The Gateway Hypothesis of substance abuse: developmental, biological and societal perspectives.
The Gateway Hypothesis describes how tobacco or alcohol use precedes marijuana and other illicit drug use. We review the epidemiological data, explore the underlying molecular mechanisms in mice and discuss the societal implications of the hypothesis, including the use of e-cigarettes by young people.


CONCLUSIONS
Our mouse model identifies biological processes underlying the hypothesis, showing that nicotine is a gateway drug that exerts a priming effect on cocaine through increased global acetylation in the striatum.
Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Mailman School of Public Health, Columbia University, New York, NY, USA; New York State Psychiatric Institute, New York, NY, USA.
Denise
D
Kandel
Eric
E
Kandel
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D005731:Ganglionic Stimulants / Q000494:pharmacology; D006801:Humans; D009538:Nicotine / Q000494:pharmacology; D019966:Substance-Related Disorders / Q000453:epidemiology / Q000209:etiology* / Q000378:metabolism / Q000523:psychology
D018765:Dopamine Uptake Inhibitors; D005731:Ganglionic Stimulants; D009538:Nicotine; D003042:Cocaine
Cocaine; E-cigarettes; Gateway Hypothesis; Histone acetylation; Nicotine