“This study aims to investigate the effects of cannabinoid (CB)-1 and CB2 receptor ligands on intestinal motor function and muscular electrophysiological activity in rodent gastrointestinal (GI) tract…
This is one of the first reports on neuronal regulation of intestinal motility through CB-dependent pathways with potential application in the treatment of inflammatory and functional GI disorders.”
“The cannabinoid receptors CB1 and CB2 are localized in the urinary bladder and play a role in the regulation of its function. We investigated the pathomechanisms through which hyperosmolarity induces detrusor overactivity (DO)…
These results demonstrate that hyperosmolar-induced DO is mediated by CB1 and CB2 receptors. Therefore, the cannabinoid pathway could potentially be a target for the treatment of urinary bladder dysfunction.”
“The endocannabinoid system plays protective roles against the growth and the spreading of several types of carcinomas.
Because estrogens regulate this system both in physiological states and cancer, in this paper we evaluated its involvement in endometrial carcinoma, a well-known estrogen-dependent tumor.
In conclusion, the endocannabinoid system seems to play an important role in human endometrial carcinoma, and modulation of CB(2) activity/expression may account for a tumor-suppressive effect.”
“There are anecdotal reports that some Cannabis preparations may be useful for bladder dysfunctions.
Here, we investigated the effect of a number of non- psychotropic phytocannabinoids, namely cannabidiol (CBD), cannabigerol (CBG), cannabidivarin (CBDV), Δ9-tetrahydrocannabivarin (THCV) and cannabichromene (CBC) on mouse bladder contractility in vitro.
CBG, THCV, CBD and CBDV, but not CBC, at concentration ranging from 10(-8) M to 10(-4) M, decreased (with similar potency), the contractions induced by acetylcholine without significantly modifying the contractions induced by electrical stimulation.
The rank order of efficacy was CBG=THCV>CBD>CBDV.
In depth studies on CBG showed that the effect of this phytocannabinoid on acetylcholine-induced contractions was not affected by CB1 or CB2 receptor antagonists.
Additionally, CBG also reduced acetylcholine-induced contractions in the human bladder.”
“Phytocannabinoids (pCBs) are lipid-soluble phytochemicals present in the plant, Cannabis sativa L. and non-cannabis plants which have a long history in traditional and recreational medicine.
The plant and constituents were central in the discovery of the endocannabinoid system, the most new target for drug discovery.
The endocannabinoid system includes two G protein-coupled receptors; the cannabinoid receptors-1 and -2 (CB1 and CB2) for marijuana’s psychoactive principle ∆(9)-tetrahydrocannabinol (∆9-THC), their endogenous small lipid ligands; namely anandamide (AEA) and 2-arachidonoylglycerol (2-AG), also known as endocannabinoids and the proteins for endocannabinoid biosynthesis and degradation such as fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL).
The endocannabinoid system has been suggested as a pro-homeostatic and pleiotropic signaling system activated in a time- and tissue-specific way during pathological conditions including cancer.
Targeting the CB1 receptors become a concern because of adverse psychotropic reactions. Hence, targeting the CB2 receptors or the endocannabinoid metabolizing enzyme by phytocannabinoids obtained from non-cannabis plant lacking psychotropic adverse reactions has garnered interest in drug discovery.
These pCBs derived from plants beyond cannabis appear safe and effective with a wider access and availability.
In recent years, several pCBs derived other than non-cannabinoid plants have been reported to bind to and functionally interact with cannabinoid receptors and appear promising candidate for drug development in cancer therapeutics.
Several of them also target the endocannabinoid metabolizing enzymes that control endocannabinoid levels. In this article, we summarize, critically discuss the updates and future prospects of the pCBs as novel and promising candidates for cancer therapeutics.”
“Emerging evidence indicated that anandamide (AEA) stimulated vasorelaxation in both spontaneously hypertensive rats (SHRs) and L-NAME-induced hypertensive rats. Yet it remains unknown whether AEA modulates vasomotion of aorta in renovascular hypertensive (RVH) rats.
The aim of present study was to explore the effect of AEA on relaxation of thoracic aortas in two-kidney one-clip (2K1C)-induced RVH rats.
Taken together, the present study demonstrated that AEA enhanced endothelium-dependent aortic relaxation through activation of both CB1 and CB2 receptors and P-eNOS/NO pathway in 2K1C rats.”
“Alcohol use disorder represents a significant human health problem that leads to substantial loss of human life and financial cost to society. Currently available treatment options do not adequately address this human health problem, and thus, additional therapies are desperately needed.
The endocannabinoid system has been shown, using animal models, to modulate ethanol-motivated behavior, and it has also been demonstrated that chronic ethanol exposure can have potentially long-lasting effects on the endocannabinoid system.
For example, chronic exposure to ethanol, in either cell culture or preclinical rodent models, causes an increase in endocannabinoid levels that results in down-regulation of the cannabinoid receptor 1 (CB1) and uncoupling of this receptor from downstream G protein signaling pathways.
Using positron emission tomography (PET), similar down-regulation of CB1 has been noted in multiple regions of the brain in human alcoholic patients.
In rodents, treatment with the CB1 inverse agonist SR141716A (Rimonabant), or genetic deletion of CB1 leads to a reduction in voluntary ethanol drinking, ethanol-stimulated dopamine release in the nucleus accumbens, operant self-administration of ethanol, sensitization to the locomotor effects of ethanol, and reinstatement/relapse of ethanol-motivated behavior.
Although the clinical utility of Rimonabant or other antagonists/inverse agonists for CB1 is limited due to negative neuropsychiatric side effects, negative allosteric modulators of CB1 and inhibitors of endocannabinoid catabolism represent therapeutic targets worthy of additional examination.”
“In this study we evaluated the effects of the CB1/CB2 cannabinoid receptor agonist on antigen-induced asthma-like reaction in sensitized guinea pigs…
These findings suggest that targeting cannabinoid receptors could be a novel preventative therapeutic strategy in asthmatic patients.”
“The pharmacological (and recreational) effects of cannabis have been known for centuries.
However, it is only recently that one has identified two subtypes of G-protein-coupled receptors, namely CB1 and CB2-receptors, which mediate the numerous effects of delta9-tetrahydrocannabinol and other cannabinoids.
Logically, the existence of cannabinoid-receptors implies that endogenous ligands for these receptors (endocannabinoids) exist and exert a physiological role.
Hence, arachidonoylethanolamide (anandamide) and sn-2 arachidonoylglycerol, the first two endocannabinoids identified, are formed from plasma membrane phospholipids and act as CB1 and/or CB2 agonists.
The presence of both CB1 and CB2-receptors in the rat heart is noteworthy.
This endogenous cardiac cannabinoid system is involved in several phenomena associated with cardioprotective effects.
Endocannabinoids and synthetic cannabinoids, the latter through either CB1 or CB2-receptors, exert direct cardioprotective effects in rat isolated hearts.
The ability of cannabinoids to reduce infarct size has been confirmed in vivo in anesthetized mice and rats.
This latter effect appears to be mediated through CB2-receptors.
Thus, the endogenous cardiac cannabinoid system, through activation of CB2-receptors, appears to be an important mechanism of protection against myocardial ischemia.”
“Delta-9-tetrahydrocannabinol (THC), the major active component of marijuana, has a beneficial effect on the cardiovascular system during stress conditions…
The present study was designed to investigate the central (CB1) and the peripheral (CB2)cannabinoid receptor expression in neonatal cardiomyoctes and possible function in the cardioprotection of THC from hypoxia.
The antagonist for the CB2, but not CB1 receptor antagonist abolished the protective effect of THC.
In agreement with these results using RT-PCR, it was shown that neonatal cardiac cells express CB2, but not CB1 receptors.
Involvement of NO in the signal transduction pathway activated by THC through CB2 was examined. It was found that THC induces nitric oxide (NO) production by induction of NO synthase (iNOS) via CB2 receptors.
L-NAME (NOS inhibitor, 100 microM) prevented the cardioprotection provided by THC.
Taken together, our findings suggest that THC protects cardiac cells against hypoxia via CB2 receptor activation by induction of NO production.
An NO mechanism occurs also in the classical pre-conditioning process; therefore, THC probably pre-trains the cardiomyocytes to hypoxic conditions.”