Tag Archives: Hemp

The Interplay between the Immune and the Endocannabinoid Systems in Cancer

Posted on by

cells-logo“The therapeutic potential of Cannabis sativa has been recognized since ancient times. Phytocannabinoids, endocannabinoids and synthetic cannabinoids activate two major G protein-coupled receptors, subtype 1 and 2 (CB1 and CB2). Cannabinoids (CBs) modulate several aspects of cancer cells, such as apoptosis, autophagy, proliferation, migration, epithelial-to-mesenchymal transition and stemness. Moreover, agonists of CB1 and CB2 receptors inhibit angiogenesis and lymphangiogenesis in vitro and in vivo. Low-grade inflammation is a hallmark of cancer in the tumor microenvironment (TME), which contains a plethora of innate and adaptive immune cells. These cells play a central role in tumor initiation and growth and the formation of metastasis. CB2 and, to a lesser extent, CB1 receptors are expressed on a variety of immune cells present in TME (e.g., T cells, macrophages, mast cells, neutrophils, NK cells, dendritic cells, monocytes, eosinophils). The activation of CB receptors modulates a variety of biological effects on cells of the adaptive and innate immune system. The expression of CB2 and CB1 on different subsets of immune cells in TME and hence in tumor development is incompletely characterized. The recent characterization of the human cannabinoid receptor CB2-Gi signaling complex will likely aid to design potent and specific CB2/CB1 ligands with therapeutic potential in cancer.”

https://pubmed.ncbi.nlm.nih.gov/34064197/

https://www.mdpi.com/2073-4409/10/6/1282

β-Caryophyllene, A Natural Dietary CB2 Receptor Selective Cannabinoid can be a Candidate to Target the Trinity of Infection, Immunity, and Inflammation in COVID-19

Posted on by

Frontiers in Pharmacology (@FrontPharmacol) | Twitter“Coronavirus disease (COVID-19), caused by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an ongoing pandemic and presents a public health emergency. It has affected millions of people and continues to affect more, despite tremendous social preventive measures. Identifying candidate drugs for the prevention and treatment of COVID-19 is crucial. The pathogenesis and the complications with advanced infection mainly involve an immune-inflammatory cascade. Therefore, therapeutic strategy relies on suppressing infectivity and inflammation, along with immune modulation.

One of the most promising therapeutic targets for the modulation of immune-inflammatory responses is the endocannabinoid system, particularly the activation of cannabinoid type 2 receptors (CB2R), a G-protein coupled receptor which mediates the anti-inflammatory properties by modulating numerous signaling pathways. To pharmacologically activate the CB2 receptors, a naturally occurring cannabinoid ligand, beta-caryophyllene (BCP), received attention due to its potent anti-inflammatory, antiviral, and immunomodulatory properties. BCP is recognized as a full selective functional agonist on CB2 receptors and produces therapeutic effects by activating CB2 and the nuclear receptors, peroxisome proliferator-activated receptors (PPARs).

BCP is regarded as the first dietary cannabinoid with abundant presence across cannabis and non-cannabis plants, including spices and other edible plants. BCP showed tissue protective properties and favorably modulates numerous signaling pathways and inhibits inflammatory mediators, including cytokines, chemokines, adhesion molecules, prostanoids, and eicosanoids. Based on its pharmacological properties, molecular mechanisms, and the therapeutic potential of BCP as an immunomodulator, anti-inflammatory, organ-protective, and antiviral, we hypothesize that BCP could be a promising therapeutic and/or preventive candidate to target the triad of infection, immunity, and inflammation in COVID-19. In line with numerous studies that proposed the potential of cannabinoids in COVID-19,

BCP may be a novel candidate compound for pharmaceutical and nutraceutical development due to its unique functional receptor selectivity, wide availability and accessibility, dietary bioavailability, nonpsychoactivity, and negligible toxicity along with druggable properties, including favorable pharmacokinetic and physicochemical properties. Based on reasonable pharmacological mechanisms and therapeutic properties, we speculate that BCP has potential to be investigated against COVID-19 and will inspire further preclinical and clinical studies.”

https://pubmed.ncbi.nlm.nih.gov/34054510/

“Over the past few months, it has been suggested that modulation of the endocannabinoid system by cannabinoids, including cannabidiol, could be useful in prophylaxis and treatment of COVID-19 and may improve prognosis. Recently, extract of Cannabis sativa containing phytocannabinoids and terpenes were shown to modulate the inflammatory mediators in alveolar epithelial cells (A549) in COVID-19-associated inflammation and suggested that the phytocannabinoid mix formulation exerted better activity in comparison with individual fractions from cannabis. Many cannabinoids, including cannabidiol, have been suggested for their possible potential as preventive agents or therapeutic adjuvants with other agents in targeting the trinity of infection, inflammation, and immunity in COVID-19.”

https://www.frontiersin.org/articles/10.3389/fphar.2021.590201/full

“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.”   http://www.ncbi.nlm.nih.gov/pubmed/23138934

“Beta-caryophyllene is a dietary cannabinoid.”   https://www.ncbi.nlm.nih.gov/pubmed/18574142

Cannabidiol Modulates Mitochondrial Redox and Dynamics in MCF7 Cancer Cells: A Study Using Fluorescence Lifetime Imaging Microscopy of NAD(P)H

Posted on by

Archive of "Frontiers in Molecular Biosciences".“The cannabinoid, cannabidiol (CBD), is part of the plant’s natural defense system that when given to animals has many useful medicinal properties, including activity against cancer cells, modulation of the immune system, and efficacy in epilepsy.

Our results support the use of NAD(P)H autofluorescence as an investigative tool and provide further evidence that CBD can modulate mitochondrial function and morphology in a dose-dependent manner, with clear evidence of it inducing oxidative stress at higher concentrations.

This continues to support emerging data in the literature and may provide further insight into its overall mode of action, not only in cancer, but potentially its function in the plant and why it can act as a medicine.”

https://pubmed.ncbi.nlm.nih.gov/34046425/

“Uncontrolled cell growth, or cancer, is frequently associated with increased aerobic glycolysis (the Warburg effect) and alterations in mitochondrial function.

A plant’s ability to develop tumors could explain why so many secondary plant phenolic compounds appear to have anticancer activity in both plant and animal models; over 3,000 species of plants have anticancer activity in animals, with many modulating mitochondrial function and apoptosis

CBD, along with Δ9-tetrahydrocannabinol (THC), is a major phytocannabinoid and both are well described components of medicines.

A growing number of studies have demonstrated the anticancer properties of CBD, in both in vitro and in vivo models.”

https://www.frontiersin.org/articles/10.3389/fmolb.2021.630107/full

Cannabis and cannabinoid use in autism spectrum disorder: a systematic review

Posted on by

SciELO (Scientific Electronic Library Online) | UOC Library“Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by persistent deficits in social communication and social interaction, associated with the presence of restricted and repetitive patterns of behavior, interests, or activities. Cannabis has been used to alleviate symptoms associated with ASD.

Method: We carried out a systematic review of studies that investigated the clinical effects of cannabis and cannabinoid use on ASD, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA checklist). The search was carried out in four databases: MEDLINE/PubMed, Scientific Electronic Library Online (SciELO), Scopus, and Web of Science. No limits were established for language during the selection process. Nine studies were selected and analyzed.

Results: Some studies showed that cannabis products reduced the number and/or intensity of different symptoms, including hyperactivity, attacks of self-mutilation and anger, sleep problems, anxiety, restlessness, psychomotor agitation, irritability, aggressiveness perseverance, and depression. Moreover, they found an improvement in cognition, sensory sensitivity, attention, social interaction, and language. The most common adverse effects were sleep disorders, restlessness, nervousness and change in appetite.

Conclusion: Cannabis and cannabinoids may have promising effects in the treatment of symptoms related to ASD, and can be used as a therapeutic alternative in the relief of those symptoms. However, randomized, blind, placebo-controlled clinical trials are necessary to clarify findings on the effects of cannabis and its cannabinoids in individuals with ASD.”

https://pubmed.ncbi.nlm.nih.gov/34043900/

 

“Cannabis and cannabinoids have very promising effects in the treatment of autistic symptoms and can be used in the future as an important therapeutic alternative to relieve those symptoms, especially bouts of self-mutilation and anger, hyperactivity, sleep problems, anxiety, restlessness, psychomotor agitation, irritability, and aggressiveness; as well as improve sensory sensitivity, cognition, attention, social interaction, language, perseverance, and depression.”

https://www.scielo.br/j/trends/a/LBmJK6d8bqr5jVK6fp3CHXt/?lang=en

Therapeutic Prospects of Cannabinoids in the Immunomodulation of Prevalent Autoimmune Diseases

Posted on by

View details for Cannabis and Cannabinoid Research cover image“Cannabinoids such as ▵-9-THC and CBD can downregulate the immune response by modulating the endocannabinoid system. This modulation is relevant for the treatment of prevalent autoimmune diseases (ADs), such as multiple sclerosis (MS), systemic lupus erythematosus (SLE), diabetes mellitus type 1 (DMT1), and rheumatoid arthritis (RA). These conditions require new therapeutic options with fewer side effects for the control of the autoimmune response. Objective: to conduct a literature review of preclinical scientific evidence that supports further clinical investigations for the use of cannabinoids (natural or synthetic) as potential immunomodulators of the immune response in ADs. 

Methodology: A systematic search was carried out in different databases using different MeSH terms, such as Cannabis sativa L., cannabinoids, immunomodulation, and ADs. Initially, 677 journal articles were found. After filtering by publication date (from 2000 to 2020 for SLE, DMT1, and RA; and 2010 to 2020 for MS) and removing the duplicate items, 200 articles were selected and analyzed by title and summary associated with the use of cannabinoids as immunomodulatory treatment for those diseases. 

Results: Evidence of the immunomodulatory effect of cannabinoids in the diseases previously mentioned, but SLE that did not meet the search criteria, was summarized from 24 journal articles. CBD was found to be one of the main modulators of the immune response. This molecule decreased the number of Th1 and Th17 proinflammatory cells and the production of the proinflammatory cytokines, interleukin (IL)-1, IL-12, IL-17, interferon (IFN)-γ, and tumor necrosis factor alpha, in mouse models of MS and DMT1. Additionally, new synthetic cannabinoid-like molecules, with agonist or antagonist activity on CB1, CB2, TRPV1, PPAR-α, and PPAR-γ receptors, have shown anti-inflammatory properties in MS, DMT1, and RA. 

Conclusion: Data from experimental animal models of AD showed that natural and synthetic cannabinoids downregulate inflammatory responses mediated by immune cells responsible for AD chronicity and progression. Although synthetic cannabinoid-like molecules were evaluated in just two clinical trials, they corroborated the potential use of cannabinoids to treat some ADs. Notwithstanding, new cannabinoid-based approaches are required to provide alternative treatments to patients affected by the large group of ADs.”

https://pubmed.ncbi.nlm.nih.gov/34030476/

https://www.liebertpub.com/doi/10.1089/can.2020.0183

CBG, CBD, Δ9-THC, CBN, CBGA, CBDA and Δ9-THCA as antioxidant agents and their intervention abilities in antioxidant action

Posted on by

Fitoterapia“Positive effect of some cannabinoids in the treatment and prophylaxis of a wide variety of oxidation-associated diseases and growing popularity of supplements containing cannabinoids, mainly cannabinoid oils (e.g. CBD oil, CBG oil), in the self-medication of humans cause a growing interest in the antioxidant properties of these compounds, especially those not showing psychotropic effects.

Herein, we report the antioxidant activity of cannabigerol (CBG), cannabidiol (CBD), Δ9-tetrahydrocannabinol (Δ9-THC), cannabinol (CBN), cannabigerolic acid (CBGA), cannabinolic acid (CBDA) and Δ9-tetrahydrocannabinolic acid (Δ9-THCA) estimated by spectrophotometric methods: ABTS, DPPH, ORAC, beta-carotene CUPRAC and FRAP.

The presented data prove that all the examined cannabinoids exhibit antioxidant activity manifested in their ability to scavenge free radicals, to prevent the oxidation process and to reduce metal ions. Although the intensity of these activities is not the same for the individual cannabinoids it is comparable for all of them with that of E vitamin.”

https://pubmed.ncbi.nlm.nih.gov/33964342/

“The present paper discusses the antioxidant properties of CBG, CBN, CBDA, CBGA and Δ9-THCA which, beside CBD and Δ9-THC, are also supposed to be bioactive compounds useful in the therapeutic treatment of different diseases. According to the literature, CBD and Δ9-THC exhibit strong antioxidant activity, stronger than vitamins C, A and E.

The presented data prove that all the examined cannabinoids – CBG, CBD, Δ9-THC, CBN, CBGA CBDA and Δ9-THCA – exhibit antioxidant activity manifesting itself in their ability to scavenge free radicals, to protect oxidation process and to reduce metal ions. Although, the intensity of these activities for individual cannabinoids is not the same, it is generally comparable to that of E vitamin.”  https://www.sciencedirect.com/science/article/pii/S0367326X21000903?via%3Dihub

Anti-Bacterial Properties of Cannabigerol Toward Streptococcus mutans

Posted on by

Frontiers in Microbiology: Multidrug Resistance in Pasteurellaceae“Streptococcus mutans (S. mutans) is a gram-positive facultatively anaerobic bacterium and the most common pathogen associated with tooth caries. The organism is acid tolerant and can undergo physiological adaptation to function effectively in acid environments such as carious dental plaque.

Some cannabinoids have been found to have potent anti-microbial activity against gram-positive bacteria. One of these is the non-psychoactive, minor phytocannabinoid Cannabigerol (CBG). Here we show that CBG exhibits anti-bacterial activities against S. mutans.

In summary, we present here data showing the mechanisms by which CBG exerts its anti-bacterial effect against S. mutans.”

https://pubmed.ncbi.nlm.nih.gov/33967995/

“Cannabigerol (CBG) is a non-psychotropic Cannabis-derived cannabinoid (CB). In summary, the present study demonstrates an anti-bacterial effects of the Cannabis component CBG toward the cariogenic bacteria S. mutans. The interference of CBG with the caries causative S. mutans may provide a novel innovative way to combat dental caries.” https://www.frontiersin.org/articles/10.3389/fmicb.2021.656471/full

Cannabidiol Isolated From Cannabis sativa L. Protects Intestinal Barrier From In Vitro Inflammation and Oxidative Stress

Posted on by

Frontiers in Pharmacology (@FrontPharmacol) | Twitter“The relevance and incidence of intestinal bowel diseases (IBD) have been increasing over the last 50 years and the current therapies are characterized by severe side effects, making essential the development of new strategies that combine efficacy and safety in the management of human IBD. Herbal products are highly considered in research aimed at discovering new approaches for IBD therapy and, among others, 

Cannabis sativa L. has been traditionally used for centuries as an analgesic and anti-inflammatory remedy also in different gastrointestinal disorders. This study aims to investigate the effects of different C. sativa isolated compounds in an in vitro model of intestinal epithelium. The ability of treatments to modulate markers of intestinal dysfunctions was tested on Caco-2 intestinal cell monolayers.

Our results, obtained by evaluation of ROS production, TEER and paracellular permeability measurements and tight junctions evaluation show Cannabidiol as the most promising compound against intestinal inflammatory condition. Cannabidiol is able to inhibit ROS production and restore epithelial permeability during inflammatory and oxidative stress conditions, suggesting its possible application as adjuvant in IBD management.”

https://pubmed.ncbi.nlm.nih.gov/33995048/

https://www.frontiersin.org/articles/10.3389/fphar.2021.641210/full

Protective Effects of Cannabidivarin and Cannabigerol on Cells of the Blood-Brain Barrier Under Ischemic Conditions

Posted on by

View details for Cannabis and Cannabinoid Research cover image“Preclinical studies have shown cannabidiol is protective in models of ischemic stroke. Based on results from our recent systematic review, we investigated the effects of two promising neuroprotective phytocannabinoids, cannabigerol (CBG) and cannabidivarin (CBDV), on cells of the blood-brain barrier (BBB), namely human brain microvascular endothelial cells (HBMECs), pericytes, and astrocytes.

Results: In astrocytes CBG and CBDV attenuated levels of interleukin-6 (IL-6) and lactate dehydrogenase (LDH), whereas CBDV (10 nM-10 μM) also decreased vascular endothelial growth factor (VEGF) secretion. CBDV (300 nM-10 μM) attenuated levels of monocyte chemoattractant protein (MCP)-1 in HBMECs. In astrocytes, CBG decreased levels of DNA damage proteins, including p53, whereas CBDV increased levels of DNA damage markers. Antagonists for CB1, CB2, PPAR-γ, PPAR-α, 5-HT1A, and TRPV1 had no effect on CBG (3 μM) or CBDV (1 μM)-mediated decreases in LDH in astrocytes. GPR55 and GPR18 were partially implicated in the effects of CBDV, but no molecular target was identified for CBG.

Conclusions: We show that CBG and CBDV were protective against OG mediated injury in three different cells that constitute the BBB, modulating different hallmarks of ischemic stroke pathophysiology. These data enhance our understanding of the protective effects of CBG and CBDV and warrant further investigation into these compounds in ischemic stroke. Future studies should identify other possible neuroprotective effects of CBG and CBDV and their corresponding mechanisms of action.”

https://pubmed.ncbi.nlm.nih.gov/33998890/

“This study provides novel data on the neuroprotective and anti-inflammatory properties of CBG and CBDV in an in vitro model of IR. These data, together with evidence from other studies, corroborate the protective properties of these compounds and further studies are needed to elucidate the mechanism of action of CBG and CBDV and whether they can modulate BBB permeability in more clinically relevant in vivo models of ischemic stroke. There is lack of effective treatments for ischemic stroke, a condition that will increase in prevalence in coming years, to which cannabinoids may offer a unique therapeutic strategy.” 

https://www.liebertpub.com/doi/10.1089/can.2020.0159

The effectiveness of inhaled Cannabis flower for the treatment of agitation/irritability, anxiety, and common stress

Posted on by

Special Issue Springer/Nature BMC Medical Informatics & Decision Making - Explainable-AI | human-centered.ai“An observational research design was used to evaluate which types of commonly labeled Cannabis flower product characteristics are associated with changes in momentary feelings of distress-related symptoms.

Results: In total, a decrease in symptom intensity levels was reported in 95.51% of Cannabis usage sessions, an increase in 2.32% of sessions, and no change in 2.16% of sessions. Fixed effects models showed, on average, respondents recorded a maximum symptom intensity reduction of 4.33 points for agitation/irritability (SE = 0.20, p < 0.01), 3.47 points for anxiety (SE = 0.13, p < 0.01), and 3.98 for stress (SE = 0.12, p < 0.01) on an 11-point visual analog scale. Fixed effects regressions showed that, controlling for time-invariant user characteristics, mid and high tetrahydrocannabinol (THC) levels were the primary independent predictor of increased symptom relief, and that when broken out by symptom type, this effect was only statistically significant for our largest sample of users, those reporting anxiety rather than agitation/irritability or stress. Cannabidiol (CBD) levels were generally not associated with changes in symptom intensity levels. In a minority of cannabis use sessions (< 13%), cannabis users reported anxiogenic-related negative side effects (e.g., feeling anxious, irritable, paranoid, rapid pulse, or restless), whereas in a majority of sessions (about 66%), users reported positive anxiolytic side effects (e.g., feeling chill, comfy, happy, optimistic, peaceful, or relaxed).

Conclusions: The findings suggest the majority of patients in our sample experienced relief from distress-related symptoms following consumption of Cannabis flower, and that among product characteristics, higher THC levels were the strongest predictors of relief.”

https://pubmed.ncbi.nlm.nih.gov/33526145/

“Our findings suggest that self-directed use of Cannabis flower, especially that with higher THC levels, is associated with significant improvements in at least short-term feelings of distress in many users, likely a contributing factor to its widespread popularity and consumption in the U.S.”

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-020-00051-z