Clinical TrialDepressive DisordersPsilocybinRecruiting

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

Open-label single-group pilot (n=20) with weekly psychological support and two psilocybin sessions (15 mg/70 kg at week 4; 15 or 25 mg/70 kg at week 6) for depression in people with MCI or early Alzheimer’s disease.

Target Enrollment
20 participants
Study Type
Phase I interventional
Design
Non-randomized

Detailed Description

This open-label pilot evaluates psilocybin administered in two sessions alongside weekly psychological support in up to 20 participants with Mild Cognitive Impairment or early Alzheimer’s disease and clinically significant depressive symptoms.

Dosing: first session 15 mg/70 kg (week 4); second session 15 or 25 mg/70 kg (week 6) per study team discretion. Primary outcome is change in depressed mood one week after the second session versus pre-treatment; follow-up extends to six months.

Study Protocol

Preparation

8 sessions

Dosing

2 sessions

Integration

sessions

Therapeutic Protocol

support

Study Arms & Interventions

Psilocybin

experimental

Single-group course with weekly psychological support and two psilocybin dosing sessions (weeks 4 and 6).

Interventions

  • Psilocybin15 - 25 mg
    via Oral• two sessions• 2 doses total

    15 mg/70 kg first session; second session 15 or 25 mg/70 kg per study team discretion.

Participants

Ages
18 – 85
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • Must meet either A) 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
  • Mini-Mental State Examination score >18
  • Montreal Cognitive Assessment score <26
  • Cornell Scale for Depression in Dementia (CSDD) patient score >=6, or Geriatric Depression Scale-Short Form score >=5
  • Acetylcholinesterase inhibitors allowed if dose stable >6 weeks
  • Concurrent pharmacotherapy with SSRIs, SNRIs, and/or bupropion allowed if type and frequency stable for >=2 months; allowable bupropion doses <=300 mg/day
  • Have a close friend or family member willing and able to serve as community observer/informant

Exclusion Criteria

  • Exclusion Criteria:
  • Individuals 86 years of age or older
  • Currently taking antipsychotics, monoamine oxidase (MAO) inhibitors, or antidepressant medications other than SSRIs, SNRIs, or bupropion
  • Long-acting opioid pain medications allowed only if timing criteria around dosing met
  • Must agree not to take sildenafil, tadalafil, or similar within 72 hours of each psilocybin administration
  • Cardiovascular conditions: angina, clinically significant ECG abnormality (e.g. atrial fibrillation or QTc >450 ms), TIA in last 6 months, stroke, artificial heart valves, or uncontrolled hypertension (resting BP systolic >150 or diastolic >95)
  • Minimum acceptable heart rate at screening is 50 bpm unless cleared by a cardiologist
  • Seizure disorder
  • Insulin dependent diabetes mellitus
  • Renal disease (creatinine clearance <40 ml/min)
  • Baseline liver enzyme elevation >2x ULN
  • Current or past history of schizophrenia, psychotic disorder (unless substance-induced or due to medical condition), or Bipolar I Disorder
  • Family (1st degree) history of schizophrenia, psychotic disorder (unless substance-induced or due to medical condition), or Bipolar I Disorder
  • Past-year hallucinogen use

Study Details

  • Status
    Recruiting
  • Phase
    Phase I
  • Type
    interventional
  • Design
    Non-randomized
  • Target Enrollment20 participants
  • Timeline
    Start: 2021-03-24
    End: 2023-12-30
  • Compound
    Psilocybin
  • Topic
    Depressive Disorders

Locations

Behavioral Pharmacology Research Unit — Baltimore, Maryland, United States

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