Cannabis constituents for chronic neuropathic pain; reconciling the clinical and animal evidence

Chronic neuropathic pain is a debilitating pain syndrome caused by damage to the nervous system that is poorly served by current medications. Given these problems, clinical studies have pursued extracts of the plant Cannabis sativa as alternative treatments for this condition. The vast majority of these studies have examined cannabinoids which contain the psychoactive constituent delta-9-tetrahydrocannabinol (THC). While there have been some positive findings, meta-analyses of this clinical work indicates that this effectiveness is limited and hampered by side-effects. This review focuses on how recent preclinical studies have predicted the clinical limitations of THC-containing cannabis extracts, and importantly, point to how they might be improved. This work highlights the importance of targeting channels and receptors other than cannabinoid CB1 receptors which mediate many of the side-effects of cannabis.image Chronic neuropathic pain is an abnormal pain syndrome caused by damage to the nervous system. Some clinical studies have shown that the whole cannabis, delta-9-tetrahydrocannabinol (THC) and nabiximols (THC plus cannabidiol (CBD) formulations) have efficacy against neuropathic pain. However, meta-analyses indicates that this effectiveness is limited and hampered by side-effects. By contrast, pre-clinical animal studies indicate that cannabis constituents are highly effective in several models of neuropathic pain. We here review recent pre-clinical studies on THC, nabiximols, and CBD.image