Cannabinoid receptor 1 is a major mediator of renal fibrosis.

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“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

Synthetic cannabis: a comparison of patterns of use and effect profile with natural cannabis in a large global sample.

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“Natural cannabis was preferred to synthetic cannabis by 93% of users, with natural cannabis rated as having greater pleasurable effects when high and being more able to function after use. Synthetic cannabis was associated with more negative effects, hangover effects, and greater paranoia…

Users report a strong preference for natural over synthetic cannabis…”

http://www.ncbi.nlm.nih.gov/pubmed/23291209

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

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“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

Protective Role of CB2 Receptor Activation in Galactosamine/LPS-induced Acute Liver Failure Through Regulation of Macrophage Polarization and miRNAs.

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“Acute liver failure (ALF) is a potentially life threatening disorder without any effective treatment strategies. D-Galactosamine/LPS (GalN/LPS)-induced ALF is a widely used animal model to identify novel hepato-protective agents.

In the present study, we investigated the potential of a Cannabinoid receptor 2 (CB2) agonist, in the amelioration of GalN/LPS induced ALF…

Together, these data demonstrate for the first time that CB2 activation attenuates GalN/LPS-induced ALF by inducing an M1 to M2 shift in macrophages and by regulating the expression of unique miRs that target key molecules involved in TLR4 pathway.”

http://www.ncbi.nlm.nih.gov/pubmed/25749929

Safety, pharmacodynamics, and pharmacokinetics of multiple oral doses of delta-9-tetrahydrocannabinol in older persons with dementia

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“In this randomized, double-blind, placebo-controlled, crossover trial, we evaluated the safety, pharmacodynamics, and pharmacokinetics of THC…

Older people with dementia and physical comorbidity could greatly benefit from the therapeutic application of cannabinoids. Recent studies have demonstrated that low doses of THC are effective in protecting the brain from neuroinflammation-induced cognitive damage.

Our findings suggest that low THC doses are safe and well tolerated by frail older persons with dementia.”

http://link.springer.com/article/10.1007/s00213-015-3889-y

“Our findings suggest that low THC doses are safe and well tolerated by frail older persons with dementia.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4480847/

 

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

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“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

The cannabinoid receptor 2 is involved in acute rejection of cardiac allografts.

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“Acute rejection of cardiac allografts is a major risk factor limiting survival of heart transplant recipients. Rejection is triggered by dendritic cell (DC) mediated activation of host T cells, amongst others CD4+ T helper (TH)1- and TH17 cells.

The cannabinoid receptor 2 (CB2) is an important modulator of cellular immune responses…

These results demonstrate that CB2 modulates in vitro cytokine responses via DCs and directly via its influence on TH1/TH17 differentiation.

These findings and the fact that allograft rejection is enhanced in Cnr2-/- mice suggest that CB2 may be a promising therapeutic target in organ transplantation.”

http://www.ncbi.nlm.nih.gov/pubmed/25744392

delta 9-tetrahydrocannabinol in clinical oncology.

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“After anecdotal reports of marijuana’s providing antiemetic activity in cancer chemotherapy patients refractory to standard agents, orally administereddelta 9-tetrahydrocannabinol (THC) was formally studied by a number of investigators.

In six of seven well-controlled studies, orally administered THC was a superior antiemetic agent compared with control agents.

Overall, the benefits of orally administered THC use represent a major advance in antiemetic therapy.”

http://www.ncbi.nlm.nih.gov/pubmed/6262541

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

Antiemetic effect of delta 9-tetrahydrocannabinol in chemotherapy-associated nausea and emesis as compared to placebo and compazine.

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“delta 9-Tetrahydrocannabinol (THC), prochlorperazine, and placebo were compared.

Nausea was absent in 40 of 55 patients receiving THC, in 8 of 55 patients receiving prochlorperazine, and in 5 of 55 in the placebo group.

THC appeared to be more efficacious in controlling the emesis associated with cyclophosphamide, 5-fluorouracil, and doxorubicin and less so for nitrogen mustard and the nitrosourea.

THC appears to offer significant control of nausea in most patients and exceeds by far that provided by prochlorperazine.”

http://www.ncbi.nlm.nih.gov/pubmed/6271846

delta 9-Tetrahydrocannabinol for refractory vomiting induced by cancer chemotherapy.

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“Fifty-three patients receiving antineoplastic chemotherapy who had experienced severe nausea and vomiting refractory to standard antiemetic agents were treated with delta 9-tetrahydrocannabinol (THC).

These patients were given THC 8 to 12 hours before, during, and for 24 hours after chemotherapy.

Ten patients (19%) had no further nausea and vomiting; 28 (53%) had at least a 50% reduction of nausea and vomiting compared to previous courses with the same agents.

We suggest that, since THC is a useful antimetic agent in patients having refractory chemotherapy-induced vomiting, existing restrictions prohibiting its therapeutic use should promptly be eased.”

http://www.ncbi.nlm.nih.gov/pubmed/6244418