Marijuana's Effects on Brain Studied

Users May Be More Vulnerable to `Hard' Drugs, Research Groups Find

By Curt Suplee
Washington Post Staff Writer

Marijuana may be a far more insidious drug than generally thought, and
apparently alters the brain chemistry of pot smokers in ways that may
make them particularly vulnerable to "hard" drugs such as heroin or
cocaine, two independent research groups have found.

An AmericanSpanish team reports in today's issue of the journal
Science that abrupt cessation of longterm marijuana use widely
regarded as a comparatively innocuous practice with a low risk of
addiction causes the same kind of cellular withdrawal reactions in
lab rats as "those produced by other major drugs of abuse."

Although they seem fairly mild to the marijuana user, those withdrawal
effects can prompt changes in nerve function that "prime" the
potsmoker's brain for greater susceptibility to opiate, cocaine or
alcohol abuse, the researchers suggest.

In a second report, Italian scientists show that the major active
ingredient in marijuana smoke has precisely the same impact as heroin
on a key brain site that influences addiction to numerous drugs.

If confirmed by further investigation, the discoveries could tip the
scales in the ongoing national debate over whether marijuana is a
relatively harmless recreational drug or serves as a "gateway" to
abuse of other, more dangerous substances a presumption supported
by the fact that more than 90 percent of hard drug users say that
marijuana was their first drug.

The question is urgent because marijuana is the most prevalent illegal
drug in America, with about 10 million occasional or frequent users.
Nearly 36 percent of U.S. high school seniors smoke or have smoked it,
according to the latest federal survey. About 3 million children
between the ages of 12 to 17 use it, the Department of Health and
Human Services has determined, and use in that age group has nearly
doubled since 1990. Approximately 100,000 Americans a year seek
treatment for marijuana dependence.

Neither report immediately alters marijuana's reputation as one of the
least hazardous of routinely abused substances. But taken together,
the new findings not only suggest that marijuana is capable of
"causing physical dependence," said Alan I. Leshner, director of the
National Institute on Drug Abuse, but seem to confirm the growing
suspicions of experts about the nature of all habitforming drugs.

"More and more over the course of the last few years," he said, "we
have come to understand that there is a common set of characteristics
of all abusable substances."

On the face of it, that may seem incomprehensible. After all, cocaine,
heroin, alcohol and THC (the principal mindaltering component of
marijuana) affect completely different kinds of messenger chemicals,
known as neurotransmitters, in different parts of the brain and body.
Moreover, cocaine is a stimulant, whereas alcohol and opiates such as
heroin are powerful depressants. Superficially, they appear to have
almost nothing in common.

Yet they do. For one thing, withdrawal from any of those drugs causes
the same kind of distress response among nerve cells in a brain
structure called the amygdala, part of a centralbrain system
intimately involved in controlling emotions. When a habitual user
suddenly quits, neurons in the amygdala start pumping out a substance
called corticotropinreleasing factor (CRF), which is part of the
brain's response to stress and the panicky tension of withdrawal.

That effect has been observed repeatedly in the case of hard drugs,
but has never been seen convincingly for marijuana because THC is
eliminated very slowly from the body. When chronic pot smokers
suddenly stop, they frequently report restlessness, sleep disturbance
and high anxiety. But the effects are muted because THC persists in
fatty tissues: 30 hours after smoking pot, about half the THC is still
in circulation, even though the user has quit feeling high.

So NIDAfunded researchers from Scripps Research Institute in
California and the Universidad Complutense de Madrid in Spain set out
to see what what would happen if they somehow could bring marijuana's
effects to a screeching neurological halt. They gave rats a daily dose
of a THClike substance for two weeks and then injected them with a
newly concocted compound that blocks the THC receptors, forcing the
dopeaddled rodents to go cold turkey.

When the scientists looked at the rats' brains, they found exactly the
same kind of increased CRF production seen in opium, cocaine or
alcohol withdrawal. Activating the CRF system, many experts believe,
can promote addiction of all kinds by making the person more sensitive
to unpleasant sensations and thereby prone to take another drug dose.
Thus repeated marijuana use, the researchers write, may leave the
brain "primed" for "future vulnerability to drug dependence."

A second surprising and recently uncovered similarity among popularly
abused drugs is that all of them appear to cause a buildup of a potent
messenger chemical called dopamine in another central brain section
called the nucleus accumbens. Dopamine is a crucial constituent of the
neural pleasure response or "high," much of which is triggered in the
nucleus accumbens and telegraphed to other brain areas.

Morphine, cocaine, amphetamines and nicotine all produce drastically
increased dopamine transmission in the nucleus accumbens, and
scientists from the University of Cagliari in Italy wanted to find out
if THC and heroin would do the same. They gave rats intravenous doses
of both drugs, and found that both brought on a dopamine spike. In
addition, they gave other rats a drug called naloxone that completely
blocks the action of heroin in the brain. That drug, they found, also
prevented THC activity indicating that heroin and marijuana effect
some highly similar, if not identical, changes in brain chemistry.

"Although our results do not provide direct evidence for a causal
relation between [marijuana] and heroin use," the scientists write,
"they are nonetheless consistent with this possibility."

Many physicians encourage marijuana or THC use by chemotherapy
patients and AIDS sufferers a practice recently made legal in
California and Arizona.

"I don't think our study in any way undermines the potential
therapeutic use of marijuana," said Scripps researcher George F. Koob.
"But [the drug] has abuse potential, and I don't think we can stick
our heads in the sand and ignore that."

(c)Copyright 1997 The Washington Post Company

_________________________________________________________________

Effects of LongTerm Marijuana Use on the Brain Shown Similar To
Other Addicting Drugs , released 6/26/97.

http://www.nida.nih.gov/MedAdv/MAsyr97.html#626