Michelle Ren, MS; Shahrdad Lotfipour, PhD


Western J Emerg Med. 2019;20(5):696-709. 

In This Article


We present epidemiological and clinical findings supporting the gateway hypothesis (Table 1), and emphasize that early adolescent nicotine exposure in various rodent models increases the acquisition and intake of nicotine, alcohol, cocaine, and methamphetamine; co-use of nicotine and alcohol; and the rewarding effects of nicotine, cocaine, methamphetamine, and opioids (Table 2). Although thousands of constituents make up combustible cigarettes, the animal studies highlighted in this review investigate the effects of isolated nicotine, which is more translationally relevant to electronic cigarette use than tobacco/cigarette smoking. This review emphasizes the emerging theme that nicotine hijacks the brain's reward pathway, particularly during adolescence when the brain is rapidly maturing, by inducing long-term changes in brain chemistry and function.

Nicotine interacts with other neurotransmitter systems and as a result increases the rewarding effects of other drugs by enhanced activation of reward circuitry. Developing brains are incredibly susceptible to long-lasting changes from perturbations during maturation, leading to behavioral changes that continue into adulthood. The prevalence of nicotine use among adolescents and the extensive interactions between nicotinic receptors and drugs of abuse highlight the critical need to better understand how nicotine modulates long-term consequences on brain and behavior related to addiction vulnerability.

This comprehensive review was performed to provide insight into how teenage experimentation with nicotine can induce drastic, ongoing consequences on reward and reinforcement of other drugs of abuse. Alterations in nicotinic acetylcholine receptors are only part of what influence adolescent substance abuse, and the reasons why adolescents decide to use tobacco products and/or nicotine delivery devices need to be further studied. Recognizing adolescent nicotine use as a possible predisposition to addiction to nicotine itself or other substances may decrease illicit drug experimentation and the incidence of drug addiction. Thus, healthcare professionals should take caution when dealing with adolescents with a history of e-cigarette use and continue to inform about its risks. Given the biochemical adaptations as a consequence of adolescent nicotine exposure, physicians may take an individualized approach to treatment and provide additional resources for patients and their families. This increased education and advocacy may improve care coordination and lead to greater adherence to a discharge plan and improved clinical outcomes. Regulatory agencies should continue to establish age limits on the purchase of nicotine products, and increase education and awareness of the risks of smoking and/or vaping during adolescence.