Reducing Cannabis Overuse With Prazosin

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.