Lorcaserin Hydrochloride

Cocaine use disorder (CUD) is a major public health problem for which there is no approved pharmacotherapy. The primary purpose of this study was to evaluate the ability of lorcaserin, a 5-hydroxytryptamine_2 C (5-HT_2 C) receptor agonist, to facilitate abstinence in individuals seeking treatment for CUD.

This was a 12-site, randomized, parallel arm study with a 13-week Treatment Phase that included a 1-week, single-blind run-in period when all participants received twice daily 15mg acetazolamide capsules (a medication adherence marker), followed by randomization to either twice daily 10mg lorcaserin or placebo capsules for the remaining 12 weeks. Pre-randomization data were utilized in an enrichment strategy aimed at achieving high levels of medication adherence and low placebo response rates in a subgroup of participants that qualified for the "efficacy population." For lorcaserin vs. placebo, the primary efficacy endpoint was the proportion of participants in the efficacy population achieving abstinence during the last three weeks of treatment, as evidenced by self-report of no cocaine use, confirmed by urine testing.

Within the efficacy population, 1.1% of 91 participants receiving lorcaserin and 4.3% of 92 receiving placebo achieved abstinence during the last 3 weeks of treatment. Among all randomized participants, 2.5% of 118 receiving lorcaserin and 5.6% of 124 receiving placebo achieved similar abstinence. Study participants receiving lorcaserin exhibited significantly greater reductions in body weight and BMI, indicating that medication adherence was sufficient to produce a pharmacological effect.

Twice daily 10mg lorcaserin failed to demonstrate efficacy in the treatment of CUD.

Lorcaserin, a selective serotonin 2C (5-HT_2C) receptor agonist, was approved for treating obesity and has been investigated for treating substance use disorders including those involving opioids. Although lorcaserin was withdrawn from the market, interest in the therapeutic potential of drugs acting at 5-HT_2C receptors continues, supporting the need to further characterize potential adverse effects especially when combined with drugs of abuse. This study examined acute effects of lorcaserin on opioid-induced ventilatory depression, which is the primary cause of overdose, and opioid self-administration, which models factors contributing to opioid abuse, in male and female rhesus monkeys. In one group (n = 4), effects of morphine (0.178 to 5.6 mg/kg, s.c.), fentanyl (0.0032 to 0.1 mg/kg, s.c.), and lorcaserin (0.1 to 1.78 mg/kg, s.c.) alone as well as effects of lorcaserin with each opioid on ventilation were determined using head plethysmography. Another group (n = 5) responded under a food versus fentanyl (0.1 to 3.2 μg/kg/infusion, i.v.) choice procedure, and lorcaserin (0.32 to 1.78 mg/kg, i.v.) was given as a pretreatment. Lorcaserin dose-dependently decreased minute volume to below 70 % of baseline when administered alone and increased the potency of morphine and fentanyl. Consistent with previous studies, lorcaserin failed to alter choice of fentanyl over food. This study demonstrates the novel finding that lorcaserin alone decreases ventilation and enhances the ventilatory-depressant effects of opioids. Taken together with previous studies, these results suggest that combining a 5-HT_2C receptor agonist such as lorcaserin with an opioid could increase the risk of ventilatory depression without the benefit of decreasing abuse.