“Targeting the CB2 receptor afforded neuroprotection in SOD1G93A mutant mice, a model of amyotrophic lateral sclerosis (ALS). The neuroprotective effects of CB2 receptors were facilitated by their up-regulation in the spinal cord in SOD1G93A mutant mice. Herein, we have investigated whether a similar CB2 receptor up-regulation, as well as parallel changes in other endocannabinoid elements, are evident in the spinal cord of dogs with degenerative myelopathy (DM), caused from mutations in the superoxide dismutase 1 gene (SOD1). In summary, our results demonstrated a marked up-regulation of CB2 receptors occurring in the spinal cord in canine DM, which was concentrated in activated astrocytes. Such receptors may be used as a potential target to enhance the neuroprotective effects exerted by these glial cells.” https://www.ncbi.nlm.nih.gov/pubmed/28069688]]>
Brain cannabinoid receptor 2: expression, function and modulation.
“Cannabis sativa (marijuana) is a fibrous flowering plant that produces an abundant variety of molecules, some with psychoactive effects. At least 4% of the world’s adult population uses cannabis annually, making it one of the most frequently used illicit drugs in the world. The psychoactive effects of cannabis are mediated primarily through cannabinoid receptor (CBR) subtypes. The prevailing view is that CB1Rs are mainly expressed in the central neurons, whereas CB2Rs are predominantly expressed in peripheral immune cells. However, this traditional view has been challenged by emerging strong evidence that shows CB2Rs are moderately expressed and function in specific brain areas. New evidence has demonstrated that brain CB2Rs modulate animal drug-seeking behaviors, suggesting that these receptors may exist in brain regions that regulate drug addiction. Recently, we further confirmed that functional CB2Rs are expressed in mouse ventral tegmental area (VTA) dopamine (DA) neurons and that the activation of VTA CB2Rs reduces neuronal excitability and cocaine-seeking behavior. In addition, CB2R-mediated modulation of hippocampal CA3 neuronal excitability and network synchronization has been reported. Here, we briefly summarize recent lines of evidence showing how CB2Rs modulate function and pathophysiology in the CNS.”
https://www.ncbi.nlm.nih.gov/pubmed/28065934
Development of new inhibitors for N-acylethanolamine-hydrolyzing acid amidase as promising tool against bladder cancer.
“The endocannabinoid system is a signaling system involved in a wide range of biological effects. Literature strongly suggests the endocannabinoid system role in the pathogenesis of cancer and that its pharmacological activation produces therapeutic benefits. Last research promotes the endocannabinoid system modulation by inhibition of endocannabinoids hydrolytic enzymes instead of direct activation of endocannabinoid receptors to avoid detrimental effects on cognition and motor control. Here we report the identification of N-acylethanolamine-hydrolyzing acid amidase (NAAA) inhibitors able to reduce cell proliferation and migration and cause cell death on different bladder cancer cell lines. These molecules were designed, synthesized and characterized and active compounds were selected by a fluorescence high-throughput screening method set-up on human recombinant NAAA that also allows to characterize the mechanism of inhibition. Together our results suggest an important role for NAAA in cell migration and in inducing tumor cell death promoting this enzyme as pharmacological target against bladder cancer.” https://www.ncbi.nlm.nih.gov/pubmed/28062195]]>
Potential roles of (endo)cannabinoids in the treatment of glaucoma: from intraocular pressure control to neuroprotection.
“Recent evidence shows that the endocannabinoid system is involved in the pathogenesis of numerous neurodegenerative diseases of the central nervous system. Pharmacologic modulation of cannabinoid receptors or the enzymes involved in the synthesis, transport, or breakdown of endogenous cannabinoids has proved to be a valid alternative to conventional treatment of these diseases.
In this review, we will examine recent findings that demonstrate the involvement of the endocannabinoid system in glaucoma, a major neurodegenerative disease of the eye that is a frequent cause of blindness.
Experimental findings indicate that the endocannabinoid system contributes to the control of intraocular pressure (IOP), by modulating both production and drainage of aqueous humor.
There is also a growing body of evidence of the involvement of this system in mechanisms leading to the death of retinal ganglion cells, which is the end result of glaucoma.
Molecules capable of interfering with the ocular endocannabinoid system could offer valid alternatives to the treatment of this disease, based not only on the reduction of IOP but also on neuroprotection.”
https://www.ncbi.nlm.nih.gov/pubmed/18929127
“The leading cause of irreversible blindness is glaucoma, a disease normally characterized by the development of ocular hypertension and consequent damage to the optic nerve at its point of retinal attachment. This results in a narrowing of the visual field, and eventually results in blindness.
A number of drugs are available to lower intraocular pressure (IOP), but, occasionally, they are ineffective or have intolerable side-effects for some patients and can lose efficacy with chronic administration.
The smoking of marijuana has decreased IOP in glaucoma patients.