Cannabis constituent synergy in a mouse neuropathic pain model.

Cannabis and its psychoactive constituent Δ9-tetrahydrocannabinol (THC) have efficacy against neuropathic pain however, this is hampered by their side-effects. It has been suggested that co-administration with another major constituent cannabidiol (CBD) might enhance the analgesic actions of THC and minimise its deleterious side-effects. We examined the basis for this phytocannabinoid interaction in a mouse chronic constriction injury (CCI) model of neuropathic pain. Acute systemic administration of THC dose-dependently reduced CCI-induced mechanical and cold allodynia, but also produced motor incoordination, catalepsy and sedation. CBD produced a lesser dose-dependent reduction in allodynia, but did not produce the cannabinoid side-effects. When co-administered in a fixed ratio, THC and CBD produced a biphasic dose-dependent reduction in allodynia. At low doses, the THC:CBD combination displayed a 200-fold increase in anti-allodynic potency, but had lower efficacy compared to that predicted for an additive drug interaction. By contrast, high THC:CBD doses had lower potency, but greater anti-allodynic efficacy compared to that predicted for an additive interaction. Only the high dose THC:CBD anti-allodynia was associated with cannabinoid side-effects and these were similar to those of THC alone. Unlike THC, the low dose THC:CBD anti-allodynia was not cannabinoid receptor mediated. These findings demonstrate that CBD synergistically enhances the pain relieving actions of THC in an animal neuropathic pain model, but has little impact on the THC-induced side-effects. This suggests that low dose THC:CBD combination treatment has potential in the treatment of neuropathic pain.