Towards a healthier cannabis? Examining neurobehavioural interactions between THC and CBD in mice

Abstract Cannabis is the most widely used illicit drug in the world, however over the past decade there has been increasing interest in its utility as a potential therapeutic. Despite the reported beneficial effects of cannabis constituent Δ9-tetrahydrocannabinol (THC), its psychoactivity has curtailed its therapeutic use. There has been increasing interest in combining non-psychoactive cannabis constituent cannabidiol (CBD with THC to inhibit THC’s adverse effects, leading to generation of medications which contain ~1:1 CBD to THC dose ratios which are currently used for the treatment of spasticity in multiple sclerosis and pain relief. However there is a limited evidence base regarding to what extent CBD might modulate the pharmacological effects of THC at equal doses. The scientific examination of pharmacological interactions between these chemicals is therefore of major medical and public health significance. This thesis examines whether an equivalent dose of CBD is able to ameliorate the neuropharmacological effects of THC in mice following acute and repeated dosing in adulthood and adolescence, using doses relevant to human consumption. We report that CBD acutely inhibited some (but not all) of the neurobehavioural measures taken, suggesting potential benefits of CBD in reducing the unwanted effects of THC. However, the unexpected activation of mesolimbic circuitry when THC and CBD were combined suggests enthusiasm should be tempered until these effects are better understood. Adolescent mice exposed to a modest THC dose equivalent to most recreational and medicinal users did not display long-term behavioural deficits, and hence no reversal of negative outcomes by CBD could be measured. CBD alone produced no behavioural changes following acute or repeated exposure in adult mice, although adolescent CBD exposure reduced depression-like behaviour in adult mice, an intriguing effect warranting further study