The gateway drug hypothesis refers to the pattern of substance use during adolescence whereby legal substances, such as nicotine and alcohol, precede the progressive use of illicit substances like cocaine and heroin. This concept of a gateway progression related to addiction vulnerability has had important implications with respect to biology, society, and public policy. The gateway drug hypothesis was initially formulated by epidemiological studies which, aiming to characterize the natural history of substance use, were not designed to address the issue of ‘causality’ and therefore garnered substantial controversy. Specifically, opponents argued that since the initial studies could not distinguish between a drug’s direct effect and other confounding variables (eg, environment), the term gateway drug was misleading. To address such criticisms, controlled animal experiments over the past few decades have helped to provide causal neurobiological insights relevant to the gateway hypothesis and drug addiction vulnerability.

Fredriksson et al (2016), being a recent example, tested the gateway hypothesis by assessing the effect of alcohol exposure on future cocaine use disorder in self-administering rats. Based on a comprehensive set of experiments, the researchers ultimately found that exposure to moderate or high amounts of alcohol beginning in late adolescence/early adulthood (and extending for 7 weeks) does not impact subsequent cocaine self-administration when examined later in adulthood. This study importantly builds on previous animal studies that, as opposed to assessing self-administration, had measured behavioral proxies of addiction such as novelty-seeking and conditioned place preference. The current findings nicely contribute to the field’s growing knowledge base, but the multifaceted complexity of substance use disorder requires several factors to be kept in mind that, if incorporated into future experiments, may address remaining questions that thoroughly evaluate the gateway drug hypothesis.

Log in or create a free account to read this content

Gain free access to this article, as well as selected content from this journal and more on nature.com

Access through your institution

or

Sign in or create an account
Continue with Google
Continue with ORCiD