THC Total Health Care

A comprehensive encyclopedia of THC related medical research articles

Cannabis Sativa Revisited-Crosstalk between microRNA Expression, Inflammation, Oxidative Stress, and Endocannabinoid Response System in Critically Ill Patients with Sepsis.

Posted on February 6, 2020 by David Worrell

“Critically ill patients with sepsis require a multidisciplinary approach, as this situation implies multiorgan distress, with most of the bodily biochemical and cellular systems being affected by the condition. Moreover, sepsis is characterized by a multitude of biochemical interactions and by dynamic changes of the immune system. At the moment, there is a gap in our understanding of the cellular, genetic, and molecular mechanisms involved in sepsis.

One of the systems intensely studied in recent years is the endocannabinoid signaling pathway, as light was shed over a series of important interactions of cannabinoid receptors with biochemical pathways, specifically for sepsis. Furthermore, a series of important implications on inflammation and the immune system that are induced by the activity of cannabinoid receptors stimulated by the delta-9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) have been noticed.

One of the most important is their ability to reduce the biosynthesis of pro-inflammatory mediators and the modulation of immune mechanisms. Different studies have reported that cannabinoids can reduce oxidative stress at mitochondrial and cellular levels.

The aim of this review paper was to present, in detail, the important mechanisms modulated by the endocannabinoid signaling pathway, as well as of the molecular and cellular links it has with sepsis. At the same time, we wish to present the possible implications of cannabinoids in the most important biological pathways involved in sepsis, such as inflammation, redox activity, immune system, and epigenetic expression.”

https://www.ncbi.nlm.nih.gov/pubmed/32012914

https://www.mdpi.com/2073-4409/9/2/307

The ameliorating effect of cannabinoid type 2 receptor activation on brain, lung, liver and heart damage in cecal ligation and puncture-induced sepsis model in rats.

Posted on November 27, 2019 by David Worrell

International Immunopharmacology “Uncontrolled infection and increased inflammatory mediators might cause systemic inflammatory response. It is already known that Cannabinoid Type 2 (CB2) receptors, which are commonly expressed in immune cells and in many other tissues, have an effect on the regulation of immune response.

In the present study of ours, the effects of CB2 receptor agonist JWH-133 was investigated on cecal ligation and puncture (CLP)-induced polymicrobial sepsis model in rats.

The JWH-133 treatment decreased the histopathological damage in brain, heart, lung, and liver and reduced the caspase-3, p-NF-κB, TNF-α, IL-1β, IL-6 levels in these tissues. In addition to this, JWH-133 treatment also decreased the serum TNF-α, IL-1β, IL-6 levels, which were increased due to CLP, and increased the anti-inflammatory cytokine IL-10 levels.

In the present study, it was determined that the CB2 receptor agonist JWH-133 decreases the CLP-induced inflammation, and reduces the damage in brain, lung, liver and heart.

Our findings show the therapeutic potential of the activation of CB2 receptors with JWH-133 in sepsis.”

https://www.ncbi.nlm.nih.gov/pubmed/31767546

“CB2 receptors are expressed in many tissues including immune cells. Activation of CB2 receptors has been shown to have anti-inflammatory effect.”

https://www.sciencedirect.com/science/article/pii/S1567576919318351?via%3Dihub

Cannabinoid CB1 Receptor Antagonist Rimonabant Decreases Levels of Markers of Organ Dysfunction and Alters Vascular Reactivity in Aortic Vessels in Late Sepsis in Rats.

Posted on December 20, 2018 by David Worrell

“Sepsis is a life-threatening condition with high mortality rates that is caused by dysregulation of the host response to infection. We previously showed that treatment with the cannabinoid CB₁ receptor antagonist rimonabant reduced mortality rates in animals with sepsis that was induced by cecal ligation and puncture (CLP). This improvement in the survival rate appeared to be related to an increase in arginine vasopressin (AVP) levels 12 h after CLP. The present study investigated the effects of rimonabant on organ dysfunction, hematologic parameters, and vascular reactivity in male Wistar rats with sepsis induced by CLP. Intraperitoneal treatment with rimonabant (10 mg/kg, 4 h after CLP) abolished the increase in the plasma levels of lactate, lactate dehydrogenase, glucose, and creatinine kinase MB without altering hematological parameters (i.e., leukopenia and a reduction of platelet counts). CLP increased plasma levels of nitrate/nitrite (NOx) and induced vasoconstriction in the tail artery. The treatment of CLP rats with rimonabant did not alter NOx production but reduced the vasoconstriction. Rimonabant also attenuated the hyperreactivity to AVP induced by CLP without affecting hyporesponsiveness to phenylephrine in aortic rings. These results suggest that rimonabant reduces organ dysfunction during sepsis, and this effect may be related to AVP signaling in blood vessels. This effect may have contributed to the higher survival rate in rimonabant-treated septic animals.”

https://www.ncbi.nlm.nih.gov/pubmed/30556096

https://link.springer.com/article/10.1007%2Fs10753-018-0919-z

]]>

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

Posted on June 12, 2018 by David Worrell

“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.”

https://www.ncbi.nlm.nih.gov/pubmed/29317072

https://www.medical-hypotheses.com/article/S0306-9877(17)30861-7/fulltext

]]>

Cannabinoid receptor 2: a potential novel therapeutic target for sepsis?

Posted on April 26, 2018 by David Worrell

“Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. It is the most common cause of death among critically ill patients in non-coronary intensive care units and the incidence continues to rise. Although advanced management was applied, the prognosis of sepsis patients remains poor. As a G-protein coupled receptor, cannabinoid receptor 2 (CB2R) was implicated in a wide variety of diseases. In this study, we aimed to investigate the role of CB2R in sepsis.

With the anti-inflammatory and immunomodulatory effects, CB2R is a novel and promising therapeutic target in the management of sepsis. Indeed, specific CB2R agonists have been reported to attenuate leukocyte recruitment, oxidative burst, systemic inflammatory mediator release, bacteremia, and lung tissue damage, while improving survival in different sepsis models.

In addition, autophagy has also been implicated in the protective role of CB2R activation in sepsis. However, almost all of the current outcomes result from animal studies or in vitro cultured cells. Due to the lack of clinical evidence and the ambiguous mechanisms underlying, the clinical application of CB2R stimulation in sepsis is limited. Further studies are needed to delineate the therapeutic effect and the related-pathways of CB2R agonists in sepsis.”

https://www.ncbi.nlm.nih.gov/pubmed/29694303 https://www.tandfonline.com/doi/abs/10.1080/17843286.2018.1461754?journalCode=yacb20]]>

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

Posted on January 11, 2018 by David Worrell

https://www.ncbi.nlm.nih.gov/pubmed/29317072

http://www.medical-hypotheses.com/article/S0306-9877(17)30861-7/fulltext

]]>

Parameters of the Endocannabinoid System as Novel Biomarkers in Sepsis and Septic Shock.

Posted on November 7, 2017 by David Worrell

“Sepsis represents a dysregulated immune response to infection, with a continuum of severity progressing to septic shock. This dysregulated response generally follows a pattern by which an initial hyperinflammatory phase is followed by a state of sepsis-associated immunosuppression.

Major challenges in improving sepsis care include developing strategies to ensure early and accurate identification and diagnosis of the disease process, improving our ability to predict outcomes and stratify patients, and the need for novel sepsis-specific treatments such as immunomodulation.

Biomarkers offer promise with all three of these challenges and are likely also to be the solution to determining a patient’s immune status; something that is critical in guiding effective and safe immunomodulatory therapy. Currently available biomarkers used in sepsis lack sensitivity and specificity, among other significant shortcomings.

The endocannabinoid system (ECS) is an emerging topic of research with evidence suggesting a ubiquitous presence on both central and peripheral tissues, including an intrinsic link with immune function. This review will first discuss the state of sepsis biomarkers and lack of available treatments, followed by an introduction to the ECS and a discussion of its potential to provide novel biomarkers and treatments.”

https://www.ncbi.nlm.nih.gov/pubmed/29104224

http://www.mdpi.com/2218-1989/7/4/55

Targeting the Endocannabinoid System to Treat Sepsis

Posted on September 26, 2017 by David Worrell

“Sepsis is a complex immune disorder that can affect the function of almost all organ systems in the body. This disorder is characterised by a malfunctioning immune response to an infection that involves both pro-inflammatory and immunosuppressive mediators. This leads to severe damage and failure of vital organs, resulting in patient death. Sepsis, septic shock, and systemic inflammatory response syndrome are the leading causes of mortality in surgical intensive care unit patients internationally. The current lack of viable therapeutic treatment options for sepsis underscores our insufficient understanding of this complex disease. The endocannabinoid system, a key regulator of essential physiological functions including the immune system, has recently emerged as a potential therapeutic target for sepsis treatment. The endocannabinoid system acquires its name from the plant Cannabis Sativa, which has been used medically to treat a variety of ailments, as well as recreationally for centuries. Cannabis Sativa contains more than 60 active phytocannabinoids with the primary phytocannabinoid Δ9-tetrahydrocannabinol (THC), (6) activating both endogenous endocannabinoid receptors. The endocannabinoid system represents a potential therapeutic target in sepsis due to the presence of cannabinoid receptors (CB2) on immune cells. In this review we discuss how various targets within the endocannabinoid system can be manipulated to treat the immune consequences of sepsis. One of the targets outlined are the endocannabinoid receptors and modulation of their activity through pharmacological agonists and antagonists. Another therapeutic target covered in this review is the modulation of the endocannabinoid degradative enzyme’s activity. Modulation of degradative enzyme activity can change the levels of endogenous cannabinoids thereby altering immune activity. Overall, activation of the CB2 receptors causes immunosuppression and can be beneficial during the hyperactivated immune state of sepsis, while suppression of the CB2 receptors may be beneficial during a hypoimmune septic state. The endocannabinoid system modulates the immune response in experimental sepsis. Manipulating the endocannabinoid system may have potential therapeutic benefit in clinical sepsis where immune and inflammatory dysfunction can be detrimental. Multiple targets exist within the endocannabinoid system, e.g. the system can be targeted at the level of receptors by administration of synthetic compounds, similar to the endocannabinoids, which either increase or inhibit receptor activation to provide the desired therapeutic effect. Alternatively, the endogenous enzymes that degrade endocannabinoids or cannabinoid-like lipids can also be targeted in order to manipulate the levels of endocannabinoids. Proper identification of the septic stage is crucial to determine the adequate therapeutic response that will be most beneficial. Due to the biphasic nature of sepsis immunopathology, immune suppression through endocannabinoid modulation can help mitigate the hyper-immune response during the early septic state, while immune activation may be beneficial in later stages.” http://www.signavitae.com/2013/05/targeting-the-endocannabinoid-system-to-treat-sepsis/ http://www.signavitae.com/2013/05/targeting-the-endocannabinoid-system-to-treat-sepsis/]]>

Treatment with cannabidiol reverses oxidative stress parameters, cognitive impairment and mortality in rats submitted to sepsis by cecal ligation and puncture.

Posted on September 26, 2017 by David Worrell

“Oxidative stress plays an important role in the development of cognitive impairment in sepsis. Here we assess the effects of acute and extended administration of cannabidiol (CBD) on oxidative stress parameters in peripheral organs and in the brain, cognitive impairment, and mortality in rats submitted to sepsis by cecal ligation and perforation (CLP). Our data provide the first experimental demonstration that CBD reduces the consequences of sepsis induced by CLP in rats, by decreasing oxidative stress in peripheral organs and in the brain, improving impaired cognitive function, and decreasing mortality.” https://www.ncbi.nlm.nih.gov/pubmed/20561509 http://www.sciencedirect.com/science/article/pii/S0006899310013582?via%3Dihub

“Antioxidant treatment reverses mitochondrial dysfunction in a sepsis animal model.” https://www.ncbi.nlm.nih.gov/pubmed/18417427

]]>

In vitro Antimicrobial and Antioxidant Activity of Extracts from Six Chemotypes of Medicinal Cannabis

Posted on December 17, 2016 by David Worrell

“Nowadays, medicinal cannabis (Cannabis sativa L) is in the focus of the researches not only for its high content of tetrahydrocannabinol (THC), but for other cannabinoids as well.

It has been reported that some of the identified substances (e.g. cannabidiol, cannabinochromene) possess anti-inflammatory and antimicrobial properties, which corresponds to its traditional use as wound healing agent at Pakistan.

The aim of this study was to evaluate antimicrobial and antioxidant ability of extracts from high potent Cannabis sativa chemotypes.

The six ethanolic extracts prepared from dried inflorescence of five medicinal cannabis chemotypes (Nurse Jackie, Jilly Bean, Nordle, Jack Cleaner, Conspiracy Kush) were tested by standard microdilution method against Staphylococcus aureus (three strains), Streptococcus pyogenes and the yeast Candida albicans.

Those microbial strains are present on skin and can cause complication during wound healing process.

The antioxidative activity, which plays an important role in wound healing process, was tested by oxygen radical absorbance capacity test (ORAC).

All tested extracts demonstrated high antimicrobial activity against two strains of S. aureus and S. pyogenes (MIC ranged from 4 – 16 µg·mL^-1), moreover high antioxidant capacity was observed (ORAC ranged from 800 – 1300 µg TE/mg of extract).

The results indicate that cannabis has high potential to be used in ointments and other material for wound healing.

However, further research on the identification of the active components is needed.”

https://www.thieme-connect.com/DOI/DOI?10.1055/s-0036-1596302