Behavioral Phenotypes Associated with Cannabis and Alcohol Substitution

Objective: Alcohol and cannabis co-use is the most common form of polysubstance use in the U.S. Some evidence suggests that there is an association between cannabis use and reduced alcohol consumption and associated harms, however further research is needed to elucidate the individual factors influencing whether individuals may benefit from using cannabis as a harm reduction substitute for alcohol. Method: The present study leverages data within-subjects, crossover co-administration laboratory study to identify behavioral phenotypes of individuals who self-administered less alcohol after using flower cannabis (CA) compared to alcohol alone (AO) (i.e., “substituters”; n = 23) compared to those who self-administered the same (i.e., “non-substituters”; n = 32). We utilized t-tests and ANOVAs (non-parametric equivalents) to compare baseline group differences in personality traits, psychological functioning, and substance use, as well as laboratory self-administration measures, drawing on domains from the Addictions Neuroclinical Assessment (ANA) framework. Results: Substituters had significantly lower scores on measures corresponding to ANA domains of negative emotionality (BDI, BAI, DASS, DERS) and executive function (UPPS-P Impulsivity) compared to non-substituters. Regarding incentive salience, substituters endorsed significantly higher positive cannabis expectancies (MCQ) compared to non-substituters. They also had significantly higher baseline blood THC concentrations at session CA compared to AO, whereas was no difference for non-substituters.Conclusions: Findings hold important implications for harm reduction approaches for individuals who drink alcohol, suggesting that those with lower levels of negative emotionality and impulsivity may be more likely to benefit from cannabis as a substitute for alcohol.