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Approximately one million Americans are dependent on heroin, prescription painkillers and other opioids, but the vast majority of them--as many as 800,000--aren't receiving any treatment.

Opiate substitutes that prevent withdrawal are among the most effective treatments for such addictions, when combined with psychological counseling, researchers say. But until recently, only two such drugs--methadone and levo-alpha-acetyl methadol (LAAM)--were available, and only licensed treatment clinics were authorized to dispense them. Many addicts avoid opiate treatment programs (OTPs) because of their inconvenience or perceived stigma, and even those who would like to enroll sometimes can't because of limited treatment slots.

The approval of a new medication by the Food and Drug Administration (FDA) last fall, however, could reshape the landscape of opiate addiction treatment in the United States, making pharmacotherapy available and attractive to patients who previously shunned it, say researchers.

Psychologists have played a key role in developing the medication--buprenorphine--by conducting the basic and clinical research that defined its unusual pharmacology. They are continuing to shape its use by influencing training programs for physicians. And they are developing the behavioral and psychosocial treatments that are a critical part of any effective substance abuse treatment program.

And as the network of physicians who are certified to prescribe buprenorphine grows, it should also provide new opportunities for psychologists to get involved in pharmacotherapy-based substance abuse treatment by making such treatments available in a wide variety of settings and increasing the number of patients who use pharmacotherapies--and who therefore need the counseling and behavioral treatments that psychologists can provide.

"It's a very, very exciting time to be involved with buprenorphine work," says psychologist Leslie Amass, PhD, of the Friends Research Institute in Santa Monica, Calif., who has been studying the use of buprenorphine as a treatment for opiate addiction since the early 1990s. "For those of us who have been involved with the medication from very early on, it's rewarding to see it get to this point and be offered to patients."

Unique pharmacology

Buprenorphine has been under development for several decades, during which time psychologists have discovered a great deal about its unusual pharmacology, says Amass.

Their discoveries have been made possible, in large part, by support from the National Institute on Drug Abuse (NIDA) and other government agencies concerned with substance abuse. NIDA's Division of Treatment Research and Development, headed by Frank Vocci, PhD, has played an especially important leadership role, says Geoff Mumford, PhD, APA's science policy director.

Like heroin, methadone and many prescription painkillers, buprenorphine acts on the brain's mu-opioid receptors to cause analgesia, euphoria and other effects. But unlike them, it is a partial agonist--a drug that has mechanisms of action that are similar to pure agonists, such as heroin, but with less potency. Even when it occupies almost all of the brain's mu-opioid receptors, buprenorphine has only about 40 percent of heroin's effect, says psychologist Mark Greenwald, PhD, of Wayne State University's Addiction Research Institute in Detroit.

Another pharmacological factor that makes buprenorphine well-suited to addiction treatment is its high affinity for the mu-opioid receptor, says psychologist James Woods, PhD, of the University of Michigan, who has studied buprenorphine's pharmacology in animals.

"It has an absolutely fascinating course of action," says Woods. Even after it's been removed from the blood by elimination and metabolism, he says, buprenorphine stays firmly attached to the brain's receptors, blocking the effect of other drugs with lower affinities. That means that opiate-dependent individuals who take buprenorphine won't get any additional kick from using other opiates, such as heroin.

Buprenorphine's stickiness has another advantage, says Greenwald. Because it clings to the receptor long after it has been administered, it can make the detoxification process gentler--more like sliding down a hill than falling off a cliff. "You get a softer landing, if you will, as you detoxify someone from buprenorphine," he says. It also means that buprenorphine doesn't have to be administered every day to be effective.

But while buprenorphine's stickiness and partial-agonist effects make it ideal for many addiction treatment applications, they also limit its effectiveness with the most heavily dependent individuals, researchers say. In such individuals, buprenorphine's insistent weakness--its ability to monopolize mu-opioid receptors while providing only a fraction of the effect of drugs such as heroin--can actually trigger withdrawal symptoms.

Although buprenorphine has been tested extensively in humans and nonhuman animals, there is still much to learn, researchers say. "There are very elemental things about the way it interacts with the receptor that we don't understand yet," notes Woods.

In ongoing efforts to resolve those uncertainties, psychologists' scientific training has been and will be critical, says Greenwald. "Their ability to design controlled studies--using valid and sensitive models that are relevant to drug dependence--gives them a unique opportunity to contribute," he notes.

Translation to practice

Psychologists have also played a key role in determining how buprenorphine can best be used clinically. The consensus is that, as with other medications used to treat addiction, buprenorphine will be most effective when paired with psychological treatments.

"No one feels that buprenorphine alone is going to be that successful in the treatment of a complex disorder such as addiction without appropriate counseling, psychotherapy, etc.," says psychologist Charles Schuster, PhD, of Wayne State University, who has been involved in both the research and regulatory aspects of buprenorphine's development.

"Now that the medication has been approved, psychologists trained in substance abuse treatment will be essential partners in this important new treatment paradigm," agrees H. Westley Clark, MD, JD, director of the Center for Substance Abuse Treatment (CSAT) at the Substance Abuse and Mental Health Services Administration (SAMHSA).

Clark notes that the legislation that authorized office-based prescription of buprenorphine--the Drug Abuse Treatment Act of 2000 (DATA)--explicitly acknowledges the importance of behavioral treatments. The law requires certified physicians to have the capacity to refer patients to qualified behavioral health treatment providers.

One of the psychologists who has studied buprenorphine the longest is Warren Bickel, PhD, of the University of Vermont. Bickel and his colleagues have shown that buprenorphine can still be effective when given on alternate days or even every third, fourth or fifth day. That, Bickel notes, could make a huge difference in states such as Vermont, where patients sometimes have to drive for hours to get to the nearest certified doctor or OTP.

The availability of buprenorphine in physicians' offices offers great opportunities, but it also raises new challenges, says Bickel. For instance, OTPs provide integrated pharmacotherapy and psychotherapy in a single setting--something that many patients who go to their physicians for buprenorphine won't find, he says.

"It's imperative that these patients not only receive medication, but also receive the additional services that they really need to do well," he says. "But getting that to happen, I think, is the challenge that faces us in this new era."

As buprenorphine use spreads, there is also the risk that the drug might be diverted from patients to abusers. Rickitt Benckiser Pharma- ceuticals offers two formulations of the drug: Subutex, which contains just buprenorphine, and Suboxone, which contains a combination of buprenorphine and naloxone, an opiate antagonist. Neither formulation appears to have a large potential for abuse relative to other opioids. (Suboxone, which is expected to be the standard formulation, is an effective opiate substitute when taken under the tongue, but can trigger withdrawal if injected.)

But the FDA isn't taking any chances. Wayne State psychologist Schuster has been picked to lead a large-scale surveillance effort that includes ethnographic reports, surveys of physicians, monitoring of chat rooms, news groups and other Internet resources, and interviews with patients --all in the hopes of catching signs of buprenorphine abuse before it spreads.

The surveillance effort is slated to run for five years, with Schuster's research team providing quarterly reports to an advisory group. "If a problem is emerging, we want to catch it early," he says.

Building a network

Buprenorphine's transition from a promising experimental drug to a prescription medication was made possible by two events: the enactment of DATA and the FDA's approval, both of which were the culmination of many years of research and lobbying. But turning it into an effective treatment will require building a network of certified physicians and psychologists prepared to offer the kinds of therapy that are essential to the medication's success.

To aid patients and treatment providers in finding local physicians who can prescribe buprenorphine, CSAT offers an online Buprenorphine Physician Locator at http:// buprenorphine.samhsa.gov/bwns_ locator. Meanwhile, progress in training physicians--using curricula that have been shaped by psychologists--has been rapid.

For its part, APA has been trying to help build the buprenorphine network by encouraging appropriately trained psychologists to make themselves available as referral resources. In a recent letter to state psychological associations, APA CEO Norman B. Anderson, PhD, emphasized the importance of collaboration in realizing buprenorphine's potential. "Buprenorphine offers yet another opportunity to demonstrate the important contribution that psychologists can make in partnership with our physician colleagues," he wrote.

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