Abstract   Cannabinoids have been increasingly gaining attention for their therapeutic potential in treating various cardiovascular disorders. These disorders include myocardial infarction, hypertension, atherosclerosis, arrhythmias, and metabolic disorders. The aim of this review is to cover the main actions of cannabinoids on the cardiovascular system by examining the most recent advances in this field and major literature reviews. It is well recognized that the actions of cannabinoids are mediated by either cannabinoid 1 or cannabinoid 2 receptors (CB2 Rs). Endocannabinoids produce a triphasic response on blood pressure, while synthetic cannabinoids show a tissue‑specific and species‑specific response. Blocking cannabinoid 1 receptors have been shown to...

Abstract The purpose of this review is to examine human and preclinical data that are relevant to the following hypotheses. The first hypothesis is that deficient CB1R-mediated signaling results in symptoms that mimic those seen in depression. The second hypothesis is that activation of CB1R-mediated signaling results in behavioral, endocrine and other effects that are similar to those produced by currently used antidepressants. The third hypothesis is that conventional antidepressant therapies act through enhanced CB1R mediated signaling. Together the available data indicate that activators of CB1R signaling, particularly inhibitors of fatty acid amide hydrolase, should be considered for clinical trials for the treatment of...

Abstract The endocannabinoid system (eCS), is a complex system, comprising the main endogenous ligands anandamide and 2-arachidonoyl glycerol, the cannabinoid receptors CB1 and CB2 and the biosynthetic and degrading enzymes. Cumulative evidence shows that the eCS plays an important role in reproduction, from egg fertilization to parturition. Therefore, alterations in this system, either by recreation/therapeutic use of cannabis or deregulation of the endogenous cannabinoids, might lead to adverse pregnancy outcomes, including retardation in embryo development, poor blastocyst implantation, inhibition of decidualization, miscarriage and compromised placentation. Nevertheless, the molecular mechanisms by which the eCS participates in different stages of pregnancy remain poorly understood. In this...

Abstract Introduction: We recently uncovered a signaling mechanism by which the endocannabinoid anandamide mediates the action of oxytocin, a neuropeptide that is crucial for social behavior, to control social reward. Oxytocin signaling has been implicated in autism spectrum disorder (ASD), and social reward is a key aspect of social functioning that is thought to be disrupted in ASD. Therefore, as a proof of principle for the core component of ASD—social impairment—we tested an endocannabinoid-enhancing compound on two widely studied mouse models of ASD, the BTBR and fmr1/ (model of Fragile X Syndrome). Methods: We used the established three-chambered social approach test. We specifically increased...

There has been increasing interest in the role of endocannabinoids as critical modulators of the female reproductive processes. Endocannabinoids are natural ligands of cannabinoid, vanilloid, and peroxisome proliferator-activated receptors. Together with their receptors, enzymes and downstream signaling targets, they form the endocannabinoid system (ECS). While the ECS is known to modulate pain and neurodevelopment, it is also known to impact the female reproductive system where it affects folliculogenesis, oocyte maturation, and ovarian endocrine secretion. In addition, the ECS affects oviductal embryo transport, implantation, uterine decidualization and placentation. There is a complex interplay between the ECS and the hypothalamic-pituitary-ovarian axis, and an intricate crosstalk between...

The marijuana plant Cannabis sativa and its derivatives,cannabinoids, have grown increasingly popular as a potential therapy for inflammatory bowel disease (IBD). Studies have shown that modulation of the endocannabinoid system, which regulates various functions in the body and has been shown to play a key role in the pathogenesis of IBD, has a therapeutic effect in mouse colitis. Epidemiologic data and human therapy studies reveal a possible role for cannabinoids in the symptomatic treatment of IBD, although it has yet to be determined in human populations whether cannabinoids have therapeutic anti-inflammatory effects in IBD or are simply masking its many debilitating symptoms. Large, doubleblind,...

Modulating the activity of the endocannabinoid system influences various gastrointestinal physiological and pathophysiological processes, and cannabinoid receptors as well as regulatory enzymes responsible for the synthesis or degradation of endocannabinoids representing potential targets to reduce the development of gastrointestinal mucosal lesions, hemorrhage and inflammation. Direct activation of CB1 receptors by plant-derived, endogenous or synthetic cannabinoids effectively reduces both gastric acid secretion and gastric motor activity, and decreases the formation of gastric mucosal lesions induced by stress, pylorus ligation, nonsteroidal anti-inflammatory drugs (NSAIDs) or alcohol, partly by peripheral, partly by central mechanisms. Similarly, indirect activation of cannabinoid receptors through elevation of endocannabinoid levels by globally...

Endocannabinoids act as a major neuromodulatory system in a variety of physiological and behavioral functions. Three major lines of evidence suggest that the endocannabinoid system interacts with gonadal hormones. First, the endocannabinoid system is implicated in behaviors and physiological functions that are known to be regulated in part by gonadal hormones. Second, receptors and metabolic enzymes of the endocannabinoid system are localized extensively on structures in the hypothalamic-pituitary-gonadal axis. Third, changes in levels of gonadal hormones alter endocannabinoid signaling. Here we reviewed and summarized the current evidence regarding the interaction between the endocannabinoid system and androgens, estrogens, and progesterone. Overall, it appears that bidirectional...

Our understanding of the Endocannabinoid System of animals, and its ubiquitous presence in nearly all members of Animalia, has opened the door to novel approaches targeting pain management, cancer therapeutics, modulation of neurologic disorders, stress reduction, anxiety management, and inflammatory diseases. Both endogenous and exogenous endocannabinoid-related molecules are able to function as direct ligands or, otherwise, influence the EndoCannabinoid System (ECS). This review article introduces the reader to the ECS in animals, and documents its potential as a source for emerging therapeutics.

Abstract Experimental data suggest that the endogenous cannabinoid system is involved in gastric function in different animal species. In most of them, CB1 receptors have been localized on vagal terminals innervating the external wall of the stomach. We aimed at studying the putative presence and distribution of these receptors in the human gastric mucosa. To this end, we first performed Western blotting, RT-PCR, in situ hybridization, and immunohistochemical analysis of CB1 protein distribution in biopsy samples of healthy individuals. To determine the precise cell populations expressing CB1 receptors, we performed double immunofluorescence plus confocal microscopy analysis of the same samples. Our results show that CB1 receptors are present...