Former Vice President Joe Biden says he is not prepared to support ending the federal ban on marijuana until science clarifies "whether or not it is a gateway drug." Taking him at his word, that means Biden, a leading contender for the 2020 Democratic presidential nomination, will never support marijuana legalization.

During a town hall in Las Vegas on Saturday, Biden said states should be free to legalize marijuana but once again reserved judgment about whether national prohibition should be repealed. "The truth of the matter is, there's not nearly been enough evidence that has been acquired as to whether or not it is a gateway drug," he said. "It's a debate, and I want a lot more before I legalize it nationally. I want to make sure we know a lot more about the science behind it….It is not irrational to do more scientific investigation to determine, which we have not done significantly enough, whether or not there are any things that relate to whether it's a gateway drug or not."

Contrary to Biden's implication, there has been a lot of research on this question during the last half-century or so. While studies have consistently found an association between cannabis consumption and use of other illegal drugs, the nature of that relationship remains controversial, and it probably always will.

One possible explanation for the correlation that worries Biden is that the experience of using marijuana makes people more likely to try other illegal drugs. That's the explanation Biden has in mind when he says marijuana might be a "gateway drug," a concern he also voiced during the Obama administration. But another possible explanation is that people who use marijuana are different from people who don't in ways that also affect their likelihood of using other drugs. Pre-existing differences in genetics, personality, and environment could explain both tendencies.

The psychologist Andrew Morral and his colleagues at the RAND Drug Policy Research Center have shown that an underlying propensity to use drugs, combined with the relative availability of different intoxicants, could entirely account for the three phenomena emphasized by advocates of the gateway theory: 1) that people tend to use marijuana before other illegal drugs, 2) that people who use marijuana are more likely to use other illegal drugs, and 3) that the likelihood of progression increases with the frequency of marijuana use. Their mathematical model did not disprove the gateway theory, but it did prove that the gateway theory is not necessary to explain these observations. Morral et al. concluded that "available evidence does not favor the marijuana gateway effect over the alternative hypothesis that marijuana and hard drug initiation are correlated because both are influenced by individuals' heterogenous liabilities to try drugs."

Several studies have sought to test the gateway theory by taking into account other variables that may be independently associated with drug use. A longitudinal study of teenagers and young adults in New Zealand, for example, found a strong association between frequency of cannabis consumption and use of other illegal drugs after adjustment for nearly three dozen potential confounding variables. But as Morral et al. pointed out, even such extensive efforts to control for confounders are unlikely to do so perfectly. They calculated that when adjustment for confounding "fails to capture just 2% of the variance in drug use propensity," marijuana users "appear to have odds of initiating hard drugs that are twice as great as non-users of marijuana." Hence "it is hardly surprising that controlling for these covariates does not eliminate the association between marijuana and hard drug use."

Another approach examines this association in twins, who share the same home environment and have similar or, in the case of monozygotic pairs, identical genes. An Australian study found that in cases where one twin had used marijuana before turning 17 and the other had not, the first twin was more than twice as likely to use opioids, regardless of whether the twins were identical or fraternal and even after adjusting for several potential confounders. A similar study based on the Vietnam Era Twin Registry found that subjects who had used marijuana before turning 18 were nearly three times as likely to use opiates as co-twins who had not. In a study of Dutch twins, the risk ratios were even higher: The subjects who had used marijuana at 17 or younger were more than 16 times as likely as their co-twins to report "hard drug" use, for instance.

Even these seemingly compelling results do not rule out the possibility that pre-existing differences account for the associations. Whatever situational factors explain why one twin uses marijuana as a minor and the other does not may also explain why one uses "hard drugs" and the other does not. "The observation that familial factors do not entirely explain the association between early cannabis use and subsequent [drug] use, while suggesting a potential causal role for cannabis use in the development of other illicit drug use, does not prove such an association," the authors of the Dutch study noted. "There may be other factors, especially aspects of the non-shared environment (e.g., peer affiliations) preceding the onset of cannabis use that might account for the observed associations."

Even if it's true that trying marijuana makes people more likely to try other drugs, the policy implications are not obvious. If "the legal status of marijuana makes it a gateway drug," as a 1999 report from the organization that became the National Academies of Sciences, Engineering, and Medicine surmised, legalizing cannabis could reduce consumption of other drugs. There is some evidence that has happened in states that have legalized marijuana for medical or recreational use.

It's not clear what sort of research Biden imagines will answer this question once and for all, barring a controlled, randomized experiment with human subjects, which would be unethical as well as impractical. Possibly he is just leaving himself wiggle room to eventually support federal legalization (which two-thirds of Americans and three-quarters of Democrats favor) without alienating voters who are still leery of the idea.

Before New York Gov. Andrew Cuomo decided to support marijuana legalization last December, he likewise worried that "marijuana leads to other drugs, and there is a lot of proof that is true." Less than two years later, Cuomo changed his mind. The issue was not decisively resolved in the interim.