Ian D. Meng, PhD

Mechanisms of Cannabinoid Analgesia

Cannabinoids (drugs that act at cannabinoid receptors, including the CB1/CB2 mixed agonist delta-9-tetrahydrocannabinol (THC) reduce pain behaviors in virtually every animal model of pain. These include both acute (mechanical and thermal stimulation) and chronic (allodynia and hyperalgesia following nerve injury of inflammation) pain models. Cannabinoids also produce motor deficits, including hypomotility and, at high enough doses, catalepsy. injury), on spinal cord nociceptive neurons, and on neurons in the brain ( activating descending inhibitiry pain pathways). Additional studies have demonstrated that cannabinoids can potentiate the analgesic effect of opiates, with an effect that is greater than additive.

Anecdotal reports indicate that people use marijuana to control pain. Human studies using experimental pain models are inconsistant; however, most studies show either no effect or INCREASED pain after marijuana. Controlled human studies in clinical pain populations suggest that cannabinoids may be effective analgesics. These results, however, are not clear-cut and side effects (including sedation and anxiety) can be significant. So what is the future of cannabinoids in pain management ? Several unknowns must first be addressed. The analgesic effects appear to be extremely variable in humans; contributing factors may include differences in drug absorption (especially with oral administration of THC), previous experience with marijuana, personality of the person, and the type of pain (need for mechanism-based treatment in pain). Once these variables are known, it may be possible to predict which pain patients will best respond to treatment with cannabinoids. Furthermore, given the differences in side-effect profiles and the possibility of a potentiated effect, a combination of cannabinoid and opiate therapy may prove to be partially benificial.