Pubdate: Fri, 26 Oct 2001 Source: Washington City Paper (DC) Copyright: 2001 Washington Free Weekly Inc. Contact: http://www.washingtoncitypaper.com/ Details: http://www.mapinc.org/media/489 Author: Garance Franke-Ruta MAGIC PILL Scientists work to unravel the human compulsion to get high. To get to the largest addiction-research laboratory in the country, you have to travel through the down-at-the-heels neighborhoods of East Baltimore, where addiction is a fact of life. Tall weeds that have been growing all summer choke sidewalks lined with careworn buildings and faded shops. Taverns and bars boldly proclaim the signs of urban decay, advertising "Go-Go Girls." Other signs can be read on the grim visages of men and women in nylon track suits who walk unstably down the streets, on the impassive faces of idled laborers sitting outside a cut-rate furniture shop that boasts of a "complete dining set" for $138. The Bayview Campus of the Johns Hopkins University, where the National Institute on Drug Abuse Intramural Research Program is located, rises up on a grassy hill overlooking the gritty scene. The carefully landscaped campus is blocked off on one side by a small, moatlike artificial lake, while a series of highway interchanges guards the other entrance against casual pedestrian visits. At this intersection of two worlds, cutting-edge science butts up against the trailing end of the economy-and 300 research scientists work to unravel the mysterious biochemistry of the learned human compulsion to get high. The scientists call their work "clinical psychopharmacology," "molecular neuropsychiatry," or "biopsychiatry," depending on whether they're studying people, animals, or petri dishes. But whatever you call it, it's clear that they are working at a nexus where the distinction between biology and psychology breaks down. At the Intramural Research Program, the pernicious consequences of low socioeconomic status and negative cultural background get measured and mapped at the intracellular level. Some researchers at the center study brain images of addicts. Others work with addicts in clinical studies of new medications that might help boost willpower or decrease drug cravings. Many work with animal models of addiction. One Intramural researcher, for example, recently won accolades from his peers for finally training monkeys to smoke marijuana voluntarily. (Most animals don't enjoy marijuana or hallucinogens, and they have to undergo a rigorous behavioral modification program before they'll routinely seek them out. Still, the lower orders aren't wholly abstemious-with a little prompting, researchers have discovered, animals take to cocaine and heroin like fish to water.) Still other scientists at the Intramural Research Program are trying to teach addicts new ways of responding to their environments and new strategies for coping with stress, adding the results to the steadily growing understanding of just how drugs hijack the brain's natural pathways and turn chosen behaviors into involuntary compulsions. "Drug addiction is the quintessential biobehavioral disorder," says Alan Leshner, Ph.D., director of the Rockville-based National Institute on Drug Abuse (NIDA), one of the National Institutes of Health and the Baltimore program's parent organization. Biology may be the main focus of the NIDA scientists, but that doesn't mean that they think addicts can wash their hands of their own responsibility in responding to addiction. "Even if you have a brain disease, you must be responsible for your own treatment," says Leshner. It's sadly appropriate for NIDA's groundbreaking work to be carried out in Baltimore , a city with a major addiction problem. Baltimore has three times more cocaine-related emergency-room admissions than Washington, according to NIDA's Community Epidemiology Working Group, and a considerable heroin problem. The main NIDA building on the Hopkins campus mixes the decrepit and the state-of-the-art. It was constructed in 1950 and still features what look like the original postwar elevators. A display case of drug-research memorabilia in the building's lobby houses a faded brown marijuana leaf sheathed in plastic, yellowed newspaper articles, and a dated bottle of Mallinckrodt Inc.-brand research-grade cocaine hydrochloride. "Flaky crystals," it says. "Poison." Alane Kimes, Ph.D., runs one of the most advanced parts of the Intramural Research Program. The Neuroimaging Research Branch uses a state-of-the-art Siemens ECAT Positron Emission Tomography (PET) scanner to precisely map blood flow and energy use in the brains of addicts as they go about the business of craving drugs, crashing from a high, or taking psychiatric tests. On this Monday in October, Kimes is planning her next study. She wants to look at where nicotine byproducts go in the brain and what they do there. The brain-cell receptor that nicotine attaches to is meant for acetylcholine, one of the three main neurotransmitters, along with serotonin and dopamine, that carry chemical messages between brain cells. Studies in rhesus monkeys show that the highest concentration of these receptors lies in the thalamus, a primitive brain nodule that relays sensory information and is involved in pain perception. Other receptors can be found in an area that modulates dopamine, which, among other things, regulates sensations of pleasure. But smoking changes the chemistry of the brain: It increases the number of nicotine-sensitive acetylcholine receptors, enhancing the brain's ability to feel certain things. Nicotine also increases pleasure-enhancing dopamine levels, and individuals who are heavier smokers tend to use more drugs. Kimes believes that smoking changes the way the brain processes other "drugs of abuse." "Eighty-five to 90 percent of drug addicts smoke," says Kimes. "If you look at kids, they will start smoking first and then move on to other drugs of abuse." The "gateway theory" of drug addiction, touted by the White House Office of National Drug Control Policy, suggests that kids get acclimated to cigarettes and then move on to illegal drugs, looking for bigger kicks. Kimes has a more refined theory. "Does smoking lead to a change in the brain that makes them more susceptible to drug addiction?" she wonders. In animals, at least, that does seem to be the case. "If you give them nicotine first, they seem to start liking cocaine a lot quicker," says Kimes. "Treat rats with nicotine and cocaine becomes more rewarding." Drug and cigarette cravings are also intimately connected. Another Intramural Research Program study showed that if you mention smoking to a heroin or cocaine addict who smokes cigarettes, you can routinely stimulate cravings for cocaine or heroin as well. Indeed, the best predictor of how likely a heroin or cocaine addict is to get clean and succeed in a treatment program, according to another NIDA study, is how much that individual smokes. The more the addict smokes, the less likely he or she is to complete treatment. "There's always been a concern" about the connection between smoking and drug use, says Frank Vocci, Ph.D., director of the treatment and research program at NIDA's Rockville office, which funds treatment-development studies at research hospitals across the country. For example, he says, "you're trying to stop them from crack-cocaine addiction. Do you want to take their cigarettes, too? I think the answer is yes." When Prozac was approved by the U.S. Food and Drug Administration (FDA), in 1987, it profoundly changed the way America looked at depression. For the first time, people began to regard this common mental illness as something that might be biological in nature, rather than the fault of the sufferer. Other antidepressants, such as lithium, had been in use for decades, but these new drugs gave scientists something the earlier antidepressants didn't: proof that they understood some fundamental aspects of the disorder's neurobiology. Prozac and its sister drugs, Zoloft and Paxil, approved in the early '90s, are selective serotonin-reuptake inhibitors (SSRIs). Highly specific medications, they boost levels of a neurotransmitter that is abnormally low in depressed individuals by blocking the receptor that would otherwise reabsorb the molecule. Psychiatrist Peter Kramer's best-seller Listening to Prozac and Elizabeth Wurtzel's Prozac Nation, both published in 1993, further destigmatized the disease. And the use of the drugs expanded from treating depression to treating obsessive-compulsive disorder, panic attacks, and bulimia. The underlying neuropathologies all seemed to be related. Soon, new syndromes, such as social anxiety disorder and premenstrual dysphoric disorder, seemed to come out of the woodwork, as drug companies lured by potential profits studied the drugs in populations with other disorders. Heavy advertising by companies further raised the profile of the new psychopharmacology, making it seem as normal to take Prozac for the blues as to take Allegra for allergies. Just how interconnected some syndromes are, though, is only beginning to become apparent. Take smoking, for example. In 1997, the FDA approved the first aid to help people stop smoking that didn't contain nicotine. Sold by Glaxo Wellcome under the brand name Zyban-and heavily advertised on television-it has rapidly eclipsed such nicotine-replacement devices as patches, gums, and inhalers as a way to help smokers quit, when used with a targeted behavioral modification program. Just what is this new miracle drug, Zyban? Buproprion-the same medicine as the antidepressant Wellbutrin, first approved by the FDA in 1986. It more than doubles the rate at which smokers can quit but does not otherwise seem to alter their moods. It decreases cigarette cravings and nicotine-withdrawal symptoms, but its precise mechanism of action remains unclear for both depression and smoking cessation. One thing it is known to do is raise levels of the neurotransmitters dopamine and norepinephrine-a chemical relative of adrenaline, which raises heart rate and blood pressure-both of which are lower than average in depressed individuals. Dopamine mediates feelings of pleasure and contentment, and the ability to move. Parkinson's disease, for example, is characterized by a severe dopamine deficiency, causing tremors, lack of facial expressions, slowness of movement, and, over time, immobility and intellectual decline. Tourette's syndrome, on the other hand, is characterized by excessive dopamine production and dopamine receptors that are supersensitive-resulting in involuntary twitches, jerks, and outbursts of cursing. Karl J. Besteman has been treating drug addicts for 44 years. Currently the director of the Oasis Clinic on Bladensburg Road NE, owned by CMAC Inc., he remembers the days back before methadone was approved as a narcotic substitute to treat heroin addicts in 1968. In the old days, before the drug began to be used to "maintain" addicts, the process of heroin withdrawal was so painful that many addicts found themselves unable to quit. "Now we can take a patient in here today and get them stabilized in three to seven days. And they can continue to function enough so we can sit down and interview them and get a coherent story about their treatment and treatment goals," says Besteman. Methadone may only be a crutch, says Besteman, but there is no doubt that it helps addicts stay in treatment. "Most of the patients who want to stay in treatment are heroin users," he says. "In D.C., the vast majority of treatment resources are medication-based programs-at least three-fourths of the clinics." But methadone is also controversial. Like heroin, it can be addictive. It is regulated as a controlled substance and distributed only at licensed clinics. Michael, who asked that his last name not be used, is among the users of the medication. A 53-year-old recovering heroin addict who has been enrolled in the Oasis Clinic's program-and on methadone-for the last two years, Michael is a large man with a limp from an osteoarthritic hip. A former maintenance man at the D.C. Department of Parks and Recreation, he wears an Oakland Raiders jersey with Tim Brown's number, 81, on the October Monday that we meet. Michael started shooting up in the late '60s-just "experimenting," he says-and didn't become a full-fledged heroin addict until the early '70s, when the drug culture was flourishing and heroin use surged across the country. This is his third go at treatment. He got clean for a year and a half in the mid-'80s, after his parents died. Their deaths, three weeks apart, had hit him hard. "I guess you could say I was strung out bad. I stayed in what you call shooting dens, experimented with smoking cocaine, PCP, everything," he recalls. "I don't know if I had a subconscious death wish, but I just really didn't care, didn't care about anything. I was very depressed. My parents, my past, 30 years of my life-something was missing. I just wasn't happy." In treatment, he started with methadone and then weaned himself off the substance. But he relapsed and started shooting up again after losing a job. He tried to quit again in the early '90s, but failed, he says, because his heart wasn't really in it. Two years ago, he made a fresh start and went back on methadone with renewed determination. "I wasn't in a program. I tried to kick without meds, and physically I just couldn't do it," he says. "I just didn't have the strength. When I was younger I could do it. But 50 years old-that's kind of hard." For cocaine addiction, there is no medication comparable to methadone or LAAM, a newer long-acting form of the drug that allows addicts to go days without having to take a medication. Though the neuroscientific understanding of the impact of the drug on the brain has advanced so that cocaine addiction is no longer considered purely psychological, it remains without pharmaceutical treatment. Yet the connection between this addiction and underlying neurological syndromes is becoming clearer. "Many of the individuals who become cocaine-dependent-20 to 25 percent-have attention-deficit disorder," explains Vocci. In part, he says, this correlation may reflect a more general inability of the body to keep the dopamine system balanced in such individuals. People with attention-deficit/hyperactivity disorder (ADHD) create too little dopamine naturally, and this deficit can make them unfocused. ADHD is treated with methylphenidate, brand name Ritalin. Both cocaine and Ritalin bind to dopamine-transporter receptors. Cocaine does so for a very short period of time and stimulates such receptors intensely. Ritalin binds over a longer period and provides less stimulation. And like cocaine, it can be addictive. That, says Leshner, puts it into the category of drugs such as morphine, which can be both medicines and drugs of abuse. "Depression would be a similar kind of thing" to ADHD, says Vocci, "where you're having some kind of...imbalance, and cocaine use makes that imbalance go down." Even when addicts don't suffer from depression or other diagnosable mental illnesses, they are more likely to suffer from irregular dopamine systems and greater problems achieving a balanced mix of neurotransmitters, Vocci says-characteristics that make them vulnerable to becoming addicted. Treating underlying depressive symptoms among cocaine addicts is just one route researchers are exploring. Recent studies have shown that desipramine, an antidepressant and panic-disorder treatment that has been on the market since 1964, may prove useful in cocaine-addicted patients with a history of depression. It raises serotonin and norepinephrine levels, though more crudely than the SSRIs. A recent NIDA study, as yet unpublished, shows that desipramine seems to allow even nondepressed addicts to more easily change what they value and to boost their willpower. The study placed addicts in a "therapeutic workplace" where they worked toward rewards-money or vouchers-under what's known as a "contingency-management" scheme. It may sound like bribery, but it's more like joining a weight-loss program that promises you half your money back if you meet your weight-loss goal by a certain date-an incentive system. Instead of prizing cocaine above all else, those participants taking desipramine began to be able to value the more tangible rewards being offered. Fully 80 percent of those receiving desipramine as well as behavioral intervention were able to get clean during a 12-week period, compared with 40 percent with behavioral intervention alone. "Cocaine may exacerbate the [dopamine] imbalance over the long term, but acutely, it may actually correct the imbalance," Vocci says. "So one of the theories is that after a while, people use cocaine to feel normal again. Thus, compounds that increase dopamine may increase the addict's internal sense of well-being and reduce desire to use cocaine." NIDA has also been searching for and studying dopamine-reuptake inhibitors. A compound called GBR 12909 (vanoxerine) is the most promising candidate so far. First synthesized in the late '70s, it was originally tested in Europe as an antidepressant. In animals, it suppresses cocaine-seeking activity without affecting normal behaviors, such as food seeking. (You don't want to suppress all cravings.) Just one shot of a long-acting form of the drug reduced cocaine-seeking 75 percent in rhesus monkeys for a 24-day period. It not only blocks the dopamine-transporter receptor-which is what cocaine itself does-but blocks it so effectively that it prevents cocaine from attaching to the receptor. Because the dopamine receptor is blocked, the neurotransmitter is forced to stay in the space between cells, where it can keep working on its feel-good mission. It's the same basic mechanism that Prozac and Zoloft use to keep serotonin levels high. Vanoxerine and another potential dopamine-reuptake inhibitor, NS-2359, are entering second-stage studies in cocaine addicts. Vocci oversees NIDA's clinical effort to develop medications for drug addiction from a corner office reached through a rabbit warren of blank, indistinguishable hallways on the eighth floor of a Rockville office building. Only a decade old, the Division of Treatment Research and Development has already succeeded in identifying 60 drugs with potential to treat addiction, some of which have already made it to the stage of broad-scale testing in humans. The program is now conducting seven clinical trials in 18 states, and it funds many more studies at private research institutions around the country. Although the "war on drugs" was announced by President Richard Nixon in 1971, it wasn't until much later that the fight was translated into research dollars for scientists. Over the last 15 years, a massive increase in congressional funding for substance-abuse research-and scientific research more generally-has fueled a boom in neuroscientific approaches to drug addiction. In 1986, NIDA had a budget of $60 million. Today, NIDA's budget is more than 10 times that: $781 million. "You can fund a lot of clinical studies and a lot of clinical science work and a lot of clinical pharmacology" for that, says Vocci. NIDA-funded researchers have found signs that a number of medications may be able to affect the complex neurobiology of addiction. Only some of these medications target the dopamine system. For others, the source of the effect is not yet clear. Several studies suggest that the anti-alcoholism drug disulfiram-which creates nausea and hot flashes when people taking it drink-may have broader anti-addiction properties. Three preliminary trials have shown that it decreases cocaine cravings in addicts, although it isn't yet clear how. Decreasing cravings is only one potential way of changing the balance of forces in the addicted mind. NIDA research is also targeting "priming," a form of noncognitive memory that develops in the nervous and immune systems when individuals are exposed to an external substance, such as a drug or virus. When an addict smokes or shoots up even a small dose of a drug that he or she was previously dependent on, that person will have a far greater nervous system response to it than will nonaddicts. And that overwhelming nervous-system response predisposes him or her to taking more of the drug-and to losing control altogether. This priming effect was intuitively understood by the founders of Alcoholics Anonymous, who believed that recovering alcoholics who had even one glass of alcohol could react so powerfully that they'd fall off the wagon altogether-hence the AA total ban on drinking. One experimental approach to modifying the priming effect is a cocaine vaccine, manufactured by United Kingdom-based Cantab Pharmaceuticals, which would trick the immune system into clearing cocaine out of the relapsing addict's body before it could reach the brain and trigger renewed-and powerful-cravings. Another factor that NIDA researchers are targeting is the stress response, a complex cascade of hormones and neurotransmitters triggered by unpleasant or threatening events. If animals are stressed, the stress acts as a more powerful inducement than priming for them to seek out drugs. Scientists have discovered that the stress-related increase in drug-seeking behavior is mediated by corticotropin releasing factor (CRF), a hormone the body releases under adverse conditions. In animals, anti-CRF medicines block the drug-seeking stress response in dramatic fashion. Already, two pharmaceutical companies-Pfizer Inc. and Janssen Pharmaceutica-have put these anti-stress-hormone drugs into clinical trials for the treatment of anxiety, depression, and other disorders aggravated by stress. Researchers are also targeting the phenomenon known as "cuing." When Russian scientist Ivan Pavlov fed his dogs right after a bell was rung, they eventually began to involuntary salivate in response to the ringing of the bell alone. In humans, the same pairing of an event or action with, for example, a crack high transforms that stimulus into a powerful provoker of, for example, crack craving. Cues, says Vocci, can be people associated with drug use, places, or even, for some addicts, just getting a paycheck. Once the anticipatory properties of the cue are activated, they can increase behaviors directed toward getting high, and-over time-erode inhibitory systems in the frontal cortex, the neurobiological networks that govern willpower and self-control. Vocci calls this the "double whammy" effect: Experiencing a cue can make people crave drugs-as well make them more impulsive and likely to give in to the craving. Two different types of drugs now entering testing may be beneficial in terms of treating this aspect of cocaine addiction: One mimics part of the dopamine molecule; the other targets the powerful cue of nicotine. Greater Southeast Community Hospital on Southern Avenue SE is not often looked to as a leader in cutting-edge medicine. But in September 1996, it opened the doors to a new program that demonstrates that clinicians aren't waiting for a miracle pill to be approved before they'll start applying the lessons of the new neuroscience in their practices. Footprints, a 20-person outpatient day-treatment program, focuses on treating people with "dual diagnoses" of addiction and mental illness. A 20-bed dual-diagnosis inpatient facility takes patients referred by the emergency room for a three-to seven-day acute-care stay, before sending them across the street to Footprints. There are now six programs citywide that provide dual-diagnosis treatment. The program rooms at Footprints are clean and calm. A schedule for participants lists meetings that keep them busy and off the streets from 8:30 a.m. to 8 p.m., Monday through Friday, for the duration of the 60- to 90-day program. There are groups for grief counseling, anger management, stress management, and "life-skills education." Peer groups, HIV-positive groups, and gender-specific groups. Mental health and medication groups. Meetings for weekday and weekend goal-setting. And, of course, relapse prevention. And then there is Prozac. And Zoloft. And Effexor. And Haldol. (Three antidepressants and an anti-psychotic.) "We're very medication-focused," says Gloria Martin, who was for several years the psychiatry clinical manager at Footprints. Footprints is determined to succeed where so many other programs fail: in treating the underlying conditions that can lead many mentally ill people into lives of addiction-as well as the mental illnesses that can be caused by addiction. Though many mentally ill people never try illegal drugs, the National Alliance for the Mentally Ill reports that up to half of people with mental illnesses also develop substance-abuse problems, and studies show that two-thirds of cocaine addicts suffer from at least one major mental illness at some point in their lives. For some, the addiction is secondary to the psychiatric problem: They've turned to alcohol, marijuana, or cocaine as a way of self-medicating their troubles-and their troubled neurobiology. For others, the addiction itself-and the loss of control that flows from it-induces mental illness: Cocaine has been shown to routinely induce depression, and it can even lead to temporary psychosis. The goal of dual-diagnosis therapy is to help patients accept and learn to manage their underlying problem-be it depression, bipolar disease (manic-depression), or schizophrenia. At the start of group meetings, Footprints patients must admit not only their addictions but also their particular psychiatric diagnoses. That's when it becomes clear that, although much of the social stigma associated with depression may have faded with the advent of drugs such as Prozac, the embarrassment caused by many other psychiatric syndromes persists. Being open about their mental illness is, for many, the hardest part of the Footprints program. "People are more willing to deal with the drug issue than the mental-health issue. They'd rather be seen as a drug addict than a schizophrenic," says Martin. "There's a lot of cultural hesitancy. No one wants to be associated with that." "Alcoholism, crack cocaine, and drugs are just a symptom. There's an emotional mental illness going on that's the real issue," adds George Vincent, the program's former administrative director. (Bill Wasserman succeeded him in the position this month.) "We found out that the substance abuse induces depression, or sometimes comes before it." Depressed patients say crack "lifts their spirits." Schizophrenics say it silences their auditory hallucinations and can lessen their feelings of social isolation. It makes the depressed and despondent feel euphoric and in control-for a while. Then they crash again. And the mental illnesses return, exacerbated. So Footprints tries to stabilize the psychiatric problems, giving patients a better chance of being able to recover from their addictions. And the new psychopharmacology plays a central role in this process. "For time, money, and efficiency, medication is the best thing we can do," says Martin. Of course, treatment tends to attract the most troubled users. An individual who tries cocaine five times and crack once will not seek out treatment, nor will someone who snorts cocaine recreationally once every few months. But a crack addict who is sentenced by the courts to a treatment facility will have to go. Footprints gears its program to the most complex and difficult cases. "Generally, people who present for treatment are in worse condition, because they don't believe they have a problem and it's not until they are forced to confront it-either by the courts or some other circumstance-that they admit they have a problem," says Dr. H. Westley Clark, director of the Federal Center for Substance Abuse Treatment at the U.S. Department of Health and Human Services. AA and its drug-abuse sister program, Narcotics Anonymous (NA), call this process "bottoming out." Greater Southeast sees mainly women in its dual-diagnosis program. Not only are women in the general population diagnosed with depression more frequently than men, female crack addicts are more apt to suffer from depression than male addicts, who are more likely to suffer from anti-social personality disorders that land them in jail, not dual-diagnosis treatment programs. And because female crack addicts often have children, says Martin, they have more incentive to recover-and reclaim kids removed by the D.C. Child and Family Services Agency. "Their issues are a lot more serious than men's," says Belinda Robinson, a mental-health counselor at Footprints, rattling off the gamut of problems these women have confronted: "Sexual abuse, molestation, incest, the issue of being a parent, a single mother." And, as is the case for health care in general, men are more reluctant to seek help. The lives of most Footprint patients, says Martin, have been characterized by disorder. Many have been in foster care. They often lacked a father at home, or came from families where each child had a different father. With surprising regularity, many report that they were first introduced to drugs by mothers and siblings. For those on the front lines of drug-addiction treatment-who face down such overwhelmingly troubled patients every day-the idea of a pill that could miraculously save them seems laughable. "You can't simply say, 'Take a pill and go away,'" says Clark. "When you're dealing with illegal drug use, you are also dealing with the environment and the psychological issues-victims of domestic violence, post-traumatic stress disorder. You can't just deal with cocaine and say, 'I solved the problem.' "In our sample," he adds of a Health and Human Services study of more than 1,700 women on crack, "94 percent were unemployed, 99 percent had less than a high school diploma, one-third had experienced homelessness, 61 percent had child-protective services involvement, 50 to 80 percent had mental-health problems, 33 percent had a history of suicide attempts, 57 percent had a history of parental abuse, and 50 percent were involved with the criminal-justice system." That's not a life that can be turned around with a pill. For Michael, his circumstances, though less extreme, have led to repeated attempts to get and stay clean. And they have also required repeated and increasingly serious attempts to change how he thinks, how he understands himself, and how he relates to the world. "You don't just drink methadone," says Michael. "You go through counseling, participate in NA meetings. For me, that's the most important part of the whole process-the recovery, the socialization process. Because you can drink methadone and stop using heroin, but that doesn't mean you stop your behavior....You have people out here that don't use anything, but their behavior is just like a drug addict's-selfish and self-centered." Methadone may have stabilized Michael and allowed him to detox from heroin without undergoing the physical trauma of the withdrawal process. But, as he sees it, that was only the first step. Two years into his third attempt at recovery, Michael, who is unemployed and on disability because of his hip, estimates that he spends about 25 hours a week in counseling sessions or NA meetings. That kind of experience leaves clinicians like Besteman with lots of questions about the role medications may someday play in the management of addiction. "Do I want medications development to succeed?" asks Besteman. "Yes. Particularly around the area of cocaine and stimulants. But how many users do you know who have stopped? Gosh, plenty of them. And they didn't have [any new] medication. On a clinical level, we can't sit and wait." CP - --- MAP posted-by: Keith Brilhart