Drug abuse and addiction continue to be among the largest and most challenging health and social problems facing society. They affect both the well-being of the individual and the health of the public. In 2001, 15.9 million Americans 12 years and older reported using an illicit drug in the past month, and more than 4.6 million met the DSM-IV criteria for requiring treatment (Substance Abuse and Mental Health Services Administration [SAMHSA], 2002). The encouraging news is that breakthrough discoveries in science continue to refine our understanding of drug abuse and addiction and are yielding new opportunities to translate basic research findings into tangible treatment products.
The processes underlying drug abuse and addiction are complex, and recent findings suggest that addiction does not just involve changes in the neural substrates of positive reinforcement but changes in motivational and cognitive systems as well. The challenge then, is to identify the mechanisms that dampen drug cravings or rewards without interfering with motivation for natural rewards.
The National Institute on Drug Abuse (NIDA) medications development program relies on two approaches to developing medications. The "top-down" approach takes advantage of screening medications, such as fluoxetine (Prozac) or venlafaxine (Zoloft), that have been already marketed and for which there is a good rationale for testing in addicted subjects. The second is a "bottom up" approach, which relies much more heavily on a discovery-driven process. It is in the combination of these two approaches where much of the work for developing treatments for cocaine addiction falls.
Progress in Opiate-Addiction Treatment
Since the inception of the medications development program in 1990, NIDA has established a large screening program and clinical research networks that allow us to co-develop new medications with pharmaceutical company partners. Our most recent success was the October 2002 approval by the U.S. Food and Drug Administration of buprenorphine (Subutex) and a combination of buprenorphine and naloxone (Suboxone) for opiate addiction. These products are the first medications to come out of NIDA's relatively short involvement in medications development since the approval of levomethadyl acetate hydrochloride (LAAM) in 1993. The partial agonist properties of buprenorphine products will allow qualified physicians to prescribe the medication in office-based settings, thus expanding the availability of treatment for opiate addiction.
New Treatments for Cocaine Addiction
An array of NIDA-sponsored projects are testing FDA-approved drugs as possible treatments for cocaine addiction. These drugs include medications that are already being used in the treatment and management of other ailments, including opiate addiction, alcoholism and Parkinson's disease. One that shows promise, disulfiram (Antabuse), is marketed as a therapy for treating alcoholism. Three efficacy trials conducted with different populations of cocaine-addicted individuals suggested that disulfiram in combination with a behavioral intervention (cognitive-behavioral treatment, 12-step facilitation or clinical management) might be effective in treating cocaine addiction (Carroll et al., 1998). A common abuse pattern in cocaine users is concomitant use of alcohol. In cocaine/alcohol abusers, disulfiram treatment showed sustained effect on reduced cocaine and alcohol use one year after cessation of the therapy. This may be because disulfiram may block the anti-anxiety effects of alcohol that lead to increased uses of cocaine. Moreover, McCance-Katz et al. (1998) have shown that disulfiram can increase the anxiogenic qualities of cocaine.
Petrakis et al. (2000) and George et al. (2000) showed a reduction in cocaine use in opiate-dependent cocaine users (a difficult-to-treat group) being treated with disulfiram in addition to methadone (Methadose, Dolophine) and buprenorphine, respectively. A large-scale, Phase III, multicenter trial of this medication is planned by NIDA.
The opioid antagonist naltrexone (ReVia), approved to treat alcohol and opioid addiction, is another potential treatment option being explored at the clinical level. A study by Schmitz et al. (2001) reported that abstinent cocaine-dependent patients showed less relapse to cocaine use over time in the group receiving naltrexone in combination with relapse-prevention therapy (but not another behavioral therapy). This intriguing finding suggests that medications may interact with certain behavioral therapies and not others.
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