RecruitingEarly Phase 1NCT04123314

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

Sponsor

Johns Hopkins University

Enrollment

20 participants

Start Date

Mar 24, 2021

Study Type

INTERVENTIONAL

Conditions

Depression Depressive Symptoms Alzheimer Disease Mild Cognitive Impairment

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.

Eligibility

Min Age: 18 YearsMax Age: 85 Years

Inclusion Criteria7

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 Criteria13

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.

Interventions

DRUGPsilocybin

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.