Sex-Dependent Effects of Alcohol Administration on the Urge to Use Cannabis

Public Health Significance Despite their frequent co-use, the underlying mechanisms and sex-dependent nature of alcohol and cannabis couse remain poorly understood. In a sample of non-treatment-seeking heavy drinkers, males reported an increased urge for cannabis at rising BrACs, whereas females did not. This may imply that the pharmacological effects of alcohol on the urge for cannabis are sex-dependent, suggesting a possible mechanism by which males in particular report alcohol and cannabis co-use. Alcohol and cannabis couse is highly prevalent and associated with various negative consequences. The likelihood of same day couse is high, especially among men, however, underlying mechanisms to their couse and its sex-dependent nature remain poorly understood. This study aims to elucidate the effects of controlled alcohol administration on the urge to use cannabis and considers sex-dependent effects. A community sample of non-treatment-seeking heavy drinkers (N = 37, 46% female) reporting cannabis use in the past 6 months completed an alcohol administration paradigm. Participants rated their urge to use cannabis and drink alcohol at baseline and at rising levels of breath alcohol concentration (BrAC). Mixed model analyses examined the effects of BrAC, sex, and their interaction on craving for cannabis. The relationships across urge for cannabis, urge for alcohol, and subjective responses to alcohol were also tested. There was a significant BrAC x Sex interaction on the urge to use cannabis, such that males reported increases in the urge to use cannabis at rising BrACs but females did not. Urge for alcohol significantly predicted urge for cannabis across rising levels of BrAC and this relationship was stronger in males than in females. Lastly, stimulation, but not sedation, during alcohol administration was positively associated with the urge for cannabis. Overall, these results suggest that the pharmacological effects of alcohol on the urge to use cannabis are sex-dependent and that the stimulant effects of alcohol are associated with a higher urge for cannabis.