scholarly journals Cannabinoids in health and disease: pharmacological potential in metabolic syndrome and neuroinflammation

2018 ◽  
Vol 36 (2) ◽  
Author(s):  
Andrea Mastinu ◽  
Marika Premoli ◽  
Giulia Ferrari-Toninelli ◽  
Simone Tambaro ◽  
Giuseppina Maccarinelli ◽  
...  
Keyword(s):  
Cannabis Sativa ◽  
Cannabinoid Receptor ◽  
Receptor Type ◽  
History Of ◽  
Health And Disease ◽  
Pharmacological Potential ◽  
The Brain ◽  
Synthesis And Degradation

Abstract The use of different natural and/or synthetic preparations of Cannabis sativa is associated with therapeutic strategies for many diseases. Indeed, thanks to the widespread diffusion of the cannabinoidergic system in the brain and in the peripheral districts, its stimulation, or inhibition, regulates many pathophysiological phenomena. In particular, central activation of the cannabinoidergic system modulates the limbic and mesolimbic response which leads to food craving. Moreover, cannabinoid agonists are able to reduce inflammatory response. In this review a brief history of cannabinoids and the protagonists of the endocannabinoidergic system, i.e. synthesis and degradation enzymes and main receptors, will be described. Furthermore, the pharmacological effects of cannabinoids will be outlined. An overview of the involvement of the endocannabinoidergic system in neuroinflammatory and metabolic pathologies will be made. Finally, particular attention will also be given to the new pharmacological entities acting on the two main receptors, cannabinoid receptor type 1 (CB1) and cannabinoid receptor type 2 (CB2), with particular focus on the neuroinflammatory and metabolic mechanisms involved.

scholarly journals Potential Mechanisms Underlying the Deleterious Effects of Synthetic Cannabinoids Found in Spice/K2 Products

2019 ◽  
Vol 9 (1) ◽  
pp. 14 ◽  
Author(s):  
Balapal Basavarajappa ◽  
Shivakumar Subbanna
Keyword(s):  
Plant Material ◽  
Cannabinoid Receptors ◽  
Cannabis Sativa ◽  
Cannabinoid Receptor ◽  
Synthetic Cannabinoids ◽  
Receptor Type ◽  
Surface Receptors ◽  
Cellular Origin ◽  
The Brain

The chief psychoactive constituent of many bioactive phytocannabinoids (Δ9-tetrahydrocannabinol, Δ9-THC) found in hemp, cannabis or marijuana plants are scientifically denoted by the Latin term, Cannabis sativa, acts on cell surface receptors. These receptors are ubiquitously expressed. To date, two cannabinoid receptors have been cloned and characterized. Cannabinoid receptor type 1 (CB1R) is found to serve as the archetype for cannabinoid action in the brain. They have attracted wide interest as the mediator of all psychoactive properties of exogenous and endogenous cannabinoids and they are abundantly expressed on most inhibitory and excitatory neurons. Recent evidence established that cannabinoid receptor type 2 (CB2R) is also expressed in the neurons at both presynaptic and postsynaptic terminals and are involved in neuropsychiatric effects. Distinct types of cells in many regions in the brain express CB2Rs and the cellular origin of CB2Rs that induce specific behavioral effects are emerging. To mimic the bliss effects of marijuana, synthetic cannabinoids (SCBs) have been sprayed onto plant material, and this plant material has been consequently packaged and sold under brand name “Spice” or “K2”. These SCBs have been shown to maintain their affinity and functional activity for CB1R and CB2R and have been shown to cause severe harmful effects when compared to the effects of Δ9-THC. The present review discusses the potential brain mechanisms that are involved in the deleterious effects of SCBs.

scholarly journals Cannabinoid Receptors: An Update on Cell Signaling, Pathophysiological Roles and Therapeutic Opportunities in Neurological, Cardiovascular, and Inflammatory Diseases

2020 ◽  
Vol 21 (20) ◽  
pp. 7693
Author(s):  
Dhanush Haspula ◽  
Michelle A. Clark
Keyword(s):  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Inflammatory Diseases ◽  
Endocannabinoid System ◽  
Future Directions ◽  
The Past ◽  
Health And Disease ◽  
Made In

The identification of the human cannabinoid receptors and their roles in health and disease, has been one of the most significant biochemical and pharmacological advancements to have occurred in the past few decades. In spite of the major strides made in furthering endocannabinoid research, therapeutic exploitation of the endocannabinoid system has often been a challenging task. An impaired endocannabinoid tone often manifests as changes in expression and/or functions of type 1 and/or type 2 cannabinoid receptors. It becomes important to understand how alterations in cannabinoid receptor cellular signaling can lead to disruptions in major physiological and biological functions, as they are often associated with the pathogenesis of several neurological, cardiovascular, metabolic, and inflammatory diseases. This review focusses mostly on the pathophysiological roles of type 1 and type 2 cannabinoid receptors, and it attempts to integrate both cellular and physiological functions of the cannabinoid receptors. Apart from an updated review of pre-clinical and clinical studies, the adequacy/inadequacy of cannabinoid-based therapeutics in various pathological conditions is also highlighted. Finally, alternative strategies to modulate endocannabinoid tone, and future directions are also emphasized.

scholarly journals Premature delivery and cannabinoid receptor expression in the placenta after delivery: an observational study.

2020 ◽  
Author(s):  
Stepan Feduniw ◽  
Izabela Woś ◽  
Katarzyna Pogoda ◽  
Piotr Laudanski ◽  
Jacek Tabarkiewicz ◽  
...  
Keyword(s):  
Preterm Delivery ◽  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Receptor Expression ◽  
Receptor Type ◽  
Premature Delivery ◽  
Study Group ◽  
Cannabinoid Receptor Type 2 ◽  
History Of

Objective: To investigate the relationship between cannabinoid receptor expression within the placenta after delivery and the problem of preterm delivery. Design, setting, and participants: The retrospective, observational study was conducted on a multicenter material of 150 women. The study group included 115 women after premature delivery. The control group consisted of 35 women after term delivery. Methods. To determine the expression of cannabinoid receptors after the end of the third stage of labour, several sections were taken from the placenta. RNA isolation, reverse transcription, and Real-Time PCR were performed to assess the expression of the cannabinoid receptors in the placenta. Results: Cannabinoid receptor type 2 expression was lower in the placentas of women after preterm delivery. Urinary tract infections and bleeding at any stage of pregnancy occurred statistically more frequently in the study group and correlated with cannabinoid receptor type 2 expression. In the study group, the history of preterm labor, history of intrauterine fetal deaths, pregnancies terminated by a Caesarean section, and uterine tenderness correlated with lower expression of cannabinoid receptor type 2 and 1a. Conclusions: Cannabinoid receptors mRNA were present in human placental tissue during pregnancy. Decreased cannabinoid receptor type 2 expression in preterm delivered placentas should be further investigated, as perinatal endocannabinoid receptor expression could serve as a predicting tool of preterm birth. For example, liquid-based cytology could be used as a noninvasive perinatal method of measuring the expression level of cannabinoid receptors in decidual cells during pregnancy. KEYWORDS: Cannabinoid receptor; CB2; endocannabinoid system; preterm delivery; PTB

scholarly journals Daytime-Dependent Changes of Cannabinoid Receptor Type 1 and Type 2 Expression in Rat Liver

2017 ◽  
Vol 18 (9) ◽  
pp. 1844 ◽  
Author(s):  
Ivonne Bazwinsky-Wutschke ◽  
Alexander Zipprich ◽  
Faramarz Dehghani
Keyword(s):  
Rat Liver ◽  
Cannabinoid Receptor ◽  
Receptor Type ◽  
Cannabinoid Receptor Type 1

Diabetes and the Brain—An Overview of Existing Knowledge and Discussions and Future Implications

2010 ◽  
Vol 06 (01) ◽  
pp. 28 ◽  
Author(s):  
Amir A Moheet ◽  
Elizabeth R Seaquist ◽  
◽  
Keyword(s):  
Type 2 Diabetes ◽  
Imaging Techniques ◽  
Future Research ◽  
Organ Systems ◽  
History Of ◽  
Underlying Mechanisms ◽  
Multiple Domains ◽  
The Brain

Diabetes affects many organ systems including the brain. Both type 1 and type 2 diabetes have been associated with reduced performance on multiple domains of cognitive function, including memory, psychomotor efficiency and executive function. In addition, structural abnormalities in the brain have been noted in subjects with both type 1 and type 2 diabetes using a variety of imaging techniques. The underlying pathophysiological mechanisms causing these changes in cognition and structure are not well understood but hyperglycemia, insulin resistance and vascular disease are likely to have key roles. Future research is needed to better understand of the natural history of the cerebral complications of diabetes and to identify the underlying mechanisms that lead to changes in brain function and structure.

Cannabinoid receptor type 2 ligands: an analysis of granted patents since 2010

2021 ◽  
Author(s):  
Benjamin Brennecke ◽  
Thais Gazzi ◽  
Kenneth Atz ◽  
Jürgen Fingerle ◽  
Pascal Kuner ◽  
...  
Keyword(s):  
Neurodegenerative Disorders ◽  
Cannabinoid Receptor ◽  
Therapeutic Potential ◽  
Receptor Type ◽  
Protective Effects ◽  
Cannabinoid Receptor Type 2 ◽  
Preclinical Animal Models ◽  
G Protein Coupled

The G-protein-coupled cannabinoid receptor type 2 (CB2R) is a key element of the endocannabinoid (EC) system. EC/CB2R signaling has significant therapeutic potential in major pathologies affecting humans such as allergies, neurodegenerative disorders, inflammation or ocular diseases. CB2R agonism exerts anti-inflammatory and tissue protective effects in preclinical animal models of cardiovascular, gastrointestinal, liver, kidney, lung and neurodegenerative disorders. Existing ligands can be subdivided into endocannabinoids, cannabinoid-like and synthetic CB2R ligands that possess various degrees of potency on and selectivity against the cannabinoid receptor type 1. This review is an account of granted CB2R ligand patents from 2010 up to the present, which were surveyed using Derwent Innovation®.

scholarly journals URB597 abrogates anxiogenic and depressive behaviors in the methamphetamine-withdrawal mice: Role of the cannabinoid receptor type 1, cannabinoid receptor type 2, and transient receptor potential vanilloid 1 channels

2020 ◽  
pp. 026988112096593
Author(s):  
Mohaddeseh Ebrahimi-Ghiri ◽  
Fatemeh Khakpai ◽  
Mohammad-Reza Zarrindast
Keyword(s):  
Transient Receptor Potential ◽  
Cannabinoid Receptor ◽  
Endocannabinoid System ◽  
Receptor Potential ◽  
Receptor Type ◽  
Anxiety And Depression ◽  
Transient Receptor Potential Vanilloid ◽  
Transient Receptor

Background: Methamphetamine is an addictive stimulant that possesses toxicity in the brain when taken repeatedly or at higher doses. Methamphetamine neurotoxicity is associated with numerous forms of mental impairment, including depression and anxiety. Evidence has also demonstrated that the endocannabinoid system is involved in the regulation of anxiety and depression. Aims: This study was designed to determine the involvement of the endocannabinoid system in anxiety- and depression-related behaviors in methamphetamine-withdrawal male NMRI mice. Methods: The elevated plus maze and forced swim test were used to assess the level of anxiety and depression. Results: We found that methamphetamine (30 mg/kg, intraperitoneal) evoked depressive- and anxiogenic-like effects at 3 days post-administration. Injection of URB597 (5–10 ng/mouse, intracerebroventricular), 10 min before the test, prevented the emotional deficits induced by methamphetamine withdrawal. Moreover, the cannabinoid receptor type 1 antagonist AM251 (1 μg/mouse) or cannabinoid receptor type 2 antagonist AM630 (5 and 10 μg/mouse) suppressed the antidepressant activity in the methamphetamine-withdrawal mice treated with URB597. The transient receptor potential vanilloid 1 antagonist capsazepine (25 μg/mouse) prevented while capsazepine (100 μg/mouse) potentiated the antidepressant efficacy in the methamphetamine-withdrawal mice treated with URB597. The higher dose of AM630 and two higher doses of capsazepine had antidepressant efficacy, by themselves. Furthermore, capsazepine (50 μg/mouse) increased locomotion in the methamphetamine-withdrawal mice treated with URB597. Conclusions: The results suggest that URB597 has a potential for preventing methamphetamine withdrawal-evoked anxiety and depression. Cannabinoid type 1 receptors, cannabinoid type 2 receptors and transient receptor potential vanilloid 1 differently affect depression-related behaviors in methamphetamine-withdrawal mice treated with URB597.

scholarly journals In vitro and in vivo pharmacological activity of minor cannabinoids isolated from Cannabis sativa

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ayat Zagzoog ◽  
Kawthar A. Mohamed ◽  
Hye Ji J. Kim ◽  
Eunhyun D. Kim ◽  
Connor S. Frank ◽  
...  
Keyword(s):  
Cannabinoid Receptors ◽  
Cannabis Sativa ◽  
Cannabinoid Receptor ◽  
Partial Agonist ◽  
Chinese Hamster ◽  
Cannabidiolic Acid

AbstractThe Cannabis sativa plant contains more than 120 cannabinoids. With the exceptions of ∆9-tetrahydrocannabinol (∆9-THC) and cannabidiol (CBD), comparatively little is known about the pharmacology of the less-abundant plant-derived (phyto) cannabinoids. The best-studied transducers of cannabinoid-dependent effects are type 1 and type 2 cannabinoid receptors (CB1R, CB2R). Partial agonism of CB1R by ∆9-THC is known to bring about the ‘high’ associated with Cannabis use, as well as the pain-, appetite-, and anxiety-modulating effects that are potentially therapeutic. CB2R activation by certain cannabinoids has been associated with anti-inflammatory activities. We assessed the activity of 8 phytocannabinoids at human CB1R, and CB2R in Chinese hamster ovary (CHO) cells stably expressing these receptors and in C57BL/6 mice in an attempt to better understand their pharmacodynamics. Specifically, ∆9-THC, ∆9-tetrahydrocannabinolic acid (∆9-THCa), ∆9-tetrahydrocannabivarin (THCV), CBD, cannabidiolic acid (CBDa), cannabidivarin (CBDV), cannabigerol (CBG), and cannabichromene (CBC) were evaluated. Compounds were assessed for their affinity to receptors, ability to inhibit cAMP accumulation, βarrestin2 recruitment, receptor selectivity, and ligand bias in cell culture; and cataleptic, hypothermic, anti-nociceptive, hypolocomotive, and anxiolytic effects in mice. Our data reveal partial agonist activity for many phytocannabinoids tested at CB1R and/or CB2R, as well as in vivo responses often associated with activation of CB1R. These data build on the growing body of literature showing cannabinoid receptor-dependent pharmacology for these less-abundant phytocannabinoids and are critical in understanding the complex and interactive pharmacology of Cannabis-derived molecules.

scholarly journals Endocannabinoidome and its role in neurological disorders-A comprehensive update of existing literature

2021 ◽  
Vol 5 (1) ◽  
pp. 034-047
Author(s):  
Rajib Dutta
Keyword(s):  
Neurological Disorders ◽  
Cannabinoid Receptor ◽  
Endocannabinoid System ◽  
Receptor Type ◽  
Cannabinoid Receptor Type 2 ◽  
Medical Benefits ◽  
Related Compounds

Medical benefits of cannabis and related compounds is widely known. Discovery of psychotropic plant cannabinoid Δ9-tetrahydrocannabinol have urged researchers to study more about the cannabinoid system and related therapeutics in the field of neurology and medicine. Where activation of cannabinoid receptor type 1 (CB1R) yielded in unwanted and serious side effects, discovery of cannabinoid receptor type 2 (CB2R) and its ligands gave a new hope. Till now there is limited success in this field because of complex expanded endocannabinoid system comprising of receptors, ligands and enzymes. In this review we will update about the role of endocannabinoidome relevant to neurological disorders.

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