Response variability across the lifespan is an important consideration in toxicology and risk assessment, and the toxic effects of drugs and chemicals during adolescence need more research. This paper summarizes a workshop presented in March 2019, at the Society of Toxicology Annual Meeting in Baltimore, Maryland, that brought together experts in research on drug dependence and toxicity related to nicotine, cannabis, cocaine, and other illicit drugs during adolescence. The goal of the workshop was to address the following issues: (1) Do the effects of adolescent exposure differ from the same exposure in adults? (2) Are there unique biological markers of adolescent brain development? If so, what are they and how reliable are they? (3) Since multiple factors influence substance use disorder, can we disentangle risk factors for abuse and/or toxicity? What are the underlying biological susceptibilities that lead to dependence and neurotoxicity? What are the social, psychosocial and environmental factors that contribute to abuse susceptibilities? This paper reviews drug policy and national trends in adolescent substance use; the public health consequences of e-cigarettes; rat models of adolescent-onset nicotine self-administration and persisting effects of gestational nicotine; sex-dependent effects of delta-9-tetrahydrocannabinol on adolescent brain-behavior relationships; and translational approaches for identifying adolescent risk factors for transition to drug dependence. There is strong evidence that drug exposure prior to adulthood has longer lasting effects on behavior and the underlying neural circuitry. These effects, which are sex-dependent and influenced by stress, may be candidates as predictors of adolescent vulnerability. A major challenge to determining if adolescents have a unique susceptibility to dependence is whether and to what extent the human data allow distinction between the increased risk due to biological immaturity, an underlying biological susceptibility to dependence, or psychosocial and environmental factors for substance dependence. Factors important to consider for development of animal models include the timing and pattern of exposure as it relates to adolescence; age of assessment, and direct comparison with similar effects following exposures to adults to demonstrate that these effects are unique to adolescence. Here we provide a roadmap for further research into what makes adolescent brain development unique.

整个生命周期的反应变异性是毒理学和风险评估的一个重要考虑因素，青春期药物和化学品的毒性作用需要更多研究。本文总结了 2019 年 3 月在马里兰州巴尔的摩举行的毒理学学会年会上举办的研讨会，该研讨会汇集了与尼古丁、大麻、可卡因和其他青春期非法药物相关的药物依赖和毒性研究的专家。研讨会的目标是解决以下问题：(1) 青少年暴露的影响是否与成人相同的暴露不同？(2) 青少年大脑发育是否有独特的生物学标志物？如果是这样，它们是什么以及它们的可靠性如何？(3) 由于多种因素影响物质使用障碍，我们能否解开滥用和/或毒性的风险因素？导致依赖性和神经毒性的潜在生物学易感性是什么？哪些社会、心理社会和环境因素会导致滥用易感性？本文回顾了青少年药物使用的毒品政策和国家趋势；电子烟对公众健康的影响；青春期尼古丁自我给药和妊娠尼古丁持续作用的大鼠模型；delta-9-四氢大麻酚对青少年大脑行为关系的性别依赖性影响；确定青少年向药物依赖过渡的危险因素的转化方法。有强有力的证据表明，成年前接触药物对行为和潜在的神经回路有更持久的影响。这些效果，性别依赖和受压力影响，可能是青少年脆弱性的预测指标。确定青少年是否具有独特的依赖易感性的一个主要挑战是人类数据是否以及在多大程度上允许区分由于生物不成熟导致的风险增加、潜在的生物依赖易感性或物质依赖的心理社会和环境因素。开发动物模型需要考虑的重要因素包括与青春期相关的暴露时间和模式；评估年龄，并与成人暴露后的类似影响进行直接比较，以证明这些影响是青春期独有的。在这里，我们为进一步研究使青少年大脑发育独特的原因提供了路线图。