scholarly journals Bioactive Chemical Composition of Cannabis Extracts and Cannabinoid Receptors

Molecules ◽  
2020 ◽  
Vol 25 (15) ◽  
pp. 3466 ◽  
Author(s):  
Yi Yang ◽  
Rupali Vyawahare ◽  
Melissa Lewis-Bakker ◽  
Hance A. Clarke ◽  
Albert H. C. Wong ◽  
...  
Keyword(s):  
Chemical Composition ◽  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Therapeutic Drug ◽  
Chemical Compositions ◽  
Least Squares Regression ◽  
Medical Cannabis ◽  
Cb2 Receptors ◽  
The Relationship

Cannabis is widely used as a therapeutic drug, especially by patients suffering from psychiatric and neurodegenerative diseases. However, the complex interplay between phytocannabinoids and their targets in the human receptome remains largely a mystery, and there have been few investigations into the relationship between the chemical composition of medical cannabis and the corresponding biological activity. In this study, we investigated 59 cannabis samples used by patients for medical reasons. The samples were subjected to extraction (microwave and supercritical carbon dioxide) and chemical analyses, and the resulting extracts were assayed in vitro using the CB1 and CB2 receptors. Using a partial least squares regression analysis, the chemical compositions of the extracts were then correlated to their corresponding cannabinoid receptor activities, thus generating predictive models that describe the receptor potency as a function of major phytocannabinoid content. Using the current dataset, meaningful models for CB1 and CB2 receptor agonism were obtained, and these reveal the insignificant relationships between the major phytocannabinoid content and receptor affinity for CB1 but good correlations between the two at CB2 receptors. These results also explain the anomalies between the receptor activities of pure phytocannabinoids and cannabis extracts. Furthermore, the models for CB1 and CB2 agonism in cannabis extracts predict the cannabinoid receptor activities of individual phytocannabinoids with reasonable accuracy. Here for the first time, we disclose a method to predict the relationship between the chemical composition, including phytocannabinoids, of cannabis extracts and cannabinoid receptor responses.

scholarly journals Therapeutic Attributes of Endocannabinoid System against Neuro-Inflammatory Autoimmune Disorders

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3389
Author(s):  
Ishtiaq Ahmed ◽  
Saif Ur Rehman ◽  
Shiva Shahmohamadnejad ◽  
Muhammad Anjum Zia ◽  
Muhammad Ahmad ◽  
...  
Keyword(s):  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Therapeutic Potential ◽  
Endocannabinoid System ◽  
Cell Types ◽  
Autoimmune Disorders ◽  
Specific Receptors ◽  
Different Cell Types

In humans, various sites like cannabinoid receptors (CBR) having a binding affinity with cannabinoids are distributed on the surface of different cell types, where endocannabinoids (ECs) and derivatives of fatty acid can bind. The binding of these substance(s) triggers the activation of specific receptors required for various physiological functions, including pain sensation, memory, and appetite. The ECs and CBR perform multiple functions via the cannabinoid receptor 1 (CB1); cannabinoid receptor 2 (CB2), having a key effect in restraining neurotransmitters and the arrangement of cytokines. The role of cannabinoids in the immune system is illustrated because of their immunosuppressive characteristics. These characteristics include inhibition of leucocyte proliferation, T cells apoptosis, and induction of macrophages along with reduced pro-inflammatory cytokines secretion. The review seeks to discuss the functional relationship between the endocannabinoid system (ECS) and anti-tumor characteristics of cannabinoids in various cancers. The therapeutic potential of cannabinoids for cancer—both in vivo and in vitro clinical trials—has also been highlighted and reported to be effective in mice models in arthritis for the inflammation reduction, neuropathic pain, positive effect in multiple sclerosis and type-1 diabetes mellitus, and found beneficial for treating in various cancers. In human models, such studies are limited; thereby, further research is indispensable in this field to get a conclusive outcome. Therefore, in autoimmune disorders, therapeutic cannabinoids can serve as promising immunosuppressive and anti-fibrotic agents.

scholarly journals GPR18, GPR55 and GPR119 (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

2019 ◽  
Vol 2019 (4) ◽  
Author(s):  
Stephen P.H. Alexander ◽  
Andrew J. Irving
Keyword(s):  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Structural Similarity ◽  
Synthetic Cannabinoid ◽  
Receptor Ligands ◽  
Orphan Status ◽  
Endogenous Cannabinoid

GPR18, GPR55 and GPR119 (provisional nomenclature), although showing little structural similarity to CB1 and CB2 cannabinoid receptors, respond to endogenous agents analogous to the endogenous cannabinoid ligands, as well as some natural/synthetic cannabinoid receptor ligands [98]. Although there are multiple reports to indicate that GPR18, GPR55 and GPR119 can be activated in vitro by N-arachidonoylglycine, lysophosphatidylinositol and N-oleoylethanolamide, respectively, there is a lack of evidence for activation by these lipid messengers in vivo. As such, therefore, these receptors retain their orphan status.

Abstinence from chronic methylphenidate exposure modifies cannabinoid receptor 1 levels in the brain in a dose-dependent manner

2021 ◽  
Vol 27 ◽  
Author(s):  
Carly Connor ◽  
John Hamilton ◽  
Lisa Robison ◽  
Michael Hadjiargyrou ◽  
David Komatsu ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
High Dose ◽  
Dependent Manner ◽  
Water Control ◽  
Cannabinoid Receptor 1 ◽  
The Brain ◽  
Abstinence Period

Introduction: Methylphenidate (MP) is a widely used psychostimulant prescribed for Attention Deficit Hyperactivity Disorder, and is also used illicitly by healthy individuals. Chronic exposure to MP has been shown to affect physiology, behavior, and neurochemistry. Methods: The present study examined its effect on the endocannabinoid system. Adolescent rats had daily oral access to either water (control), low dose MP (4/10 mg/kg), or high dose MP (30/60 mg/kg). After 13 weeks of exposure, half of the rats in each group were euthanized, however the remaining rats underwent a four-week long abstinence period. Cannabinoid receptor 1 binding (CB1) was measured with in vitro autoradiography using [3H] SR141716A. Results: Rats who underwent a 4-week abstinence period after exposure to chronic HD MP showed increased binding compared to rats with no abstinence period in several cortical and basal ganglia regions of the brain. In contrast to this, rats who underwent a 4-week abstinence period after exposure to chronic LD MP showed lower binding compared to rats with no abstinence period in mainly the basal ganglia regions and in the hindlimb region of the somatosensory cortex. Following 4 weeks of drug abstinence, rats who were previously given HD MP showed higher [ 3H] SR141716A binding than rats given LD MP in many of the cortical and basal ganglia regions examined. These results highlight biphasic effects of MP treatment on cannabinoid receptor levels. Abstinence from HD MP seemed to increase CB1 receptor levels while abstinence from LD MP seemed to decrease CB1 levels. Conclusion: Given the prolific expression of cannabinoid receptors throughout the brain, many types of behaviors may be affected as a result of MP abstinence. Further research will be needed to help identify these behavioral changes.

scholarly journals β-Caryophyllene Reduces the Inflammatory Phenotype of Periodontal Cells by Targeting CB2 Receptors

Biomedicines ◽  
2020 ◽  
Vol 8 (6) ◽  
pp. 164 ◽  
Author(s):  
Giacomo Picciolo ◽  
Giovanni Pallio ◽  
Domenica Altavilla ◽  
Mario Vaccaro ◽  
Giacomo Oteri ◽  
...  
Keyword(s):  
Oral Mucositis ◽  
Cannabinoid Receptor ◽  
Therapeutic Potential ◽  
Preclinical Model ◽  
Mrna Levels ◽  
Innovative Strategies ◽  
Inflammatory Phenotype ◽  
Cb2 Receptors ◽  
Vitro Model

Human gingival fibroblasts (GF) and human oral mucosa epithelial cells (EC) with an inflammatory phenotype represent a valuable experimental paradigm to explore the curative activity of agents to be used in oral mucositis. The role of cannabinoid receptor 2 (CB2) has not yet been investigated in oral mucositis. The aim of this study was to evaluate the therapeutic potential of β-Caryophyllene (BCP), a CB2 agonist, in an in vitro model of oral mucositis. GF and EC were stimulated with LPS (2 µg/mL) alone or in combination with BCP; a group of LPS challenged GF and EC were treated with BCP and AM630, a CB2 antagonist. LPS increased the inflammatory cytokines TNF-α, IL-1β, IL-6 and IL-17A whereas it decreased the anti-inflammatory cytokine IL-13. The upstream signals were identified in an augmented expression of NF-κB and STAT-3 and in reduced mRNA levels of PPARγ and PGC-1α. BCP blunted the LPS-induced inflammatory phenotype and this effect was reverted by the CB2 antagonist AM630. These results suggest that CB2 receptors are an interesting target to develop innovative strategies for oral mucositis and point out that BCP exerts a marked curative effect in a preclinical model of oral mucositis which deserves to be confirmed in a clinical setting.

The relationship between milk yield, composition and tissue damage in a case of subclinical mastitis

1963 ◽  
Vol 30 (1) ◽  
pp. 23-33 ◽  
Author(s):  
R. Waite ◽  
P. S. Blackburn
Keyword(s):  
Chemical Composition ◽  
Milk Yield ◽  
Tissue Damage ◽  
Subclinical Mastitis ◽  
Bacteriological Examination ◽  
Cell Content ◽  
Upper Level ◽  
The Relationship ◽  
Number Of Cells

SummaryA chemical, cytological and bacteriological examination of the milk from each quarter of a cow suffering from subclinical mastitis, but giving 5–6 gal of milk per day, was made at weekly intervals during the first 84 days after parturition. The infection, caused by micrococcal and staphylococcal bacteria, resisted repeated treatments with various antibiotics administered via the teat canals and also intramuscularly, although in vitro the bacteria were susceptible to all the antibiotics used. The cow was slaughtered and a histological examination made of the udder in an attempt to establish the cause of the continuing infection and to assess the extent of tissue damage. Two quarters each contained large abscesses in the upper level of the udder and these could have acted as reservoirs of infection; no cause was established for the other two quarters and it can only be assumed that reinfection occurred from the two abscessed quarters.The amount of active lesions in the lobules of all the quarters was small, 1–6%, but half or more of all the lobules were involuted, although only a minority appeared to have involuted as a result of infection. In the two abscessed quarters there was extensive damage to the duct system, 23 and 31% showing lesions.When the milk contained an abnormally large number of cells the chemical composition was also abnormal, containing less lactose (and hence less solids-not-fat) and having a nitrogen distribution in which there was more blood serum albumin and globulin and less casein than usual. Cell content and chemical composition were better indicators of tissue damage than the presence of mastitis organisms. It is estimated that the solids-not-fat content of the milk of the whole udder as a result of the infections was considerably lower than it would otherwise have been (8·0 instead of 8·8%) and that the daily loss in milk yield was about 9 lb.

scholarly journals Pregnancy success in mice requires appropriate cannabinoid receptor signaling for primary decidua formation

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Yingju Li ◽  
Amanda Dewar ◽  
Yeon Sun Kim ◽  
Sudhansu K Dey ◽  
Xiaofei Sun
Keyword(s):  
Endothelial Cells ◽  
Stromal Cells ◽  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Angiogenic Factors ◽  
Permeable Barrier ◽  
Size Dependent ◽  
Decidual Cells ◽  
Avascular Zone

With implantation, mouse stromal cells begin to transform into epithelial-like cells surrounding the implantation chamber forming an avascular zone called the primary decidual zone (PDZ). In the mouse, the PDZ forms a transient, size-dependent permeable barrier to protect the embryo from maternal circulating harmful agents. The process of decidualization is critical for pregnancy maintenance in mice and humans. Mice deficient in cannabinoid receptors, CB1 and CB2, show compromised PDZ with dysregulated angiogenic factors, resulting in the retention of blood vessels and macrophages. This phenotype is replicated in Cnr1-/- but not in Cnr2-/-mice. In vitro decidualization models suggest that Cnr1 levels substantially increase in mouse and human decidualizing stromal cells, and that neutralization of CB1 signaling suppresses decidualization and misregulates angiogenic factors. Taken together, we propose that implantation quality depends on appropriate angiogenic events driven by the integration of CB2 in endothelial cells and CB1 in decidual cells.

scholarly journals Effect of Inoculations of Trichoderma viride and Saccharomyces cerevisiae Mixed Culture on Chemical Composition, Fiber, Digestibility and Theobromine Cocoa Pod Fermentation

2016 ◽  
Vol 4 (2) ◽  
pp. 178 ◽  
Author(s):  
Muhammad Askari Zakariah
Keyword(s):  
Chemical Composition ◽  
Mixed Culture ◽  
Crude Protein ◽  
Trichoderma Viride ◽  
In Vitro Digestibility ◽  
Chemical Compositions ◽  
Fiber Fraction ◽  
Nitrogen Free Extract ◽  
Significant Difference

The objective of the study was to identify the effect of Trichoderma viride andSaccharomyces cerevisiae inoculant on chemical compositions, digestibility, and theobromineconcentration of fermented cocoa pod. This experiment consisted of four treatments,namely cocoa pods without fermentation as control (R0); fermentation of cocoa pods withinoculant T. viride (R1); fermentation of cocoa pods with inoculant S. cerevisiae (R2); andfermentation of cocoa pods with inoculant T. viride and S. cerevisiae mixed culture (R3).Each treatment had 3 replicates, and then was fermented for 10 days. Variables observedwere the chemical compositions i.e dry matter (DM), organic matter (OM), crude protein(CP), ether extract (EE), crude fiber (CF), nitrogen free extract (NFE), fiber fraction (Neutraldetergent fiber and acid detergent fiber), in vitro digestibility, and theobromine concentration.Data were analysed by one-way analysis of variance and followed by Duncan’s new multiplerange test (DMRT), if there were any significant difference. Results showed the inoculumaffected (P<0.05) the chemical composition, fiber fraction and in vitro digestibility. However,theobromine was not detected on cocoa pod without fermentation and fermentation.Compared to group R0, inoculation with T. viride and S. cerevisiae mixed culture (P<0.05)resulted in higher DM concentration (92.78% vs 89.72% respectively), higher CP (7.43% vs5.63% respectively), higher NDF (79.41% vs 61.18% respectively), higher ADF (73.04%vs 47.94% respectively), but was not significantly different on DM and OM digestibility(21.22% vs 22.24%, and 22.67% vs 24.31% respectively) than cocoa pod without fermentation.It is concluded that inoculant T. viride and S. cerevisiae mixed culture increased CPconcentration, but had no effect on in vitro digestibility.

scholarly journals Discovery of Orexant and Anorexant Agents with Indazole Scaffold Endowed with Peripheral Antiedema Activity

Biomolecules ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 492 ◽  
Author(s):  
Dimmito ◽  
Stefanucci ◽  
Pieretti ◽  
Minosi ◽  
Dvorácskó ◽  
...  
Keyword(s):  
Feeding Behavior ◽  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Methyl Esters ◽  
Endocannabinoid System ◽  
Tail Flick ◽  
Binding Assays ◽  
Tail Flick Test

The endocannabinoid system represents an integrated neuronal network involved in the control of several organisms’ functions, such as feeding behavior. A series of hybrids of 5-(4-chlorophenyl)-1-(2,4-dichloro-phenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide (mimonabant), a well-known inverse agonist of the type-1 cannabinoid receptor (CB1), once used as an antiobesity drug, and the N-(2S)-substitutes of 1-[(4-fluorophenyl)methyl]indazole-3-carboxamide with 1-amino-3-methyl-1-oxobutane (AB-Fubinaca), 1-amino-3,3-dimethyl-1-oxobutane (ADB-Fubinaca), and 3-methylbutanoate (AMB-Fubinaca), endowed with potent agonistic activity towards cannabinoid receptors CB1 and CB2 were in solution as C-terminal amides, acids, methyl esters and N-methyl amides. These compounds have been studied by binding assays to cannabinoid receptors and by functional receptor assays, using rat brain membranes in vitro. The most active among them as an agonist, (S)-1-(2,4-dichlorobenzyl)-N-(3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl)-1H-indazole-3-carboxamide (LONI11), and an antagonist, (S)-2-(1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxamido)-3-methylbutanoic acid (LONI4), were tested in vivo in mic, to evaluate their ability to stimulate or suppress feeding behavior after intraperitoneal (i.p.) administration. For a LONI11 formalin test and a tail flick test after an administration by the subcutaneous (s.c.) and intracerebroventricular (i.c.v.) routes, respectively, were also carried out in vivo in mice to investigate the antinociceptive property at the central and peripheral levesl. We observed a significant orexant effect for LONI11 and an intense anorexant effect for (S)-methyl 2-(1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxamido)-3,3-dimethylbutanoate (LONI2) and LONI4. In zymosan-induced edema and hyperalgesia, LONI11 reduced the percent of paw volume increase and paw latency after s.c. administration, also suggesting a possible peripheral anti-inflammatory activity.

scholarly journals Assessment of select synthetic cannabinoid receptor agonist bias and selectivity between the type 1 and type 2 cannabinoid receptor

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ayat Zagzoog ◽  
Asher L. Brandt ◽  
Tallan Black ◽  
Eunhyun D. Kim ◽  
Riley Burkart ◽  
...  
Keyword(s):  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Partial Agonist ◽  
Synthetic Cannabinoid ◽  
Receptor Subtype ◽  
Service Agency ◽  
Subtype Selectivity ◽  
Insight Into

AbstractThe first synthetic cannabinoid receptor agonists (SCRAs) were designed as tool compounds to study the endocannabinoid system’s two predominant cannabinoid receptors, CB1R and CB2R. Unfortunately, novel SCRAs now represent the most rapidly proliferating novel psychoactive substances (NPS) of abuse globally. Unlike ∆9-tetrahydrocannabinol, the CB1R and CB2R partial agonist and the intoxicating constituent of Cannabis, many SCRAs characterized to date are full agonists of CB1R. Gaining additional insight into the pharmacological activity of these SCRAs is critical to assess and regulate NPSs as they enter the marketplace. The purpose of this study was to assess select SCRAs recently identified by Canadian police, border service agency, private companies and the illicit market as potential CB1R and CB2R agonists. To this end, fifteen SCRAs were screened for in vitro activity and in silico interactions at CB1R and CB2R. Several SCRAs were identified as being highly biased for cAMP inhibition or βarrestin2 recruitment and receptor subtype selectivity between CB1R and CB2R. The indazole ring and halogen-substituted butyl or pentyl moieties were identified as two structural features that may direct βarrestin2 bias. Two highly-biased SCRAs—JWH-018 2′-napthyl-N-(3-methylbutyl) isomer (biased toward cAMP inhibition) and 4-fluoro MDMB-BINACA (biased toward βarrestin2 recruitment) displayed unique and differential in vivo activity in mice. These data provide initial insight into the correlations between structure, signalling bias, and in vivo activity of the SCRAs.

Prediction of Chemical Composition in Sunflower Whole Plant and Silage (Helianthus Annus L.) by near Infrared Reflectance Spectroscopy

2007 ◽  
Vol 15 (3) ◽  
pp. 201-207 ◽  
Author(s):  
A. Fassio ◽  
A. Gimenez ◽  
E. Fernandez ◽  
D. Vaz Martins ◽  
D. Cozzolino
Keyword(s):  
Chemical Composition ◽  
Near Infrared ◽  
Cross Validation ◽  
Reference Method ◽  
Reflectance Spectroscopy ◽  
Least Squares Regression ◽  
Near Infrared Reflectance ◽  
Whole Plant ◽  
Calibration Models

The aim of this study was to investigate the potential use of near infrared (NIR) reflectance spectroscopy to predict chemical composition in both sunflower whole plant (WPSun) and sunflower silage (SunS). Samples of both WPSun ( n = 73) and SunS ( n = 50) were analysed by reference method and scanned in reflectance using a NIR monochromator instrument (400–2500 nm). Calibration models were developed between NIR data and reference values for dry matter (DM), crude protein (CP), ash, acid detergent fibre (ADFom), neutral detergent fibre (aNDFom), in vitro organic matter digestibility (OMD), ether extract (EE) and pH using partial least squares regression (PLS). Due to the limited number of samples full cross-validation was used to test the calibration models. The best correlations (R 2cal) and lowest standard errors in cross-validation (SECV) were obtained for DM (R 2cal > 0.82, SECV: 27.0 and 35.8 g kg−1), CP (R 2cal> 0.85, SECV: 9.9 and 10.1 g kg−1) and ash (R2cal> 0.85, SECV 11.2 and 8.2 g kg−1) in both WPSun and SunS samples, respectively. For ADFom, aNDFom and OMD the calibrations were considered to be poor (R 2cal < 0.85). In SunS samples a good correlation was found for EE (R 2cal = 0.94, SECV: 15.3 g kg−1).

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