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Review
. 2023 Dec 1:16:43-50.
doi: 10.1016/j.ibneur.2023.11.005. eCollection 2024 Jun.

The effect of cannabinoid type 2 receptor agonist on morphine tolerance

Affiliations
Review

The effect of cannabinoid type 2 receptor agonist on morphine tolerance

Di Cui et al. IBRO Neurosci Rep. .

Abstract

Pain highly impacts the quality of life of patients. Morphine is used for pain treatment; however, its side effects, especially morphine tolerance, limit its use in the clinic. The problem of morphine tolerance has plagued health workers and patients for years. Unfortunately, the exact mechanism of morphine tolerance has not been fully clarified. The mechanisms of morphine tolerance that are currently being studied may include μ-opioid receptor (MOR) desensitization and internalization, mitogen-activated protein kinase (MAPK) pathway activation and crosstalk, the effects of microglia and the increase in inflammatory factors. Morphine tolerance can be alleviated by improving the pathophysiological changes that lead to morphine tolerance. Previous studies have shown that a cannabinoid type 2 (CB2) receptor agonist could attenuate morphine tolerance in a variety of animal models. Many studies have shown an interaction between the cannabinoid system and the opioid system. The CB2 receptor may modulate the effect of morphine through a pathway that is common to the MOR, since both receptors are G protein-coupled receptors (GPCRs). This study introduces the potential mechanism of morphine tolerance and the effect of CB2 receptor agonists on reducing morphine tolerance, which can provide new ideas for researchers studying morphine and provide beneficial effects for patients suffering from morphine tolerance.

Keywords: Cannabinoid type 2 receptor; Inflammatory cytokines; Microglia; Morphine tolerance; Opioid receptor.

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Conflict of interest statement

The authors have no conflicts of interest to declare.

Figures

Fig. 1
Fig. 1
The mechanisms of morphine tolerance.

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References

    1. Adhikary Sabina, Li Hongbo, Heller Joshua, Skarica Mario, Zhang Ming, Ganea Doina, Tuma Ronald F. Modulation of inflammatory responses by a cannabinoid-2-selective agonist after spinal cord injury. J. Neurotrauma. 2011;28:2417–2427. - PMC - PubMed
    1. Ahmet Altun, Kema Yildirim, Ercan Ozdemir, Ihsan Bagcivan, Sinan Gursoy, Nedim Durmus. Attenuation of morphine antinociceptive tolerance by cannabinoid CB1 and CB2 receptor antagonists. J. Physiol. Sci. 2015;65(5):407–415. 2015. - PMC - PubMed
    1. Anand Uma, Otto William R., Sanchez-Herrera Daniel, Facer Paul, Yiangou Yiangos, Korchev Yuri, Birch Rolfe, Benham Christopher, Bountra Chas, Chessell Iain P., Anand Praveen. Cannabinoid receptor CB2 localisation and agonist-mediated inhibition of capsaicin responses in human sensory neurons. Pain. 2008;138:667–680. - PubMed
    1. Arttamangkul Seksiri, Quillinan Nidia, Low Malcolm J., Zastrow Mark, von, Pintar John, Williams John T. Differential activation and trafficking of micro-opioid receptors in brain slices. Mol. Pharm. 2008;74:972–979. - PMC - PubMed
    1. Bohn L.M., Gainetdinov R.R., Lin F.T., Lefkowitz R.J., Caron M.G. Mu-opioid receptor desensitization by beta-arrestin-2 determines morphine tolerance but not dependence. Nature. 2000;408:720–723. - PubMed