SEROTONERGIC MECHANISMS OF COCAINE EFFECTS IN HUMANS

The objective of this study was to investigate the role of serotonin ( 5-HT) in mediating the effects of cocaine in humans. To accomplish thi s, 12 subjects each participated in two randomized, double-blind test sessions separated by 1 week. In one session, subjects underwent acute depletion of the 5-HT amino acid precursor tryptophan (TRP), followed by a test dose of intranasal cocaine. In the other session, the cocai ne test dose was preceded by sham depletion. Subject ratings of cocain e ''high'' were significantly lower following active TRP depletion tha n after the sham procedure. Subjects also showed an earlier but less s ustained rise in self-rated nervousness during active TRP depletion. T hese findings are consistent with the hypothesis that 5-HT may be invo lved in mediating the euphorigenic and modulating the anxiogenic effec ts of cocaine in humans, either directly or through actions on other ( e.g., dopaminergic) systems.