Henningfield Jack E, Wang Daniel W, Huestis Marilyn A
PinneyAssociates, Inc., Bethesda, MD, United States.
Front Pharmacol. 2022 Jan 28;12:775073. doi: 10.3389/fphar.2021.775073. eCollection 2021.
Drugs are regulated in the United States (US) by the Controlled Substances Act (CSA) if assessment of their abuse potential, including public health risks, show such control is warranted. An evaluation via the 8 factors of the CSA provides the comprehensive assessment required for permanent listing of new chemical entities and previously uncontrolled substances. Such an assessment was published for two kratom alkaloids in 2018 that the Food and Drug Administration (FDA) have identified as candidates for CSA listing: mitragynine (MG) and 7-hydroxymitragynine (7-OH-MG) (Henningfield et al., 2018a). That assessment concluded the abuse potential of MG was within the range of many other uncontrolled substances, that there was not evidence of an imminent risk to public health, and that a Schedule I listing (the only option for substances that are not FDA approved for therapeutic use such as kratom) carried public health risks including drug overdoses by people using kratom to abstain from opioids. The purpose of this review is to provide an updated abuse potential assessment reviewing greater than 100 studies published since January 1, 2018. These include studies of abuse potential and physical dependence/withdrawal in animals; receptor binding; assessments of potential efficacy treating pain and substance use disorders; pharmacokinetic/pharmacodynamic studies with safety-related findings; clinical studies of long-term users with various physiological endpoints; and surveys of patterns and reasons for use and associated effects including dependence and withdrawal. Findings from these studies suggest that public health is better served by assuring continued access to kratom products by consumers and researchers. Currently, Kratom alkaloids and derivatives are in development as safer and/or more effective medicines for treating pain, substances use disorders, and mood disorders. Placing kratom in the CSA via scheduling would criminalize consumers and possession, seriously impede research, and can be predicted to have serious adverse public health consequences, including potentially thousands of drug overdose deaths. Therefore, CSA listing is not recommended. Regulation to minimize risks of contaminated, adulterated, and inappropriately marketed products is recommended.
在美国，如果对药物滥用潜力（包括公共健康风险）的评估表明有必要进行管控，那么这些药物就会受到《管制物质法》（CSA）的监管。通过CSA的8个因素进行评估，可为新化学实体和以前不受管制的物质的永久列管提供所需的全面评估。2018年针对两种 kratom生物碱发布了这样一份评估报告，美国食品药品监督管理局（FDA）已将其确定为CSA列管的候选物质：帽柱木碱（MG）和7-羟基帽柱木碱（7-OH-MG）（亨宁菲尔德等人，2018a）。该评估得出结论，MG的滥用潜力在许多其他不受管制物质的范围内，没有证据表明对公众健康存在紧迫风险，且将其列入附表一（对于未获FDA批准用于治疗用途的物质，如kratom，这是唯一选择）会带来公共健康风险，包括使用kratom来戒除阿片类药物的人出现药物过量情况。本综述的目的是提供一份更新的滥用潜力评估报告，回顾自2018年1月1日以来发表的100多项研究。这些研究包括动物的滥用潜力和身体依赖性/戒断研究；受体结合研究；对治疗疼痛和物质使用障碍的潜在疗效评估；具有安全性相关发现的药代动力学/药效学研究；具有各种生理终点的长期使用者的临床研究；以及关于使用模式、原因和相关影响（包括依赖性和戒断）的调查。这些研究的结果表明，确保消费者和研究人员能够继续获取kratom产品，能更好地维护公众健康。目前，kratom生物碱及其衍生物正在开发中，有望成为治疗疼痛、物质使用障碍和情绪障碍更安全和/或更有效的药物。通过制定时间表将kratom列入CSA会将消费者和持有行为定为犯罪，严重阻碍研究，并且可以预见会产生严重的不良公共健康后果，包括可能导致数千例药物过量死亡。因此，不建议将其列入CSA。建议进行监管，以尽量减少受污染、掺假和销售不当产品的风险。
