Category Archives: Endocannabinoid System

Δ(9)-THC and N-arachidonoyl glycine regulate BV-2 microglial morphology and cytokine release plasticity: implications for signaling at GPR18.

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“Microglial cells are extremely plastic and undergo a variety of CNS-prompted shape changes relative to their location and current role. Signaling molecules from neurons also regulate microglial cytokine production. Neurons are known to employ the endogenous cannabinoid system to communicate with other cells of the CNS.

N-arachidonoyl glycine (NAGly) and Δ(9)-tetrahydrocannabinol (Δ(9)-THC) signaling via GPR18 has been introduced as an important new target in microglial-neuronal communication…

These data add to an emerging profile that emphasizes NAGly as a component of an endogenous system present in the CNS that tightly integrates microglial proliferation, recruitment, and adhesion with neuron-glia interactivity and tissue remodeling.”

http://www.ncbi.nlm.nih.gov/pubmed/24427137

Effects of cannabinoid receptor type 2 on endogenous myocardial regeneration by activating cardiac progenitor cells in mouse infarcted heart.

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“Cannabinoid receptor type 2 (CB2) activation is recently reported to promote proliferation of some types of resident stem cells (e.g., hematopoietic stem/progenitor cell or neural progenitor cell).

Resident cardiac progenitor cell (CPC) activation and proliferation are crucial for endogenous cardiac regeneration and cardiac repair after myocardial infarction (MI). This study aims to explore the role and possible mechanisms of CB2 receptor activation in enhancing myocardial repair…

In conclusion, AM1241 could induce myocardial regeneration and improve cardiac function, which might be associated with PI3K/Akt/Nrf2 signaling pathway activation.

Our findings may provide a promising strategy for cardiac endogenous regeneration after MI.”

http://www.ncbi.nlm.nih.gov/pubmed/24430557

The Novel Endocannabinoid Receptor GPR18 is Expressed in the Rostral Ventrolateral Medulla and Exerts Tonic Restraining Influence on Blood Pressure.

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“Systemic administration of the GPR18 agonist abnormal cannabidiol (Abn CBD) lowers blood pressure (BP).

These findings are the first to demonstrate GPR18 expression in the RVLM, and to suggest sympathoinhibitory role for this receptor. The findings yield new insight into the role of a novel cannabinoid receptor (GPR18) in central BP control.”

http://www.ncbi.nlm.nih.gov/pubmed/24431468PR

The endocannabinoid system: an emerging key player in inflammation.

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“The purpose of this review is to illustrate the expanding view of the endocannabinoid system (ECS) in relation to its roles in inflammation…

Diet is among the main factors determining synthesis and release of endocannabinoids and related mediators.

SUMMARY:

The complexity of what may be called the ‘endocannabinoidome’ requires approaches that take into account its dynamics and interconnections with other regulatory systems. This endocannabinoidome continues to offer possibilities for prevention and intervention, but multiple target approaches will probably provide the only keys to success.”

http://www.ncbi.nlm.nih.gov/pubmed/24419242

Pharmacological blockade of either cannabinoid CB1 or CB2 receptors prevents both cocaine-induced conditioned locomotion and cocaine-induced reduction of cell proliferation in the hippocampus of adult male rat.

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“Addiction to major drugs of abuse, such as cocaine, has recently been linked to alterations in adult neurogenesis in the hippocampus. The endogenous cannabinoid system modulates this proliferative response as demonstrated by the finding that pharmacological activation/blockade of cannabinoid CB1 and CB2 receptors not only modulates neurogenesis but also modulates cell death in the brain.

In the present study, we evaluated whether the endogenous cannabinoid system affects cocaine-induced alterations in cell proliferation…

These results indicate that the changes in neurogenic, apoptotic and gliotic processes that were produced by repeated cocaine administration were normalized by pharmacological blockade of CB1 and CB2. The restorative effects of cannabinoid receptor blockade on hippocampal cell proliferation were associated with the prevention of the induction of conditioned locomotion but not with the prevention of cocaine-induced sensitization.”

http://www.ncbi.nlm.nih.gov/pubmed/24409127

CB2 Receptor Deficiency Increases Amyloid Pathology and Alters Tau Processing in a Transgenic Mouse Model of Alzheimer’s Disease.

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“The endocannabinoid CB2 receptor system has been implicated in the neuropathology of Alzheimer’s disease (AD)…

The results confirm the constitutive role of the CB2 receptor system both in reducing amyloid plaque pathology in AD and also support the potential of cannabinoid therapies targeting CB2 to reduce Aβ…”

http://www.ncbi.nlm.nih.gov/pubmed/24408112

Cannabinoid-hypocretin cross-talk in the central nervous system: what we know so far

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“Emerging findings suggest the existence of a cross-talk between hypocretinergic and endocannabinoid systems…

The present review attempts to piece together what is known about this interesting interaction and describes its potential therapeutic implications.”

http://www.frontiersin.org/Neuropharmacology/10.3389/fnins.2013.00256/abstract

Endocannabinoid and Cannabinoid-Like Fatty Acid Amide Levels Correlate with Pain-Related Symptoms in Patients with IBS-D and IBS-C: A Pilot Study.

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“Irritable bowel syndrome (IBS) is a functional gastrointestinal (GI) disorder, associated with alterations of bowel function, abdominal pain and other symptoms related to the GI tract. Recently the endogenous cannabinoid system (ECS) was shown to be involved in the physiological and pathophysiological control of the GI function. The aim of this pilot study was to investigate whether IBS defining symptoms correlate with changes in endocannabinoids or cannabinoid like fatty acid levels in IBS patients.

CONCLUSION:

IBS subtypes and their symptoms show distinct alterations of endocannabinoid and endocannabinoid-like fatty acid levels. These changes may partially result from reduced FAAH expression. The here reported changes support the notion that the ECS is involved in the pathophysiology of IBS and the development of IBS symptoms.”

Sativex(®) (tetrahydrocannabinol + cannabidiol), an endocannabinoid system modulator: basic features and main clinical data.

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“Sativex(®) (nabiximols, USAN name) oromucosal spray contains the two main active constituents of Cannabis sativa, tetrahydrocannabinol and cannabidiol in a 1:1 molecular ratio, and acts as an endocannabinoid system modulator. Randomized, controlled clinical trials of Sativex as add-on therapy provide conclusive evidence of its efficacy in the treatment of more than 1500 patients with multiple sclerosis (MS)-related resistant spasticity…

Sativex oromucosal spray appears to be a useful and welcomed option for the management of resistant spasticity in MS patients. Although the management of MS has been improved by the availability of disease-modifying agents that target the underlying pathophysiological processes of the disease, a clear need remains for more effective symptomatic treatments, especially as regards MS-related spasticity and pain.”

http://www.ncbi.nlm.nih.gov/pubmed/21449855

Endocannabinoid pathways and their role in multiple sclerosis-related muscular dysfunction.

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“Modulation of the endocannabinoid system has been shown to have therapeutic potential in a number of disease states.

Sativex(®) (nabiximols, USAN name) contains the two main phytocannabinoids from Cannabis sativa, tetrahydrocannabinol and cannabidiol in a 1:1 ratio, and it acts as an endocannabinoid system modulator.

In an experimental mouse model of MS-related spasticity, Sativex dose-dependently improved hind limb flexion/stiffness and a dosage of 10 mg/kg was shown to be as effective as the most widely established anti-spasticity treatment baclofen (5 mg/kg).

These findings with Sativex are very promising and offer encouragement for MS patients, the majority of whom will develop spasticity-related disabling and recalcitrant symptoms. Furthermore, research into the endocannabinoid system may offer potential in other neurodegenerative, inflammatory and pain disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/21449854