TRYPTOPHAN DEPLETION AND ATTENUATION OF CUE-INDUCED CRAVING FOR COCAINE

Objective: Although cocaine is a potent serotonin (5-HT) reuptake bloc ker, the role of 5-HT systems in cocaine craving and relapse in humans has been unclear. The authors evaluated whether acute reductions in c entral 5-HT synthesis modulated craving for cocaine in cocaine-depende nt patients. Method: Twenty-five cocaine-dependent male inpatients wer e exposed to cocaine-craving cues while their 5-HT levels were lowered and during a placebo condition in a counterbalanced, double-blind des ign. 5-HT levels were reduced by rapidly lowering plasma levels of its precursor, tryptophan; tryptophan levels were reduced by stimulating protein synthesis with a large drink of amino acids devoid of tryptoph an. During the placebo condition the patients drank an identical amino acid drink containing tryptophan. Craving was induced by exposing pat ients to cocaine paraphernalia and a videotape depicting drug use. Cra ving was assessed 7 hours after ingestion of the drink. Visual analog ratings of craving for cocaine were administered before and after cue exposure at each test session. Results: Patients reported less desire for cocaine stimulated by cue exposure after drinking amino acids with out tryptophan than they did after drinking placebo. The order that tr yptophan depletion and placebo tests were performed influenced the imp act of tryptophan depletion on cue-induced craving. Conclusions: Serot onergic systems modulate cue-induced craving for cocaine, a factor imp licated in relapse to cocaine use.