"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 ratsÕ dopamine receptors hyperactive caused a surge in
anandamide, a lipid that binds to the same receptors in the brain as marijuana.
Now PiomelliÕs 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 didnÕt 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. ÒItÕs
the brainÕs response to bring this dopamine activity down,Ó 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 drugÕs 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. ÒI donÕt think the patient wants to be high,Ó he
says. ÒI think the patient wants to feel better.Ó 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. ÒIt is imperative to continue with
a larger sample,Ó says Piomelli. The researchers are now testing fluid from
more patients to see if the correlation still holds true. Health officials in
Geneva have suppressed the publication of a politically sensitive analysis that
confirms what ageing hippies have known for decades: cannabis is safer than
alcohol or tobacco. According to a document leaked to New Scientist, the
analysis concludes not only that the amount of dope smoked worldwide does less
harm to public health than drink and cigarettes, but that the same is likely to
hold true even if people consumed dope on the same scale as these legal
substances. The comparison was due to appear in a report on the harmful effects
of cannabis published last December by the WHO. But it was ditched at the last
minute following a long and intense dispute between WHO officials, the cannabis
experts who drafted the report and a group of external advisers. As the WHO's
first report on cannabis for 15 years, the document had been eagerly awaited by
doctors and specialists in drug abuse. The official explanation for excluding
the comparison of dope with legal substances is that "the reliability and
public health significance of such comparisons are doubtful". However,
insiders say the comparison was scientifically sound and that the WHO caved in
to political pressure. It is understood that advisers from the US National
Institute on Drug Abuse and the UN International Drug Control Programme warned
the WHO that it would play into the hands of groups campaigning to legalise
marijuana. One member of the expert panel which drafted the report, says:
"In the eyes of some, any such comparison is tantamount to an argument for
marijuana legalisation." Another member, Billy Martin of the Medical
College of Virginia in Richmond, says that some WHO officials "went
nuts" when they saw the draft report. The leaked version of the excluded
section states that the reason for making the comparisons was "not to
promote one drug over another but rather to minimise the double standards that
have operated in appraising the health effects of cannabis". Nevertheless,
in most of the comparisons it makes between cannabis and alcohol, the illegal
drug comes out better--or at least on a par--with the legal one. The report
concludes, for example, that "in developed societies cannabis appears to
play little role in injuries caused by violence, as does alcohol". It also
says that while the evidence for fetal alcohol syndrome is "good", the
evidence that cannabis can harm fetal development is "far from
conclusive". Cannabis also fared better in five out of seven comparisons of
long-term damage to health. For example, the report says that while heavy
consumption of either drug can lead to dependence, only alcohol produces a
"well defined withdrawal syndrome". And while heavy drinking leads to
cirrhosis, severe brain injury and a much increased risk of accidents and
suicide, the report concludes that there is only "suggestive evidence that
chronic cannabis use may produce subtle defects in cognitive functioning".
Two comparisons were more equivocal. The report says that both heavy drinking
and marijuana smoking can produce symptoms of psychosis in susceptible people.
And, it says, there is evidence that chronic cannabis smoking "may be a
contributory cause of cancers of the aerodigestive tract". HEAVYusers of
marijuana who suddenly go cold turkey have aggressive impulses as powerful as
those felt by Frank Spooner The reaction is far less intense than the withdrawal
symptoms of alcoholics or people addicted to cocaine or heroin, and may reflect
a psychological dependence on the drug, rather than a genuine physiological
addiction. But it still might be enough to keep some marijuana users from
kicking their habit, says Elena Kouri, a psychologist at Harvard Medical School
in Boston. Kouri and her colleagues recruited 17 volunteers who had smoked
marijuana on at least 5000 occasions, and who continued to be heavy users of the
drug. They also studied 20 people who either took marijuana occasionally, or who
had already given it up. None of the volunteers had a history of violence or any
other psychiatric disturbance. The researchers used a computer game to measure
the volunteers' aggressive behaviour during a 28-day period of abstinence from
marijuana, which was monitored by daily, supervised urine tests. The volunteers
sat alone at a computer screen with two buttons. The first added money to an
account in their name, but they were told that a second would subtract money
from the account of their opponent, sitting at a similar screen in the next
room. On the day they gave up marijuana, and one, three, seven and 28 days
later, the two players were given 20 minutes to take it in turns to push one or
other button, after which they could keep the money left in their account. In
reality, there was no opponent. The researchers had instead arranged for the
computer to provoke the volunteers by frequently subtracting money from their
account. When tested on the third and seventh days of abstinence, this ersatz
"nasty opponent" managed to get the heavy users noticeably hot under
the collar. Says Kouri: "Subjects that on day zero hadn't cared at all that
they were losing points started swearing and punching the keyboard, yelling 'I'm
going to get you back!'" The heavy users hit the "punishment
button" more than twice as often as the control group on days three and
seven-- an increase in aggression that compares roughly with that produced by a
three-week course of testosterone supplements in another study by Kouri. The
increased aggression had subsided completely by the time the volunteers were
tested again at the end of the abstinence period, however (Psychopharmacology,
vol 143, p 302). The study is the first to measure aggression during withdrawal
from a long period of heavy marijuana use. But Margaret Haney, a psychologist at
Columbia University in New York, says that people who show aggressive tendencies
in the laboratory do not necessarily become violent in the real world. "I
would hesitate to say that it would translate to physical violence," she
says.