The study was led by Jonathan Brodie, M.D., Ph.D., the Marvin Stern Professor of Psychiatry at NYU School of Medicine, along with colleagues Stephen L. Dewey, Ph.D., of Brookhaven National Laboratory, and Emilia Figueroa, M.D., who directs several addiction treatment clinics in Mexico. It is published in the September 22 online edition of the journal Synapse.
The addicts in the study took GVG, which stands for gamma-vinyl-GABA. It is also known as vigabatrin and by the trade name Sabril. The drug has been used in Europe and many other countries to treat infantile spasms and epilepsy, but it is not approved by the Food and Drug Administration for use in the United States.
"Our results, in which 40 percent of hard-core addicts were able to stay clean for more than 60 days, were more spectacular than we would have ever dreamed," says Dr. Brodie. "These addicts were able to stay clean even without leaving the environment that had fostered their addiction. They gained weight, they got jobs, and they are now living with their families."
"For the first time it seems that we might have a way to treat people suffering from the life-threatening consequences of cocaine addiction," says Dr. Figueroa.
"Our results suggest that this drug, in combination with psychosocial therapy, offers a potential treatment for cocaine addiction," says Dr. Dewey. "We now need to confirm and extend these results in a large double-blind, placebo-controlled trial."
Financial support for this study was provided by the Biological Psychiatry Fund of NYU School of Medicine, and partly by the U.S. Department of Energy and the National Institute on Drug Abuse.
Over the past decade Drs. Dewey and Brodie and their colleagues have studied GVG in animals, and have published numerous articles showing that the treatment in animals blocks the rise in dopamine levels produced by cocaine, nicotine and many other addicting substances. Dopamine is a brain chemical associated with the pleasurable effects of addicting drugs.
The animal studies drew the interest of Dr. Figueroa, who treats addicts at the Clinica Integral de Tratamiento Contra Las Adicciones in Mexicali. She first contacted Dr. Dewey and then Dr. Brodie last year and told them that she wanted to test the treatment in cocaine addicts. Her pleas were persuasive. "She was really insistent. She told me many times that she felt completely helpless because there was nothing she could do for the cocaine addicts who came to her clinic," says Dr. Dewey.
Finally, Drs. Brodie and Dewey designed a clinical trial protocol that was approved by the state of Baja California and the Mexican federal government. This study was entirely investigator initiated and conducted without assistance from any pharmaceutical company. The researchers purchased GVG from local pharmacies. GVG is available in Mexico as an epilepsy treatment.
Twenty addicts, 19 men and one woman, who had been using cocaine daily for three to 15 years, were enrolled. All of the addicts had expressed a desire to kick their habit. Under the trial's guidelines, they had to provide urine samples twice a week and answer daily questionnaires about their drug use and cravings. Their urine was screened for several drugs, including cocaine, heroin, methamphetamine, and tetrayhdrocannabinol, the active ingredient in marijuana. In addition, the addicts received psychosocial counseling at the clinic.
In the first week of the trial, subjects received escalating doses of GVG up to a maximum of 3 grams daily. They were then put on a daily maintenance dose of 4 grams. In order to complete the trial, they had to remain free of cocaine for 28 consecutive days. After this four-week cocaine-free period, they were tapered by one gram per day per week for each of the following three weeks before they ended their treatment.
In the first 10 days of the trial, eight subjects dropped out because they didn't want to stop using cocaine. Among the 12 remaining subjects, eight (or 40 percent of the total enrolled) completed the trial and were tapered off GVG. At the time of the study's online publication, all eight of the subjects remain free of cocaine more than four weeks after their GVG treatment ended. Moreover, the people who quit using cocaine reported that their craving did not return once they tapered off GVG.
Four of the 12 subjects who remained in the study more than ten days were never able to stop using cocaine during the trial, even though they also took GVG. However, three of these people were able to reduce the amount of cocaine they took substantially, by 50 to 80 percent, according to the study.
None of the subjects in the study reported disturbances in their vision, a known potential side effect of GVG. The only major side effects were daytime sleepiness and headaches that occasionally persisted for several weeks but were never serious enough for affected subjects to request leaving the trial. In addition, all of the people who stopped using cocaine gained weight.
Side Effects Associated with GVG
In the late 1990s, GVG was being evaluated as a treatment for epilepsy in clinical trials in the United States. When reports appeared showing that the drug constricted peripheral vision in a small group of patients with epilepsy, that treatment application for the drug was no longer pursued.
Noting the concern about visual field defects, the NYU and Brookhaven researchers said that the doses of GVG required to treat cocaine addiction would fall far below the doses associated with causing these defects. The researchers did not include an ophthalmologic component in the current study due to its short-term nature; the defects have only been reported in patients taking GVG for long periods of time. However, the researchers expect that future studies of GVG in addicts will assess the subjects' vision.
Over the past two decades, GVG has been used to treat more than 250,000 children worldwide. Recent studies have estimated that visual field changes may be measured in as many as 30 to 40 percent of patients on long-term therapy with GVG, says Dr. Brodie, although he notes that these changes are asymptomatic for the vast majority of people treated. There are contradictory reports in the medical literature about whether the eyesight defects can be reversed once the treatment is stopped.
"While all side effects have to be taken into consideration, we shouldn't over-emphasize any side effect that isn't observed in short-term administration," says Dr. Brodie. "We aren't proposing that GVG be given to addicts indefinitely," he adds. "Clinical experience suggests that if you can break the cycle of addiction, then you have the opportunity of giving people back their lives."