Opioids and cannabinoids interactions: involvement in pain management

Among several pharmacological properties, analgesia is the most common feature shared by either opioid or cannabinoid systems. Cannabinoids and opioids are distinct drug classes that have been historically used separately or in combination to treat different pain states. Indeed, it is widely known that activation of either opioid or cannabinoid systems produce antinociceptive properties in different pain models. Moreover, several biochemical, molecular and pharmacological studies support the existence of reciprocal interactions between both systems, suggesting a common underlying mechanism. Further studies have demonstrated that the endogenous opioid system could be involved in cannabinoid antinociception and recent data have also provided evidence for a role of the endogenous cannabinoid system in opioid antinociception. These interactions may lead to additive or even synergistic antinociceptive effects, emphasizing their clinical relevance in humans in order to enhance analgesic effects with lower doses and consequently fewer undesirable side effects. Thus, the present review is focused on bidirectional interactions between opioids and cannabinoids and their potent repercussions on pain modulation.