Psilocybin-assisted Treatment for Cannabis Use Disorder

Pilot Study of Psilocybin-assisted Treatment for Cannabis Use Disorder

This pilot study will evaluate the therapeutic potential of psilocybin in people with Cannabis Use Disorder (CUD). This study will examine the impact of psilocybin treatment on cannabis use and related variables in 12 people with CUD. This is an open-label proof-of-concept trial in which participants will complete a 12-week course of study treatment including two psilocybin sessions with psychological support, and follow-up assessments 3 and 6 months after the first psilocybin session.

Study Overview

• Status: Recruiting
• Conditions: Cannabis Use Disorder
• Intervention / Treatment: Drug: Psilocybin

Detailed Description

This pilot study will evaluate the therapeutic potential of psilocybin to produce significant reduction in cannabis use compared to pre-treatment in a sample of 12 treatment-seeking patients with Cannabis Use Disorder (CUD). Upon enrollment, participants will complete a 12-week course of study treatment including two psilocybin sessions, with follow-up assessment 3 and 6 months after the first psilocybin session. After 4 weekly preparatory meetings including a targeted cognitive behavioral therapy (CBT) intervention for CUD, participants will receive a moderately high dose (25mg) of psilocybin in week 5 of the 12-week counseling, and either another moderately high dose (25mg) or a high dose (35mg) in week 7. After each psilocybin session, participants will complete a follow-up meeting within 3 days (i.e. integration meeting), as well as continued weekly meetings through week 12. Participants will complete post-session assessments in approximately weeks 12 (End of Treatment), 17 (3 months after 1st psilocybin session, and 29 (6 months after 1st psilocybin session). Some study meetings may be held virtually via a secure web-based video conference platform (e.g., Zoom).

Self-reported cannabis use and biomarkers of recent use will be assessed at baseline (screening), weekly throughout the 12-week intervention, and at approximately weeks 17 (3 months after 1st psilocybin session), and 29 (6 months after 1st psilocybin session).

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Ian Geithner, MPS; Phone Number: 410-550-1972; Email: igeithn1@jhmi.edu
• Study Contact Backup: Name: Albert Garcia-Romeu, PhD; Email: agarci33@jhmi.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Recruiting
      • Johns Hopkins Center for Psychedelic and Consciousness Research
      • Contact: Albert Garcia-Romeu, PhD; Email: agarci33@jhmi.edu
      • Contact: Ian Geithner, MPS; Phone Number: 786-239-7990; Email: agromeu77@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• ≥ 18 years of age.
• Capable of providing written informed consent for participation into the study.
• Willingness to allow the study team to review past medical records.
• Currently meets criteria for The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnosis of Cannabis Use Disorder.
• Be medically stable as determined by screening for medical problems via a personal interview, a medical questionnaire, a physical examination, an electrocardiogram (ECG), and routine medical blood and urinalysis laboratory tests.
• Concurrent pharmacotherapy with selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), 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.

Exclusion Criteria:

• Meeting DSM-5 criteria for another moderate or severe substance use disorder (excluding tobacco) within the past 5 years.
• 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.
• Currently taking lithium or other primary centrally-acting serotonergic medications, whether over-the-counter or prescription (e.g., efavirenz, 5-hydroxytryptophan, St. John's wort).
• Cardiovascular conditions: angina, a clinically significant ECG abnormality (e.g. atrial fibrillation or corrected QT interval (QTc) > 450 msec), transient ischemic attack (TIA) in the last 6 months, stroke, artificial heart valves, or uncontrolled hypertension with resting blood pressure systolic >139 or diastolic >89, or heart rate >90 bpm.
• Body weight at screening <50kg.
• Renal disease (creatinine clearance < 60 ml/min using the Cockraft and Gault equation).
• Abnormal screening labs values for hemoglobin, white blood count, creatinine, potassium, and bilirubin outside of the normal lab reference rage.
• Transaminases greater than x2 the upper limit of normal lab reference range.
• 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 or II 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.
• Epilepsy with history of seizures.
• Insulin-dependent diabetes; if taking oral hypoglycemic agent, then no history of hypoglycemia.
• Current dementia or related disorders including but not limited to, Alzheimer's Disease, vascular dementia, Lewy body dementia, and frontotemporal disorders.
• Current or past major immunosuppressive illness or medications.
• Currently pregnant or nursing.
• Currently of childbearing potential and not using effective methods of contraception (i.e., intrauterine systems/devices, hormonal methods including implant, shot, patch, ring, or oral contraceptive, condom, diaphragm, sterilization, abstinence, and fertility-awareness methods).
• Not fluent in English.
• High risk for suicidal ideation or behavior (i.e., individuals who report suicidal ideation with intent or behavior on the Columbia Suicide Severity Rating Scale (C-SSRS) at screening, or individuals with a suicide attempt within the past 3 years).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Psilocybin; Open-label psilocybin will be administered with psychological support to each participant at two dosing sessions approximately 2 weeks apart.	Drug: Psilocybin; Participants will receive a moderately high dose (25mg) of psilocybin in week 5 of the 12-week counseling, and either another moderately high dose (25mg) or a high dose (35mg) in week 7.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Self-reported cannabis use as assessed by a modified Timeline Follow-Back interview	This information will be collected using a modified Timeline Follow-Back (TLFB) interview. The TLFB (past 30 days), uses a calendar with specific anchor dates to identify the quantity and frequency of use.	Baseline, weekly up to 3 months
Biomarkers of recent cannabis use	Urine samples will be collected and tested for the presence of biomarkers indicating cannabis use.	Baseline, 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Beck Depression Inventory-II (BDI-II) score	The BDI-II is a widely-used, 21-item measure of cognitive and vegetative depressive symptoms. It has good reliability and validity, and can be scored to include as well as exclude somatic symptoms. The total score can range from 0 to 63, with higher scores indicating more severe symptoms.	Baseline, 3 months
Pittsburgh Sleep Quality Index (PSQI) score	The PSQI is a 19-item self-report inventory that provides measures of daytime dysfunction; sleep latency, duration, disturbance, quality and efficiency. The component scores are summed to produce a global score (range 0 to 21). Higher scores indicate worse sleep quality.	Baseline, 3 months

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: Center for Psychedelic and Consciousness Research
• Investigators: Principal Investigator: Albert Garcia-Romeu, Ph.D., Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): November 8, 2024
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: October 24, 2024
• First Submitted That Met QC Criteria: October 24, 2024
• First Posted (Actual): October 28, 2024

Study Record Updates

• Last Update Posted (Actual): March 18, 2026
• Last Update Submitted That Met QC Criteria: March 16, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: cannabis; cannabis dependence
• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Marijuana Abuse; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Alkaloids; Indoles; Indole Alkaloids; Indolizidines; Indolizines; Tryptamines; Psilocybin
• Other Study ID Numbers: IRB00327911

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No