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.