Molecular targets of cannabidiol in cocaine memory

Abstract

Psychostimulant abuse is a significant problem worldwide, with cocaine being one of the most commonly abused psychostimulant drugs. However, cocaine use can cause significant short- and long-term burden for the individual and society. There is no current FDA-approved medications to treat cocaine addiction, and counselling remains the only option for individuals suffering with this addiction. However many individuals facing cocaine addiction do not completely respond to psychosocial treatments such as counselling and social support and often quickly face relapse. Cannabidiol (CBD) has recently been proposed as a potential pharmacotherapy for psychostimulant addiction due to its anti-addiction-like properties that can potentially alleviate cocaine-induced neuroadaptations. Due to research supporting the effectiveness of CBD as a potential therapeutic for cocaine addiction, this thesis aimed to evaluate the effect of CBD on molecular markers of cocaine memory. This study examined how 10 mg/kg CBD administered during abstinence affected memory of a cocaine-associated environment, using a conditioned place preference (CPP) paradigm. This present study found that adult male C57BL/6 mice treated with 10 mg/kg CBD during abstinence of cocaine (15 mg/kg) including test days, found a persistence of cocaine preference compared to the VEH group. Whereas adult male C57BL/6 mice treated with 10 mg/kg CBD during abstinence of cocaine (15 mg/kg) excluding test days found no significant effect of treatment suggesting that the CBD administration on test days affected memory reconsolidation. Protein analysis of brain tissue found upregulation of CB1 receptors within the HPC but not the STR or PFC in CBD-treated mice, and no significant differences from FAAH or 5-HT1A expression in either the HPC, STR or PFC when compared between CBD- or VEH-treated mice. From this, we suggest that CBD is acting via CB1 upregulation in the HPC to cause memory reconsolidation disruption. Future research into the effects of CBD on cocaine CPP when administered during abstinence should be considered, as well as investigating differing CBD doses and age of test animals to further assess the effect of chronic CBD treatment on protein expression following cocaine CPP. In conclusion, this study suggests that CBD has potential for therapeutic value for modulating memory reconsolidation within cocaine abuse patients.

Date of Award	2022
Original language	English