The Role of the Cannabinoid System in Opioid Analgesia and Tolerance

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Özdemir E.

MINI-REVIEWS IN MEDICINAL CHEMISTRY, cilt.20, ss.875-885, 2020 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Derleme
  • Cilt numarası: 20
  • Basım Tarihi: 2020
  • Doi Numarası: 10.2174/1389557520666200313120835
  • Dergi Adı: MINI-REVIEWS IN MEDICINAL CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Biotechnology Research Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE
  • Sayfa Sayıları: ss.875-885
  • Anahtar Kelimeler: Cannabinoids, cannabinoid receptors, cannabinoid analgesia, opioid analgesia, opioid tolerance, analgesic, MORPHINE ANTINOCICEPTIVE TOLERANCE, TYPE-2 RECEPTOR AGONIST, CYCLIC-AMP ACCUMULATION, NEUROPATHIC PAIN, LOCUS-COERULEUS, RHESUS-MONKEYS, RAT MODEL, SYNERGISTIC INTERACTIONS, ENDOGENOUS OPIOIDS, ANIMAL-MODELS
  • Sivas Cumhuriyet Üniversitesi Adresli: Evet

Özet

Opioid receptor agonist drugs, such as morphine, are very effective for treating chronic and severe pain; but, tolerance can develop with long-term use. Although there is a lot of information about the pathophysiological mechanisms of opioid tolerance, it is still not fully clarified. Suggested mechanisms for opioid tolerance include opioid receptor desensitisation, reduction of sensitivity G-proteins, activation of Mitogen-Activated Protein Kinase (MAPK), altered intracellular signaling pathway including nitric oxide, and activation of mammalian Target of Rapamycin (mTOR). One way to reduce opioid tolerance and increase the analgesic potential is to use low doses. Combination of cannabinoids with opioids has been shown to manifest the reduction of the opioid dose. Experimental studies revealed an interaction of the endocannabinoid system and opioid antinociception. Cannabinoid and opioid receptor systems use common pathways in the formation of analgesic effect and demonstrate their activity via G Protein Coupled Receptors (GPCR). Cannabinoid drugs modulate opioid analgesic activity at a number of distinct levels within the cell, ranging from direct receptor associations to post-receptor interactions through shared signal transduction pathways. This review summarizes the data indicating that with combining cannabinoids and opioids drugs may be able to produce long-term analgesic effects, while preventing the opioid analgesic tolerance.