Chris Christie said that marijuana is a “gateway drug” while arguing for enforcement of its federal status as an illegal substance. Though there are correlations between marijuana use and other drugs, there is no conclusive evidence that one actually causes the other. The science on this topic is far from settled.

In an interview on Hugh Hewitt’s radio show on April 14, Christie, the governor of New Jersey and a potential 2016 presidential candidate, said he would crack down on marijuana sales and use in Washington and Colorado, which in 2012 were the first two states to legalize marijuana for recreational use. “Marijuana is a gateway drug,” Christie said. “We have an enormous addiction problem in this country.”

The “gateway hypothesis” or theory refers to the idea that one substance — marijuana, in this case — leads users to subsequently use and/or abuse other drugs. If Christie’s point is simply that the use of marijuana tends to precede the use of other drugs, then he is correct — but that’s not the whole story.

Though studies of large populations of people have indeed found that those who smoke marijuana are more likely to use other drugs, these studies show a correlation without showing causation — a commonly misunderstood phenomenon in science. In short, just because marijuana smokers might be more likely to later use, say, cocaine, does not imply that using marijuana causes one to use cocaine.

A 1999 report from the Institute of Medicine, which is part of the National Academy of Sciences, laid out this issue clearly (see pages 100-101): “In the sense that marijuana use typically precedes rather than follows initiation into the use of other illicit drugs, it is indeed a gateway drug. However, it does not appear to be a gateway drug to the extent that it is the cause or even that it is the most significant predictor of serious drug abuse; that is, care must be taken not to attribute cause to association.”

We spoke with several experts and reviewed the available scientific literature on gateway theory. Christie’s definitive statement is unsupported by evidence — there is some evidence in favor of a gateway effect, but the scientific community shares no consensus on the issue and there is little evidence on the underlying cause of that effect.

Biological Mechanisms

Importantly, there are two distinct ways in which marijuana or other drugs might act as a gateway: biological or pharmacological reasons why marijuana would lead to other drugs (sometimes known as the “stepping stone” theory); and social or cultural reasons for the jump from one drug to another. In the case of the first idea, some research has found plausible biological ways in which marijuana — and, notably, nicotine and alcohol — could “prime” the brain and make one more likely to abuse other drugs, but this research is largely in rats and is not conclusive.

“There are some studies that have been done in animals and they suggest that there may be changes that marijuana produces in the brain that can be long lasting when the animal is exposed to it as an adolescent,” said Susan Weiss, the associate director for scientific affairs at the National Institute on Drug Abuse, which is part of the National Institutes of Health, in a phone call.

For example, in one study published in 2007 in the journal Neuropsychopharmacology, researchers treated some adolescent rats with THC, the main active compound in marijuana. The rats were then given the opportunity to “self-administer” heroin as adults. The THC-treated rats consistently increased their heroin usage, while those rats that had not been treated with THC maintained a steady level of heroin intake.

Another study, published in 2014 in European Neuropsychopharmacology, similarly found that adolescent THC exposure in rats seemed to change the rodents’ brains. The rats treated with THC exhibited more anxiety-like behaviors, and also exhibited more “heroin-seeking” behavior later in life. The authors concluded that, at least in rats, chronic exposure to THC during adolescence could indeed be responsible for “increased vulnerability to drug relapse in adulthood.” Another rat study, from Biological Psychiatry in 2004, also found that THC exposure induced “cross-tolerance” that could increase later usage of cocaine, morphine, and amphetamine.

Notably though, these findings are not unique to marijuana. Weiss told us that nicotine and alcohol, two other drugs that are widely available to young people and are often among the first drugs used, have been found to have similar effects in animal studies. One such study, published in the journal Science Translational Medicine in 2011, showed that treating mice with nicotine induced genetic changes that increased the response to cocaine. Interestingly, this only worked in one direction, when the mice were treated with nicotine and then co-treated with both nicotine and cocaine; if cocaine was administered first, the effect was not seen, suggesting there may be a gateway effect from nicotine to cocaine.

The studies on brain chemistry and the influence of marijuana on responses to other drugs only has taken place in those animal studies, meaning extrapolation to humans is problematic. We do have some hints of biological gateway effects in humans, though, from studies involving twins.

One such study, which was published in the Journal of the American Medical Association in 2003, and involved 311 twin pairs “discordant” for early marijuana use — that is, one of each set of twins had used marijuana before the age of 17, and the other had not. The twin that did use marijuana early in life had between a 2.1- and 5.2-times higher risk of other drug use, alcohol dependence, and drug abuse/dependence than their sibling. This means that associations between marijuana use and later drug use can’t be explained by genetic factors, and gives support to the gateway theory.

But even this leaves a lot of unanswered questions, according to Weiss. “Did marijuana change that twin and make them more likely to use other drugs? What was it about that one twin that made them use marijuana while the other twin didn’t? We don’t know the answer to that. Did he happen to have friends that were more deviant? It’s very difficult to completely interpret these things; most likely there is probably some convergence of factors.”

And indeed, a subsequent twin study published in Development and Psychopathology in 2008 called the results of the first into question. The paper found a similar difference between twins with regard to early marijuana use and later drug use, but only in non-identical twins. To the authors, this supported the idea that there are too many factors to conclude in one direction or the other: “[T]he longitudinal pattern of drug use that has been interpreted as the ‘gateway effect’ might be better conceptualized as a genetically influenced developmental trajectory.”

Hidden Causes and International Patterns

Clearly, the biological evidence for a gateway effect is varied and difficult to interpret. Unfortunately, specific evidence for the other possible mechanisms are also far from clear and definitive.

The cultural and social version of the gateway theory posits that simply by being around marijuana and the people who use it one might be more likely to end up trying and using other drugs as well. There is also the idea that an individual who uses marijuana habitually may simply be more likely to engage in risk-taking behavior, and thus will seek out the other drugs. This would suggest there is no causal link from marijuana to other drugs, it is only a function of marijuana’s general availability versus other more difficult-to-obtain substances.

Some researchers, though, think there is almost certainly a causal link — it’s just not clear what it is. David Fergusson is a professor at the University of Otago in Christchurch, New Zealand, and he has been leading the Christchurch Health and Development Study, a 35-year, ongoing look at 1,265 New Zealanders born in 1977. Several papers on drug use and the gateway effect have emerged from this study.

“There is a very strong association between the use of cannabis in adolescence and subsequent use of other illicit drugs,” Fergusson told us in an email. He said that one analysis from his study published in the journal Addiction used a statistical test that “clearly suggest the existence of some kind of causative association in which the use of cannabis increases the likelihood that the user will go on to use other illicit drugs. … Where things get murky is in the area of the nature of the causal processes.”

Another possible contributor to those processes is simply the availability of a given drug that might lead it to be used first, rather than any particular biological reason for moving from one to another. A large international collaboration produced a study published in the journal Drug and Alcohol Dependence in 2010 that looked at patterns of drug use across 17 countries. The study found that “[w]ith few exceptions, substances earlier in the ‘gateway’ sequence predicted drug use later in the sequence.” That finding, though, differed in strength across countries.

Those early-sequence drugs included marijuana, alcohol, or nicotine. Different countries had different patterns of drug use in general, and also different patterns of gateway “violations” — that is, when people used other illicit drugs without ever trying those early drugs. For example, Japan had very low rates of marijuana use (1.6 percent by age 29), and also had more people use other illicit drugs before the early-use drugs than in other countries. The authors wrote, “a lack of exposure and/or access to substances earlier in the normative sequence did not correspond to reductions in overall levels of other illicit drug use.” In other words: limiting access to marijuana might not have any effect on heroin and cocaine use.

That study also provides a hint that marijuana’s illegal status may contribute to its gateway effects. The mechanism here is simple: accessing one illegal drug simply means a marijuana user would be more likely to have access to other illegal drugs, through social interactions and the act of actually buying the drug. The Drug and Alcohol Dependence study found that marijuana use was less strongly associated with other illicit drug use in the Netherlands, where marijuana can legally be purchased in so-called coffee shops, than in other countries including the United States.

A working report from the Rand Drug Policy Research Center looked at the Dutch experience with legalized marijuana as well. According to that paper, the U.S. actually has slightly higher rates of use than the Netherlands, and there is evidence for a “weakened gateway” in the Netherlands: about 15 of every 100 cannabis users have tried cocaine in that country, a lower rate than others where marijuana is illegal such as Scotland, Italy, and Norway. The same is true for amphetamine use.

Fergusson told us that more research is still needed to truly understand what the causal link between marijuana and other drugs might be. “It is my view that when the jury comes in, what will be found is a complex multivariate situation in which the greater susceptibility of cannabis to illicit drug use is the end point of a complex mix of factors including: the neurophysiological effects of cannabis; social and peer influences; and the legal status of cannabis,” he said.

Weiss, of NIDA, said that scientifically a gateway effect cannot be ruled out, but a conclusive “yes” is also not possible at this point. “The scientific community is still arguing about it,” she told us. “It really is a complicated thing to tease out. It has been very contentious over the years. And I don’t know how useful it is as a concept, but it’s something that people latch on to.”

Christie is entitled to his opinions on the legality of marijuana and the statutes in Washington and Colorado, and he is right that marijuana use “typically precedes” the use of other illegal drugs, as the Institute of Medicine report said. But there is no firm ground to stand on when making claims of the drug’s gateway effect.

Editor’s Note: SciCheck is made possible by a grant from the Stanton Foundation.

– Dave Levitan