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Oral Nutritional Supplements and Appetite Stimulation Therapy
Published in Michael M. Rothkopf, Jennifer C. Johnson, Optimizing Metabolic Status for the Hospitalized Patient, 2023
Michael M. Rothkopf, Jennifer C. Johnson
This class includes pharmaceuticals and natural products. Cannabinoids (CBs) are believed to act through CB receptors within the central nervous system, specifically CB1 (Zou and Kumar 2018). Blocking the CB1 receptor was shown to induce anorexia and was the basis for the weight loss drug rimonabant (never approved in the US). Stimulating this receptor seems to induce orexia (Osei-Hyiaman et al. 2005). CBs may also inhibit emesis through brainstem responses and suppress the synthesis and activity of some prostaglandins.
Endogenous Cannabinoid Receptors and Medical Cannabis
Published in Sahar Swidan, Matthew Bennett, Advanced Therapeutics in Pain Medicine, 2020
Where significant patient outcome problems have been seen is with drugs that block cannabinoid receptor activity. The role of endocannabinoids in metabolism and appetite has made the ECS a target for the development of drugs to treat metabolic syndrome. Rimonabant (Acomplia® or SR141716) is one such drug that works as an inverse agonist at CB1 to reduce hunger and weight gain, but at considerable cost to overall endocannabinoid tone. Although weight loss was documented with rimonabant, serious adverse side effects included nausea, seizures, depression, and suicidality, leading to withdrawal of the drug after two years on the foreign market.79 In this case, drug development failed to appreciate the full extent of the CB1 endocannabinoid receptor’s broad range of non-specific central effects.
Obesity
Published in Geoffrey P. Webb, Nutrition, 2019
Rimonabant is a new type of anti-obesity agent that was licensed for a short period for use in the UK. This compound blocks the endocannabinoid receptors in the brain where active ingredients of cannabis (cannabinoids) bind and where endogenously produced cannabinoids also bind. Endogenous cannabinoids and those taken in the form of cannabis are known to increase appetite – the increased appetite associated with cannabis use is sometimes referred to as “the munchies”. This drug was licensed in 2006 in the UK after successful clinical trials in the USA and in Europe and was for a time licensed for use in over 50 countries. A Cochrane review by Curioni and Andre (2006) included a meta-analysis of four controlled trials of rimonabant for weight loss. A daily dose of 20 mg of rimonabant for a year resulted in around 5 kg more weight loss than a placebo and improved several cardiovascular risk factors. A 5 mg dose had much less effect upon weight loss and cardiovascular risk factors. At the higher dose, there were significant numbers of adverse effects reported which were mainly psychiatric and gastrointestinal problems. Rimonabant was withdrawn from sale in 2008 and its approval withdrawn because its beneficial effects did not outweigh its adverse effects, particularly its adverse psychiatric effects.
The function of the endocannabinoid system in the pancreatic islet and its implications on metabolic syndrome and diabetes
Published in Islets, 2023
Edgardo Cortes-Justo, Sergio H Garfias-Ramírez, Alonso Vilches-Flores
The synthetic compound SR141716A, also called rimonabant, is a highly selective antagonist for CB1 receptor, suggested for the treatment of overweight, obesity and diabetes, but suspended until today.42,60,61 Clinical studies demonstrated rimonabant reduced significantly adipose mass on obese and diabetic patients, increasing adiponectin expression, lipolysis, and decreasing pro-inflammatory and other cardiovascular risk factors.60–64 The study of rimonabant in obesity (RIO) showed several benefits in obese and non-obese patients: 20 mg/day treatment improved carbohydrate and lipid metabolisms in peripheral tissues, mainly skeletal muscle, adipose tissue and liver.63 The effects on insulin secretion and sensitivity induced a significant reduction in glycated hemoglobin percent and LDL level.63
Novel therapeutic and drug development strategies for tobacco use disorder: endocannabinoid modulation
Published in Expert Opinion on Drug Discovery, 2020
Arguably one of the most promising candidates for smoking cessation in recent years was rimonabant, an anti-obesity drug and inverse agonist at the cannabinoid (CB) receptor 1. Indeed, abstinence at the end of 10 weeks of treatment with rimonabant (20 mg/day) and at 48 weeks follow-up was higher than placebo in a pooled analysis of three randomized double-blind controlled trials [17]. However, the high rate of psychiatric side effects, notably the induction of anxiety and depression and risk of emergence of suicidal ideation [18], led to the voluntary withdrawal of rimonabant from the European market in 2008 [19]. Nevertheless, there is an increasing understanding of the role of the endocannabinoid system in reward processing and addiction [20,21] suggesting that there may still be potential tobacco smoking cessation candidates found that work via endocannabinoid modulation.
The limits and challenges of antiobesity pharmacotherapy
Published in Expert Opinion on Pharmacotherapy, 2020
Kishore M Gadde, Katelyn D Atkins
In 2007, the FDA issued an updated guidance which also recommended that new antiobesity drugs be tested in a dedicated phase 3 trial of overweight/obese patients with T2D [15]. Between 1997 and 1999, sibutramine and orlistat were approved for long-term obesity treatment. In 2006, rimonabant, a cannabinoid receptor-1 (CB-1) antagonist, failed to win FDA advisory committee recommendation due to high incidence of psychiatric adverse events [16], although it was already approved by the European Medicines Agency (EMA). In 2008, rimonabant was withdrawn from Europe and other markets as more reports confirmed the increased risk of depression and suicidal ideation with the drug [17]. Sibutramine was withdrawn in the US and several countries in 2010 following review of the results of a cardiovascular outcomes trial (CVOT) among patients with preexisting CVD or those at high risk. The results of this trial revealed a slightly increased risk of major adverse cardiovascular events (MACE) in the drug group compared with the placebo group (11.4% vs 10.0%; hazard ratio, 1.16; 95% CI, 10.3–1.31; P = 0.02), corresponding to approximately 4 excess events per 1,000 patient years [18]. Nevertheless, sibutramine remains legally marketed in a few countries, e.g., Russia [19]. In 2010, three new antiobesity drugs – phentermine plus topiramate, lorcaserin, and naltrexone plus bupropion – failed to win FDA approval, but were subsequently approved between 2012 and 2014 along with liraglutide 3.0 mg (higher than the 1.8 mg dose approved for T2D).