P&S Journal: Winter 1998, Vol.18, No.1
Drugs--Some Legal,--Some Not--Under the Microscope
|Using unconventional research tools--crack pipes, video monitors, and scanners that record the bar codes on packages of food--researchers in the Division on Substance Abuse seek to explain cravings for cocaine and carbohydrates or show links between productivity and drug use in the work place.|
8:00 a.m. Though much of CPMC is still quiet, the day has already begun in a small office in the Irving Center for Clinical Research. There, in the cocaine laboratory, a nurse prepares to insert two intravenous lines in the arms of a volunteer. One line will carry either a medication being tested for its ability to inhibit the effects of cocaine or a placebo. The other line will be used to draw blood for various assays or administer emergency medications if needed.
As the volunteer settles back into his reclining chair, the experimental medication flows through the IV line and into his body. A blood pressure cuff and EKG electrodes automatically monitor his heart and blood pressure.
Using a computer directly in front of him, the man responds to a series of statements--such as "I want cocaine" and "I feel stimulated"--by moving a cursor along a horizontal line labeled "not at all" on one end and "extremely" on the other. When he finishes, he must pick one of two choices displayed on the computer screen. One choice is a dose of cocaine (although some volunteers will get a placebo when they request cocaine). The other choice is a non-drug alternative, such as a $5 voucher to spend in a local store. Today, the volunteer chooses the first option, the cocaine (or placebo), by tapping the computer's space bar 200 times. Shortly afterward, a nurse brings in a crack pipe with a pellet of cocaine, which the volunteer smokes. He then completes another series of questions about how he feels.
9:00 a.m. In a residential lab
on the fourth floor of the New York State Psychiatric Institute, four
women sit at computers, ready to start their"jobs² for the day. One
of their first projects is an incredibly boring task in which they push
a button on a computer keyboard hundreds of times. The task is designed
to test how hard the volunteers--all of whom are obese--are willing to
work in order to earn a variety of reinforcers, in this case snack foods
such as ice cream and chocolate. It is just one of the many measures of
their eating behavior the volunteers will undergo as participants in a
study at the Substance Use Research Center. This study--to determine whether
Prozac affects the motivational aspects of eating in obese individuals--will
help researchers better understand the role of neurotransmitters in eating
behavior. The volunteers will spend three weeks living and working in
the labıs four small bedrooms and one large communal living room.
11:00 a.m. With a slide of a coca plant projected onto a screen behind him, Dr. Kleber is teaching first-year medical students about cocaine.The coca leaf was used for centuries by Andean Indians as a mild stimulant before the Spanish conquest of South America," he says. "But the active ingredient, cocaine, was not isolated until the late 1800s in Europe. Initially used in patent medicines, wines, and soft drinks, it eventually became a major drug of abuse both in Europe and the United States." Among the psychological effects of cocaine: intense euphoria, increased energy, decreased appetite, and sexual arousal. After heavy use, however, these effects are followed by their opposites: depression, fatigue, lack of pleasure, decreased interest in sex, irritability, and paranoia. The smoked form of cocaine--crack--is the most addicting drug Dr. Kleber has encountered in his 30 years in the field, increasing the importance of developing a medication to treat it. As part of his lecture, Dr. Kleber also projects a slide of PET scans of the brain, showing that the damage cocaine causes can last months after the last dose.
For several reasons, physicians traditionally have not asked patients about problems with substance abuse, says Dr. Kleber. First, they're not optimistic that they would know how to treat a problem if the patient reveals one. They may be concerned that patients will be offended by such questions or they may feel uncomfortable broaching the topic. In fact, many doctors do not have adequate training in how to evaluate and treat substance abuse,
notes Dr. Kleber. With lectures such as the ones Dr. Kleber gives, medical schools are taking steps to change that situation: Since 1992, the amount of time that medical students at P&S spend on the topic of substance abuse has increased four-fold. "We're now trying to develop innovative methods to train more doctors," he says. "First, we have to convince the students that it's important--and the best way to get medical students, interns, and residents to pay attention is if they know they're going to be tested. We're working with specialty boards to increase the number of questions that relate to substance abuse."
1:00 p.m. In a room on the fourth floor of the Psychiatric Institute, Drs. Adam Bisaga, substance abuse training fellow; Sandra Comer, assistant professor of psychiatry; Richard Foltin, associate professor of psychiatry and co-director of the Substance Use Research Center; Suzette Evans, assistant professor of clinical psychiatry; and Crawford Clark, research scientist, discuss the design of a study that will monitor the response of women to the pain of cold water during various phases of their menstrual cycles. The study, which Dr. Comer will lead, is in response to a request for applications by the National Institute of Dental Research for work on gender differences in response to painful stimuli and response to medications targeting that pain. The study marks the beginning of the division's interest in evaluating brain mechanisms involved in pain and the alleviation of pain.
The women will put their arms in a warm water bath first," says one of the researchers.
It's important to equalize the temperature before beginning the cold pressor test, interrupts Dr. Foltin.And we need to be sure that we include information about the superiority of this test in differentiating the response of men and women." The group then goes on to discuss alternative tests and their strengths and weaknesses for this study, concluding that this will be one of two tests proposed for the study to ensure that both the sensory and emotional aspects of pain are addressed. The study is one of many outpatient trials conducted at the center.
The substance abuse division is one of three in the country that have
fellowship programs to train physicians for careers in substance abuse
research. Fellows are involved in basic lab inpatient and outpatient studies
and treatment research protocols.
2:00 p.m. Back in the residential lab of the center, the four women volunteers are cleaning up from lunch and getting ready to resume their jobs. The lab's staff stocks the refrigerators and the women each carefully scan in the bar codes on the packages of the food they eat. During the three weeks of the study, the women may have no contact with the outside world--no phones, no televisions, no newspapers. From 9 to 5 they work at computer tasks specifically designed for the study; at night they can watch video tapes from the lab's ample supply, use the lab's video games, or read books and magazines from the shelves. A washer and dryer allow them to do their laundry whenever they wish. All of their activities in the lab are monitored through cameras and microphones.
The outside world is screened out to keep the variables of every study the same, says Dr. Fischman. "We're interested in the flow of behavior in the absence of artificial constraints, unless we design those constraints into the study.
Other residential lab research has studied the workplace effects of alcohol, amphetamines, marijuana, and benzodiazepines, but not heroin or cocaine use, which requires closer monitoring.Our studies have found that if participants are paid for their work output, then during working hours they will not take any drug that interferes with their work output," says Dr. Fischman. "In contrast, workplaces in which individuals are paid hourly wages with no contingencies placed on output are ideal environments for fostering drug use.
An upcoming residential lab study will examine the physical dependence and withdrawal effects of marijuana. "These type of studies are important for teaching adolescents about drugs," she says. "There's far too much teaching based on scare tactics and not enough based on empirical data. It's likely that marijuana does have physical-dependence-producing effects, and youngsters need to know that."
4:00 p.m. As the work day draws to a close for the participants in the residential lab, it's just beginning for the lab's 4 p.m. to midnight shift. One full-time person and one part-time person work the shift each day to monitor the study and to offer help to the resident participants during their hours awake. (Participants and staff are allowed to meet in the vestibule of the residential lab--the only place where participants are allowed a limited interaction with the "outside" world.) From midnight to 8 a.m., one staff person monitors the lab. The night staff person remains there, sitting just outside in a control room--surrounded by a bank of computer screens and monitors--until the next morning when the volunteers wake up, ready to begin another day in the lab.
The Division on Substance Abuse has the unique ability to examine substance abuse issues at three levels: in non-human primates, in controlled laboratory research with human subjects, and in clinical treatment of cocaine and heroin-abusing patients, says Dr. Herbert Kleber, professor of psychiatry and director of the division. Faculty conduct their own research and foster collaborative research at the New York State Psychiatric Institute and throughout CPMC. A sampling of research projects under way in the division:
Cocaine lab studies
Heroin treatment studies
| The Ethical Issues
Research in the Division on Substance Abuse--especially studies that provide drugs to drug abusers who show no interest in treatment--can be controversial. Dr. Herbert Kleber, director, and Dr. Marian Fischman, co-director, deal with critical questions head on.
The motto of the cocaine lab--and the entire division--is that substance use and dependence are issues that can be studied scientifically, says Dr. Kleber. "Through research we can learn how drugs affect the brain and thus develop better treatment methods." "This research is badly needed," says Dr. Fisch-man, "and we believe that to refrain from doing it would be unethical. Drug abuse and dependence remain a staggering public health problem. There continues to be high morbidity and mortality associated with the abuse of such drugs as cocaine and heroin, underscoring the need for research to develop better drug abuse prevention and treatment methods. In addition to the personal suffering associated with drug abuse, its contribution to other social problems such as AIDS, crime, and family disintegration makes necessary continued research in this area."
The division's research focuses on several aspects of the problem of drug abuse. One of these is the continued testing of medications that might be useful in treating drug abusers. First, researchers test medications in a laboratory. "We are able, with relatively few individuals and in a relatively short period of time, to provide answers to questions related to the safety of the medication being tested when it is combined with cocaine or heroin." Addicts in treatment generally combine the medication with the illicit drug, since there is no such thing as a "silver bullet" for treating drug abusers. "Secondly, we can provide information about the likelihood that the medications in question will block or change the effects of cocaine or heroin so that addicts will be less likely to abuse them and more likely to stay in treatment." Once medications look promising in the lab, researchers can proceed to treatment in the clinic with the assurance that the effects of the medication are understood.
"Our research is not undertaken lightly,² says Dr. Fischman. "Because there are questions that can only be answered through research with human participants, we believe that the work we are doing is important, necessary, and carried out in a safe and ethical fashion."The research includes these safeguards and benefits:
|Dr. Marian Fischman: "This research is badly needed, and we believe that to refrain from doing it would be unethical."||Dr. Herbert Kleber: "Through research we can learn how drugs affect the brain and thus develop better treatment methods."|