, nearly all TRPV1-expressing neurons had anti-CB1 immuno- reactivity in wild-type and CB1 fl mice -TRPV1 TRPV1 Overlay -CB1 -Nav1.8 Nav1.8 Overlay CB1 � Wt CB1-expressingcells (%total) ...

Three-dimensional quantitative structure-selectivity relationships analysis guided rational design of a highly selective ligand for the cannabinoid receptor 2. ... Probing the cannabinoid CB1/CB2 receptor subtype selectivity limits of ...

The endocannabinoid system consists of the endogenous cannabinoids (endocannabinoids), cannabinoid receptors and the enzymes that synthesise and degrade endocannabinoids. Many of the effects of cannabinoids and endocannabinoids are mediated by two G protein-coupled receptors (GPCRs), CB(1) and ...

Extended access to cocaine produces an increase in cocaine self-administration in rats that mimics aspects of compulsive drug intake in human addicts. While emerging evidence implicates the endogenous cannabinoid system in aspects of opioid and ethanol addiction, a role of the endocannabinoid system in cocaine addiction remains largely inconclusive. Here, we investigate the ...

% in controlizing step is displayed below on an expanded time scale (B2) to slices, n 17, control data not shown; p.C., and Walker, J.M. (1999). Cannabinoid CB1 receptors are localized primarily on cholecysto- kinin signalinhibition" (DSI). Here, we report that DSI is absent in mice which lack cannabinoid ...

Corneal epithelial injury induces release of endogenous metabolites that are cannabinoid receptor 1 (CB1) and transient receptor potential vanilloid 1 (TRPV1) agonists. We determined the functional contributions by CB1 and TRPV1 activation to eliciting re...

Anandamide is an endogenous ligand at both the inhibitory cannabinoid CB(1) receptor and the excitatory vanilloid receptor 1 (VR1). The CB(1) receptor and vanilloid VR1 receptor are expressed in about 50% and 40% of dorsal root ganglion neurons, respectively. While all vanilloid VR1 receptor-expressing cells belong to the calcitonin ...

Chronic cannabis (marijuana, hashish) smoking can result in dependence. Rodent studies show reversible downregulation of brain cannabinoid CB(1) (cannabinoid receptor type 1) receptors after chronic exposure to cannabis. However, whether downregulation occurs in humans who chronically smoke cannabis is unknown. ...

The endogenous cannabinoid system is involved in the regulation of the central reward pathway. Running wheel and sucrose consumption have rewarding and reinforcing properties in rodents, and share many neurochemical and behavioral characteristics with drug addiction. In this study, we investigated whether running wheel or sucrose consumption altered the sensitivity of striatal ...

The cannabinoid receptor type 1 (CB1) and its endogenous ligands, the endocannabinoids, are involved in the regulation of food intake. Here we show that the lack of CB1 in mice with a disrupted CB1 gene causes hypophagia and leanness. As compared with WT ...

Cannabinoid drugs exert their effects primarily through activation of cannabinoid CB1 and CB2 receptors. Both CB1 and CB2 receptors have been implicated in a number of cardiovascular processes, including vasodilation, cardiac protection, modulation of the baroreceptor ...

Cannabinoids have been used medicinally and recreationally for thousands of years and their effects were proposed to occur mainly via activation of the G-protein-coupled receptor CB1/CB2 (cannabinoid receptor 1/2). Discovery of potent synthetic analogs of the natural cannabinoids as clinically ...

Cannabinoids are cell membrane-derived signalling molecules that are released from nerves, blood cells and endothelial cells, and have diverse biological effects. They act at two distinct types of G-protein-coupled receptors, cannabinoid CB(1) and CB(2) receptors. Cannabinoid ...

Cannabinoids, the active components of the hemp plant Cannabis sativa, along with their endogenous counterparts and synthetic derivatives, have elicited anti-cancer effects in many different in vitro and in vivo models of cancer. While the various cannabinoids have been examined in a variety of cancer models, recent studies have focused on the role of ...

amine, is conju- gated with arachidonic acid in the brain and the spinal cord to form the potent TRPV1 to increased levels of endogenous cannabinoids (11�15). TRPV1 and cannabinoid CB1 receptors are both pres- ent-fos in the spinal cord of neuro- pathic rats, an effect inhibited by both TRPV1 and ...

CB1 receptor antagonists that are peripherally restricted were targeted. Compounds with permanent charge as well as compounds that have increased polar surface area were made and tested against CB1 for binding and activity. Sulfonamide and sulfamide with high polar surface area and good activity at CB1 were ...

The cannabinoid CB1 receptor system is critically involved in the control of associative fear memory formation within the amygdala-prefrontal cortical pathway. The CB1 receptor is found in high concentrations in brain structures that are critical for emotional processing, including the basolateral amygdala (BLA) and the prelimbic ...

Cannabinoid agonists exert complex actions on modulatory neurotransmitters involved in attention and cognition. Previous studies have demonstrated that acute systemic administration of the synthetic cannabinoid agonist, WIN 55,212-2, increases norepinephrine efflux in the rat frontal cortex. In an effort to elucidate whether ...

Cannabinoid agonists exert complex actions on modulatory neurotransmitters involved in attention and cognition. Previous studies have demonstrated that acute systemic administration of the synthetic cannabinoid agonist, WIN 55,212-2, increases norepinephrine efflux in the rat frontal cortex. In an effort to elucidate whether ...

MJ15, a novel cannabinoid CB(1) receptor selective antagonist was discovered. In receptor binding assays, MJ15 displayed a high affinity for rat cannabinoid CB(1) receptor (K(i)=27.2 pM, and IC(50)=118.9 pM), but a much lower affinity for rat ...

Adenosine, dopamine and endocannabinoids strictly modulate the release of one another in the dorsolateral striatum thereby controlling synaptic plasticity. As a second level of interaction, they regulate the action of one another via receptor heteromer formation. Here we investigated a putative third level of interaction, i.e. the possible control by cannabinoids of synaptic ...

Investigation of cannabinoid pharmacology in a vertebrate with a phylogenetic history distinct from that of mammals may allow better understanding of the physiological significance of cannabinoid neurochemistry. Taricha granulosa, the roughskin newt, was used here to characterize an amphibian cannabinoid receptor. Behavioral ...

For about 5,000 years, cannabis has been used as a therapeutic agent. There has been growing interest in the medical use of cannabinoids. This is based on the discovery that cannabinoids act with specific receptors (CB1 and CB2). CB1 receptors are located in specific brain ...

The discovery, synthesis and structure-activity relationship (SAR) of a novel series of cannabinoid 1 (CB(1)) and cannabinoid 2 (CB(2)) receptor ligands are reported. Based on the aminoalkylindole class of cannabinoid receptor agonists, a biphenyl moiety was introduced as novel lipophilic ...

In veterinary medicine, there is an increasing interest in the study of the endo-cannabinoid system and the possible use of the cannabinoids for the treatment of several diseases. Cannabinoid receptors (CB) are widely distributed in human and laboratory animal tissues, justifying the involvement of the ...

Here are reported the antiproliferative effects of the cannabinoid agonist WIN upon human melanoma cells expressing mRNA and protein for both CB1 and CB2 receptors. While WIN exerted antimitogenic effects, selective CB1 or CB2 agonists were unable to reproduce such effects and selective ...

The endocannabinoid system is a critical regulator of energy homeostasis and food intake. Through cannabinoid (CB)1 receptors in the brain and periphery, endocannabinoids exert powerful effects on the systems of the body that coordinate the balance between food intake, metabolism, and energy expenditure. These integrative systems ...

A novel series of 1-sulfonyl-4-acylpiperazines as selective cannabinoid-1 receptor (CB1R) inverse agonists was discovered through high throughput screening (HTS) and medicinal chemistry lead optimization. Potency and in vivo properties were systematically optimized to afford orally bioavailable, highly efficacious, and selective ...