Cocaine use disorder is a serious public health issue for which there is no effective pharmacotherapy. One strategy to speed development of medications for cocaine use disorder is to repurpose drugs already approved for use in humans based on their ability to interact with targets known to be important for addiction. Two such drugs, lorcaserin (Belviq; a drug with serotonin [5-HT]2C receptor agonist properties) and buspirone (Buspar; a drug with 5-HT1A receptor partial agonist and dopamine D3/D4 receptor antagonist properties) can produce modest decreases in cocaine self-administration in rhesus monkeys. The current study evaluated the effectiveness of mixtures of lorcaserin and buspirone (at fixed dose ratios of 3:1, 1:1, and 1:3 relative to each drug's ID50) to reduce responding for 0.032 mg/kg/inf cocaine under a progressive ratio schedule of reinforcement in 2 male and 2 female rhesus monkeys. Dose addition analyses were used to determine if the effects of the drug mixtures differed from those predicted for an additive interaction between lorcaserin and buspirone. Dose-dependent reductions of cocaine self-administration were observed when lorcaserin and buspirone were administered alone, as well as when they were administered as 3:1, 1:1, and 1:3 fixed ratio mixtures of lorcaserin + buspirone. The effects of the 1:1 mixture of lorcaserin + buspirone on cocaine self-administration were supraadditive, whereas the effects of 3:1 and 1:3 mixtures were additive. Together, these results indicate that a combination therapy containing a mixture of lorcaserin and buspirone might be more effective than either drug alone at treating cocaine use disorder. (PsycINFO Database Record (c) 2018 APA, all rights reserved).