Prazosin for Cannabis Use Disorder

(ReCOUP Trial)

Overseen By Rebekah Rein, JD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: VA Puget Sound Health Care System

Must not be taking: Synthetic cannabinoids, Trazodone

Disqualifiers: Cognitive disorder, Severe TBI, Others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether prazosin, a medication known to help with PTSD-related sleep issues, can also aid those with cannabis use disorder (CUD). People with PTSD often use cannabis to manage symptoms like insomnia and anxiety, which can lead to dependency and withdrawal issues. Prazosin might reduce the need for cannabis by addressing these symptoms. Individuals who have frequently used cannabis in the past month and are experiencing these challenges might be a good fit for the trial. As a Phase 4 trial, this research focuses on understanding how this FDA-approved and effective treatment can benefit more patients.

Do I have to stop taking my current medications for the trial?

The trial requires a 2-week period without taking trazodone before starting the study treatment. For other medications, the protocol does not specify if you need to stop taking them.

What is the safety track record for prazosin?

Previous studies have shown that prazosin is generally safe for people. Most side effects are mild and temporary, with common ones including dizziness, headaches, and fatigue, which usually resolve on their own. Prazosin has been used to reduce symptoms like nightmares and sleep problems, especially in people with PTSD. This suggests it might help those trying to reduce cannabis use by addressing similar symptoms. Overall, prazosin is well-tolerated and has a reassuring safety record for those considering this treatment. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Prazosin is unique because it targets the brain's stress response system by blocking alpha-1 adrenergic receptors, which is different from most current treatments for Cannabis Use Disorder that focus on behavioral therapies or other medications like gabapentin and N-acetylcysteine. Researchers are excited about prazosin because it offers a novel approach to reducing withdrawal symptoms and cravings, potentially making it easier for individuals to quit cannabis use. Additionally, prazosin is already FDA-approved for other conditions, suggesting it has a well-understood safety profile, which could expedite its availability for treating Cannabis Use Disorder.

What evidence suggests that prazosin might be an effective treatment for cannabis use disorder?

Research has shown that prazosin, a medication that reduces the effects of adrenaline in the brain, effectively decreases nightmares and sleep issues related to PTSD in many studies. Although no FDA-approved treatment exists for cannabis use disorder (CUD), prazosin has shown promise in helping people with PTSD who use cannabis to manage their symptoms. Specifically, some patients reduced or stopped cannabis use when treated with prazosin. This trial will explore prazosin's potential to help those with CUD by easing the PTSD symptoms that cannabis users often try to manage. This evidence supports the idea that prazosin could help people reduce cannabis use, especially if they also have PTSD symptoms. ^{1 2 3 5 6}

Who Is on the Research Team?

Garth E Terry, MD, PhD

Principal Investigator

University of Washington

Are You a Good Fit for This Trial?

This trial is for adults aged 18-80 who use cannabis at least four days a week and want to reduce their usage. They must be in good health, not using substances other than tobacco or alcohol, and agree to birth control if applicable. Those with PTSD symptoms may benefit especially.

Inclusion Criteria

Have a confirmed diagnosis on the Mini-International Neuropsychiatric Interview (MINI).

I am in good overall health.

Persons of childbearing potential must agree to use an effective means of birth control.

Exclusion Criteria

You have had an allergic reaction or a bad reaction in the past to prazosin or other similar medications.

Positive urine drug screen for any drug of abuse other than cannabis at screening visit

You are experiencing severe emotional distress or crisis, including suicidal or homicidal thoughts.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

Approximately 2 weeks

1 visit (in-person)

Treatment

Open-label administration of prazosin for cannabis use disorder in individuals with or without PTSD

12 weeks

Regular visits for monitoring and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

Quantification of cannabis consumption

Assessment of cannabis use through self-report and objective testing

16 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Prazosin Hydrochloride

Trial Overview The study tests Prazosin Hydrochloride's ability to help individuals with or without PTSD reduce cannabis overuse by treating symptoms like insomnia and nightmares that often lead them to use cannabis.

How Is the Trial Designed?

Group I: Open-label prazosin treatment Experimental Treatment 1 Intervention

Open-label administration of prazosin

Prazosin Hydrochloride is already approved in United States, European Union for the following indications:

Approved in United States as Minipress for:

• Hypertension
• Post-traumatic stress disorder (PTSD) symptoms including nightmares

Approved in European Union as Prazosin for:

• Hypertension

Who Is Running the Clinical Trial?

VA Puget Sound Health Care System

Lead Sponsor

Trials

67

Recruited

225,000+

VA Mental Illness Research, Education and Clinical Centers

Collaborator

Trials

2

Recruited

60+

University of Washington

Collaborator

Trials

1,858

Recruited

2,023,000+

Published Research Related to This Trial

Prazosin hydrochloride is a new antihypertensive medication that shows mild-to-moderate effectiveness in treating mild-to-moderate hypertension, but its effectiveness is lower than that of hydrochlorothiazide based on a study of 14 patients.

The best use of prazosin may be in combination with other medications, such as thiazide diuretics and beta-blockers, particularly for patients with severe hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prazosin-new hypertensive agent. A double-blind crossover study in the treatment of hypertension. Schirger, A., Sheps, SG.[2019]

Prazosin is effective in treating both hypertension and congestive heart failure, showing comparable results to nitroprusside in long-term therapy, which involves balanced arterial and venous dilation.

The drug is generally well tolerated, with the main side effect being orthostatic hypotension, which can be minimized by starting treatment at a low dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prazosin update. A review of its pharmacological properties and therapeutic use in hypertension and congestive heart failure. Stanaszek, WF., Kellerman, D., Brogden, RN., et al.[2018]

Prazosin is an effective treatment for hypertension and congestive heart failure, providing sustained antihypertensive effects without significantly increasing heart rate or plasma norepinephrine levels, making it a safer option compared to other medications.

While postural hypotension can occur after the first dose, most side effects are mild and do not limit therapy, and long-term use has shown continued effectiveness and improvement in symptoms, even during exercise.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alpha-adrenergic receptor blockade with prazosin. Consideration of hypertension, heart failure, and potential new applications. Colucci, WS.[2019]

Prazosin is an effective antihypertensive medication that works well for all levels of hypertension and is particularly beneficial for patients with specific conditions like impaired renal function or diabetes, based on clinical experience with 22,000 patients.

The side effects of prazosin are generally mild, with a very low incidence of serious issues like syncope (0.15%), and strategies such as starting with a low dose and taking it at bedtime can help minimize adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of prazosin as initial antihypertensive therapy. Okun, R.[2019]

In a multicenter study involving 366 patients with arterial hypertension, prazosin (Minipress) significantly reduced both systolic and diastolic blood pressure over a 3-month treatment period, with about two-thirds of patients responding well to the drug as a monotherapy.

While 27% of patients experienced side effects, only 5% discontinued the medication due to these effects, indicating that prazosin is generally safe and well-tolerated for treating high blood pressure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Minipress in the treatment of arterial hypertension in light of results from a multicenter study. I. 3-month treatment: monotherapy versus combination treatment]. Sznajderman, M.[2013]

In a study of 24 outpatients with uncontrolled hypertension, prazosin effectively lowered blood pressure, achieving normotensive levels in 9 out of 24 patients, demonstrating its efficacy in treating severe hypertension.

Prazosin was generally well-tolerated, with a low incidence of side effects, primarily postural hypotension, which affected 3 patients and led to their withdrawal from the trial, indicating a need for monitoring in some individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prazosin in the therapy of uncontrolled hypertension. Lubbe, WF.[2014]

Prazosin is an effective antihypertensive agent that lowers blood pressure primarily through direct vasodilation of arterioles without causing excessive increases in heart rate, making it a safer option for managing hypertension.

The drug works by increasing intracellular levels of cyclic AMP in blood vessels and cyclic GMP in the heart, which supports its mechanism of action and has been validated through pharmacologic and tissue distribution studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prazosin: biochemistry and structure-activity studies. Hess, HJ.[2014]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04721353

NCT04721353 | Reducing Cannabis Overuse With Prazosin Prazosin, a drug that blocks the negative effects of brain adrenaline, has demonstrated effectiveness in robustly reducing PTSD-related nightmares and sleep ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6167169/

A randomized, placebo-controlled, clinical trial of prazosin ... Prazosin did not significantly affect rate of reduction in alcohol use in the intent to treat sample (n=36) compared to placebo, but did significantly increase ...

3. withpower.com withpower.com/trial/phase-4-stress-disorders-post-traumatic-10-2020-7720f

Prazosin for Cannabis Use Disorder (ReCOUP Trial) Prazosin is effective in treating both hypertension and congestive heart failure, showing comparable results to nitroprusside in long-term therapy, which ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7511147/

The Use of Prazosin in Treatment of Drug Dreams in ... This case report presents 2 scenarios in which administration of prazosin to adolescent patients with DD was associated with positive treatment response.

5. go.drugbank.com go.drugbank.com/conditions/DBCOND0031098

Cannabis Dependence (DBCOND0031098) Associated Data ; NCT04721353. Reducing Cannabis Overuse With Prazosin. Prazosin ; NCT02088177. Study of Long-Acting Injectable Naltrexone to Treat Cannabis ...

6. app.leg.wa.gov app.leg.wa.gov/committeeschedules/Home/Document/222468

Cannabis Research in WA State: Prazosin as a treatment for Cannabis Use Disorder ... Cannabis Use Disorder (CUD) or addiction to cannabis, particularly among young people.