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To compare the clinical efficacy of different doses of levomethadyl acetate hydrochloride (known as LAAM) in the treatment of opioid dependence.A randomized controlled, double-blind, parallel group, 17-week study.Outpatient facilities at Johns Hopkins University Bayview Medical Center, Baltimore, Md.Opioid-dependent volunteers (N=180) applying to a treatment-research clinic.Thrice-weekly (Monday/Wednesday/Friday) oral LAAM dose conditions of 25/25/35 mg, 50/50/70 mg, and 100/100/140 mg and nonmandatory counseling.Retention in treatment, self-reported heroin use, and opioid-positive urine specimens.Retention was independent of subjects' sex and dose. Self-reported heroin use decreased in a dose-related manner. At final assessment, patients in the high-dose condition reported using heroin 2.5 of 30 days as compared with 4.1 or 6.3 days for patients in the medium-dose and low-dose conditions, respectively (high dose vs low dose, P.05); urinalysis results were similarly dose related. Overall, 20 (34%) of 59 patients in the high-dose condition remained opioid-abstinent for 4 consecutive weeks, as compared with 8 (14%) of 59 in the medium-dose and 7 (11%) of 62 in the low-dose conditions (P.01). Self-report and urinalysis data are consistent with a greater than 90% reduction in illicit opioid use by the high-dose group relative to pretreatment levels.Opioid substitution treatment with LAAM substantially reduces illicit opioid use. The clinical efficacy of LAAM is positively related to dose.

The extent to which daily caffeine use is associated with a substance dependence syndrome similar to that associated with other psychoactive drugs is unknown. The purpose of this study was to assess volunteers who reported problems with their use of caffeine for evidence suggesting a diagnosis of caffeine dependence based on the generic criteria for substance dependence from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV).Case-series evaluations.An academic research center.Self-identified adults who believed they were psychologically or physically dependent on caffeine.Diagnoses made by a psychiatrist using a structured clinical interview that included a section on caffeine dependence based on genetic criteria for DSM-IV substance dependence.Double-blind caffeine-withdrawal evaluation.Ninety-nine subjects were screened for the study, and 16 were identified as having a diagnosis of caffeine dependence. Median daily caffeine intake was 357 mg, and 19% of subjects consumed less than the national (US) daily average of caffeine. Criteria used for making diagnoses (and rates of their prevalence) were as follows: withdrawal (94%), use continued despite knowledge of a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by caffeine use (94%), persistent desire or unsuccessful efforts to cut down or control use (81%), and tolerance (75%). Eleven subjects underwent the double-blind caffeine-withdrawal evaluation portion of the study, and nine (82%) of the 11 showed objective evidence of caffeine withdrawal, including eight of 11 with functional impairment.These results, together with other experimental evidence, suggest that caffeine exhibits the features of a typical psychoactive substance of dependence. It is valuable to recognize caffeine dependence as a clinical syndrome, since some people feel compelled to continue caffeine use despite desires and recommendations to the contrary.