“Peripherally acting cannabinoid 1 (CB1) receptor antagonists are considered as potential therapeutics for the treatment of obesity with desired efficacy and reduced central nervous system side effects.
The prediction accuracy and reliability of the best developed CoMSIA model have been validated using well-established methods. Using the inputs from the best CoMSIA contour maps, several novel highly selective peripherally acting CB1 receptor antagonists have been designed and reported herein.”
“We have studied cannabis use to enhance both sportive and non-sportive performance among French sport university students.
Males were more prone to have already used cannabis to enhance non-sportive performance as well as sportive performance. The simultaneous equation model indicated that both kinds of enhancing-substance use were endogenous: cannabis use to enhance sportive performance leads to cannabis use to enhance non-sportive performance and reciprocally.
Moreover, the relaxing properties of cannabis may be frequently used to enhance performance. Cannabis use to enhance sportive performance was positively related to the competitive level and to sliding sports.
The present study helps to improve understanding on an empirical paradox about the relationship between doping agents use and so-called ‘recreational’ drug use among athletes. Indeed, people who use doping agents may also use ‘recreational’ drugs for a ‘non-recreational’ purpose.”
“Policies regarding cannabis use are rapidly changing, yet public officials have limited access to scientific information that might inform the creation of these policies.
One important area in which to begin investigations is the link between recreational cannabis use and health, specifically exercise.
There are common anecdotal reports that cannabis decreases motivation, including motivation to exercise. On the other hand, there are also anecdotal reports that cannabis is used prior to athletic activity.
In fact, the World Anti-Doping Agency includes cannabis as a prohibited substance in sport, partly because it is believed that it may enhance sports performance.
Given recent political, cultural, and legal trends, and the growing acceptance of recreational cannabis use, it is important to develop a more nuanced understanding of the relationship between cannabis and exercise, specifically the potential effects of use on exercise performance, motivation, and recovery.”
“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.”
“Inflammation plays a pivotal role in the pathogenesis of many diseases in the central nervous system.
Caudate nucleus (CN), the largest nucleus in the brain, is also implicated in many neurological disorders.
2-Arachidonoylglycerol (2-AG), the most abundant endogenous cannabinoid and the true natural ligand for CB1 receptors, has been shown to exhibit neuroprotective effects through its anti-inflammatory action from proinflammatory stimuli in hippocampus.
In the present study, we discovered that 2-AG significantly protects CN neurons in culture against lipopolysaccharide (LPS)-induced inflammatory response.
Our study suggests the therapeutic potential of 2-AG for the treatment of some inflammation-induced neurological disorders and pain.”
“Homocysteine (Hcy) is a high risk factor for Alzheimer’s disease (AD). Caudate nucleus (CN), the major component of basal ganglia in the brain, is also involved in many neurological disorders.
2-Arachidonoylglycerol (2-AG), the true natural ligand for cannabinoid type-1 (CB1) receptors and the most abundant endogenous cannabinoid, has been shown to exhibit neuroprotective effects through its anti-inflammatory action from proinflammatory stimuli in the hippocampus and CN.
In the present work, we explored that 2-AG significantly protects CN neurons in culture against Hcy-induced response.
2-AG is capable of inhibiting elevation of Hcy-induced cyclooxygenase-2 expression associated with nuclear factor-kappaB/p38MAPK/ERK1/2 signaling pathway through CB1 receptors-dependent way in primary cultured CN neurons.
Our study reveals the therapeutic potential for 2-AG for the treatment of neurodegenerative diseases, such as AD.”
“Homocysteine (Hcy) is an important risk factor for Alzheimer’s disease (AD) and other neurodegenerative diseases. Caudate nucleus (CN), the largest nucleus in the brain, is also implicated in many neurological disorders.
2-Arachidonoylglycerol (2-AG), the most abundant endogenous cannabinoid, has been shown to exhibit neuroprotective effects from many stimuli in the central nervous system (CNS).
Furthermore, it has been reported that voltage-gated sodium channels (VGSCs) are the common targets of many neuronal damages and drugs.
However, it is still not clear whether VGSCs are involved in the neurotoxicity of Hcy and the neuroprotective effect of 2-AG in CN neurons. In the present study, whole-cell patch clamp recording was used to invest the action of Hcy on sodium currents in primary cultured rat CN neurons and its modulation by 2-AG.
The results showed that in cultured CN neurons, pathological concentration of Hcy (100 μM) significantly increased the voltage-gated sodium currents (I Na) and produced a hyperpolarizing shift in the activation-voltage curve of I Na.
The further data demonstrated 2-AG is capable of suppressing elevation of Hcy-induced increase in I Na and hyperpolarizing shift of activation curves most partly through CB1 receptor-dependent way.
Our study provides a better understanding of Hcy-associated neurological disorders and suggests the therapeutic potential for 2-AG for the treatment of these diseases.”
“The function of the endocannabinoid system (ECS) in the renal tissue is not completely understood.
We studied the effect of compounds modulating the activity of cannabinoid CB receptors on the active reabsorption of Na+ in LLC-PK1 cells.
“The function of the endocannabinoid system (ECS) in the renal tissue is not completely understood. Kidney function is closely related to ion reabsorption in the proximal tubule, the nephron segment responsible for the reabsorption of 70- 80% of the filtrate.
We studied the effect of compounds modulating the activity of cannabinoid CB receptors on the active reabsorption of Na+ in LLC-PK1 cells.
ECS is expressed in LLC-PK1 cells. Both CB1 and TRPV1 regulate (Na+ +K+ )-ATPase activity in these cells, and are modulated by lipid and peptide CB1 ligands, which act via different signaling pathways.”
“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.”