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A properly implemented agonist treatment regimen should improve retention and reduce illicit drug use. Cocaine-dependent subjects (N = 128) were enrolled in a 12-week randomized, double-blind, placebo-controlled trial. In the multistage dosing design, subjects initially received placebo (PBO) or 15 to 30 mg of dextroamphetamine sulfate, sustained-release capsules. At week 5, the dose doubled to 30 mg or 60 mg for active groups. Subjects attended the clinic twice a week, provided urine samples, obtained medication, and had one behavioral therapy session a week. Retention was best for the 15- to 30-mg group, whereas the proportion of benzoylecgonine-positive urine screens was, from lowest to highest, 30 to 60 mg, 15 to 30 mg, and PBO at study end. Dosing must be refined. The results provide support for additional examination of the agonist model in psychostimulant-dependence treatment.

A partial blockade of the multiple actions of cocaine is one strategy by which cocaine dependence may be treated. Risperidone, a 5-hydroxytryptamine and dopamine D2 antagonist, is an atypical antipsychotic and was a candidate medication for the treatment of cocaine dependence. One hundred ninety-three cocaine-dependent subjects were enrolled in a 12-week, randomized, double-blind, placebo-controlled trial. Subjects initially received either placebo or 4 or 8 mg of risperidone, with a subsequent change to active doses of 2 mg and 4 mg. Subjects attended the clinic twice each week, provided urine samples, obtained medication, and underwent one behavioral therapy session per week. The study was terminated at the interim analysis. Retention was worse for the 4- and 8-mg active medication groups. Side effects were primarily associated with the 8-mg dose, although neither 2 mg nor 4 mg was well accepted by subjects. There was no reduction in cocaine use associated with risperidone. The results suggest that although antagonists might be a useful treatment approach, such as in the treatment of opiate dependence, risperidone is unlikely to find broad acceptance with the treatment-seeking population.

Two experiments examined the effects of methylphenidate in male and female patients enrolled in an outpatient treatment program for primary cocaine dependence. The first study was a component of a double-blind efficacy trial wherein 57 patients were first tested in a human laboratory for their initial responsiveness to medication. Patients were randomly assigned to receive either placebo or methylphenidate treatment and received their first dose in the human laboratory environment before continuing in outpatient treatment. Methylphenidate was given as a 20-mg sustained-release dose (twice daily) plus an additional 5-mg immediate-release dose combined with the morning dose. Methylphenidate increased heart rate and subjective ratings; however, the subjective effects were primarily of a "dysphoric" nature, and significant effects were limited to increases in anxiety, depression, and anger on the Profile of Mood States; shaky/jittery ratings on a visual analog scale; and dysphoria on the lysergic acid diethylamide (LSD) scale of the Addiction Research Center Inventory. Methylphenidate did not increase cocaine craving nor ratings suggesting abuse potential (i.e., Morphine-Benzedrine Group or drug-liking scores, etc.). None of the drug effects observed in the human laboratory was of clinical concern, and no subject was precluded from continuing in the outpatient study. After outpatient treatment completion, 12 patients were brought back into a second double-blind human laboratory study in which three doses (15, 30, and 60 mg) of immediate-release methylphenidate were administered in an ascending series preceded and followed by placebo. Methylphenidate produced dose-related increases in heart rate, subjective ratings of shaky/jittery, and LSD/dysphoria without significantly altering cocaine craving or stimulant euphoria ratings. These results suggest that stimulant substitution-type approaches to the treatment of cocaine dependence are not necessarily contraindicated because of cardiovascular toxicity or medication abuse potential. However, they also suggest that the subjective effects of methylphenidate may not be positive enough for an adequate replacement approach.

Two studies examined contingent take-home medication doses during treatment of opiate or cocaine dependence. In the first study, methadone maintenance patients were randomly assigned to one of two 8-week baseline take-home (TH) conditions differing in frequency of clinic visits per week. This was followed by a 12-week contingency management (CM) procedure in which frequent THs resulted from drug-free urines. Participants receiving more frequent THs during baseline had lower illicit drug use during the first 6 weeks of CM. In the second study, fluoxetine (0-, 20-, 40-mg) TH doses were similarly contingent in treatment of cocaine dependence. The 40-mg group used less cocaine during contingency than did other groups. The combination of fluoxetine and environmental contingencies may produce benefit where neither alone is sufficient.

Agonists, or "replacement medications," are useful adjuncts in treatment of opiate and nicotine dependence. They have not been systematically examined in cocaine dependence. Results of early open trials with methylphenidate for treatment of cocaine dependence were equivocal. Twenty-four cocaine-dependent subjects were enrolled in an 11-week double-blind, placebo-controlled study of methylphenidate. Assignment was random. Intake included a 2-day human laboratory procedure in which subjects received initial doses of methylphenidate or placebo. Subjects attended the clinic Monday through Friday and received oral doses of methylphenidate (5 mg plus 20-mg sustained release) or placebo at 8:00 a.m., with afternoon and weekend take-home doses (20 mg sustained-release or placebo) provided in Medication Events Monitoring System bottles to monitor compliance. Clinic visits included therapy sessions, electrocardiograms, self-report measures, and twice-weekly urine screens. The two groups were equivalent in terms of retention (methylphenidate 48% and placebo 42%) and had similar cocaine use outcomes (40% benzoylecgonine-positive urine screens). There were no significant adverse effects. The doses were sufficient to permit detection of psychoactive effects ("stimulant," "more energy") and side effects ("jitteriness," "eating less") without increased "craving." Additional medications with different effects profiles are being studied to further evaluate the replacement model in cocaine dependence.

This study reports on a survey of smoking behaviors among 39 healthcare professionals in Sarajevo, Bosnia-Herzogovina. The hypothesis that cigarette smoking would decrease as a result of an 800% price increase was not supported. Cultural, pharmacological, and psychological reasons that may have contributed to the present findings are discussed.

Cocaine dependence has proved difficult to treat, whether occurring alone or in combination with opiate dependence. No medication has been demonstrated to be uniquely effective. Fluoxetine was examined as a candidate in two randomized, double-blind, placebo-controlled trials, one with cocaine-dependent patients (study 1) and the other with patients both cocaine and opiate dependent (study 2). It was selected for known specific action, antidepressant effects, minimum side effects, and data showing reduced cocaine effect and self-administration. Clinic visit frequency requirement, a variable with implications for treatment and cost, was also examined in study 1. A total of 228 patients in study 1 and 21 patients in study 2 completed consent and intake procedures. Patients with serious medical or DSM-III-R diagnoses other than cocaine dependence (study 1) or opiate and cocaine dependence (study 2) were excluded. Study 1 patients were assigned to one of two visit frequency schedules (2 or 5 days/week) and one of three medication doses (0, 20, or 40 mg of fluoxetine/day). Study 2 patients received placebo or 20 mg of fluoxetine and 65 to 80 mg of methadone and attended the clinic 5 days/week. All patients participated in individual therapy sessions. Urine screens were conducted twice weekly. A fluoxetine dose response relationship emerged in study 1 for retention with groups from best to worst being placebo, 20 mg, and 40 mg. Dose effect order was the same for both visit conditions. Cocaine use persisted in all groups. The two visits/week condition was correlated with better retention than the five visits/week condition. A significant interaction emerged between intake urine and visit frequency; patients with benzoylecognine screens at intake used cocaine significantly less in the 5 days/week condition, while exhibiting no reduction in the 2 days/week condition. Patients cocaine positive at intake were better retained with infrequent visits. In study 2, a transient reduction in benzoylecognine-positive drug screens emerged for the fluoxetine group. These complementary studies demonstrate that fluoxetine is ineffective in reducing cocaine use or craving. Study 1 also points to setting conditions modulating treatment outcome.

An innovative model for organising social services in a community, the Imbrication Model, is contrasted with two traditional models, the Entrepreneurial and the Umbrella Agency. The structural characteristics and dynamics of the three models are illustrated with actual case histories. Imbrication Model calls for the interlocking of personnel from several agencies, with the purpose of redirecting the dysfunctional interagency rivalry prevalent in the traditional models. Imbrications at all organisational levels--Board of Directors, Administrators and Staff--facilitate adoption of the superordinate goal of providing clients with the best services available, regardless of which particular agency delivers the service. Few observers of the current social service scene would challenge the statement that needs for service are unlimited and resources limited. In the USA the imbalance between needs and resources persists despite a decade of massive governmental programmes intended to alleviate social ills. Recent substantial cutbacks in federal funds, moreover are not likely to improve the situation. The resource shortage involves more than a limitation of funds. Deliverers of service and competent programme administrators are also on critically short supply. These shortages are more often than not exacerbated by a chronic spirit of competition among agencies and programmes at the local level. Three organizational models for the delivery and administration of social services, two conventional and one of more recent date, are examined in this article. The innovative model, which has been named the Imbrication Model, explicitly calls for redirecting interagency rivalry and competition. Its ambitious goal is to integrate the efforts of those attempting to meet a community's social service needs.