Cannabinoid–opioid interactions during neuropathic pain and analgesia

Abstract

Opiates and exogenous cannabinoids, both potent analgesics used for the treatment of patients with neuropathic pain, bind to and activate class A G-protein coupled receptors (GPCRs). Several lines of evidence have recently suggested that opioid and cannabinoid receptors can functionally interact in the central nervous system (CNS). These interactions may be direct, such as through receptor heteromerization, or indirect, such as through signaling cross-talk that includes agonist-mediated release and/or synthesis of endogenous ligands that can activate downstream receptors. Interactions between opioid and cannabinoid receptors may mediate many of the behavioral phenomena associated with use of these drugs, including the production of acute antinociception and the development of tolerance and cross-tolerance to the antinociceptive effects of opioid and cannabinoid-specific ligands. This review summarizes behavioral, anatomical, and molecular data characterizing these interactions during the development of neuropathic pain and during antinociceptive treatment with these drugs alone or in combination. These studies are critical for understanding how the receptor systems involved in pain relief are altered during acute or chronic pain, and for designing better antinociceptive drug therapies, such as the combined use of opioid and cannabinoid receptor agonists or selective activation of receptor heteromers, that directly target the altered neurophysiology of patients experiencing pain.

Genotype-dependent responsivity to inflammatory pain: A role for TRPV1 in the periaqueductal grey

“…Analgesics targeting the endogenous opioid system are the most commonly prescribed (Trescot et al, 2008) and the opioid system is well recognised to modulate acute, inflammatory and neuropathic pain (Bushlin et al, 2010;Przewłocki and Przewłocka, 2001). This system is composed of the μ (mu)-, δ (delta)-, and κ(kappa)-opioid receptors.…”

Phytotherapeutical implications in pain perception - focusing on schizophrenia

“…Thus, they propose combining opioid and cannabinoid agonists or targeting receptor heteromers directly. These new ideas are in need of exploration, but show promising potential in diminishing chronic pain [96], representing a starting point in the new avenue unfolding in the story of pain treatment.…”

“…Moreover, an interesting connection between cannabinoids and opioids has been recently highlighted, that might open new opportunities in the treatment of neuropathic pain and in the development of new analgesics. There has been emphasized on the synergism between the cannabinoid-opioid receptor systems, showing that low doses of cannabinoid agonists combined with opioid agonist have a promising outcome [96]. Although, tolerance and cross-tolerance must not be ignored, occurrence of addiction phenomenon is another impediment adding to their limiting usage on the long run [96].…”

“…There has been emphasized on the synergism between the cannabinoid-opioid receptor systems, showing that low doses of cannabinoid agonists combined with opioid agonist have a promising outcome [96]. Although, tolerance and cross-tolerance must not be ignored, occurrence of addiction phenomenon is another impediment adding to their limiting usage on the long run [96]. In effect, strategies have been developed in order to reduce the side-effects encountered.…”

Cannabis and Its Derivatives: Review of Medical Use

“…Evidence has been accumulating from molecular and cell-signaling studies that suggest that the opioids and cannabinoid systems can interact synergistically to enhance analgesic effects. 49 Animal studies have shown that topical cannabinoid enhances the action of topical morphine, 50 an effect that is preserved in a morphine-tolerant state. 51 Moreover, cannabinoids are increasingly being recognized in animal models for their potential sparing effects with opioids 52 of neuropathic pain and arthritic pain.…”