Pharmacotherapeutic effects of cannabidiol in autism spectrum disorders

Abstract

Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by social deficits and restrictive/repetitive behaviour. ASD is diagnosed in roughly 1-2% of the global population. Despite the prevalence of ASD, very few pharmaceutical interventions have been approved for its treatment. The endocannabinoid system (ECS) has recently gained interest as a potential target for treating ASD. Cannabidiol (CBD), a compound found in the Cannabis (C. Sativa) plant, has been highlighted as a potential drug through which the ECS can be mediated. Due to its non-psychoactive nature, and its efficacy in ameliorating ASD-associated symptoms in Fragile X syndrome (FXS) patients, an investigation into its effectiveness in treating ASD is warranted. In this present thesis, we aimed to evaluate the efficacy of CBD in treating social deficits and restrictive/repetitive behaviours in Fmr1 and Shank3 knockout mice. These models serve as two well-characterized monogenetic animal models of ASD. To account for a knowledge gap in the literature surrounding the treatment of ASD, both male and female mice were used. Mice were assigned to the 3-chamber social test, or self-grooming and open field tests. Mice received subcutaneous injections of either vehicle or CBD (5mg/kg for males, 50mg/kg for females). On the first day, mice performed their respective tests to establish a baseline for behaviour. For the 4 following days, mice received 1 injection daily. On the 6 th day, mice were given another injection. An hour later, they were subjected to their post-injection behavioural testing. Results from the 3-chamber social test showed that both knockout models displayed deficits in social novelty. This deficit was recovered following the administration of CBD. Self-grooming analysis and open-field testing showed no effect of CBD.These findings suggest CBD exerts its therapeutic effects through regions specific to social memory, likely the CA1 and CA2 regions of the hippocampus.