POT'S EFFECTS: MORE THAN MUNCHIES

NEW YORK -- Dawn was 12 when she started smoking marijuana with her
friends. It was just something the cool kids did to relax and forget their
problems, she says.

But, after a while, the cigar-shaped "blunts" she smoked also seemed to
make learning difficult. "I would just forget school stuff," said Dawn, now
17. "I'd learn something one day and the next day I'd have no idea what the
teacher was talking about." At first Dawn limited her marijuana smoking to
the weekends, but soon it became an everyday habit that ultimately landed
her in a treatment program.

The debate over whether marijuana is harmful and habit-forming, as Dawn
found, or a fairly benign intoxicant, is an old one. And until recently
little research had been done to settle the controversy. For several
decades, research on marijuana lagged that for other illicit substances as
scientists focused on such drugs as cocaine and heroin with more obvious
addictive qualities and more drastic and dire effects.

But in the past decade, and in particular over the last year or so,
interest in cannabis has surged, driven in part by the debate over its use
for pain relief, nausea and loss of appetite by people with AIDS, cancer
and other debilitating diseases. In addition, experts are intrigued by the
discovery of molecules that naturally occur in the body, known as
endogenous cannabinoids, or endocannabinoids, which are remarkably similar
to the active ingredient in marijuana.

Researchers have discovered that receptors for the endocannabinoids are
sprinkled liberally throughout the body and the brain, suggesting that they
play important roles in regulating a variety of processes. Recent research
into the ways that cannabinoids regulate appetite, pain and memory may not
only shed light on the abundance of sensations experienced by marijuana
users - the mellow, the munchies and the fuzzy memory - but may help
scientists develop new, more directed medications to help control appetite,
ease pain and improve memory.

Scientists have also learned that the drug, which an estimated 70 million
Americans have at least tried, may be highly addictive to a small
percentage of those who use it.

Marijuana smokers report a diverse collection of sensations, and
researchers now suspect that is because the drug's main active ingredient -
delta-9-trans-tetrahydrocannabinol, or THC - is so similar in shape to the
endocannabinoids, which are involved in many body and brain functions.
Rachel Wilson, a researcher at Caltech, discovered when she was at the
University of California at San Francisco that endocannabinoids played an
important role in the hippocampus, a part of the brain involved in learning
and memory, according to a report published this spring in Nature.

No one has figured out exactly how endocannabinoids are used in the
hippocampus, but based on the abundance of cannabinoid receptors in this
part of the brain and on the experiences of marijuana users, Ms. Wilson
suspects that these molecules help lay down new memories by strengthening
the connections between nerve cells. But when the brain is flooded with
cannabinoids through marijuana use, forgetfulness results, Ms. Wilson said.
It is probably a case of too much of a good thing, she added. When
cannabinoids are abundant, every experience becomes strongly linked in our
minds, she believes. But when everything is marked for memory, the system
is overwhelmed and nothing is remembered.

Ms. Wilson and others also reported last year on another important role
played by cannabinoids. They appear to tone down the production of certain
neurotransmitters, acting like the brakes of a car when the system is
racing too fast.

Perhaps the most contentious issue has been the question of whether
marijuana could be addictive. For the many Americans whose experience with
marijuana was pleasant and brief, it may be hard to believe that the drug
can be strongly addictive.

But scientists focusing on cannabis have come up with a complicated
picture. While a majority of people seem to be able to quit, there appears
to be a small segment of the population - some 10 to 14 percent - that can
become strongly dependent on the drug.

Some addiction experts fear that this possibility will have serious
consequences for the young, noting that addiction among teenagers is on the
rise in certain cities (New York and San Francisco among them). Marijuana
use in teenagers like Dawn can block social development and derail career
plans, said Alan Leshner, former director of the National Institute on Drug
Abuse.

People often fail to notice that a friend or neighbor has a marijuana
problem because the consequences of cannabis use are less striking than
those associated with other drugs, said Alan Budney, associate professor at
the University of Vermont and director of its Treatment Research Center.

"You don't see the severe acute consequences you get with alcohol or
cocaine," Mr. Budney said. "People don't embarrass themselves. They don't
wreck the car. They don't spend all their money on a binge.

"That doesn't mean it's not addictive," he continued. "It can be insidious.
It gets into your lifestyle and then you can't get it out."

For years, even addiction experts have argued over the effect of cannabis.

"There is still some debate regarding the degree, or extent, or magnitude
of dependence and what the real consequences of that dependence might be,"
said Billy Martin, a professor and chairman of pharmacology at Virginia
Commonwealth University in Richmond.

One sticking point was the absence of an animal model. But about a year ago
scientists at the National Institute on Drug Abuse showed that monkeys give
themselves THC in amounts comparable to that inhaled by people who smoke
marijuana, according to a study published in Nature Neuroscience. Such
self-administration of drugs by animals has been shown to be a hallmark of
addictive substances.

And more recent reports have described a withdrawal syndrome that can last
several weeks, another sign of addiction.

In a study that followed heavy marijuana users, Mr. Budney found that when
people quit using the drug, they experienced a host of unpleasant symptoms,
including craving, decreased appetite, sleep difficulty, weight loss,
aggression, anger, irritability, restlessness and strange dreams.

Often these symptoms drove people back to using the drug, said Mr. Budney,
who noted that the marijuana withdrawal syndrome was very similar to what
cigarette smokers experienced when they quit.

Still, compared with alcohol, the physical side of marijuana withdrawal is
mild, experts say.