School of Pharmacy, China Pharmaceutical University, Nanjing, China.
Office of China National Narcotics Control Commission, China Pharmaceutical University Joint Laboratory on Key Technologies of Narcotics Control, Beijing, China.
Addict Biol. 2023 Feb;28(2):e13265. doi: 10.1111/adb.13265.
Carfentanil, as a fentanyl analogue, is a potent synthetic opioid. It has been controlled in many countries, and its emergence has been highlighted by many recent reports. However, although discriminative stimulus effects of carfentanil in rats had been reported, its abuse potential has not been fully evaluated. In this study, we evaluated the abuse potential of carfentanil via the tests of conditioned place preference (CPP), drug self-administration and naloxone-precipitated opioid withdrawal assay, compared with fentanyl and heroin. Carfentanil exhibited significant place preference at a minimum dose of 1 μg/kg in mice, whereas fentanyl and heroin induced significant place preference at the minimum doses of 100 μg/kg and 1000 μg/kg, respectively. In the drug-substitution test in heroin self-administered rats (50 μg/kg/infusion), carfentanil and fentanyl acquired significant self-administrations above saline levels from 0.05-0.1 and 0.1-10.0 μg/kg/infusion, respectively. Carfentanil induced the maximum number of infusions at 0.1 μg/kg, whereas fentanyl and heroin at 1 and 25 μg/kg, respectively. In short, carfentanil showed the highest potency to induce CPP and self-administration. Furthermore, repeated treatment with escalating doses of carfentanil, fentanyl or heroin induced typical withdrawal symptoms in mice, including a greater number of jumping and weight loss than saline group. This indicated that carfentanil could produce physical dependence similar to fentanyl and heroin. Taken together, the present study demonstrated the higher abuse potential of carfentanil compared with fentanyl and heroin. The rank order of abuse potential for these compounds is carfentanil > fentanyl > heroin.
卡芬太尼作为芬太尼类似物，是一种强效合成阿片类药物。它已在许多国家受到管制，其出现也被许多近期报告所强调。然而，尽管已经报道了卡芬太尼在大鼠中的辨别刺激效应，但它的滥用潜力尚未得到充分评估。在这项研究中，我们通过条件位置偏好（CPP）、药物自我给药和纳洛酮引发的阿片类药物戒断试验评估了卡芬太尼的滥用潜力，与芬太尼和海洛因进行了比较。卡芬太尼在小鼠中以 1μg/kg 的最小剂量表现出显著的位置偏好，而芬太尼和海洛因分别在 100μg/kg 和 1000μg/kg 的最小剂量下诱导出显著的位置偏好。在海洛因自我给药大鼠的药物替代试验中（50μg/kg/输注），卡芬太尼和芬太尼分别在 0.05-0.1 和 0.1-10.0μg/kg/输注的剂量上获得了高于生理盐水水平的显著自我给药。卡芬太尼在 0.1μg/kg 时诱导的输注次数最多，而芬太尼和海洛因则分别在 1 和 25μg/kg 时达到最大。总之，卡芬太尼显示出诱导 CPP 和自我给药的最高效力。此外，重复给予递增剂量的卡芬太尼、芬太尼或海洛因在小鼠中引起了典型的戒断症状，包括比生理盐水组更多的跳跃和体重减轻。这表明卡芬太尼可以产生类似于芬太尼和海洛因的身体依赖性。综上所述，本研究表明卡芬太尼的滥用潜力高于芬太尼和海洛因。这些化合物的滥用潜力排序为卡芬太尼>芬太尼>海洛因。
