New study shows hope for treating inhalant abuse

GVG may reduce addictive effects of ’huffing’

A new study by scientists at the U.S. Department of Energy’s Brookhaven National Laboratory suggests that vigabatrin (a.k.a. gamma vinyl-GABA or GVG) may block the addictive effects of toluene, a substance found in many household products commonly used as inhalants. These results broaden the promise of GVG as a potential treatment for a variety of addictions. The study will be published in the December 1, 2004 issue of Synapse, available online September 30.

Inhalant abuse or “huffing” continues to grow as a serious health problem: According to the National Institute on Drug Abuse, the number of new inhalant users increased from 627,000 in 1994 to 1.2 million in 2000. The chronic use of inhalants has been associated with heart, liver, kidney, and brain damage — and can even result in sudden death.

The Brookhaven Lab study demonstrates that animals previously trained to expect toluene in a given location spent far less time “seeking” toluene in that location after being treated with GVG than animals treated with a placebo. This elimination of conditioned place preference — a model of craving in which animals develop a preference for a place where they have previously had access to a drug, even when the drug is absent — is similar to the aversion seen in Brookhaven’s earlier studies of GVG with nicotine and heroin.

“The findings of this study extend the potential value of GVG to treat addiction,” says Stephen Dewey, the Brookhaven Lab neuroanatomist who led the study. “More importantly, our results show promise in treating inhalant abuse as it continues to grow as a problem among adolescents.” There are currently no pharmaceutical treatments for inhalant abuse.

The study was conducted by putting rats through a series of conditioning tests. The tests were intended to condition the animals to learn which chambers of a three-chambered apparatus contained toluene vapors. On the final day of the study, scientists randomly administered either saline or GVG to the rats one hour before the testing. They then gave the rats free access to the chambers with no toluene present while monitoring the animals’ behavior.

Researchers found that animals treated with GVG spent 80 seconds on the side of the chamber where they had previously received toluene as compared to the saline-treated animals, which spent 349 seconds in the “toluene” chamber. “GVG significantly blocked toluene-seeking behavior in these rats,” Dewey said.

Earlier research at Brookhaven Lab demonstrated the addictive nature of inhalants. A team led by Dewey found that toluene elevates dopamine in the same regions of the brain as other addictive drugs, such as cocaine. The neurotransmitter dopamine is associated with the activation of pleasure and reward circuits in the brain.

Inhalant abuse is among the most common forms of drug abuse, particularly among pre- and early adolescents, who inhale or “huff” chemical vapors found in many common household products that are not generally thought of as drugs. Seventy-one percent of inhalant users are 12 to 25 year olds, according to the 2002 National Survey on Drug Use and Health performed by the U.S. Substance Abuse & Mental Health Services Administration.

Stephen Dewey and Jonathan Brodie, a psychiatrist at the New York University School of Medicine, have collaborated at Brookhaven Lab on a large body of preclinical research on GVG as a potential treatment for addiction, and on two small-scale trials of GVG in Mexico [one published http://www.bnl.gov/bnlweb/pubaf/pr/2003/bnlpr092203a.asp, one yet-to-be published]. Results from the preclinical and early clinical trials show that GVG holds promise as a treatment for addiction to a variety of abused drugs (see: http://www.bnl.gov/pet/GVG/default.asp).

In October 2002, Catalyst Pharmaceutical Partners of Coral Gables, Florida (http://www.catalystpharma.com), received an exclusive worldwide license from Brookhaven Science Associates, operator of Brookhaven National Laboratory, for the use of the drug GVG for its application in treating drug addiction.