Cannabinoid receptor 1 is a major mediator of renal fibrosis.

“Chronic kidney disease, secondary to renal fibrogenesis, is a burden on public health.

There is a need to explore new therapeutic pathways to reduce renal fibrogenesis.

To study this, we used unilateral ureteral obstruction (UUO) in mice as an experimental model of renal fibrosis and microarray analysis to compare gene expression in fibrotic and normal kidneys.

The cannabinoid receptor 1 (CB1) was among the most upregulated genes in mice, and the main endogenous CB1 ligand (2-arachidonoylglycerol) was significantly increased in the fibrotic kidney.

Interestingly, CB1 expression was highly increased in kidney biopsies of patients with IgA nephropathy, diabetes, and acute interstitial nephritis. Both genetic and pharmacological knockout of CB1 induced a profound reduction in renal fibrosis during UUO. While CB2 is also involved in renal fibrogenesis, it did not potentiate the role of CB1. CB1 expression was significantly increased in myofibroblasts, the main effector cells in renal fibrogenesis, upon TGF-β1 stimulation.

The decrease in renal fibrosis during CB1 blockade could be explained by a direct action on myofibroblasts. CB1 blockade reduced collagen expression in vitro. Rimonabant, a selective CB1 endocannabinoid receptor antagonist, modulated the macrophage infiltrate responsible for renal fibrosis in UUO through a decrease in monocyte chemoattractant protein-1 synthesis.

Thus, CB1 has a major role in the activation of myofibroblasts and may be a new target for treating chronic kidney disease.”

http://www.ncbi.nlm.nih.gov/pubmed/25760323

Risk of emergency medical treatment following consumption of cannabis or synthetic cannabinoids in a large global sample.

“Synthetic cannabinoids (SCs) have become increasingly popular in recent years. Often marketed to reflect their similar effects to cannabis, their use has been associated with a range of negative health effects. We sought to determine the relative risk of seeking emergency medical treatment (EMT) following use of SCs and natural cannabis.

The relative risk associated with the use of SCs was 30 (95% CI 17.5-51.2) times higher than that associated with cannabis. Significantly more symptoms (p=0.03) were reported by respondents seeking treatment for SCs than for cannabis.

CONCLUSIONS:

Whilst these findings must be treated with caution, SCs potentially pose a greater risk to users’ health than natural forms of cannabis. Regulation is unlikely to remove SCs from the market, so well-informed user-focused health promotion messages need to be crafted to discourage their use.”

http://www.ncbi.nlm.nih.gov/pubmed/25759401

Safety and Pharmacokinetics of Oral Cannabidiol When Administered Concomitantly With Intravenous Fentanyl in Humans.

“Objectives: Cannabidiol (CBD) is hypothesized as a potential treatment for opioid addiction, with safety studies an important first step for medication development. We determined CBD safety and pharmacokinetics when administered concomitantly with a high-potency opioid in healthy subjects.

Conclusions: Cannabidiol does not exacerbate adverse effects associated with intravenous fentanyl administration. Coadministration of CBD and opioids was safe and well tolerated. These data provide the foundation for future studies examining CBD as a potential treatment for opioid abuse.”

http://journals.lww.com/journaladdictionmedicine/Abstract/publishahead/Safety_and_Pharmacokinetics_of_Oral_Cannabidiol.99700.aspx

Emerging targets and therapeutic approaches for the treatment of osteoarthritis pain.

“Osteoarthritis is a complex and often painful disease that is inadequately controlled with current analgesics. This review discusses emerging targets and therapeutic approaches that may lead to the development of better analgesics…

Aberrant excitability in peripheral and central pain pathways drives osteoarthritis pain, reversing this via modulation of nerve growth factor, voltage-gated sodium channel, voltage-gated calcium channel and transient receptor potential vanilloid one activity, and increasing inhibitory mechanisms through modulation of cannabinoid and descending modulatory systems hold promise for osteoarthritis pain therapy.”

http://www.ncbi.nlm.nih.gov/pubmed/25730180

http://www.thctotalhealthcare.com/category/osteoarthritis/

 

Peripheral cannabinoid receptor, CB2, regulates bone mass.

“Here we show that CB2-deficient mice have a markedly accelerated age-related trabecular bone loss and cortical expansion, although cortical thickness remains unaltered.

These changes are reminiscent of human osteoporosis and may result from differential regulation of trabecular and cortical bone remodeling…

These results demonstrate that the endocannabinoid system is essential for the maintenance of normal bone mass by osteoblastic and osteoclastic CB2 signaling.

Hence, CB2 offers a molecular target for the diagnosis and treatment of osteoporosis, the most prevalent degenerative disease in developed countries.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1334629/

http://www.thctotalhealthcare.com/category/osteoporosis-2/

 

Marijuana: A Time-Honored but Untested Treatment for Epilepsy.

Image result for marijuana

“The biology of the endocannabinoid system in the brain provides a possible basis for a beneficial pharmacological effect of marijuana on seizures.

However, evidence for efficacy of cannabis treatment of epilepsy is anecdotal because no acceptable randomized controlled trials have been done.

Proper dosage and means of administration remain unknown.

Cannabis is safer than other controlled substances, including tobacco or alcohol, and appears to be relatively safe compared with most pharmaceuticals used to treat epilepsy.”

 http://www.ncbi.nlm.nih.gov/pubmed/25715711

http://www.thctotalhealthcare.com/category/epilepsy-2/

The role of cannabinoids in regulation of nausea and vomiting, and visceral pain.

“Marijuana derived from the plant Cannabis sativa has been used for the treatment of many gastrointestinal (GI) disorders, including anorexia, emesis, abdominal pain, diarrhea, and others.

Several cannabinoid receptors, which include the cannabinoid receptor 1 (CB1), CB2, and possibly GPR55, have been identified throughout the GI tract.

These receptors may play a role in the regulation of food intake, nausea and emesis, gastric secretion and gastroprotection, GI motility, ion transport, visceral sensation, intestinal inflammation, and cell proliferation in the gut.

…the regulation of nausea and vomiting by cannabinoids and the endocannabinoid system has shed new knowledge in this field.

Novel drug targets such as FAAH and monoacylglycerol lipase (MAGL) inhibitors appear to be promising in animal models, but more studies are necessary to prove their efficiency.

The promise of emerging drugs that are more selective and peripherally acting suggest that, in the near future, cannabinoids will play a major role in managing an array of GI diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/25715910

Are Cannabinoids Effective for Orofacial Pain States?

“…there is increasing attention being given in the media as well as in the biomedical sciences to the use as analgesic agents of the crude extracts of plants of the genus Cannabis (eg, marijuana) and their active ingredient delta 9-tetrahydrocannabinol (Δ9-THC).

These cannabinoid compounds have been reported in the biomedical literature to be beneficial in the treatment of some types of neuropathic pain and other pain states…

This review has found evidence indicating that they may be effective analgesic agents for neuropathic pain conditions refractory to other therapeutic approaches…

The clinical findings pointing to the usefulness of the cannabinoids for pain relief are supported by a growing body of evidence from basic science investigations addressing the possible efficacy and mechanisms of action of the cannabinoids in animal models of acute or chronic pain.

These preclinical findings add to the growing evidence that cannabinoid receptor agonists may be effective agents for the treatment of neuropathic pain and other types of pain.

They also point to their possible clinical utility in acute or chronic orofacial pain conditions, and thereby suggest an affirmative answer applies to the question posed in the title of this editorial.”

http://www.quintpub.com/journals/ofph/abstract.php?article_id=15025#.VPBsU033-iw

http://www.thctotalhealthcare.com/category/pain-2/

P414 Cannabidiol for symptomatic treatment of ulcerative colitis: Results from a randomised, double-blind, placebo-controlled, parallel group, multi-centred pilot study

“There is accumulating evidence that cannabidiol (CBD) has anti-inflammatory properties that could be exploited for the symptomatic relief of IBD.

This proof-of-concept double blind, randomised, placebo controlled trial assessed the efficacy, safety and tolerability of CBD botanical drug substance (BDS) in patients with mild to moderate UC…

…several signals suggest that GWP42003 may be beneficial for the symptomatic treatment of UC…”

https://www.ecco-ibd.eu/index.php/publications/congress-abstract-s/abstracts-2015/item/p414-cannabidiol-for-symptomatic-treatment-of-ulcerative-colitis-results-from-a-randomised-double-blind-placebo-controlled-parallel-group-multi-centred-pilot-study.html

http://www.thctotalhealthcare.com/category/colitis/

Neuroprotective Effect of(−)Δ9-Tetrahydrocannabinol and Cannabidiol in N-Methyl-d-Aspartate-Induced Retinal Neurotoxicity

“In glaucoma, the increased release of glutamate is the major cause of retinal ganglion cell death. Cannabinoids have been demonstrated to protect neuron cultures from glutamate-induced death.

In this study, we test the hypothesis that glutamate causes apoptosis of retinal neurons via the excessive formation of peroxynitrite, and that the neuroprotective effect of the psychotropic Δ9-tetrahydroxycannabinol (THC) or nonpsychotropic cannabidiol (CBD) is via the attenuation of this formation…

The neuroprotection by THC and CBD was because of attenuation of peroxynitrite.

The effect of THC was in part mediated by the cannabinoid receptor CB1.

These results suggest the potential use of CBD as a novel topical therapy for the treatment of glaucoma.

THC and CBD, are similarly potent antioxidants that protect neuron cultures from glutamate-induced cell death or oxidative stress…

In addition to possessing neuroprotective or retinal neuroprotective activity… cannabinoids, such as THC, have been demonstrated to induce dose-related reductions in intraocular pressure in human and in animal models. 

This suggests that cannabinoids may offer a multifaceted therapy for glaucoma.

In conclusion, our results indicate that lipid peroxidation and ONOO− formation play an important role in NMDA-induced retinal neurotoxicity and cell loss in the retina, and that THC and CBD, by reducing the formation of these compounds, are effective neuroprotectants.

The present studies could form the basis for the development of new topical therapies for the treatment of glaucoma.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1892413/

http://www.thctotalhealthcare.com/category/glaucoma-2/