Reducing Cannabis Overuse With Prazosin

NCT04721353 | Completed Phase 4 FDA Drug

• 1 other identifier: STUDY00010457
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

Cannabis use disorder (CUD) is a significant and expanding health problem, and no FDA approved treatments are currently available. Persons with posttraumatic stress disorder (PTSD) may use cannabis to help control symptoms. Relief from PTSD insomnia, nightmares, anxiety, and preoccupying thoughts have been reported as troublesome symptoms targeted by cannabis users. Risks from cannabis use by individuals with PTSD have been reported. Chronic use of cannabis can lead to tolerance, requiring increased use for symptom relief, and withdrawal symptoms upon stopping. CUD is more frequent and severe in those with PTSD than those without. Many symptoms of cannabis withdrawal overlap with troubling symptoms of PTSD and thus may be interpreted as a relapse of PTSD symptoms. Those attempting to reduce or stop cannabis use may experience cannabis withdrawal symptoms including insomnia and distressing dreams, anxiety, irritability, and/or excessive sweating that they may misattribute to re-emerging or untreated PTSD symptoms. Excessive brain adrenaline activity is arguably the best-described neurobiological contribution to the pathophysiology of PTSD. Prazosin, a drug that blocks the negative effects of brain adrenaline, has demonstrated effectiveness in robustly reducing PTSD-related nightmares and sleep disturbance in active duty Servicemembers and recently discharged combat Veterans in most, but not all, clinical trials, as well as in civilians with non-combat trauma. Clinically, the investigators have observed that several patients with PTSD using cannabis to treat insomnia and/or trauma-related nightmares and wanting to reduce their cannabis use were able to achieve reduction or cessation of cannabis use once they were treated with an effective dose of prazosin. Therefore, we have wondered if prazosin may provide sufficient treatment of PTSD symptoms otherwise targeted by cannabis, supporting those individuals' efforts to reduce cannabis use. This open-label pilot study aims to study the feasibility of prazosin as a treatment for CUD in individuals with or without comorbid PTSD, and to evaluate if additional research on a larger scale is warranted.

Conditions

Cannabis Dependence; Posttraumatic Stress Disorder; Cannabis Use Disorder

Keywords

Prazosin; Cannabis

Outcome Measures

Primary Outcomes (4)

• Recruitment

  Proportion of potential participants referred to the study meeting inclusion/exclusion criteria and complete the baseline visit

  Approximately 2 weeks

• Retention

  Mean and median weeks participants remained in the study between baseline and end of treatment at week 12

  12 weeks

• Acceptability of participation

  Total score from a 7-item exit questionnaire each with 5 point scale responses assessing: likelihood of repeat participation, difficulty of participation, difficulty of attending study visits, difficulty of taking study medication, satisfaction with study team, likelihood of referral, overall satisfaction of participation

  16 weeks

• Quantifying cannabis consumption

  Regression comparison of semi-quantitative urine tetrahydrocannabinol (THC) metabolite and self-reported cannabis use by timeline follow back over the course of the study

  16 weeks

Secondary Outcomes (1)

• Treatment outcome (exploratory)

  16 weeks

Study Arms (1)

Open-label prazosin treatment

EXPERIMENTAL

Open-label administration of prazosin

Drug: Prazosin Hydrochloride

Interventions

Prazosin Hydrochloride DRUG

prazosin hydrochloride oral 1-25 mg/day

Also known as: minipress

Open-label prazosin treatment

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men, women, and persons of all races and ethnic backgrounds are eligible.
• Age 18 to 80 years inclusive
• Ability to complete self-assessments and other clinical assessments in English
• Meet criteria for CUD within the last 30 days
• Report a minimum of 4 days a week or more of cannabis use (as assessed by 30 day TLFB at screening visit)
• Have a positive cannabinoid urine test
• Be in good general health
• Persons of childbearing potential must agree to use an effective means of birth control.
• Have a confirmed diagnosis on the Mini-International Neuropsychiatric Interview (MINI).

You may not qualify if:

• Presence of a cognitive disorder
• Current or past 3 months substance use disorder of any substance other than cannabis or tobacco (e.g., AUD, opioid use disorder)
• Current and/or ongoing use of any substance other than cannabis, tobacco, or alcohol within the last 30 days
• Current and/or ongoing use of synthetic cannabinoids (e.g., Spice, K2) within the last 30 days
• Positive urine drug screen for any drug of abuse other than cannabis at screening visit
• Persons of childbearing potential who are pregnant, planning to become pregnant, or nursing during the study period
• Allergy or previous adverse reaction to prazosin or other alpha-1 adrenoceptor antagonist
• Previously diagnosed but untreated severe sleep apnea
• Psychiatric instability or severe situational life crises, including evidence of being actively suicidal or homicidal
• Any unstable medical illness that may place the participant at increased risk in the judgment of the clinician
• Potential participants who have been taking trazodone will undergo a 2-week washout period before beginning study treatment to reduce risk of priapism.

Sponsors & Collaborators

• VA Puget Sound Health Care System: lead
• University of Washington: collaborator
• VA Mental Illness Research, Education and Clinical Centers: collaborator

Study Sites (1)

VA Puget Sound Health Care System

Seattle, Washington, 98108, United States

Location

Related Links

• Study group website

MeSH Terms

Conditions

Marijuana Abuse; Stress Disorders, Post-Traumatic

Interventions

Prazosin

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Stress Disorders, Traumatic; Trauma and Stressor Related Disorders

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Garth E Terry, MD, PhD

  University of Washington

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: FED
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, School of Medicine

Model Details: Open-label study of prazosin for treatment of cannabis use disorder

Study Record Dates

• First Submitted: January 14, 2021
• First Posted: January 22, 2021
• Study Start: November 9, 2020
• Primary Completion: December 31, 2024
• Study Completion: June 1, 2025
• Last Updated: June 15, 2025

Record last verified: 2025-06

Locations

US (1)