Evaluation of the abuse potential of lorcaserin, a serotonin 2C (5-HT2C) receptor agonist, in recreational polydrug users

Clin Pharmacol Ther. 2011 May;89(5):683-92. doi: 10.1038/clpt.2011.20. Epub 2011 Mar 16.


Lorcaserin is a selective and potent serotonin 2C receptor subtype (5-HT(2C)) agonist under development for the treatment of obesity. This study assessed the drug's abuse potential on the basis of its pharmacological profile. For this purpose, a double-blind, double-dummy, placebo-controlled, randomized seven-way crossover study with single oral doses of lorcaserin (20, 40, and 60 mg), zolpidem (15 and 30 mg), ketamine (100 mg), and placebo was conducted in recreational polydrug users (N = 35). Subjective and objective measures were assessed up to 24 h after the dose. We found that zolpidem and ketamine had significantly higher peak scores relative to placebo on the primary measures as well as on most of the secondary measures. The subjective effects of a 20-mg dose of lorcaserin were similar to those of placebo, whereas supratherapeutic doses of lorcaserin were associated with significant levels of dislike by users as compared with placebo, zolpidem, and ketamine. Perceptual effects were minimal after administration of lorcaserin and significantly lower than after administration of either ketamine or zolpidem. The findings suggest that, at supratherapeutic doses, lorcaserin is associated with distinct, primarily negative, subjective effects and has low abuse potential.

Trial registration: ClinicalTrials.gov NCT00828659.

Publication types

  • Comparative Study
  • Controlled Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Benzazepines / therapeutic use*
  • Cross-Over Studies
  • Double-Blind Method
  • Female
  • Humans
  • Illicit Drugs*
  • Ketamine / therapeutic use
  • Male
  • Middle Aged
  • Obesity / drug therapy
  • Obesity / psychology
  • Pyridines / therapeutic use
  • Serotonin 5-HT2 Receptor Agonists / therapeutic use*
  • Substance-Related Disorders* / diagnosis
  • Substance-Related Disorders* / prevention & control
  • Young Adult
  • Zolpidem


  • Benzazepines
  • Illicit Drugs
  • Pyridines
  • Serotonin 5-HT2 Receptor Agonists
  • lorcaserin
  • Ketamine
  • Zolpidem

Associated data

  • ClinicalTrials.gov/NCT00828659