“The objectives of this study were to determine basic oral pharmacokinetics, and assess safety and analgesic efficacy of a cannabidiol (CBD) based oil in dogs with osteoarthritis (OA). Results: Pharmacokinetics revealed an elimination half-life of 4.2 h at both doses and no observable side effects. Clinically, canine brief pain inventory and Hudson activity scores showed a significant decrease in pain and increase in activity (p < 0.01) with CBD oil. Veterinary assessment showed decreased pain during CBD treatment (p < 0.02). No side effects were reported by owners, however, serum chemistry showed an increase in alkaline phosphatase during CBD treatment (p < 0.01). Clinical significance: This pharmacokinetic and clinical study suggests that 2 mg/kg of CBD twice daily can help increase comfort and activity in dogs with OA.” https://www.ncbi.nlm.nih.gov/pubmed/30083539 https://www.frontiersin.org/articles/10.3389/fvets.2018.00165/full]]>
Tag Archives: cannabinoid
EHP-101, an oral formulation of the cannabidiol aminoquinone VCE-004.8, alleviates bleomycin-induced skin and lung fibrosis.
“Systemic sclerosis (SSc) or scleroderma is a chronic multi-organ autoimmune disease characterized by vascular, immunological, and fibrotic abnormalities.
The etiology of SSc is unknown, but there is growing evidence that dysfunction of the endocannabinoid system (ECS) plays a critical role in its development.
Since the semi-synthetic cannabinoquinoid VCE-004.8 could alleviate bleomycin (BLM)-induced skin fibrosis, we have investigated an oral lipid formulation (EHP-101) of this dual PPARγ/CB2 receptors activator for the prevention of skin- and lung fibrosis and of collagen accumulation in BLM challenged mice.
Taken together, these data provide a rationale for further developing VCE-004.8 as an orally active agent to alleviate scleroderma and, possibly, other fibrotic diseases as well.”
Effect of chronic THC administration in the reproductive organs of male mice, spermatozoa and in vitro fertilization.
“The increased use of cannabis as a therapeutic drug in recent years has raised some concerns due to its potential effects on reproductive health. With regards to the male, the endocannabinoid system is involved in the spermatogenesis and in the sperm function.
The chronic use of tetrahidrocannabinol (THC) has been associated with sperm anomalies, decreased sperm motility and structural changes in the testis. However, whether THC affects sperms ability to fertilize and to generate embryos remains unclear.
The aim of this study was to evaluate this effect using a mice model of THC chronic treatment. For this purpose, a chronic treatment with THC was carried out. Mice were randomly allocated into two groups: an experimental group treated with a daily dose of 10 mg/kg-body weight THC for a period of 30 days and a control group treated with a vehicle.
The THC-mice cortex showed a significant decrease of mRNA of Cnr1 compared to control-mice while, in the testis, the expression of Cnr1 was not affected. The weight of testis and epididymis and the histological analysis did not show any change between groups.
On the other hand, no changes were observed in the sperm motility or the sperm concentration. The chronic use of THC did not generate any methylation change in the three CpG regions of Cnn1 analysed, neither in the brain nor in the embryos generated by in vitro fertilization (IVF).
Finally, the embryo production by IVF was no different using spermatozoa from both THC and control mice. This work contradicts the belief that THC consumption has a negative effect on male reproductive processes.”
“The life expectancy for pancreatic cancer patients has seen no substantial changes in the last 40 years as very few and mostly just palliative treatments are available. As the five years survival rate remains around 5%, the identification of novel pharmacological targets and development of new therapeutic strategies are urgently needed.
Here we demonstrate that inhibition of the G protein-coupled receptor GPR55, using genetic and pharmacological approaches, reduces pancreatic cancer cell growth in vitro and in vivo and we propose that this may represent a novel strategy to inhibit pancreatic ductal adenocarcinoma (PDAC) progression.
Specifically, we show that genetic ablation of Gpr55 in the KRASWT/G12D/TP53WT/R172H/Pdx1-Cre+/+ (KPC) mouse model of PDAC significantly prolonged survival.
Importantly, KPC mice treated with a combination of the GPR55 antagonist Cannabidiol (CBD) and gemcitabine (GEM, one of the most used drugs to treat PDAC), survived nearly three times longer compared to mice treated with vehicle or GEM alone.
Mechanistically, knockdown or pharmacologic inhibition of GPR55 reduced anchorage-dependent and independent growth, cell cycle progression, activation of mitogen-activated protein kinase (MAPK) signalling and protein levels of ribonucleotide reductases in PDAC cells. Consistent with this, genetic ablation of Gpr55 reduced proliferation of tumour cells, MAPK signalling and ribonucleotide reductase M1 levels in KPC mice.
Combination of CBD and GEM inhibited tumour cell proliferation in KPC mice and it opposed mechanisms involved in development of resistance to GEM in vitro and in vivo. Finally, we demonstrate that the tumour suppressor p53 regulates GPR55 protein expression through modulation of the microRNA miR34b-3p.
Our results demonstrate the important role played by GPR55 downstream of p53 in PDAC progression. Moreover our data indicate that combination of CBD and GEM, both currently approved for medical use, might be tested in clinical trials as a novel promising treatment to improve PDAC patients’ outcome.”
“Rett syndrome (RTT) is a rare neurodevelopmental disorder, characterized by severe behavioural and physiological symptoms. RTT is caused by mutations in the MECP2 gene in about 95% of cases and to date no cure is available.
The endocannabinoid system modulates several physiological processes and behavioural responses that are impaired in RTT and its deregulation has been associated with neuropsychiatric disorders which have symptoms in common with RTT.
The present study evaluated the potential therapeutic efficacy for RTT of cannabidivarin (CBDV), a non-psychotropic phytocannabinoid from Cannabis sativa that presents antagonistic properties on the G protein-coupled receptor 55 (GPR55), the most recently identified cannabinoid receptor.
Present results demonstrate that systemic treatment with CBDV (2, 20, 100 mg/Kg ip for 14 days) rescues behavioural and brain alterations in MeCP2-308 male mice, a validated RTT model. The CBDV treatment restored the compromised general health status, the sociability and the brain weight in RTT mice. A partial restoration of motor coordination was also observed. Moreover, increased levels of GPR55 were found in RTT mouse hippocampus, suggesting this G protein-coupled receptor as new potential target for the treatment of this disorder.
Present findings highlight for the first time for RTT the translational relevance of CBDV, an innovative therapeutic agent that is under active investigation in the clinical setting.”
“To shed more light on the influence of chronic 
“Multipotent mesenchymal stromal cells (MSCs) support wound healing processes. These cells express toll-like receptors (TLRs). TLRs perform important key functions when the immune system is confronted with danger signals. TLR ligation by lipopolysaccharides (LPS) activates MSCs and induces intracellular signaling cascades, which affect their differentiation profile, increase the release of inflammatory cytokines and the production of reactive oxygen species. Continuing exposure to LPS triggers prolonged inflammatory reactions, which may lead to deleterious conditions, e.g. non-healing wounds.