Cannabidiol (CBD) does not reduce cocaine reward or self-administration in a mouse model of schizophrenia genetic susceptibility

Cannabidiol (CBD) is a non-intoxicating Cannabis sativa plant compound with some preclinical studies reporting efficacy for the treatment of psychiatric disorders, including schizophrenia and substance abuse. Considering that there are high rates of substance use in individuals with schizophrenia, CBD may be effective in the simultaneous treatment of both disorders. However, this exciting possibility has not been investigated preclinically, and CBD has only been evaluated for substance use treatment in healthy animals. Thus, to address this question thereby focusing on cocaine as an example for substance use, we used a mouse model of genetic risk for schizophrenia, heterozygous transmembrane domain neuregulin 1 mice (Nrg1 TM HET), which importantly show addiction-like responses to cocaine and altered schizophrenia-relevant behaviours to cannabinoids. We examined the efficacy of intraperitoneal administration of selected doses of CBD in reducing cocaine-induced conditioned place preference and locomotion (at a dose of 10 mg/kg) as well as in decreasing cocaine self-administration (at a dose of 20 mg/kg) in male Nrg1 TM HET and wildtype-like controls. The effects of prior CBD administration on the cessation and relapse-like behaviour for cocaine self-administration were also determined. The selected dose of CBD reduced cocaine place preference, cocaine locomotion and cocaine self-administration in wildtype-like littermates. However, CBD was ineffective in reducing these behaviours in Nrg1 TM HET mice. Furthermore, prior CBD treatment did not affect cessation of cocaine self-administration or relapse-like behaviour in either genotype, indicating that acute CBD administration may be needed to reduce these behaviours. Together, our findings show that CBD at the dose chosen can reduce cocaine reward, locomotion and self-administration in healthy animals. Importantly, the selected CBD treatment designs may not be effective in reducing cocaine-induced mouse behaviours in the presence of schizophrenia risk mutations including mutant Nrg1 TM. These findings advocate for research evaluating CBD's efficacy in models of substance use susceptibility or other psychiatric disorders, to determine the circumstances and treatment designs under which CBD is and is not effective for substance use treatment.