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

“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

High-intensity cannabis use associated with lower plasma human immunodeficiency virus-1 RNA viral load among recently infected people who use injection drugs.

“Cannabis use is common among people who are living with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS).

While there is growing pre-clinical evidence of the immunomodulatory and anti-viral effects of cannabinoids, their possible effects on HIV disease parameters in humans are largely unknown. Thus, we sought to investigate the possible effects of cannabis use on plasma HIV-1 RNA viral loads (pVLs) among recently seroconverted illicit drug users…

Consistent with the findings from recent in vitro and in vivo studies, including one conducted among lentiviral-infected primates, we observed a strong association between cannabis use and lower pVL following seroconversion among illicit drug-using participants.

Our findings support the further investigation of the immunomodulatory or antiviral effects of cannabinoids among individuals living with HIV/AIDS.”

http://www.ncbi.nlm.nih.gov/pubmed/25389027

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

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

“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

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/

 

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

“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.”

Cannabinoid receptor 2: potential role in immunomodulation and neuroinflammation.

Figure 2

“The cannabinoids are a group of terpenophenolic compounds present in the marijuana plant, Cannabis sativa. At present, three general types of cannabinoids have been identified: phytocannabinoids present uniquely in the cannabis plant, endogenous cannabinoids produced in humans and animals, and synthetic cannabinoids generated in a laboratory. It is worth noting that Cannabis sativa produces over 80 cannabinoids…

An accumulating body of evidence suggests that endocannabinoids and cannabinoid receptors type 1 and 2 (CB(1), CB(2)) play a significant role in physiologic and pathologic processes, including cognitive and immune functions.

…there is growing appreciation of the therapeutic potential of cannabinoids in multiple pathologic conditions involving chronic inflammation (inflammatory bowel disease, arthritis, autoimmune disorders, multiple sclerosis, HIV-1 infection, stroke, Alzheimer’sdisease to name a few), mainly mediated by CB(2) activation.

This review attempts to summarize recent advances in studies of CB(2) activation in the setting of neuroinflammation, immunomodulation and HIV-1 infection.

The full potential of CB2 agonists as therapeutic agents remains to be realized.

Despite some inadequacies of preclinical models to predict clinical efficacy in humans and differences between the signaling of human and rodent CB2 receptors, the development of selective CB2 agonists may open new avenues in therapeutic intervention.

Such interventions would aim at reducing the release of pro-inflammatory mediators particularly in chronic neuropathologic conditions such as HAND or MS.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3663904/

 

Cannabinoid inhibits HIV-1 Tat-stimulated adhesion of human monocyte-like cells to extracellular matrix proteins.

“The aim of this study was to assess the effect of select cannabinoids on human immunodeficiency virus type 1 (HIV-1) transactivating (Tat) protein-enhanced monocyte-like cell adhesion to proteins of the extracellular matrix (ECM)…

KEY FINDINGS:

THC and CP55,940 inhibited Tat-enhanced attachment of U937 cells to ECM proteins in a mode that was linked to the cannabinoidreceptor type 2 (CB2R). The cannabinoid treatment of Tat-activated U937 cells was associated with altered β1-integrin expression and distribution of polymerized actin, suggesting a modality by which these cannabinoids inhibited adhesion to the ECM.

SIGNIFICANCE:

The blood-brain barrier (BBB) is a complex structure that is composed of cellular elements and an extracellular matrix (ECM). HIV-1 Tat promotes transmigration of monocytes across this barrier, a process that includes interaction with ECM proteins.

The results indicate that cannabinoids that activate the CB2R inhibit the ECM adhesion process. Thus, this receptor has potential to serve as a therapeutic agent for ablating neuroinflammation associated with HIV-elicited influx of monocytes across the BBB.”

http://www.ncbi.nlm.nih.gov/pubmed/24742657

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

[Therapeutic use of cannabis derivatives].

“The therapeutic use of cannabis has generated a lot of interest in the past years, leading to a better understanding of its mechanisms of action…

Cannabinoids such as dronabinol, Sativex and nabilone have been tested for the treatment of acute and chronic pain. These agents are most promising to relieve chronic pain associated with cancer, with human immunodeficiency virus infection and with multiple sclerosis…”

http://www.ncbi.nlm.nih.gov/pubmed/24701869

HIV/AIDS Cure May Be Found In Marijuana: Study

“It is even more evidence of our need for the government to stop punishing patients for using this relatively safe and non-toxic treatment method … ”

Curtis Rood,36, a Cohen House resident with limited mobility, smokes marijuana with the assistance of another resident on Sunday, Nov. 30,1997 in San Francisco. Cohen House provides an assisted living environment for individuals with the AIDS virus. Most of the residents use marijuana for its medicine benefits in alleviating nausua, pain, and helping to stimulate the appetite. Curtis' parrot and self proclaimed best friend, Kona, rests on his shoulder while in the backyard of Cohen House. (AP photo/Julie Stupsker)

“For years, many Americans with HIV/AIDS have used medical marijuana to relieve some common symptoms associated with the illness such as nausea, vomiting and appetite loss.

Now, a new study published last week in the journal AIDS Researcher and Human Retroviruses found that a daily dosage of marijuana’s psychoactive ingredient tetrahydrocannabinol, or THC, may actually fight the HIV/AIDS virus itself.”

More: http://www.mintpressnews.com/hivaids-cure-may-be-found-in-marijuana-study/179398/

HIV Infections Cured With Cannabis a Real Possibility

“Researchers are looking into the use of THC (tetrahydrocannabinol), the active ingredient in marijuana, to help stop the spread of HIV infection.

Hundreds of marijuana researchers have reported that THC was able to pierce the RIV virus in monkeys. That particular virus is almost identical to the HIV virus found in humans, so this news is very encouraging.

The greatest drawbacks to this excellent news are the current laws preventing testing on human candidates.

With the changing of these restrictive laws, HIV infections have a great chance of being cured, with cannabis as a real possible player in the race to stop the disease.”

More: http://guardianlv.com/2014/02/hiv-infections-cured-with-cannabis-a-real-possibility/