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 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.

Cannabinoids Inhibit the CXCL12-Induced Migration of T Lymphocytes.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2667-2667
Author(s):  
Sharmistha Ghosh ◽  
Ramesh K. Ganju ◽  
Jerome E. Groopman
Keyword(s):  
Immune System ◽  
T Lymphocytes ◽  
T Lymphocyte ◽  
Cannabinoid Receptors ◽  
Cannabis Sativa ◽  
Cannabinoid Receptor ◽  
Synthetic Cannabinoids ◽  
Dependent Manner ◽  
T Lymphocyte Proliferation ◽  
Endogenous Cannabinoids

Abstract Cannabinoids are both exogenous compounds produced by Cannabis sativa, known for their psychoactive properties, and a family of related endogenous ligands whose functions have been recently characterized. The reported effects of cannabinoids on the immune system include inhibition of T lymphocyte proliferation, altered production of cytokines by T helper cells and decreased antibody formation by B cells. Cannabinoid receptors have been detected in several immune cells, including monocytes, macrophages, basophils and B and T lymphocytes. CB2 (Cannabinoid Receptor 2) appears to be the predominant cannabinoid receptor in the immune system, while the CB1 receptor is found primarily in the brain. We observed high levels of CB2 expression in the Jurkat T lymphocyte cell line, while others have reported expression of the CB2 receptor in CD8+ T lymphocytes. Here, we studied the ability of synthetic and endogenous cannabinoids to modulate a key function of T lymphocytes: chemotactic migration in response to the chemokine CXCL12 (also known as stromal cell-derived factor-1). We observed a 40–50% inhibition of CXCL12-induced chemotaxis in Jurkat T cells with the endogenous cannabinoid anandamide (at 15 μM concentration) and with the synthetic cannabinoids CP55,940 and Win-55,212–2 (each at 10 μM concentration). Inhibition occurred in a dose-dependent manner, indicating that it is a regulated, receptor-mediated process. Further studies showed that the inhibition of migration involved, in part, significant down-regulation of the CXCL12 receptor, CXCR4. We are currently elucidating the signaling cascade whereby endogenous cannabinoids may limit T cell migration in response to CXCL12. Thus, cannabinoids may be novel mediators of immunosuppression when clinically desired.

scholarly journals Terpenoids, Cannabimimetic Ligands, beyond the Cannabis Plant

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1567 ◽  
Author(s):  
Elaine C. D. Gonçalves ◽  
Gabriela M. Baldasso ◽  
Maíra A. Bicca ◽  
Rodrigo S. Paes ◽  
Raffaele Capasso ◽  
...  
Keyword(s):  
Phenolic Compounds ◽  
Cannabinoid Receptors ◽  
Enzyme Inhibitors ◽  
Cannabis Sativa ◽  
Cannabinoid Receptor ◽  
Endocannabinoid System ◽  
Receptor Type ◽  
Immune Mediated ◽  
Medicinal Use ◽  
G Protein Coupled

Medicinal use of Cannabis sativa L. has an extensive history and it was essential in the discovery of phytocannabinoids, including the Cannabis major psychoactive compound—Δ9-tetrahydrocannabinol (Δ9-THC)—as well as the G-protein-coupled cannabinoid receptors (CBR), named cannabinoid receptor type-1 (CB1R) and cannabinoid receptor type-2 (CB2R), both part of the now known endocannabinoid system (ECS). Cannabinoids is a vast term that defines several compounds that have been characterized in three categories: (i) endogenous, (ii) synthetic, and (iii) phytocannabinoids, and are able to modulate the CBR and ECS. Particularly, phytocannabinoids are natural terpenoids or phenolic compounds derived from Cannabis sativa. However, these terpenoids and phenolic compounds can also be derived from other plants (non-cannabinoids) and still induce cannabinoid-like properties. Cannabimimetic ligands, beyond the Cannabis plant, can act as CBR agonists or antagonists, or ECS enzyme inhibitors, besides being able of playing a role in immune-mediated inflammatory and infectious diseases, neuroinflammatory, neurological, and neurodegenerative diseases, as well as in cancer, and autoimmunity by itself. In this review, we summarize and critically highlight past, present, and future progress on the understanding of the role of cannabinoid-like molecules, mainly terpenes, as prospective therapeutics for different pathological conditions.

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.

Cannabinoid Receptor Type 1 in the Brain Regulates the Affective Component of Visceral Pain in Mice

Neuroscience ◽  
2018 ◽  
Vol 384 ◽  
pp. 397-405 ◽  
Author(s):  
Danica Bajic ◽  
Krisztina Monory ◽  
Andrea Conrad ◽  
Christina Maul ◽  
Roland M. Schmid ◽  
...  
Keyword(s):  
Cannabinoid Receptor ◽  
Visceral Pain ◽  
Receptor Type ◽  
Affective Component ◽  
Cannabinoid Receptor Type 1 ◽  
The Brain

scholarly journals Development of [18F]LU14 for PET Imaging of Cannabinoid Receptor Type 2 in the Brain

2021 ◽  
Vol 22 (15) ◽  
pp. 8051
Author(s):  
Rodrigo Teodoro ◽  
Daniel Gündel ◽  
Winnie Deuther-Conrad ◽  
Lea Ueberham ◽  
Magali Toussaint ◽  
...  
Keyword(s):  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Biological Evaluation ◽  
Emission Tomography ◽  
Tailored Therapy ◽  
Positron Emission ◽  
Cannabinoid Receptor Type 2 ◽  
Attractive Therapeutic Target ◽  
The Brain

Cannabinoid receptors type 2 (CB2R) represent an attractive therapeutic target for neurodegenerative diseases and cancer. Aiming at the development of a positron emission tomography (PET) radiotracer to monitor receptor density and/or occupancy during a CB2R-tailored therapy, we herein describe the radiosynthesis of cis-[18F]1-(4-fluorobutyl-N-((1s,4s)-4-methylcyclohexyl)-2-oxo-1,2-dihydro-1,8-naphthyridine-3-carboxamide ([18F]LU14) starting from the corresponding mesylate precursor. The first biological evaluation revealed that [18F]LU14 is a highly affine CB2R radioligand with >80% intact tracer in the brain at 30 min p.i. Its further evaluation by PET in a well-established rat model of CB2R overexpression demonstrated its ability to selectively image the CB2R in the brain and its potential as a tracer to further investigate disease-related changes in CB2R expression.

Mitochondrial Localization of CB1 in Progesterone-producing Cells of Ovarian Interstitial Glands of Adult Mice

2021 ◽  
pp. 002215542110635
Author(s):  
Anussara Kamnate ◽  
Juthathip Sirisin ◽  
Masahiko Watanabe ◽  
Hisatake Kondo ◽  
Wiphawi Hipkaeo ◽  
...  
Keyword(s):  
Lipid Droplets ◽  
Cannabinoid Receptor ◽  
Receptor Type ◽  
Mitochondrial Localization ◽  
Mitochondrial Membranes ◽  
Synthetic Process ◽  
Outer Membranes ◽  
Adult Mice

Localization of cannabinoid receptor type 1 (CB1) immunoreactivity on mitochondrial membranes, at least their outer membranes distinctly, was detected in progesterone-producing cells characterized by mitochondria having tubular cristae and aggregations of lipid droplets in ovarian interstitial glands in situ of adult mice. Both immunoreactive and immunonegative mitochondria were contained in one and the same cell. Considering that the synthesis of progesterone is processed in mitochondria, the mitochondrial localization of CB1 in the interstitial gland cells suggests the possibility that endocannabinoids modulate the synthetic process of progesterone in the cells through CB1:

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