Ryff Psychological Well-Being Scales, Neuropsychiatric Inventory Questionnaire (NPI-Q), Quality of Life in Alzheimer s Disease (QOL-AD) Scale, Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI) with psilocybin followed by cognitive training, compared to cognitive training alone.
  • Subjective Effects Questionnaires: Scores on the Mystical Experience Questionnaire (MEQ30), Challenging Experience Questionnaire (CEQ-Challenge), Ego-Dissolution Inventory (EDI), and Drug Effects Questionnaire (DEQ) following each psilocybin session.
02

Conditions studied

  • Alzheimer's Disease

Browse trials for

Keywords

  • Aging
  • Psilocybin
  • Cognitive Training
03

In context

Alzheimer Disease

3,965 studies on the registry are indexed under Alzheimer Disease; 926 are open to participants now.

This study's planned enrollment of 200 is above the median of 70 across 3,019 interventional studies indexed under Alzheimer Disease.

Browse Alzheimer Disease studies →

Lead sponsor

National Institute on Aging (NIA) is the lead sponsor of 160 studies on the registry; 13 are open to participants now.

Of its 7 completed or terminated interventional studies of FDA-regulated products, 2 (29%) have results posted.

Browse National Institute on Aging (NIA) studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

The criteria were revised on the registry on Oct 9, 2026. See what changed

Ages eligible
65 Years to 120 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Eligibility criteria

  • Pending Web Eligibility
05

Study design

Phase
Phase 2
Primary purpose
Other
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
200 participants (estimated)

Study arms

  • Active comparator
    early-stage Alzheimer's Disease (AD) population - cognitive training only

    older adults with early-stage AD, 4 weeks of cognitive training alone

    Other: Cognitive Training

  • Experimental
    early-stage Alzheimer's Disease (AD) population - cognitive training plus psilocybin

    older adults with early-stage AD, two oral doses of 25mg of psilocybin, administered two weeks apart, plus cognitive training for four weeks

    Drug: Psilocybin · Other: Cognitive Training

  • Active comparator
    Normal Cognition population - cognitive training only

    Older adults with normal cognition, 4 weeks of cognitive training alone

    Other: Cognitive Training

  • Experimental
    Normal Cognition population - cognitive training plus psilocybin

    Older adults with normal cognition, two oral doses of 25mg of psilocybin, administered two weeks apart, plus cognitive training for four weeks

    Drug: Psilocybin · Other: Cognitive Training

Interventions

  • DrugPsilocybin

    25 mg orally x 2 (2 weeks apart)

  • OtherCognitive Training

    daily for 4 weeks

06

What researchers measure

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.

    Time frame: 4 weeks

Secondary outcomes

  1. Assess the safety and tolerability of psilocybin in cognitively healthy older adults and individuals with early-stage AD.

    two doses, 25 mg each, of psilocybin given two weeks apart plus 4 weeks of cognitive training vs. cognitive training alone.

    Time frame: 6 weeks

07

Study locations

1 of 1 sites recruiting
08

References and documents

Individual participant data

Plan to share: No

09

Timeline

30 registry updates since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedDate before it movedWhere the date was before it movedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Start is estimated for Nov 2026; primary completion for Dec 2030, 49 months later.

Of 127 non-industry phase 2 interventional studies under Alzheimer Disease, half reached primary completion within 54 months of starting (the median), counting those still running; a quarter within 37 and three quarters within 69. This study's planned 49 months is close to that.

Counting every sponsor, half of 257 studies reached it within 37 months; a quarter within 21 and three quarters within 58.

Start moved 30 times since we started tracking on Sep 25, 2026: Oct 2026 → Nov 2026, last on Nov 10, 2026.

Earlier changes are on the record history on ClinicalTrials.gov ↗

How these figures are worked out, and which studies are left out of them.

Registered
Jul 22, 2026
First posted
Jul 23, 2026
StartEst.
Nov 15, 2026was Oct 2026
Primary completionEst.
Dec 31, 2030
CompletionEst.
Dec 31, 2030
Last update
Nov 10, 2026
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
Status
Not yet recruiting→Recruiting
changed Oct 8, 2026
Sites
National Institute of Aging, Clinical Research Unit is now Recruiting
Oct 8, 2026
Start date
Oct 1, 2026→Nov 15, 2026
moved 30 times, Sep 29, 2026 – Nov 10, 2026
Eligibility
Criteria revised in 3 updates
What changed on Oct 7, 2026
Exclusion criteria
  • EditedResting heart rate (HR) <= 55 bpm or > 100 bpm or clinically significant arrythmia: HR will be assessed concurrently with the blood pressure protocol above.
  • EditedParticipants who previously received any anti-am...
What changed on Oct 8, 2026
Exclusion criteria
  • EditedResting heart rate (HR) <= 55 bpm or > 100 bpm or clinically significant arrythmia: HR will be assessed concurrently with the blood pressure protocol above.
  • EditedParticipants who previously received any anti-am...
What changed on Oct 9, 2026
  • AddedPending Web Eligibility
Inclusion criteria
  • RemovedIn order to be eligible to participate in this study, an individual must meet all of the following criteria:
  • RemovedCapacity to provide informed consent.
  • RemovedStated willingness to comply with all study procedures and availability for the duration of the study.
  • RemovedMale or female, age >= 65 years old.
  • RemovedCognitive Status:
  • RemovedEarly-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.
  • RemovedCognitively normal population: No cognitive impairment based on history and examination, with a CDR score of 0 and MoCA score >= 26.
  • RemovedFor participants with early-stage AD, evidence of underlying AD pathology by the only FDA-approved blood-based test, Lumipulse G p217-Tau/Abeta42 ratio >= 0.00738. Alternatively, participants who 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 results 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.
  • RemovedAbsence 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).
  • RemovedAcetylcholinesterase 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 remain stable through the psilocybin dosing period and primary outcome assessments, unless a change is medically necessary.
  • RemovedConcurrent pharmacotherapy with a single selective serotonin reuptake inhibitor (SSRI), serotonin and norepinephrine reuptake inhibitor (SNRI), tricyclic anti-depressant (TCA) or monoamine oxidase inhibitor (MAOI) is allowed if the participant is willing and able to taper off this medication after Visit 1 (Screening) and stay 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.
  • RemovedAbsence 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.
  • RemovedFor 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 not mandated as eligibility criterion.
  • RemovedAbility to take oral medication.
  • RemovedPregnancy prevention:
  • RemovedParticipants of childbearing potential must have a negative urine pregnancy test at screening and prior to psilocybin on Visits 3 and 7, and agree to use highly effective birth control beginning at least 14 days before any psilocybin dosing day and continuing through 30 days after the last psilocybin dose.
  • RemovedMale participants with partners of childbearing potential must agree to use condoms and to ensure their partner uses a highly effective contraceptive method during the same window. Sperm donation is not permitted during the study and for 30 days after the last psilocybin dose.
Exclusion criteria
  • RemovedAn individual who meets any of the following criteria will be excluded from participation in this study:
  • Removed-Medical history
  • Removed--Neurological disorders (besides AD): Brain disorders, either previously diagnosed or revealed through screening exams or baseline neuroimaging, including:
  • RemovedStroke (except single asymptomatic old lacune)
  • RemovedTransient Ischemic Attack (TIA) within the past year, unless work-up shows no ongoing risk
  • RemovedExtensive microvascular pathology or microbleeds
  • RemovedMultiple sclerosis or demyelinating disorders
  • RemovedParkinson s disease or movement disorders (e.g., Multiple Systems Atrophy, Progressive Supranuclear Palsy)
  • RemovedBrain tumors
  • RemovedHistory of meningitis or encephalitis
  • RemovedHistory of moderate/severe traumatic brain injury (Glasgow Coma Scale <= 12)
  • RemovedOther dementias
  • RemovedEpilepsy
  • RemovedStable, mild neurological conditions (e.g., migraine, essential tremor, peripheral neuropathy) may be allowed at the discretion of the medically responsible investigator.
  • Removed--Psychiatric disorders:
  • RemovedCurrent or past moderate-to-severe mood disorders
  • RemovedHistory of psychotic disorders unless remote, short-lived, and directly attributable to medication misuse or overdose
  • RemovedActive suicidal ideation (C-SSRS severity 2-5) within the past 1 month or any suicidal behavior within the past 6 months; or current elevated acute risk in the opinion of the medically responsible investigator
  • RemovedSevere PTSD, defined as a Primary Care PTSD Screen for DSM-5 (PC-PTSD-5) score >= 4 in men or >= 3 in women
  • RemovedAnxiety or personality disorders, if moderate to severe, as determined by the medically responsible investigator.
  • RemovedMild depression and/or anxiety may be permitted if successfully treated with psychotherapy and/or single anti-depressant. Participants taking a single SSRI, SNRI, TCA, or MAOI may still be eligible only if they are willing and able to taper off this medication after Visit 1 (Screening) and complete 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). Tapering requires participant agreement, prescribing-clinician agreement, and investigator determination of no elevated risk. A written taper/monitoring plan and point of contact must be documented. Weekly safety check-ins will assess discontinuation symptoms, mood/anxiety, sleep, and suicidality. If clinically significant worsening occurs, taper may be slowed, paused, stopped, or the participant excluded for safety.
  • RemovedCardiovascular conditions:

…and 39 more changes, on the record history on ClinicalTrials.gov ↗

across 3 updates, Oct 7, 2026 – Oct 9, 2026
Show all 30 updates
  1. Nov 10, 2026
    Start date Nov 12, 2026→Nov 15, 2026
  2. Nov 9, 2026
    Start date Nov 11, 2026→Nov 12, 2026
  3. Nov 6, 2026
    Start date Nov 10, 2026→Nov 11, 2026
  4. Nov 5, 2026
    Start date Nov 9, 2026→Nov 10, 2026
  5. Nov 4, 2026
    Start date Nov 8, 2026→Nov 9, 2026
  6. Nov 3, 2026
    Start date Nov 5, 2026→Nov 8, 2026
  7. Nov 2, 2026
    Start date Nov 4, 2026→Nov 5, 2026
  8. Oct 30, 2026
    Start date Nov 3, 2026→Nov 4, 2026
  9. Oct 29, 2026
    Start date Nov 2, 2026→Nov 3, 2026
  10. Oct 28, 2026
    Start date Nov 1, 2026→Nov 2, 2026
  11. Oct 27, 2026
    Start date Oct 29, 2026→Nov 1, 2026
  12. Oct 26, 2026
    Start date Oct 28, 2026→Oct 29, 2026
  13. Oct 23, 2026
    Start date Oct 27, 2026→Oct 28, 2026
  14. Oct 22, 2026
    Start date Oct 26, 2026→Oct 27, 2026
  15. Oct 21, 2026
    Start date Oct 25, 2026→Oct 26, 2026
  16. Oct 20, 2026
    Start date Oct 22, 2026→Oct 25, 2026
    + 2 other changes: verification date and references
  17. Oct 19, 2026
    Start date Oct 21, 2026→Oct 22, 2026
  18. Oct 16, 2026
    Start date Oct 20, 2026→Oct 21, 2026
  19. Oct 15, 2026
    Start date Oct 19, 2026→Oct 20, 2026
  20. Oct 14, 2026
    Start date Oct 18, 2026→Oct 19, 2026
  21. Oct 13, 2026
    Start date Oct 14, 2026→Oct 18, 2026
  22. Oct 9, 2026
    Start date Oct 13, 2026→Oct 14, 2026
    Eligibility Criteria largely rewritten (79 changes)
    What changed in the criteria
    • AddedPending Web Eligibility
    Inclusion criteria
    • RemovedIn order to be eligible to participate in this study, an individual must meet all of the following criteria:
    • RemovedCapacity to provide informed consent.
    • RemovedStated willingness to comply with all study procedures and availability for the duration of the study.
    • RemovedMale or female, age >= 65 years old.
    • RemovedCognitive Status:
    • RemovedEarly-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.
    • RemovedCognitively normal population: No cognitive impairment based on history and examination, with a CDR score of 0 and MoCA score >= 26.
    • RemovedFor participants with early-stage AD, evidence of underlying AD pathology by the only FDA-approved blood-based test, Lumipulse G p217-Tau/Abeta42 ratio >= 0.00738. Alternatively, participants who 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 results 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.
    • RemovedAbsence 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).
    • RemovedAcetylcholinesterase 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 remain stable through the psilocybin dosing period and primary outcome assessments, unless a change is medically necessary.
    • RemovedConcurrent pharmacotherapy with a single selective serotonin reuptake inhibitor (SSRI), serotonin and norepinephrine reuptake inhibitor (SNRI), tricyclic anti-depressant (TCA) or monoamine oxidase inhibitor (MAOI) is allowed if the participant is willing and able to taper off this medication after Visit 1 (Screening) and stay 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.
    • RemovedAbsence 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.
    • RemovedFor 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 not mandated as eligibility criterion.
    • RemovedAbility to take oral medication.
    • RemovedPregnancy prevention:
    • RemovedParticipants of childbearing potential must have a negative urine pregnancy test at screening and prior to psilocybin on Visits 3 and 7, and agree to use highly effective birth control beginning at least 14 days before any psilocybin dosing day and continuing through 30 days after the last psilocybin dose.
    • RemovedMale participants with partners of childbearing potential must agree to use condoms and to ensure their partner uses a highly effective contraceptive method during the same window. Sperm donation is not permitted during the study and for 30 days after the last psilocybin dose.
    Exclusion criteria
    • RemovedAn individual who meets any of the following criteria will be excluded from participation in this study:
    • Removed-Medical history
    • Removed--Neurological disorders (besides AD): Brain disorders, either previously diagnosed or revealed through screening exams or baseline neuroimaging, including:
    • RemovedStroke (except single asymptomatic old lacune)
    • RemovedTransient Ischemic Attack (TIA) within the past year, unless work-up shows no ongoing risk
    • RemovedExtensive microvascular pathology or microbleeds
    • RemovedMultiple sclerosis or demyelinating disorders
    • RemovedParkinson s disease or movement disorders (e.g., Multiple Systems Atrophy, Progressive Supranuclear Palsy)
    • RemovedBrain tumors
    • RemovedHistory of meningitis or encephalitis
    • RemovedHistory of moderate/severe traumatic brain injury (Glasgow Coma Scale <= 12)
    • RemovedOther dementias
    • RemovedEpilepsy
    • RemovedStable, mild neurological conditions (e.g., migraine, essential tremor, peripheral neuropathy) may be allowed at the discretion of the medically responsible investigator.
    • Removed--Psychiatric disorders:
    • RemovedCurrent or past moderate-to-severe mood disorders
    • RemovedHistory of psychotic disorders unless remote, short-lived, and directly attributable to medication misuse or overdose
    • RemovedActive suicidal ideation (C-SSRS severity 2-5) within the past 1 month or any suicidal behavior within the past 6 months; or current elevated acute risk in the opinion of the medically responsible investigator
    • RemovedSevere PTSD, defined as a Primary Care PTSD Screen for DSM-5 (PC-PTSD-5) score >= 4 in men or >= 3 in women
    • RemovedAnxiety or personality disorders, if moderate to severe, as determined by the medically responsible investigator.
    • RemovedMild depression and/or anxiety may be permitted if successfully treated with psychotherapy and/or single anti-depressant. Participants taking a single SSRI, SNRI, TCA, or MAOI may still be eligible only if they are willing and able to taper off this medication after Visit 1 (Screening) and complete 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). Tapering requires participant agreement, prescribing-clinician agreement, and investigator determination of no elevated risk. A written taper/monitoring plan and point of contact must be documented. Weekly safety check-ins will assess discontinuation symptoms, mood/anxiety, sleep, and suicidality. If clinically significant worsening occurs, taper may be slowed, paused, stopped, or the participant excluded for safety.
    • RemovedCardiovascular conditions:

    …and 39 more changes, on the record history on ClinicalTrials.gov ↗

  23. Oct 8, 2026
    Not yet recruiting→Recruiting
    National Institute of Aging, Clinical Research Unit is now Recruiting
    Start date Oct 12, 2026→Oct 13, 2026
    Eligibility 2 exclusion criteria edited
    What changed in the criteria
    Exclusion criteria
    • EditedResting heart rate (HR) <= 55 bpm or > 100 bpm or clinically significant arrythmia: HR will be assessed concurrently with the blood pressure protocol above.
    • EditedParticipants who previously received any anti-am...
    + 1 other change: verification date
  24. Oct 7, 2026
    Start date Oct 11, 2026→Oct 12, 2026
    Eligibility 2 exclusion criteria edited
    What changed in the criteria
    Exclusion criteria
    • EditedResting heart rate (HR) <= 55 bpm or > 100 bpm or clinically significant arrythmia: HR will be assessed concurrently with the blood pressure protocol above.
    • EditedParticipants who previously received any anti-am...
  25. Oct 6, 2026
    Start date Oct 8, 2026→Oct 11, 2026
  26. Oct 5, 2026
    Start date Oct 7, 2026→Oct 8, 2026
  27. Oct 2, 2026
    Start date Oct 6, 2026→Oct 7, 2026
  28. Oct 1, 2026
    Start date Oct 5, 2026→Oct 6, 2026
  29. Sep 30, 2026
    Start date Oct 4, 2026→Oct 5, 2026
  30. Sep 29, 2026
    Start date Oct 1, 2026→Oct 4, 2026

From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗

10

Registry details

Key details

Study ID
NCT07721467
Lead sponsor
National Institute on Aging (NIA)
Responsible party
Sponsor
First posted
Jul 23, 2026
Start date
Nov 15, 2026 (estimated)
Primary completion
Dec 31, 2030 (estimated)
Completion
Dec 31, 2030 (estimated)
Last update
Nov 10, 2026

Study contacts

Sierra D Kunkosi
Contact
sierra.kunkoski@nih.gov
(410) 350-3941
Dimitrios I Kapogiannis, M.D.
Contact
kapogiannisd@mail.nih.gov
(667) 391-0063
Dimitrios I Kapogiannis, M.D.
principal investigator · National Institute on Aging (NIA)

Oversight

FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

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Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Studies of the drug tested here: Psilocybin

Other studies in this condition

Alzheimer Disease →

Other studies from this sponsor

National Institute on Aging (NIA) →

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