Tag Archives: plant

Inhibitory Effect of Cannabidiol on the Activation of NLRP3 Inflammasome Is Associated with Its Modulation of the P2X7 Receptor in Human Monocytes.

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 Go to Volume 0, Issue 0“Cannabidiol (CBD), a phytocannabinoid, has been reported to have anti-inflammatory effects associated with NLRP3 inflammasome activation, but its mechanism of anti-inflammasome action remains unclear.

Herein, we report CBD’s effect on NLRP3 inflammasome activation and its modulation of P2X7, an inflammasome activation-related receptor, in human THP-1 monocytes.

Overall, the observed CBD suppressive effect on NLRP3 inflammasome activation in THP-1 monocytes was associated with decreased potassium efflux, as well as in silico prediction of P2X7 receptor binding.

CBD inhibitory effects on the NLRP3 inflammasome may contribute to the overall anti-inflammatory effects reported for this phytocannabinoid.”

https://www.ncbi.nlm.nih.gov/pubmed/32374168

https://pubs.acs.org/doi/10.1021/acs.jnatprod.0c00138

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SARS-CoV2 induced respiratory distress: Can Cannabinoids be added to anti-viral therapies to reduce lung inflammation?

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Brain, Behavior, and Immunity“Coronavirus disease-2019 (COVID-19), caused by Severe Acute Respiratory Syndrome coronoavirus-2 (SARS-CoV2) has emerged as a global pandemic, which was first reported in Wuhan, China. Recent reports have suggested that acute infection is associated with a cytokine superstorm, which contributes to the symptoms of fever, cough, muscle pain and in severe cases bilateral interstitial pneumonia characterized by ground glass opacity and focal chest infiltrates that can be visualized on computerized tomography scans. Currently, there are no effective antiviral drugs or vaccines against SARS-CoV2. In the recent issue of BBI, Zhang et al. thoroughly summarized the current status of potential therapeutic strategies for COVID-19. One of them, anti-IL6 receptor (Tocilizumab) antibody, resulted in clearance of lung consolidation and recovery in 90% of the 21 treated patients. Although promising, it has also produced adverse effects like pancreatitis and hypertriglyceridemia, which make it imperative to explore effective alternative anti-inflammatory strategies. Here, we intend to highlight the potential effects of cannabinoids, in particular, the non-psychotropic cannabidiol (CBD), that has shown beneficial anti-inflammatory effects in pre-clinical models of various chronic inflammatory diseases and is FDA approved for seizure reduction in children with intractable epilepsy.

Like Δ9-tetrahydrocannabinol (Δ9-THC), the most well-studied cannabinoid, CBD decreased lung inflammation in a murine model of acute lung injury potentially through the inhibition of proinflammatory cytokine production by immune cells and suppressing exuberant immune responses. CBD can inhibit the production of proinflammatory cytokines like interleukin (IL)-2, IL-6, IL-1α and β, interferon gamma, inducible protein-10, monocyte chemoattractant protein-1, macrophage inflammatory protein-1α, and tumor necrosis factor-α that have been associated with SARS-CoV2 induced multi-organ pathology and mortality. In a murine model of chronic asthma, CBD reduced proinflammatory cytokine production, airway inflammation and fibrosis. Moreover, CBD can effectively inhibit the JAK-STAT pathway including the production and action of type I interferons without leading to addiction, alterations in heart rate or blood pressure and adverse effects on the gastrointestinal tract and cognition. In simian immunodeficiency virus (SIV)-infected rhesus macaques (RMs), we reported THC mediated attenuation of IFN stimulated gene expression in the intestine. Similar to CBD, chronic THC administration blocked inflammation induced fibrosis in lymph nodes of chronically SIV-infected RMs. Unlike THC, CBD has a high margin of safety and is well tolerated pharmacologically even after treatments of up to 1500 mg/day for two weeks in both animals and humans, which suggests its feasibility to reduce SARS-CoV2 induced lung inflammation/pathology and disease severity.

The many uncertainties associated with the COVID-19 pandemic such as status of the economy, employment and loss of connection can fuel depression, fear and anxiety. CBD has shown promise as an alternative therapy for the clinical management of anxiety disorders. Based on its anxiolytic and anti-depressant properties, it has been suggested that CBD could be used to improve the mental and somatic health of patients suffering from anxiety and emotional stress after recovering from Ebola disease. Like Ebola, patients recovering from COVID-19 may experience various psychological and social stressors that may be triggered by residual chronic inflammation and autoimmune reactions. Therefore, randomized clinical trials to test the efficacy of CBD on alleviating anxiety and fear associated with COVID-19 infection and its consequences on people’s physical, social and psychological well-being may be beneficial in the future. Additionally, severely ill COVID-19 patients exhibited neurological symptoms like cerebrovascular disease, headache and disturbed consciousness (Reviewed in. Brain edema, neuronal degeneration and presence of SARS-CoV2 in the cerebrospinal fluid (CSF) were confirmed at autopsy. Therefore, longitudinal CSF sampling using non-human primate (NHP) studies may help clarify whether and when SARS-CoV2 invades the brain, and if this happens, does it result in neuroinflammation and more importantly, whether cannabinoids can modulate these events.

Being a negative allosteric modulator of the cannabinoid receptor-1, CBD can counter the psychotropic effects of THC when co-administered with THC. Although Remdesivir reduced the mortality rate of seriously ill COVID-19 patients needing invasive ventilation, similar studies in rhesus macaques revealed minimal subpleural inflammatory cellular infiltrates in the lungs of clinically recovered Remdesivir treated RMs at necropsy. This suggests persistence of inflammation and may partly explain the 20–30% reduction in lung function in COVID-19 patients after recovery, which if left unresolved may lead to pulmonary fibrosis. Collectively, these findings support the investigation of cannabinoids as a plausible option to be added as an adjunct to Remdesivir or any new antivirals on SARS-CoV2 induced lung inflammation.”

https://www.ncbi.nlm.nih.gov/pubmed/32360437

https://www.sciencedirect.com/science/article/pii/S0889159120307078?via%3Dihub

“Cannabis Indica speeds up Recovery from Coronavirus”   https://www.researchgate.net/publication/339746853_Cannabis_Indica_speeds_up_Recovery_from_Coronavirus

Cannabidiol and Other Non-Psychoactive Cannabinoids for Prevention and Treatment of Gastrointestinal Disorders: Useful Nutraceuticals?

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ijms-logo“Cannabis sativa is an aromatic annual flowering plant with several botanical varieties, used for different purposes, like the production of fibers, the production of oil from the seeds, and especially for recreational or medical purposes.

Phytocannabinoids (terpenophenolic compounds derived from the plant), include the well-known psychoactive cannabinoid Δ9-tetrahydrocannabinol, and many non-psychoactive cannabinoids, like cannabidiol.

The endocannabinoid system (ECS) comprises of endocannabinoid ligands, enzymes for synthesis and degradation of such ligands, and receptors. This system is widely distributed in the gastrointestinal tract, where phytocannabinoids exert potent effects, particularly under pathological (i.e., inflammatory) conditions.

Herein, we will first look at the hemp plant as a possible source of new functional food ingredients and nutraceuticals that might be eventually useful to treat or even prevent gastrointestinal conditions.

Subsequently, we will briefly describe the ECS and the general pharmacology of phytocannabinoids. Finally, we will revise the available data showing that non-psychoactive phytocannabinoids, particularly cannabidiol, may be useful to treat different disorders and diseases of the gastrointestinal tract.

With the increasing interest in the development of functional foods for a healthy life, the non-psychoactive phytocannabinoids are hoped to find a place as nutraceuticals and food ingredients also for a healthy gastrointestinal tract function.”

https://www.ncbi.nlm.nih.gov/pubmed/32357565

https://www.mdpi.com/1422-0067/21/9/3067

Innovative methods for the preparation of medical Cannabis oils with a high content of both cannabinoids and terpenes.

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Journal of Pharmaceutical and Biomedical Analysis“Cannabis-based medications are being increasingly used for the treatment of different clinical conditions.

Among all galenic formulations, olive oil extracts from medical Cannabis are the most prescribed ones for their easy preparation and usage. A great variety of methods have been described so far for the extraction of medical Cannabis oils to reach a high yield of Δ9-tetrahydrocannabinol (Δ9-THC), but poor attention has been paid to the preservation of the terpene fraction from the plant, which may contribute to the overall bioactivity of the extracts.

In this context, the present study was aimed at the chemical characterization of different medical Cannabis oils prepared by following both innovative and existing extraction protocols, with particular attention to cannabinoids and terpenes, in order to set up a suitable method to obtain an extract rich in these chemical classes. In particular, six different extraction procedures were followed, based on different techniques, of which all but one included a decarboxylation of the plant material.

The profile of cannabinoids was studied in detail by means of HPLC-ESI-MS/MS, while terpenes were characterized by means both GC-MS and GC-FID techniques coupled with solid-phase microextraction operated in the head-space mode (HS-SPME). An innovative method that is based on the extraction of the oil by dynamic maceration at room temperature from plant inflorescences, which were partially decarboxylated in a closed system at a moderate temperature and partially pre-extracted with ethanol, produced similar yields of bioactive compounds as that obtained by using a microwave-assisted distillation of the essential oil from the plant material, in combination with a maceration extraction of the oil from the residue.

Both these new methods provided a higher efficiency over already existing extraction procedures of medical Cannabis oils and they can be applied to obtain a product with a high therapeutic value.”

https://www.ncbi.nlm.nih.gov/pubmed/32334134

“New methods were developed for the extraction of medical Cannabis oils.”

https://www.sciencedirect.com/science/article/abs/pii/S0731708520303897?via%3Dihub

CBD modulates DNA methylation in mice prefrontal cortex and hippocampus of mice exposed to forced swim.

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Behavioural Brain Research“Cannabidiol (CBD), a non-psychotomimetic component of Cannabis sativa plant, shows therapeutic potential in psychiatric disorders, including depression.

The molecular mechanisms underlying the antidepressant-like effects of CBD are not yet understood. Previous studies in differentiated skin cells demonstrated that CBD regulates DNA methylation, an overall repressive epigenetic mechanism. Both stress exposure and antidepressant treatment can modulate DNA methylation in the brain, and lead to gene expression changes associated with depression neurobiology.

We investigated herein if the antidepressant effect of CBD could be associated with changes in DNA methylation in the prefrontal cortex (PFC) and hippocampus (HPC) of mice submitted to the forced swimming test (FST).

Altogether, our results indicate that CBD regulates DNA methylation in brain regions relevant for depression neurobiology, suggesting that this mechanism could be related to CBD-induced antidepressant effects.”

https://www.ncbi.nlm.nih.gov/pubmed/32348868

“Cannabidiol (CBD) shows antidepressant-like properties in mice.”

https://www.sciencedirect.com/science/article/pii/S0166432820303260?via%3Dihub

Antimicrobial and antibiofilm activity of Cannabis sativa L. seeds extract against Staphylococcus aureus and growth effects on probiotic Lactobacillus spp.

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LWT“The growing concern on the antibiotic resistance spreading among bacteria has stimulated the search for valuable alternatives from plant sources.

This study dealt with the potential use of hemp (Cannabis sativa L.) seeds extract to inhibit the growth of selected pathogenic enterobacteria and the biofilm formation by Staphylococcus aureus, representing severe risks of food-borne illnesses. Effects on probiotic bacteria were also examined. A double-staining viability/mortality assay was used to examine potential S. aureus membrane damage.

Our results highlighted a selective antimicrobial activity of C. sativa extract against pathogenic strains and no inhibitory effects on the growth of probiotic strains belonging to the Bifidobacterium and Lactobacillus genera. This selective inhibition is of outmost importance for the maintenance of healthy gut microbiota.

The double-staining assay showed that the C. sativa extract was capable of inhibiting the biofilm producer S. aureus ATCC 35556 strain; this antibacterial action was only partially linked to membrane damage. Biofilm formation was inhibited as well; inhibition occurs at lower concentration with respect to planktonic cells (0.5 mg/ml vs 1 mg/ml, respectively).

Therefore, hemp seeds extracts represent a new exploitable and valuable antimicrobial and antibiofilm agent for the food and nutraceutical industry as a possible alternative to antibiotics/antibacterial compounds.

•Cannabis sativa L. seeds showed antimicrobial and antibiofilm activity.

•C. sativa L. seeds selectively inhibit the growth of potentially pathogenic strains.

•C. sativa L. seeds did not exert antimicrobial activity against probiotic bacteria.

•C. sativa L. seeds inhibit the biofilm formation by Staphylococcus aureus.”

https://www.sciencedirect.com/science/article/pii/S0023643820301377

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“Antimicrobial Activity of Cannabis sativa L.”  https://www.scirp.org/journal/PaperInformation.aspx?PaperID=18123

“Antimicrobial studies of the leaf of cannabis sativa L.”  https://www.ncbi.nlm.nih.gov/pubmed/16414764

Cannabis and Canabidinoids on the Inflammatory Bowel Diseases: Going Beyond Misuse.

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ijms-logo“Inflammatory bowel diseases (IBD) are characterized by a chronic and recurrent gastrointestinal condition, including mainly ulcerative colitis (UC) and Crohn’s disease (CD). Cannabis sativa (CS) is widely used for medicinal, recreational, and religious purposes. The most studied compound of CS is tetrahydrocannabinol (THC) and cannabidiol (CBD). Besides many relevant therapeutic roles such as anti-inflammatory and antioxidant properties, there is still much controversy about the consumption of this plant since the misuse can lead to serious health problems. Because of these reasons, the aim of this review is to investigate the effects of CS on the treatment of UC and CD. The literature search was performed in PubMed/Medline, PMC, EMBASE, and Cochrane databases. The use of CS leads to the improvement of UC and CD scores and quality of life. The medical use of CS is on the rise. Although the literature shows relevant antioxidant and anti-inflammatory effects that could improve UC and CD scores, it is still not possible to establish a treatment criterion since the studies have no standardization regarding the variety and part of the plant that is used, route of administration and doses. Therefore, we suggest caution in the use of CS in the therapeutic approach of IBD until clinical trials with standardization and a relevant number of patients are performed.”

https://www.ncbi.nlm.nih.gov/pubmed/32331305

https://www.mdpi.com/1422-0067/21/8/2940

Cannabinoids in epilepsy: Clinical efficacy and pharmacological considerations.

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Neurología“Advances in the development of drugs with novel mechanisms of action have not been sufficient to significantly reduce the percentage of patients presenting drug-resistant epilepsy. This lack of satisfactory clinical results has led to the search for more effective treatment alternatives with new mechanisms of action.

The aim of this study is to examine epidemiological aspects of the use of cannabis-based products for the treatment of epilepsy, with particular emphasis on the main mechanisms of action, indications for use, clinical efficacy, and safety.

In recent years there has been growing interest in the use of cannabis-based products for the treatment of a wide range of diseases, including epilepsy. The cannabis plant is currently known to contain more than 100 terpenophenolic compounds, known as cannabinoids. The 2 most abundant are delta-9-tetrahydrocannabinol and cannabidiol.

Studies of preclinical models of epilepsy have shown that these cannabinoids have anticonvulsant properties, and 100% purified cannabidiol and cannabidiol-enriched cannabis extracts are now being used to treat epilepsy in humans. Several open-label studies and randomised controlled clinical trials have demonstrated the efficacy and safety of these products.”

https://www.ncbi.nlm.nih.gov/pubmed/32317123

https://www.sciencedirect.com/science/article/pii/S0213485320300402?via%3Dihub

Cannabinoids.

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Cover of StatPearls“Cannabinoids, broadly speaking, are a class of biological compounds that bind to cannabinoid receptors. They are most frequently sourced from and associated with the plants of the Cannabis genus, including Cannabis sativa, Cannabis indica, and Cannabis ruderalis.

The earliest known use of cannabinoids dates back 5,000 years ago in modern Romania, while the documentation of the earliest medical dates back to around 400 AD. However, formal extraction, isolation, and structural elucidation of cannabinoids have taken place rather recently in the late 19th and early 20th centuries. Since then, numerous advancements have been made in further isolating naturally occurring cannabinoids, synthesizing artificial equivalents, and discovering the endogenous the endocannabinoid system in mammals, reptiles, fish, and birds.”

https://www.ncbi.nlm.nih.gov/pubmed/32310522

https://www.ncbi.nlm.nih.gov/books/NBK556062/

Cannabidiol (CBD).

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Cover of StatPearls“Cannabis sativa or Indian hemp (subfamily Cannaboideae of family Moraceae) is an annual herbaceous plant, native to central and western Asia, cultivated for medicinal properties and for hemp, which is a natural textile fiber. The plant contains over 400 chemical compounds, of which approximately 80 biologically active chemical molecules. The most important cannabis compounds are cannabinoids formed by a terpene combined with resorcinol, or, according to a different nomenclature, by a benzopyranic ring system. There are about sixty cannabinoids, of which the most important psychoactive compound is tetrahydrocannabinol (TCH), in particular the isomer delta (Δ9-THC). Other identified compounds are cannabidiol (CBD), cannabigerol (CBG), cannabinol (CBN), cannabichromene (CBC), and olivetol. In addition to cannabinoids, the plant contains terpenoids such as beta-myrcene, beta-caryophyllene, d-limonene, linalool, piperidine, and p-cymene, as well as flavonoids such as quercetin.”

https://www.ncbi.nlm.nih.gov/pubmed/32310508

https://www.ncbi.nlm.nih.gov/books/NBK556048/