Studies Back ‘Gateway’ Role of Pot
In a finding sure to add fuel to the debate over the medical and recreational use of marijuana, two new studies released today strongly suggest that pot is a “gateway” drug whose use leads some people on to abuse of so-called hard drugs, such as cocaine and heroin.
One study in the journal Science, produced by a team at the Scripps Research Institute in La Jolla, demonstrates that the stress and anxiety associated with withdrawal from long-term use of marijuana produce the same biochemical changes associated with withdrawal from the harder drugs. This is the “negative reinforcement” that causes a person to take more drugs to alleviate the stress.
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A second study, also in Science, from Italy emphasizes the opposite side of the coin: positive reinforcement. It demonstrates for the first time that marijuana activates the same pleasure centers in the brain that are targeted by heroin, cocaine and alcohol, again providing a reason to seek out the drug.
“We now have . . . a smoking gun--a biological mechanism by which this gateway phenomenon could be occurring,” said Dr. Herbert Kleber, medical director of the National Center on Addiction and Substance Abuse at Columbia University.
The new studies are unlikely to provide the final word in the ongoing, often vitriolic dispute about the risks associated with marijuana use, both sides agreed. But they offer powerful arguments for those opposed to marijuana use and may change the terms of the debate somewhat, said Scripps neuroscientist George F. Koob.
“This blurs the distinction between what is considered a hard drug and a soft drug,” Koob said, “because they all do the same thing.”
The backdrop to the argument is government statistics--unquestioned by both sides--which show that an individual who uses marijuana is 17 times more likely to use cocaine than one who never smoked pot. Comparable figures are not available for heroin but are thought to be about the same.
But the interpretation of these statistics varies dramatically. Marijuana proponents argue that there may be a progression because a person who smokes pot has to buy it from an illegal dealer and is thus much more likely to be around dealers of other illicit drugs.
Alternatively, proponents argue, use of marijuana might simply be a marker for deviant behavior in general, and that type of behavior is likely to include use of other drugs.
Opponents, however, argue that marijuana use triggers a biochemical pathway that, in effect, primes the brain for the use of other drugs. The two new papers support this possibility.
In one, neuroscientist Gaetano Di Chiara and his colleagues at the University of Cagliari in Italy explored the so-called reward pathway in the brains of rats. The key event in this pathway is the release of a crucial brain chemical, dopamine, by a small cluster of cells in a brain region called the nucleus accumbens. That release triggers a pleasurable sensation.
The researchers infused tetrahydrocannabinol, or THC--the primary active ingredient of marijuana--into the rats and found that levels of dopamine in their nucleus accumbens doubled. That was about the same increase observed when they infused heroin instead.
The finding was emphasized by additional studies with a drug called naloxone, which binds to receptors in the brain and prevents the pleasurable effects of heroin. Di Chiara and his colleagues found that it also blocked the effects of marijuana, indicating that the two drugs use the same biochemical pathway.
“I’m not saying [marijuana] is as dangerous as heroin,” Di Chiara told Science, “but I’m hoping people will approach marijuana far more cautiously than they have before.”
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Not everyone agrees with this interpretation. “This doesn’t prove anything,” countered Dr. Lester Grinspoon of Harvard University. “To the extent the effects of pot have something to do with the pleasure centers in the brain, it has something in common with heroin or cocaine,” he said. “But it also has something in common with sex and chocolate.”
Neuropharmacologist Friedbert Weiss and Koob have previously shown that the emotionally wringing process of withdrawal from alcohol, opiates and cocaine is associated with the release of a hormone called corticotropin-releasing factor, or CRF, in a brain structure called the amygdala.
When alcohol-addicted rats, for example, are prevented from drinking, the level of CRF in the amygdala quadruples. To relieve the stress and anxiety produced by CRF, the rats--and humans as well--seek more of the drug to which they are addicted.
The Scripps team and their associates from Complutense University of Madrid treated 50 rats with THC for two weeks, then sent them into withdrawal by injecting a drug that blocked the activity of the pot ingredient.
The rats demonstrated teeth chattering, exaggerated grooming and other characteristics associated with stress and anxiety. More important, the levels of CRF in their amygdala rose to two to three times the level in rats not forced into withdrawal.
Together, said Dr. Alan I. Lesher, director of the National Institute on Drug Abuse, the two studies “show that marijuana use shares common brain changes and mechanisms with other drugs of abuse.”
Koob, for one, does not think the new findings necessarily argue against the medical uses of marijuana. “There are lots of drugs of abuse that have dramatic medical uses,” he said.
“We need a more rational understanding of how to use marijuana medicinally to its best advantage,” he concluded. “But we can’t bury our heads in the sand and say that it doesn’t have abuse potential, because it does.”
Staff writer Eric Bailey in Sacramento contributed to this story.
