Pharmacological Treatment of Comorbid Alcohol and Marijuana Withdrawal and Dependence

Phase 2

Completed

Conditions: Cannabis Dependence
Alcohol Dependence
Cannabis Use Disorder
Alcohol Use Disorder

Interventions: Drug: Placebo
Drug: aprepitant
Behavioral: Manual-guided behavioral counseling

Brief Summary: The primary aim of the supplemental study is to provide POC testing of aprepitant as a treatment for comorbid alcohol and cannabis dependence. The data analysis plan specified in the parent grant will likewise be applied to the supplemental project to test for effects of aprepitant vs placebo on measures of alcohol and cannabis use and protracted withdrawal. The primary hypothesis is that subjects treated with aprepitant will have significantly less alcohol and marijuana use than subjects treated with placebo.

Detailed Description: Consistent with the scope and methods of the parent grant, this was a randomized, double-blind, placebo-controlled, parallel groups, Phase II, single-site, 8-week clinical trial of aprepitant 125 mg/d or placebo. Participants were 20 outpatients seeking treatment for concurrent alcohol and cannabis dependence. All participants received weekly protocol-specific counseling. Research assessments occurred weekly through the treatment phase of the 8-week study. Post treatment follow-up assessments occurred at Weeks 9 and 12.

Recruitment & Eligibility

Inclusion Criteria

Males or females from 18-70 years of age
Meets DSM IV criteria for current alcohol and cannabis dependence
Seeking research-based outpatient treatment for alcohol and cannabis dependence that involves daily oral medication
Negative BAC and a CIWA score < 9 at randomization

Exclusion Criteria

Significant medical disorders or use of medications that will increase potential risk or influence study outcomes
Females who are pregnant, nursing or who are sexually active with child-bearing potential and refuse to use an effective, non hormonal method of birth control during the study and for up to 4 weeks after study termination• Treatment with an investigational drug during the previous month
Prior treatment with NK1 antagonists
Participants for whom treatment is being mandated by a legal authority• Inability to understand and/or comply with the provisions of the protocol and consent form

Arm && Interventions

Group	Intervention	Description
Experimental: aprepitant 125 mg/day	Manual-guided behavioral counseling	125 mg aprepitant daily for 8 weeks given in conjunction with 8 weeks of manual-guided behavioral counseling.
Placebo 125mg/d	Placebo	Matched placebo pill given daily for 8 weeks given in conjunction with 8 weeks of manual-guided behavioral counseling.
Placebo 125mg/d	Manual-guided behavioral counseling	Matched placebo pill given daily for 8 weeks given in conjunction with 8 weeks of manual-guided behavioral counseling.
Experimental: aprepitant 125 mg/day	aprepitant	125 mg aprepitant daily for 8 weeks given in conjunction with 8 weeks of manual-guided behavioral counseling.

Primary Outcome Measures

Name	Time	Method
Change From Week 0 in Cannabis Use Using Urinary CN-THCCOOH Levels at Week 8	Week 0 and Week 8	Urinary THC/Cr ratio, also known as CN-THCCOOH (creatinine normalized tetrahydrocannabinol carboxylic acid), is a highly sensitive and specific quantitative analytic procedure to determine current marijuana metabolite levels in the urine as well as new marijuana use or abstinence. Gas chromatography mass spectrometric levels of 11-nor-9-carboxy-9-THC (THC-COOH), the primary marijuana metabolite, are normalized to the urine creatinine (CN) concentration to reduce the variability of drug measurement attributable to urine dilution. Negative values indicate decreased use. Change = (Week 8 value - Week 0 value).
Change From Week 0 in Drinking Quantity and Frequency Using Drinks Per Week at Week 8	Week 0 and Week 8	Standard drinks are equivalent to 14 grams of pure alcohol and number of drinks are assessed with Timeline Follow-Back (TLFB) methods. Change = (Week 8 - Week 0). More negative values indicate less use of alcohol.

Secondary Outcome Measures