Addiction Treatment Proves Successful In Animal Weight Loss Study

Vigabatrin is currently undergoing U.S. Food and Drug Administration (FDA)-approved Phase II clinical trials against cocaine and methamphetamine addiction across the U.S.

In the current study, animals genetically bred to be obese experienced a loss of up to 19 percent of their total weight while non-obese animals lost 12 to 20 percent following short-term vigabatrin administration.

"Our results appear to demonstrate that vigabatrin induced satiety in these animals," said Amy DeMarco, who led the study, working in the laboratory of Brookhaven Lab senior scientist Stephen Dewey. Dewey first identified vigabatrin as a potential addiction treatment and has conducted more than 20 years of preclinical research with this promising medication.

Earlier studies at Brookhaven Lab found a strong connection between obesity and addiction, including similar changes in the brains of the obese and those addicted to drugs like cocaine. Based on these connections, Dewey hypothesized that vigabatrin would quench food cravings in the lab rats.

"Given the growing obesity epidemic, we felt that examining vigabatrin's therapeutic efficacy for obesity was particularly relevant," Dewey said. A total of 50 adolescent and adult animals, both genetically bred "fat" and normal-weight animals, were assigned to either a control group or groups that received vigabatrin at various dose levels and were monitored for up to 40 days. The controls received daily salt water (saline) injections, while those in the study groups received up to 300 milligrams (mg) of vigabatrin a day. All animals received injections for two 7-13-day periods, with breaks in between.

At the end of the 40-day period, all animals receiving vigabatrin weighed significantly less than the controls. The obese animals receiving the 300mg dose weighed far less and consumed less food than the 150 and 75mg groups. The obese animals receiving vigabatrin lost an average of 19 percent of their initial weight, while non-obese animals lost between 12 and 20 percent of their weight.

"The fact that these results occurred in genetically obese animals offers hope that this drug could potentially treat severe obesity," said Dewey. "This would appear to be true even if the obesity results from binge eating, as this disorder is characterized by eating patterns that are similar to drug-taking patterns in those with cocaine dependency."

Dewey and Jonathan Brodie, a professor of psychiatry at New York University School of Medicine, have conducted extensive studies on animals at Brookhaven Lab showing that vigabatrin attenuates or blocks neurological and behavioral changes associated with drug addiction. Vigabatrin has been tested in humans in two small open-label studies, as well as in a 103-patient double-blinded, placebo-controlled trial. Vigabatrin is now being commercialized by Catalyst Pharmaceutical Partners, which is currently conducting two FDA-approved Phase II trials. 

This research was funded by the National Institute on Drug Abuse at the National Institutes of Health and by the Office of Biological and Environmental Research within DOE's Office of Science. Brookhaven Lab has a world-renowned research program aimed at understanding the neurological mechanisms and consequences of drug addiction and other addictive behaviors. This program is fueled, in part, by DOE's long-standing support of brain-imaging technologies developed as a direct outgrowth of their commitment to basic physics and nuclear chemistry research.

All research involving laboratory animals at Brookhaven National Laboratory is conducted under the jurisdiction of the Lab's Institutional Animal Care and Use Committee in compliance with the Public Health Service (PHS) Policy on Humane Care and Use of Laboratory Animals, the U.S. Department of Agriculture's Animal Welfare Act, and the National Academy of Sciences' Guide for the Care and Use of Laboratory Animals. This research has enhanced understanding of a wide array of human medical conditions including cancer, drug addiction, Alzheimer's and Parkinson's diseases, and normal aging and has led to the development of several promising treatment strategies.

Pre-clinical (animal) studies have:

• demonstrated that vigabatrin blocks dopamine increases triggered by environmental cues related to drug use
• demonstrated that vigabatrin blocks the process in the brain that causes cocaine's "high"
• demonstrated that vigabatrin does the same for nicotine
• shown that vigabatrin may block the addictive effects of toluene, a commonly used inhalant

Clinical milestones include:

• the first small clinical trial of vigabatrin showed prolonged abstinence and elimination of drug craving in long-term cocaine addicts
• the second small clinical trial of vigabatrin showed prolonged abstinence and no visual problems in cocaine and methamphetamine abusers
• vigabatrin's first Phase II, double-blind placebo-controlled trial shows positive results in treating cocaine abuse an FDA-sanctioned, Phase II multicenter study of vigabatrin starts
• The neurobiology of eating disorders and obesity and their treatment is another major focus of research at Brookhaven Lab. Earlier studies at the Lab have:
• identified brain circuits that may cause the obese to overeat
• shown that levels of dopamine receptors, which receive chemical messages of well being and reward in the brain, are decreased in the brains of obese individuals
• demonstrated that parts of the brain responsible for sensation in the tongue, mouth, and lips are more active in the obese
• revealed that the mere sight and smell of favorite foods spikes levels of dopamine in the brains of food-deprived people - just as it spikes this pleasure chemical in the brains of those with drug addictions in response to their drug of choice

The study will be published online August 20, 2008, by the journal Synapse.