The serotonin-2C agonist Lorcaserin delays intravenous choice and modifies the subjective and cardiovascular effects of cocaine: A randomized, controlled human laboratory study

• Published in: Pharmacology, biochemistry and behavior Vol. 180; pp. 52 - 59
• Main Authors: Pirtle, Jimmie L., Hickman, Melissa D., Boinpelly, Varun C., Surineni, Kamalakar, Thakur, Hemant K., Grasing, Kenneth W.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-05-2019
• Subjects: Administration, Intravenous; Administration, Oral; Adult; Benzazepines - administration & dosage; Benzazepines - adverse effects; Benzazepines - pharmacology; Blood Pressure - drug effects; Cocaine - administration & dosage; Cocaine - adverse effects; Cocaine - pharmacology; Cocaine-related disorders; Cocaine-Related Disorders - drug therapy; Craving - drug effects; Cross-Over Studies; Depression, Chemical; Dose-response relationship; Double-Blind Method; Drug interactions; Drug Therapy, Combination; Heart Rate - drug effects; Humans; Infusions; Intravenous; Male; Middle Aged; Self Administration; Serotonin 5-HT2 Receptor Agonists - administration & dosage; Serotonin 5-HT2 Receptor Agonists - adverse effects; Serotonin 5-HT2 Receptor Agonists - pharmacology; Serotonin receptor agonists; Stimulation, Chemical; Treatment Outcome; Vasoconstrictor Agents - administration & dosage; Vasoconstrictor Agents - adverse effects; Vasoconstrictor Agents - pharmacology; Cocaine-related disorders; Self-administration; Intravenous; Serotonin receptor agonists; Drug interactions; Dose-response relationship; Infusions
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/j.pbb.2019.02.010

Lorcaserin is a modestly selective agonist for 2C serotonin receptors (5-HT2CR) approved for weight-loss therapy. This class can attenuate cue-induced responding and drug taking in preclinical studies, but effects in humans have not been reported.
We evaluated effects of single 10 mg doses of lorcaserin on the subjective and reinforcing effects of cocaine, using a randomized, double-blind, within-subject, cross-over design. Male, non-treatment-seeking, regular cocaine users received either single doses of oral placebo (n = 9) or lorcaserin (n = 9), followed by low- or high- doses of intravenous cocaine (0.23 or 0.46 mg/kg-injection). They were then allowed to self-administer the lower dose of cocaine.
Cocaine was well tolerated after lorcaserin pretreatment. Oral lorcaserin did not modify the number of cocaine injections self-administered. However, it prolonged the time over which participants made intravenous choices relative to the duration of monetary (cash) decisions. Lorcaserin increased ratings of ‘high’ and ‘stimulated’ after low-dose cocaine or vehicle, but decreased craving for cocaine after intravenous vehicle. It also caused small but significant increases in heart rate following noncontingent injections of intravenous placebo or cocaine. When active cocaine was self-administered, lorcaserin decreased heart rate after selection of a monetary choice, but increased it following an intravenous choice.
Combined treatment with cocaine and lorcaserin was safe in a limited number of subjects, but did not diminish cocaine-motivated behavior or drug-induced ‘high’. Some positive subjective effects of cocaine were enhanced by lorcaserin, and it delayed intravenous choices and decreased craving under some conditions. Effects on heart rate depended on the type of reinforcer being self-administered.
clinicaltrials.gov Identifier, NCT02680288.
•Lorcaserin is a modestly selective agonist for 2C serotonin receptors (5-HT2CR).•It can attenuate drug taking in animals, but effects in humans are unknown.•Non-treatment-seeking regular cocaine users received single 10 mg doses of lorcaserin.•Neither cocaine self-administration nor ‘high’ were decreased by lorcaserin.•Lorcaserin delayed operant responding and diminished craving under some conditions.