Cannabigerolic acid, a major biosynthetic precursor molecule in cannabis, exhibits divergent effects on seizures in mouse models of epilepsy

British Journal of Pharmacology, Journal Year: 2021, Volume and Issue: 178(24), P. 4826 - 4841

Published: Aug. 12, 2021

Background and Purpose Cannabis has been used to treat epilepsy for millennia, with such use validated by regulatory approval of cannabidiol (CBD) Dravet syndrome. Unregulated artisanal cannabis‐based products children intractable epilepsies often contain relatively low doses CBD but are enriched in other phytocannabinoids. This raises the possibility that cannabis constituents might have anticonvulsant properties. Experimental Approach We Scn1a +/− mouse model syndrome investigate plant phytocannabinoids effects against hyperthermia‐induced seizures. The most promising, cannabigerolic acid (CBGA), was further examined spontaneous seizures survival mice electroshock seizure models. Pharmacological CBGA were surveyed across multiple drug targets. Key Results initial screen identified three novel properties: CBGA, cannabidivarinic (CBDVA) cannabigerovarinic (CBGVA). potent potentiated clobazam seizures, MES threshold test. However, proconvulsant 6‐Hz test a high dose increased frequency mice. found interact numerous epilepsy‐relevant targets including GPR55, TRPV1 channels GABA A receptors. Conclusion Implications These results suggest CBDVA CBGVA may contribute childhood epilepsy. Although these potential could be lead compounds development programmes, several liabilities would need overcome before is superseded another this class.

Language: Английский

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A Phase 2 Randomised Clinical Trial Assessing the Tolerability of Two Different Ratios of Medicinal Cannabis in Patients With High Grade Gliomas

Frontiers in Oncology, Journal Year: 2021, Volume and Issue: 11

Published: May 21, 2021

Cannabis for cancer is very topical and, given the use of illicit cannabis preparations used in this vulnerable population, research investigating standardised, quality-assured medicinal critical to inform clinicians and assist patient safety.A randomized trial involving adult patients diagnosed with a high-grade glioma, no history substance abuse, liver or kidney damage myocardial infarction were eligible inclusion tolerability study on two different ratios cannabis. Baseline screening brain morphology, blood pathology, functional status, cognition was conducted. A retrospective control group comparison secondary outcomes.Participants (n=88) average 53.3 years old. paired t-test assessed Functional Assessment Cancer Therapy Brain (FACT-Br) between groups from baseline week 12 found that 1:1 ratio favoured both physical (p=0.025) (p=0.014) capacity improved sleep (p=0.009). Analysis changes also 11% 61 participants had reduction disease, 34% stable, 16% slight enhancement, 10% progressive disease. No serious adverse events occurred. Side effects included dry mouth, tiredness at night, dizziness, drowsiness.This demonstrated single nightly dose THC-containing safe, well tolerated patients. Medicinal significantly sleep, wellbeing, quality life.Australian New Zealand Clinical Trials Registry (ANZCTR) http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373556&isReview=true, identifier ACTRN12617001287325.

Language: Английский

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Molecular and Biochemical Mechanism of Cannabidiol in the Management of the Inflammatory and Oxidative Processes Associated with Endometriosis

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(10), P. 5427 - 5427

Published: May 12, 2022

Endometriosis is usually associated with inflammation and chronic pelvic pain. This paper focuses the attention on anti-inflammatory, anti-oxidant analgesic effects of cannabidiol (CBD) its potential role in endometriosis. We employed an vivo model endometriosis administered CBD daily by gavage. administration strongly reduced lesions diameter, volume area. In particular, it was able to modify lesion morphology, reducing epithelial glands stroma. showed lipid peroxidation, expression Nox-1 Nox-4 enzymes. restored oxidative equilibrium endogenous cellular defense as SOD activity GSH levels lesions. also important antifibrotic Masson trichrome staining downregulated MMP-9, iNOS TGF-β. reduce both harvested lesions, increased Ikb-α COX2 cytosolic expressions NFkB nuclear localization, peritoneal fluids decreased TNF-α, PGE2 IL-1α levels. has mast cells recruitment spinal cord release neuro-sensitizing pro-inflammatory mediators. conclusion, collected data that effective coordinated suppression.

Language: Английский

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Modulatory Effect of Gut Microbiota on the Gut-Brain, Gut-Bone Axes, and the Impact of Cannabinoids

Metabolites, Journal Year: 2022, Volume and Issue: 12(12), P. 1247 - 1247

Published: Dec. 10, 2022

The gut microbiome is a collection of microorganisms and parasites in the gastrointestinal tract. Many factors can affect this community's composition, such as age, sex, diet, medications, environmental triggers. relationship between human host microbiota crucial for organism's survival development, whereas disruption lead to various inflammatory diseases. Cannabidiol (CBD) tetrahydrocannabinol (THC) are used treat muscle spasticity associated with multiple sclerosis. It now clear that these compounds also benefit patients neuroinflammation. CBD THC treatment inflammation. significant source nutrients, including vitamins B K, which products. While play role brain bone development function, influence on gut-brain gut-bone axes extends further continues receive increasing scientific scrutiny. has been demonstrated be vital optimal functions stress suppression. Additionally, several studies have revealed developing maintaining skeletal integrity mineral density. maintenance matrix. presence actions specific T regulatory cells, formation proliferation. In addition, its metabolites prevent loss. help maintain bone's equilibrium metabolic diseases, osteoporosis. review, dual plays regulating axis impact roles discussed.

Language: Английский

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Targeting Cell Signaling Pathways in Lung Cancer by Bioactive Phytocompounds

Cancers, Journal Year: 2023, Volume and Issue: 15(15), P. 3980 - 3980

Published: Aug. 5, 2023

Lung cancer is a heterogeneous group of malignancies with high incidence worldwide. It the most frequently occurring in men and second common women. Due to its frequent diagnosis variable response treatment, lung was reported as top cause cancer-related deaths worldwide 2020. Many aberrant signaling cascades are implicated pathogenesis cancer, including those involved apoptosis (B cell lymphoma protein, Bcl-2-associated X first signal ligand), growth inhibition (tumor suppressor protein or gene serine/threonine kinase 11), promotion (epidermal factor receptor/proto-oncogenes/phosphatidylinositol-3 kinase). Accordingly, these pathways their molecules have become promising targets for chemopreventive chemotherapeutic agents. Recent research provides compelling evidence use plant-based compounds, known collectively phytochemicals, anticancer This review discusses major contributing pathophysiology well currently available treatments prospective drug candidates. The potential naturally bioactive compounds context also discussed, critical analysis mechanistic actions presented by preclinical clinical studies.

Language: Английский

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