Methadone, the granddaddy of replacement treatments for addiction to heroin and other opioid drugs, has been available for 30 years. Surprisingly, studies that show clearly which doses are best at keeping patients from using illegal opioids are rare. Research by Johns Hopkins scientists reported in this week's Journal of the American Medical Association bucks this trend, however: It shows that larger than typical doses of methadone may work best in controlling addicted patients' drug use.

The study also is the largest and most recent to underscore that even at moderate doses, methadone remains the most effective treatment for addiction to illicit opioid drugs, the Hopkins scientists say.

"It's troubling that the dosage of methadone apparently varies so widely across the country," says psychiatrist Eric C. Strain, who led the study. Some clinics have daily maintenance doses of less than 30 mg, while in others the average dose jumps to 60 mg, Strain says. "This probably stems from uncertainty brought about by clinical trials' long history of controversial or conflicting results."

To avoid the earlier problems, the Hopkins researchers conducted the study at a single location and for the 10-month trial randomly assigned a large number of patients--192--to a moderate dose group (40 to 50 mg of methadone) or to a high dose (80 to 100 mg) group. The scientists measured "street" opioid use largely through urine testing. In both groups, illicit drug use dropped sharply: Patients went from as many as 26 uses a week to fewer than three.

The highest reduction, Strain says, was in the high-dose group, which was two to three times lower than in patients given moderate doses. Both groups, he adds, had a relatively low dropout rate.

"Some patients may need dosages higher than 100 mg for optimal benefit, though more testing's needed on that," Strain says. Federal law discourages methadone dosages greater than 100 mg. Meanwhile, he adds, "our results show that significant improvement occurs with daily doses of 80 mg or greater, though the 40 to 50 mg minimum dose still benefits the public's health."

The study was supported by U.S. Public Health Service grants. Other researchers include George E. Bigelow, Ira A. Liebson and Maxine L. Stitzer.