Therapeutic Potential of Non-Psychotropic Cannabidiol in Ischemic Stroke

Posted on November 13, 2014 by David

“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/

Cannabinoids inhibit migration of microglial-like cells to the HIV protein Tat.

Posted on November 8, 2014 by David

“Microglia are a population of macrophage-like cells in the central nervous system (CNS) which, upon infection by the human immunodeficiency virus (HIV), secrete a plethora of inflammatory factors, including the virus-specified trans-activating protein Tat.

Tat has been implicated in HIV neuropathogenesis since it elicits chemokines, cytokines, and a chemotactic response from microglia. It also harbors a β-chemokine receptor binding motif, articulating a mode by which it acts as a migration stimulus.

Since select cannabinoids have anti-inflammatory properties, cross the blood-brain barrier, and target specific receptors, they have potential to serve as agents for dampening untoward neuroimmune responses.

The aim of this study was to investigate the effect of select cannabinoids on the migration of microglial-like cells toward Tat.

…it was demonstrated that the exogenous cannabinoids Delta-9-tetrahydrocannabinol (THC) and CP55940 exerted a concentration-related reduction in the migration of BV-2 cells towards Tat.

These results indicate that cannabinoid-mediated inhibition of BV-2 microglial-like cell migration to Tat is linked functionally to the CB2R…”

http://www.ncbi.nlm.nih.gov/pubmed/21735070

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

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

Posted on November 8, 2014 by David

“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/

Chronic administration of Δ9-tetrahydrocannabinol induces intestinal anti-inflammatory microRNA expression during acute SIV infection of rhesus macaques.

Posted on November 8, 2014 by David

“In SIV-infected macaques, chronic administration of Δ9-tetrahydrocannabinol (Δ9-THC), inhibited viral replication, intestinal inflammation and slowed disease progression.

Persistent gastrointestinal disease/inflammation has been proposed to facilitate microbial translocation, systemic immune activation and promote disease progression. Cannabinoids including Δ9-THC attenuated intestinal inflammation in mouse colitis models and SIV-infected rhesus macaques…

Gastrointestinal tract (GI) disease/inflammation is a hallmark of HIV/SIV infection. Previously, we showed that chronic treatment of SIV-infected macaques with Δ9 tetrahydrocannabinol (Δ9-THC) increased survival and decreased viral replication and infection induced gastrointestinal inflammation.

Here, we show that chronic THC administration to SIV-infected macaques induced an anti-inflammatory microRNA expression profile…

Overall, our results show that selective upregulation of anti-inflammatory miRNA expression, contributes to THC-mediated suppression of gastrointestinal inflammation and maintenance of intestinal homeostasis.”

http://www.ncbi.nlm.nih.gov/pubmed/25378491

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

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

Posted on October 31, 2014 by David

Image result for immunopharmacology and immunotoxicology

“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

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

Posted on October 3, 2014 by David

“… 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

Δ(9)-tetrahydrocannabinol targeting estrogen receptor signaling: the possible mechanism of action coupled with endocrine disruption.

Posted on September 30, 2014 by David

“Δ(9)-Tetrahydrocannabinol (Δ(9)-THC), a biologically active constituent of marijuana, possesses a wide variety of pharmacological and toxicological effects (e.g., analgesia, hypotension, reduction of inflammation, and anti-cancer effects).

Among Δ(9)-THC’s biological activities, its recognized anti-estrogenic activity has been the subject of investigations.

… Δ(9)-THC is used as both a drug of abuse (marijuana) and as a preventive therapeutic to treat pain and nausea in cancer patients undergoing chemotherapy…

…important to investigate the mechanistic basis underlying the anti-estrogenic activity of Δ(9)-THC…

We have recently reported that ERβ, a second type of ER, is involved in the Δ(9)-THC abrogation of E2/ERα-mediated transcriptional activity. Here we discuss the possible mechanism(s) of the Δ(9)-THC-mediated disruption of E2/ERα signaling by presenting our recent findings as well.”

http://www.ncbi.nlm.nih.gov/pubmed/25177025

Tapping into the endocannabinoid system to ameliorate acute inflammatory flares and associated pain in mouse knee joints.

Posted on September 28, 2014 by David

“During the progression of rheumatoid arthritis (RA), there are frequent but intermittent flares in which the joint becomes acutely inflamed and painful.

Although a number of drug therapies are currently used to treat RA, their effectiveness is variable and side effects are common.

Endocannabinoids have the potential to ameliorate joint pain and inflammation, but these beneficial effects are limited by their rapid degradation.

One enzyme responsible for endocannabinoid break down is fatty acid amide hydrolase (FAAH). The present study examined whether URB597, a potent and selective FAAH inhibitor, could alter inflammation and pain in a mouse model of acute synovitis.

Conclusions: These results suggest that the endocannabinoid system of the joint can be harnessed to decrease acute inflammatory reactions and the concomitant pain associated with these episodes.”

http://www.ncbi.nlm.nih.gov/pubmed/25260980

http://www.thctotalhealthcare.com/category/rheumatoid-arthritis-2/

Neuroprotective Properties of Cannabigerol in Huntington’s Disease: Studies in R6/2 Mice and 3-Nitropropionate-lesioned Mice.

Posted on September 26, 2014 by David

“Different plant-derived and synthetic cannabinoids have shown to be neuroprotective in experimental models of Huntington’s disease (HD) through cannabinoid receptor-dependent and/or independent mechanisms.

Herein, we studied the effects of cannabigerol (CBG), a nonpsychotropic phytocannabinoid, in 2 different in vivo models of HD.

CBG was extremely active as neuroprotectant in mice intoxicated with 3-nitropropionate (3NP), improving motor deficits and preserving striatal neurons against 3NP toxicity.

In addition, CBG attenuated the reactive microgliosis and the upregulation of proinflammatory markers induced by 3NP, and improved the levels of antioxidant defenses that were also significantly reduced by 3NP.

We also investigated the neuroprotective properties of CBG in R6/2 mice. Treatment with this phytocannabinoid produced a much lower, but significant, recovery in the deteriorated rotarod performance typical of R6/2 mice.

Using HD array analysis, we were able to identify a series of genes linked to this disease (e.g., symplekin, Sin3a, Rcor1, histone deacetylase 2, huntingtin-associated protein 1, δ subunit of the gamma-aminobutyric acid-A receptor (GABA-A), and hippocalcin), whose expression was altered in R6/2 mice but partially normalized by CBG treatment.

We also observed a modest improvement in the gene expression for brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), and peroxisome proliferator-activated receptor-γ (PPARγ), which is altered in these mice, as well as a small, but significant, reduction in the aggregation of mutant huntingtin in the striatal parenchyma in CBG-treated animals.

In conclusion, our results open new research avenues for the use of CBG, alone or in combination with other phytocannabinoids or therapies, for the treatment of neurodegenerative diseases such as HD.”

http://www.ncbi.nlm.nih.gov/pubmed/25252936

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

Cannabinoid receptor type 2 activation in atherosclerosis and acute cardiovascular diseases.

Posted on September 24, 2014 by David

“In the last decades, the cannabinoid system (comprising synthetic and endogenous cannabinoid agonists and antagonists, their receptors and degrading enzymes) has been shown to induce potent immunomodulatory activities in atherogenesis and acute ischemic complications.

Differently from the other cannabinoid receptors in which controversial results are reported, the selective activation of the cannabinoid receptor type 2 (CB2) has been shown to play anti-inflammatory and protective actions within atherosclerotic vessels and downstream ischemic peripheral organs.

CB2 is a transmembrane receptor that triggers protective intracellular pathways in cardiac, immune and vascular cells in both in human and animal models of atherosclerosis…

medications activating CB2 function in the circulation or peripheral target organs might be a promising approach against atherogenesis.

This review updates evidence from preclinical studies on different CB2-triggered pathways in atherosclerosis and acute ischemic events.”

http://www.ncbi.nlm.nih.gov/pubmed/25245379