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Effects of endocannabinoid system modulation on social behaviour: A systematic review of animal studies
Mashal Ahmed1, Laura M Best2, Christina F Pereira2
1Institute of Medical Science, University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada; Brain Health Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario M5T 1R8, Canada; Schulich School of Medicine and Dentistry, University of Western Ontario, 1151 Richmond Street, London, Ontario N6A 5C1, Canada.
Abstract:
There is a clear link between psychiatric disorders and social behaviour, and evidence suggests the involvement of the endocannabinoid system (ECS). A systematic review of preclinical literature was conducted using MEDLINE (PubMed) and PsychINFO databases to examine whether pharmacological and/or genetic manipulations of the ECS alter social behaviours in wildtype (WT) animals or models of social impairment (SIM). Eighty studies were included. Risk of bias (RoB) was assessed using SYRCLE's RoB tool. While some variability was evident, studies most consistently found that direct cannabinoid receptor (CBR) agonism decreased social behaviours in WT animals, while indirect CBR activation via enzyme inhibition or gene-knockout increased social behaviours. Direct and, more consistently, indirect CBR activation reversed social deficits in SIM. These CBR-mediated effects were often sex- and developmental-phase-dependent and blocked by CBR antagonism. Overall, ECS enzyme inhibition may improve social behaviour in SIM, suggesting the potential usefulness of ECS enzyme inhibition as a therapeutic approach for social deficits. Future research should endeavour to elucidate ECS status in neuropsychiatric disorders characterized by social deficits.
