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Almost 3 million Americans have abused heroin. The most effective treatment for this concerning epidemic is opioid replacement therapy. Although, from a historical perspective, acceptance of this therapy has been slow, growing evidence supports its efficacy. There are 3 approved medications for opioid maintenance therapy: methadone hydrochloride, levomethadyl acetate, and buprenorphine hydrochloride. Each has unique characteristics that determine its suitability for an individual patient. Cardiac arrhythmias have been reported with methadone and levomethadyl, but not with buprenorphine. Due to concerns about cardiac risk, levomethadyl use has declined and the product may ultimately be discontinued. These recent safety concerns, specifics about opioid detoxification and maintenance, and new federal initiatives were studied. Opioid detoxification has a role in both preventing acute withdrawal and maintaining long-term abstinence. Although only a minority of eligible patients are engaged in treatment, opioid maintenance therapy appears to offer the greatest public health benefits. There is growing interest in expanding treatment into primary care, allowing opioid addiction to be managed like other chronic illnesses. This model has gained wide acceptance in Europe and is now being implemented in the United States. The recent Drug Addiction Treatment Act enables qualified physicians to treat opioid-dependent patients with buprenorphine in an office-based setting. Mainstreaming opioid addiction treatment has many advantages; its success will depend on resolution of ethical and delivery system issues as well as improved and expanded training of physicians in addiction medicine.

• Various schedules exist for inducting heroin addicts newly admitted to treatment into methadyl acetate maintenance and crossover schedules for the transition from methadone maintenance to methadyl acetate maintenance. A sample of 255 street addicts was randomized to three induction schedules: methadyl acetate three times a week (tiw) with placebos on alternate days; methadyl acetate tiw supplemented with decreasing doses of methadone on alternate days; methadyl acetate six days a week with diminishing doses on three days. Treatment was double-blind for four weeks and single-blind for six. All schedules were considered feasible, but supplementation with methadyl acetate or methadone had no advantage. A sample of 310 patients receiving methadone maintenance was randomized to comparable supplementation groups, except that the group receiving supplementary methadyl acetate received it along with the regular dose. This schedule was not successful. Supplementing with methadone had no advantage.

• Memory tests were administered to 30 patients taking methadone hydrochloride and 31 taking levomethadyl acetate (levo-alpha-acetylmethadol, LAAM) both prior to treatment and after one and three months of continuous treatment. A group of nonopiate using matched control subjects was administered the tests at similar intervals. No statistically significant difference in test performance was found among these groups at any of the three sessions. The methadone and control groups also did not differ significantly in the frequency of subjective reports of decreased memory function. Previous reports of memory deficits during long-term methadone administration may be a result of comparing methadone and control groups at a single point in time and assuming that prior to methadone maintenance the groups were equivalent.

• A randomized clinical trial compared four methods of outpatient withdrawal from heroin. Sixty-one subjects were assigned in a double-blind manner to treatment with either methadone or methadyl acetate. Within each drug group, subjects were assigned to detoxification programs either within the standard three-week period or in an extended six weeks of treatment. Outcome measures included retention to the end of the dosing schedule, use of illicit drugs during treatment, subjective discomfort, satisfaction, staff ratings of global progress, and durability of change at a three-month follow-up. Methadyl acetate performed similarly to methadone in most respects. Six-week withdrawal showed some temporary benefits over standard treatment, but these advantages should be weighed against the greater cost of the longer treatment and similarity of follow-up outcome.

• Chromosomes of peripheral leukocytes were examined in 28 addicts participating in a Veterans Administration-Special Action Office for Drug Abuse Prevention (SAODAP) cooperative study of methadyl acetate vs methadone. Blood samples for 72-hour leukocyte cultures were drawn after nearly 40 weeks of maintenance therapy while subjects were receiving active medication. For comparison, ten nondrug users were also studied. The frequency of chromosome damage was not greater in subjects maintained on methadyl acetate or methadone than in nondrug users.

• This was an open clinical trial of methadyl acetate (LAAM) compared with methadone in the maintenance of 636 heroin addicts who had previously been stabilized on a maintenance regimen of methadone. The starting sample assembled by the 13 cooperating clinics were randomly assigned to continued maintenance on methadone (= 308) or crossed over to methadyl acetate (= 328) for a period of 40 weeks. The starting dose was identical to the previously established dose of methadone, but beginning with the second visit, dosage was flexible. Safety was evaluated by clinical and laboratory observations conducted at four-week intervals throughout the study. Relative efficacy was evaluated by illicit drug use, program retention and attendance, and global staff judgments. It is concluded that methadyl acetate is as safe as methadone and, when given three times a week, is an acceptable and effective maintenance drug for many heroin addicts.

• Sixty-eight heroin addicts maintained for 40 weeks on a regimen of methadyl acetate or methadone hydrochloride in a double-blind study were transferred to a uniform dose of 60 mg of methadone daily at the end of their tenure in the study. They were observed for the ensuing six weeks, during which their daily methadone doses were adjusted according to their clinical needs. Patients were observed for symptoms and signs of discomfort and for the amount of illicit drug use during this period of transition. The results indicate that patients maintained on a regimen of methadyl acetate can be readily restabilized with methadone and that sudden decrease of the methadone dose tends to result in the patient's supplementing with illicit heroin. Conversely, increasing methadone doses resulted in a corresponding reduction in illicit drug use. It is suggested that a chronic covert abstinence syndrome may exist in some patients receiving long-term methadone maintenance therapy, and that while it may contribute to their continued illicit drug use, it may have a different pathophysiologic basis and require different therapeutic considerations.

• The analgesic effect of racemic alpha acetylmethadol was studied in 49 patients suffering chronic pain due to cancer, 10 recovering after surgery, and 17 in chronic or transient pain from other causes. Doses of 5 to 10 mg. given three or four times daily were highly effective on continued use. Good relief from pain was obtained by either oral administration or subcutaneous injection. A few patients complained of lethargy. Hypnotics were usually needed for sleep. It was possible in several patients to discontinue use of frequent injections of large doses of morphine or meperidine and to change over completely to the oral use of acetylmethadol without causing withdrawal symptoms. Constipation was bothersome with large daily doses (30 to 50 mg.). Other side-effects were infrequent. The toxic effects of cumulation with large doses can be avoided by taking into account the patient's metabolic and excretory status. In the majority of patients in this series, the oral administration of acetylmethadol has afforded relief from chronic pain for several months without severe untoward effects.