Psilocybin-facilitated Treatment for Cocaine Use

NCT02037126 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: IND_121000
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The primary purpose of this study is to evaluate the feasibility and estimate the efficacy of psilocybin-facilitated treatment for cocaine use. We also will monitor the impact of psilocybin-facilitated treatment on the use of other drugs and outcomes relevant to cocaine involvement. MRI assessment is a unique aspect of this study. As a potential biological mechanism of psilocybin's effect includes changes in default mode network functional connectivity (Carhart-Harris et al., 2012), we will determine if psilocybin's therapeutic effects are mediated by such changes. Moreover, as Glx (a brain metabolite that reflects glutamate) abnormalities have been shown to play a role in cocaine addiction, we will determine if psilocybin impacts Glx in the anterior cingulate cortex and hippocampus.

Conditions

Cocaine-Related Disorders

Outcome Measures

Primary Outcomes (3)

• The difference between the psilocybin and placebo groups in the percentage of days abstinent from cocaine, verified by urine drug screen.

  Percentage of days abstinent from cocaine among subjects in each of the arms (subjects receiving psilocybin and subjects receiving placebo) assessed with the Timeline Followback Interview and with biochemically verified cocaine presence as assessed via a urine drug screen.

  From the psilocybin or placebo administration session to end-of-treatment (approximately 4 weeks in most participants), from end-of-treatment to 12 weeks after end-of-treatment, and from 12 weeks after end-of-treatment to 24 weeks after end-of-treatment.

• The difference between the psilocybin and placebo groups in sustained/complete abstinence from cocaine, verified by urine drug screen.

  Sustained/complete abstinence from cocaine among subjects in each of the arms (subjects receiving psilocybin and subjects receiving placebo) assessed with the Timeline Followback Interview and with biochemically verified cocaine presence as assessed via a urine drug screen.

  From the psilocybin or placebo administration session to 24 weeks after end-of-treatment.

• The difference between the psilocybin and placebo groups in time to cocaine lapse.

  Number of days to first use of cocaine after the drug administration session among subjects in each of the arms (subjects receiving psilocybin and subjects receiving placebo) assessed with the Timeline Followback Interview and with biochemically verified cocaine presence as assessed via a urine drug screen.

  From the psilocybin or placebo administration session to 24 weeks after end-of-treatment.

Secondary Outcomes (12)

• The difference between the psilocybin and placebo groups in the severity of cocaine dependence.

  Within 48 hours after psilocybin or placebo administration, at end-of-treatment (approximately 4 weeks after psilocybin or placebo administration in most participants), at 12 weeks after end-of-treatment, and at 24 weeks after end-of-treatment.

• The difference between the psilocybin and placebo groups in the severity of cocaine withdrawal symptoms.

  Within 48 hours after psilocybin or placebo administration, at end-of-treatment (approximately 4 weeks after psilocybin or placebo administration in most participants), at 12 weeks after end-of-treatment, and at 24 weeks after end-of-treatment.

• The difference between the psilocybin and placebo groups in cocaine craving.

  Within 48 hours after psilocybin or placebo administration, at end-of-treatment (approximately 4 weeks after psilocybin or placebo administration in most participants), at 12 weeks after end-of-treatment, and at 24 weeks after end-of-treatment.

• The difference between the psilocybin and placebo groups in situational cocaine abstinence self-efficacy.

  Within 48 hours after psilocybin or placebo administration, at end-of-treatment (approximately 4 weeks after psilocybin or placebo administration in most participants), at 12 weeks after end-of-treatment, and at 24 weeks after end-of-treatment.

• The difference between the psilocybin and placebo groups in motivation to quit/remain abstinent, confidence in the ability to quit/remain abstinent, and perceived difficulty quitting/remaining abstinent.

  Within 48 hours after psilocybin or placebo administration, at end-of-treatment (approximately 4 weeks after psilocybin or placebo administration in most participants), at 12 weeks after end-of-treatment, and at 24 weeks after end-of-treatment.

Study Arms (2)

Psilocybin administration

EXPERIMENTAL

Psilocybin will be administered in pill form at a dose of .36 mg/kg. Psilocybin will be administered in one session over the course of 8 hours.

Drug: Psilocybin

Diphenhydramine administration

ACTIVE COMPARATOR

Diphenhydramine will be administered in pill form at a dose of 100 mg. Diphenhydramine will be administered in one session over the course of 8 hours.

Drug: Diphenhydramine

Interventions

Psilocybin DRUG

this has been used in treating obsessive-compulsive disorders, cluster headaches, anxiety, and drug dependence.

Also known as: psychedelic compound

Psilocybin administration

Diphenhydramine DRUG

This drug will be used as the control. Diphenhydramine is a histamine blocker.

Also known as: Benadryl

Diphenhydramine administration

Eligibility Criteria

• Age: 25 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age and older
• Score of at least 3 on the Severity of Dependence Scale
• Desire to cease cocaine use as indicated by a goal of complete cocaine abstinence on the Thoughts about Abstinence questionnaire
• Ability to read/write in English
• No prior hallucinogen use or it will have been at least 3 years since their last use of a hallucinogen
• Availability of a friend or family member into whose care the participant can be released following their drug administration session.
• In good general health as assessed by detailed medical history and physical examination
• Abstinence from cocaine for at least 7 days prior to experimental drug administration as confirmed via urinalysis and no signs of intoxication on other drugs.

You may not qualify if:

• years of age and younger
• Women who are pregnant or breast feeding
• Current psychiatric diagnoses other than substance abuse/dependence
• Current hypertension (exceeding 140 systolic and 90 diastolic at resting as described below)
• Use of tricyclic antidepressants, lithium, Selective Serotonin Reuptake Inhibitors, Monoamine Oxidase Inhibitors, haloperidol, St. John's Wort, or other antipsychotic medications, mood stabilizers, or medications with serotonin activity
• History of any psychotic disorders
• History of bipolar I or II disorder
• First or second-degree relatives with any psychotic disorders, or bipolar I or II disorders
• Current suicidal or homicidal ideation
• Planning to move from the Birmingham area in the next 6 months
• Contraindications of MRI (metallic objects in the body, claustrophobia, difficulty with prior MRI)

Sponsors & Collaborators

• University of Alabama at Birmingham: lead

Study Sites (1)

UAB Outpatient Clinical Research Unit

Birmingham, Alabama, 35294, United States

Location

MeSH Terms

Conditions

Cocaine-Related Disorders

Interventions

Psilocybin; Diphenhydramine

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines; Ethylamines; Amines; Organic Chemicals; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Peter S. Hendricks, Ph.D.

  UAB Department of Psychiatry

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Independent statisticians
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: University Professor

Study Record Dates

• First Submitted: January 13, 2014
• First Posted: January 15, 2014
• Study Start: May 1, 2015
• Primary Completion: May 1, 2024
• Study Completion: May 1, 2024
• Last Updated: August 1, 2025

Record last verified: 2025-07

Locations

US (1)