Marijuana In Detail
"Marijuana causes long-term changes in the brain similar to those seen with
other drugs of abuse . . ." Back in the 1970s, animal experiments led to
groundless fears that marijuana blew holes in brain tissue. The experiments
organisations like NIDA now fund are more sophisticated but the controversy
still rages. George Koob, an addiction researcher from The Scripps Research

Institute in La Jolla, California, claims the new message from the animals is
simple: "The more we discover about the neurobiology of addiction the more
common elements we\'re seeing between THC (tetrahydrocannabinol, the main active
ingredient in cannabis) and other drugs of abuse." And for Koob, one of
these newly discovered "common elements" is marijauna\'s ability to
trigger chemical changes in the brain that lead to strong withdrawal symptoms.

In humans, some researchers claim to see clear evidence of insomnia, anxiety and
even flu-like symptoms in heavy cannabis users who abstain. But if there\'s a
consensus, it\'s that symptoms are mild and variable. By contrast, Koob\'s rats
are shivering wrecks. Does this mean marijuana is more addictive than we think?

Not a bit of it, says Roger Pertwee, a university pharmacologist and president
of the Cannabinoid Research Society. That\'s because those symptoms aren\'t so
much observed as manufactured. The animals are injected with high doses of THC,
then injected with a second chemical to block cannabis receptors in the brain.

Without the block, the sharp withdrawal symptoms can\'t be seen because cannabis
clears so slowly that even heavily doped rats are likely to experience a gentle
wind down. Another debate rages over animal studies into the short-term effects
of marijuana on brain chemistry. Heroin, cocaine, alcohol and nicotine all
trigger a surge in the chemical dopamine in a small midbrain structure called
the nucleus accumbens. Many researchers regard this as a hallmark of an
addictive substance. Last year, experiments showed that cannabis presses the
same dopamine button in rats, leading to claims that the drug must be more
addictive than previously thought. To critics, it is just another example of
those old exaggerated fears. What nobody tells you, says John Morgan, a
pharmacologist at City University of New York Medical School, is that rats don\'t
like cannabis. It\'s easy for them to get hooked on heroin or cocaine -- but not
marijuana. Nor, Morgan claims, are researchers exactly open about awkward
observations, such as the fact that there are plenty of nonaddictive drugs that
stimulate dopamine in the brain. It\'s easy to understand why biologists want to
find simple chemical traits that are shared by all addictive drugs.

Unfortunately, the differences are as important as the similarities when it
comes to weighing the relative risks and pleasures involved in taking drugs. And
subjectively at least, the intense rush of cocaine and orgasm-like high of
heroin have little in common with dope\'s subtler effects. A compound related to
the active ingredient in marijuana may be accumulating in the spinal fluid of
people with schizophrenia. This might explain why many sufferers smoke pot. Many
researchers blame schizophrenia on an overactive dopamine system in the brain.

Daniele Piomelli and colleagues at the University of California at Irvine
already knew that making rats’ dopamine receptors hyperactive caused a surge in
anandamide, a lipid that binds to the same receptors in the brain as marijuana.

Now Piomelli’s group has examined cerebrospinal fluid from 10 schizophrenic
patients, taken for diagnostic purposes at the Medical College of Hannover in

Germany. They found that fluid from schizophrenic patients had on average twice
as much anandamide as fluid from people who didn’t have schizophrenia (NeuroReport,
vol 10, p 1665). One explanation for the higher levels in schizophrenics is that
the brain is attempting to compensate for a hyperactive dopamine system. “It’s
the brain’s response to bring this dopamine activity down,” says Piomelli. But
the brain cannot keep the amount of anandamide high enough to lower dopamine
levels, he says. This might also explain why schizophrenics often smoke
marijuana. The drug’s active agent, THC, and anandamide both bind to the same
receptor, so patients might be treating themselves, he says. But because pot
does not act selectively in the brain, Piomelli does not consider it a useful
treatment for schizophrenia. “I don’t think the patient wants to be high,” he
says. “I think the patient wants to feel better.” One weakness in the data so
far is that five of the patients were taking medication for their symptoms and
three others were using marijuana daily. The effects of these drugs on
endogenous cannabinoid levels is not known. “It is imperative to continue with
a larger sample,” says Piomelli. The researchers are now