Effects of Delta-9-Tetrahydrocannabinol and Cannabidiol on Cisplatin-Induced Neuropathy in Mice.
Sativex, a cannabinoid extract with a 1 1 ratio of tetrahydocannabinol and cannabidiol, has been shown to alleviate neuropathic pain associated with chemotherapy. This research examined whether tetrahydocannabinol or cannabidiol alone could attenuate or prevent cisplatin-induced tactile allodynia. In experiment 1, mice (C57BL6) received eight administrations of 2.3 mgkg cisplatin or saline solution IP every other day to induce tactile allodynia. Mice were then administered vehicle, 100 mgkg gabapentin, 2 mgkg tetrahydocannabinol, or 2 mgkg cannabidiol IP and tested 60 min later on an electronic Von Frey. In experiment 2, prevention studies, cannabidiol (0.0, 0.5, 1.0, and 2.0 mgkg) or tetrahydocannabinol (0.0, 0.5, 1.0, and 2.0 mgkg) was given IP 30 min prior to cisplatin administration (2.3 or 1.0 mgkg) utilizing a six-dose alternate day protocol. In both studies, tactile responses to the hind paws were quantified in g of force using an electronic Von Frey prior to and after the cisplatin administration protocol. Cisplatin produced a reduction in g of force indicative of neuropathy that was attenuated by gabapentin, tetrahydocannabinol, and cannabidiol but not prevented by either cannabinoid. These data demonstrate that each of the major constituents of Sativex alone can achieve analgesic effects against cisplatin neuropathy.