The October approval of buprenorphine by the U.S. Food and Drug Administration for treatment of opiate dependence marks a historic milestone for drug abuse research and treatment. Buprenorphine crowns more than two decades of NIDA-supported research on the neurobiology of drug addiction with a medication that has the potential to increase the safety, availability, and acceptance of opioid abuse treatment in the United States.
As the first medication for opioid maintenance treatment that physicians can dispense in their offices to patients addicted to heroin and prescription pain relievers, buprenorphine creates a new therapeutic option whose convenience and relative privacy should appeal to many patients and may facilitate the integration of drug abuse therapy with attention to patients' other medical needs.
Buprenorphine's availability culminates the collaborative efforts of NIDA's medication development program and the pharmaceutical division of the firm Reckitt Benckiser. Over the last decade, these entities conducted clinical trials with more than 2,400 patients that established buprenorphine's safety and efficacy in treating opiate dependence. At the same time, Federal legislators enacted the Drug Abuse Treatment Act of 2000 (DATA), which removed numerous regulatory barriers to the use of approved opiate treatment medications in doctors' offices. More than 2,000 physicians already have qualified under DATA to use buprenorphine in their practices.
Buprenorphine's distinctive pharmacology gives it the safety margin and low potential for diversion to illicit use required for office-based use. The medication's unique mechanism of action -- how it works to achieve its therapeutic effect and reduce the likelihood it will be abused -- is grounded in decades of basic and clinical research on the biological and behavioral underpinnings of drug addiction.
Using fundamental knowledge derived from NIDA-funded research about where and how opiates such as heroin work to achieve their euphoric effects, NIDA researchers identified buprenorphine as a potential opiate treatment medication in the late 1970s. Subsequent research with the compound showed that it interacts in similar but significantly different ways at the same mu opioid receptor in the brain where heroin, morphine, and prescription pain relievers as well as the treatment medication methadone initiate their effects.
As a partial agonist at this receptor, buprenorphine blocks heroin's effects, reduces craving for the drug, and prevents unpleasant withdrawal symptoms. Moreover, its potential for abuse is limited because it produces less stimulation and physical dependence than full agonist medications, such as methadone, and its euphoric effect peaks at a moderate level no matter how much is taken.
NIDA's medications development program further refined buprenorphine by developing two formulations for use at different stages of treatment for opiate addiction. Patients generally will make the transition from illicit opiate drugs to Subutex -- a medication containing only buprenorphine -- in a few days under their physician's direct supervision when they begin treatment. Once they adjust to Subutex, patients will be switched to Suboxone, which contains buprenorphine and an opiate antagonist called naloxone. This combination of ingredients further reduces the medication's potential for illicit injection; if a Suboxone tablet is crushed and injected in an attempt to accelerate and intensify buprenorphine's agonist effects, naloxone blocks the mu receptor and can induce opiate withdrawal. Suboxone will be the main prescription medication patients take home for long-term treatment of the physiological changes wrought by chronic opiate abuse, for use in conjunction with counseling and support services to help them live stable, productive lives.
Office-based treatment with buprenorphine will give clinicians a powerful new tool to treat opiate addiction; it will not replace medications now used to treat this disorder. Much research and clinical experience has shown that methadone, administered regularly in a comprehensive treatment program, can reduce or eliminate heroin injection and the attendant risk of AIDS and other infectious diseases. A longer lasting form of methadone, LAAM (the first medication developed by NIDA's medication development program) gives clinicians additional flexibility in managing opiate dependence. As full agonists at the mu opioid receptor, both methadone and LAAM address heroin's harmful effects but also produce strong physical dependence and, compared to buprenorphine, have a higher potential for abuse and greater danger of overdose. As a result, they remain subject to strict Federal, State, and local regulations that limit their use to licensed narcotic addiction treatment clinics.
Methadone clinics will continue to play a crucial role in treating heroin addiction, but they are able to treat only one-fifth of the estimated 1 million Americans who are dependent on opiates. Office-based treatment with buprenorphine will help fill this treatment gap by providing more treatment options for the 800,000 opiate-addicted individuals not now being treated. People who abuse heroin or prescription pain medications but have avoided methadone clinics because of the stigma associated with them, and likewise, adolescents and young adults who have become addicted to heroin through snorting the drug are among the prospective new patients expected to get the medical help they need from their physicians. In addition, some stable methadone patients may transfer from clinic care to office-based treatment to eliminate the burden of daily methadone clinic visits. As a result of such transfers, methadone treatment slots will open up for the many heroin abusers waiting to enter treatment.
The public-private initiatives that have made it possible for patients to be treated with buprenorphine in their doctors' offices are based on scientific understanding of drug addiction as a chronic, relapsing brain disease that can be treated medically as we treat other chronic diseases, such as diabetes or hypertension. Office-based treatment with buprenorphine advances the day when all distinctions between drug abuse and other medical treatment disappear and primary care physicians and treatment professionals work together to provide patients with the most effective medications and psychosocial treatments available for their disease.