Methods This is a randomized, cross-over, double-blind, placebo-controlled, single-center, multiple-panel evaluation of the potential for oral lorcaserin to modify cocaine self-administration in a laboratory setting. Up to 32 non-treatment-seeking, regular cocaine users will receive treatment with single doses of oral placebo, lorcaserin 10 mg (Panel 1), or lorcaserin 20 mg (Panel 2). Script-guided imagery of autobiographical memories will be developed based on experiences related to cocaine use, anger, and a neutral event. Following treatment with lorcaserin, script-induced emotional states will be assayed. Sampling doses of cocaine (0.0, 0.23, and 0.46 mg/kg) will be administered, and participants will choose between self-administering additional intravenous doses or receiving monetary alternatives. Detailed measures of the negative and positive subjective effects of intravenous infusions will also be made. As noncontingent infusions of cocaine are administered, the pharmacokinetics of cocaine and lorcaserin will be determined.