Category Archives: Endocannabinoid System

Anandamide deficiency and heightened neuropathic pain in aged mice.

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“Damaging of peripheral nerves may result in chronic neuropathic pain for which the likelihood is increased in the elderly. We assessed in mice if age-dependent alterations of endocannabinoids contributed to the heightened vulnerability to neuropathic pain at old age.

We assessed nociception, endocannabinoids and the therapeutic efficacy of R-flurbiprofen in young and aged mice in the spared nerve injury model of neuropathic pain.

 R-flurbiprofen was used because it is able to reduce neuropathic pain in young mice in part by increasing anandamide.

Aged mice developed stronger nociceptive hypersensitivity after sciatic nerve injury than young mice.

This was associated with low anandamide levels in the dorsal root ganglia, spinal cord, thalamus and cortex, which further decreased after nerve injury…”

 More: http://www.ncbi.nlm.nih.gov/pubmed/23597506

Controlling 2-arachidonoylglycerol metabolism as an anti-inflammatory strategy.

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“The endocannabinoid system is implicated in, and regulates, several physiological processes, ranging from food intake and energy balance to pain and inflammation.

 2-Arachidonoylglycerol (2-AG) is a full agonist at the cannabinoid receptors which classically mediate its effects. The activity of this bioactive lipid is dependent on its endogenous levels, which are tightly controlled by several hydrolases, monoacylglycerol lipase and α/β-hydrolase domain 6 and 12.

 Moreover, 2-AG is also a substrate of cyclooxygenase-2, and this reaction leads to the formation of prostaglandin glycerol esters, the effects of which remain to be fully elucidated.

 In this review we discuss the multiple mechanisms by which 2-AG controls inflammation and the therapeutic potential of 2-AG metabolism inhibitors.”

http://www.ncbi.nlm.nih.gov/pubmed/23891880

The endocannabinoid system in advanced liver cirrhosis: pathophysiological implication and future perspectives.

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“Endogenous cannabinoids (EC) are ubiquitous lipid signalling molecules providing different central and peripheral effects that are mediated mostly by the specific receptors CB1 and CB2. The EC system is highly upregulated during chronic liver disease and consistent experimental and clinical findings indicate that it plays a role in the pathogenesis of liver fibrosis and fatty liver disease associated with obesity, alcohol abuse and hepatitis C.

Furthermore, a considerable number of studies have shown that EC and their receptors contribute to the pathogenesis of the cardio-circulatory disturbances occurring in advanced cirrhosis, such as portal hypertension, hyperdynamic circulatory syndrome and cirrhotic cardiomyopathy.

More recently, the EC system has been implicated in the development of ascites, hepatic encephalopathy and the inflammatory response related to bacterial infection. Rimonabant, a selective CB1 antagonist, was the first drug acting on the EC system approved for the treatment of obesity. Unfortunately, it has been withdrawn from the market because of its neuropsychiatric side effects.

Compounds able to target selectively the peripheral CB1 receptors are under evaluation.

In addition, molecules stimulating CB2 receptor or modulating the activity of enzymes implicated in EC metabolism are promising areas of pharmacological research.

Liver cirrhosis and the related complications represent an important target for the clinical application of these compounds.”

http://www.ncbi.nlm.nih.gov/pubmed/23890208

Anti-inflammatory activity of topical THC in DNFB-mediated mouse allergic contact dermatitis independent of CB1 and CB2 receptors.

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“∆9 -Tetrahydrocannabinol (THC), the active constituent of Cannabis sativa, exerts its biological effects in part through the G-protein-coupled CB1 and CB2 receptors, which were initially discovered in brain and spleen tissue, respectively. However, THC also has CB1/2 receptor-independent effects. Because of its immune-inhibitory potential, THC and related cannabinoids are being considered for the treatment of inflammatory skin diseases.

Here we investigated the mechanism of the anti-inflammatory activity of THC and the role of CB1 and CB2 receptors…

CONCLUSIONS:

Topically applied THC can effectively attenuate contact allergic inflammation by decreasing keratinocyte-derived pro-inflammatory mediators that orchestrate myeloid immune cell infiltration independent of CB1/2 receptors.

This has important implications for the future development of strategies to harness cannabinoids for the treatment of inflammatory skin diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/23889474

A Link Between Autism and Cannabinoids

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“Two autism-related mutations in a synapse-adhesion protein lead to deficits in prolonged endocannabinoid signaling in mice. It’s a surprising connection that suggests such signaling problems could be implicated in autism spectrum disorders, according to a paper published today (April 11) in Neuron.

Tonic endocannabinoid signaling is long-lasting and contrasts with the brief pulses characteristic of phasic signaling. Endocannabinoid signaling in general affects memory formation, learning, pain, and other important processes, but the distinctions between tonic and phasic signaling have been poorly understood.

“It’s a very stimulating finding which could be a real turning point in understanding tonic endocannabinoids and how this otherwise mysterious lipid signaling really works,” said Bradley Alger, a neuroscientist at the University of Maryland School of Medicine…

Alger added that, if the endocannabinoid system does turn out to be connected to autism in humans, medical marijuana could turn out to hold possibility for treating autism.”

More: http://www.the-scientist.com/?articles.view/articleNo/35088/title/A-Link-Between-Autism-and-Cannabinoids/

Role of the cannabinoid system in the transit of beta-amyloid across the blood–brain barrier

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“Emerging evidence suggests beta-amyloid (Aβ) deposition in the Alzheimer’s disease (AD) brain is the result of impaired clearance, due in part to diminished Aβ transport across the blood–brain barrier (BBB). Recently, modulation of the cannabinoid system was shown to reduce Aβ brain levels and improve cognitive behavior in AD animal models…

 The purpose of the current studies was to investigate the role of the cannabinoid system in the clearance of Aβ across the BBB.

  The current studies demonstrate, for the first time, a role for the cannabinoid system in the transit of Aβ across the BBB.

These findings provide insight into the mechanism by which cannabinoid treatment reduces Aβ burden in the AD brain and offer additional evidence on the utility of this pathway as a treatment for AD.”

http://www.sciencedirect.com/science/article/pii/S104474311300064X

Marijuana May Be Legitimate Treatment for Alzheimer’s Disease, Report Says

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“Researchers at the Roskamp Institute in Florida recently published a study in the journal Molecular and Cellular Neuroscience revealing that cannabinoids could delay the effects of Alzheimer’s disease, and could quite plausibly terminate the disease entirely.”

medical marijuana alzheimers Marijuana May Be Legitimate Treatment for Alzheimers Disease, Report Says

“Corbin Bachmeier, Ph.D, lead researcher of the study, declared that Alzheimer’s disease is “the result of impaired Aβ [Amyloid-β protein] clearance from the brain”. According to this particular study, cannabinoids can resolve this problem, which makes it a prospective treatment.

Bachmeier’s examination determined that “modulation of the cannabinoid system was shown to reduce Aβ [Amyloid-β protein] brain levels and improve cognitive behavior in Alzheimer’s disease animal models.”

The study’s abstract states that the objective of the study was to “investigate the role of the cannabinoid system in the clearance of Aβ across the blood–brain barrier (BBB).”

For the first time in recorded history, the study in question establishes that the cannabinoid system does indeed play a role in the transit of Amyloid-β protein across the blood-brain barrier.

Bachmeier concluded that his discoveries “provide insight into the mechanism by which cannabinoid treatment reduces Aβ [Amyloid-β protein] burden in the AD [Alzheimer’s disease] brain and offer additional evidence on the utility of this pathway as a treatment for AD.”

This is good news for individuals suffering with this specific ailment and for their loved ones. Cannabinoids seem to be boundless in respect to the medicinal benefits they have to offer.”

http://ivn.us/2013/07/24/marijuana-may-be-legitimate-treatment-for-alzheimers-disease-report-says/

Cannabis Use, Effect And Potential Therapy For Alzheimer’s, MS and Parkinson’s

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“The illegal status and wide-spread use of cannabis made basic and clinical cannabis research difficult in the past decades; on the other hand, it has stimulated efforts to identify the psychoactive constituents of cannabis. As a consequence, the endocannabinoid system was discovered, which was shown to be involved in most physiological systems — the nervous, the cardiovascular, the reproductive, the immune system, to mention a few.

One of the main roles of endocannabinoids is neuroprotection, but over the last decade they have been found to affect a long list of processes, from anxiety, depression, cancer development, vasodilatation to bone formation and even pregnancy.

Cannabinoids and endocannabinoids are supposed to represent a medicinal treasure trove which waits to be discovered…

The endocannabinoid system acts as a guardian against various attacks on the mammalian body.

Conclusion

The above described research concerning the endocannabinoid-system is of importance in both basic science and in therapeutics:

  • The discovery of the cannabis plant active constituent has helped advance our understanding of cannabis use and its effects.
  • The discovery of the endocannabinoids has been of central importance in establishing the existence of a new biochemical system and its physiological roles — in particular in neuroprotection.
  • These discoveries have opened the door for the development of novel types of drugs, such as THC for the treatment of nausea and for enhancing appetite in cachectic patients.
  • The endocannabinoid system is involved in the protective reaction of the mammalian body to a long list of neurological diseases such as multiple sclerosis, Alzheimer’s and Parkinson’s disease which raises hope for novel therapeutic opportunities for these diseases.”

More: http://www.sciencedaily.com/releases/2007/10/071014163644.htm

CB1 agonists, locally applied to the cortico-thalamic circuit of rats with genetic absence epilepsy, reduce epileptic manifestations.

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“Drugs that modulate the endocannabinoid system and endocannabinoids typically play an anticonvulsant role although some proconvulsant effects have been reported both in humans and animal models.

 This study aims to characterize the role of cannabinoids in specific areas of the cortico-thalamic network involved in oscillations that underlie seizures in a genetic animal model of absence epilepsy, the WAG/Rij rat.

These results, together with previous reports, support therapeutic potential for endocannabinoid system modulators in absence epilepsy and highlight that attenuated endocannabinergic function may contribute to the generation and maintenance of seizures. Furthermore, the entire cortico-thalamic network responds to cannabinoid treatment, indicating that in all areas considered, CB receptor activation inhibits the pathological synchronization that subserves absence seizures.

 In conclusion, our result might be useful for the identification of future drug therapies in absence epilepsy.”

http://www.ncbi.nlm.nih.gov/pubmed/23860329

Epigenetic Control of Skin Differentiation Genes by Phytocannabinoids.

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“A role for endocannabinoid signaling has been reported in the control of epidermal physiology, whereby anandamide is able to regulate the expression of skin differentiation genes through DNA methylation. Here, we have investigated the possible epigenetic regulation of these genes by selected phytocannabinoids, plant-derived cannabinoids holding potential as novel therapeutics for various human diseases.

CONCLUSIONS AND IMPLICATIONS:

These findings identify the phytocannabinoids cannabidiol and cannabigerol as transcriptional repressors that can control cell proliferation and differentiation, suggesting (especially for cannabidiol) a possible exploitation as lead compounds to be used in the development of novel therapeutics for skin diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/23869687