With the rapid and alarming rise in the obesity epidemic that continues to plague both developed and developing nations, increasing efforts are being directed toward solving this pressing issue that is associated with multiple metabolic complications. Research efforts continue to target this population for greater insight as to causes, preventative measures and treatment options that may provide health benefits to those suffering from the physical and psychological manifestations of this newly classified neurobiological disease, in addition to cut down on excruciating obesity-related costs affecting the current health care budget. Alongside an emphasis on physical activity and proper nutrition to both prevent and ameliorate the effects of obesity, pharmacological treatment has garnered an appreciable appeal as an additional interventional approach in an urgency to slow the progression of this widespread problem. The introduction of lorcaserin (Belviq®), a serotonin (5-hydroxytryptamine, 5-HT) agonist that selectively targets the 5-HT receptor subtype 2C (5-HT2C), has already exhibited great potential for combating the obesity epidemic since it was approved by the Food and Drug Administration (FDA) in 2012. With its ability to decrease appetite and enhance weight loss with few side effects, lorcaserin is a promising treatment option. However, the mechanisms behind the drug are still not fully known. Determining the exact role that lorcaserin plays in appetite control would provide valuable insight into appetite regulation and could illustrate the medication's potential for reversing the health-impairing effects of obesity on our current populations. This study examined, through the use of functional magnetic resonance imaging (fMRI), the effects of lorcaserin on the centers of the brain that control appetite and food intake, in addition to areas of cognition that are thought to be affected by obesity. Due to the nature of the double-blind trial, only baseline characteristics were obtained and analyzed. However, observed correlations from these data largely confirm previously established relationships seen in obese populations providing support for the validity of this study. These correlations were also important to obtain to set the stage for assessing any short-term or long-term neuroimaging changes and neurocognitive effects of lorcaserin on brain responses to high and low calorie food imagery.

Class of 2015 Abstract / Objectives: To retrieve data from RCTs for lorcaserin and phentermine and topiramate combination on weight loss, BMI reduction, and other factors from the placebo groups and to determine if there is a difference in weight loss between those groups. Methods: Design: Meta-analysis Inclusion criteria: RCTs that compared lorcaserin or phentermine/topiramate to placebo as submitted to the FDA and posted to the FDA website. The studies needed to report weight loss or BMI values at baseline and post-treatment. Measures: The primary dependent variables were weight lost in kilograms, change in BMI, and percent who achieved 5% weight loss in the placebo arm. Data Collection: A standardized data collection form was used to extract data from the selected trials. Data was independently extracted by 3 researchers and discrepancies were resolved by consensus. Data Analysis: Data was analyzed by constructing a forest plot of the amount of weight lost in the placebo arm stratified by type of drug. A funnel plot and Kendall’s tau were used to assess publication bias. Heterogeneity was assessed with I2. The a priori alpha level was 0.05. Results: Statistically significant weight loss was achieved in the placebo arm in all 6 RCTs Weight loss was consistent across type of study Lorcaserin studies, mean = 2.42 kg Phentermine/topiramate studies, mean = 2.14 kg Overall rate of 5% weight loss was 0.32 No data was reported on actual caloric intake or actual quantity of exercise Funnel plot and Kendall’s tau (p = 0.85) indicated there was no publication bias There was heterogeneity in the lorcaserin studies resulting from one study reporting a large effect Conclusions: Participants in the placebo arm lost weight with monthly counseling on calorie intake and exercise, however, actual caloric intake or quantity of exercise that resulted in the weight loss is unknown.

Opioids, such as oxycodone, morphine, and fentanyl, are commonly used medications in the treatment of moderate to severe pain. In spite of their efficacious analgesic properties, their increased prescribing rates by physicians and inherent abuse-related effects have led to the ongoing opioid epidemic. Their clinical utility is limited by the risk of adverse dose-dependent side effects, such as constipation and respiratory depression, and the development of tolerance and dependence. Opioid-sparing adjunctive therapies are sought to address these issues by reducing the dose of opioid needed to achieve analgesia through alternative non-opioidergic mechanisms and as a result, reduce the incidence of the previously mentioned side effects. Serotonin type-2C receptor agonists have demonstrated antinociceptive efficacy in preclinical models of chronic pain. Lorcaserin is a selective 5-HT2C receptor agonist and was reported to attenuate the abuse-related effects of oxycodone. The antinociceptive properties of 5-HT2C receptor agonists and their potential to alter the abuse-related effects of commonly abused drugs suggest that lorcaserin may be a potential opioid-sparing therapeutic. The goal of these studies was to evaluate the utility of lorcaserin, in combination with opioids, in a preclinical model of acute pain. Based on previous studies demonstrating the antinociceptive activity of 5-HT2C agonists, the hypotheses for these studies were that lorcaserin would increase the acute antinociceptive effects of opioids and would attenuate the development of tolerance associated with chronic opioid consumption. The results demonstrate that the acute antinociceptive effects and the time-course of activity of opioids were enhanced by doses of lorcaserin. These effects were mediated through activation of the 5-HT2C receptor and were not blocked by administration of naloxone. Additionally, the acute effects of lorcaserin to increase opioid potency and time course was not mediated through changes in opioid distribution in the blood or central tissues. Opioid tolerance was evaluated in vivo, and tolerance was developed using two methods of treatment: an acute (single dose administration) model of tolerance and a multiple-injection model. Testing the effect of lorcaserin in these models was important because current research suggests that the mechanisms that underlie both models of tolerance are distinct from one another. The results demonstrate that lorcaserin significantly blocked the development of acute tolerance in the whole animal and on a single cell level in dorsal root ganglion cell cultures. In the multiple-day tolerance model, lorcaserin partially attenuated the development of opioid antinociceptive tolerance. Chronic administration of an opioid is associated with desensitization of the MOR, and the effect of lorcaserin on opioid tolerance may be mediated through changes in MOR functional activity. Upon further investigation using agonist-stimulated [35S]GTPyS, the results showed that lorcaserin altered basal binding of [35S]GTPyS but not agonist-stimulated binding in mice that received chronic opioid treatment. These data suggest that the effect of lorcaserin on opioid tolerance, in the multiple-injection model, is not mediated through changes in MOR functional activity. Collectively, the tolerance studies suggest that the effect of 5-HT2C receptor activation by lorcaserin has differential effects on the stages of opioid tolerances and further supports the notion that the mechanisms that underlie the stages of opioid tolerance are distinct. Given the efficacy of lorcaserin to increase the acute antinociceptive effects of opioids and its ability to impair the development of opioid tolerance, collectively, these data suggest that lorcaserin may be a useful opioid-sparing adjunctive therapy.

The Side Effects of Drugs Annuals forms a series of volumes in which the adverse effects of drugs and adverse reactions to them are surveyed. The series supplements the contents of Meyler's Side Effects of Drugs: The International Encyclopedia of Adverse Drug Reactions and Interactions. The purpose of this supplement is to provide a concise reference of the newly available literature to support the existing information regarding the known adverse effects of commonly prescribed medications or abused drugs. The information covers peer-reviewed publications from January 2016 to December 2016. This review focused on CNS stimulants and drugs that suppress appetite. It covers amphetamines (including lisdexamfetamine, methamphetamine and 3,4-methylenedioxymetamphetamine), methylphenidate, atomoxetine, modafinil and armodafinil, methylxanthines (caffeine), monotherapies and combinational therapies that suppress appetite (lorcaserin, phentermine, phentermine/topiramate) and medications used in Alzheimer's disease and cognitive decline (rivastigmine, donepezil and memantine).