flupenthixol-decanoate and Substance-Related-Disorders

The effect of decanoate forms of flupenthixol and haloperidol on cocaine self-administration was evaluated. Forty-two male Wistar rats were implanted with chronically indwelling jugular cannulae and trained to self-administer cocaine (0.6 mg/inj) either on a fixed ratio (FR) 1 schedule or a progressive ratio (PR) schedule. After a stable response pattern was established, animals received a single i.m. injection of either flupenthixol (2.0 mg), haloperidol (2.5 mg) or vehicle (0.1 ml oil). Both neuroleptics produced a long lasting increase in cocaine intake on a FR 1 schedule which reached a peak on post-injection day three and diminished slowly over the next seven days. All animals maintained on a PR schedule showed a long lasting decline in breaking points. These data suggest that the decanoate forms of flupenthixol and haloperidol may attenuate the reinforcing effects of cocaine and indicate that the therapeutic value of depot neuroleptics as anti-cocaine treatments would depend on the economics of cocaine availability.

Topics: Animals; Cocaine; Flupenthixol; Haloperidol; Injections, Intramuscular; Male; Rats; Rats, Wistar; Reinforcement Schedule; Self Administration; Substance-Related Disorders; Tranquilizing Agents

Topics: Administration, Oral; Adult; Clopenthixol; Delayed-Action Preparations; Female; Flupenthixol; Humans; Injections, Intravenous; Male; Substance-Related Disorders

"Crack" cocaine abuse often produces severe cocaine dependence that is refractory to available pharmacological and outpatient psychotherapeutic treatments. We conducted two preliminary investigations evaluating the efficacy of flupenthixol decanoate, a depot xanthene requiring infrequent intramuscular administration, in the treatment of cocaine withdrawal. Ten outpatient crack cocaine smokers with poor prognoses were administered flupenthixol decanoate in an open-label, open-ended trial. Flupenthixol decanoate was well tolerated and appeared to decrease cocaine craving and use markedly and rapidly, producing a 260% increase in the average time retained in treatment among these subjects. These promising but preliminary data, combined with the magnitude of problems presented by crack, warrant rapid, expanded double-blind assessment of flupenthixol decanoate in cocaine-abuse treatment.

Topics: Adult; Ambulatory Care; Cocaine; Female; Flupenthixol; Humans; Male; Substance-Related Disorders; Thioxanthenes