Researchers seek genetic clues to identify addicts and patients who will benefit from treatment

Toxicology experts have long known that individuals can exhibit a wide range of physiological responses when exposed to identical doses of opiate- or morphine-based drugs. This drug class includes illicit drugs such as heroin, as well as regulated drugs like methadone and oxycontin, which have legitimate uses in addiction treatment and pain management. Unfortunately, an individual’s response to these drugs can be gauged only after the drug has been administered, leaving care givers to make an educated guess as to how much drug to give in order to achieve the intended effect.

Now, a team of researchers suggests that “pharmacogenomic” testing may be a way to help drug-treatment centers select appropriate treatment regimens for their opiate-addicted patients, and it may also provide valuable information in the care of patients who require substantial levels of pharmacological pain management.

Background

The most common treatment for heroin addiction is methadone, used because of its ability to produce psychic and physical dependence, but with significantly milder withdrawal symptoms than heroin. Previously published studies have documented methadone toxicity and noted a higher risk in the initial treatment periods for some patients.

Scientists know that the toxicity of this synthetic narcotic is affected in part by a patient’s metabolism of the drug. Methadone is metabolized by enzymes CYP1A2, CYP2D6 and CYP 3A4. CYP 2D6 is unique in that it is also a key to the metabolism of other opioids, such as codeine and tricyclic antidepressants.

A recent peer-reviewed article—“Pharmacogenomics as Molecular Autopsy for Forensic Pathology/Toxicology: Does Genotyping CYP 296 Serve as an Adjunct for Certifying Methadone Toxicity?”—looks at the possibility of using laboratory-based testing to identify genetic polymorphisms that affect the way an individual metabolizes the opioid class of drugs. The authors are Steven H. Wong, PhD; Michael A. Wagner, PhD; Jeffrey M. Jentzen, MD; Chuck Shur; Jeanette Bjerke; Susan B. Gock; and Chung-Che Jeffrey Chang, MD, PhD, all with the Department of Pathology, Medical College of Wisconsin in Milwaukee. Drs. Wong, Wagner, Jentzen, and Ms. Gock are also affiliated with the Milwaukee County Medical Examiner’s Office.

Results

In their current study, the authors conclude that complex medical and prescription histories often make it difficult to conclude that a CYP 2D6-encoded enzyme deficiency is the sole cause of a methadone mortality, or even contributed to death. They also note that the results generated by their genotyping investigations would not have prompted a change in the medical examiners ruling on cause of death. Nevertheless, the authors say that their study is an important first step in the effort to link genotyping with individuals’ responses to treatment therapies such as methadone, and that establishing this relationship will have a great impact in drug-abuse treatment and pain management.

This study is being presented at the 54th Annual Meeting of the American Association for Clinical Chemistry (AACC) in Orlando, Fla., July 29-August 1, 2002. AACC (http://www.aacc.org/) is the scientific organization for clinical laboratory professionals, physicians, and research scientists. Their primary commitment is the understanding of laboratory testing to identify, monitor and treat human disease. More than 14,000 attendees are expected for the meeting, which is being held at the Orange County Convention Center, Orlando, Fla., July 28-August 1, 2002.