Cannabis DependencePhase 4ReCOUPNCT04721353
Reducing Cannabis Overuse With Prazosin
A Phase 4 study testing Prazosin Hydrochloride in people with Cannabis Dependence and Posttraumatic Stress Disorder, run by VA Puget Sound Health Care System at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Cannabis Dependence, Posttraumatic Stress Disorder, Cannabis Use Disorder
- What is being tested?
- Prazosin Hydrochloride
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Nov 2020to 1 Jun 2025
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- 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).
Who cannot join
- Presence of a cognitive disorder
- History of moderate or severe traumatic brain injury (mild traumatic brain injury is not exclusionary)
- 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
Show all 12Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
VA Puget Sound Health Care System
Seattle, Washington, 98108
About this study
Official title: Pilot Study to Assess the Feasibility of Prazosin for Cannabis Use Disorder in Individuals With or Without Post-traumatic Stress Disorder
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.
Read the detailed description
This pilot study aims to assess 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. In particular, the investigators will evaluate their ability to recruit and retain individuals with CUD, evaluate their ability to quantify cannabis use and associated clinical outcomes, and objectively measure cannabis use in context of a clinical trial.
Although the investigators have ample experience recruiting Veterans and non-Veterans with and without PTSD for prazosin clinical trials of similar duration, they have never recruited treatment-seeking CUD participants. Treatment studies in cannabis users are known to have approximately 30% drop out rate, and thus gaining experience in recruitment and retention is critical prior to investment in larger studies.
Specific Aim 1: Assess the feasibility of recruitment and retention of participants for a clinical trial using prazosin as a treatment of CUD.
The investigators will recruit 20 treatment seeking individuals with CUD (10 with and 10 without PTSD) for 12-week open label treatment of prazosin. Given their experience conducting studies in Veterans and non-Veterans with and without PTSD and/or alcohol use disorder (AUD) achieving 61-83% retention at end of treatment, the investigators anticipate that prazosin will be well tolerated in the study population. Participants will be asked to provide qualitative assessments of treatment acceptability, or reasons for early termination for those who drop out of the study before end of treatment, so that these issues can be addressed in future study design.
Specific Aim 2: Assess the feasibility of quantifying cannabis consumption by subjective self-report and objective urine and blood testing.
Quantification of cannabis use is complex and not standard within the field. Due to the multiple routes of cannabis self-administration, variable cannabinoid concentration in cannabis products, and variable tolerance and pharmacokinetics across cannabis users, the investigators seek to gain experience in quantifying cannabis use by self-report and objective testing, as these measures will directly affect their outcome assessments expected in a subsequent clinical trial design. The investigators will assess amount and frequency of cannabis used by self-report (i.e., typical grams consumed per day, number of sessions per day of use), tracked with regular semi-quantitative urine tests and validated by quantitative blood and urine testing at selected time points. Self-reported cannabis use will be assessed by the Quantification of Cannabis Consumption (QCC), a brief questionnaire designed and preliminarily tested by the investigators, and the timeline follow back (TLFB). Symptoms of CUD and cannabis withdrawal will be assessed with validated self-report measures. Semi-quantitative urine tests will provide a relatively inexpensive and rapid means of testing cannabis use. These measures will be compared against less frequent and fully quantitative urine and blood analysis using liquid chromatography-mass spectrometry (LC/MS). If self-report and semi-quantitative urine tests are consistent with those from LC/MS, then they will be utilized in subsequent clinical trials.
Exploratory Aims: The investigators will explore if prazosin administration is well tolerated and is associated with a reduction of cannabis withdrawal symptom severity and/or cannabis use. As there are no effective treatments for CUD, a reduction of cannabis use by at least 20% from baseline to end of treatment will be considered meaningful enough to warrant future study. In comparison, rates for attaining negative urine tests in two recent medication trials paired with contingency management or psychotherapy were 22% and 29%, respectively (with identical rates in placebo and treatment groups). Adverse events will be monitored and compared their frequencies to that experienced in prior studies of prazosin conducted by the investigators as an exploratory outcome. Additional exploratory outcomes include the comparison of cannabis use throughout the study between those with and without PTSD, and the reduction of PTSD-related nightmares in the PTSD group.
- Being tested
- Prazosin Hydrochloride
- Keywords
- Prazosin, Cannabis
- Medical subject headings
- Marijuana Abuse, Stress Disorders, Post-Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Prazosin HydrochlorideDrug
Also called minipress
prazosin hydrochloride oral 1-25 mg/day
| Study group | Role | What they receive |
|---|---|---|
| Open-label prazosin treatment | Experimental | Open-label administration of prazosin Receives: Drug: Prazosin Hydrochloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recruitment
Proportion of potential participants referred to the study meeting inclusion/exclusion criteria and complete the baseline visit
Measured: Approximately 2 weeks
Retention
Mean and median weeks participants remained in the study between baseline and end of treatment at week 12
Measured: 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
Measured: 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
Measured: 16 weeks
Secondary outcomes (1)
Treatment outcome (exploratory)
Change in cannabis consumption pre/post prazosin treatment
Measured: 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2021
- Study start9 Nov 2020
- Primary completion31 Dec 2024
- Study completion1 Jun 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cannabis DependenceStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Open-label study of prazosin for treatment of cannabis use disorder
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Puget Sound Health Care System
- Sponsor type
- US federal agency
- Collaborators
- University of Washington, VA Mental Illness Research, Education and Clinical Centers
- Responsible party
- Principal investigator, Garth Terry, University of Washington
- Investigators
- Garth E Terry, MD, PhD, Principal investigator, University of Washington
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04721353
- Sponsor's protocol ID
- STUDY00010457
- Acronym
- ReCOUP
- Status last verified
- Jun 2025
- First submitted
- 14 Jan 2021
- Last updated
- 15 Jun 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study to Assess the Feasibility of Prazosin for Cannabis Use Disorder in Individuals With or Without Post-traumatic Stress Disorder
- ClinicalTrials.gov ID
- NCT04721353
- Acronym / sponsor ID
- ReCOUP / STUDY00010457
- Keywords
- Prazosin, Cannabis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- VA Puget Sound Health Care SystemUS federal agency
- Collaborators
- University of Washington, VA Mental Illness Research, Education and Clinical Centers
- Study start
- 9 Nov 2020 (actual)
- Primary completion
- 31 Dec 2024 (actual)
- Study completion
- 1 Jun 2025 (actual)
- First posted
- 22 Jan 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This pilot study aims to assess 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. In particular, the investigators will evaluate their ability to recruit and retain individuals with CUD, evaluate their ability to quantify cannabis use and associated clinical outcomes, and objectively measure cannabis use in context of a clinical trial.
Although the investigators have ample experience recruiting Veterans and non-Veterans with and without PTSD for prazosin clinical trials of similar duration, they have never recruited treatment-seeking CUD participants. Treatment studies in cannabis users are known to have approximately 30% drop out rate, and thus gaining experience in recruitment and retention is critical prior to investment in larger studies.
Specific Aim 1: Assess the feasibility of recruitment and retention of participants for a clinical trial using prazosin as a treatment of CUD.
The investigators will recruit 20 treatment seeking individuals with CUD (10 with and 10 without PTSD) for 12-week open label treatment of prazosin. Given their experience conducting studies in Veterans and non-Veterans with and without PTSD and/or alcohol use disorder (AUD) achieving 61-83% retention at end of treatment, the investigators anticipate that prazosin will be well tolerated in the study population. Participants will be asked to provide qualitative assessments of treatment acceptability, or reasons for early termination for those who drop out of the study before end of treatment, so that these issues can be addressed in future study design.
Specific Aim 2: Assess the feasibility of quantifying cannabis consumption by subjective self-report and objective urine and blood testing.
Quantification of cannabis use is complex and not standard within the field. Due to the multiple routes of cannabis self-administration, variable cannabinoid concentration in cannabis products, and variable tolerance and pharmacokinetics across cannabis users, the investigators seek to gain experience in quantifying cannabis use by self-report and objective testing, as these measures will directly affect their outcome assessments expected in a subsequent clinical trial design. The investigators will assess amount and frequency of cannabis used by self-report (i.e., typical grams consumed per day, number of sessions per day of use), tracked with regular semi-quantitative urine tests and validated by quantitative blood and urine testing at selected time points. Self-reported cannabis use will be assessed by the Quantification of Cannabis Consumption (QCC), a brief questionnaire designed and preliminarily tested by the investigators, and the timeline follow back (TLFB). Symptoms of CUD and cannabis withdrawal will be assessed with validated self-report measures. Semi-quantitative urine tests will provide a relatively inexpensive and rapid means of testing cannabis use. These measures will be compared against less frequent and fully quantitative urine and blood analysis using liquid chromatography-mass spectrometry (LC/MS). If self-report and semi-quantitative urine tests are consistent with those from LC/MS, then they will be utilized in subsequent clinical trials.
Exploratory Aims: The investigators will explore if prazosin administration is well tolerated and is associated with a reduction of cannabis withdrawal symptom severity and/or cannabis use. As there are no effective treatments for CUD, a reduction of cannabis use by at least 20% from baseline to end of treatment will be considered meaningful enough to warrant future study. In comparison, rates for attaining negative urine tests in two recent medication trials paired with contingency management or psychotherapy were 22% and 29%, respectively (with identical rates in placebo and treatment groups). Adverse events will be monitored and compared their frequencies to that experienced in prior studies of prazosin conducted by the investigators as an exploratory outcome. Additional exploratory outcomes include the comparison of cannabis use throughout the study between those with and without PTSD, and the reduction of PTSD-related nightmares in the PTSD group.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Open-label study of prazosin for treatment of cannabis use disorder
| Arm | Type | Receives |
|---|---|---|
| Open-label prazosin treatment | Experimental | Drug: Prazosin HydrochlorideOpen-label administration of prazosin |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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)
Key exclusion criteria (12 listed)
- Presence of a cognitive disorder
- History of moderate or severe traumatic brain injury (mild traumatic brain injury is not exclusionary)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Prazosin HydrochlorideAlso: minipressprazosin hydrochloride oral 1-25 mg/day | Drug | Open-label prazosin treatment |
Primary outcome
Recruitment
Time frame: Approximately 2 weeks
Proportion of potential participants referred to the study meeting inclusion/exclusion criteria and complete the baseline visit
Retention
Time frame: 12 weeks
Mean and median weeks participants remained in the study between baseline and end of treatment at week 12
Acceptability of participation
Time frame: 16 weeks
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
Quantifying cannabis consumption
Time frame: 16 weeks
Regression comparison of semi-quantitative urine tetrahydrocannabinol (THC) metabolite and self-reported cannabis use by timeline follow back over the course of the study
1 secondary outcome
Treatment outcome (exploratory)
Time frame: 16 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2025.
- Study group websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Garth E Terry, MD, PhD principal investigator
University of Washington
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Prazosin Hydrochloride in people with Cannabis Dependence and Posttraumatic Stress Disorder, run by VA Puget Sound Health Care System at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recruitment (time frame: Approximately 2 weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jun 2025.