Pubdate: Mon, 10 Jun 2002
Source: Reuters (Wire)
Copyright: 2002 Reuters Limited
Author: Linda Carroll

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-
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