Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Department of Anesthesiology and Critical Care Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
CNS Neurosci Ther. 2024 Sep;30(9):e70034. doi: 10.1111/cns.70034.
Opioid use disorder (OUD) remains a serious public health problem. Opioid maintenance treatment is effective but under-utilized, hard to access under existing federal regulations, and, once patients achieve OUD stability, challenging to discontinue. Fewer than 2% of persons with OUD stop using opioids completely. There have been calls from public advocacy groups, governmental agencies, and public health officials for new treatments for OUD. Dezocine, a non-scheduled opioid previously used in the United States and currently widely prescribed in China for pain management, could be a candidate for a novel OUD treatment medication in the U.S. Nonetheless, to date, there have been no reviews of the clinical and preclinical literature detailing dezocine's abuse potential, a key consideration in assessing its clinical utility.
There are no English language reports of human abuse, dependence, or overdose of dezocine, despite years of extensive clinical use. There are a few case reports of dezocine abuse in the Chinese literature, but there are no reports of overdose deaths. Dezocine is perceived as an opioid and is "liked" by opioid-experienced human and non-human primates, properties that are not dose-dependent and are mitigated by ceiling effects-higher doses do not result in more "liking." There is little withdrawal, spontaneous or precipitated, in humans, monkeys, rats, or mice treated chronically with dezocine alone. However, at some doses, dezocine can precipitate withdrawal in humans and monkeys dependent on other opioids. In rodents, dezocine reduces the severity of morphine withdrawal and the rewarding properties of other opioids.
Although dezocine is reinforcing in humans and monkeys with prior or concurrent opioid use within a restricted dose range, there are only a few anecdotal reports of dezocine abuse despite of the long history of use in humans. Given the evidence of dezocine's limited abuse potential, it could be useful both as a treatment for OUD. However, in-depth studies would be required for dezocine to be re-considered for clinical use.
阿片类药物使用障碍(OUD)仍然是一个严重的公共卫生问题。阿片类药物维持治疗是有效的,但利用率低,在现有联邦法规下难以获得,而且一旦患者达到 OUD 稳定,就很难停止使用。只有不到 2%的 OUD 患者完全停止使用阿片类药物。公众倡导团体、政府机构和公共卫生官员呼吁为 OUD 提供新的治疗方法。地佐辛,一种以前在美国使用的非管制类阿片类药物,目前在中国广泛用于疼痛管理,可能成为美国新型 OUD 治疗药物的候选药物。尽管如此,迄今为止,还没有对详细描述地佐辛滥用潜力的临床和临床前文献进行综述,而这是评估其临床效用的关键考虑因素。
尽管地佐辛已经广泛应用于临床多年,但没有关于人类滥用、依赖或过量使用地佐辛的英文报告。在中国文献中有一些地佐辛滥用的病例报告,但没有过量死亡的报告。地佐辛被认为是一种阿片类药物,并且受到有阿片类药物使用经验的人类和非人类灵长类动物的“喜爱”,这些特性与剂量无关,并且受到天花板效应的缓解——更高的剂量不会导致更多的“喜爱”。单独使用地佐辛治疗的人类、猴子、大鼠或小鼠几乎没有自发或诱发的戒断。然而,在某些剂量下,地佐辛可以在依赖其他阿片类药物的人类和猴子中引发戒断。在啮齿动物中,地佐辛减轻了吗啡戒断的严重程度和其他阿片类药物的奖赏特性。
尽管地佐辛在有或没有先前或同期阿片类药物使用史的人类和猴子中具有强化作用,但在人类使用历史悠久的情况下,仅有少数地佐辛滥用的传闻报告。鉴于地佐辛滥用潜力有限的证据,它可能对 OUD 的治疗有用。然而,需要进行深入的研究才能重新考虑将地佐辛用于临床。