In the 1880s, Sigmund Freud noted that cocaine had a number of pleasing effects--euphoria, tirelessness, heightened mental acuity--and thought it might even help one of his friends, Ernst von Fleischl-Marxow, recover from a devastating morphine addiction. Needless to say, he was wrong. Fleischl's cocaine addiction proved to be much worse than his morphine addiction had been, and eventually--but too late for Fleischl--Freud realized his mistake and retracted his support for the drug.
Preventing that kind of disaster from recurring is one of the reasons that researchers since have tried to develop rigorous, reliable methods of determining whether new medications have any potential for abuse, and why U.S. lawmakers have developed strict regulations for the medical use of drugs with high abuse potential.
But with new drugs constantly being developed--some of which have pharmacologies fundamentally different from those of cocaine, heroin and other conventionally abused drugs--that challenge continues to grow. At a recent conference in Bethesda, Md., researchers, drug developers and federal regulators met to assess the state-of-the-art in drug-abuse liability assessment (ALA) and to draw up a list of recommendations and research priorities for the field. The conference was sponsored by the College on Problems of Drug Dependence (CPDD), APA and a number of other professional and scientific societies.
Identifying key questions
The central question in ALA, according to Wayne State psychologist Charles Schuster, PhD, one of the meeting's organizers and a former director of the National Institute on Drug Abuse, is about how to balance the needs of patients who might benefit from new medications with the need to reduce the incidence of drug abuse.
"A variety of new medications are being developed that have interesting therapeutic usefulness for the treatment of a variety of psychiatric disorders, but that also have the potential for misuse and abuse," he says. "How can we properly evaluate them so that we can prevent drugs with high abuse potential from being marketed without any warning to physicians, and without regulation? And also, on the other hand, ensure that regulators in the federal government don't overly regulate drugs and thereby prevent access to drugs with great medical potential?"
Another key question, says Virginia Commonwealth University psychologist Robert Balster, PhD, who presented one of the meeting's background papers, is whether the techniques that have served researchers well in assessing the abuse liability of older drugs will succeed when applied to the new kinds of drugs moving through the pipeline.
"We know best how to perform scientific research on drugs that are similar to heroin, cocaine, alcohol and barbiturates," he says. "We don't know so much about drugs with other kinds of pharmacologies, such as ketamine-like drugs [e.g., PCP] or cannabinoids."
Determining the best way to track the abuse of a drug after it has been released into the market is also a high priority, says meeting organizer Chris-Ellyn Johanson, PhD, of Wayne State University.
That question has gained more importance recently, she says, because the Food and Drug Administration (FDA) has increased its emphasis on risk management. Instead of asking pharmaceutical companies only to demonstrate that a drug has low abuse potential in studies that take place before the drug is marketed, she says, the agency is now also asking them to answer the question, "If you have evidence that a drug is being abused, how are you going to handle it?
"It's now realized that regardless of how much you study a drug [before marketing it], we don't have perfect models, so things can slip through," says Johanson. "The problem is that the survey systems that are in place don't really get you that evidence until several years down the pike."
With the rise of the Internet, it has become easier than ever for drug abusers to share information about the abuse potential of new medications through e-mail, chat rooms and Web sites. Now researchers are trying to find similarly effective ways of tracking patterns of drug abuse. One solution may lie in post-marketing surveillance, the subject of a conference presentation by Theodore Cicero, PhD, of Washington University.
The goal of post-marketing surveillance is to detect a drug-abuse "signal"--an early warning that a new medication is being abused by patients or the drug abusing population. In some cases, post-marketing surveillance might show that the FDA's restrictions on new drugs are tougher than they need to be, says Johanson; in other cases, unexpected abuse of a drug after marketing could lead to tightened restrictions.
The conference's final conclusions and recommendations will not be published until this spring, when they are expected to appear in a special issue of the journal Drug and Alcohol Dependence, but a preliminary outline was presented at the end of the meeting. According to APA Science Policy Director Geoff Mumford, PhD, who helped organize the meeting, the outline largely affirmed that existing animal and human laboratory methods provide valid assessments of abuse potential, but it also pointed out avenues for improvement.
"There was general agreement that the science base for drug-abuse liability assessment is strong," he says, "but the discussions also highlighted some new opportunities."
For example, it would be easy to collect data relevant to drug abuse from patients as part of most clinical trials, he says, but that rarely happens. The panel also made the following recommendations:
The drug-abuse liability assessment field should identify a set of measures and methods that are essential to valid drug-abuse liability assessment.
Although an effective scientific framework for assessing the abuse liability of new drugs is in place--one that relies heavily on laboratory-based behavioral tests in animals--researchers should continue to update and refine that framework to incorporate new findings and to address questions raised by new drug classes.
Current methods of post-marketing surveillance are limited in their usefulness; new techniques should be developed to monitor drug abuse in various communities.
The results of the meeting will help fill a temporary gap left by the dissolution of the Drug Abuse Advisory Committee, which was commissioned by the FDA in 1978 to provide expert advice on drug-abuse liability assessment, says Mumford. The committee was dissolved in 2000 and then reconstituted as a standing subcommittee of the Drug Safety and Risk Management Advisory Committee in 2002.
The meeting also accomplished another important result: lowering the barriers to communication that separate the diverse professional groups that participate in ALA. According to Drug Enforcement Administration psychologist Christine Sannerud, PhD, for instance, such meetings provide valuable opportunities for federal regulators to explain how the results of scientific research enter into the scheduling process.
Meeting organizer Johanson agrees. "It's unusual to have all the stakeholders--academic, government and industry--together in a single meeting," she says, "but it is very important that all of these people talk to each other."
A new video, "Importance of lab Animal Research in Psychology: Pscyhopharmacology," is available for high school and undergraduate classroom use. The video--which has a running time of approximately 13 minutes--is the second in a series of videos produced by the APA Science Directorate and the Committee on Animal Research Ethics. It will be available through the APA Order Department late this month.
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