Among individuals with alcohol use disorders (AUDs), cannabis use disorder (CUD) is the most prevalent comorbid drug use disorder [1-3]. Marijuana use has been associated with greater number of heavy drinking episodes [2, 4-7] and worse AUD treatment outcomes . Among patients with alcohol dependence, marijuana use following alcohol treatment appears to reduce sustained remission from alcohol and increases risk of alcohol relapse [9, 10]. Marijuana enhances the subjective effects of alcohol  and increases motivation for alcohol use [12-16], which may explain why it hinders alcohol treatment and maintains heavy drinking. Mechanisms whereby marijuana may acutely increase alcohol motivation include marijuana-induced positive subjective effects; higher marijuana dose may also induce aversive effects (e.g., anxiety) that may in turn lead to anticipation of relief from such negative affective state with alcohol; marijuana may affect executive functions including disinhibition and working memory, which could increase preference for alcohol, potentially at excessive levels. However, no human studies have fully examined whether and how marijuana increases motivation for alcohol and alcohol consumption [11,17,18]. This laboratory study will employ a repeated measures experimental design to examine the effect of high (6.9% THC) and moderate (3% THC) dose of marijuana, relative to placebo, on alcohol craving and on behavioral economic measure of alcohol demand after exposure to alcohol cues, and on subsequent drinking in an alcohol choice task in which participants choose either to drink or receive monetary reinforcement for drinks not consumed [19, 20]. Moderators of the marijuana's effects on alcohol-related dependent variables will be tested: DSM5 alcohol use disorder severity, affective vulnerability (anxiety sensitivity, distress intolerance), and trait impulsivit. The study will recruit 150 non-treatment seeking heavy episodic alcohol drinkers who smoke marijuana at least twice weekly. The findings will inform researchers and clinicians about how marijuana acutely increases alcohol craving and consumption. The strategy of this proposal is to use the most comprehensive controlled test characterizing marijuana's putative effects on alcohol. Empirical evidence on marijuana's deleterious effects on alcohol craving and relapse-related behaviors from this study can guide clinical decisions with respect to targeted treatment recommendations for marijuana users seeking treatment for AUDs or making reductions in heavy drinking patterns. The current trend to legalize marijuana along with the significant health and economic impact of excessive alcohol consumption in the U.S. highlight the urgency to investigate effects of marijuana smoking on alcohol consumption in order to inform marijuana policy and prevention. This research is well-aligned with the objectives of the NIH partnership, the Collaborative Research on Addiction at NIH (CRAN) , and has the potential to yield substantial information about the mechanisms whereby marijuana may pose a risk for the maintenance of problem drinking and alcohol use disorders.
The widespread concurrent use of alcohol and marijuana and society's costs associated with this comorbidity are of substantial public health concern. This application uses a human laboratory model of marijuana-alcohol reactivity to determine how marijuana places individuals at greater risk for heavy drinking and ultimately alcohol use disorders. Proliferating marijuana legislation and public endorsement of marijuana legalization along with significant health and economic impact of excessive alcohol consumption in the U.S. highlight the urgency to investigate effects of marijuana smoking on alcohol consumption in order to inform marijuana policy, prevention, and treatment of alcohol use disorders.