Clinical TrialDepressive DisordersPlaceboPsilocybinPsilocybinPsilocybinRecruiting

Exploratory Study of Low Dose Psilocybin

Randomised, double-blind, quadruple-masked, parallel-group early-phase study (n=60) testing once-weekly low-dose psilocybin (0, 1, 2.5, 5 mg) for demoralization.

Target Enrollment
60 participants
Study Type
Phase I interventional
Design
Randomized, quadruple Blind

Detailed Description

This parallel-group, randomized, quadruple-masked early-phase trial will evaluate feasibility, initial signals of efficacy, and mechanisms of action of once-weekly low doses of oral psilocybin (0, 1, 2.5, 5 mg) over five weekly 6-hour administration sessions in adults with moderate to severe demoralization.

Assessments include baseline medical and psychiatric evaluation, repeated self-report VAS measures during each 6-hour session, EEG tasks at peak drug effects across sessions, and brief qualitative interviews after each session; blood pressure and ECG monitoring with clinical thresholds for intervention are specified.

Primary aims are feasibility and early efficacy signals on demoralization; secondary aims include mechanistic evaluation using EEG and safety/tolerability through adverse event monitoring and vital signs.

Study Protocol

Preparation

2 sessions

Dosing

5 sessions
360 min each

Integration

sessions

Study Arms & Interventions

Placebo

inactive

0 mg psilocybin once weekly for 5 weeks (placebo).

Interventions

  • Placebo0 mg
    via Oral• weekly• 5 doses total

    Inert placebo administered once weekly for 5 weeks.

1 mg

experimental

Psilocybin 1 mg once weekly for 5 weeks (microdose).

Interventions

  • Psilocybin1 mg
    via Oral• weekly• 5 doses total

    Low-dose psilocybin (microdose) given once weekly for 5 weeks.

2.5 mg

experimental

Psilocybin 2.5 mg once weekly for 5 weeks (microdose).

Interventions

  • Psilocybin2.5 mg
    via Oral• weekly• 5 doses total

    Low-dose psilocybin (microdose) given once weekly for 5 weeks.

5 mg

experimental

Psilocybin 5 mg once weekly for 5 weeks (microdose).

Interventions

  • Psilocybin5 mg
    via Oral• weekly• 5 doses total

    Low-dose psilocybin (microdose) given once weekly for 5 weeks.

Participants

Ages
25 – 65
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • 1. Ability to read and write in English
  • 2. Between 25 and 65 years old
  • 3. Demoralization Scale-II (DS-II) score of > 8
  • 4. No prior hallucinogen use or it would have been 3 years since the last use of a hallucinogen
  • 5. Availability of a friend, family member, or other form of transportation (e.g., Uber) to drive participants home after their drug administration sessions
  • 6. In good general health as assessed by detailed medical history interview and physical examination

Exclusion Criteria

  • Exclusion Criteria:
  • 1. 24 years of age or younger; 66 years of age or older
  • 2. Women who are pregnant (pregnancy status confirmed via urine pregnancy test) or breastfeeding
  • 3. Current hypertension (exceeding 140 systolic and/or 90 diastolic at resting)
  • 4. Use of methylphenidate or other medications for ADHD, benzodiazepines or other medications for anxiety (e.g., beta-blockers), tricyclic antidepressants, MAOIs, SSRIs, SNRIs or other medications for depression, lithium or other mood stabilizers, haloperidol or other antipsychotic medications, any medications or supplements with serotonin activity (e.g., St. John's Wort), or any other pharmacologic or biologic agent used to treat depression or anxiety (e.g., magnesium, cannabis)
  • 5. Personal or family history (first or second degree relatives) of psychotic or bipolar I or II disorders
  • 6. Any suicidal ideation of type 4 or type 5 on the Columbia Suicide Severity Rating Scale (C-SSRS) in the 3 months prior to screening (i.e., active suicidal thought with method and intent but without a specific plan, or active suicidal thought with method, intent and plan).
  • 7. History of head trauma, loss of consciousness, or neurological disease
  • 8. Receiving treatment within the past 30 days for depression, anxiety, or substance use disorder
  • 9. Participation within the past 30 days in a clinical trial for the treatment of depression, anxiety, or substance use disorder
  • 10. Any current substance use disorder diagnosis (substance abstinence confirmed via urine drug screen)
  • 11. History of immoderate alcohol consumption within the past 3 months per NIAAA definitions: more than 4 drinks per day or 14 drinks per week for men; more than 3 drinks per day or 7 drinks per week for women
  • 12. Any headache disorder (i.e., migraine, tension-type headache, or cluster headache) in the past year
  • 13. Planning to move from the Birmingham area in the next 3 months

Study Details

Locations

University of Alabama at Birmingham — Birmingham, Alabama, United States

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