The endocannabinoid system and its therapeutic exploitation

Marzo, Vincenzo Di; Bifulco, Maurizio; Petrocellis, Luciano De

doi:10.1038/nrd1495

Cited by 970 publications

(837 citation statements)

References 151 publications

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“…The most likely hypothesis accounting for similar changes of circulating AEA in individuals who are at the opposite of the ED spectrum is provided by the observed changes in leptin signalling. In fact, leptin has been shown to inhibit endogenous AEA levels in both rodent brain and uterus and human blood (Maccarrone et al, 2003;Di Marzo et al, 2004;Maccarrone et al, 2005), and since its plasma concentration was drastically reduced in underweight subjects with AN, it is likely that increased levels of plasma AEA in these patients were secondary to their leptin deficiency. In patients with BED, where an increase in leptin production occurred because of their enhanced fat stores, one would expect decreased rather than enhanced plasma levels of AEA.…”

Section: Discussionmentioning

confidence: 99%

“…The endocannabinoid system (Di Marzo et al, 2004), consisting of two cannabinoid receptors (CB 1 and CB 2 ) and the endogenous ligands anandamide (arachidonoylethanolamide (AEA)) and 2-arachidonoylglycerol (2-AG), has been shown to control feeding in both animals and humans (Cota et al, 2003). Indeed, both exogenous and endogenous cannabinoids stimulate food intake through several mechanisms.…”

Section: Introductionmentioning

confidence: 99%

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Blood Levels of the Endocannabinoid Anandamide are Increased in Anorexia Nervosa and in Binge-Eating Disorder, but not in Bulimia Nervosa

Monteleone

Matías

Martiadis

et al. 2005

Neuropsychopharmacol

244

149

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The endocannabinoid system, consisting of two cannabinoid receptors (CB 1 and CB 2 ) and the endogenous ligands anandamide (arachidonoylethanolamide (AEA)) and 2-arachidonoylglycerol (2-AG), has been shown to control food intake in both animals and humans, modulating either rewarding or quantitative aspects of the eating behavior. Moreover, hypothalamic endocannabinoids seem to be part of neural circuitry involved in the modulating effects of leptin on energy homeostasis. Therefore, alterations of the endocannabinoid system could be involved in the pathophysiology of eating disorders, where a deranged leptin signalling has been also reported. In order to verify this hypothesis, we measured plasma levels of AEA, 2-AG, and leptin in 15 women with anorexia nervosa (AN), 12 women with bulimia nervosa (BN), 11 women with binge-eating disorder (BED), and 15 healthy women. Plasma levels of AEA resulted significantly enhanced in both anorexic and BED women, but not in bulimic patients. No significant change occurred in the plasma levels of 2-AG in all the patients' groups. Moreover, circulating AEA levels were significantly and inversely correlated with plasma leptin concentrations in both healthy controls and anorexic women. These findings show for the first time a derangement in the production of the endogenous cannabinoid AEA in drug-free symptomatic women with AN or with BED. Although the pathophysiological significance of this alteration awaits further studies to be clarified, it suggests a possible involvement of AEA in the mediation of the rewarding aspects of the aberrant eating behaviors occurring in AN and BED.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Blood Levels of the Endocannabinoid Anandamide are Increased in Anorexia Nervosa and in Binge-Eating Disorder, but not in Bulimia Nervosa

Monteleone

Matías

Martiadis

et al. 2005

Neuropsychopharmacol

244

149

View full text Add to dashboard Cite

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“…In addition, the development of 'neutral' CB 1 antagonists, that do not show any significant signs of inverse agonism, has provided very promising results at the preclinical level, particularly in terms of their reversal of insulin and leptin resistance (105) . Furthermore, in the light of the fact that the increased endocannabinoid tone observed in metabolic disorders can be attributed to increased endocannabinoid biosynthesis, an alternative strategy to regulate dysregulated endocannabinoid tone in obesity might be to use DAGL inhibitors with consequent reduction in 2-AG biosynthesis (106) .…”

Section: Endocannabinoids In Obesitymentioning

confidence: 99%

“…It was 1992 when the first endocannabinoid was isolated from brain and named anandamide (from Sanskrit word ananda 'supreme joy') (2,3) . This is the ethanolamide of arachidonic acid, and is thought to be a partial CB 1 and CB 2 receptor agonist as well as a transient receptor potential vanilloid (TRPV)1 receptor agonist (2,(4)(5)(6) . The other widely investigated endocannabinoid, 2-arachidonoylglycerol (2-AG), is the arachidonate ester of glycerol that was isolated from peripheral tissues.…”

mentioning

confidence: 99%

PUFA-derived endocannabinoids: an overview

Cascio

2013

Proc. Nutr. Soc.

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Following on from the discovery of cannabinoid receptors, of their endogenous agonists (endocannabinoids) and of the biosynthetic and metabolic enzymes of the endocannabinoids, significant progress has been made towards the understanding of the role of the endocannabinoid system in both physiological and pathological conditions. Endocannabinoids are mainly n-6 long-chain PUFA (LCPUFA) derivatives that are synthesised by neuronal cells and inactivated via a two-step process that begins with their transport from the extracellular to the intracellular space and culminates in their intracellular degradation by hydrolysis or oxidation. Although the enzymes responsible for the biosynthesis and metabolism of endocannabinoids have been well characterised, the processes involved in their cellular uptake are still a subject of debate. Moreover, little is yet known about the roles of endocannabinoids derived from n-3 LCPUFA such as EPA and DHA. Here, I provide an overview of what is currently known about the mechanisms for the biosynthesis and inactivation of endocannabinoids, together with a brief analysis of the involvement of the endocannabinoids in both food intake and obesity. Owing to limited space, recent reviews will be often cited instead of original papers.

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“…5,6 Unlike most intercellular signaling systems, the endocannabinoids are made on demand. The biosynthetic pathways for their synthesis and subsequent degradation have now been identified and the distribution of these enzymes suggests, at least in parts of the central nervous system, that they represent a class of key regulators that shape synaptic responses over spatially and temporally restricted areas.…”

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confidence: 99%

Endocannabinoids: biology, mechanism of action and functions

Sharkey

2006

Int J Obes

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The isolation and identification of endogenous cannabinoid ligands (endocannabinoids) as a family of intercellular signaling molecules that act at the same receptors as the plant-derived cannabinoids has significantly changed our understanding of cellular physiology and metabolism. In the early 1990s, two G-protein coupled receptors termed the cannabinoid CB-1 receptor (CB 1 ) and CB-2 receptor (CB 2 ) were isolated and cloned. 1 Their widespread distribution in the central and peripheral nervous system (CB 1 receptor) and the immune system (CB 2 receptor) led to a search, and subsequent identification, for endogenous ligands of these receptors. In 1992, arachidonoylethanolamide (anandamide) was discovered and shown to be a specific receptor agonist for the CB 1 receptor (subsequently it was also found to be a CB 2 receptor agonist). 2 After 3 years, 2-arachidonoylglycerol (2-AG) was shown to be a second endocannabinoid with efficacy at both CB receptors. 3,4 A number of other putative endocannabinoids have now been proposed. Some 10 years after their isolation, the role of endocannabinoids in regulating food intake and energy balance has been widely recognized, leading to the organization of a symposium, whose proceedings are reported in this issue of International Journal of Obesity. Four speakers, whose presentations are summarized in the reviews following this article, covered the biology, physiology and pharmacology of the endocannabinoids and their receptors; focusing on the role of endocannabinoids in energy homeostasis. In this short overview, a perspective on these topics will be provided.The endocannabinoid family is expanding and now includes both endogenous agonists and a putative endogenous antagonist, virodhamine. 5,6 Unlike most intercellular signaling systems, the endocannabinoids are made on demand. The biosynthetic pathways for their synthesis and subsequent degradation have now been identified and the distribution of these enzymes suggests, at least in parts of the central nervous system, that they represent a class of key regulators that shape synaptic responses over spatially and temporally restricted areas. 7 As pointed out by Matias et al. in their article, many of the biosynthetic enzymes, transporters, intracellular binding proteins (if they exist) and degradative systems have still to be fully described in most of the systems, especially in the periphery, in which endocannabinoids are thought to play key roles. The balance between synthesis, reuptake and degradation represents the limiting factor for the duration of action of endocannabinoids. The conditions for activation of endocannabinoid synthesis are not fully established, particularly concerning the plethora of potential cellular mediators, which may enhance or initiate their synthesis through increasing intracellular calcium. Drugs that increase the apparent extracellular concentrations of the endocannabinoids by inhibiting their uptake into cells have been very valuable tools that have helped establish many physiological or path...

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The endocannabinoid system and its therapeutic exploitation

Cited by 970 publications

References 151 publications

Blood Levels of the Endocannabinoid Anandamide are Increased in Anorexia Nervosa and in Binge-Eating Disorder, but not in Bulimia Nervosa

Blood Levels of the Endocannabinoid Anandamide are Increased in Anorexia Nervosa and in Binge-Eating Disorder, but not in Bulimia Nervosa

PUFA-derived endocannabinoids: an overview

Endocannabinoids: biology, mechanism of action and functions

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