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Dopamine Cannabinoids

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https://www.readbyqxmd.com/read/27853201/the-effects-of-%C3%AE-9-tetrahydrocannabinol-on-the-dopamine-system
#1
Michael A P Bloomfield, Abhishekh H Ashok, Nora D Volkow, Oliver D Howes
The effects of Δ(9)-tetrahydrocannabinol (THC), the main psychoactive ingredient in cannabis, are a pressing concern for global mental health. Patterns of cannabis use are changing drastically owing to legalization, the availability of synthetic analogues (commonly termed spice), cannavaping and an emphasis on the purported therapeutic effects of cannabis. Many of the reinforcing effects of THC are mediated by the dopamine system. Owing to the complexity of the cannabinoid-dopamine interactions that take place, there is conflicting evidence from human and animal studies concerning the effects of THC on the dopamine system...
November 16, 2016: Nature
https://www.readbyqxmd.com/read/27810775/chemogenomics-knowledgebase-and-systems-pharmacology-for-hallucinogen-target-identification-salvinorin-a-as-a-case-study
#2
Xiaomeng Xu, Shifan Ma, Zhiwei Feng, Guanxing Hu, Lirong Wang, Xiang-Qun Xie
Drug abuse is a serious problem worldwide. Recently, hallucinogens have been reported as a potential preventative and auxiliary therapy for substance abuse. However, the use of hallucinogens as a drug abuse treatment has potential risks, as the fundamental mechanisms of hallucinogens are not clear. So far, no scientific database is available for the mechanism research of hallucinogens. We constructed a hallucinogen-specific chemogenomics database by collecting chemicals, protein targets and pathways closely related to hallucinogens...
August 8, 2016: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/27760835/n-arachidonoyl-dopamine-inhibits-nras-neoplastic-transformation-by-suppressing-its-plasma-membrane-translocation
#3
Min Wu, Jinyan Huang, Jianming Zhang, Cyril Benes, Bo Jiao, Ruibao Ren
RAS oncogenic mutations are common in human cancers, but RAS proteins have been difficult to target. We sought to identify pharmacological agents to block the RAS oncogenic signaling by a distinct mechanism. Since the biological activity of RAS proteins rely upon lipid modifications and RAS regulates lipid metabolisms in cancer cells, we screened a bioactive lipid library using a RAS specific cell viability assay. We report the discovery of a new class of inhibitors for RAS transformation. Compounds in the class represented by endocannabinoid N-arachidonoyl dopamine (NADA) can induce cell oncosis, independent of its ability to engage cannabinoid receptors...
October 19, 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27746343/revealing-the-role-of-the-endocannabinoid-system-modulators-sr141716a-urb597-and-vdm-11-in-sleep-homeostasis
#4
Eric Murillo-Rodríguez, Sergio Machado, Nuno Barbosa Rocha, Henning Budde, Ti-Fei Yuan, Oscar Arias-Carrión
The endocannabinoid system comprises receptors (CB1 and CB2 cannabinoid receptors), enzymes (Fatty Acid Amide Hydrolase [FAAH], which synthesizes the endocannabinoid anandamide), as well as the anandamide membrane transporter (AMT). Importantly, previous experiments have demonstrated that the endocannabinoid system modulates multiple neurobiological functions, including sleep. For instance, SR141716A (the CB1 cannabinoid receptor antagonist) as well as URB597 (the FAAH inhibitor) increase waking in rats whereas VDM-11 (the blocker of the AMT) enhances sleep in rodents...
December 17, 2016: Neuroscience
https://www.readbyqxmd.com/read/27734824/-cannabinoid-and-cathinone-designer-drugs-the-workings-and-selected-methods-of-analysis
#5
REVIEW
Jadwiga Nędza, Renata Polaniak, Rafał J Bułdak, Milena Majchrzak, Joanna Margasiń-Ska, Marcin Rojkiewicz, Rafał Celiński, Elżbieta Grochowska-Niedworok
Recently, there has been an increase in the consumption of designer drugs, substances aimed at producing psychoactive, energizing, euphoric or anesthetic effects. Designer drugs are substitutes of actual narcotics, whose possession is banned under Polish law according to the Act of 29 July 2005. The latest reports suggest that the number of synthetic psychoactive substances is increasing. In the span of 2012, a total of 28 new synthetic cannabinoids were discovered in member states of the European Union. Synthetic psychoactive substances appear in different forms on the market: tablets (often very colourful and interestingly-shaped), seeds, dried product (sprayed with synthetic substance and redried), crystals or powder...
July 29, 2016: Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/27639448/seeing-through-the-smoke-human-and-animal-studies-of-cannabis-use-and-endocannabinoid-signalling-in-corticolimbic-networks
#6
Mason M Silveira, Jonathon C Arnold, Steven R Laviolette, Cecilia J Hillard, Marta Celorrio, María S Aymerich, Wendy K Adams
Public opinion surrounding the recreational use and therapeutic potential of cannabis is shifting. This review describes new work examining the behavioural and neural effects of cannabis and the endocannabinoid system, highlighting key regions within corticolimbic brain circuits. First, we consider the role of human genetic factors and cannabis strain chemotypic differences in contributing to interindividual variation in the response to cannabinoids, such as THC, and review studies demonstrating that THC-induced impairments in decision-making processes are mediated by actions at prefrontal CB1 receptors...
September 14, 2016: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/27618677/antipsychotic-like-effects-of-m4-positive-allosteric-modulators-are-mediated-by-cb2-receptor-dependent-inhibition-of-dopamine-release
#7
Daniel J Foster, Jermaine M Wilson, Daniel H Remke, M Suhaib Mahmood, M Jashim Uddin, Jürgen Wess, Sachin Patel, Lawrence J Marnett, Colleen M Niswender, Carrie K Jones, Zixiu Xiang, Craig W Lindsley, Jerri M Rook, P Jeffrey Conn
Muscarinic receptors represent a promising therapeutic target for schizophrenia, but the mechanisms underlying the antipsychotic efficacy of muscarinic modulators are not well understood. Here, we report that activation of M4 receptors on striatal spiny projection neurons results in a novel form of dopaminergic regulation resulting in a sustained depression of striatal dopamine release that is observed more than 30 min after removal of the muscarinic receptor agonist. Furthermore, both the M4-mediated sustained inhibition of dopamine release and the antipsychotic-like efficacy of M4 activators were found to require intact signaling through CB2 cannabinoid receptors...
September 21, 2016: Neuron
https://www.readbyqxmd.com/read/27589957/interaction-between-interleukin-1%C3%AE-and-type-1-cannabinoid-receptor-is-involved-in-anxiety-like-behavior-in-experimental-autoimmune-encephalomyelitis
#8
Antonietta Gentile, Diego Fresegna, Alessandra Musella, Helena Sepman, Silvia Bullitta, Francesca De Vito, Roberta Fantozzi, Alessandro Usiello, Mauro Maccarrone, Nicola B Mercuri, Beat Lutz, Georgia Mandolesi, Diego Centonze
BACKGROUND: Mood disorders, including anxiety and depression, are frequently diagnosed in multiple sclerosis (MS) patients, even independently of the disabling symptoms associated with the disease. Anatomical, biochemical, and pharmacological evidence indicates that type-1 cannabinoid receptor (CB1R) is implicated in the control of emotional behavior and is modulated during inflammatory neurodegenerative diseases such as MS and experimental autoimmune encephalomyelitis (EAE). METHODS: We investigated whether CB1R could exert a role in anxiety-like behavior in mice with EAE...
September 2, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27549374/brain-imaging-studies-on-the-cognitive-pharmacological-and-neurobiological-effects-of-cannabis-in-humans-evidence-from-studies-of-adult-users
#9
A Weinstein, A Livny-Ezer, A Weizman
Cannabis is the most widely used illicit drug worldwide. Regular cannabis use has been associated with a range of acute and chronic mental health problems, such as anxiety, depression, psychotic symptoms and neurocognitive impairments and their neural mechanisms need to be examined. This review summarizes and critically evaluates brain-imaging studies of cannabis in recreational and regular cannabis users between January 2000 and January 2016. The search has yielded eligible 103 structural and functional studies...
August 22, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27534533/cb2-receptor-activation-prevents-glial-derived-neurotoxic-mediator-production-bbb-leakage-and-peripheral-immune-cell-infiltration-and-rescues-dopamine-neurons-in-the-mptp-model-of-parkinson-s-disease
#10
Young C Chung, Won-Ho Shin, Jeong Y Baek, Eun J Cho, Hyung H Baik, Sang R Kim, So-Yoon Won, Byung K Jin
The cannabinoid (CB2) receptor type 2 has been proposed to prevent the degeneration of dopamine neurons in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. However, the mechanisms underlying CB2 receptor-mediated neuroprotection in MPTP mice have not been elucidated. The mechanisms underlying CB2 receptor-mediated neuroprotection of dopamine neurons in the substantia nigra (SN) were evaluated in the MPTP mouse model of Parkinson's disease (PD) by immunohistochemical staining (tyrosine hydroxylase, macrophage Ag complex-1, glial fibrillary acidic protein, myeloperoxidase (MPO), and CD3 and CD68), real-time PCR and a fluorescein isothiocyanate-labeled albumin assay...
2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27528659/peripheral-and-central-cb1-cannabinoid-receptors-control-stress-induced-impairment-of-memory-consolidation
#11
Arnau Busquets-Garcia, Maria Gomis-González, Raj Kamal Srivastava, Laura Cutando, Antonio Ortega-Alvaro, Sabine Ruehle, Floortje Remmers, Laura Bindila, Luigi Bellocchio, Giovanni Marsicano, Beat Lutz, Rafael Maldonado, Andrés Ozaita
Stressful events can generate emotional memories linked to the traumatic incident, but they also can impair the formation of nonemotional memories. Although the impact of stress on emotional memories is well studied, much less is known about the influence of the emotional state on the formation of nonemotional memories. We used the novel object-recognition task as a model of nonemotional memory in mice to investigate the underlying mechanism of the deleterious effect of stress on memory consolidation. Systemic, hippocampal, and peripheral blockade of cannabinoid type-1 (CB1) receptors abolished the stress-induced memory impairment...
August 30, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27527584/effect-of-the-novel-synthetic-cannabinoids-akb48-and-5f-akb48-on-tetrad-sensorimotor-neurological-and-neurochemical-responses-in-mice-in-vitro-and-in-vivo-pharmacological-studies
#12
Isabella Canazza, Andrea Ossato, Claudio Trapella, Anna Fantinati, Maria Antonietta De Luca, Giulia Margiani, Fabrizio Vincenzi, Claudia Rimondo, Fabiana Di Rosa, Adolfo Gregori, Katia Varani, Pier Andrea Borea, Giovanni Serpelloni, Matteo Marti
RATIONALE: AKB48 and its fluorinate derivate 5F-AKB48 are two novel synthetic cannabinoids belonging to a structural class with an indazole core structure. They are marketed as incense, herbal preparations or chemical supply for their psychoactive Cannabis-like effects. OBJECTIVES: The present study was aimed at investigating the in vitro and in vivo pharmacological activity of AKB48 and 5F-AKB48 in male CD-1 mice and comparing their in vivo effects with those caused by the administration of Δ(9)-THC and JWH-018...
October 2016: Psychopharmacology
https://www.readbyqxmd.com/read/27521837/the-novel-cannabinoid-antagonist-sm-11-reduces-hedonic-aspect-of-food-intake-through-a-dopamine-dependent-mechanism
#13
G R Fois, L Fattore, G Murineddu, A Salis, G Pintore, B Asproni, G A Pinna, M Diana
Cannabinoids, endogenous and exogenously administered, are known to positively regulate food intake and energy balance. Since CB1 receptor antagonists reduce food intake and antagonize overweight, we developed a new CB1 receptor antagonist in an attempt to identify a compound with potential application in overeating disorders. The newly developed SM-11 compound dose-dependently decreases food intake in rats by 15-20%. Moreover, SM-11 reduces self-administration of palatable food in both food restricted and ad libitum fed rats, suggesting an action on the hedonic component of food intake...
August 10, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27506997/cannabinoid-induced-depression-of-synaptic-transmission-is-switched-to-stimulation-when-dopaminergic-tone-is-increased-in-the-globus-pallidus-of-the-rodent
#14
Rene Nahum Caballero-Florán, Israel Conde-Rojas, Aldo Oviedo Chávez, Hernán Cortes-Calleja, Luis F Lopez-Santiago, Lori L Isom, Jorge Aceves, David Erlij, Benjamín Florán
Because activation of D2 receptors reverses the neurochemical effects of cannabinoids, we examined whether increasing dopaminergic tone in the globus pallidus (GPe) switches cannabinoid induced depression of synaptic transmission. GABAergic synaptic currents evoked in pallidal neurons by stimulation of striatal projections (IPSCs) were depressed by perfusion with the CB1R agonist ACEA. Coactivation of D2Rs with quinpirole converted the depression into stimulation. Pretreatment with pertussis toxin (PTX) to limit Gi/o protein coupling also switched the CB1R-induced depression of IPSCs...
November 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27473611/ca-2-signaling-and-emesis-recent-progress-and-new-perspectives
#15
Weixia Zhong, Andrew J Picca, Albert S Lee, Nissar A Darmani
Cisplatin-like chemotherapeutics cause vomiting via calcium (Ca(2+))-dependent release of multiple neurotransmitters (dopamine, serotonin, substance P, etc.) from the gastrointestinal enterochromaffin cells and/or the brainstem. Intracellular Ca(2+) signaling is triggered by activation of diverse emetic receptors (including tachykininergic NK1, serotonergic 5-HT3, dopaminergic D2, cholinergic M1, or histaminergic H1), whose activation in vomit-competent species can evoke emesis. Other emetogens such as cisplatin, rotavirus NSP4 protein and bacterial toxins can also induce intracellular Ca(2+) elevation...
July 26, 2016: Autonomic Neuroscience: Basic & Clinical
https://www.readbyqxmd.com/read/27421270/new-pharmacological-agents-to-aid-smoking-cessation-and-tobacco-harm-reduction-what-has-been-investigated-and-what-is-in-the-pipeline
#16
REVIEW
Emma Beard, Lion Shahab, Damian M Cummings, Susan Michie, Robert West
A wide range of support is available to help smokers to quit and to aid attempts at harm reduction, including three first-line smoking cessation medications: nicotine replacement therapy, varenicline and bupropion. Despite the efficacy of these, there is a continual need to diversify the range of medications so that the needs of tobacco users are met. This paper compares the first-line smoking cessation medications with (1) two variants of these existing products: new galenic formulations of varenicline and novel nicotine delivery devices; and (2) 24 alternative products: cytisine (novel outside Central and Eastern Europe), nortriptyline, other tricyclic antidepressants, electronic cigarettes, clonidine (an anxiolytic), other anxiolytics (e...
October 2016: CNS Drugs
https://www.readbyqxmd.com/read/27373649/efficient-n-acyldopamine-synthesis
#17
Yotaro Matsumoto, Akihiro Ito, Motonari Uesugi, Atsushi Kittaka
N-Acyldopamines are endogenous analogs of capsaicin that exhibit cannabinoid-like activities and were identified from brain extracts. Among them, N-arachidonoyldopamine (AADA) and N-oleoyldopamine (ODA) were characterized as transient receptor potential vanilloid type V1 channel (TRPV1) ligands. Recently, it was shown that N-acyldopamines may possess diverse physiological roles in addition to their ligand activities. To study the multiple functions and action mechanisms of endogenous N-acyldopamines, a simple and efficient method of N-acyldopamine synthesis was investigated...
2016: Chemical & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/27320243/pharmacological-hypothermia-a-potential-for-future-stroke-therapy
#18
Kaiyin Liu, Hajra Khan, Xiaokun Geng, Jun Zhang, Yuchuan Ding
Mild physical hypothermia after stroke has been associated with positive outcomes. Despite the well-studied beneficial effects of hypothermia in the treatment of stroke, lack of precise temperature control, intolerance for the patient, and immunosuppression are some of the reasons which limit its clinical translation. Pharmacologically induced hypothermia has been explored as a possible treatment option following stroke in animal models. Currently, there are eight classes of pharmacological agents/agonists with hypothermic effects affecting a multitude of systems including cannabinoid, opioid, transient receptor potential vanilloid 1 (TRPV1), neurotensin, thyroxine derivatives, dopamine, gas, and adenosine derivatives...
June 2016: Neurological Research
https://www.readbyqxmd.com/read/27318096/fatty-acid-amide-hydrolase-inhibition-for-the-symptomatic-relief-of-parkinson-s-disease
#19
Marta Celorrio, Diana Fernández-Suárez, Estefanía Rojo-Bustamante, Víctor Echeverry-Alzate, María J Ramírez, Cecilia J Hillard, José A López-Moreno, Rafael Maldonado, Julen Oyarzábal, Rafael Franco, María S Aymerich
Elements of the endocannabinoid system are strongly expressed in the basal ganglia where they suffer profound rearrangements after dopamine depletion. Modulation of the levels of the endocannabinoid 2-arachidonoyl-glycerol by inhibiting monoacylglycerol lipase alters glial phenotypes and provides neuroprotection in a mouse model of Parkinson's disease. In this study, we assessed whether inhibiting fatty acid amide hydrolase could also provide beneficial effects on the time course of this disease. The fatty acid amide hydrolase inhibitor, URB597, was administered chronically to mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and probenecid (MPTPp) over 5weeks...
October 2016: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/27296152/cannabidiol-modulates-fear-memory-formation-through-interactions-with-serotonergic-transmission-in-the-mesolimbic-system
#20
Christopher Norris, Michael Loureiro, Cecilia Kramar, Jordan Zunder, Justine Renard, Walter Rushlow, Steven R Laviolette
Emerging evidence suggests that the largest phytochemical component of cannabis, cannabidiol (CBD), may possess pharmacotherapeutic properties in the treatment of neuropsychiatric disorders. CBD has been reported to functionally interact with both the mesolimbic dopamine (DA) and serotonergic (5-HT) receptor systems. However, the underlying mechanisms by which CBD may modulate emotional processing are not currently understood. Using a combination of in vivo electrophysiological recording and fear conditioning in rats, the present study aimed to characterize the behavioral, neuroanatomical, and pharmacological effects of CBD within the mesolimbic pathway, and its possible functional interactions with 5-HT and DAergic transmission...
November 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
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