Claim: Nicotine makes brain more vulnerable to cocaine addiction

Do you believe in the gateway theory when it comes to drug use? Well, a group of scientists at Columbia University claims to have proven the theory.

It has often been said that cigarettes and alcohol act as gateway drugs that lead to the use of marijuana, cocaine and other drugs. This belief in a “gateway sequence” is something that has been widely disputed among the public for a long time.


However, an article in Science Translational Medicine by Amir Levine, MD, Denise Kandel, PhD; Eric Kandel, MD; and colleagues at Columbia University Medical Center offers a molecular explanation for the gateway sequence. They claim to have shown – with mice – that nicotine causes certain changes in the brain, making it more defenseless against cocaine addiction.


Various levels of exposure to nicotine and cocaine were analyzed, with researchers determining that a pretreatment regime with nicotine dramatically changes the response to cocaine in terms of addiction-related behavior and synaptic plasticity in the striatum, a brain region critical for addiction-related rewards.


At the molecular level, nicotine also primes the response to cocaine by impeding the activity of an enzyme – histone deacetylase – in the striatum. This limitation increases cocaine’s ability to turn on a gene named the FosB gene, which stimulates addiction.


Interestingly enough, the chemical relationship between nicotine and cocaine does not go both ways. This means that while nicotine radically augments the response to cocaine, there is no effect of cocaine on the response to nicotine.

Thus, nicotine’s ability to inhibit histone deacetylase provides a molecular mechanism for the gateway sequence of drug use. Yet, nicotine boosts the effects of cocaine only when it is taken for many days before the cocaine treatment and it actually has to be given with cocaine.

The research results inspired a new analysis of human epidemiological data; as it seems to show that most cocaine users begin ingesting the substance only after they have started smoking and while they are still active smokers. Essentially, those who begin cocaine use after taking up cigs have a higher risk of cocaine dependency in comparison to people who use cocaine first and then start smoking.


“These studies raise interesting questions that can now be explored further in animal models,” said study author Denise Kandel, a professor of Sociomedical Sciences at the Mailman School of Public Health.


“Do alcohol and marijuana – the two other gateway drugs – prime the brain by the same mechanism as nicotine? Is there a single mechanism for all gateway sequences, or does each sequence utilize a distinct mechanism?”


Keep in mind that epidemiological studies and data do not prove causation, they can only prove that they are associated with each other. This means that the research is showing that cocaine dependency is associated with nicotine, but does not prove that nicotine use will cause someone to become a cocaine addict.


The scientists also claim that the results underline the need for the creation of effective public health prevention programs that deal with all nicotine products, especially those targeted toward young people. Useful interventions would not only prevent smoking and related health problems, but could also decrease the risk of progression to chronic use of illicit drugs.


Of course, the real question remains: was this research published because of a genuine health concern, or was it conducted to generate more support for the gateway theory and the ongoing war against drugs? Both possibilities seem likely at this point. 

To ensure full recovery from addiction, a former drug addict should utterly avoid even the simplest substances that could serve as a gateway to other drugs.