“MAGL (monoacylglycerol lipase) is an enzyme that hydrolyzes the endocannabinoid 2-arachidonoylglycerol and regulates the production of arachidonic acid and prostaglandins-substances that mediate tissue inflammatory response. Here, we have studied the effects of the selective MAGL inhibitors JZL184 and MJN110 and their underlying molecular mechanisms on 3 different experimental models of focal cerebral ischemia.
Monthly Archives: February 2018
Role of the endocannabinoid system in the formation and development of depression.
“Two types of cannabinoid (CB) receptors have been described in the human body: CB1 and CB2 receptors. CB1 receptor distribution may be related to the cannabinoid functions of memory and cognition regulation as well as motor control. In addition, the endocannabinoid system (ECS) related to CB1 receptors may be involved in human emotion regulation, especially depression occurrence. Indeed, CB1 receptors are all distributed in depression associated neuroanatomical structures and neural circuits. Both animal experiments and clinical studies have demonstrated that impairment of the ECS pathway is present in depression models and patients, and application of both CB1 receptor agonists and anandamide (cannabinoid-like substance) degradation inhibitors produce similar biochemical and behavioral effects as antidepressants. These findings provide a solid basis for understanding the ECS role in the formation and development of depression. Therefore, it can be inferred that the ECS may have an important function in both depression treatment and the effects of antidepressants.” https://www.ncbi.nlm.nih.gov/pubmed/29441900]]>
The Use of Cannabis and Cannabinoids in Treating Symptoms of Multiple Sclerosis: a Systematic Review of Reviews.
“Pharmaceutical cannabinoids such as nabiximols, nabilone and dronabinol, and plant-based cannabinoids have been investigated for their therapeutic potential in treating multiple sclerosis (MS) symptoms.
This review of reviews aimed to synthesise findings from high quality systematic reviews that examined the safety and effectiveness of cannabinoids in multiple sclerosis. We examined the outcomes of disability and disability progression, pain, spasticity, bladder function, tremor/ataxia, quality of life and adverse effects.
We identified 11 eligible systematic reviews providing data from 32 studies, including 10 moderate to high quality RCTs. Five reviews concluded that there was sufficient evidence that cannabinoids may be effective for symptoms of pain and/or spasticity in MS. Few reviews reported conclusions for other symptoms. Recent high quality reviews find cannabinoids may have modest effects in MS for pain or spasticity. Future research should include studies with non-cannabinoid comparators; this is an important gap in the evidence.” https://www.ncbi.nlm.nih.gov/pubmed/29442178 https://link.springer.com/article/10.1007%2Fs11910-018-0814-x]]>Cannabinoid-induced cell death in endometrial cancer cells: involvement of TRPV1 receptors in apoptosis.
“Among a variety of phytocannabinoids, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are the most promising therapeutic compounds. Besides the well-known palliative effects in cancer patients, cannabinoids have been shown to inhibit in vitro growth of tumor cells.
Likewise, the major endocannabinoids (eCBs), anandamide (AEA) and 2-arachidonoylglycerol (2-AG), induce tumor cell death.
The purpose of the present study was to characterize cannabinoid elements and evaluate the effect of cannabinoids in endometrial cancer cell viability.
These data indicate that cannabinoids modulate endometrial cancer cell death.
Selective targeting of TPRV1 by AEA, CBD, or other stable analogues may be an attractive research area for the treatment of estrogen-dependent endometrial carcinoma.
Our data further support the evaluation of CBD and CBD-rich extracts for the potential treatment of endometrial cancer, particularly, that has become non-responsive to common therapies.”
https://www.ncbi.nlm.nih.gov/pubmed/29441458
https://link.springer.com/article/10.1007%2Fs13105-018-0611-7
The Association of Unfavorable Traffic Events and Cannabis Usage: A Meta-Analysis
“In the last years were published many epidemiological articles aiming to link driving under the influence of cannabis (DUIC) with the risk of various unfavorable traffic events (UTEs), with sometimes contradictory results.
The primary objective of this study was to analyze whether there is a significant association between DUIC and UTEs.
Our analysis suggests that the overall effect size for DUIC on UTEs is not statistically significant, but there are significant differences obtained through subgroup analysis. This result might be caused by either methodological flaws (which are often encountered in articles on this topic), the indiscriminate employment of the term “cannabis use,” or an actual absence of an adverse effect. A positive test for cannabis (i.e., blood) does not necessarily imply that drivers were impaired, as THC/metabolites might be detected in blood a long time after impairment, especially in chronic cannabis users, which could also induce an important bias in the analysis of the results. When a driver is found, in traffic, with a positive reaction suggesting cannabis use, the result should be corroborated by either objective data regarding marijuana usage (like blood analyses, with clear cut-off values), or a clinical assessment of the impairment, before establishing his/her fitness to drive.” https://www.frontiersin.org/articles/10.3389/fphar.2018.00099/full]]>Learning and Memory is Modulated by Cannabidiol When Administered During Trace Fear-Conditioning.
“Cannabidiol (CBD) is thought to have therapeutic potential for treating psychiatric conditions that affect cognitive aspects of learning and memory, including anxiety and post-traumatic stress disorder (PTSD).
Studies have shown that CBD enhances extinction of fear memory when given after conditioning. This led us to hypothesize that CBD, if administered prior to fear conditioning, might modulate cognitive learning and memory processes in additional ways that would further guide its potential use for treating PTSD.
Therefore, we designed a study to investigate effects of CBD on fear learning and memory when administered to mice prior to administering a trace fear conditioning protocol which imposes cognitive demands on the learning and memory process.
Overall, the memory-modulating effects of a single pre-conditioning dose of CBD, which we show here, demonstrate the need to more fully characterize its basic effects on memory, suggest caution when using it clinically as an anxiolytic, and point to a need for more research into its potential as a therapeutic for treating memory-loss disorders.”
https://www.ncbi.nlm.nih.gov/pubmed/29432803
https://www.sciencedirect.com/science/article/pii/S1074742718300224
“Ischemia not only activates cell death pathways but also triggers endogenous protective mechanisms. However, it is largely unknown what is the essence of the endogenous neuroprotective mechanisms induced by preconditioning. In this study we demonstrated that systemic injection of JZL195, a selective inhibitor of eCB clearance enzymes, induces in vivo long-term depression at CA3-CA1 synapses and at PrL-NAc synapses produces neuroprotection. JZL195-elicited long-term depression is blocked by AM281, the antagonist of cannabinoid 1 receptor (CB1R) and is abolished in mice lacking cannabinoid CB1 receptor (CB1R) in astroglial cells, but is conserved in mice lacking CB1R in glutamatergic or GABAergic neurons. Blocking the glutamate NMDA receptor and the synaptic trafficking of glutamate AMPA receptor abolishes both long-term depression and neuroprotection induced by JZL195. Mice lacking CB1R in astroglia show decreased neuronal death following cerebral ischemia. Thus, an acute elevation of extracellular eCB following eCB clearance inhibition results in neuroprotection through long-term depression induction after sequential activation of astroglial CB1R and postsynaptic glutamate receptors.”
“Cannabinoid 1 receptors (CB1Rs) are expressed in peripheral tissues, including islets of Langerhans, where their function(s) is under scrutiny. Using mouse β-cell lines, human islets and CB1R-null (CB1R-/- ) mice, we have now investigated the role of CB1Rs in modulating β-cell function and glucose responsiveness. Synthetic CB1R agonists diminished GLP-1-mediated cAMP accumulation and insulin secretion as well as glucose-stimulated insulin secretion in mouse β-cell lines and human islets. In addition, silencing CB1R in mouse β cells resulted in an increased expression of pro-insulin, glucokinase (GCK) and glucose transporter 2 (GLUT2), but this increase was lost in β cells lacking insulin receptor. Furthermore, CB1R-/- mice had increased pro-insulin, GCK and GLUT2 expression in β cells. Our results suggest that CB1R signalling in pancreatic islets may be harnessed to improve β-cell glucose responsiveness and preserve their function. Thus, our findings further support that blocking peripheral CB1Rs would be beneficial to β-cell function in type 2 diabetes.”