The importance of considering polysubstance use: lessons from cocaine research

Polysubstance use (PSU) is prevalent among individuals with substance use disorders, but the vast majority of preclinical substance use research has focused on individual substances in isolation. Cocaine has been prevalent in the repertoire of persons who use more than one illicit substance.

We conducted a meta-analysis combining results from literature searches and secondary data analyses to estimate the prevalence of simultaneous and concurrent cocaine + alcohol and cocaine + cannabis use among cocaine users. We next summarized the small body of literature on behavioral, cognitive and neurobiological consequences of cocaine PSU across species, with a focus on alcohol and cannabis. Finally, we used systematic literature searches to assess the extent to which human and animal studies on the neurobiological consequences of cocaine include PSU subjects.

The estimated prevalence of simultaneous and concurrent alcohol use among human cocaine users was 74% and 77%, respectively. The estimated prevalence of simultaneous and concurrent cannabis use among cocaine users was 38% and 64%, respectively. Consumption of alcohol or cannabis with cocaine enhances subjective responses to cocaine, concomitant with changes in cocaine metabolism that increase blood cocaine levels, and, in the case of alcohol, produce the psychoactive metabolite cocaethylene. There is also consistent evidence for neurobiological effects of cocaine + alcohol combinations. However, animal PSU research with cocaine lags behind human research.

Based on the prevalence and known consequences of PSU, consideration of PSU in both human and animal research is vital for understanding patterns of substance use.