Cannabinoid Attenuation of Intestinal Inflammation in Chronic SIV-Infected Rhesus Macaques Involves T Cell Modulation and Differential Expression of Micro-RNAs and Pro-inflammatory Genes.

Posted on May 24, 2019 by David

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“Cannabis use is frequent in HIV-infected individuals for its appetite stimulation and anti-inflammatory effects. To identify the underlying molecular mechanisms associated with these effects, we simultaneously profiled micro-RNA (miRNA) and mRNA expression in the colon of chronically simian immunodeficiency virus (SIV)-infected rhesus macaques administered either vehicle (VEH/SIV; n = 9) or Δ⁹-tetrahydrocannabinol (Δ⁹-THC; THC/SIV; n = 8).

Pro-inflammatory miR-130a, miR-222, and miR-29b, lipopolysaccharide-responsive miR-146b-5p and SIV-induced miR-190b were significantly upregulated in VEH/SIV rhesus macaques. Compared to VEH/SIV rhesus macaques, 10 miRNAs were significantly upregulated in THC/SIV rhesus macaques, among which miR-204 was confirmed to directly target MMP8, an extracellular matrix-degrading collagenase that was significantly downregulated in THC/SIV rhesus macaques. Moreover, THC/SIV rhesus macaques failed to upregulate pro-inflammatory miR-21, miR-141 and miR-222, and alpha/beta-defensins, suggesting attenuated intestinal inflammation.

Further, THC/SIV rhesus macaques showed higher expression of tight junction proteins (occludin, claudin-3), anti-inflammatory MUC13, keratin-8 (stress protection), PROM1 (epithelial proliferation), and anti-HIV CCL5. Gomori one-step trichrome staining detected significant collagen deposition (fibrosis) in the paracortex and B cell follicular zones of axillary lymph nodes from all VEH/SIV but not in THC/SIV rhesus macaques, thus demonstrating the ability of Δ⁹-THC to prevent lymph node fibrosis, a serious irreversible consequence of HIV induced chronic inflammation.

Furthermore, using flow cytometry, we showed that Δ⁹-THC suppressed intestinal T cell proliferation/activation (Ki67/HLA-DR) and PD-1 expression and increased the percentages of anti-inflammatory CD163⁺ macrophages. Finally, while Δ⁹-THC did not affect the levels of CD4⁺ T cells, it significantly reduced absolute CD8⁺ T cell numbers in peripheral blood at 14 and 150 days post-SIV infection.

These translational findings strongly support a role for differential miRNA/gene induction and T cell activation in Δ⁹-THC-mediated suppression of intestinal inflammation in HIV/SIV and potentially other chronic inflammatory diseases of the intestine.”

https://www.ncbi.nlm.nih.gov/pubmed/31114576

https://www.frontiersin.org/articles/10.3389/fimmu.2019.00914/full

Effect of Cannabis Use on HIV DNA during Suppressive ART.

Posted on May 11, 2019 by David

Infectious Diseases Society of America

“Cannabis use is frequent among people living with HIV and is associated with reduced systemic inflammation. We observed a faster HIV DNA decay during antiretroviral therapy among cannabis users, compared to no drug use. No cannabis-effect was observed on cellular HIV RNA transcription.”

https://www.ncbi.nlm.nih.gov/pubmed/31074488

Oral cannabinoids in people living with HIV on effective antiretroviral therapy: CTN PT028-study protocol for a pilot randomised trial to assess safety, tolerability and effect on immune activation.

Posted on January 20, 2019 by David

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“Cannabis when taken orally may represent a way to reduce inflammation and strengthen immune responses.”

https://www.ncbi.nlm.nih.gov/pubmed/30659041 https://bmjopen.bmj.com/content/9/1/e024793

Activation of GPR55 induces neuroprotection of hippocampal neurogenesis and immune responses of neural stem cells following chronic, systemic inflammation.

Posted on November 24, 2018 by David

Brain, Behavior, and Immunity

“New neurons are continuously produced by neural stem cells (NSCs) within the adult hippocampus. Numerous diseases, including major depressive disorder and HIV-1 associated neurocognitive disorder, are associated with decreased rates of adult neurogenesis. A hallmark of these conditions is a chronic release of neuroinflammatory mediators by activated resident glia.

Recent studies have shown a neuroprotective role on NSCs of cannabinoid receptor activation. Yet, little is known about the effects of GPR55, a candidate cannabinoid receptor, activation on reductions of neurogenesis in response to inflammatory insult.

In the present study, we examined NSCs exposed to IL-1β in vitro to assess inflammation-caused effects on NSC differentiation and the ability of GPR55 agonists to attenuate NSC injury.

Taken together, these results suggest a neuroprotective role of GPR55 activation on NSCs in vitro and in vivo and that GPR55 provides a novel therapeutic target against negative regulation of hippocampal neurogenesis by inflammatory insult.”

https://www.ncbi.nlm.nih.gov/pubmed/30465881

https://www.sciencedirect.com/science/article/pii/S0889159118303246?via%3Dihub

Cannabinoids and reduced risk of hepatic steatosis in HIV-HCV co-infection: paving the way for future clinical research

Posted on August 21, 2018 by David

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“Whether or not cannabis itself or cannabinoids contained in it may help to reduce hepatic steatosis in HIV-HCV coinfected patients remains an open question. The existing body of knowledge on the interactions between cannabis and the liver suggest a protective effect of cannabinoids on insulin resistance, diabetes, and NAFLD in the general population. Clinical research with randomized study designs is needed to evaluate the efficacy and safety of cannabis-based pharmacotherapies in HIV-HCV coinfected patients. Targeting the endocannabinoid system seems essential to differently manage several pathological conditions such as intestinal inflammation, obesity, diabetes and fatty liver disease. However, to date, few drugs have been tested in clinical trials. CB1-antagonists and CB2 agonists appear to be viable therapeutic options that need to be explored for the management of liver diseases. As HCV cure rates are coming close to 100% in the era of direct-acting antivirals, it is especially important to be able to identify modifiable risk factors of complications and death in HIV-HCV coinfected patients, as well as possible levers for intervention. Given the persistence of metabolic risk factors after HCV eradication, cannabis-based therapies need to be evaluated both as preventive and therapeutic tools in patients living with or at risk of liver steatosis, possibly in combination with existing conventional approaches.”

https://www.tandfonline.com/doi/full/10.1080/14787210.2018.1473764

Interferon- α-mediated Activation of T Cells from Healthy and HIV-infected Individuals is Suppressed by Δ 9 -Tetrahydrocannabinol

Posted on July 23, 2018 by David

Journal of Pharmacology and Experimental Therapeutics

“HIV patients routinely use medicinal cannabinoids to treat neuropathic pain, anxiety, and HIV-associated wasting. However, Δ ⁹ -Tetrahydrocannabinol (THC), the primary psychoactive cannabinoid in cannabis, suppresses T cell function and secretion of interferons, both critically important in the anti-viral immune response.

Interferon- α (IFN α), a key cytokine in T cell activation and peripheral control of HIV infection, can potentiate responsiveness to IL-7, a crucial homeostatic cytokine for peripheral T cell maintenance. . The objective of this investigation was to compare the response of T cells to stimulation by IFNα and IL-7 in T cells from healthy and HIV+ donors in the absence and presence of THC.

T cells from healthy and HIV+ donors were stimulated in vitrowith IFN α and IL-7 in the absence and presence of THC followed by measurements of signaling events through IFNAR, IFN α-induced expression of IL-7Rα, cognate signaling through IL-7R, and on IL-7-mediated T cell proliferation by flow cytometry and RT-qPCR. CD8⁺ T cells from HIV+ donors showed a diminished response to IFN α-induced pSTAT1 compared to CD8⁺ T cells from healthy donors while CD4⁺ T cells from HIV+ donors and healthy donors were comparable. Treatment with IFN α promoted IL-7R expression and potentiated IL-7-induced STAT5 phosphorylation to augment IL-7-mediated proliferation by T cells from healthy and HIV+ donors. Finally, HIV+ donors exhibited reduced sensitivity to THC-mediated suppression by IFN α and IL-7-mediated stimulation compared to healthy donors.

These results further support THC as immune suppressive while identifying putatively beneficial aspects of cannabinoid-based therapies in HIV+ patients.

https://www.ncbi.nlm.nih.gov/pubmed/30026298

http://jpet.aspetjournals.org/content/early/2018/07/19/jpet.118.250308

Marijuana Use Is Not Associated With Progression to Advanced Liver Fibrosis in HIV/Hepatitis C Virus-coinfected Women.

Posted on May 9, 2018 by David

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“Marijuana (hereafter “tetrahydrocannabinol [THC]”) use has been associated with liver fibrosis progression in retrospective analyses of patients with chronic hepatitis C (HCV). We studied long-term effects of THC on fibrosis progression in women coinfected with human immunodeficiency virus (HIV)/HCV enrolled in the Women’s Interagency HIV Study (WIHS).

CONCLUSIONS:

In this large cohort of HIV/HCV-coinfected women, THC was not associated with progression to significant liver fibrosis. Alcohol use was independently associated with liver fibrosis, and may better predict fibrosis progression in HIV/HCV-coinfected women.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4967608/

https://academic.oup.com/cid/article/63/4/512/2595097

Marijuana smoking does not accelerate progression of liver disease in HIV-hepatitis C coinfection: a longitudinal cohort analysis.

Posted on May 9, 2018 by David

Issue Cover

“Marijuana smoking is common and believed to relieve many symptoms, but daily use has been associated with liver fibrosis in cross-sectional studies. We aimed to estimate the effect of marijuana smoking on liver disease progression in a Canadian prospective multicenter cohort of human immunodeficiency virus/hepatitis C virus (HIV/HCV) coinfected persons.

In this prospective analysis we found no evidence for an association between marijuana smoking and significant liver fibrosis progression in HIV/HCV coinfection.”

https://www.ncbi.nlm.nih.gov/pubmed/23811492

“To conclude, in this first prospective evaluation of liver disease progression among HIV-HCV infected persons, we could not demonstrate any important effect of marijuana on liver disease outcomes. A causal association is unlikely: hazard ratios were weak and most importantly were attenuated when accounting for temporality in the exposure-disease relationship and there was no dose-response relationship. It is likely that previous studies have been biased by reverse causality as patients use more marijuana to relieve symptoms as liver disease progresses.”

https://academic.oup.com/cid/article/57/5/663/312934

Dronabinol oral solution in the management of anorexia and weight loss in AIDS and cancer.

Posted on April 21, 2018 by David

“The true incidence of anorexia secondary to human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) and cancer is not well classified owing to the fact that there is a lack of standardized definitions and recent clinical data in these settings.

Dronabinol, or Δ-9-tetrahydrocannabinol, is a synthetic molecule that closely mimics the action of Cannabis sativa L., a naturally occurring compound activated in the central nervous system by cannabinoid receptors.

Dronabinol exerts its effects by directly acting on the vomiting and appetite control centers in the brain, which in turn increases appetite and prevents vomiting.

In the USA, dronabinol is currently available in two dosage formulations – oral capsule and oral solution. While the oral capsule was initially approved by the US Food and Drug Administration in 1985, the recent approval of the oral solution in 2016 presents an “easy-to-swallow” alternative for patients using or intending to use dronabinol.

Dronabinol is indicated in adult patients with HIV/AIDS for the treatment of anorexia and weight loss. However, there is no approved indication in the setting of cancer-related anorexia and weight loss. This review aims at presenting available data on the use of oral dronabinol in the management of anorexia and weight loss in HIV/AIDS and cancer, as well as characterizing and highlighting the pharmacotherapeutic considerations of the newest formulation of dronabinol.”

https://www.ncbi.nlm.nih.gov/pubmed/29670357

https://www.dovepress.com/dronabinol-oral-solution-in-the-management-of-anorexia-and-weight-loss-peer-reviewed-article-TCRM

Heavy Cannabis Use Associated With Reduction in Activated and Inflammatory Immune Cell Frequencies in Antiretroviral Therapy–Treated Human Immunodeficiency Virus–Infected Individuals

Posted on February 20, 2018 by David

“Cannabis is a widely used drug in the United States, and the frequency of cannabis use in the human immunodeficiency virus (HIV)–infected population is disproportionately high. Previous human and macaque studies suggest that cannabis may have an impact on plasma viral load; however, the relationship between cannabis use and HIV-associated systemic inflammation and immune activation has not been well defined.

Heavy cannabis users had decreased frequencies of human leukocyte antigen (HLA)-DR⁺CD38⁺CD4⁺ and CD8⁺ T-cell frequencies, compared to frequencies of these cells in non-cannabis-using individuals. Heavy cannabis users had decreased frequencies of intermediate and nonclassical monocyte subsets, as well as decreased frequencies of interleukin 23– and tumor necrosis factor-α–producing antigen-presenting cells.

Conclusions

While the clinical implications are unclear, our findings suggest that cannabis use is associated with a potentially beneficial reduction in systemic inflammation and immune activation in the context of antiretroviral-treated HIV infection.”

https://www.ncbi.nlm.nih.gov/pubmed/29471387

https://academic.oup.com/cid/advance-article-abstract/doi/10.1093/cid/cix1116/4869752?redirectedFrom=fulltext

www.thctotalhealthcare.com

Category Archives: HIV/AIDS