Therapeutic Potential of Non-Psychotropic Cannabidiol in Ischemic Stroke

“Cannabis contains over 60 different terpeno-phenol compounds…

cannabidiol (CBD), cannabigerol (CBG), cannabidivarin (CBDV) are known as non-psychoactive components of cannabis.

These compounds have shown anti-inflammatory, immunosuppressive, analgesic, anxiolytic and anti-cancer effects…

Cannabinoids may play a role in neuroprotection in disorders such as stroke, Parkinson’s disease, traumatic brain injury and epilepsy…

It is well-known that delta9-THC and other cannabinoid CB1 receptor agonists are neuroprotective during global and focal ischemic injury…

Accumulating data now suggest that cannabinoid CB1 receptors contribute to neuroprotection… Emerging data now support the evidence of the anti-inflammatory action of CBD…

 We have previously reported that CBD  has a potent and long-lasting neuroprotective effect when administered both pre- and post-ischemia, whereas only pre-ischemic treatment with delta9-THC reduced the infarction size…

These results suggest that CBD may prevent post-ischemic injury progressively induced by ischemic stroke….

…anti-inflammatory, anti-oxidant, and neuroprotective effects of CBD. In particular, CBD exerts positive pharmacological effects in ischemic stroke and other chronic diseases, including Parkinson’s disease, Alzheimer’s disease, and rheumatoid arthritis.

The cerebroprotective action of CBD is CB1 receptor-independent, long-lasting, and has potent anti-oxidant activity. Importantly, CBD use does not lead to tolerance.

In the last 10 years, it has been possible to demonstrate that CBD has the following unique therapeutic profile: 1) a cannabinoid receptor-independent mechanism, 2) long-lasting cerebro- protective effect after ischemic stroke, and lack of development of tolerance.

Moreover, CBD has almost no side effects, including psychotropic activity.

Preliminary studies highlight the fact that the multifunctional actions of CBD may lead to benefits in more complex systems within the brain after ischemic stroke.

CBD offers new therapeutic possibilities for treating ischemic stroke…”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4036658/

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

Cannabinoid inhibition of macrophage migration to the trans-activating (Tat) protein of HIV-1 is linked to the CB(2) cannabinoid receptor.

“Macrophages and macrophage-like cells are important targets of HIV-1 infection at peripheral sites and in the central nervous system…

 

Collectively, the pharmacological and biochemical knockdown data indicate that cannabinoid-mediated modulation of macrophage migration to the HIV-1 Tat protein is linked to the CB(2)cannabinoid receptor.

Furthermore, these results suggest that the CB(2) cannabinoid receptor has potential to serve as a therapeutic target for ablation of HIV-1-associated untoward inflammatory response.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2846023/

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

 

Cannabidiol improves lung function and inflammation in mice submitted to LPS-induced acute lung injury.

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“We have previously shown that the prophylactic treatment with cannabidiol (CBD) reduces inflammation in a model of acute lung injury (ALI).

In this work we analyzed the effects of the therapeutic treatment with CBD in mice subjected to the model of lipopolysaccharide (LPS)-induced ALI on pulmonary mechanics and inflammation.

The results show that CBD decreased total lung resistance and elastance, leukocyte migration into the lungs, myeloperoxidase activity in the lung tissue, protein concentration and production of pro-inflammatory cytokines (TNF and IL-6) and chemokines (MCP-1 and MIP-2) in the bronchoalveolar lavage supernatant.

Thus, we conclude that CBD administered therapeutically, i.e. during an ongoing inflammatory process, has a potent anti-inflammatory effect and also improves the lung function in mice submitted to LPS-induced ALI.

Therefore the present and previous data suggest that in the future cannabidiol might become a useful therapeutic tool for the attenuation and treatment of inflammatory lung diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/25356537

Cannabinoid Type 1 and Type 2 Receptor Antagonists Prevent Attenuation of Serotonin-Induced Reflex Apneas by Dronabinol in Sprague-Dawley Rats.

“The prevalence of obstructive sleep apnea (OSA) in Americans is 9% and increasing…

Vagal afferent neurons are inhibited by cannabinoid type 1 (CB1) or cannabinoid type 2 (CB2) receptors in animal models of vagally-mediated behaviors…

These findings underscore the therapeutic potential of dronabinol (THC) in the treatment of OSA and implicate participation of both cannabinoid receptors in dronabinol’s apnea suppression effect.”

http://www.ncbi.nlm.nih.gov/pubmed/25350456

http://www.thctotalhealthcare.com/category/sleep-apnea/

Endocannabinoids, Related Compounds and Their Metabolic Routes.

“Endocannabinoids are lipid mediators able to bind to and activate cannabinoid receptors, the primary molecular targets responsible for the pharmacological effects of the Δ9-tetrahydrocannabinol.

These bioactive lipids belong mainly to two classes of compounds: N-acylethanolamines and acylesters, being N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG), respectively, their main representatives.

During the last twenty years, an ever growing number of fatty acid derivatives (endocannabinoids and endocannabinoid-like compounds) have been discovered and their activities biological is the subject of intense investigations.

Here, the most recent advances, from a therapeutic point of view, on endocannabinoids, related compounds, and their metabolic routes will be reviewed.”

http://www.ncbi.nlm.nih.gov/pubmed/25347455

Evaluation of the tolerability and efficacy of Sativex in multiple sclerosis.

“Refractory spasticity, central neuropathic pain and bladder dysfunction are common clinical problems in patients with multiple sclerosis (MS). None of the currently available oral medications has proven to be reliably effective and can be limited by toxicity.

Cannabinoids have shown therapeutic effects on those MS-associated symptoms.

Delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) Sativex (nabiximols) is an oromucosal spray formulation that contains THC and CBD in an approximate 1:1 ratio and is described as an endocannabinoid system modulator.

The efficacy of THC/CBD on MS-associated spasticity, pain and bladder dysfunction has been studied in clinical trials as well as in clinical practice studies. Adverse effects are usually mild or moderate and the low rate of drug discontinuation provides good evidence of long-term tolerability. This article focuses on the pharmacological properties, clinical efficacy and tolerability of THC/CBD in MS patients.”

http://www.ncbi.nlm.nih.gov/pubmed/25331416

Type-2 cannabinoid receptor regulates proliferation, apoptosis, differentiation, and OPG/RANKL ratio of MC3T3-E1 cells exposed to Titanium particles.

“The type-2 cannabinoid receptor (CB2) is expressed in osteoblasts and plays a role in bone metabolism through regulation on bone mass and bone turnover, but the functional importance of CB2 in osteoblasts under Titanium (Ti) stimulation is incompletely understood.

This study aimed to investigate the CB2 expression in osteoblasts under Ti stimulation and the effects of CB2 activation on proliferation, apoptosis, differentiation, mineralization, OPG, and RANKL expression of MC3T3-E1 cells exposed to Ti particles…

In conclusion, CB2 activation has a favorable inhibitory effect on Ti-induced reactions in MC3T3-E1 cell through modulating proliferation, apoptosis, differentiation, and RANKL expression.

These findings suggest that activation of CB2 might be an effective therapeutic strategy to promote bone formation and reduce bone dissolution.”

http://www.ncbi.nlm.nih.gov/pubmed/25292314

Cannabinoids Alleviate Experimentally Induced Intestinal Inflammation by Acting at Central and Peripheral Receptors.

“… an attempt to further investigate the role of cannabinoid (CB) system in the pathogenesis of inflammatory bowel diseases…

CONCLUSIONS:

This is the first evidence that central and peripheral CB receptors are responsible for the protective and therapeutic action of cannabinoids in mouse models of colitis.

Our observations provide new insight to CB pharmacology and validate the use of novel ligands AM841 and CB13 as potent tools in CB-related research.”

http://www.ncbi.nlm.nih.gov/pubmed/25275313

Using the endocannabinoid system as a neuroprotective strategy in perinatal hypoxic-ischemic brain injury.

“One of the most important causes of brain injury in the neonatal period is a perinatal hypoxic-ischemic event. This devastating condition can lead to long-term neurological deficits or even death. After hypoxic-ischemic brain injury, a variety of specific cellular mechanisms are set in motion, triggering cell damage and finally producing cell death.

Effective therapeutic treatments against this phenomenon are still unavailable because of complex molecular mechanisms underlying hypoxic-ischemic brain injury. After a thorough understanding of the mechanism underlying neural plasticity following hypoxic-ischemic brain injury, various neuroprotective therapies have been developed for alleviating brain injury and improving long-term outcomes.

Among them, the endocannabinoid system emerges as a natural system of neuroprotection.

The endocannabinoid system modulates a wide range of physiological processes in mammals and has demonstrated neuroprotective effects in different paradigms of acute brain injury, acting as a natural neuroprotectant.

The aim of this review is to study the use of different therapies to induce long-term therapeutic effects after hypoxic-ischemic brain injury, and analyze the important role of the endocannabinoid system as a new neuroprotective strategy against perinatal hypoxic-ischemic brain injury.”

http://www.ncbi.nlm.nih.gov/pubmed/25206720

Oxidative stress and cannabinoid receptor expression in type-2 diabetic rat pancreas following treatment with Δ9 -THC.

“We can suggest that Δ9 -THC may be an important agent for the treatment of oxidative damages induced by diabetes…

Furthermore, the present study for the first time emphasizes that Δ9 -THC may improve pancreatic cells via cannabinoid receptors in diabetes.

The aim of present study was to elucidate the effects of Δ9 -THC, a natural cannabinoid receptor agonist, on the expression and localization of cannabinoid receptors, and oxidative stress statue in type-2 diabetic rat pancreas.

Results demonstrate that the cannabinoid receptors are presented in both Langerhans islets and duct regions.

The curative effects of Δ9 -THC can be occurred via activation of cannabinoid receptors in diabetic rat pancreas.

Moreover, it may provide a protective effect against oxidative damage induced by diabetes.

Thus, it is suggested that Δ9 -THC can be a candidate for therapeutic alternatives of diabetes symptoms.”

http://www.ncbi.nlm.nih.gov/pubmed/25187240

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