MARIJUANA'S EFFECTS: MORE THAN MUNCHIES

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, a Long Islander, limited her marijuana smoking to the
weekends, but soon it became an everyday habit that ultimately landed her
in a residential treatment program run by Phoenix House.

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 the drugs like cocaine and heroin with
more obvious addictive qualities and more drastic and dire effects on users.

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 medical
marijuana 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.

Dr. 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, Dr. 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, Dr. 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.

Dr. 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.

Another study published this last year in Nature may explain why marijuana
users get a case of the munchies. An international group of researchers
found that mice that were genetically engineered to be deficient in
cannabinoid receptors ate 40 percent less than normal mice. And in a
separate experiment, the researchers showed that an interplay existed
between the cannabinoids and leptin, a hormone that produces satiety.

In the study, obese rats that were genetically modified to have low levels
of leptin produced higher amounts of endocannabinoids. When the rats were
given leptin, the endocannabinoid levels dropped.

Yet another study on cannabinoids published last year may explain why
marijuana makes people feel good. According to the study published in
Science, cannabinoids, through a complex chain of events, rev up the
dopamine system.

Like other addictive substances, marijuana appears to hijack brain
circuitry that evolved to help people find their way back to a food source
or sexual partner. Normally the neurotransmitters and receptors "are doing
a long, slow dance," Dr. Wilson said. "Drugs of abuse crash the party and
bring the booze."

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. And 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 Dr. Alan I. 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 Dr. Alan J. 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," Dr. 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. 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 Dr. Billy R. Martin, a professor and chairman of pharmacology at
Virginia Commonwealth University in Richmond.

One sticking point was the absence of an animal model. But slightly over 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 recently, reports have described a withdrawal syndrome that can
last several weeks, another sign of addiction.

In a study that followed heavy marijuana users, Dr. 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 Dr. 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.

Nevertheless, for those with a predisposition to be hooked by cannabis, the
pull of the drug is intense.

For Mark, a restaurant owner from Vermont, the craving for cannabis was too
strong to ignore. Mark, 40, started smoking it when he was 13 and was
smoking daily by the time he hit college. "When I woke up I genuinely
didn't feel well until I smoked," he said.

Although he tried many times to quit over the years, he did not succeed
until he attended a treatment program.

Still, not everyone is convinced that marijuana is a threat.

"Everything is relative," said Dr. Donald Jasinksi, a professor of medicine
at the Johns Hopkins medical school and director of the Center for Chemical
Dependence at Johns Hopkins Bayview Medical Center. "Does it destroy as
many lives as alcohol? No. Does it kill as many people as cigarettes? No.
Does it have as many deaths associated with it as aspirin overdose? No."

Mark, however, wistfully wonders what his life might have been like without
marijuana. "I'm the only one in my family who wasn't an Ivy Leaguer," he
said. "I went to a crummy college. I should have been right up there with
the rest of them."