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

20 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

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.

Is prazosin generally safe for humans?

Prazosin is generally considered safe for humans, with most side effects being mild and temporary. Common side effects include postural hypotension (a drop in blood pressure when standing up) and, rarely, fluid retention. Serious side effects are uncommon, and the drug is well-tolerated in most patients. ^{1 2 3 4 5}

How does the drug prazosin differ from other treatments for cannabis use disorder?

Prazosin is unique because it is primarily used as a blood pressure medication, working by blocking alpha-1 adrenergic receptors to relax blood vessels. Its use for cannabis use disorder is novel, as it is not a standard treatment for this condition, and it may offer a different approach by potentially affecting stress-related pathways involved in substance use. ^{1 3 5 6 7}

Research Team

Garth E Terry, MD, PhD

Principal Investigator

University of Washington

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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]

References

1. South Africa pubmed.ncbi.nlm.nih.gov

Prazosin in the therapy of uncontrolled hypertension. [2014]

2. Poland 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]. [2013]

3. United States pubmed.ncbi.nlm.nih.gov

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

4. United States pubmed.ncbi.nlm.nih.gov

Effectiveness of prazosin as initial antihypertensive therapy. [2019]

5. England pubmed.ncbi.nlm.nih.gov

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

6. New Zealand pubmed.ncbi.nlm.nih.gov

Prazosin update. A review of its pharmacological properties and therapeutic use in hypertension and congestive heart failure. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

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