BNL Addiction Symposium

Abstract Details

February 16, 2007, San Francisco, CA  |  Symposium Home

Imaging the Causes and Consequences of Inhalant Abuse

Author: Stephen Dewey, Ph.D.
Senior Scientist, Brookhaven National Laboratory

It is estimated that more than 2.1 million children between the ages of 12 and 17 have used an inhalant for the purpose of getting high. Furthermore, 1 out of 5 school-aged children in America has intentionally abused a common household product to get high by the time they reach the eighth grade. Inhalants are readily accessible. Therefore, they tend to be a drug of first use. In fact, they are as popular as marijuana among young people. There are more than a 1,400 products which are potentially dangerous when inhaled. Most are common products that can be found in the home, garage, office, school or as close as the local convenience or large home shopping store.

Inhalant abuse (also known as "sniffing" and "huffing") usually begins at age 10 or 11. Children as young as six, however, experiment with inhalants. No one knows for certain how many lives inhalant abuse claims each year because these deaths often are attributed to other causes. In fact, children can die the very first time they abuse an inhalant. This is called Sudden Sniffing Death Syndrome. Inhalant abuse damages the brain and other vital organs, including the heart, kidneys and liver. So, children who don't die may become brain-damaged or otherwise severely impaired.

Inhalants are highly addictive. In fact, inhalant use disorders meet DSM-IV and ICD-10 dependence criteria. Thus, addicted individuals may progress to abusing illegal drugs or alcohol. For this reason, inhalants are often referred to as "gateway drugs."

As a growing worldwide problem, inhalant abuse is associated with serious health and social cost. The neurological and psychiatric consequences of inhalant abuse include paranoid psychosis, cognitive impairment, and cerebellar dysfunction. These may reflect detrimental changes in the dopamine system. Furthermore, inhalant use or exposure is often associated with alcohol and nicotine dependence. This association has also been established for poly-abuse of sedatives, dissociative anesthetics, and hallucinogens.

Despite recognition of considerable morbidity and mortality there has been surprisingly little research on the mechanisms underlying inhalant abuse when compared to other addictive drugs. The importance of the problem and the lack of information place a sense of urgency on the need to better understand the interactions of inhaled drugs with brain neurotransmitter systems. Among abused inhalants, toluene is considered to be a major chemical constituent contributing to the morbidity associated with solvent abuse.

Imaging studies from our lab using positron emission tomography (PET) in combination with radiolabeled toluene, butane, and acetone demonstrate that these compounds have unique distributions in the brain and body. Furthermore, their rate of brain clearance is strikingly different, suggesting that not all inhalants act through the same mechanism and they may not all have the same addictive liability. Short-term exposure to toluene also produces a marked change in brain glucose metabolism that appears to be reversible over time. High field magnetic resonance imaging (MRI) and specific histochemical staining techniques demonstrate that short-term exposure to toluene produces marked changes in white matter pathways in the brain. These changes may underlie movement disorders that have been reported in many inhalant abusing patient populations.

Behavioral studies from our lab also demonstrate that only certain inhalants produce a conditioned place preference (CPP). That is, animals exposed to toluene quickly associated specific environments with this exposure while animals exposed to acetone were less likely to develop a similar response. Again, these findings demonstrate that not all inhalants produce similar effects in the brain and suggest that further studies should be targeted at specifically addressing the unique differences between inhalants.
Recent studies from our lab using PET and in vivo microdialysis techniques, in combination with the work of others, demonstrate that toluene increases brain dopamine levels in brain areas also affected by cocaine, methamphetamine, nicotine, and alcohol. This elevation is thought to play a significant role in the addictive liability of toluene.

Finally, using gamma vinyl-GABA (GVG), a drug that has proven to be effective in a host of pre-clinical studies and two small open-labeled clinical trials in cocaine and methamphetamine abusing patients, we demonstrated that toluene-induced increases in brain dopamine can be blocked. Further, the expression of toluene-induced CPP — thought to be associated with these increases — was also blocked by pre-administration of GVG. Thus, these early studies indicated that GVG may represent an effective treatment strategy for inhalant abuse.

Last Modified: January 31, 2008

One of ten national laboratories overseen and primarily funded by the Office of Science of the U.S. Department of Energy (DOE), Brookhaven National Laboratory conducts research in the physical, biomedical, and environmental sciences, as well as in energy technologies and national security. Brookhaven Lab also builds and operates major scientific facilities available to university, industry and government researchers. Brookhaven is operated and managed for DOE's Office of Science by Brookhaven Science Associates, a limited-liability company founded by Stony Brook University, the largest academic user of Laboratory facilities, and Battelle, a nonprofit, applied science and technology organization.

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