scholarly journals Targeting the Endocannabinoid CB1 Receptor to Treat Body Weight Disorders: A Preclinical and Clinical Review of the Therapeutic Potential of Past and Present CB1 Drugs

Biomolecules ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 855 ◽  
Author(s):  
Thomas Murphy ◽  
Bernard Le Foll
Keyword(s):  
Body Weight ◽  
Therapeutic Potential ◽  
Treatment Options ◽  
Endocannabinoid System ◽  
Cb1 Receptor ◽  
Obese Subjects ◽  
Treatment Of Obesity ◽  
Psychiatric Side Effects ◽  
Preclinical And Clinical Studies ◽  
The Impact

Obesity rates are increasing worldwide and there is a need for novel therapeutic treatment options. The endocannabinoid system has been linked to homeostatic processes, including metabolism, food intake, and the regulation of body weight. Rimonabant, an inverse agonist for the cannabinoid CB1 receptor, was effective at producing weight loss in obese subjects. However, due to adverse psychiatric side effects, rimonabant was removed from the market. More recently, we reported an inverse relationship between cannabis use and BMI, which has now been duplicated by several groups. As those results may appear contradictory, we review here preclinical and clinical studies that have studied the impact on body weight of various cannabinoid CB1 drugs. Notably, we will review the impact of CB1 inverse agonists, agonists, partial agonists, and neutral antagonists. Those findings clearly point out the cannabinoid CB1 as a potential effective target for the treatment of obesity. Recent preclinical studies suggest that ligands targeting the CB1 may retain the therapeutic potential of rimonabant without the negative side effect profile. Such approaches should be tested in clinical trials for validation.

scholarly journals Elhízott populációra jellemző talpnyomásminták vizsgálata

2016 ◽  
Vol 157 (48) ◽  
pp. 1919-1925 ◽  
Author(s):  
Eleonóra Leidecker ◽  
Péter Kellermann ◽  
Mónika Galambosné Tiszberger ◽  
Bálint Molics ◽  
Aliz Bohner-Beke ◽  
...  
Keyword(s):  
Body Weight ◽  
Contact Area ◽  
Plantar Pressure ◽  
Peak Pressure ◽  
Maximum Pressure ◽  
Foot Health ◽  
Working Age ◽  
Obese Subjects ◽  
The Impact ◽  
Plantar Area

Introduction: Although the role of body weight on foot health and load has been widely documented in research, the effect of the extra load due to body weight on plantar pressure characteristics is not well known. Aim: The aim of this study was to evaluate the impact of obesity on plantar pressure patterns among the working-age population. Method: 180 participants were involved. Two groups were evaluated according to body mass index categories regarding eight regions of the plantar area, focusing on the following parameters: contact area, maximum pressure and peak pressure. Results: Compared with non-obese subjects, the peak pressure was the highest on the midfoot (p<0.001) and the forefoot (p<0.001). Regarding the maximum force, significant statistical difference was detected on the toes (p<0.001), with a value lower among the obese group. The contact area on the total foot and the midfoot was lower among the non-obese subjects (p<0.001). Conclusions: Loading is greatly increasing on the whole plantar area, especially at the midfoot and the forefoot region. Orv. Hetil., 2016, 157(48), 1919–1925.

scholarly journals Elaiophylin reduces body weight and lowers glucose levels in obese mice by activating AMPK

2021 ◽  
Vol 12 (11) ◽  
Author(s):  
Ruoxuan Bao ◽  
Yongmei Meng ◽  
Haibo Zhang ◽  
Chen Yang ◽  
Wei Li ◽  
...  
Keyword(s):  
Body Weight ◽  
Chronic Diseases ◽  
Therapeutic Potential ◽  
In Vivo Studies ◽  
Pharmacological Intervention ◽  
Obese Mouse ◽  
Acid Oxidation ◽  
Dependent Manner ◽  
Glucose Levels ◽  
Treatment Of Obesity

AbstractObesity is an epidemic affecting 13% of the global population and increasing the risk of many chronic diseases. However, only several drugs are licensed for pharmacological intervention for the treatment of obesity. As a master regulator of metabolism, the therapeutic potential of AMPK is widely recognized and aggressively pursued for the treatment of metabolic diseases. We found that elaiophylin (Ela) rapidly activates AMPK in a panel of cancer-cell lines, as well as primary hepatocytes and adipocytes. Meanwhile, Ela inhibits the mTORC1 complex, turning on catabolism and turning off anabolism together with AMPK. In vitro and in vivo studies showed that Ela does not activate AMPK directly, instead, it increases cellular AMP/ATP and ADP/ATP ratios, leading to AMPK phosphorylation in a LKB1-dependent manner. AMPK activation induced by Ela caused changes in diverse metabolic genes, thereby promoting glucose consumption and fatty acid oxidation. Importantly, Ela activates AMPK in mouse liver and adipose tissue. As a consequence, it reduces body weight and blood glucose levels and improves glucose and insulin tolerance in both ob/ob and high-fat diet-induced obese mouse models. Our study has identified a novel AMPK activator as a candidate drug for the treatment of obesity and its associated chronic diseases.

Investigating the Impact of Deconditioning Anxiety on Weight Loss

1990 ◽  
Vol 66 (2) ◽  
pp. 595-600 ◽  
Author(s):  
William Nagler ◽  
Anne Androff
Keyword(s):  
Eating Disorder ◽  
Progressive Relaxation ◽  
Control Group ◽  
Relaxation Techniques ◽  
Calorie Diet ◽  
Obese Subjects ◽  
Preliminary Study ◽  
Treatment Of Obesity ◽  
The Impact ◽  
Experience Difficulty

The effectiveness of a new model for the treatment of obesity was studied. This model assumed that obesity was not an eating disorder but a “not eating” disorder. Obese individuals do not have a problem eating, they are overly good at it. Obese individuals have a problem not eating. They experience difficulty or anxiety when they do not eat. The model assumed that removal of anxiety associated with “not eating” would allow obese subjects to lose weight. Wolpe and Lazarus' progressive relaxation techniques were used to decondition anxiety assumed associated with “not eating” in subjects. Inferred anxiety was deconditioned under conditions of “not eating” when imagining hunger, emotions, and cravings. Twenty-five subjects were instructed not to follow a diet after deconditioning but to eat less and be hungry to lose weight. A control group of 10 was instructed to follow a balanced 1000-calorie diet to lose weight. The former group lost a statistically significant amount of weight (7.5% of their body weight) over 11.9 months, while the control group subjects gained 6.5% of their weight. The model appears to be effective for the treatment of some individuals who wish to lose weight, based upon this preliminary study. Replication with other and larger groups is essential.

scholarly journals The Role of Endocannabinoid System in Menopause and Its Related-Diseases

2021 ◽  
Vol 8 (4) ◽  
Author(s):  
Torella M ◽  
◽  
Tortora C ◽  
Argenziano M ◽  
Riemma G ◽  
...  
Keyword(s):  
Body Weight ◽  
Cardiovascular Diseases ◽  
Food Intake ◽  
Cancer Progression ◽  
Cannabinoid Receptors ◽  
Ovarian Function ◽  
Endocannabinoid System ◽  
Osteoclast Activity ◽  
Leading Role ◽  
The Impact

Menopause is a crucial event in women’s health, characterized by the cessation of ovarian function. The estrogens deficiency exposes women to several diseases, including obesity, osteoporosis, cardiovascular diseases and cancer. Menopause-related diseases deeply impact on women’s quality of life and represent a serious public and economic health burden. The Endocannabinoid System (ECS) includes Cannabinoid Type 1 (CB1) and Cannabinoid Type 2 (CB2) receptors, endocannabinoids and all the enzymes involved in their biosynthesis and degradation. It plays a significant role in energy balance, bone metabolism, muscular contractility, vascular tone and cancer progression. CB1 activation is responsible for increasing food intake and body weight, stimulating osteoclast activity, inhibiting oxidative stress and preventing cancer progression. Conversely, the stimulation of CB2 induces a reduction in food intake and in body weight, inhibits osteoclast activity, prevents vascular risk and reduces cancer cells proliferation. Moreover, several polymorphic variants of cannabinoid receptors genes are involved into obesity and osteoporosis. In menopause, the alteration of cannabinoid receptors expression and endocannabinoids levels as well as their role in hormone-related pathways could act a leading role in different pathologies (obesity, osteoporosis, cardiovascular diseases and cancer). Therefore, ECS could be considered a possible prognostic marker and a therapeutic target to oppose the harmful effects of these menopause-related diseases. In this review we aimed to summarize the current state-of-knowledge concerning the impact of ECS on major health issues of postmenopausal women.

scholarly journals Leptin, Obesity, and Leptin Resistance: Where Are We 25 Years Later?

Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2704 ◽  
Author(s):  
Andrea G. Izquierdo ◽  
Ana B. Crujeiras ◽  
Felipe F. Casanueva ◽  
Marcos C. Carreira
Keyword(s):  
Body Weight ◽  
Blood Brain Barrier ◽  
Clinical Utility ◽  
Molecular Mechanisms ◽  
Brain Barrier ◽  
Leptin Resistance ◽  
Blood Brain ◽  
Obese Subjects ◽  
Treatment Of Obesity ◽  
New Strategies

Leptin, a hormone that is capable of effectively reducing food intake and body weight, was initially considered for use in the treatment of obesity. However, obese subjects have since been found to have high levels of circulating leptin and to be insensitive to the exogenous administration of leptin. The inability of leptin to exert its anorexigenic effects in obese individuals, and therefore, the lack of clinical utility of leptin in obesity, is defined as leptin resistance. This phenomenon has not yet been adequately characterized. Elucidation of the molecular mechanisms underlying leptin resistance is of vital importance for the application of leptin as an effective treatment for obesity. Leptin must cross the blood–brain barrier (BBB) to reach the hypothalamus and exert its anorexigenic functions. The mechanisms involved in leptin transportation across the blood–brain barrier continue to be unclear, thereby preventing the clinical application of leptin in the treatment of obesity. In recent years, new strategies have been developed to recover the response to leptin in obesity. We have summarized these strategies in this review.

scholarly journals Body Weight After Stroke

Stroke ◽  
2011 ◽  
Vol 42 (12) ◽  
pp. 3646-3650 ◽  
Author(s):  
Nadja Scherbakov ◽  
Ulrich Dirnagl ◽  
Wolfram Doehner
Keyword(s):  
Body Weight ◽  
Nutritional Status ◽  
Metabolic Regulation ◽  
Current Knowledge ◽  
Treatment Options ◽  
Obesity Paradox ◽  
Current Data ◽  
Metabolic Efficiency ◽  
Body Tissues ◽  
The Impact

Background and Purpose— Outcome after acute stroke is determined to a large extent by poststroke complications. Nutritional status and metabolic balance may substantially contribute to outcome after stroke. Key mechanisms of stroke pathophysiology can induce systemic catabolic imbalance with impaired metabolic efficiency and degradation of body tissues. Summary— Tissue wasting, sarcopenia, and cachexia may impair and delay poststroke rehabilitation and worsen the prognosis. Although current guidelines for secondary prevention after stroke recommend weight reduction, increasing evidence suggests that patients who are overweight and mildly obese may actually have a better outcome. An “obesity paradox” has been identified to describe the contrasting impact of being overweight in patients with chronic illness compared with healthy populations. We present an overview on the metabolic regulation in patients with stroke and evaluate current data on the impact of body weight and weight change after stroke. The emerging picture suggests that being overweight and obese may impact patients with stroke differently than it does healthy subjects. Conclusions— We propose that current knowledge on obesity and its management in primary prevention cannot be transferred to patients with established stroke. Systematic studies on changes in body composition after stroke and on treatment options are warranted to establish the pathophysiology and evidence-driven management of nutritional status in these patients.

scholarly journals Overcoming the Psychiatric Side Effects of the Cannabinoid CB1 Receptor Antagonists: Current Approaches for Therapeutics Development

2019 ◽  
Vol 19 (16) ◽  
pp. 1418-1435 ◽  
Author(s):  
Thuy Nguyen ◽  
Brian F. Thomas ◽  
Yanan Zhang
Keyword(s):  
Side Effects ◽  
Large Body ◽  
Cb1 Receptor ◽  
Allosteric Modulators ◽  
Cannabinoid Cb1 Receptor ◽  
Physiological Pathways ◽  
Treatment Of Obesity ◽  
Psychiatric Side Effects ◽  
Anxiety Depression ◽  
Cb1 Receptor Antagonists

The Cannabinoid CB1 Receptor (CB1R) is involved in a variety of physiological pathways and has long been considered a golden target for therapeutic manipulation. A large body of evidence in both animal and human studies suggests that CB1R antagonism is highly effective for the treatment of obesity, metabolic disorders and drug addiction. However, the first-in-class CB1R antagonist/inverse agonist, rimonabant, though demonstrating effectiveness for obesity treatment and smoking cessation, displays serious psychiatric side effects, including anxiety, depression and even suicidal ideation, resulting in its eventual withdrawal from the European market. Several strategies are currently being pursued to circumvent the mechanisms leading to these side effects by developing neutral antagonists, peripherally restricted ligands, and allosteric modulators. In this review, we describe the progress in the development of therapeutics targeting the CB1R in the last two decades.

scholarly journals Personalized treatment of obesity complicated with obstructive sleep apnea syndrome

2014 ◽  
Vol 11 (1) ◽  
pp. 48-52
Author(s):  
N V Strueva ◽  
L V Saveleva ◽  
G A Melnichenko ◽  
M G Poluektov ◽  
N V Gegel
Keyword(s):  
Obstructive Sleep Apnea ◽  
Body Weight ◽  
Sleep Apnea ◽  
Patient Adherence ◽  
Sleep Apnea Syndrome ◽  
Obstructive Sleep ◽  
Osa Treatment ◽  
Treatment Of Obesity ◽  
Clinical Conditions ◽  
The Impact

Obstructive sleep apnea (OSA) and obesity are mutually burdening clinical conditions. Weight loss is quite effective for the control of breathing disorders during sleep, but the impact of OSA treatment on the dynamics of body weight in obese patients remains poorly studied. Presented clinical case features a significant reduction in body weight in a patient with morbid obesity complicated by severe OSA with contemporary approach and without CPAP therapy due to high patient adherence to therapy and absence of comorbidities.

Cannabinoids, Body Weight, Feeding, and Appetite

2017 ◽  
Author(s):  
Linda A. Parker
Keyword(s):  
Body Weight ◽  
Side Effects ◽  
Feeding Behaviour ◽  
Endocannabinoid System ◽  
Homeostatic Regulation ◽  
Reward Circuitry ◽  
Important Regulator ◽  
New Treatments ◽  
Psychiatric Side Effects ◽  
The Brain

The endcoannabinoid system is an important regulator of appetite, food preference and body weight. It not only regulates metabolic feeding related hormones (leptin, ghrelin) in the brain and gut, but also regulates the brain reward circuitry involved in palatability based feeding. One of the primary roles of the endocannabinoid system is in the homeostatic regulation of feeding behaviour. New treatments for obesity are being developed that attempt to harvest the anti-obesity effects of the CB1 antagonist, rimonabant, but that are devoid of the psychiatric side effects that became clearly known only after it was widely prescribed.

scholarly journals The psychiatric side-effects of rimonabant

2009 ◽  
Vol 31 (2) ◽  
pp. 145-153 ◽  
Author(s):  
Fabrício A. Moreira ◽  
José Alexandre S. Crippa
Keyword(s):  
Smoking Cessation ◽  
Side Effects ◽  
Endocannabinoid System ◽  
Cb1 Receptor ◽  
Receptor Antagonists ◽  
Literature Searches ◽  
Antidepressant Effects ◽  
Psychiatric Side Effects ◽  
New Compounds ◽  
Cb1 Receptor Antagonists

OBJECTIVE: Experimental evidence has suggested that drugs that enhance cannabinoid type-1 (CB1) receptor activity may induce anxiolytic and antidepressant effects, whilst the opposite has been reported with antagonists. Thus, the objective of the present review is to discuss the potential psychiatric side-effects of CB1 receptor antagonists, such as rimonabant, which has been recently marketed in several countries for the treatment of smoking cessation, obesity and associated metabolic disorders. METHOD: Literature searches were performed in PubMed and SciELO databases up to February 2009. The terms searched were "obesity", "rimonabant", "cannabinoids", "unwanted effects", "diabetes", "smoking cessation" and "side-effects". RESULTS: Clinical trials have revealed that rimonabant may promote weight loss in obese patients, although it may also induce symptoms of anxiety and depression. DISCUSSION: Patients taking CB1 receptor antagonists should be carefully investigated for psychiatric side-effects. These drugs should not be prescribed for those already suffering from mental disorders. Nevertheless, the development of new compounds targeting the endocannabinoid system for the treatment of several conditions would be necessary and opportune.

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