Drug for Cocaine Addicts Causes Weight Loss

Is Vigabatrin the next big diet pill?

The U.S. Department of Energy's Brookhaven National Laboratory announced that obese rats lost weight on the experimental anti-cocaine drug vigabatrin, reinforcing the idea that certain forms of obesity--particularly binge eating--result from the same kinds of neurotransmitter disturbances that underlie vulnerability to addictive drugs like cocaine.

Amy DeMarco, lead author of the study, said in a press release from Brookhaven that the results "appear to demonstrate that vigabatrin induced satiety in these animals."

Earlier, the U.S. Food and Drug Administration (FDA) had given Fast Track designation to vigabatrin, an anticonvulsant, for evaluation as an anti-craving drug for cocaine and methamphetamine addiction. If successful, it would be the first medication ever approved for the treatment of addiction to stimulants. The FDA has yet to approve the drug for use in the U.S., citing concerns about reports of retinal damage in patients overseas.

First synthesized as a drug treatment for epilepsy in 1974, vigabatrin increases brain levels of the neurotransmitter GABA, an inhibitory compound also implicated in alcoholism. According to a press release from Ovation Pharmaceuticals, a marketer of the drug under the trade name Sabril, “Sabril may block the euphoria associated with cocaine administration in humans and may suppress craving by increasing brain levels of gamma-aminobutyric acid (GABA).” Increased brain levels of GABA, an inhibitory transmitter, result in higher levels of dopamine and serotonin. Catalyst Pharmaceutical Partners is also testing a version of vigabatrin called CPP-109.

The weight loss study involved 50 genetically obese lab animals, and 50 normal animals. Each of the animals was given doses of vigabatrin or placebo for forty days. At the end of that period, the obese animals had lost 19 per cent of their body weight, while the non-obese animals lost from 12 to 20 per cent of their weight.

Brookhaven senior scientist Stephen Dewey, who did much of the early work on vigabatrin, said: "The fact that these results occurred in genetically obese animals offers hope that this drug could potentially treat severe obesity." In the lab press release, Dewey also observed that "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."

Perhaps. But ten years ago, the research community was just as enthusiastic when a serotonin-boosting diet pill called Redux (dexfenfluramine) won full FDA approval in 1996. Redux was the first drug ever approved in the U.S. for the long-term treatment of obesity. But the euphoria didn’t last long. By the time Redux made the cover of Time, researchers were already rumbling about continued reports of high toxicity and hypertension in rat studies. Concerns about pulmonary hypertension arose, and in August, 1997, doctors at the Mayo Clinic in Minnesota reported serious heart valve abnormalities in 24 women taking the "phen-fen" combination.

A month later, at the FDA’s request, phen-fen and Redux were permanently pulled off the market.

Graphics Credit: SheKnows.com

The Biology of Bulimia

The binge-and-purge addiction.

By 2000, the biological substrate unifying alcoholism, addiction, depression, and certain eating disorders had become irrefutable. Population surveys had shown that nearly half of alcoholic patients had a long history of coexisting depression and/or anxiety disorders. Overall, about a third of patients with depression or panic disorder have had lifelong problems with drug abuse. These are estimates, best clinical guesses, but associating depression and addiction is no longer a speculative venture.

As with more familiar forms of addiction, bulimia was coming to be seen as another serotonin/dopamine-mediated medical condition. As noted, serotonin is involved in both the binge and the purge. Once researchers began performing the necessary double blind, placebo-controlled studies, it became clear that serotonin-boosting drugs dramatically lessened bulimic behavior in general, and associated carbohydrate binging in particular, in a large number of diagnosed bulimics. (Anorexia nervosa, another eating disorder, does not show the same serotonin affinities in action.)

Bulimics often maintain a normal weight, but can suffer serious physical consequence—heart rhythm irregularities, electrolyte imbalances, low blood pressure, and damage to the esophagus. Once the binge-purge cycle has been established, some researchers believe, drug-like changes in serotonin 5HT receptor distributions help reinforce the pattern. It is not surprising to learn that Prozac and other serotonin reuptake inhibitors such as dexfenfluramine were prominent among the drugs being tested against bulimia in the 1990s. By 1995, a paper presented at the National Social Science Association Conference in San Diego stated: “The serotonin hypothesis of bulimia nervosa suggests that bulimia is the behavioral manifestation of functional underactivity of serotonin in the central nervous system.”

In 1997, Prozac became the first drug ever licensed by the Food and Drug Administration (FDA) for the treatment of bulimia nervosa, as this chronic disorder is officially known. The drug’s formal approval was based on three clinical studies showing median reductions in binging of as much as 67 per cent for Prozac, compared with 33 per cent for placebo. Vomiting was reduced by 56 per cent, compared to 5 per cent for female placebo users. (About 10 per cent of diagnosed bulimics are males.) There is often a family history of alcoholism and/or eating disorders. The locus of “serotonergic dysfunction” appears to be the hypothalamus. Low levels of serotonin and dopamine metabolites have been documented in the cerebrospinal fluid of bulimic patients. Evidence exists for the involvement of norepinephrine as well.

Bulimia, like alcoholism and other drug addictions, has its psychosocial side, but twins studies show that there is very probably a genetics of bulimia to be pursued. In one influential study, an identical twin stood a one-in-four chance of developing bulimia, if the other twin was diagnosed with the disorder. A combination of SSRI drugs and some form of structured cognitive therapy is the recommended approach.

--Excerpted from
The Chemical Carousel: What Science Tells Us About Beating Addiction © Dirk Hanson 2008, 2009

Photo Credit: Graham Menzies Foundation