Cannabis use is associated with reduced prevalence of progressive stages of alcoholic liver disease.

Liver International

 

“Abusive alcohol use has well-established health risks including causing liver disease (ALD) characterized by alcoholic steatosis (AS), steatohepatitis (AH), fibrosis, cirrhosis (AC) and hepatocellular carcinoma (HCC). Strikingly, a significant number of individuals who abuse alcohol also use Cannabis, which has seen increased legalization globally. While cannabis has demonstrated anti-inflammatory properties, its combined use with alcohol and the development of liver disease remains unclear.

To determine the effects of cannabis use on the incidence of liver disease in individuals who abuse alcohol.

We analyzed the 2014 Healthcare Cost and Utilization Project – Nationwide Inpatient Sample (NIS) discharge records of patients 18years and older, who had a past or current history of abusive alcohol use(n=319,514). Using the International Classification of Disease, Ninth Edition codes, we studied the four distinct phases of progressive ALD with respect to three cannabisexposure groups: non-cannabis-users (90.39%), non-dependent-cannabis-users (8.26%) and dependent cannabis users (1.36%). We accounted for the complex survey sampling methodology and estimated the adjusted odds ratio (AOR) for developing AS, AH, AC and HCC with respect to cannabis use (SAS 9.4).

 

Our study revealed that among alcohol users, individuals who additionally use cannabis (dependent and non-dependent cannabis use) showed significantly lower odds of developing AS, AH, AC and HCC (AOR: 0.55[0.48-0.64], 0.57[0.53-0.61], 0.45[0.43-0.48] & 0.62[0.51-0.76]). Further, dependent users had significantly lower odds than non-dependent users for developing liver disease.

CONCLUSIONS:

Our findings suggest that cannabis use is associated with reduced incidence of liver disease in alcoholics.”

https://www.ncbi.nlm.nih.gov/pubmed/29341392

http://onlinelibrary.wiley.com/doi/10.1111/liv.13696/abstract

Benefits of VCE-003.2, a cannabigerol quinone derivative, against inflammation-driven neuronal deterioration in experimental Parkinson’s disease: possible involvement of different binding sites at the PPARγ receptor.

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“Neuroprotection with cannabinoids in Parkinson’s disease (PD) has been afforded predominantly with antioxidant or anti-inflammatory cannabinoids. In the present study, we investigated the anti-inflammatory and neuroprotective properties of VCE-003.2, a quinone derivative of the non-psychotrophic phytocannabinoid cannabigerol (CBG), which may derive its activity at the peroxisome proliferator-activated receptor-γ (PPARγ). The compound is also an antioxidant.

We have demonstrated that VCE-003.2 is neuroprotective against inflammation-driven neuronal damage in an in vivo model of PD and in in vitro cellular models of neuroinflammation. Such effects might involve PPARγ receptors, although in silico and in vitro experiments strongly suggest that VCE-003.2 targets PPARγ by acting through two binding sites at the LBP, one that is sensitive to T0070907 (canonical binding site) and other that is not affected by this PPARγ antagonist (alternative binding site).”

https://www.ncbi.nlm.nih.gov/pubmed/29338785

https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-018-1060-5

Anti-Inflammatory Drugs and Herbs with Special Emphasis on Herbal Medicines for Countering Inflammatory Diseases and Disorders – A Review.

“Diseases with inflammatory etiopathology have increased in incidence in recent times. Drugs used for therapeutic management of such inflammatory diseases are relieving the ailment but at the same time also countering serious life-threatening consequences. Moreover, they are costly and rarely available at all places. In this context, research and development on medicinal herbs have opened a new era in the prophylactic and therapeutic management of inflammatory diseases.

OBJECTIVE:

To highlight the importance of anti-inflammatory medicine-synthetic drugs and natural herbs, their constituents, mechanism of action, benefits, side effects and future prospects. The overall aim is to provide better health services to patiens regardless of their background on equality basis.

RESULTS:

Anti-inflammatory herbs have proven beneficial by combating inflammatory responses that lead to severe abnormality in body systems. Inflammation though a protective response to infection or injury and may result in pathological outcome when aggravated or of severe degree thus needs an early intervention for proper resolution. Medicinal plants or their constituents are considered beneficial due to the properties i.e., satisfactory potency, ease of availability, cheapness, less or no side effects, safer and efficient as compared to the synthetic counterparts. These medicinal herbs contain phytoconstituents that can prevent undesirable inflammatory processes and also posses anti-inflammatory activity. Steroids, glycosides, phenolics, flavonoids, alkaloids, polysaccharides, terpenoids, cannabinoids, fatty acids are common phytoconstituents present in these plants. Different mechanisms have been explored for the anti-inflammatory action of these active ingredients. They may synergize the anti-inflammatory pathway enzymes, factors, proteins or interfere with these in the inflammatory pathway like lipooxygenases, cyclooxygenases, tumor necrosis factors, interleukins, prostaglandin, nitric oxide, mitogen-activated protein, nuclear factor, etc. Considering all the above-mentioned factors, further research from molecular to cellular level will enable a better understanding of the mechanisms. Common anti-inflammatory herbal plants are Curcuma longa, Zingiber officinale, Rosmarinus officinalis, Borago officinalis, Urtica dioica, Uncaria tomentosa, Vaccinium myrtillus, Olea europaea and much more. They are believed to be without side effects unlike the chemical counterparts or synthetic anti-inflammatory agents e.g. steroids, nonsteroid anti-inflammatory drugs, and immunosuppressant used for controlling and suppressing inflammatory crisis. A proper phytochemical, pharmacological and physiological evaluation will enable their safe and effective use in inflammatory conditions. Many of these anti-inflammatory drugs and herbal preparations have been patented with some under consideration.

CONCLUSION:

Natural herbs are safe, effective and better options as anti-inflammatory agents than synthetic ones. The phytoconstituents are as effective with the comparable mechanism of action as synthetic molecules. Future research should focus on molecular mechanisms of different beneficial applications of these herbal plants in various diseases. Recent patents on anti-inflammatory drugs and herbal plants have been covered which provide insight into the current status and future prospects in this field.”

https://www.ncbi.nlm.nih.gov/pubmed/29336271  http://www.eurekaselect.com/159064/article

“Cannabinoids as novel anti-inflammatory drugs”  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2828614/

“Cannabinoids for the treatment of inflammation.” http://www.ncbi.nlm.nih.gov/pubmed/17520866

“Cannabis-based drugs have been shown to be effective in inflammatory diseases.” https://www.ncbi.nlm.nih.gov/pubmed/29110674

http://www.thctotalhealthcare.com/tag/anti-inflammatory/

Betacaryophyllene – A phytocannabinoid as potential therapeutic modality for human sepsis?

Medical Hypotheses Home

“Sepsis is a clinical condition resulting from a dysregulated immune response to an infection that leads to organ dysfunction. Despite numerous efforts to optimize treatment, sepsis remains to be the main cause of death in most intensive care units.

The endogenous cannabinoid system (ECS) plays an important role in inflammation. Cannabinoid receptor 2 (CB2R) activation is immunosuppressive, which might be beneficial during the hyper-inflammatory phase of sepsis.

Beta-caryophyllene (BCP) is a non-psychoactive natural cannabinoid (phytocannabinoid) found in Cannabis sativa and in essential oils of spices and food plants, that acts as a selective agonist of CB2R.

We propose BCP administration as novel treatment to reduce hyper-inflammation in human sepsis.”

WWL70 protects against chronic constriction injury-induced neuropathic pain in mice by cannabinoid receptor-independent mechanisms.

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“Targeting the endocannabinoid system has emerged as an effective strategy for the treatment of inflammatory and neurological diseases.

Unlike the inhibition of the principal 2-arachidonyl glycerol (2-AG) hydrolytic enzyme monoacylglycerol lipase (MAGL), which leads to 2-AG overload and cannabinoid receptor desensitization, selective inhibition of the minor 2-AG hydrolytic enzyme alpha, beta-hydrolase domain 6 (ABHD6) can provide therapeutic benefits without producing cannabimimetic side effects. We have shown that inhibition of ABHD6 significantly reduces neuroinflammation and exerts neuroprotection in animal models of traumatic brain injury and multiple sclerosis. However, the role of ABHD6 inhibition on neuropathic pain has not been explored.

CONCLUSIONS:

This study reveals a novel mechanism for the antinociceptive effect of the 2-AG catabolic enzyme ABHD6 inhibitor WWL70. Understanding the interaction between endocannabinoid and eicosanoid pathways might provide a new avenue for the treatment of inflammatory and neuropathic pain.”

Investigating the relationships between alcohol consumption, cannabis use and circulating cytokines: a preliminary analysis.

Alcoholism: Clinical and Experimental Research

“In recent years, human and animal studies have converged to support altered inflammatory signaling as one molecular mechanism underlying the pathophysiology of alcohol use disorders (AUDs). Alcohol binds to receptors on immune cells, triggering signaling pathways that produce pro-inflammatory cytokines. Chronic inflammation is associated with tissue damage, which may contribute to negative effects of AUD.

Conversely, cannabis is associated with decreased inflammatory signaling, and animal studies suggest that cannabinoids may impact alcohol-induced inflammation.

We explored the relationship between self-reported alcohol and cannabis use and circulating levels of the pro-inflammatory cytokines IL-6, IL-8 and IL-1β in the blood.

A positive association between alcohol and IL-6 emerged. We also observed a negative association between cannabis and IL-1β.

These preliminary findings suggest that cannabinoid compounds may serve to mitigate inflammation associated with alcohol use.”

https://www.ncbi.nlm.nih.gov/pubmed/29286537

http://onlinelibrary.wiley.com/doi/10.1111/acer.13592/abstract;jsessionid=CE6DC7E1CC2712861F31EF048D2F7118.f02t04

Anti-inflammatory activity of cannabinoid receptor 2 ligands in primary hPDL fibroblasts.

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“Approximately 65 million adults in the US have periodontitis, causing tooth loss and decreased quality of life.

 Cannabinoids modulate immune responses, and endocannabinoids are prevalent during oral cavity inflammation. Targets for intervention in periodontal inflammation are cannabinoid type 1 and 2 receptors (CB1R, CB2R), particularly CB2R because its levels increase during inflammation.

We previously demonstrated that SMM-189 (CB2R inverse agonist) decreased pro-inflammatory cytokine production in primary microglial cells. The hypothesis of this study was that cannabinoids anandamide (AEA), HU-308 (CB2R selective agonist), and SMM-189 decrease pro-inflammatory IL-6 and MCP-1 production by primary human periodontal ligament fibroblasts (hPDLFs) stimulated with P. gingivalis LPS, TNF-α, or IL-1β.

CONCLUSION:

The effective inhibition of LPS, TNF-α, IL-1β stimulated IL-6 and MCP-1 production by CB2R ligands in hPDLFs suggests that targeting the endocannabinoid system may lead to development of novel drugs for periodontal therapy, aiding strategies to improve oral health.”

https://www.ncbi.nlm.nih.gov/pubmed/29274621

Cannabidiol restores intestinal barrier dysfunction and inhibits the apoptotic process induced by Clostridium difficile toxin A in Caco-2 cells.

 SAGE Journals

“Clostridium difficile toxin A is responsible for colonic damage observed in infected patients.

Drugs able to restore Clostridium difficile toxin A-induced toxicity have the potential to improve the recovery of infected patients. Cannabidiol is a non-psychotropic component of Cannabis sativa, which has been demonstrated to protect enterocytes against chemical and/or inflammatory damage and to restore intestinal mucosa integrity.

The purpose of this study was to evaluate (a) the anti-apoptotic effect and (b) the mechanisms by which cannabidiol protects mucosal integrity in Caco-2 cells exposed to Clostridium difficile toxin A.

RESULTS:

Clostridium difficile toxin A significantly decreased Caco-2 cells’ viability and reduced transepithelial electrical resistence values and RhoA guanosine triphosphate (GTP), bax, zonula occludens-1 and occludin protein expression, respectively. All these effects were significantly and concentration-dependently inhibited by cannabidiol, whose effects were completely abolished in the presence of the cannabinoid receptor type 1 (CB1) antagonist, AM251.

CONCLUSIONS:

Cannabidiol improved Clostridium difficile toxin A-induced damage in Caco-2 cells, by inhibiting the apoptotic process and restoring the intestinal barrier integrity, through the involvement of the CB1 receptor.”

https://www.ncbi.nlm.nih.gov/pubmed/29238589

“In the last decade, cannabinoids extracted from the marijuana plant (Cannabis sativa) and synthetic cannabinoids have shown numerous beneficial effects on gastrointestinal (GI) functions. Non-psychotropic phytocannabinoid cannabidiol (CBD) is one of the most interesting compounds, since it exerts a wide range of beneficial pharmacological actions on GI functions, ranging from antioxidant to antinflammatory activities. CBD has been shown to act as a non-competitive negative allosteric modulator of CB1 receptors. Notably, CBD is able to restore in vitro intestinal permeability increased by ethylenediaminetetraacetic acid (EDTA) or pro-inflammatory stimuli.

Clostridium difficile infection is the leading cause of hospital-acquired diarrhoea and pseudomembranous colitis. Clostridium difficile-Toxin A significantly affects enterocytes permeability leading to apoptosis and colonic mucosal damage.

In the present study, we showed that Cannabidiol, a non-psychotropic component of Cannabis sativa significantly inhibit the apoptosis rate in TcdA-exposed cells and restores barrier function by a significant RhoA GTP rescue.

We also provide evidence that the effects of Cannabidiol are mediated by CB-1 receptor.

Given the absence of any significant toxic effect in humans, cannabidiol may ideally represent an effective adjuvant treatment for Clostridium difficile-associated colitis.”   http://journals.sagepub.com/doi/10.1177/2050640617698622

HIV-infected cannabis users have lower circulating CD16+ monocytes and IP-10 levels compared to non-using HIV patients.

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“Chronic immune activation and elevated numbers of circulating activated monocytes (CD16) are implicated in HIV-associated neuroinflammation.

The objective was to compare the level of circulating CD16 monocytes and interferon-γ-inducible protein 10 (IP-10) between HIV-infected cannabis users (HIV+MJ+) and non-cannabis users (HIV+MJ-), and determine whether in vitro Δ-Tetrahydrocannabinol (THC), a constituent of cannabis, affected CD16 expression as well as IP-10 production by monocytes.

RESULTS:

HIV+MJ+ donors possessed a lower level of circulating CD16 monocytes and serum IP-10, compared to HIV+MJ- donors. Further, monocytes from HIV+MJ+ donors were unable to induce CD16 expression when treated with in vitro IFNα, while HIV-MJ- and HIV+MJ- donors displayed pronounced CD16 induction, suggesting anti-inflammatory effects by cannabis.

CONCLUSIONS:

Components of cannabis, including THC, may decelerate peripheral monocyte processes that are implicated in HIV-associated neuroinflammation.”   https://www.ncbi.nlm.nih.gov/pubmed/29194121

http://journals.lww.com/aidsonline/Abstract/publishahead/HIV_infected_cannabis_users_have_lower_circulating.97348.aspx

“Medical Cannabis May Improve Neurocognitive Disorder in Patients With HIV. Medical marijuana could help prevent the development of neurocognitive disorders in patients with HIV, according to a new study. Tetrahydrocannabinol (THC), the prominent compound in marijuana, was found to slow the process of neurodegeneration — a condition common in about half of all patients with HIV — according to a study from researchers at Michigan State University (MSU).” https://www.specialtypharmacytimes.com/news/medical-cannabis-may-improve-neurocognitive-disorder-in-patients-with-hiv

Marijuana may help HIV patients keep mental stamina longer. Norbert Kaminski, director of Michigan State University‘s Institute for Integrative Toxicology, has found that a chemical in marijuana, known as THC, can potentially slow the process of mental decline that can occur in up to 50 percent of HIV patients.” https://medicalxpress.com/news/2017-12-marijuana-hiv-patients-mental-stamina.html

“New Research Says A Chemical in Marijuana May Help HIV Patients Maintain Their Mental Fortitude. “The patients who didn’t smoke marijuana had a very high level of inflammatory cells compared to those who did use. In fact, those who used marijuana had levels pretty close to a healthy person not infected with HIV.”” http://game360.co/2017/12/new-research-says-chemical-marijuana-may-help-hiv-patients-maintain-mental-fortitude/

“Cannabis could prevent mental decline in up to 50 percent of HIV sufferers, new research reveals. Patients who use marijuana have fewer inflammatory white blood cells, which are involved in the immune system, a study found. This could save infected people from mental decline, which affects up to 50 percent of sufferers due to ongoing inflammation in the brain as a result of the immune system constantly fighting the virus. Lead author Professor Norbert Kaminski from Michigan State University, said: ‘Those who used marijuana had [inflammatory cell] levels pretty close to a healthy person not infected with HIV.'” http://www.dailymail.co.uk/health/article-5174379/Cannabis-prevent-mental-decline-HIV-sufferers.html

“Marijuana may help increase mental strength in HIV patients”  http://www.timesnownews.com/health/article/marijuana-may-help-increase-mental-strength-in-hiv-patients/145504

Extract of Fructus Cannabis Ameliorates Learning and Memory Impairment Induced by D-Galactose in an Aging Rats Model.

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“Hempseed (Cannabis sativa L.) has been used as a health food and folk medicine in China for centuries.

In the present study, we sought to define the underlying mechanism by which the extract of Fructus Cannabis (EFC) protects against memory impairment induced by D-galactose in rats.

To accelerate aging and induce memory impairment in rats, D-galactose (400 mg/kg) was injected intraperitoneally once daily for 14 weeks. EFC (200 and 400 mg/kg) was simultaneously administered intragastrically once daily in an attempt to slow the aging process.

We found that EFC significantly increased the activity of superoxide dismutase, while lowering levels of malondialdehyde in the hippocampus. Moreover, EFC dramatically elevated the organ indices of some organs, including the heart, the liver, the thymus, and the spleen. In addition, EFC improved the behavioral performance of rats treated with D-galactose in the Morris water maze. Furthermore, EFC inhibited the activation of astrocytes and remarkably attenuated phosphorylated tau and suppressed the expression of presenilin 1 in the brain of D-galactose-treated rats.

These findings suggested that EFC exhibits beneficial effects on the cognition of aging rats probably by enhancing antioxidant capacity and anti-neuroinflammation, improving immune function, and modulating tau phosphorylation and presenilin expression.”