By Lori Whitten, NIDA NOTES Staff Writer

In the Anti-Drug Abuse Act of 1988, Congress mandated NIDA to promote the development of medications "to treat the symptoms and disease of drug abuse." Research by NIDA-supported scientists and others had by then made clear that drug abuse is a neurological disorder treatable by pharmacotherapy, but only three anti-addiction medications were available (disulfiram, methadone, and naltrexone), all developed in the 1960s and early 1970s. Congress recognized the need for Federal leadership and, because of NIDA's resources and expertise, entrusted the Institute with facilitating the development of pharmacotherapies to treat addiction.

With an initial appropriation of $8 million, NIDA launched a Medications Development Program that same year and formally established the Medications Development Division in 1990. From its beginning, the Division has supported and coordinated academic and private sector scientists engaged in every stage of medications development—from the creation of new compounds in the laboratory to the testing of products in clinical trials. The Division's efforts have been instrumental in bringing buprenorphine and buprenorphine-naloxone—safe and effective treatments for opiate addiction, the latter suitable for office-based therapy—to the Nation's clinics and pharmacy shelves. Among other current priorities, the Division supports work to establish the safety and efficacy of the smoking-cessation aids nicotine replacement and bupropion for people with psychiatric conditions, pregnant women, and adolescents.

Under the leadership of Division Director Dr. Frank Vocci, Dr. Nora Chiang, Chief of the Chemistry and Pharmaceutics Branch, manages laboratory research grants designed to develop new compounds with therapeutic potential; Dr. Jane Acri, Director of the Addiction Treatment Discovery Program, leads a multidisciplinary team that screens compounds and advances those with therapeutic potential into testing for safety and efficacy; and Dr. Ahmed Elkashef, Chief of the Clinical/Medical Branch, coordinates the evaluation of data from clinical trials.

The Division pursues a dual strategy that balances the need to advance scientific discovery and the need to find safe and effective treatments as rapidly as possible. On one track, NIDA intramural and funded scientists seek new medications. Researchers in the Cocaine Treatment Discovery Program have identified and evaluated more than 3,000 compounds whose molecular characteristics or performance in animal studies suggested they might reduce cocaine craving and prevent relapse. This process has, for example, identified a new compound called JDTic, which has anti-stress and antidepressant characteristics and prevents relapse in animals, and is developing the agent for potential clinical testing. Under the second approach, NIDA has established a network of clinical investigators to screen marketed medications with neurochemical effects that suggest a potential for reducing drug abuse (see chart). Among 65 medications examined so far, eight potential treatments for cocaine abuse—including topiramate, disulfiram, and modafinil—have advanced to the confirmatory stage of clinical trials in cocaine-dependent patients.

Throughout the 1990s, as well, the Division advanced research on vaccines that prevent drugs from reaching the brain. A vaccine to prevent cocaine addiction and another for nicotine abuse are now being tested for safety and efficacy.

Because medication development is an enormously complex and costly enterprise, the Division collaborates with other Government agencies, particularly the U.S. Food and Drug Administration (FDA), and the pharmaceutical industry. The relationship with FDA has been vital to overcoming scientific and regulatory barriers to evaluating new medications for opiate addiction and shepherding buprenorphine through the necessary approvals. The Division's relationships with industry frequently have been formalized as Cooperative Research and Development Agreements (CRADAs). In this type of arrangement, NIDA provides expertise, equipment, and facilities to test a corporate-owned compound as a potential pharmacotherapy; if the results are as hoped and a marketable medication results, the company maintains the commercial rights and NIDA retains a license to perform further research. Under a current CRADA, NIDA is working with Teva (formerly IVAX Corporation) to determine whether talampanel, a compound in clinical testing for treatment of epilepsy, may help cocaine abusers overcome their addiction.

Dr. Vocci says, "Our first 15 years have taught us the importance of developing treatments that patients will accept and readily use, and that medications are most effective in combination with psychotherapy or counseling. We now apply these lessons to all efforts." Looking ahead, Dr. Vocci lists Division goals for the next 5 years:

• Validate the effectiveness of promising medications for cocaine addiction;
• Advance compounds that have shown promise in animal research to clinical testing in people who are addicted to methamphetamine and marijuana;
• Advance a new smoking cessation aid into clinical trials (possibly selegiline, which has shown promise in preliminary studies);
• Determine optimal immunization schedules for nicotine and cocaine vaccines and obtain FDA approval;
• Identify medications to curb cognitive problems that limit patients' ability to benefit from behavioral therapies;
• Continue preliminary clinical studies of interactions between HIV infection, antiviral therapies, and anti-addiction pharmacotherapies and identify interventions that slow the progress of the infection in drug abusers; and
• Collaborate with other branches of NIH and industry partners to test a vaccine for hepatitis C among drug-abusing populations.

"Bringing a new medication to market is a lengthy and expensive endeavor, but physicians and patients need a choice of many treatment options. The progress in anti-addiction pharmacotherapies shows the strength of the dual strategy of medications development, which will continue to provide us with the best hope for novel approaches to treating addiction," says Dr. Vocci.

Volume 20, Number 6 (July 2006)