PRINCIPAL INVESTIGATOR: MASON, BARBARA J.
GRANT NUMBER: R01 DA030988-04S1
ABSTRACT: This administrative supplement request has the aim of meeting the goal of PA-13-275, Collaborative Research on Addiction at NIH (CRAN): Comorbidity-Related Research. CRAN specifically encourages applications for supplementary funding to collect and analyze data on one or more addictive substances in an existing clinical study that currently focuses on only one substance. The primary aim of our parent grant is to evaluate the efficacy of aprepitant, a NK1 antagonist, for the treatment of cannabis dependence in a randomized, controlled trial. The primary aim of the supplemental study is to provide proof-of-concept (POC) testing of aprepitant as a treatment for comorbid alcohol and cannabis dependence in a randomized, controlled trial. We propose to leverage the existing scientific resources of our parent grant DA030988, “Pharmacological Treatment of Cannabis Withdrawal and Dependence,” by collecting and analyzing data from a sample of 40 otherwise eligible cannabis dependent volunteers who are now excluded from randomization on the basis of meeting criteria for concurrent alcohol dependence. These supplemental data will provide POC testing of aprepitant for the treatment of the highly prevalent comorbidity of alcohol and cannabis dependence, for which there are no available pharmacotherapies. Consistent with the scope and methods of the parent grant, this will be a randomized, double-blind, placebo-controlled, parallel groups, Phase II, single-site, 8-week, clinical trial of aprepitant 125 mg/d or placebo. Subjects will be 40 outpatients seeking treatment for concurrent alcohol and cannabis dependence. All subjects will receive motivational interviewing at Weeks -1 and 0 to promote setting protocol-specific alcohol and MJ quit dates and to decrease the risk of drop out. Thereafter, all subjects will receive weekly individual cognitive-behavioral coping skills therapy aimed at helping the subject identify triggers for alcohol and MJ use, and strategies for avoiding or coping with these triggers without using alcohol or MJ (Weeks 1-8). Research assessments will occur weekly through the treatment phase of the 8-week study. Post treatment follow-up assessments will occur at Weeks 9 and 12. Urinary THC data from the parent grant indicates a group sample size of 20 per arm will provide 82% power to detect a difference of at least 259 units in the CN-THCCOOH ratio between drug and placebo group cumulative means, assuming 50% CVs and a 2- sided alpha of 0.05. The data analysis plan specified in the parent grant will be applied to the supplemental project to test for effects of aprepitant vs placebo on measures of cannabis use and withdrawal, craving, mood and sleep, cognitive executive functioning, and safety parameters in subjects with concurrent alcohol and cannabis dependence. For the purpose of assessing the effect of aprepitant on alcohol use in comorbid subjects in the supplemental study, we will also test for effects of aprepitant vs placebo on the number of heavy drinking days per week, the number of drinks consumed per week, and the rates of alcohol abstinence, no heavy drinking, and abstinence from both alcohol and cannabis over the 8-week study.