Endocannabinoid signaling at the periphery: 50 years after THC

Trends in Pharmacological Sciences, Год журнала: 2015, Номер 36(5), С. 277 - 296

Опубликована: Март 28, 2015

Язык: Английский

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From Phytocannabinoids to Cannabinoid Receptors and Endocannabinoids: Pleiotropic Physiological and Pathological Roles Through Complex Pharmacology

Physiological Reviews, Год журнала: 2016, Номер 96(4), С. 1593 - 1659

Опубликована: Сен. 15, 2016

Apart from having been used and misused for at least four millennia for, among others, recreational medicinal purposes, the cannabis plant its most peculiar chemical components, cannabinoids (phytocannabinoids), have merit to led humanity discover one of intriguing pleiotropic endogenous signaling systems, endocannabinoid system (ECS). This review article aims describe critically discuss, in comprehensive possible manner, multifaceted aspects 1) pharmacology potential impact on mammalian physiology all major phytocannabinoids, not only famous Δ 9 -tetrahydrocannabinol, 2) adaptive pro-homeostatic physiological, or maladaptive pathological, roles ECS cells, tissues, organs. In doing so, we respected chronological order milestones millennial route medicinal/recreational beyond, as it is now clear that some early steps this long path, which were originally neglected, are becoming important again. The emerging picture rather complex, but still supports belief more discoveries human physiology, new therapies, might come future knowledge field.

Язык: Английский

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Cardiovascular effects of marijuana and synthetic cannabinoids: the good, the bad, and the ugly

Nature Reviews Cardiology, Год журнала: 2017, Номер 15(3), С. 151 - 166

Опубликована: Сен. 14, 2017

Язык: Английский

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Bioactive lipids, inflammation and chronic diseases

Advanced Drug Delivery Reviews, Год журнала: 2020, Номер 159, С. 133 - 169

Опубликована: Янв. 1, 2020

Язык: Английский

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Mechanisms of podocyte injury and implications for diabetic nephropathy

Clinical Science, Год журнала: 2022, Номер 136(7), С. 493 - 520

Опубликована: Апрель 1, 2022

Abstract Albuminuria is the hallmark of both primary and secondary proteinuric glomerulopathies, including focal segmental glomerulosclerosis (FSGS), obesity-related nephropathy, diabetic nephropathy (DN). Moreover, albuminuria an important feature all chronic kidney diseases (CKDs). Podocytes play a key role in maintaining permselectivity glomerular filtration barrier (GFB) injury podocyte, leading to foot process (FP) effacement podocyte loss, unifying underlying mechanism glomerulopathies. The metabolic insult hyperglycemia paramount importance pathogenesis DN, while insults damage are poorly defined other However, shared mechanisms have been identified. Herein, we will review haemodynamic oxidative stress, inflammation, lipotoxicity, endocannabinoid (EC) hypertone, mitochondrial autophagic dysfunction damage, focussing particularly on their DN. Gaining better insight into may provide novel targets for treatment. strategies boosting repair open way regenerative medicine.

Язык: Английский

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Goods and Bads of the Endocannabinoid System as a Therapeutic Target: Lessons Learned after 30 Years

Pharmacological Reviews, Год журнала: 2023, Номер 75(5), С. 885 - 958

Опубликована: Май 10, 2023

The cannabis derivative marijuana is the most widely used recreational drug in Western world and consumed by an estimated 83 million individuals (∼3% of population). In recent years, there has been a marked transformation society regarding risk perception cannabis, driven its legalization medical use many states United States worldwide. Compelling research evidence Food Drug Administration cannabis-derived cannabidiol approval for severe childhood epilepsy have confirmed large therapeutic potential itself, Δ

Язык: Английский

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Role of the endocannabinoid system in diabetes and diabetic complications

British Journal of Pharmacology, Год журнала: 2015, Номер 173(7), С. 1116 - 1127

Опубликована: Июнь 16, 2015

Increasing evidence suggests that an overactive endocannabinoid system (ECS) may contribute to the development of diabetes by promoting energy intake and storage, impairing both glucose lipid metabolism, exerting pro-apoptotic effects in pancreatic beta cells facilitating inflammation islets. Furthermore, hyperglycaemia associated with has also been implicated triggering perturbations ECS amplifying pathological processes mentioned above, eventually culminating a vicious circle. Compelling from preclinical studies indicates influences diabetes-induced oxidative stress, inflammation, fibrosis subsequent tissue injury target organs for diabetic complications. In this review, we provide update on contribution pathogenesis microvascular (retinopathy, nephropathy neuropathy) cardiovascular The therapeutic potential targeting is discussed.This article part themed section Endocannabinoids. To view other articles visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.7/issuetoc.

Язык: Английский

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The therapeutic potential of second and third generation CB1R antagonists

Pharmacology & Therapeutics, Год журнала: 2020, Номер 208, С. 107477 - 107477

Опубликована: Янв. 9, 2020

Endocannabinoids acting via CB1 receptors (CB1R) play a critical role in regulating energy homeostasis, which was the rationale for pharmaceutical development of CB1R antagonists treatment obesity. Although first-in-class antagonist rimonabant proved to be effective mitigating obesity and its multiple cardiometabolic complications, it withdrawn from clinical use due CNS-mediated neuropsychiatric side effects, halted further therapeutic whole class these compounds. Compared brain, CB1Rs are expressed at low yet functional levels peripheral organs involved including liver, skeletal muscle, adipose tissue endocrine pancreas. In recent preclinical studies, selective targeting by 'second generation' peripherally restricted replicated metabolic benefits rodent models diabetes without causing effects. Increased activity also contributes complex, multifactorial disorders such as various forms fibrosis, may benefit simultaneous engagement more than one target. Accordingly, novel 'third hybrid inhibitors inducible NO synthase were tested mouse liver pulmonary fibrosis where their antifibrotic efficacy found exceed drugs that inhibit only targets. this review, we will discuss challenges opportunities offered second third generation potential uses.

Язык: Английский

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Neuroprotection in Oxidative Stress-Related Neurodegenerative Diseases: Role of Endocannabinoid System Modulation

Antioxidants and Redox Signaling, Год журнала: 2017, Номер 29(1), С. 75 - 108

Опубликована: Май 12, 2017

Significance: Redox imbalance may lead to overproduction of reactive oxygen and nitrogen species (ROS/RNS) subsequent oxidative tissue damage, which is a critical event in the course neurodegenerative diseases. It still not fully elucidated, however, whether stress primary trigger or consequence process neurodegeneration. Recent Advances: Increasing evidence suggests that involved propagation neuronal injury consequent inflammatory response, concert promote development pathological alterations characteristic most common Critical Issues: Accumulating recent also there an important interplay between lipid endocannabinoid system [ECS; comprising main cannabinoid 1 2 receptors (CB1 CB2), endocannabinoids, their synthetic metabolizing enzymes] various key redox-dependent processes. Future Directions: Targeting ECS modulate redox state-dependent cell death decrease preceding response holds therapeutic potential multitude stress-related acute chronic disorders from stroke traumatic brain Alzheimer's Parkinson's diseases multiple sclerosis, just name few, will be discussed this overview. Antioxid. Signal. 29, 75–108.

Язык: Английский

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G Protein–Coupled Receptors Targeting Insulin Resistance, Obesity, and Type 2 Diabetes Mellitus

Pharmacological Reviews, Год журнала: 2017, Номер 70(1), С. 39 - 67

Опубликована: Дек. 12, 2017

G protein–coupled receptors (GPCRs) continue to be important discovery targets for the treatment of type 2 diabetes mellitus (T2DM). Many GPCRs are directly involved in development insulin resistance and β-cell dysfunction, etiology inflammation that can lead obesity-induced T2DM. This review summarizes current literature describing a number well-validated GPCR targets, but also outlines several new promising drug discovery. We highlight importance understanding role these disease pathology, their basic pharmacology, which will pave way novel pharmacological probes enable fulfill promise metabolic disorders.

Язык: Английский

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