Cannabidiol in medicinal usage of stress: Modeling investigations into cocaine

To date, no pharmacological agents have been approved specifically for cocaine use disorder, with only some medications prescribed to decrease the negative impact associated with its abstinence. In order to find novel therapeutical options, new drugs have been tested with not much success. In the last years, a non-psychotomimetic compound found in the plan Cannabis sativa, named cannabidiol, has proven a medicinal potential for stress-related conditions, including the different stages of cocaine addiction as modeled in rodents. This review focuses on describing the literature reporting the potential use of cannabidiol for cocaine use disorder both at preclinical and clinical levels. With regard to what has been published so far, we argue that although cannabidiol has shown certain beneficial effects on improving some aspects of cocaine-induced behavioral changes in rodents (mainly done in adult males), the clinical literature is still scarce and does not align with the preclinical data. Also, the neurochemical aspects of cannabidiol's actions need to be further characterized. In conclusion, future experiments should deepen into cannabidiol's actions in the context of preventing cocaine-motivated behaviors and neurochemical correlates, but including sex as a biological variable (given the lack of preclinical studies on females), and different ages of cannabidiol's exposure (given the importance of preventing early drug initiation during adolescence), to better translate the results into upcoming clinical trials.