Exploratory Study of Low Dose Psilocybin

NCT05227742 | Withdrawn Early Phase 1 DMC FDA Drug

• 1 other identifier: IRB-300008551
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the present study is to evaluate the feasibility, initial signals of efficacy, and potential mechanisms of action of "microdoses" of psilocybin (i.e., low doses of psilocybin that are not believed to produce mystical-type, transcendent, hallucinogenic, or other overtly salient subjective effects that limit functionality) in the treatment of moderate to severe demoralization (feelings of hopelessness and meaningless that frequently accompany medical illness and other life hardship).

Conditions

Demoralization

Keywords

Psilocybin; Low dose; Demoralization

Outcome Measures

Primary Outcomes (14)

• Demoralization

  Demoralization as assessed by the Demoralization Scale-II (DS-II; possible range = 0 to 32, with higher scores reflecting worse outcomes)

  Study Termination at Week 8

• Mystical Experience

  Mystical experience as assessed by the Mystical Experience Questionnaire (MEQ; possible range = 0 to 5, with higher scores reflecting more mystical experience)

  At the conclusion of Drug Administration #1 at Week 3

• Mystical Experience

  Mystical experience as assessed by the Mystical Experience Questionnaire (MEQ; possible range = 0 to 5, with higher scores reflecting more mystical experience)

  At the conclusion of Drug Administration #2 at Week 4

• Mystical Experience

  Mystical experience as assessed by the Mystical Experience Questionnaire (MEQ; possible range = 0 to 5, with higher scores reflecting more mystical experience)

  At the conclusion of Drug Administration #3 at Week 5

• Mystical Experience

  Mystical experience as assessed by the Mystical Experience Questionnaire (MEQ; possible range = 0 to 5, with higher scores reflecting more mystical experience)

  At the conclusion of Drug Administration #4 at Week 6

• Mystical Experience

  Mystical experience as assessed by the Mystical Experience Questionnaire (MEQ; possible range = 0 to 5, with higher scores reflecting more mystical experience)

  At the conclusion of Drug Administration #5 at Week 7

• Challenging Experience

  Challenging experience as assessed by the Challenging Experience Questionnaire (CEQ; possible range = 0=5, with higher scores reflection more challenging experiences)

  At the conclusion of Drug Administration #1 at Week 3

• Challenging Experience

  Challenging experience as assessed by the Challenging Experience Questionnaire (CEQ; possible range = 0=5, with higher scores reflection more challenging experiences)

  At the conclusion of Drug Administration #2 at Week 4

• Challenging Experience

  Challenging experience as assessed by the Challenging Experience Questionnaire (CEQ; possible range = 0=5, with higher scores reflection more challenging experiences)

  At the conclusion of Drug Administration #3 at Week 5

• Challenging Experience

  Challenging experience as assessed by the Challenging Experience Questionnaire (CEQ; possible range = 0=5, with higher scores reflection more challenging experiences)

  At the conclusion of Drug Administration #4 at Week 6

• Challenging Experience

  Challenging experience as assessed by the Challenging Experience Questionnaire (CEQ; possible range = 0=5, with higher scores reflection more challenging experiences)

  At the conclusion of Drug Administration #5 at Week 7

• PASAT

  Executive functioning as assessed by the Paced Auditory Serial Addition Test (PASAT)

  At hour 2 of Drug Administration #3 at Week 5

• Trail Making

  Executive functioning as assessed by the Delis-Kaplan Trail Making Test

  At hour 2 of Drug Administration #4 at Week 6

• CPT-3

  Attention and cognitive control as assessed by Conner's Continuous Performance Test (CPT-3)

  At hour 2 of Drug Administration #5 at Week 7

Study Arms (4)

Placebo (0 mg psilocybin)

PLACEBO COMPARATOR

Participants in this arm will receive 0 mg of psilocybin once per week for 5 weeks.

Drug: Placebo

1 mg psilocybin

EXPERIMENTAL

Participants in this arm will receive 1 mg psilocybin once per week for 5 weeks.

Drug: Psilocybin

2.5 mg psilocybin

EXPERIMENTAL

Participants in this arm will receive 2.5 mg psilocybin once per week for 5 weeks.

Drug: Psilocybin

5 mg psilocybin

EXPERIMENTAL

Participants in this arm will receive 5 mg psilocybin once per week for 5 weeks.

Drug: Psilocybin

Interventions

Psilocybin DRUG

Participants will receive oral psilocybin once per week for 5 weeks.

1 mg psilocybin; 2.5 mg psilocybin; 5 mg psilocybin

Placebo DRUG

Participants will receive inert placebo once per week for 5 weeks.

Placebo (0 mg psilocybin)

Eligibility Criteria

• Age: 25 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• years of age or younger; 66 years of age or older
• Women who are pregnant (pregnancy status confirmed via urine pregnancy test) or breastfeeding
• Current hypertension (exceeding 140 systolic and/or 90 diastolic at resting)
• 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)
• Personal or family history (first or second degree relatives) of psychotic or bipolar I or II disorders
• 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).
• History of head trauma, loss of consciousness, or neurological disease
• Receiving treatment within the past 30 days for depression, anxiety, or substance use disorder
• Participation within the past 30 days in a clinical trial for the treatment of depression, anxiety, or substance use disorder
• Any current substance use disorder diagnosis (substance abstinence confirmed via urine drug screen)
• 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
• Any headache disorder (i.e., migraine, tension-type headache, or cluster headache) in the past year
• Planning to move from the Birmingham area in the next 3 months

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• Diamond Therapeutics Inc.: collaborator

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35209, United States

Location

MeSH Terms

Interventions

Psilocybin

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: This is a double-blind, placebo-controlled clinical trial.

Study Record Dates

• First Submitted: January 13, 2022
• First Posted: February 7, 2022
• Study Start: August 15, 2023
• Primary Completion: March 1, 2026
• Study Completion: March 1, 2026
• Last Updated: March 11, 2026

Record last verified: 2026-03

Locations

US (1)