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

Early Phase 1

Recruiting

• Conditions: Depressive Symptoms; Depression; Alzheimer Disease; Mild Cognitive Impairment
• Interventions: Drug: Psilocybin

• Registration Number: NCT04123314
• Lead Sponsor: Johns Hopkins University

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.

Detailed Description

This is a pilot study evaluating the potential efficacy of psilocybin to produce improvement in depression compared to pre-treatment in people with Mild Cognitive Impairment (MCI) or early Alzheimer's Disease (AD) and clinically significant symptoms of depression. The study will be an open-label trial in a sample of up to 20 treatment-seeking participants with a diagnosis of MCI or early AD. Participants will complete an 8-week course of study treatment including two psilocybin sessions (15 mg/70 kg in week 4 and 15 or 25 mg/70 kg in week 6), with follow-up assessments up to 6 months after the final psilocybin session. The study will assess changes in depressed mood at 1 week after the second psilocybin session compared to pre-treatment, and quality of life in participants from pre- to post-treatment.

Study Timeline

• Study First Submitted: 2019-10-09
• Study First Submitted QC: 2019-10-09
• Study First Posted: 2019-10-10
• Study Start: 2021-03-24
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-14
• Last Update Posted: 2024-08-16
• Primary Completion: 2025-09-30
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 20

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

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Psilocybin	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.

Primary Outcome Measures

Name	Time	Method
Change in Cornell Scale for Depression in Dementia (CSDD) score	Baseline and 1 week after second psilocybin session	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.

Secondary Outcome Measures

Name	Time	Method
Change in Quality of Life Alzheimer's Disease (QOL-AD) scale score	Baseline and 2 weeks after second psilocybin session	The Quality of Life Alzheimer's Disease (QOL-AD) scale is a 13-item measure administered via patient and informant interviews to assess overall mood, physical and cognitive function, and quality of relationships in people with Alzheimer's Disease. Each item is scored 1 to 4, with higher score indicating better quality of life. Total score range from 13 to 52.

Trial Locations

Locations (1)

Behavioral Pharmacology Research Unit; 🇺🇸 Baltimore, Maryland, United States