Single and combined effects of Δ⁹-tetrahydrocannabinol and cannabidiol in a mouse model of chemotherapy-induced neuropathic pain

Background and Purpose: The non-psychoactive phytocannabinoid cannabidiol (CBD) can affect the pharmacological effects of Δ⁹-tetrahydrocannabinol (THC). We tested the possible synergy between CBD and THC in decreasing mechanical sensitivity in a mouse model of paclitaxel-induced neuropathic pain. We also tested the effects of CBD on oxaliplatin- and vincristine-induced mechanical sensitivity. Experimental Approach: Paclitaxel-treated mice (8.0 mg·kg⁻¹ i.p., days 1, 3, 5 and 7) were pretreated with CBD (0.625–20.0 mg·kg⁻¹ i.p.), THC (0.625–20.0 mg·kg⁻¹ i.p.) or CBD + THC (0.04 + 0.04–20.0 + 20.0 mg·kg⁻¹ i.p.), and mechanical sensitivity was assessed on days 9, 14 and 21. Oxaliplatin-treated (6.0 mg·kg⁻¹ i.p., day 1) or vincristine-treated mice (0.1 mg·kg⁻¹ i.p. days 1–7) were pretreated with CBD (1.25–10.0 mg·kg⁻¹ i.p.), THC (10.0 mg·kg⁻¹ i.p.) or THC + CBD (0.16 mg·kg⁻¹ THC + 0.16 mg·kg⁻¹ CBD i.p.). Key Results: Both CBD and THC alone attenuated mechanical allodynia in mice treated with paclitaxel. Very low ineffective doses of CBD and THC were synergistic when given in combination. CBD also attenuated oxaliplatin- but not vincristine-induced mechanical sensitivity, while THC significantly attenuated vincristine- but not oxaliplatin-induced mechanical sensitivity. The low dose combination significantly attenuated oxaliplatin- but not vincristine-induced mechanical sensitivity. Conclusions and Implications: CBD may be potent and effective at preventing the development of chemotherapy-induced peripheral neuropathy, and its clinical use may be enhanced by co-administration of low doses of THC. These treatment strategies would increase the therapeutic window of cannabis-based pharmacotherapies.