RecruitingPhase EARLY_1

Psilocybin for Depression in People With Mild Cognitive Impairment or Early Alzheimer's Disease

Pilot Study of Serotonin 2A Receptor (5-HT2A) Agonist Psilocybin for Depression in Patients With Mild Cognitive Impairment or Early Alzheimer's Disease

Lead sponsor

Johns Hopkins University

Asset

Psilocybin

Listed sites

Recruiting sites

Enrollment

estimated

Study population

Alzheimer’s disease, MCI / preclinical Alzheimer’s

Key I/E criteria

•MMSE ≥18•MoCA ≤26

Primary endpoint

•Cornell Scale for Depression in Dementia (CSDD) score

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Org study IDIRB00175915

NCT IDNCT04123314

Timeline

Milestones

Study first posted2019-10-10actual

Study start2021-03-24actual

Last update posted2026-03-16actual

Primary completion2026-09-30estimated

Study completion2026-12-31estimated

Assets

Drug assets

Psilocybin

Study populations

Who this study enrolls

Alzheimer’s diseaseMCI / preclinical Alzheimer’s

Eligibility

Who can enroll

Minimum age18 Years

Maximum age85 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•Must meet either A) Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5) criteria for Mild Neurocognitive Disorder due to AD or Major Neurocognitive Disorder due to AD with Mild severity (including probable), or B) meet criteria for MCI including a subjective memory complaint relative to previous functioning and confirmed by Clinical Dementia Rating (CDR) Memory score at screening of >0.5

•Have Mini-Mental State Examination scores >18

•Have a Montreal Cognitive Assessment score <26.

•Have Cornell Scale for Depression in Dementia (CSDD) patient score >/= 6, or Geriatric Depression Scale-Short Form score ≥ 5, indicating at minimum a mild to moderate degree of distress.

•Acetylcholinesterase inhibitors are allowed so long as the dose has been stable for > 6 weeks.

•Concurrent pharmacotherapy with selective serotonin reuptake inhibitors (SSRI), serotonin and norepinephrine reuptake inhibitors (SNRI), and/or bupropion is allowed if the type and frequency of the therapy has been stable for at least two months prior to screening. Allowable bupropion doses for participants will be ≤300mg/day.

•Have a close friend or family member willing and able to serve the role of community observer / informant for data collection procedures

Exclusion criteria

•Individuals 86 years of age or older will be excluded.

•Currently taking antipsychotics, monoamine oxidase (MAO) inhibitors, or antidepressant medications other than SSRIs, SNRIs, or bupropion. Allowable bupropion doses for participants will be ≤300mg/day.

•Long-acting opioid pain medications (e.g. oxycodone sustained release, morphine sustained release - which are usually taken at 12 hour intervals) will be allowed if the last dose occurred at least 2 hours before psilocybin administration and the next dose was not scheduled until at least 8 hours after psilocybin administration.

•Participants must agree not to take sildenafil, tadalafil, or similar medications within 72 hours of each psilocybin administration, as these medications may potentiate hypotensive reactions to psilocybin

•Cardiovascular conditions: angina, a clinically significant ECG abnormality (e.g. atrial fibrillation or heart-rate corrected QT interval (QTc) >450msec), Transient Ischemic Attack (TIA) in the last 6 months, stroke, artificial heart valves, or uncontrolled hypertension with resting blood pressure systolic >150 or diastolic >95

•Minimum acceptable heartrate at screening is 50 bpm unless the individual is cleared for participation by a cardiologist, in accord with the American College of Cardiology's 2018 guidelines for bradycardia

•Seizure disorder

•Insulin dependent diabetes mellitus

•Renal disease (creatinine clearance < 40 ml/min using the Cockcroft and Gault equation)

•Baseline liver enzyme elevation >2x the upper limit of normal

•Current or past history of meeting DSM-5 criteria for Schizophrenia, Psychotic Disorder (unless substance-induced or due to a medical condition), or Bipolar I Disorder

•Family (i.e., 1st degree relative) history of Schizophrenia, Psychotic Disorder (unless substance-induced or due to a medical condition), or Bipolar I Disorder

•Past-year hallucinogen use.

Endpoints (2)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Global cognition

Behavior / neuropsychiatric

Global cognition

1 endpoint

Secondary/protocol endpoint

Change in Quality of Life Alzheimer's Disease (QOL-AD) scale score

Time frame:Baseline and 2 weeks after second psilocybin session

change from baseline, improvement

Behavior / neuropsychiatric

1 endpoint

Primary/protocol endpoint

Change in Cornell Scale for Depression in Dementia (CSDD) score

Time frame:Baseline and 1 week after second psilocybin session

change from baseline, improvement

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableno registry results posted yet

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.