Using psilocybin to treat 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

This study is testing if psilocybin can help improve mood and quality of life for people with mild cognitive impairment or early Alzheimer's disease who are feeling depressed.

Quick facts

• Phase: EARLY_PHASE1
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years to 85 Years
• Sex: All
• Sponsor: Johns Hopkins University (other)
• Locations: 1 site (Baltimore, Maryland)
• Trial ID: NCT04123314 on ClinicalTrials.gov

What this trial studies

This open-label pilot study investigates the safety and effectiveness of psilocybin, a hallucinogenic drug, for alleviating depressive symptoms in individuals diagnosed with Mild Cognitive Impairment (MCI) or early Alzheimer's Disease (AD). The study involves up to 20 participants who will undergo an 8-week treatment course, including two psilocybin sessions. Assessments will be conducted to evaluate changes in mood and quality of life from pre-treatment to post-treatment, with follow-ups extending up to 6 months after the final session.

Who should consider this trial

Good fit: Ideal candidates include individuals diagnosed with Mild Cognitive Impairment or early Alzheimer's Disease who exhibit clinically significant depressive symptoms.

Not a fit: Patients with severe cognitive impairment or those not meeting the specific diagnostic criteria for MCI or early AD may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a novel therapeutic option for managing depression in patients with cognitive impairments.

How similar studies have performed: While the use of psilocybin in treating depression is emerging, this specific application in patients with cognitive impairment is novel and has not been extensively tested.

Eligibility criteria

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.

Where this trial is running

Baltimore, Maryland

• Johns Hopkins Center for Psychedelic and Consciousness Research — Baltimore, Maryland, United States (RECRUITING)

Study contacts

• Principal investigator: Albert Garcia-Romeu, PhD — Johns Hopkins University
• Study coordinator: Ian Geithner, MPS

Conditions: Depressive Symptoms, Depression, Alzheimer Disease, Mild Cognitive Impairment, Psilocybin, Hallucinogen, Psychedelic