Cannabinoids, the endocannabinoid system, and pain: a review of preclinical studies

Pain, Journal Year: 2021, Volume and Issue: 162(1), P. S5 - S25

Published: March 15, 2021

This narrative review represents an output from the International Association for Study of Pain's global task force on use cannabis, cannabinoids, and cannabis-based medicines pain management, informed by our companion systematic meta-analysis preclinical studies in this area. Our aims are (1) to describe value studying cannabinoids endogenous cannabinoid (endocannabinoid) system modulators preclinical/animal models pain; (2) discuss both pain-related efficacy additional pain-relevant effects (adverse beneficial) endocannabinoid as they pertain animal pathological or injury-related persistent (3) identify important directions future research. In service these goals, provides overview pharmacology modulators, with specific relevance describes pharmacokinetics rodents humans; highlights differences discrepancies between clinical Preclinical (rodent) have advanced understanding underlying sites mechanisms action suppressing nociceptive signaling behaviors. We conclude that substantial evidence supports contention hold considerable promise analgesic drug development, although challenge translating knowledge into clinically useful is not be underestimated.

Language: Английский

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Progress in approved drugs from natural product resources

Chinese Journal of Natural Medicines, Journal Year: 2024, Volume and Issue: 22(3), P. 195 - 211

Published: March 1, 2024

Language: Английский

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Treatment of Posttraumatic Stress Disorder: A State-of-the-art Review

Current Neuropharmacology, Journal Year: 2023, Volume and Issue: 22(4), P. 557 - 635

Published: May 3, 2023

Abstract: This narrative state-of-the-art review paper describes the progress in understanding and treatment of Posttraumatic Stress Disorder (PTSD). Over last four decades, scientific landscape has matured, with many interdisciplinary contributions to its diagnosis, etiology, epidemiology. Advances genetics, neurobiology, stress pathophysiology, brain imaging have made it apparent that chronic PTSD is a systemic disorder high allostatic load. The current state includes wide variety pharmacological psychotherapeutic approaches, which are evidence-based. However, myriad challenges inherent disorder, such as individual barriers good outcome, comorbidity, emotional dysregulation, suicidality, dissociation, substance use, trauma-related guilt shame, often render response suboptimal. These discussed drivers for emerging novel including early interventions Golden Hours, interventions, medication augmentation use psychedelics, well targeting nervous system. All this aims improve symptom relief clinical outcomes. Finally, phase orientation recognized tool strategize position step progression pathophysiology. Revisions guidelines systems care will be needed incorporate innovative treatments evidence emerges they become mainstream. generation well-positioned address devastating disabling impact traumatic events through holistic, cutting-edge efforts research.

Language: Английский

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The mechanism of microglia-mediated immune inflammation in ischemic stroke and the role of natural botanical components in regulating microglia: A review

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 13

Published: Feb. 2, 2023

Ischemic stroke (IS) is one of the most fatal diseases. Neuroimmunity, inflammation, and oxidative stress play important roles in various complex mechanisms IS. In particular, early proinflammatory response resulting from overactivation resident microglia infiltration circulating monocytes macrophages brain after cerebral ischemia leads to secondary injury. Microglia are innate immune cells that constantly monitor microenvironment under normal conditions. Once occurs, activated produce dual effects neurotoxicity neuroprotection, balance two determines fate damaged neurons. The activation defined as classical (M1 type) or alternative (M2 type). M1 type secrete pro-inflammatory cytokines neurotoxic mediators exacerbate neuronal damage, while M2 promote a repairing anti-inflammatory response. Fine regulation M1/M2 microglial minimize damage maximize protection has therapeutic value. This review focuses on interaction between other involved IS phenotypic characteristics, mechanism natural plant components regulating IS, providing novel candidate drugs for drug development.

Language: Английский

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Cannabidiol inhibits Nav channels through two distinct binding sites

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: June 17, 2023

Abstract Cannabidiol (CBD), a major non-psychoactive phytocannabinoid in cannabis, is an effective treatment for some forms of epilepsy and pain. At high concentrations, CBD interacts with huge variety proteins, but which targets are most relevant clinical actions still unclear. Here we show that Na v 1.7 channels at sub-micromolar concentrations state-dependent manner. Electrophysiological experiments binds to the inactivated state dissociation constant about 50 nM. The cryo-EM structure bound reveals two distinct binding sites. One IV-I fenestration near upper pore. other site directly next “wedged” position Ile/Phe/Met (IFM) motif on short linker between repeats III IV, mediates fast inactivation. Consistent producing direct stabilization state, mutating residues this greatly reduced CBD. identification may enable design compounds improved properties compared itself.

Language: Английский

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An Overview of Cannabidiol as a Multifunctional Drug: Pharmacokinetics and Cellular Effects

Molecules, Journal Year: 2024, Volume and Issue: 29(2), P. 473 - 473

Published: Jan. 18, 2024

Cannabidiol (CBD), a non-psychoactive compound derived from Cannabis Sativa, has garnered increasing attention for its diverse therapeutic potential. This comprehensive review delves into the complex pharmacokinetics of CBD, including factors such as bioavailability, distribution, safety profile, and dosage recommendations, which contribute to compound’s pharmacological profile. CBD’s role inhibitor is explored, encompassing interactions with endocannabinoid system ion channels. The anti-inflammatory effects, influencing Interferon-beta NF-κB, position it versatile candidate immune regulation interventions in inflammatory processes. historical context Sativa’s use recreational medicinal purposes adds depth discussion, emphasizing emergence pivotal phytocannabinoid. As research continues, integration clinical practice holds promise revolutionizing treatment approaches enhancing patient outcomes. evolution CBD encourages ongoing exploration, offering prospect unlocking new utility.

Language: Английский

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Mitochondrial dysfunction in chronic neuroinflammatory diseases (Review)

International Journal of Molecular Medicine, Journal Year: 2024, Volume and Issue: 53(5)

Published: April 2, 2024

Chronic neuroinflammation serves a key role in the onset and progression of neurodegenerative disorders. Mitochondria serve as central regulators neuroinflammation. In addition to providing energy cells, mitochondria also participate immunoinflammatory response disorders including Alzheimer's disease, Parkinson's multiple sclerosis epilepsy, by regulating processes such cell death inflammasome activation. Under inflammatory conditions, mitochondrial oxidative stress, epigenetics, dynamics calcium homeostasis imbalance may underlying regulatory mechanisms for these diseases. Therefore, investigating related dysfunction result therapeutic strategies against chronic neurodegeneration. The present review summarizes neuroinflammatory diseases current treatment approaches that target

Language: Английский

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Enhancing Tetrahydrocannabinol’s Therapeutic Efficacy in Inflammatory Bowel Disease: The Roles of Cannabidiol and the Cannabinoid 1 Receptor Allosteric Modulator ZCZ011

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(2), P. 148 - 148

Published: Jan. 23, 2025

Background/Objectives: Current inflammatory bowel disease (IBD) treatments focus on symptomatic relief, highlighting the need for innovative approaches. Dysregulation of cannabinoid 1 (CB1) receptor, part endocannabinoid system, is linked to colitis. While tetrahydrocannabinol (THC) alleviates colitis via CB1 activation, its psychotropic effects limit clinical use. ZCZ011, a CB1R allosteric modulator, and cannabidiol (CBD), non-psychoactive cannabinoid, offer alternatives. This study investigated combining sub-therapeutic THC doses with ZCZ011 or CBD in murine model dextran sodium sulphate (DSS)-induced Methods: Acute was induced 4% DSS 7 days, followed by 3 days water. Chronic modelled over 24 alternating concentrations. The combination 2.5 mg/kg 20 10 evaluated. Key markers were assessed determine efficacy safety, including activity index (DAI), inflammation, cytokine levels, GLP-1, organ health. Results: DSS-induced resulted increased DAI scores, cytokines, inflammation dysregulation GLP-1 ammonia. at significantly improved but ineffective 5 mg/kg. alone showed transient effects. However, either alleviated markers, restored colon integrity reestablished homeostasis. also maintained favourable haematological biochemical profiles, notable reduction colitis-induced elevated ammonia levels. Conclusions: demonstrates synergistic potential low-dose combined as novel, effective safer therapeutic strategy ulcerative

Language: Английский

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Promising Nanocarriers to Enhance Solubility and Bioavailability of Cannabidiol for a Plethora of Therapeutic Opportunities

Molecules, Journal Year: 2022, Volume and Issue: 27(18), P. 6070 - 6070

Published: Sept. 17, 2022

In recent years, the interest in cannabidiol (CBD) has increased because of lack psychoactive properties. However, CBD low solubility and bioavailability, variable pharmacokinetics profiles, poor stability, a pronounced presystemic metabolism. nanoformulations include nanosuspensions, polymeric micelles nanoparticles, hybrid nanoparticles jelled cross-linked chitosan, numerous nanosized lipid formulations, including nanostructured carriers, vesicles, SNEEDS, nanoemulsions, microemulsions. Nanoformulations have resulted high solubility, encapsulation efficiency, sustained release. Some studies assessed Cmax AUC decreased Tmax. A rational evaluation reported this review evidences how some them are very preliminary should be completed before performing clinical trials. Almost all developed simple architectures, well-known safe nanocarriers, or even nanosuspensions. addition, conventional routes administration generally investigated. As consequence, many these almost ready for forthcoming translations. nanosystems promising plethora therapeutic opportunities versatility terms release, crossing physiological barriers, number possible administration.

Language: Английский

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Endocannabinoid System: Chemical Characteristics and Biological Activity

Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(2), P. 148 - 148

Published: Jan. 19, 2023

The endocannabinoid system (eCB) has been studied to identify the molecular structures present in Cannabis sativa. eCB consists of cannabinoid receptors, endogenous ligands, and associated enzymatic apparatus responsible for maintaining energy homeostasis cognitive processes. Several physiological effects cannabinoids are exerted through interactions with various such as CB1 CB2 vanilloid recently discovered G-protein-coupled receptors (GPR55, GPR3, GPR6, GPR12, GPR19). Anandamide (AEA) 2-arachidoylglycerol (2-AG), two small lipids derived from arachidonic acid, showed high-affinity binding both receptors. plays a critical role chronic pain mood disorders extensively because its wide therapeutic potential it is promising target development new drugs. Phytocannabinoids synthetic have shown varied affinities relevant treatment several neurological diseases. This review provides description components discusses how phytocannabinoids other exogenous compounds may regulate balance. Furthermore, we show hypo- or hyperfunctionality body related disorders, even integrative complementary health practices (ICHP) harmonizing eCB.

Language: Английский

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