Neuroplasticity Enhancement From Cognitive Training Reinforced by Psilocybin

November 2, 2026 updated by: National Institute on Aging (NIA)

Neuroplasticity Enhancement From Cognitive Training Reinforced by Psilocybin (NECTAR) in Aging and Alzheimer's Disease

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
200

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21224
        • Recruiting
        • National Institute of Aging, Clinical Research Unit
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

65 years to 120 years (Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

  • Pending Web Eligibility

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

daily for 4 weeks
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
Other: Cognitive Training

daily for 4 weeks

Drug: Psilocybin

25 mg orally x 2 (2 weeks apart)
Active Comparator: Normal Cognition population - cognitive training only

Older adults with normal cognition, 4 weeks of cognitive training alone
Other: Cognitive Training

daily for 4 weeks
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
Other: Cognitive Training

daily for 4 weeks

Drug: Psilocybin

25 mg orally x 2 (2 weeks apart)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Determine whether psilocybin enhances neuroplasticity (Neuroplasticity Composite Score (NPCS))
Time Frame: 4 weeks

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

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Assess the safety and tolerability of psilocybin in cognitively healthy older adults and individuals with early-stage AD.
Time Frame: 6 weeks

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
National Institute on Aging (NIA)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Dimitrios I Kapogiannis, M.D., National Institute on Aging (NIA)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 8, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2030

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2030

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 22, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 22, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 23, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 3, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 2, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 16, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 10002693
  • 002693-AG

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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