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

Abstract

Background: Lorcaserin is a modestly selective agonist for 2C serotonin receptors (5-HT 2C R) 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. Methods and Participants: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.Results: 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

The 5‐HT2C receptor as a therapeutic target for alcohol and methamphetamine use disorders: A pilot study in treatment‐seeking individuals

“…Lorcaserin, in combination with counseling, increased abstinence rates in individuals with nicotine use disorder compared with those treated with smoking cessation counseling alone 44 . However, lorcaserin did not reduce cocaine or oxycodone use compared with placebo controls 45,46 . Lorcaserin also did not improve extended‐release naltrexone induction rates in an outpatient sample of individuals with opioid use disorder compared with placebo 47 .…”

Decline, and Regional Disparities, in Medical Cocaine Usage in the United States

“…Similarly, the amount of cocaine employed as a radioligand in Positron Emission Tomography 29 is minute. In addition to hospital use for medical purposes, ARCOS also reports on the not insignificant volume that is distributed to researchers 30,31 whose use is anticipated to continue.…”

Lorcaserin maintenance fails to attenuate heroin vs. food choice in rhesus monkeys

“…For example, repeated lorcaserin treatment decreased rates of cocaine self-Lorcaserin Effects on Heroin Choice 20 administration under fixed-ratio and progressive-ratio schedules of reinforcement Gerak et al, 2016), but failed to attenuate cocaine-vs.-food choice under a concurrent schedule of reinforcement (Banks and Negus, 2017a) in rhesus monkeys (for review, see ). Recently, lorcaserin failed to attenuate cocaine-vs.-money choice and enhanced subjective effects of cocaine in humans (Pirtle et al, 2019). Although there are currently no published human laboratory studies or clinical trials examining lorcaserin treatment effects on opioid-taking behavior, results from an unpublished human laboratory study found lorcaserin maintenance also failed to attenuate oxycodone-vs.-money choice (Comer, personal communication).…”