Cannabidiol (CBD) and its analogs: a review of their effects on inflammation.

Posted on February 24, 2015 by David

“First isolated from Cannabis in 1940 by Roger Adams, the structure of CBD was not completely elucidated until 1963.

Subsequent studies resulted in the pronouncement that THC was the ‘active’ principle of Cannabis and research then focused primarily on it to the virtual exclusion of CBD.

This was no doubt due to the belief that activity meant psychoactivity that was shown by THC and not by CBD.

In retrospect this must be seen as unfortunate since a number of actions of CBD with potential therapeutic benefit were downplayed for many years.

In this review, attention will be focused on the effects of CBD in the broad area of inflammation where such benefits seem likely to be developed.

Topics covered in this review are; the medicinal chemistry of CBD, CBD receptor binding involved in controlling Inflammation, signaling events generated by CBD, downstream events affected by CBD (gene expression and transcription), functional effects reported for CBD and combined THC plus CBD treatment.”

http://www.ncbi.nlm.nih.gov/pubmed/25703248

Cannabinoid signaling and liver therapeutics.

Posted on February 19, 2015 by David

Journal of Hepatology Home

“Over the last decade, the endocannabinoid system has emerged as a pivotal mediator of acute and chronic liver injury, with the description of the role of CB1 and CB2 receptors and their endogenous lipidic ligands in various aspects of liver pathophysiology.

A large number of studies have demonstrated that CB1 receptor antagonists represent an important therapeutic target, owing to beneficial effects on lipid metabolism and in light of its antifibrogenic properties.

Unfortunately, the brain-penetrant CB1 antagonist rimonabant, initially approved for the management of overweight and related cardiometabolic risks, was withdrawn because of an alarming rate of mood adverse effects.

However, the efficacy of peripherally-restricted CB1 antagonists with limited brain penetrance has now been validated in preclinical models of NAFLD, and beneficial effects on fibrosis and its complications are anticipated.

CB2 receptor is currently considered as a promising anti-inflammatory and antifibrogenic target, although clinical development of CB2 agonists is still awaited.

In this review, we highlight the latest advances on the impact of the endocannabinoid system on the key steps of chronic liver disease progression and discuss the therapeutic potential of molecules targeting cannabinoid receptors…

Overwhelming evidence supports the therapeutic potential of peripherally-restricted CB1 antagonists and CB2 agonists in the management of chronic liver diseases.”

http://www.journal-of-hepatology.eu/article/S0168-8278(13)00212-2/fulltext

http://www.thctotalhealthcare.com/category/liver-disease/

Cannabinoid CB2 receptors protect against alcoholic liver disease by regulating Kupffer cell polarization in mice.

Posted on February 19, 2015 by David

“Activation of Kupffer cells plays a central role in the pathogenesis of alcoholic liver disease.

Because cannabinoid CB2 receptors (CB2) display potent anti-inflammatory properties, we investigated their role in the pathogenesis of alcoholic liver disease, focusing on the impact of CB2 on Kupffer cell polarization and the consequences on liver steatosis.

Altogether, these findings demonstrate that CB2 receptors display beneficial effects on alcohol-induced inflammation by regulating M1/M2 balance in Kupffer cells, thereby reducing hepatocyte steatosis via paracrine interactions between Kupffer cells and hepatocytes.

These data identify CB2 agonists as potential therapeutic agents for the management of alcoholic liver disease.”

http://www.ncbi.nlm.nih.gov/pubmed/21735467

http://www.thctotalhealthcare.com/category/liver-disease/

Tonic Modulation of Nociceptive Behavior and Allodynia by Cannabinoid Receptors in Formalin Test in Rats.

Posted on February 18, 2015 by David

“Cannabinoids produce anti-nociceptive and anti-hyperalgesic effects in acute, inflammatory and neuropathic pain models.

The current study investigated the role of cannabinoid (CB1 and CB2) receptors in modulating formalin-induced nociceptive behavior and mechanical allodynia in the rat…

The results indicate that CB1 and CB2 receptors mediate a tonically inhibitory action on formalin-induced inflammatory pain, especially long-term allodynia, in bilateral hind paws.”

http://www.ncbi.nlm.nih.gov/pubmed/25687494

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

Decreased glial reactivity could be involved in the antipsychotic-like effect of cannabidiol.

Posted on February 15, 2015 by David

“Cannabidiol (CBD), a major non-psychotomimetic constituent of Cannabis sativa with anti-inflammatory and neuroprotective properties induces antipsychotic-like effects.

The present study evaluated if repeated treatment with CBD would attenuate the behavioral and glial changes observed in an animal model of schizophrenia…

These data reinforces the proposal that CBD may induce antipsychotic-like effects.

Although the possible mechanism of action of these effects is still unknown, it may involve CBD anti-inflammatory and neuroprotective properties.

Furthermore, our data support the view that inhibition of microglial activation may improve schizophrenia symptoms.”

http://www.ncbi.nlm.nih.gov/pubmed/25680767

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

Activation of Cannabinoid Type Two Receptors (CB2) Diminish Inflammatory Responses in Macrophages and Brain Endothelium.

Posted on February 11, 2015 by David

“Chronic neuroinflammatory disorders (such as HIV associated neurodegeneration) require treatment that decreases production of inflammatory factors by activated microglia and macrophages and protection of blood brain barrier (BBB) injury secondary to activation of brain endothelium.

Cannabioid type 2 receptor (CB2) is highly expressed on macrophages and brain microvasular enndothelial cells (BMVEC) and is upregulated in inflammation and HIV infection. It has been shown that CB2 activation dampened inflammatory responses in macrophages and BMVEC.

In this study, we assessed by PCR array the expression of a wide range of genes increased in macrophages and BMVEC in inflammation. TNFα treatment upregulated 33 genes in primary human BMVEC, and two highly selective CB2 agonists diminished expression of 31 and 32 genes.

These results were confirmed by functional assays (BBB protection after inflammatory insult and decreased migration of monocytes across BMVEC monolayers after CB2stimulation). Similarly, CB2 stimulation in primary human macrophages led to the suppression of 35 genes out of the 50 genes upregulated by LPS. Such changes in gene expression paralleled diminished secretion of proinflammatory factors.

These results indicate the potential utility of CB2agonists for the treatment of neuroinflammation.”

http://www.ncbi.nlm.nih.gov/pubmed/25666933

THE EFFECT OF PHYTOCANNABINOIDS ON AIRWAY HYPERRESPONSIVENESS, AIRWAY INFLAMMATION AND COUGH.

Posted on February 7, 2015 by David

“Cannabis has been demonstrated to have bronchodilator, anti-inflammatory and anti-tussive activity in the airways, but, information on the active cannabinoids, their receptors and the mechanisms for their effects is limited.

We compared the effects of Δ9-tetrahydrocannabinol, cannabidiol, cannabigerol, cannabichromene, cannabidiolic acid and tetrahydrocannabivarin…

The other cannabinoids did not influence cholinergic transmission and only Δ9-THC demonstrated effects on airway hyperresponsiveness, anti-inflammatory activity and antitussive activity in the airways.”

http://www.ncbi.nlm.nih.gov/pubmed/25655949

http://jpet.aspetjournals.org/content/early/2015/02/05/jpet.114.221283.long

Cannabinoid Receptor CB2 Is Involved in Tetrahydrocannabinol-Induced Anti-Inflammation against Lipopolysaccharide in MG-63 Cells.

Posted on February 6, 2015 by David

“Cannabinoid Δ9-tetrahydrocannabinol (THC) is effective in treating osteoarthritis (OA)…

Activation of cannabinoid receptor CB2 reduces inflammation; whether the activation CB2 is involved in THC-induced therapeutic action for OA is still unknown.

We hypothesized that the activation of CB2 is involved in THC-induced anti-inflammation in the MG-63 cells exposed to LPS, and the anti-inflammation is mediated by cofilin-1…

We found that THC suppressed the release of proinflammatory factors, including tumor necrosis factor α (TNF-α), interleukin- (IL-) 1β, IL-6, and IL-8, decreased nuclear factor-κB (NF-κB) expression, and inhibited the upregulation of cofilin-1 protein in the LPS-stimulated MG-63 cells.

These results suggested that CB2 is involved in the THC-induced anti-inflammation in LPS-stimulated MG-63 cells, and the anti-inflammation may be mediated by cofilin-1.”

http://www.ncbi.nlm.nih.gov/pubmed/25653478

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4310496/

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

Regulation of inflammation and proliferation of human bladder carcinoma cells by type-1 and type-2 cannabinoid receptors.

Posted on January 28, 2015 by David

“Pro-inflammatory cytokines, growth and angiogenic factors released by leukocytes are involved in carcinogenesis and cancer progression, but they are also crucial for fighting tumour growth and spreading.

We have previously demonstrated that endocannabinoids modulate cell-to-cell crosstalk during inflammation. Here, we investigated the inflammatory and tumourigenic properties of endocannabinoids in a human urinary bladdercarcinoma cell line…

Collectively, these findings suggest that CB receptors may play distinct roles in cancer biology, depending on the specific ligand employed.

CONCLUSIONS:

The in vivo assessment of the role of CB receptors in inflammation and cancer might be instrumental in broadening the understanding about bladder cancer biology.”

http://www.ncbi.nlm.nih.gov/pubmed/25445433

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

The effects of Δ9-tetrahydrocannabinol and cannabidiol alone and in combination on damage, inflammation and in vitro motility disturbances in rat colitis

Posted on January 27, 2015 by David

“Cannabis is taken as self-medication by patients with inflammatory bowel disease for symptomatic relief.

Cannabinoid receptor agonists decrease inflammation in animal models of colitis, but their effects on the disturbed motility is not known. (-)-Cannabidiol (CBD) has been shown to interact with Δ9-tetrahydrocannabinol (THC) in behavioural studies, but it remains to be established if these cannabinoids interact in vivo in inflammatory disorders.

Therefore the effects of CBD and THC alone and in combination were investigated in a model of colitis…

In this model of colitis, THC and CBD not only reduced inflammation but also lowered the occurrence of functional disturbances. Moreover the combination of CBD and THC could be beneficial therapeutically, via additive or potentiating effects.

As the two phytocannabinoids modulate the immune system and differ in their pharmacological profile, their combination could be more beneficial than either drug alone. Additionally CBD could not only potentiate the therapeutic effects of THC, but also attenuate some of its undesirable effects…”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2931570/

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