Co-exposure of cocaine and cannabinoids and its association with select biological, behavioural and health outcomes: A systematic scoping review of multi-disciplinary studies.

Cocaine use entails severe health- and social-related harms globally. Treatment options for cocaine dependence are highly limited. Benefits of cannabinoids for addiction have been documented, making it opportune to examine existing data on the possible outcomes associated with cannabinoids and cocaine co-use. We conducted a systematic scoping review following the PRISMA guidelines of peer-reviewed, English-language studies published from 2000 to 2021 in four databases (Medline, Web-of-Science, CINAHL Plus, and PsycInfo), assessing the co-exposure of cannabis/cannabinoids with cocaine on behavioural, biological or health outcomes. Both quantitative and qualitative, as well as humans and pre-clinical animals' studies (n=46) were included. Pre-clinical studies (n=19) showed mostly protective effects of cannabidiol (CBD) administration on animal models of addiction (e.g., cocaine-craving, -relapse, and -withdrawal) and cocaine-toxicity. Tetrahydrocannabinol (THC) had more inconsistent results, with both protective and counter-protective effects. Human studies (n=27) were more heterogeneous and assessed natural ongoing cannabis and cocaine use or dependence. Quantitative-based studies showed mostly enhanced harms in several outcomes (e.g., cocaine use, mental health); two available clinical trials found no effect upon CBD administration on cocaine-related treatment outcomes. Qualitative data-based studies reported cannabis use as a substitute for or to alleviate harms of crack-cocaine use. While pre-clinical studies suggest a potential of cannabinoids, especially CBD, to treat cocaine addiction, the few trials conducted in humans found no benefits. Cannabis co-use by cocaine users commonly presents a risk factor, entailing enhanced harms for users. More rigorous, controlled trials are still necessary to investigate cannabinoids' potential considering pre-clinical findings and reported benefits from specific drug users.