Recruiting
Early Phase 1

Psilocybin

Sponsor:

Johns Hopkins University

Code:

NCT04123314

Conditions

Depressive Symptoms

Depression

Alzheimer Disease

Mild Cognitive Impairment

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

Psilocybin

Study Details

Brief summary:

This open-label pilot study examines whether the hallucinogenic drug, psilocybin, given under supportive conditions, is safe and effective for depression in people with Mild Cognitive Impairment (MCI) or early Alzheimer's Disease (AD). This study will also assess whether psilocybin may improve quality of life in those individuals.

Conditions

Depressive Symptoms

Depression

Alzheimer Disease

Mild Cognitive Impairment

Study ID

NCT04123314

Start date

Mar 24, 2021

Status verified date

Sep, 2026

Completion date

Sep 30, 2027

Anticipated

Primary completion date

Jun 30, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not 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.

Study Design

Enrollment

20 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Psilocybin

Participants will complete an 8-week course of study treatment including weekly psychological support and two moderate to high dose psilocybin administrations in weeks 4 and 6.

Interventions

Psilocybin

Dosing at the first session will be 15 mg/70 kg. For the second session participants will either remain at the initial dose, or increase to 25 mg/70 kg at the discretion of the study team.

Primary outcome measure

  • Change in Cornell Scale for Depression in Dementia (CSDD) score [ Time Frame: Baseline and 1 week after second psilocybin session ]

Central Contacts and Locations

Central contacts

Ian Geithner, MPS

4105505466igeithn1@jhmi.edu

Albert Garcia-Romeu, PhD

4105501972agarci33@jhmi.edu

Locations

Johns Hopkins Center for Psychedelic and Consciousness Research

Recruiting

Baltimore, Maryland, United States, 21224

Contacts

Ian Geithner, MPS

410-550-5466igeithn1@jhmi.edu

Albert Garcia-Romeu, PhD

410-550-1972agarci33@jhmi.edu

Principal Investigator:

Albert Garcia-Romeu, PhD

More Information

Sponsor

Johns Hopkins University

Last update posted

Sep 4, 2026

Last verified

Sep, 2026

Keywords

  • Psilocybin
  • Hallucinogen
  • Psychedelic

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-27. This information was provided to ClinicalTrials.gov by Johns Hopkins University on 2026-09-04. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.