The endocannabinoid system as a novel approach for managing obesity.

Abstract

“The recent discovery of the endocannabinoid system has led to the development of promising treatments for patients with obesity and associated cardiometabolic risk factors. Basic research has demonstrated that the endocannabinoid system plays an integral role in the regulation of food intake, metabolism, and storage. Research with the endocannabinoid receptor antagonist rimonabant has demonstrated statistically significant improvements in body weight, fasting insulin levels, glucose tolerance, high-density lipoprotein cholesterol levels, serum triglyceride levels, and waist circumference, compared with placebo. Rimonabant has also produced statistically significant improvements in inflammatory markers. Research with rimonabant has demonstrated sustained efficacy for as long as 2 years when used in conjunction with a reduced-calorie diet and moderate physical activity. Rimonabant is the first cannabinoid receptor 1 antagonist to be marketed in Europe and the first to file an New Drug Application in the United States. It may provide a novel therapeutic strategy for the treatment of patients with obesity and associated cardiometabolic risk factors.”

http://www.ncbi.nlm.nih.gov/pubmed/17784530

The endocannabinoid system: its roles in energy balance and potential as a target for obesity treatment.

Abstract

“Obesity and cardiometabolic risk continue to be major public health concerns. A better understanding of the physiopathological mechanisms leading to obesity may help to identify novel therapeutic targets. The endocannabinoid system discovered in the early 1990s is believed to influence body weight regulation and cardiometabolic risk factors. This article aims to review the literature on the endocannabinoid system including the biological roles of its major components, namely, the cannabinoid receptors, their endogenous ligands the endocannabinoids and the ligand-metabolising enzymes. The review also discusses evidence that the endocannabinoid system constitutes a new physiological pathway occurring in the central nervous system and peripheral tissues that has a key role in the control of food intake and energy expenditure, insulin sensitivity, as well as glucose and lipid metabolism. Based on the important finding that there is a close association between obesity and the hyperactivity of the endocannabinoid system, interest in blocking stimulation of this pathway to aid weight loss and reduce cardiometabolic risk factor development has become an important area of research. Among the pharmacological strategies proposed, the antagonism of the cannabinoid receptors has been particularly investigated and several clinical trials have been conducted. One challenging pharmacological task will be to target the endocannabinoid system in a more selective, and hence, safe way. As the management of obesity also requires lifestyle modifications in terms of healthy eating and physical activity, the targeting of the endocannabinoid system may represent a novel approach for a multifactorial therapeutic strategy.”

http://www.ncbi.nlm.nih.gov/pubmed/20541029

Targeted modulators of the endogenous cannabinoid system: future medications to treat addiction disorders and obesity.

Abstract

“The endogenous endocannabinoid system encompasses a family of natural signaling lipids (“endocannabinoids”) functionally related to (9)-tetrahydrocannabinol, the psychoactive ingredient of marijuana (cannabis), along with proteins that modulate the endocannabinoids, including enzymes, transporters, and receptors. The endocannabinoid system’s ubiquitous regulatory actions in health and disease underscore its importance to mammalian (patho)physiology and suggest discrete targets through which it may be modulated for therapeutic gain. Medications based on the endocannabinoid system are an important focus of contemporary translational research, particularly with respect to substance abuse and obesity, two prevalent disorders with a pathogenic component of endocannabinoid system hyperactivity. Pressing health care needs have made the rational design of targeted CB1 cannabinoid-receptor modulators a promising route to future medications with significant therapeutic impact against psychobehavioral and metabolic disturbances having a reward-supported appetitive component.”

http://www.ncbi.nlm.nih.gov/pubmed/17915075

The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis

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“The therapeutic potential of cannabidiol (CBD), the major nonpsychoactive component of cannabis, was explored in murine collagen-induced arthritis (CIA).

CBD was administered after onset of clinical symptoms, and in both models of arthritis the treatment effectively blocked progression of arthritis. CBD was equally effective when administered i.p. or orally.

Clinical improvement was associated with protection of the joints against severe damage.

Taken together, these data show that CBD, through its combined immunosuppressive and anti-inflammatory actions, has a potent anti-arthritic effect in CIA.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC16904/

“In the present study, we report that CBD has a beneficial therapeutic action on established CIA, and we explore its mode of action.”   http://www.pnas.org/content/97/17/9561.long

The effects of hempseed meal intake and linoleic acid on Drosophila models of neurodegenerative diseases and hypercholesterolemia

Molecules and Cells

“Hemp seed is rich in polyunsaturated fatty acids (PUFAs), which have potential as therapeutic compounds for the treatment of neurodegenerative and cardiovascular disease.

In this study, we assessed the effects of the intake of  hempseed meal (HSM) and PUFAs on oxidative stress, cytotoxicity and neurological phenotypes, and cholesterol uptake, using Drosophila models.

HSM intake was shown to reduce H(2)O(2) toxicity markedly, indicating that HSM exerts a profound antioxidant effect.

Meanwhile, intake of HSM, as well as linoleic or linolenic acids (major PUFA components of HSM) was shown to ameliorate Aβ42-induced eye degeneration, thus suggesting that these compounds exert a protective effect against Aβ42 cytotoxicity.

Additionally, intake of HSM or linoleic acid was shown to reduce cholesterol uptake significantly.

Moreover, linoleic acid intake has been shown to delay pupariation, and cholesterol feeding rescued the linoleic acid-induced larval growth delay, thereby indicating that linoleic acid acts antagonistically with cholesterol during larval growth.

In conclusion, our results indicate that HSM and linoleic acid exert inhibitory effects on both Aβ42 cytotoxicity and cholesterol uptake, and are potential candidates for the treatment of Alzheimer’s disease and cardiovascular disease.”

http://www.ncbi.nlm.nih.gov/pubmed/21331775 

“A number of previous studies have shown that polyunsaturated fatty acids (PUFAs) and phytosterols are critically important for human health. Hempseed is a rich source of plant oil, which contains more than 80% PUFAs and 3922-6719 mg/kg of phytosterols (e.g., sitosterol and campesterol). The fatty acids in hempseed oil include a variety of essential fatty acids, including linoleic acid ”

https://link.springer.com/article/10.1007%2Fs10059-011-0042-6

Alzheimer’s disease; taking the edge off with cannabinoids?

“Thus, cannabinoids offer a multi-faceted approach for the treatment of Alzheimer’s disease by providing neuroprotection and reducing neuroinflammation, whilst simultaneously supporting the brain’s intrinsic repair mechanisms by augmenting neurotrophin expression and enhancing neurogenesis. The evidence supporting a potential role for the cannabinoid system as a therapeutic target for the treatment of Alzheimer’s disease will be reviewed herewith.”

http://www.medicalmarijuanainc.com/index.php/alzheimer-s-disease

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2190031/