“The incidence of atherosclerosis is increasing rapidly all over the world. Inflammatory processes have outstanding role in coronary artery disease (CAD) etiology and other atherosclerosis manifestations. Recently attentions have been increased about gut microbiota in many fields of medicine especially in inflammatory diseases like atherosclerosis. Ineffectiveness in gut barrier functions and subsequent metabolic endotoxemia (caused by rise in plasma lipopolysaccharide levels) is associated with low-grade chronic inflammation i.e. a recognized feature of atherosclerosis. Furthermore, the role of trimethylamine-N-oxide (TMAO), a gut bacterial metabolite has been suggested in atherosclerosis development. On the other hand, the effectiveness of gut microbiota modulation that results in TMAO reduction has been investigated. Moreover, considerable evidence supports a role for the endocannabinoid system (ECS) in atherosclerosis pathology which affects gut microbiota, but their effects on atherosclerosis are controversial. Therefore, we presented some evidence about the relationship between gut microbiota and ECS in atherosclerosis. We also presented evidences that gut microbiota modulation by pre/probiotics can have significant influence on the ECS. Even though there are many questions which have been unanswered, studies demonstrated that mucosal barrier function disruption and subsequent gut microbiota-derived endotoxemia could contribute to cardiometabolic diseases pathogenesis. As well, number of studies revealed that TMAO in systemic circulation can activate macrophages which lead to cholesterol accumulation and subsequent foam cells formation in atherosclerotic lesions. On the other hand, accumulating evidence proposes that ECS involved in many physiological processes that are related to maintenance of gut-barrier function and inflammation regulation. Hence, although present literature review provides beneficial evidence in support of crosstalk between ECS and gut microbiota, additional studies are needed to clarify whether gut microbiota modulation can alter ECS tone and inflammation levels or not.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6203867/]]>
Tag Archives: endocannabinoid system
Medical Use of Cannabinoids.
“Cannabinoid receptors, endocannabinoids and the enzymes responsible for their biosynthesis and degradation constitute the endocannabinoid system. In recent decades, the endocannabinoid system has attracted considerable interest as a potential therapeutic target in numerous pathological conditions. Its involvement in several physiological processes is well known, such as in energy balance, appetite stimulation, blood pressure, pain modulation, embryogenesis, nausea and vomiting control, memory, learning and immune response, among others, as well as in pathological conditions where it exerts a protective role in the development of certain disorders. As a result, it has been reported that changes in endocannabinoid levels may be related to neurological diseases such as Parkinson’s disease, Huntington’s disease, Alzheimer’s disease and multiple sclerosis, as well as anorexia and irritable bowel syndrome. Alterations in the endocannabinoid system have also been associated with cancer, affecting the growth, migration and invasion of some tumours. Cannabinoids have been tested in several cancer types, including brain, breast and prostate cancers. Cannabinoids have shown promise as analgesics for the treatment of both inflammatory and neuropathic pain. There is also evidence for a role of the endocannabinoid system in the control of emotional states, and cannabinoids could prove useful in decreasing and palliating post-traumatic stress disorder symptoms and anxiolytic disorders. The role of the endocannabinoid system in addictions has also been examined, and cannabinoids have been postulated as alternative and co-adjuvant treatments in some abuse syndromes, mainly in ethanol and opioid abuses. The expression of the endocannabinoid system in the eye suggests that it could be a potential therapeutic target for eye diseases. Considering the importance of the endocannabinoid system and the therapeutic potential of cannabinoids in this vast number of medical conditions, several clinical studies with cannabinoid-based medications are ongoing. In addition, some cannabinoid-based medications have already been approved in various countries, including nabilone and dronabinol capsules for the treatment of nausea and vomiting associated with chemotherapy, dronabinol capsules for anorexia, an oral solution of dronabinol for both vomiting associated with chemotherapy and anorexia, a Δ9-tetrahydrocannabinol/cannabidiol oromucosal spray for pain related to cancer and for spasticity and pain associated with multiple sclerosis, and an oral solution of cannabidiol for Dravet and Lennox-Gastaut syndromes. Here, we review the available efficacy, safety and tolerability data for cannabinoids in a range of medical conditions.” https://www.ncbi.nlm.nih.gov/pubmed/30374797 https://link.springer.com/article/10.1007%2Fs40265-018-0996-1]]>
Anandamide Effects in a Streptozotocin-Induced Alzheimer's Disease-Like Sporadic Dementia in Rats.
“Alzheimer’s disease (AD) is characterized by multiple cognitive deficits including memory and sensorimotor gating impairments as a result of neuronal and synaptic loss.
The endocannabinoid system plays an important role in these deficits but little is known about its influence on the molecular mechanism regarding phosphorylated tau (p-tau) protein accumulation – one of the hallmarks of AD -, and on the density of synaptic proteins.
Thus, the aim of this study was to investigate the preventive effects of anandamide (N-arachidonoylethanolamine, AEA) on multiple cognitive deficits and on the levels of synaptic proteins (syntaxin 1, synaptophysin and synaptosomal-associated protein, SNAP-25), cannabinoid receptor type 1 (CB1) and molecules related to p-tau degradation machinery (heat shock protein 70, HSP70), and Bcl2-associated athanogene (BAG2) in an AD-like sporadic dementia model in rats using intracerebroventricular (icv) injection of streptozotocin (STZ).
This study showed, for the first time, that the administration of an endocannabinoid can prevent AD-like effects induced by STZ, boosting further investigations about the modulation of endocannabinoid levels as a therapeutic approach for AD.”
“Altogether, our results showed, for the first time, that the administration of an endocannabinoid can prevent cognitive, synaptic and histopatological AD-like alterations induced by STZ, thus prompting endocannabinoids as a candidate therapeutic target in AD.” https://www.frontiersin.org/articles/10.3389/fnins.2018.00653/full
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Molecular Imaging of the Cannabinoid System in Idiopathic Parkinson's Disease.
“The endocannabinoid system is a modulator of neurotransmitter release and is involved in several physiological functions. Hence, it has been increasingly studied as a potential pharmacologic target of Parkinson’s disease.
Several preclinical and clinical studies evidenced a substantial rearrangement of the endocannabinoid system in the basal ganglia circuit following dopamine depletion. The endocannabinoid system has been additionally implicated in the regulation of neuroinflammation and neuroprotection through the activation of CB2 receptors, suggesting a potential target for disease modifying therapies in Parkinson’s disease.
In this chapter, current pharmacological and physiological knowledge on the role of the endocannabinoid system will be reviewed, focusing on preclinical studies animal models and clinical studies in patients with idiopathic Parkinson’s disease. The main strategies for imaging the brain cannabinoid system will be summarized to finally focus on in vivo imaging of patients with Parkinson’s disease.”
https://www.ncbi.nlm.nih.gov/pubmed/30314601
https://www.sciencedirect.com/science/article/pii/S0074774218300692?via%3Dihub
“Cannabis sativa is one of the most popular recreational and medicinal plants. Benefits from use of 
“The human body contains endogenous cannabinoids (endocannabinoids) that elicit similar effects as Δ9-tetrahydrocanabinol, the principal bioactive component of cannabis.
The endocannabinoid virodhamine (O-AEA) is the constitutional isomer of the well-characterized cardioprotective and anti-inflammatory endocannabinoid anandamide (AEA).
The chemical structures of O-AEA and AEA contain arachidonic acid (AA) and ethanolamine, however AA in O-AEA is connected to ethanolamine via an ester linkage whereas AA in AEA is connected through an amide linkage. We show that O-AEA is found at 9.6 fold higher levels than AEA in porcine left ventricle and is involved in regulating blood pressure and cardiovascular function.
On a separate note, the cytochrome P450 (CYP) epoxygenase CYP2J2 is the most abundant CYP in the heart where it catalyzes the metabolism of AA and AA-derived eCBs to bioactive epoxides that are involved in diverse cardiovascular functions. Herein, using competitive binding studies, kinetic metabolism measurements, molecular dynamics and wound healing assays we have shown that O-AEA is an endogenous inhibitor of CYP2J2 epoxygenase.
Together, the role of O-AEA as an endogenous eCB inhibitor of CYP2J2 may provide a new mode of regulation to control the activity of cardiovascular CYP2J2 in vivo and suggests a potential cross talk between the cardiovascular endocannabinoids and cytochrome P450 system.”
“Following the discovery of the endocannabinoid system and its potential as a therapeutic target for various pathological conditions, growing interest led researchers to investigate the role of cannabis and its derivatives for medical purposes. The compounds Δ9-tetrahydrocannabinol and 
“The endocannabinoid system refers to a widespread signaling system and its alteration is implicated in a growing number of human diseases.
However, the potential role of endocannabinoids in skeletal muscle disorders remains unknown. Here we report the role of the endocannabinoid CB1 receptors in Duchenne’s muscular dystrophy.
In murine and human models, CB1 transcripts show the highest degree of expression at disease onset, and then decline overtime. Similar changes are observed for PAX7, a key regulator of muscle stem cells. Bioinformatics and biochemical analysis reveal that PAX7 binds and upregulates the CB1 gene in dystrophic more than in healthy muscles.
Rimonabant, an antagonist of CB1, promotes human satellite cell differentiation in vitro, increases the number of regenerated myofibers, and prevents locomotor impairment in dystrophic mice.
In conclusion, our study uncovers a PAX7-CB1 cross talk potentially exacerbating DMD and highlights the role of CB1 receptors as target for potential therapies.”
“Osteosarcoma is the most common primary malignant tumor of bone in children and adolescents.
Bortezomib (BTZ) is an approved anticancer drug, classified as a selective reversible inhibitor of the ubiquitin-dependent proteasome system, that leads to cancer cell cycle arrest and apoptosis reducing the invasion ability of Osteosarcoma cells in vitro. It also regulates the RANK/RANKL/OPG system, involved in the pathogenesis of bone tumors and in cell migration.
A side effect of BTZ is to induce painful sensory peripheral neuropathy which lead to cessation of therapy or dose reduction.
Recently BTZ has been evaluated in combination with