Cannabinoid receptor expression in non-small cell lung cancer. Effectiveness of tetrahydrocannabinol and cannabidiol inhibiting cell proliferation and epithelial-mesenchymal transition in vitro.

Image result for plos one “Patients with non-small cell lung cancer (NSCLC) develop resistance to antitumor agents by mechanisms that involve the epithelial-to-mesenchymal transition (EMT). This necessitates the development of new complementary drugs, e.g., cannabinoid receptors (CB1 and CB2) agonists including tetrahydrocannabinol (THC) and cannabidiol (CBD).

The combined use of THC and CBD confers greater benefits, as CBD enhances the effects of THC and reduces its psychotropic activity. We assessed the relationship between the expression levels of CB1 and CB2 to the clinical features of a cohort of patients with NSCLC, and the effect of THC and CBD (individually and in combination) on proliferation, EMT and migration in vitro in A549, H460 and H1792 lung cancer cell lines.

METHODS:

Expression levels of CB1, CB2, EGFR, CDH1, CDH2 and VIM were evaluated by quantitative reverse transcription-polymerase chain reaction. THC and CBD (10-100 μM), individually or in combination (1:1 ratio), were used for in vitro assays. Cell proliferation was determined by BrdU incorporation assay. Morphological changes in the cells were visualized by phase-contrast and fluorescence microscopy. Migration was studied by scratch recolonization induced by 20 ng/ml epidermal growth factor (EGF).

RESULTS:

The tumor samples were classified according to the level of expression of CB1, CB2, or both. Patients with high expression levels of CB1, CB2, and CB1/CB2 showed increased survival reaching significance for CB1 and CB1/CB2 (p = 0.035 and 0.025, respectively).

Both cannabinoid agonists inhibited the proliferation and expression of EGFR in lung cancer cells, and CBD potentiated the effect of THC. THC and CBD alone or in combination restored the epithelial phenotype, as evidenced by increased expression of CDH1 and reduced expression of CDH2 and VIM, as well as by fluorescence analysis of cellular cytoskeleton.

Finally, both cannabinoids reduced the in vitro migration of the three lung cancer cells lines used.

CONCLUSIONS:

The expression levels of CB1 and CB2 have a potential use as markers of survival in patients with NSCLC. THC and CBD inhibited the proliferation and expression of EGFR in the lung cancer cells studied. Finally, the THC/CBD combination restored the epithelial phenotype in vitro.”

https://www.ncbi.nlm.nih.gov/pubmed/32049991

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0228909

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The Epigenetics of the Endocannabinoid System.

ijms-logo “The endocannabinoid system (ES) is a cell-signalling system widely distributed in biological tissues that includes endogenous ligands, receptors, and biosynthetic and hydrolysing machineries.

The impairment of the ES has been associated to several pathological conditions like behavioural, neurological, or metabolic disorders and infertility, suggesting that the modulation of this system may be critical for the maintenance of health status and disease treatment.

Lifestyle and environmental factors can exert long-term effects on gene expression without any change in the nucleotide sequence of DNA, affecting health maintenance and influencing both disease load and resistance. This potentially reversible “epigenetic” modulation of gene expression occurs through the chemical modification of DNA and histone protein tails or the specific production of regulatory non-coding RNA (ncRNA).

Recent findings demonstrate the epigenetic modulation of the ES in biological tissues; in the same way, endocannabinoids, phytocannabinoids, and cannabinoid receptor agonists and antagonists induce widespread or gene-specific epigenetic changes with the possibility of trans-generational epigenetic inheritance in the offspring explained by the transmission of deregulated epigenetic marks in the gametes.

Therefore, this review provides an update on the epigenetics of the ES, with particular attention on the emerging role in reproduction and fertility.”

https://www.ncbi.nlm.nih.gov/pubmed/32046164

https://www.mdpi.com/1422-0067/21/3/1113

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Cannabinoids and Terpenes as an Antibacterial and Antibiofouling Promotor for PES Water Filtration Membranes.

molecules-logo“Plant phytochemicals have potential decontaminating properties, however, their role in the amelioration of hydrophobic water filtration membranes have not been elucidated yet.

In this work, phytochemicals (i.e., cannabinoids (C) and terpenes (T) from C. sativa) were revealed for their antibacterial activity against different Gram-positive and Gram-negative bacteria.

The results of this study established cannabinoids and terpenes as an inexpensive solution for polyethersulfone (PES) membrane surface modification.

These hybrid membranes can be easily deployed at an industrial scale for water filtration purposes.”

https://www.ncbi.nlm.nih.gov/pubmed/32041149

https://www.mdpi.com/1420-3049/25/3/691

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Targeting GPCRs Against Cardiotoxicity Induced by Anticancer Treatments.

Image result for frontiers in cardiovascular medicine“Novel anticancer medicines, including targeted therapies and immune checkpoint inhibitors, have greatly improved the management of cancers. However, both conventional and new anticancer treatments induce cardiac adverse effects, which remain a critical issue in clinic.

Cardiotoxicity induced by anti-cancer treatments compromise vasospastic and thromboembolic ischemia, dysrhythmia, hypertension, myocarditis, and cardiac dysfunction that can result in heart failure. Importantly, none of the strategies to prevent cardiotoxicity from anticancer therapies is completely safe and satisfactory.

Certain clinically used cardioprotective drugs can even contribute to cancer induction. Since G protein coupled receptors (GPCRs) are target of forty percent of clinically used drugs, here we discuss the newly identified cardioprotective agents that bind GPCRs of adrenalin, adenosine, melatonin, ghrelin, galanin, apelin, prokineticin and cannabidiol.

We hope to provoke further drug development studies considering these GPCRs as potential targets to be translated to treatment of human heart failure induced by anticancer drugs.”

https://www.ncbi.nlm.nih.gov/pubmed/32039239

https://www.frontiersin.org/articles/10.3389/fcvm.2019.00194/full

“Cannabidiol Protects against Doxorubicin-Induced Cardiomyopathy by Modulating Mitochondrial Function and Biogenesis.”  https://www.ncbi.nlm.nih.gov/pubmed/25569804

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Cannabinoids in the Pathophysiology of Skin Inflammation.

molecules-logo“Cannabinoids are increasingly-used substances in the treatment of chronic pain, some neuropsychiatric disorders and more recently, skin disorders with an inflammatory component.

This paper aims to detail and clarify the complex workings of cannabinoids in the molecular setting of the main dermatological inflammatory diseases, and their interactions with other substances with emerging applications in the treatment of these conditions. Also, the potential role of cannabinoids as antitumoral drugs is explored in relation to the inflammatory component of skin cancer.

In vivo and in vitro studies that employed either phyto-, endo-, or synthetic cannabinoids were considered in this paper. Cannabinoids are regarded with growing interest as eligible drugs in the treatment of skin inflammatory conditions, with potential anticancer effects, and the readiness in monitoring of effects and the facility of topical application may contribute to the growing support of the use of these substances.

Despite the promising early results, further controlled human studies are required to establish the definitive role of these products in the pathophysiology of skin inflammation and their usefulness in the clinical setting.”

https://www.ncbi.nlm.nih.gov/pubmed/32033005

https://www.mdpi.com/1420-3049/25/3/652

“Cannabinoid Signaling in the Skin: Therapeutic Potential of the “C(ut)annabinoid” System” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6429381/

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Comparison of Efficacy of Cannabinoids versus Commercial Oral Care Products in Reducing Bacterial Content from Dental Plaque: A Preliminary Observation.

Image result for cureus journal“Dental plaque is a complex biofilm that gets formed on the teeth and acts as a reservoir of different microbes. It is the root cause for the occurrence of several dental problems and diseases, including cavities, bad breath, bleeding gums, tooth decay, and tooth loss. Therefore, it should be regularly removed using suitable oral care aids.

The present study compared the efficacy of oral care products and cannabinoids in reducing the bacterial content of dental plaques.

Sixty adults aged 18 to 45 years were categorized into six groups based on the Dutch periodontal screening index. Dental plaques of the adults were collected using paro-toothpick sticks and spread on two Petri dishes, each with four divisions. On Petri dish-A, cannabidiol (CBD), cannabichromene (CBC), cannabinol (CBN), and cannabigerol (CBG) were used, and on Petri dish-B, cannabigerolic acid (CBGA), Oral B, Colgate, and Cannabite F (a toothpaste formulation of pomegranate and algae) were used. The Petri dishes were sealed and incubated, followed by counting the number of colonies.

Results: By evaluating the colony count of the dental bacteria isolated from six groups, it was found that cannabinoids were more effective in reducing the bacterial colony count in dental plaques as compared to the well-established synthetic oral care products such as Oral B and Colgate.

Conclusion: Cannabinoids have the potential to be used as an effective antibacterial agent against dental plaque-associated bacteria. Moreover, it provides a safer alternative for synthetic antibiotics to reduce the development of drug resistance.”

https://www.ncbi.nlm.nih.gov/pubmed/32038896

“To the best of our knowledge, no such study has been published that compares the efficiency of cannabinoids with that of oral care products against dental bacteria. Our study is the first of its kind conducted to compare the efficacy of well-established commercial oral care products and cannabinoids in reducing the bacterial content of the dental plaque. Reducing the bacterial content could significantly decrease and prevent gum diseases that have become a huge global burden owing to their direct relation with systemic diseases. Here we report a preliminary observatory study on effect of cannabinoids on reducing the bacterial content of dental plaque.”

https://www.cureus.com/articles/25300-comparison-of-efficacy-of-cannabinoids-versus-commercial-oral-care-products-in-reducing-bacterial-content-from-dental-plaque-a-preliminary-observation

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Abrupt withdrawal of cannabidiol (CBD): A randomized trial.

Cover image volume 103, Issue “The rationale of this study was to assess occurrence of withdrawal symptoms induced by abrupt cessation of cannabidiol (CBD) after prolonged administration in healthy volunteers.

CONCLUSION:

In healthy volunteers, no evidence of withdrawal syndrome was found with abrupt discontinuation of short-term treatment with CBD.”

https://www.ncbi.nlm.nih.gov/pubmed/32036242

“There was no evidence of a physical withdrawal syndrome after abrupt cessation of CBD.”

https://www.epilepsybehavior.com/article/S1525-5050(19)31116-3/fulltext

Cannabidiol, a safe and non-psychotropic ingredient of the marijuana plant Cannabis sativa” https://www.ncbi.nlm.nih.gov/pubmed/19690824

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Neuroprotective effect of chronic administration of cannabidiol during the abstinence period on methamphetamine-induced impairment of recognition memory in the rats.

“Neuropsychiatric disorders, such as addiction, are associated with cognitive impairment, including learning and memory deficits.

Previous research has demonstrated that the chronic use of methamphetamine (METH) induces long-term cognitive impairment and cannabidiol (CBD), as a neuroprotectant, can reverse spatial memory deficits induced by drug abuse.

The study aimed to evaluate the effect of CBD on METH-induced memory impairment in rats chronically exposed to METH (CEM).

For the induction of CEM, animals received METH (2 mg/kg, twice/day) for 10 days. Thereafter, the effect of intracerebroventricular (ICV) administration of CBD (32 and 160 nmol) during the (10 days) abstinence period on spatial memory was evaluated using the Y-Maze test, while recognition memory was examined using the novel object recognition (NOR) test.

The results revealed a significant increase in the motor activity of METH-treated animals compared with the control group and, after the 10-day abstinence period, motor activity returned to baseline. Notably, the chronic administration of METH had impairing effects on spontaneous alternation performance and recognition memory, which was clearly observed in the NOR test.

Additionally, although the ICV administration of CBD (160 nmol) could reverse long-term memory, a lower dose (32 nmol) did not result in any significant increase in exploring the novel object during short-term memory testing.

These novel findings suggest that the chronic administration of METH induces memory impairment and presents interesting implications for the potential use of CBD in treating impairment deficits after chronic exposure to psychostimulant drugs such as METH.”

https://www.ncbi.nlm.nih.gov/pubmed/32032100

https://journals.lww.com/behaviouralpharm/Abstract/publishahead/Neuroprotective_effect_of_chronic_administration.99194.aspx

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Medical Cannabis in Children.

 Logo of rmmj“The use of medical cannabis in children is rapidly growing.

While robust evidence currently exists only for pure cannabidiol (CBD) to treat specific types of refractory epilepsy, in most cases, artisanal strains of CBD-rich medical cannabis are being used to treat children with various types of refractory epilepsy or irritability associated with autism spectrum disorder (ASD).

Other common pediatric disorders that are being considered for cannabis treatment are Tourette syndrome and spasticity.

As recreational cannabis use during youth is associated with serious adverse events and medical cannabis use is believed to have a relatively high placebo effect, decisions to use medical cannabis during childhood and adolescence should be made with caution and based on evidence.

This review summarizes the current evidence for safety, tolerability, and efficacy of medical cannabis in children with epilepsy and in children with ASD. The main risks associated with use of Δ9-tetrahydrocannabinol (THC) and CBD in the pediatric population are described, as well as the debate regarding the use of whole-plant extract to retain a possible “entourage effect” as opposed to pure cannabinoids that are more standardized and reproducible.”

https://www.ncbi.nlm.nih.gov/pubmed/32017680

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Cannabinoid and Terpenoid Doses are Associated with Adult ADHD Status of Medical Cannabis Patients.

Logo of rmmj “The aim of this cross-sectional questionnaire-based study was to identify associations between the doses of cannabinoids and terpenes administered, and symptoms of attention deficit hyperactivity disorder (ADHD).

CONCLUSION:

These findings reveal that the higher-dose consumption of  medical cannabis (MC) components (phyto-cannabinoids and terpenes) is associated with ADHD medication reduction.

In addition, high dosage of CBN was associated with a lower ASRS score.

However, more studies are needed in order to fully understand if cannabis and its constituents can be used for management of ADHD.”

https://www.ncbi.nlm.nih.gov/pubmed/32017685

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