Nav1.8, an analgesic target for nonpsychotomimetic phytocannabinoids

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(4)

Published: Jan. 21, 2025

Pain impacts billions of people worldwide, but treatment options are limited and have a spectrum adverse effects. The search for safe nonaddictive pain treatments has led to focus on key mediators nociceptor excitability. Voltage-gated sodium (Nav) channels in the peripheral nervous system—Nav1.7, Nav1.8, Nav1.9—play crucial roles signaling. Among these, Nav1.8 shown promise due its rapid recovery from inactivation role repetitive firing, with recent clinical studies providing proof-of-principal that block can reduce humans. We report here three nonpsychotomimetic cannabinoids—cannabidiol (CBD), cannabigerol (CBG), cannabinol (CBN)—effectively inhibit suggesting their potential as analgesic compounds. In particular, CBG shows significant ability effectively excitability sensory neurons. These findings highlight therapeutic cannabinoids, particularly CBG, agents may attenuate via warranting further vivo studies.

Language: Английский

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Role of cannabidiolic acid or the combination of cannabigerol/cannabidiol in pain modulation and welfare improvement in horses with chronic osteoarthritis

Frontiers in Veterinary Science, Journal Year: 2024, Volume and Issue: 11

Published: Dec. 10, 2024

Cannabidiol (CBD) is a non-psychotropic cannabinoid obtained from hemp ( Cannabis sativa L.) used for pain management in companion animals including horses. The present study aimed to evaluate the efficacy of cannabidiolic acid (CBDA) and cannabigerol/cannabidiol oil (CBG/CBD) oral administration alleviating adult horses affected by chronic osteoarthritis (OA). Twenty-four (10 geldings 14 mares), aged between 11 18 years old, were equally divided into two groups. One group received CBDA 15% other CBG/CBD (CBG20%-CBD10%) consecutive days. A standard dose 0.07 mg/kg was chosen based on mean body weight 450 ± 28 kg. Horse Chronic Pain Scale (HCPS) physiological parameters monitoring heart rate (HR), respiratory (RR), arterial blood pressure (systolic pressure- SAP, diastolic DAP) assessed before (T0) every day entire (T1-T14). Blood samples collected evaluation complete hemogram, Leukocyte subpopulation identification counting leukocyte differentiation antigens CD4 CD8 at 7 days (T7 T14). reduction HCPS scale scores number WBC, monocytes neutrophils observed with both treatment. No statistical differences found parameters. subject required rescue analgesia or showed any adverse effects. results this that may promote OA.

Language: Английский

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Comprehensive mini-review: therapeutic potential of cannabigerol – focus on the cardiovascular system

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: March 26, 2025

Backgrounds Cannabigerol (CBG) is a non-psychoactive phytocannabinoid with broad spectrum of biological effects. However, there still too little research on its safety especially effects the cardiovascular system. Due to agonist alpha-2-adrenergic receptors (α 2 AR), it speculated that may have applications in pharmacotherapy metabolic syndrome, particularly hypertension. Thus, aim our review was analyse therapeutic potential CBG diseases. Methods The based searches PubMed and Web Science databases. Keywords were used identify literature containing mechanistic information Results A shows exhibits hypotensive mice probably through α AR agonism. Other numerous vitro vivo studies show has anti-inflammatory, antioxidant also regulates cell apoptosis. improved tissue sensitivity insulin, showed efficacy inhibiting platelet aggregation. are reports adverse high doses liver architecture function, which calls into question usefulness profile. Conclusion Above mentioned beneficial properties suggest be useful treating hypertension syndrome. lack chronic administration parameters condition, necessary determine need for future other indications.

Language: Английский

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Cannabigerol (CBG): A Comprehensive Review of Its Molecular Mechanisms and Therapeutic Potential

Molecules, Journal Year: 2024, Volume and Issue: 29(22), P. 5471 - 5471

Published: Nov. 20, 2024

Cannabigerol (CBG), a non-psychoactive cannabinoid found in cannabis, has emerged as promising therapeutic agent with diverse range of potential applications. Unlike its well-known counterpart tetrahydrocannabinol (THC), CBG does not induce intoxication, making it an attractive option the clinic. Recent research shed light on CBG's intriguing molecular mechanisms, highlighting to modulate multiple physiological processes. This review delves into current understanding interactions and explores power alleviate various conditions, including cancer, metabolic, pain, inflammatory disorders, amongst others. We discuss how interacts endocannabinoid system other key signaling pathways, such CB1, CB2, TPR channels, α2-adrenoceptor, potentially influencing inflammation, neurodegeneration, ailments. Additionally, we highlight ongoing efforts aimed at elucidating full spectrum safety profile clinical settings. Through this comprehensive analysis, aim provide deeper role promoting human health pave way for future endeavors.

Language: Английский

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The Anti-Inflammatory Action of Cannabigerol Accompanied by the Antioxidant Effect of 3-O-ethyl Ascorbic Acid in UVA-Irradiated Human Keratinocytes

Journal of Pharmacology and Experimental Therapeutics, Journal Year: 2023, Volume and Issue: 387(2), P. 170 - 179

Published: Aug. 31, 2023

Excessive daily exposure of human skin to natural UVA radiation leads impaired redox homeostasis in epidermal keratinocytes, resulting changes their proteome. Commonly used antioxidants usually exhibit protection a narrowed range, which makes it necessary combine effects. Therefore, the aim this study was analyze protective effect cannabigerol (CBG) and 3-O-ethyl ascorbic acid (EAA), separately together, on proteomic profile irradiated keratinocytes. Proteomic analysis with use Q Exactive HF mass spectrometer, combined biostatistic tests, performed UVA-irradiated keratinocytes indicated enhanced lowered expression 186 160 proteins, respectively. CBG treatment after irradiation reduced these numbers 110 upregulated 49 downregulated while EAA eliminated all changes. completely UV-induced pro-inflammatory proteins significantly increased level responsible for cellular locomotion. On other hand, UVA-induced 4-hydroxynonenal protein adducts fivefold, whereas had no modification. At same time, did not modify expression/structure relation nonirradiated control case an unaccompanied or slightly modified when mixture. The effects structure allowed us obtain wider cells against radiation, compared compounds were alone. SIGNIFICANCE STATEMENT: allows conclude that eliminates keratinocyte reduces adducts. radiation.

Language: Английский

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The Minor Phytocannabinoid Delta-8-Tetrahydrocannabinol Attenuates Collagen-Induced Arthritic Inflammation and Pain-Depressed Behaviors

Journal of Pharmacology and Experimental Therapeutics, Journal Year: 2024, Volume and Issue: 391(2), P. 222 - 230

Published: June 4, 2024

Patients with arthritis report using cannabis for pain management, and the major cannabinoid Δ⁹-THC has anti-inflammatory properties, yet effects of minor cannabinoids on are largely unknown. The goal present study was to determine antiarthritic potential Δ⁸-THC collagen-induced (CIA) mouse model. Adult male DBA/1J mice were immunized boosted 21 days later an emulsion collagen complete Freund9s adjuvant. Beginning day booster, administered twice-daily injections (3 or 30 mg/kg), steroid dexamethasone (2 vehicle two weeks. Dorsal-ventral paw thickness qualitative measures recorded daily, latency fall from inverted grid measured alternating days, severity functional impairment. On final testing, spontaneous wire-climbing behavior temperature preference in a thermal gradient ring assess CIA-depressed -conditioned behavior, respectively. treatment (30 mg/kg) reduced swelling signs arthritis. also blocked climbing CIA-induced heated floor without producing locomotor but did not affect wire grid. In alignment morphological behavioral assessments in vivo, histology revealed that synovial inflammation, proteoglycan loss cartilage bone erosion foot joints dose-dependent manner. Together, these findings suggest only changes prevented caused by Significance Statement Despite increasing use products, Here, development experimentally induced preventing both pathophysiological as well disease These data support novel treatments inflammatory

Language: Английский

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Polyglactin 910 Meshes Coated with Sustained-Release Cannabigerol Varnish Inhibit Staphylococcus aureus Biofilm Formation and Macrophage Cytokine Secretion: An In Vitro Study

Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(5), P. 745 - 745

Published: May 13, 2023

Synthetic surgical meshes are commonly used in abdominal wall reconstruction surgeries to strengthen a weak wall. Common mesh-related complications include local infection and inflammatory processes. Because cannabigerol (CBG) has both antibacterial anti-inflammatory properties, we proposed that coating VICRYL (polyglactin 910) mesh with sustained-release varnish (SRV) containing CBG would prevent these complications. We an vitro model Staphylococcus aureus inflammation of lipopolysaccharide (LPS)-stimulated macrophages. Meshes coated either SRV-placebo or SRV-CBG were exposed daily S. tryptic soy medium (TSB) macrophage Dulbecco's modified eagle (DMEM). Bacterial growth biofilm formation the environment on assessed by changes optical density, bacterial ATP content, metabolic activity, crystal violet staining, spinning disk confocal microscopy (SDCM), high-resolution scanning electron (HR-SEM). The effect culture was analyzed measuring release cytokines IL-6 IL-10 from LPS-stimulated RAW 264.7 macrophages appropriate ELISA kits. Additionally, cytotoxicity assay performed Vero epithelial cell lines. observed compared SRV-placebo, segments inhibited for 9 days 86 ± 4% prevented activity surroundings days, respective 70 2% 95 0.2% reductions. incubated SRV-CBG-coated LPS-induced secretion up 6 without affecting viability. A partial also SRV-placebo. conditioned not toxic cells, which had IC50 25 µg/mL CBG. In conclusion, our data indicate potential role preventing initial period after surgery.

Language: Английский

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Recent developments in the synovial fibroblast pathobiology field in rheumatoid arthritis

Current Opinion in Rheumatology, Journal Year: 2023, Volume and Issue: 36(1), P. 69 - 75

Published: Sept. 12, 2023

Purpose of review Synovial fibroblasts are the central cells connective tissue homeostasis. In rheumatoid arthritis (RA) tissue, synovial activated because proinflammatory environment very early in disease. Epigenetic alterations RASF result a permanently stage, and involved many processes RA pathophysiology. Therefore, several recent findings last 18 months with focus on activation function summarized. Recent profoundly altered epigenome leads to an invasive phenotype increased migration, adhesion invasion into cartilage, which was further characterized studies. subtypes subtype dynamics were evaluated using high-resolution techniques better understand Many studies addressing interactions immune or stromal cell types have been published showing that interact different contributing not only their own pro-inflammatory response but also other cells. Summary Highly interesting revealing mechanisms functions published, subsets characterized, elucidated, all contribute understanding role development progression.

Language: Английский

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Editorial: Cannabinoid interactions with ion channels, receptors, and the bio-membrane

Frontiers in Physiology, Journal Year: 2023, Volume and Issue: 14

Published: May 9, 2023

EDITORIAL article Front. Physiol., 09 May 2023Sec. Membrane Physiology and Biophysics Volume 14 - 2023 | https://doi.org/10.3389/fphys.2023.1211230

Language: Английский

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Is there a place for cannabigerol in symptomatic treatment?

Medycyna Paliatywna, Journal Year: 2023, Volume and Issue: 15(2), P. 50 - 58

Published: Jan. 1, 2023

AMA Graczyk M, Pawlak Ł, Lewandowska AA. Is there a place for cannabigerol in symptomatic treatment?. Medycyna Paliatywna/Palliative Medicine. 2023. doi:10.5114/pm.2023.131449. APA Graczyk, M., Pawlak, Ł., & Lewandowska, A. (2023). https://doi.org/10.5114/pm.2023.131449 Chicago Michał, Łukasz and Agata A Lewandowska. "Is treatment?". Harvard MLA Michał et al. treatment?." Medicine, Vancouver

Language: Английский

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