“Recent research has indicated that cannabinoid-based therapies might be effective in ameliorating the most important symptoms of COPD.” “Researchers have observed that cannabinoids can be bronchodilatory, immunosuppressive, and anti-inflammatory, suggesting that cannabinoid-based therapies might offer safer and more effective treatment options for COPD.” “Additionally, studies have suggested that cannabinoids might help promote better sleep, support the immune system, work as an expectorant, relieve pain, and have anti-microbial properties.” https://copdnewstoday.com/2016/12/08/inmed-announces-progress-copd-treatment-using-cannabinoids/ http://www.thctotalhealthcare.com/category/copd-chronic-obstructive-pulmonary-disease/]]>
Tag Archives: anti-inflammatory
Cannabinoid CB2 receptor ligand profiling reveals biased signalling and off-target activity.
“The cannabinoid CB2 receptor (CB2R) represents a promising therapeutic target for various forms of tissue injury and inflammatory diseases. Although numerous compounds have been developed and widely used to target CB2R, their selectivity, molecular mode of action and pharmacokinetic properties have been poorly characterized. Here we report the most extensive characterization of the molecular pharmacology of the most widely used CB2R ligands to date. In a collaborative effort between multiple academic and industry laboratories, we identify marked differences in the ability of certain agonists to activate distinct signalling pathways and to cause off-target effects. We reach a consensus that HU910, HU308 and JWH133 are the recommended selective CB2R agonists to study the role of CB2R in biological and disease processes. We believe that our unique approach would be highly suitable for the characterization of other therapeutic targets in drug discovery research.”
Potent immunomodulatory activity of a highly selective cannabinoid CB2 agonist on immune cells from healthy subjects and patients with multiple sclerosis.
“COR167, a novel CB2-selective high affinity agonist, was found to significantly inhibit, in a dose-dependent manner, the proliferation of both peripheral blood mononuclear cells and myelin basic protein-reactive T cell lines from normal healthy subjects and patients with relapsing-remitting multiple sclerosis (MS). In MS, a significantly higher inhibition was observed in patients on treatment with disease modifying drugs compared to those naive to treatment. The inhibitory activity of COR167 was exerted through a mixed mechanism involving atypical and incomplete shift of Th1 phenotype towards Th2 phenotype associated with slight reduction of IL-4 and IL-5 as well as strongly reduced levels of Th17-related cytokines. COR167 was also able to reduce in vitro migration of stimulated immunocompetent cells through human brain endothelium associated with a significant reduction of levels of several chemokines. These findings demonstrate that COR167 exerts potent immunomodulatory effects and confirm the cannabinoid CB2 receptor as a novel pharmacological target to counteract neuroinflammation.” https://www.ncbi.nlm.nih.gov/pubmed/28041663]]>
Dietary olive oil induces cannabinoid CB2 receptor expression in adipose tissue of ApcMin/+ transgenic mice.
“Cannabinoid– 2 (CB2) receptor is known for its anti-obesity effects silencing the activated immune cells that are key drivers of metabolic syndrome and inflammation.
Nutritional interventions in experimental models of carcinogenesis have been demonstrated to modulate tissue inflammation state and proliferation.
OBJECTIVE: Aim of this study was to test, in ApcMin/+ mice, whether a diet enriched with olive oil, omega- 3 and omega-6- PUFAs affects the adipose tissue inflammation status.
RESULTS: The diet enriched with olive oil significantly induced CB2 receptor expression and it was able to control inflammatory and proliferative activity of mice adipose tissue.
CONCLUSIONS: The present findings open opportunities for developing novel nutritional strategies considering olive oil a key ingredient of a healthy dietary pattern.”
Synergistic attenuation of chronic pain using mu opioid and cannabinoid receptor 2 agonists.
“The misuse of prescription opiates is on the rise with combination therapies (e.g. acetaminophen or NSAIDs) resulting in severe liver and kidney damage. In recent years, cannabinoid receptors have been identified as potential modulators of pain and rewarding behaviors associated with cocaine, nicotine and ethanol in preclinical models. Yet, few studies have identified whether mu opioid agonists and CB2 agonists act synergistically to inhibit chronic pain while reducing unwanted side effects including reward liability.
We determined if analgesic synergy exists between the mu-opioid agonist morphine and the selective CB2 agonist, JWH015, in rodent models of acute and chronic inflammatory, post-operative, and neuropathic pain using isobolographic analysis. We also investigated if the MOR-CB2 agonist combination decreased morphine-induced conditioned place preference (CPP) and slowing of gastrointestinal transit. Co-administration of morphine with JWH015 synergistically inhibited preclinical inflammatory, post-operative and neuropathic-pain in a dose- and time-dependent manner; no synergy was observed for nociceptive pain. Opioid-induced side effects of impaired gastrointestinal transit and CPP were significantly reduced in the presence of JWH015.
Here we show that MOR + CB2 agonism results in a significant synergistic inhibition of preclinical pain while significantly reducing opioid-induced unwanted side effects.
The opioid sparing effect of CB2 receptor agonism strongly supports the advancement of a MOR-CB2 agonist combinatorial pain therapy for clinical trials.”
Cannabidiol reduces brain damage and improves functional recovery in a neonatal rat model of arterial ischemic stroke.
“Currently there is no effective treatment for neonatal arterial ischemic stroke (AIS).
Cannabidiol (CBD) is neuroprotective in models of newborn hypoxic-ischemic brain damage and adult stroke.
The purpose of this work was to study the protective effect of CBD in a neonatal rat model of AIS.
RESULTS:
CBD administration improved neurobehavioral function regarding strength, hemiparesis, coordination and sensorimotor performance as assessed at P15 and P38. MRI indicated that CBD did not reduce the volume of infarct but reduced the volume of perilesional gliosis. H+-MRS indicated that CBD reduced metabolic derangement and excitotoxicty, and protected astrocyte function. Histologic studies indicated that CBD reduced neuronal loss and apoptosis, and modulated astrogliosis and microglial proliferation and activation.
CONCLUSIONS:
CBD administration after Middle Cerebral Artery Occlusion (MCAO) led to long-term functional recovery, reducing neuronal loss and astrogliosis, and modulating apoptosis, metabolic derangement, excitotoxicity and neuro-inflammation.”
https://www.ncbi.nlm.nih.gov/pubmed/28012949
“Post-stroke administration of Cannabidiol (CBD) is neuroprotective in neonatal rats. CBD neuroprotection is sustained in the long term. CBD treatment led to functional recovery in both motor and sensorimotor domains. CBD modulated excitotoxicity, astrocyte dysfunction and microglial activation.”
https://www.sciencedirect.com/science/article/pii/S0028390816305810
CB2 receptors regulate natural killer cells that limit allergic airway inflammation in a murine model of asthma.
“Allergic asthma is a chronic airway inflammatory disease involving the complementary actions of innate and adaptive immune responses.
Endogenously generated cannabinoids, acting via CB2 receptors play important roles in both homeostatic and inflammatory processes. However, the contribution of CB2-acting eicosanoids to the innate events preceding sensitization to the common house dust mite (HDM) allergen, remain to be elucidated. We investigated the role of CB2 activation during allergen-induced pulmonary inflammation and NK cell effector function.
CONCLUSIONS:
Collectively, these results reveal that CB2 activation is crucial in regulating pulmonary NK cell function, and suggest that NK cells serve to limit ILC2 activation and subsequent allergic airway inflammation. CB2 inhibition may present an important target to modulate NK cell response during pulmonary inflammation.”
In vitro Antimicrobial and Antioxidant Activity of Extracts from Six Chemotypes of Medicinal Cannabis
“Nowadays, medicinal cannabis (Cannabis sativa L) is in the focus of the researches not only for its high content of tetrahydrocannabinol (THC), but for other cannabinoids as well.
It has been reported that some of the identified substances (e.g. cannabidiol, cannabinochromene) possess anti-inflammatory and antimicrobial properties, which corresponds to its traditional use as wound healing agent at Pakistan.
The aim of this study was to evaluate antimicrobial and antioxidant ability of extracts from high potent Cannabis sativa chemotypes.
The six ethanolic extracts prepared from dried inflorescence of five medicinal cannabis chemotypes (Nurse Jackie, Jilly Bean, Nordle, Jack Cleaner, Conspiracy Kush) were tested by standard microdilution method against Staphylococcus aureus (three strains), Streptococcus pyogenes and the yeast Candida albicans.
Those microbial strains are present on skin and can cause complication during wound healing process.
The antioxidative activity, which plays an important role in wound healing process, was tested by oxygen radical absorbance capacity test (ORAC).
All tested extracts demonstrated high antimicrobial activity against two strains of S. aureus and S. pyogenes (MIC ranged from 4 – 16 µg·mL-1), moreover high antioxidant capacity was observed (ORAC ranged from 800 – 1300 µg TE/mg of extract).
The results indicate that cannabis has high potential to be used in ointments and other material for wound healing.
However, further research on the identification of the active components is needed.”
https://www.thieme-connect.com/DOI/DOI?10.1055/s-0036-1596302
Cannabinoid 2 Receptor Agonist Improves Systemic Sensitivity to Insulin in High-Fat Diet/Streptozotocin-Induced Diabetic Mice.
“The endocannabinoid signalling (ECS) system has been known to regulate glucose homeostasis.
Previous studies have suggested that the cannabinoid 2 (CB2) receptor may play a regulatory role on insulin secretion, immune modulation and insulin resistance.
Given that diabetes and insulin resistance are attributable to elevated inflammatory tone, we investigated the role of CB2 receptor on glucose tolerance and insulin sensitivity in high-fat diet (HFD)/streptozotocin (STZ)-induced mice.
Our data suggest a lipolytic role of SER601 in HFD/STZ-induced diabetic mice, which results in significant improvement of systemic insulin sensitivity.
Thus, the CB2 receptor may be considered a promising target for therapeutic development against insulin resistance and obesity-related diabetes.”
Compensatory activation of cannabinoid CB2 receptor inhibition of GABA release in the rostral ventromedial medulla (RVM) in inflammatory pain.
“The rostral ventromedial medulla (RVM) is a relay in the descending pain modulatory system and an important site of endocannabinoid modulation of pain.
These studies demonstrate that endocannabinoid signaling to CB1- and CB2-receptors in adult RVM is altered in persistent inflammation.
The emergence of CB2 receptor function in the RVM provides additional rationale for the development of CB2 receptor-selective agonists as useful therapeutics for chronic inflammatory pain.”