Research: Marijuana can be `gateway' drug
`We now have a smoking gun,' expert says

By THOMAS H. MAUGH II
Los Angeles Times letters@latimes.com

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."