Source: Houston Chronicle, Friday, June 27, 1997, page 20A LTEs: Research: Marijuana can be `gateway' drug `We now have a smoking gun,' expert says By THOMAS H. MAUGH II Los Angeles Times 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 pot is a "gateway" drug that leads some people on to abuse of socalled hard drugs, such as cocaine and heroin. One study in Science magazine, produced by a team at the Scripps Research Institute in San Diego, demonstrates that the stress and anxiety associated with withdrawal from longterm 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. A second study, 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 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 will provide powerful arguments for those opposed to marijuana use and may change the terms of the debate somewhat, said Scripps neuroscientist George 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 showing 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 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 the first, neuroscientist Gaetano Di Chiara and his colleagues at the University of Cagliari in Italy explored the socalled reward pathway in the brains of rats. The key event in this pathway is the release of 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 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." Not everyone agrees with this interpretation. "This doesn't prove anything," counters 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. But it also has something in common with sex and chocolate."