Significant interaction between clozapine and cocaine in cocaine addicts

Because clozapine may be prescribed to cocaine abusing patients with schizo phrenia, we studied cocaine-clozapine interactions in a controlled setting. Eight male cocaine addicts underwent four oral challenges with ascending d oses of clozapine (12.5, 25 and 50 mg) and placebo followed 2 h later by a 2-mg/kg dose of intranasal cocaine. Subjective and physiological responses, and serum cocaine levels were measured over a total 4-h period. Clozapine pretreatment increased cocaine levels during the study and significantly in creased the peak serum cocaine levels in a dose dependent manner. In spite of this elevation in blood levels, clozapine pretreatment had a significant diminishing effect upon subjective responses to cocaine, including 'expect ed high', 'high' and 'rush', notably at the 50 mg dose. There was also a si gnificant effect upon 'sleepiness', 'paranoia' and 'nervous'. Clozapine cau sed a significant near-syncopal episode in one subject in the study, requir ing his removal from the study. Clozapine had no significant effect on base line pulse rate and systolic blood pressure, but it attenuated the signific ant presser effects of the single dose of intranasal cocaine. These data su ggested a possible therapeutic role for clozapine in the treatment of cocai ne addiction in humans, but also suggests caution due to the near-syncopal event and the increase in serum cocaine levels. (C) 2000 Elsevier Science I reland Ltd. All rights reserved.