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

NCT04123314 | Recruiting Early Phase 1 FDA Drug

• 1 other identifier: IRB00175915
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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

Keywords

Psilocybin; Hallucinogen; Psychedelic

Outcome Measures

Primary Outcomes (1)

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

  The Cornell Scale for Depression in Dementia (CSDD) is administered via patient and informant interviews to assess the presence and severity of depressive mood and behavioral symptoms during the past week. Has 19 items, each scored from 0 to 2 with higher scores indicating severe symptom.Total score range from 0 to 38.

  Baseline and 1 week after second psilocybin session

Secondary Outcomes (1)

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

  Baseline and 2 weeks after second psilocybin session

Study Arms (1)

Psilocybin

EXPERIMENTAL

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.

Drug: Psilocybin

Interventions

Psilocybin DRUG

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.

Psilocybin

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Johns Hopkins University: lead
• Council On Spiritual Practices: collaborator
• Heffter Research Institute: collaborator

Study Sites (1)

Johns Hopkins Center for Psychedelic and Consciousness Research

Baltimore, Maryland, 21224, United States

RECRUITING

Related Links

• Study information and application form

MeSH Terms

Conditions

Depression; Alzheimer Disease; Cognitive Dysfunction

Interventions

Psilocybin

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines

Study Officials

• Albert Garcia-Romeu, PhD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ian Geithner, MPS

CONTACT

4105505466; igeithn1@jhmi.edu

Albert Garcia-Romeu, PhD

CONTACT

4105501972; agarci33@jhmi.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 9, 2019
• First Posted: October 10, 2019
• Study Start: March 24, 2021
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: March 16, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)