Baclofen does not alter the reinforcing, subject-rated or cardiovascular effects of intranasal cocaine in humans.

摘要

RATIONALE: There is evidence from research in animals and humans that the gamma-aminobutyric acid B receptor subtype (GABA(B)) agonist baclofen may have promise as a pharmacotherapy for cocaine addiction. OBJECTIVES: In the present study, the ability of baclofen to modify the reinforcing, subject-rated and cardiovascular effects of intranasal cocaine in humans was determined. METHODS: Non-treatment-seeking volunteers ( n=7) with recent histories of cocaine use were recruited to participate in this placebo-controlled, double-blind study. Baclofen (0, 10, 20 and 30 mg) was administered orally, followed approximately 1.5 h later by intranasal cocaine (4 mg [placebo] and 45 mg). Subject-rated and cardiovascular measures were taken prior to baclofen administration and then at regular intervals after cocaine was administered. The reinforcing effects of cocaine and cocaine-baclofen combinations were assessed using the Multiple-Choice Procedure. RESULTS: Intranasal cocaine significantly increased the crossoverpoint on the Multiple-Choice Procedure relative to placebo, suggesting that this cocaine dose functioned as a reinforcer. This dose of intranasal cocaine also produced increases in subject-rated effects typical of psychostimulants and elevated cardiovascular measures. The time course for the effects of cocaine was consistent with its pharmacokinetic profile following intranasal administration; increases in subject-rated and cardiovascular effects were observed almost immediately following administration and peaked at approximately 30 min. Pretreatment with baclofen had no significant effect alone, nor in combination with cocaine, on any outcome. CONCLUSIONS: These data demonstrated that acute administration of three clinically relevant baclofen doses did not influence the acute behavioral effects of intranasal cocaine in humans.