GENE MUTATION LINKED TO DRUG ADDICTION

NEW YORK - A genetic mutation that disrupts a certain enzyme in the brain
may be linked to drug abuse, new study findings indicate.

Researchers discovered that people who had two mutated copies of a gene
that controls levels of an enzyme called fatty acid amide hydrolase (FAAH)
were far more likely to have drug abuse problems than people with two
normal copies of the gene or only one copy of the damaged gene, according
to a report published in the June 11th issue of the Proceedings of the
National Academy of Sciences.

FAAH breaks down molecules, known as endogenous cannabinoids, that
naturally occur in the human body but are remarkably similar to marijuana's
main active ingredient--THC.

The researchers decided to take a closer look at mutations of the gene that
controls FAAH because endogenous cannabinoids play a role in the brain's
pleasure and reward system, the study's lead author, Dr. Jack C. Sipe, told
Reuters Health in an interview.

Drugs of abuse powerfully lure people back because they tap into this very
primal system in the human brain. In essence, illicit drugs hijack the
brain circuitry that has evolved to help us find our way back to a food
source or a sexual partner to reproduce. Once we experience a pleasurable
moment, the brain locks this into a permanent circuit.

Earlier animal studies pointed to FAAH as having an impact on endogenous
cannabinoid levels, said Sipe, a researcher in the department of molecular
and experimental medicine at The Scripps Research Institute in La Jolla,
California. Mice that lack the gene for FAAH end up with overly high levels
of these cannabinoids in their systems.

Sipe and his colleagues discovered a naturally occurring mutation of the
FAAH gene that appears to partially cripple the enzyme. A poorly
functioning enzyme would lead to a slower breakdown of cannabinoids and
thus a higher overall level of these brain chemicals, Sipe said.

Based on previous research suggesting that marijuana or THC might influence
a person's vulnerability to other drugs of abuse, the California
researchers decided to test whether addicts might be more likely than
others to have inherited this mutation.

They tested for the mutation in street drug users, alcoholics, smokers,
drinkers and non-drug abusers.

People who abused drugs or alcohol were almost five times as likely to have
inherited two copies of the mutated gene as non-drug abusers, Sipe and his
colleagues report. But smokers and drinkers were no more likely to inherit
two copies of the gene than the general population.

"Our article is an encouraging first step towards understanding how the
endocannabinoid system may contribute to drug abuse or dependence," Sipe
said. "Now we are working to determine if the FAAH gene mutation we
described could be a risk factor for one or more of the specific drugs of
abuse, such as marijuana, cocaine, stimulants, opioids, sedatives or even
multi-drug abuse."

SOURCE: Proceedings of the National Academy of Sciences 2002;99:8394-