Optimizing the Synergistic Effects of Cannabidiol and Δ9-Tetrahydrocannabinol for the Treatment of Neuropathic Pain in Mouse Behavioural Models

Introduction: The analgesic properties of CBD and THC in cannabis can potentially be leveraged for the treatment of neuropathic pain but have not been well investigated. Some commercial analgesics, such as opioids, have unfavourable side effects including addiction, which does not exist in cannabis. Combinations of CBD and THC may not only elicit stronger analgesic effects than single-compound drugs, but also curb the psychotropic effects commonly associated with THC. We present a novel protocol to find the ideal substance ratio in a CBD-THC mixture, which elicits maximum antinociception with the least psychotropic effect. Methods: BALB/c mice will be assigned to 12 different treatment groups, representing 9 different ratios of CBD-THC mixtures, 2 positive controls (URB937 and sertraline hydrochloride), and 1 vehicle. Each mouse will be administered a compound via intraperitoneal injection and then subjected to behavioural testing. Chronic constriction injury and the Hargreaves’ Test (HT) will be used to test nociceptive behaviour while the Tail Suspension Test (TST) will be used to test depression-like behaviour. Expected Results: The ideal CBD-THC mixture will produce maximum withdrawal latency in the HT and maximum immobility time in the TST. Because the analgesic properties of combined CBD and THC still remain unclear in current literature, it is difficult to predict how withdrawal latency in the HT will change with varying CBD:THC ratios. Based on the psychotropic effects of THC, we expect increased THC concentrations to decrease immobility time in the TST. Conclusion: By determining the optimal ratio of CBD:THC for maximal pain suppression and minimal psychotropic effects, our protocol may provide justification for an alternative non-addictive therapeutic for treating neuropathic pain. In order to increase the generalizability and translatability of the results in a clinical setting, future studies could benefit from changes in dosing strategies, routes of administration, supplemental observation methods, and experimental timeframes.