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https://www.readbyqxmd.com/read/28803965/the-great-divide-separation-between-in-vitro-and-in-vivo-effects-of-psncbam-based-cb1-receptor-allosteric-modulators
#1
Thomas F Gamage, Charlotte E Farquhar, Timothy W Lefever, Brian F Thomas, Thuy Nguyen, Yanan Zhang, Jenny L Wiley
While allosteric modulators of the cannabinoid type-1 receptor (CB1) continue to be developed and characterized, the gap between the in vitro and in vivo data is widening, raising questions regarding translatability of their effects and biological relevance. Among the CB1 allosteric modulators, PSNCBAM-1 has received little attention regarding its effects in vivo. Recently, pregnenolone was reported to act as an allosteric modulator of CB1, blocking THC's effects in vitro and in vivo, highlighting the potential of CB1 allosteric modulators for treatment of cannabis intoxication...
August 10, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28800762/the-novel-cannabinoid-receptor-gpr55-mediates-anxiolytic-like-effects-in-the-medial-orbital-cortex-of-mice-with-acute-stress
#2
Qi-Xin Shi, Liu-Kun Yang, Wen-Long Shi, Lu Wang, Shi-Meng Zhou, Shao-Yu Guan, Ming-Gao Zhao, Qi Yang
The G protein-coupled receptor 55 (GPR55) is a novel cannabinoid receptor, whose exact role in anxiety remains unknown. The present study was conducted to explore the possible mechanisms by which GPR55 regulates anxiety and to evaluate the effectiveness of O-1602 in the treatment of anxiety-like symptoms. Mice were exposed to two types of acute stressors: restraint and forced swimming. Anxiety behavior was evaluated using the elevated plus maze and the open field test. We found that O-1602 alleviated anxiety-like behavior in acutely stressed mice...
August 11, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28800377/antidote-to-cannabinoid-intoxication-inverse-cannabinoid-receptor-one-cb1-agonism-by-n-piperidin-1-yl-5-4-iodophenyl-1-2-4-dichlorophenyl-4-methyl-1h-pyrazole-3-carboxamidse-am251-reverses-the-hypothermic-effects-of-cannabinoid-receptor-one-agonism-by-1-naphthalenyl
#3
Gareth Pryce, David Baker
BACKGROUND & PURPOSE: Cannabis is a recreational drug leading to intoxication, due to cannabinoid receptor one (CB1 ) stimulation. However, more recently herbs mixed with synthetic cannabinoids sometimes known as "Spice" and "Black Mamba" have been increasing used and their high CB1 receptor affinity means not only marked intoxication, but life-threatening complications and an increasing number of deaths. Whilst many studies have indicated that prophylactic CB1 receptor antagonism can block cannabimimetic effects in animals and humans...
August 11, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28799775/a-review-of-the-therapeutic-antitumor-potential-of-cannabinoids
#4
Višnja Bogdanović, Jasminka Mrdjanović, Ivana Borišev
OBJECTIVES: The aim of this review is to discuss cannabinoids from a preclinical and clinical oncological perspective and provide the audience with a concise, retrospective overview of the most significant findings concerning the potential use of cannabinoids in cancer treatment. METHODS: A literature survey of medical and scientific databases was conducted with a focus on the biological and medical potential of cannabinoids in cancer treatment. RESULTS: Cannabis sativa is a plant rich in more than 100 types of cannabinoids...
August 11, 2017: Journal of Alternative and Complementary Medicine: Research on Paradigm, Practice, and Policy
https://www.readbyqxmd.com/read/28799497/cannabis-phenolics-and-their-bioactivities
#5
Federica Pollastro, Alberto Minassi, Luigia Grazia Fresu
Although Cannabis sativa L. is one of the most versatile plant species with multipurpose use both as medical, alimentary source and as psychoactive abuse, its biomedical relevance focused the attention on major cannabinoids. Phytochemical characterization of cannabis highlights the presence of various non-cannabinoids constituents including flavonoids, spiroindans, dihyrostilbenes, dihydrophenanthrenes, lignanamides, steroids and alkaloids. Cannabis is a plant with high pharmacological and nutrition values, its potentialities and applications are not only circumscribed to cannabinoids biological activities, but also defined by non-cannabinoid compounds...
August 10, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28799288/neuroprotective-activity-of-cannabinoid-receptor-2-against-oxidative-stress-and-apoptosis-in-rat-pups-having-experimentally-induced-congenital-hypothyroidism
#6
Mehmet Eray Alcigir, Halef Okan Dogan, Sevil Atalay Vural, Fatma Meriç Yilmaz
In this study, it was aimed to show the cannabinoid receptor-2 (CB2) role, which is a part of neuroprotective endocannabinoidal system, against increasing nitric oxide synthetase (iNOS, eNOS) levels and the apoptotic activity (caspase-3, caspase-9 and DNA in situ fragmentation) within the postnatal critical period in pups of pregnant rats with artificially induced maternal thyroid hormone (TH) deficiency. Each of the 3 groups established comprised 1 male and 2 female rats, and they were coupled. Their pups were used...
August 11, 2017: Developmental Neurobiology
https://www.readbyqxmd.com/read/28796754/perioperative-patient-beliefs-regarding-potential-effectiveness-of-marijuana-cannabinoids-for-treatment-of-pain-a-prospective-population-survey
#7
Yury Khelemsky, Andrew T Goldberg, Yasmin L Hurd, Gary Winkel, Allen Ninh, Lucia Qian, Anna Oprescu, Jeffrey Ciccone, Daniel J Katz
BACKGROUND AND OBJECTIVES: Cannabinoids have an expanding presence in medicine. Perioperative patients' perceptions of the effectiveness of these compounds, and acceptance if prescribed for pain, have not been previously described. Our primary objective was to describe patients' beliefs regarding the potential effectiveness of cannabinoids for the treatment of acute and chronic pain, as well as gauge patient acceptance of these compounds if prescribed by a physician. In addition, demographic and pain history data were collected to elucidate the predictors of the aforementioned patient attitudes...
August 7, 2017: Regional Anesthesia and Pain Medicine
https://www.readbyqxmd.com/read/28794966/synthetic-cannabinoid-induced-acute-respiratory-depression-case-series-and-literature-review
#8
Mark Henry Alon, Margaret Olibrice Saint-Fleur
Synthetic Cannabinoids are a street drug that is widely attainable and cheap compared to natural cannabis, and has variable potency and unpredictable effects with no commercially available diagnostic test to confirm its presence. Similar to natural cannabis, Synthetic Cannabinoid intoxication can present in several ways with the most common emergency room presentations to be of neurologic and psychiatric manifestation. The respiratory depressive effect of Synthetic Cannabinoids has not been well documented in medical literature...
2017: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/28792725/pharmacology-of-cumyl-carboxamide-synthetic-cannabinoid-new-psychoactive-substances-nps-cumyl-bica-cumyl-pica-cumyl-5f-pica-cumyl-5f-pinaca-and-their-analogues
#9
Mitchell Longworth, Samuel D Banister, Rochelle Boyd, Richard C Kevin, Mark Connor, Iain S McGregor, Michael Kassiou
Synthetic cannabinoids (SC) are the largest class of new psychoactive substances (NPS), and are increasingly associated with serious adverse effects. The majority of SC NPS are 1,3-disubstituted indoles and indazoles featuring a diversity of subunits at the 1- and 3-positions. Most recently, cumyl-derived indole- and indazole-3-carboxamides have been detected by law enforcement agencies and by emergency departments. Herein we describe the synthesis, characterization, and pharmacology of SCs CUMYL-BICA, CUMYL-PICA, CUMYL-5F-PICA, CUMYL-PINACA, CUMYL-5F-PINACA, and related analogues...
August 11, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28792219/novel-diarylurea-based-allosteric-modulators-of-the-cannabinoid-cb1-receptor-evaluation-of-importance-of-6-pyrrolidinylpyridinyl-substitution
#10
Thuy Nguyen, Nadezhda German, Ann M Decker, Tifffany L Langston, Thomas F Gamage, Charlotte E Farquhar, Jun-Xu Li, Jenny L Wiley, Brian F Thomas, Yanan Zhang
Allosteric modulators of the cannabinoid CB1 receptor have recently been reported as an alternative approach to modulate the CB1 receptor for therapeutic benefits. In this study, we report the design and synthesis of a series of diarylureas derived from PSNCBAM-1 (2). Similar to 2, these diarylureas dose-dependently inhibited CP55,940-induced intracellular calcium mobilization and [(35)S]GTP-γ-S binding while enhancing [(3)H]CP55,940 binding to the CB1 receptor. Structure-activity relationship studies revealed that the pyridinyl ring of 2 could be replaced by other aromatic rings and the pyrrolidinyl ring is not required for CB1 allosteric modulation...
August 9, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28789932/the-effects-of-anandamide-and-oleamide-on-cognition-depend-on-diurnal-variations
#11
Pavel E Rueda-Orozco, Corinne J Montes-Rodriguez Cj, Alejandra E Ruiz-Contreras, Monica Mendez-Diaz, Oscar Prospero-Garcia
Cannabinergic receptor 1 (CB1r) is highly expressed in almost the entire brain; hence, its activation affects diverse functions, including cognitive processes such as learning and memory. On the other hand, it has been demonstrated that CB1r expression fluctuates along the light-dark cycle. In this context, the objective of this work was to characterize the cannabinergic influence over cognitive processes and its relationship with the light-dark cycle. To this aim we studied the effects of two endogenous cannabinoids, anandamide (AEA) and oleamide (ODA), on the consolidation of memory and event-related potentials (ERPs) depending on the light-dark cycle...
August 5, 2017: Brain Research
https://www.readbyqxmd.com/read/28782714/electroacupuncture-inhibits-nlrp3-inflammasome-activation-through-cb2-receptors-in-inflammatory-pain
#12
Fang Gao, Hong-Chun Xiang, Hong-Ping Li, Min Jia, Xiao-Li Pan, Hui-Lin Pan, Man Li
The therapeutic effect of electroacupuncture (EA) on inflammatory pain has been well recognized clinically. The inflammasome promotes the maturation of the inflammatory cytokines, and EA can stimulate cannabinoid CB2 receptors in inflamed tissues. In this study we investigated whether EA inhibits NLRP3 inflammasome activation through CB2 receptors and thus relieving inflammatory pain. Assay of Caspase-1 activity and western blotting revealed that complete Freund's adjuvant (CFA) injection activated the NLRP3 inflammasome in the skin tissue in rats, which was attenuated by EA treatment...
August 3, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28780734/intra-accumbal-cannabinoid-agonist-attenuated-reinstatement-but-not-extinction-period-of-morphine-induced-conditioned-place-preference-evidence-for-different-characteristics-of-extinction-period-and-reinstatement
#13
Hossein Khaleghzadeh-Ahangar, Abbas Haghparast
The brain reward system consists of the ventral tegmental area that sends its dopaminergic projections to the forebrain, cortical areas, amygdala and largely to the nucleus accumbens (NAc). The present study aims were to investigate the effects of bilateral intra-accumbal microinjection of WIN55,212-2, a CB1 receptor agonist, on the duration of extinction period and reinstatement to morphine by the conditioned place preference (CPP) paradigm in the rat. Forty-six adult male albino Wistar rats received intra-accumbal WIN55,212-2 [p0...
August 5, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28780725/a-review-of-oral-cannabinoids-and-medical-marijuana-for-the-treatment-of-chemotherapy-induced-nausea-and-vomiting-a-focus-on-pharmacokinetic-variability-and-pharmacodynamics
#14
REVIEW
Melissa E Badowski
PURPOSE: Oral cannabinoids (i.e., dronabinol, nabilone) containing the active component of marijuana, delta(Δ)9-tetrahydrocannabinol (THC), are available for the treatment of chemotherapy-induced nausea and vomiting (CINV) in patients with cancer who have failed to adequately respond to conventional antiemetic therapy. The aim of this article is to provide an overview of the efficacy, pharmacokinetics (PK), pharmacodynamics (PD), and safety of oral cannabinoids for patients with CINV...
August 5, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28779310/the-interaction-between-hippocampal-gaba-b-and-cannabinoid-receptors-upon-spatial-change-and-object-novelty-discrimination-memory-function
#15
Mohammad Nasehi, Niyousha Alaghmandan-Motlagh, Mohaddeseh Ebrahimi-Ghiri, Mohammad Nami, Mohammad-Reza Zarrindast
RATIONALE: Previous studies have postulated functional links between GABA and cannabinoid systems in the hippocampus. The aim of the present study was to investigate any possible interaction between these systems in spatial change and object novelty discrimination memory consolidation in the dorsal hippocampus (CA1 region) of NMRI mice. METHODS: Assessment of the spatial change and object novelty discrimination memory function was carried out in a non-associative task...
August 5, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28779174/a-novel-crosstalk-within-the-endocannabinoid-system-controls-gaba-transmission-in-the-striatum
#16
A Musella, D Fresegna, F R Rizzo, A Gentile, S Bullitta, F De Vito, L Guadalupi, D Centonze, G Mandolesi
The N-palmitoylethanolamine (PEA) is an endogenous member of the endocannabinoid system (ECS) with several biological functions, including a neuromodulatory activity in the central nervous system. To shed light on the neuronal function of PEA, we investigated its involvement in the control of both excitatory and inhibitory transmission in the murine striatum, a brain region strongly modulated by the ECS. By means of electrophysiological recordings, we showed that PEA modulates inhibitory synaptic transmission, through activation of GPR55 receptors, promoting a transient increase of GABAergic spontaneous inhibitory postsynaptic current (sIPSC) frequency...
August 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28777688/attitudes-and-beliefs-about-new-psychoactive-substance-use-among-electronic-dance-music-party-attendees
#17
Joseph J Palamar, Patricia Acosta, Charles M Cleland
BACKGROUND: Attitudes and beliefs about drug use have been shown to be robust correlates of use of drugs such as alcohol, marijuana, and cocaine; however, little is known regarding attitudes or beliefs about new psychoactive substances (NPS). We sought to examine attitudes and beliefs about NPS and how they relate to self-reported use in a high-risk population-electronic dance music (EDM) party attendees. METHOD: 1,048 individuals (age 18-40) were surveyed entering EDM parties in New York City in 2016...
August 4, 2017: Substance Use & Misuse
https://www.readbyqxmd.com/read/28774834/role-of-forkhead-box-class-o-proteins-in-cancer-progression-and-metastasis
#18
REVIEW
Chang Geun Kim, Hyemin Lee, Nehal Gupta, Sharavan Ramachandran, Itishree Kaushik, Sangeeta Srivastava, Sung-Hoon Kim, Sanjay K Srivastava
It is now widely accepted that several gene alterations including transcription factors are critically involved in cancer progression and metastasis. Forkhead Box Class O proteins (FoxOs) including FoxO1/FKHR, FoxO3/FKHRL1, FoxO4/AFX and FoxO6 transcription factors are known to play key roles in proliferation, apoptosis, metastasis, cell metabolism, aging and cancer biology through their phosphorylation, ubiquitination, acetylation and methylation. Though FoxOs are proved to be mainly regulated by upstream phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt signaling pathway, the role of FoxOs in cancer progression and metastasis still remains unclear so far...
July 31, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28771697/effects-of-centrally-administered-endocannabinoids-and-opioids-on-orofacial-pain-perception-in-rats
#19
Marek Zubrzycki, Anna Janecka, Andreas Liebold, Mechthild Ziegler, Maria Zubrzycka
BACKGROUND AND PURPOSE: Endocannabinoids and opioids play a vital role in mediating pain-induced analgesia. The specific effects of these compounds within orofacial region are largely unknown. In this study we tried to determine whether the increase of cannabinoid and opioid concentration in cerebrospinal fluid affects impulse transmission between the motor centers localized in the vicinity of the third and fourth cerebral ventricles. EXPERIMENTAL APPROACH: The study objectives were realized on rats using the method allowing to record the amplitude of evoked tongue jerks (ETJ) in response to noxious tooth pulp stimulation...
August 3, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28771321/activity-based-detection-of-consumption-of-synthetic-cannabinoids-in-authentic-urine-samples-using-a-stable-cannabinoid-reporter-system
#20
Annelies Cannaert, Florian Franz, Volker Auwärter, Christophe P Stove
Synthetic cannabinoids (SCs) continue to be the largest group of new psychoactive substances (NPS) monitored by the European Monitoring Center of Drugs and Drugs of Abuse (EMCDDA). The identification and subsequent prohibition of single SCs has driven clandestine chemists to produce analogues of increasing structural diversity, intended to evade legislation. That structural diversity, combined with the mostly unknown metabolic profiles of these new SCs, poses a big challenge for the conventional targeted analytical assays, as it is difficult to screen for 'unknown' compounds...
August 3, 2017: Analytical Chemistry
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