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.

阿片受体激动剂，例如吗啡，对于治疗慢性和重度疼痛非常有效。但是，长期使用会产生耐受性。尽管关于阿片样物质耐受的病理生理机制有很多信息，但仍未完全阐明。阿片类药物耐受性的建议机制包括阿片类药物受体脱敏，敏感性G蛋白降低，丝裂原活化蛋白激酶（MAPK）活化，细胞内信号传导途径（包括一氧化氮）和哺乳动物雷帕霉素靶标（mTOR）活化。降低阿片类药物耐受性和增加止痛潜力的一种方法是使用低剂量。大麻素与阿片类药物的组合已显示出阿片类药物剂量的减少。实验研究表明，内源性大麻素系统与阿片类药物的镇痛作用相互影响。大麻素和阿片受体系统在镇痛作用的形成中使用共同的途径，并通过G蛋白偶联受体（GPCR）证明其活性。大麻素药物在细胞内的许多不同水平上调节阿片类药物的镇痛活性，范围从直接的受体缔合到通过共享信号转导途径的受体后相互作用。这篇综述总结了表明大麻素和阿片类药物合用的药物可能能够产生长期镇痛作用，同时防止阿片类镇痛耐受性的数据。大麻素和阿片受体系统在镇痛作用的形成中使用共同的途径，并通过G蛋白偶联受体（GPCR）证明其活性。大麻素药物在细胞内的许多不同水平上调节阿片类镇痛活性，范围从直接的受体缔合到通过共享信号转导途径的受体后相互作用。这篇综述总结了表明大麻素和阿片类药物合用的药物可能能够产生长期镇痛作用，同时防止阿片类镇痛耐受性的数据。大麻素和阿片受体系统在镇痛作用的形成中使用共同的途径，并通过G蛋白偶联受体（GPCR）证明其活性。大麻素药物在细胞内的许多不同水平上调节阿片类镇痛活性，范围从直接的受体缔合到通过共享信号转导途径的受体后相互作用。这篇综述总结了表明大麻素和阿片类药物合用的药物可能能够产生长期镇痛作用，同时防止阿片类镇痛耐受性的数据。