Single and combined effects of delta9 -tetrahydrocannabinol and cannabidiol in a mouse model of chemotherapy-induced neuropathic pain.

BACKGROUND AND PURPOSE:

It has been suggested that the non-psychoactive phytocannabinoid cannabidiol (CBD) can impact the pharmacological effects of delta-9-tetrahydrocannabinol (THC). We tested the hypothesis that CBD and THC would significantly mitigate mechanical sensitivity in a mouse model of paclitaxel-induced neuropathic pain, and that CBD+THC combinations would produce synergistic effects. We also tested the hypothesis that CBD would attenuate oxaliplatin- and vincristine- induced mechanical sensitivity.

EXPERIMENTAL APPROACH:

Paclitaxel-treated mice (8.0 mg/kg IP, days 1, 3, 5 and 7) were pretreated with CBD (0.625 – 20.0 mg/kg IP), THC (0.625 – 20.0 mg/kg IP) or CBD+THC (0.04+0.04 – 20.0+20.0 mg/kg IP) and mechanical sensitivity was assessed on days 9, 14, and 21. Oxaliplatin-treated (6.0 mg/kg IP, day 1) or vincristine-treated mice (0.1 mg/kg IP days 1-7) were pretreated with CBD (1.25 – 10.0 mg/kg IP), THC (10.0 mg/kg IP), or THC+CBD (0.16 mg/kg THC + 0.16 mg/kg CBD IP).

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 CIPN, and its clinical utility may be enhanced by co-administration of low doses of THC. These treatment strategies would increase the therapeutic window of Cannabis-based pharmacotherapies.

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