Lorcaserin for Smoking Cessation and Associated Weight Gain: A Randomized 12-Week Clinical Trial

Shanahan, William R.; Rose, Jed E.; Glicklich, Alan; Stubbe, Scott; Sanchez-Kam, Matilde

doi:10.1093/ntr/ntw301

Cited by 32 publications

(42 citation statements)

References 36 publications

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“…It is likely that under other conditions, e.g., models of binge-eating, the effects of lorcaserin would be magnified. It is nevertheless possible that lorcaserin’s effects on food-maintained responding in the present report, though limited, are related to its projected clinical utility, e.g., for preventing weight gain in smoking cessation programs (e.g., Shanahan et al, 2016). …”

Section: Discussionmentioning

confidence: 79%

“…Additionally, lorcaserin reduced cue-induced reinstatement of extinguished IV nicotine self-administration in rats (Higgins et al, 2012), suggesting potential utility for the reduction of relapse to smoking behavior. These findings have prompted recent Phase II clinical trials with lorcaserin as a stand-alone aid for smoking cessation (Shanahan et al, 2016) or as adjunct pharmacotherapy in combination with the nicotine patch (www.clinicaltrials.gov: NCT02906644).…”

Section: Introductionmentioning

confidence: 99%

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Effects of lorcaserin (Belviq®) on nicotine- and food-maintained responding in non-human primates

Jacobs

Barkin

Kohut³

et al. 2017

Drug and Alcohol Dependence

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Background Accumulating evidence suggests that the FDA-approved serotonin 5HT2C receptor agonist, lorcaserin (Belviq®), may be a promising candidate for the management of substance use disorders, including nicotine addiction. The present study was conducted to determine the efficacy and selectivity of acute or continuous lorcaserin treatment for decreasing the reinforcing effects of nicotine in a primate species. Methods Adult rhesus monkeys (n=4) with a history of nicotine self-administration (>2 years) responded for injections of nicotine (0.32–100 µg/kg IV) or food pellets under a fixed-ratio schedule of reinforcement during daily 100-min sessions. When responding was stable, lorcaserin was administered either as an acute pretreatment (0.1–1.0 mg/kg, IM) or by continuous infusion (0.1 mg/kg/hr, SC for 3–5 days). Daily activity patterns were also monitored immediately following experimental sessions. Results Results indicate that acute lorcaserin pretreatment produced significant and dose-dependent decreases in nicotine-maintained responding across a >100-fold range of self-administered nicotine doses. Continuous lorcaserin treatment decreased intake of 10 µg/kg/inj nicotine to about 50% of baseline values. Food-maintained responding was only moderately decreased in 3 of 4 subjects after acute administration and unaffected in all subjects during continuous treatment. Daily activity also was significantly decreased—to ≤50% of control values—following experimental sessions in which acute lorcaserin was administered. Conclusions These data indicate that lorcaserin reduces IV self-administration of nicotine at a dose that decreases motoric activity but less consistently disrupts food-maintained responding. Further research into lorcaserin’s potential utility for the management of nicotine dependence is warranted.

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Section: Discussionmentioning

confidence: 79%

Section: Introductionmentioning

confidence: 99%

Effects of lorcaserin (Belviq®) on nicotine- and food-maintained responding in non-human primates

Jacobs

Barkin

Kohut³

et al. 2017

Drug and Alcohol Dependence

View full text Add to dashboard Cite

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“…The 5-HT 2C receptor has recently gained attention as a therapeutic target for psychiatric disorders that present with motivational dysfunctions. For example, the 5-HT 2C receptor agonist lorcaserin, which is FDA approved for treating obesity, has shown positive results in a clinical trial for treating nicotine dependence (Shanahan et al, 2016). Further, preclinical studies find that lorcaserin reduces selfadministration of cocaine (Harvey-Lewis et al, 2016) and opiates (Neelakantan et al, 2017), suggesting a general utility in treating substance abuse.…”

Section: Discussionmentioning

confidence: 99%

Pharmacological Modulation of 5-HT2C Receptor Activity Produces Bidirectional Changes in Locomotor Activity, Responding for a Conditioned Reinforcer, and Mesolimbic DA Release in C57BL/6 Mice

Browne

Higgins

et al. 2017

Neuropsychopharmacol

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Converging lines of behavioral, electrophysiological, and biochemical evidence suggest that 5-HT receptor signaling may bidirectionally influence reward-related behavior through an interaction with the mesolimbic dopamine (DA) system. Here we directly test this hypothesis by examining how modulating 5-HT receptor activity affects DA-dependent behaviors and relate these effects to changes in nucleus accumbens (NAc) DA release. In C57BL/6 mice, locomotor activity and responding for a conditioned reinforcer (CRf), a measure of incentive motivation, were examined following treatment with three 5-HT receptor ligands: the agonist CP809101 (0.25-3 mg/kg), the antagonist SB242084 (0.25-1 mg/kg), or the antagonist/inverse agonist SB206553 (1-5 mg/kg). We further tested whether doses of these compounds that changed locomotor activity and responding for a CRf (1 mg/kg CP809101, 0.5 mg/kg SB242084, or 2.5 mg/kg SB206553) also altered NAc DA release using in vivo microdialysis in anesthetized mice. CP809101 reduced locomotor activity, responding for a CRf, and NAc DA release. In contrast, both SB242084 and SB206553 enhanced locomotor activity, responding for a CRf, and NAc DA release, although higher doses of SB206553 produced opposite behavioral effects. Pretreatment with the non-selective DA receptor antagonist α-flupenthixol prevented SB242084 from enhancing responding for a CRf. Thus blocking tonic 5-HT receptor signaling can release serotonergic inhibition of mesolimbic DA activity and enhance reward-related behavior. The observed bidirectional effects of 5-HT receptor ligands may have important implications when considering the 5-HT receptor as a therapeutic target for psychiatric disorders, particularly those presenting with motivational dysfunctions.

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“…Mechanism of action presumably involves activation of hypothalamic POMC neurons (Xu et al, 2008;Berglund et al, 2013), without impacting energy expenditure (Martin et al, 2011). Lorcaserin modulates midbrain dopaminergic tone to suppress binge-related food intake (Higgins et al, 2016) and is now being tested for its ability to treat addictive disorders (Higgins and Fletcher, 2015;Shanahan et al, 2017). A series of CNS-related adverse events such as headache, dizziness, fatigue, and nausea have been linked to Lorcaserin treatment.…”

Section: H Lorcaserinmentioning

confidence: 99%

Anti-Obesity Therapy: from Rainbow Pills to Polyagonists

et al. 2018

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Lorcaserin for Smoking Cessation and Associated Weight Gain: A Randomized 12-Week Clinical Trial

Cited by 32 publications

References 36 publications

Effects of lorcaserin (Belviq®) on nicotine- and food-maintained responding in non-human primates

Effects of lorcaserin (Belviq®) on nicotine- and food-maintained responding in non-human primates

Pharmacological Modulation of 5-HT2C Receptor Activity Produces Bidirectional Changes in Locomotor Activity, Responding for a Conditioned Reinforcer, and Mesolimbic DA Release in C57BL/6 Mice

Anti-Obesity Therapy: from Rainbow Pills to Polyagonists

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