Researchers Suggest that E-Cigs May Promote Illicit Drug Use and Addiction

Can e-cigs lead to cocaine use?


If you were wondering how low people will sink to get a snide jab in at e-cigarettes, the answer is “depressingly low,” as the authors of  a new paper have confirmed with their recent claim that e-cigarettes lead to cocaine abuse. While we’ve gotten accustomed to hearing unsubstantiated claims about a gateway to tobacco, this takes things to a different level. While the media in the US were largely scared away from the story by a CASAA press release rightfully identifying the claim as “junk science,” UK newspapers were quite happy to repeat the stupid claims. The problem is that the research the claim is actually based on simply addresses nicotine (the same stuff in patches and gums), was conducted on mice and is based on the idea that the gateway hypothesis is true, which it probably isn’t.




  • The researchers gave mice nicotine and cocaine, either one substance alone, one before the other or one before a combination of the two, and looked at behavioral and neurological changes that resulted.


  • Mice given nicotine followed by nicotine and cocaine were more active than the other groups of mice, and were more likely to spend time in the place they received the drugs.


  • Mice given nicotine showed increased dopamine production and gene expression changes which may enhance the effects of cocaine.


  • Human evidence suggests that most cocaine users are smokers, and that higher proportions of people who smoked beforehand are addicted to cocaine than ones who used cocaine before ever smoking.


  • This is used to argue that e-cigarettes may lead to harder drugs, despite the fact that this hasn’t been observed and any nicotine use (including patches and gums) could theoretically have the same effect.


  • The study only looked at the impact of nicotine on the effects of cocaine if it’s taken, not what drives people to seek cocaine out in the first place. There is no evidence that nicotine exposure leads to increased cocaine-seeking – the behavior central to the concerns.


  • The common liability model is an alternative to the gateway model, and evidence showing that the “reverse gateway” drug use trajectory is as predictive of future addiction as the “gateway” trajectory seems to support this.


  • Studies looking at drug use patterns in multiple countries suggest that in countries with low alcohol, nicotine and marijuana use, drug addiction is no less common overall. Some other factor seems to be at play: marijuana, alcohol and nicotine merely look like gateways because they’re the most available drugs in western society.


The Experiments – Looking for a Biological Basis for the Gateway Hypothesis


The paper was published in the New England Journal of Medicine and is available in full for free. It was written by a husband and wife, doctors Eric and Denise Kandel, with the latter being one of the leading proponents of the gateway hypothesis for addictive drugs. They say that in western societies, there is a “well defined” progression from legal drugs such as alcohol and nicotine to illicit ones, usually marijuana, and then harder drugs like cocaine or heroin. They assume this to be true, and then review evidence from studies they conducted on mice looking for a biological basis for this progression from one drug to the other, in terms of changes to the structure of the brain and changes to the expression of genes.


In short, they gave mice cocaine and nicotine (sometimes nicotine before cocaine and sometimes vice-versa) or just one of the substances, then observed their behavior and looked at the physiological effects of the exposure. For example, compared to control (non-drugged) mice, those given cocaine were 58 percent more active, mice given nicotine for a day before nicotine and cocaine together were no more active, and mice given nicotine for a week and then nicotine and cocaine for four days were 98 percent more active. They did the reverse of this last protocol too, but the mice were no more active than controls when cocaine was given before nicotine.


Some of the more biological investigations looked at the impact nicotine has on the brain with respect to the potential for cocaine use. One of the experiments suggested that exposure to nicotine leads to increased dopamine production, thus enhancing the rewarding effects of cocaine, and other studies also indicated that changes in the expression of genes after exposure to nicotine might increase the effect of cocaine. The studies also indicate that nicotine has to be given to the mice repeatedly beforehand and also at around the same time as the cocaine for the effect to be notable.


After reporting these findings, the authors move on to evidence from humans, attempting to determine whether cocaine users and those addicted to the drug are more likely to be smokers. Data from a small group of students followed for just under 20 years shows that 75.2 percent of cocaine users were smoking during the same month they started using cocaine, and evidence from a larger sample suggests that the rate of cocaine dependence is the highest in people who smoked cigarettes first (20.2 percent) compared to people who started smoking after using cocaine (6.3 percent) or those who’d never smoked more than 100 cigarettes (10.2 percent).


After going over their findings in the conclusion to the paper, the authors then move – quite unexpectedly – onto e-cigarettes for the final few paragraphs. They acknowledge that e-cigarettes remove some of the morbidity associated with cigarette smoking, but say that they are “pure nicotine-delivery devices.” This line was repeated in the official press release which led many of the newspapers reporting the story to say that e-cigarette users consume pure nicotine – as if it’s impossible to use your brain before putting something like that down in print. Because they deliver nicotine, the authors say they “pose the same risk of addiction to other drugs and experiences.”


They point out that e-cigarette use is increasing “exponentially” among adolescents and young adults, based on the thoroughly misleading reading of the CDC’s youth e-cig use data, which actually showed that the rate of vaping among non-smoking teens is extremely low, and contained no true measure of regular use. Carl V. Phillips points out that if the increase in use among adolescents really was exponential – which there isn’t anywhere near enough data points to confirm – then the amount of adolescents and young adults vaping would be more than 100 percent by 2016. Obviously basic math isn’t the authors’ strong suit.


Based on the effect of nicotine on adolescent mice (increasing how much they decide to take cocaine), they implicitly suggest that e-cigarettes could lead to increased cocaine use among adolescents. They follow this with, “Whether e-cigarettes will prove to be a gateway to the use of combustible cigarettes and illicit drugs is uncertain, but it is clearly a possibility.”


The paper ends with, “Nicotine acts as a gateway drug on the brain, and this effect is likely to occur whether the exposure is from smoking tobacco, passive tobacco smoke, or e-cigarettes. More effective prevention programs need to be developed for all the products that contain nicotine, especially those targeting young people. Our data suggest that effective interventions would not only prevent smoking and its negative health consequences but also decrease the risk of progressing to illicit drug use and addiction.”


Carl Phillips draws attention to the switch from the speculative statement about the actual gateway effect to the much weaker version of the claim (as in, nicotine affects the brain) asserted more strongly, thus implying that the initial uncertain statement is more likely than it really is. This bait-and-switch then paves the way for them to suggest that prevention programs targeted at e-cigarettes would prevent smoking (which is completely unsupported by this or any other evidence) and illicit drug use and addiction.


Liking Cocaine More is Not the Same as Snorting it


Of course, one of the huge problems with this study is that something that happens to the behavior or neurology of a mouse in response to nicotine is not necessarily what you would expect in a human. Moreover, the mice participating in this type of research, often in confined spaces with little or no social interaction, are not even normal mice. In fact, in a famous experiment designed to refute the classic rat drug abuse models, a researcher gave rats a healthier place to live, with places to exercise and play, rats of the opposite sex, nice food and places to raise children, and found that even when given morphine for six weeks beforehand, the rats put in “rat park” didn’t use morphine as much as the ones in the standard laboratory cages. In other words, these animals in lab experiments are not given ordinary experiences and don’t behave like healthier animals.


Even if we accept the experiment as directly translating to ordinary humans, the findings still don’t warrant much concern about cocaine use among vapers. The big problem is that the mice in this experiment were given cocaine after use of nicotine. So even if nicotine does prime the brain for greater enjoyment of cocaine, it doesn’t mean that exposed mice or humans will actually take it. Carl Phillips points out that plenty of substances and activities (such as caffeine and extreme sports) will probably have the same effect, but it doesn’t mean they cause cocaine use, or that we need to suggest legal restrictions on them. The finding that most human cocaine users are smokers is interesting, but it obviously doesn’t mean that all smokers are cocaine users. Even though nicotine may prime the brain to enjoy cocaine more, it doesn’t mean that people know they’ll enjoy it moreor that they will go and seek cocaine out. In fact, the real thing we need to be concerned about is what makes some people seek cocaine out, rather than the biological details of why some may enjoy it more than others.


Carl Philips also points out that whenever you have an experience, something in the brain will change, but that change is only useful information if it explains real-world behavior. If some exposed to nicotine take cocaine and some don’t, then nicotine exposure obviously doesn’t wholly explain the behavior of taking cocaine. It would take a dose-response type relationship (where more nicotine exposure and consequently greater brain changes led to greater odds of cocaine use) to even start to explain the behavior. The core thing you need before you even get going, though, is clear evidence that nicotine use precedes cocaine use – without that, there’s nothing to even explain biologically in the first place.


The Gateway Hypothesis: Is it Even True? (Spoiler: Probably Not)


are e-cigs a gateway drug?


So a core point in the interpretation of this study is whether the gateway hypothesis really stands up to evidence. If it does, then perhaps the reaction of these mice to nicotine prior to cocaine provides a biological explanation for the effect. Since it’s the author’s pet theory, it’s assumed to be true for the purposes of this study. However, real-world evidence doesn’t really paint such a clear picture.


The alternate explanation for this gateway-like effect is the common liability model, which states that some other factor makes some individuals at greater risk for addiction and drug use overall, not specific substances. In this theory, the use of nicotine and alcohol would likely come first because these are the primary legal drugs in western society, and marijuana would be another of the first substances because it’s more widely available than other illicit drugs.


There are many interesting findings about the gateway hypothesis, and many seem to favor the common liability model rather than the gateway model. One example compared boys who used only legal substances, those who used legal substances before marijuana and those who used marijuana before legal substances. It found that 22.4 percent of those who used marijuana did so without a “gateway” legal substance being taken first, and that even among those who did follow the “gateway” trajectory, delinquency had a stronger association with marijuana than legal drug use. In fact, the reverse gateway sequence (marijuana then legal drugs) had the same level of predictive ability for later addiction as the gateway sequence.


Another study looked at data from across 17 different countries, with over 85,000 participants in total. This study suggested that the “gateway” pattern commonly observed is at least partially related to other causes, not an actual casual effect of use of one drug on the chances of using others. It found that the association between the use of “gateway” drugs and subsequent other drug use differed between countries, sometimes related to how common use of other drugs was in the specific country, and that countries with higher rates of use of non-gateway drugs had more “gateway violations” than other countries. Japan was the best example, because alcohol, tobacco and marijuana are less frequently used there. If the gateway theory was true (these being the key substances implicated), then the rate of illicit drug use would also have been lower there, but the study found that there was no difference.


If the common liability model is true, the use of any drug would predict use of other drugs in future, likely due to some other factor (consistent with the first study, which showed a stronger association with general delinquency than specific substances), and the precise direction of the progression would depend primarily on the availability of those drugs (as the second study suggests). All things considered, the gateway theory of drug use seems like nonsense, but in any case it’s far from proven.


For e-cigarettes, the gateway theory to other drugs doesn’t come up often, with the main concern being subsequent smoking of tobacco. The common liability model would suggest that anybody who did go from vaping to smoking would have been pre-disposed to smoking anyway. The real problem for the theory in this instance is that non-smokers, adolescent or not, barely ever start vaping anyway. But more broadly, the entire gateway theory (however it’s applied) is on shaky ground. Finding a biological effect of nicotine that increases enjoyment of cocaine is pretty useless if the theory isn’t true in the first place.


Conclusion – A Back-Handed Attempt to Criticize Vaping


It’s clear that this paper is merely a routine piece of research looking for a biological mechanism for a questionable theory, which took a wild swipe at e-cigarettes in order to drum up some interest in the findings. If that wasn’t true, why would the authors not have made the focus on tobacco cigarettes, nicotine gums, patches or inhalers? Why just e-cigarettes? According to their interpretation of the findings, it’s just as valid to say nicotine patches are gateways to cocaine abuse, but nobody would be particularly interested in regurgitating a press release that said that.


As vapers, we can only hope nobody takes this seriously, but as reasonable people, we might also hope it could lead to some much-needed questioning of the gateway hypothesis on the whole. Maybe, just maybe, complex biological, psychological and social interactions are responsible for the risk of addiction, rather than some easy-to-demonize substance. Deciding to pick on something like e-cigs, which hold potential for saving millions of lives around the world by helping people stop smoking, makes even less sense.