A Comeback for the Gateway Drug Theory?

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If you grew up as part of the D.A.R.E. generation — kids of the 1980s and ’90s who learned about drugs from alarmist public service announcements — you know all too well the dangers of so-called gateway drugs. Go to bed with marijuana or beer, you were taught, and risk waking up with cocaine or heroin.

Three decades later, scientists and politicians still debate whether using “soft” drugs necessarily leads a person down a slippery slope to the harder stuff. Critics note that marijuana has, in some cases, been shown to actually prevent people from abusing other substances. And even D.A.R.E. now acknowledges that the overwhelming majority of people who smoke pot or drink never graduate to pills and powders.

But new research is breathing fresh life into the perennially controversial theory, and the timing seems apt. As marijuana legalization and the opioid epidemic sweep across the country, parents are once again questioning the root causes of addiction. And politicians opposed to legalization, including Attorney General Jeff Sessions and Gov. Chris Christie of New Jersey, have routinely used the gateway effect as their chief argument against reform.

Is the science on their side?

A Columbia University study published in November in Science Advances showed that rats exposed to alcohol were far more likely than other rats to push a lever that released cocaine. The researchers also found that the alcohol suppressed two genes that normally act as cutoff switches for the effects of cocaine, creating a “permissive environment” for the drug within the rodents’ brains.

A similar study from 2011 — conducted by some of the same researchers, most notably Denise Kandel, who helped formulate the gateway theory in 1975 — produced comparable findings using nicotine and mice.

Most critical to the viability of gateway theory, both studies found there was no enabling effect when the order of the drugs was reversed. Taking cocaine did not make the rodents more susceptible to the effects of alcohol or nicotine, supporting the idea that some drugs are better positioned than others to act as place-setters.

“Now that we’ve done the animal experiment, we see that using one drug changes your brain in such a way that using another drug becomes more rewarding,” said Dr. Kandel, a professor of sociology at Columbia University. “And there is an order. Cocaine doesn’t create this effect.”

Critics are quick to point out the shortcomings in these studies, including the assumption that rodents and humans respond similarly to narcotics. “I think it sounds like a relatively lame attempt to resuscitate a theory that’s been largely debunked,” said Ethan Nadelmann, the founder and former executive director of the Drug Policy Alliance. “The simple fact that they’re involving studies on rats” to make claims about people is “ a real stretch,” he said.

Dr. Nadelmann also noted that many previous studies showing how one drug enhances the effect of another have contradicted the gateway theory. A 2008 paper found that by taking marijuana, chronic-pain sufferers could reduce their doses of pain-relieving opioids, for example. And people who combine marijuana with prescription opioids are not more likely to abuse alcohol or other drugs, research has shown.

Another knock on the gateway theory: In Japan, where marijuana use is far lower than in most Western countries, only 83 percent of illicit drug users started out smoking pot, according to a 2010 study. And there is now mounting evidence that factors such as poverty and poor social environment are a greater predictor of hard drug use than early exposure to soft drugs.

In 1999, reporting on the dangers of medical marijuana for Congress, the Institute of Medicine of the National Academy of Sciences declared “there is no conclusive evidence that the drug effects of marijuana are causally linked to the subsequent abuse of other illicit drugs.” The report did not address nicotine or alcohol.

What the medical community knows about addiction has evolved significantly since the 1930s, when a team of researchers introduced an early version of the gateway concept. Known as Stepping Stone Theory, it was based on the researchers’ observation that 100 percent of the heroin addicts they interviewed had first used marijuana. Their conclusion: Marijuana leads inexorably to heroin use.

Later versions of the theory focused less on the idea that using one drug necessarily causes use of the other and more on establishing the order in which addicts typically move through substances. “You’re never really able to establish a clear causal connection because there are so many factors you can’t control for,” said Dr. Kandel, whose first paper on the topic is considered seminal. “All you can say is there is an association between the use of these drugs, and there tends to be a sequence.”

But those sorts of distinctions went up in smoke once Robert L. Dupont, a former White House drug czar and director of the National Institute on Drug Abuse, coined the term gateway drug in his 1984 book, “Getting Tough on Gateway Drugs: A Guide for the Family.” With the war on drugs nearing its height, legislators and activist groups like D.A.R.E. seized on the idea that preventing kids from getting involved with booze or pot could save them from a lifetime of drug abuse.

“The program was much more didactic back then,” said Frank X. Pegueros, D.A.R.E.’s president and chief executive, when asked whether his group’s position on gateway drugs had changed. Since 2008, the program has shifted focus away from just saying no and toward the teaching of good decision-making skills, he said.

Today, health advocates tend to rally around a concept known as common liability theory, which states that certain people, by virtue of biology, environment or both, are simply more likely than others to become addicted to drugs. Part of the appeal of the theory is it explains why so many people can use so-called gateway drugs and never become addicted.

“Gateway theory only deals with the initiation of the use of various substances, and this order means exactly nothing,” said Michael M. Vanyukov, a professor of pharmaceutical sciences at the University of Pittsburgh and co-author of a 2012 paper comparing gateway and common liability theories. “What is important is why people start using drugs at all, and common liability accounts for that.”

Still, Dr. Kandel does not believe the rise of the common liability model necessarily discredits gateway theory. “I feel that the two perspectives are actually complementary,” she said.

“I think people have certain tendencies or characteristics that increase the probability that they’re going to do all kinds of deviant behavior,” she said. “But I think that the order in which you’re going to do drugs will have an impact on whether you’re going to do other drugs.”

Though Dr. Kandel’s most recent research dealt only with nicotine and alcohol, she said she is currently wrapping up a similar study on marijuana. That study is likely to be published in the first half of 2018.

In the meantime, parents looking to protect their kids from addiction should focus less on which substances their children might be using and more on the overall context, said Dr. Nadelmann. “What else do they have going on? Are there underlying psychological and mental issues not being treated? Is the person using this substance as a form of self-medication?” he said.

“Those are the questions,” he said, “but I don’t think there’s any hard and fast rule.”