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cannabis brain glutamate

Mohamed A Sherif, Jose A Cortes-Briones, Mohini Ranganathan, Patrick D Skosnik
Preclinical and clinical data suggest that the cannabinoid and glutamatergic systems are implicated in the pathophysiology of schizophrenia (SZ), the prototypical psychotic disorder. This has led to distinct "cannabis" and "ketamine" models of SZ, respectively. However, these two models need not be mutually exclusive. Indeed, in several brain regions implicated in the putative neural circuitry of SZ (e.g., hippocampus, frontal cortex, cerebellum), cannabinoid receptor type 1 (CB1Rs) and glutamate N-methyl-D-aspartate receptors (NMDARs) have direct and indirect interactions...
December 15, 2017: European Journal of Neuroscience
Silvia Rigucci, Lijing Xin, Paul Klauser, Philipp S Baumann, Luis Alameda, Martine Cleusix, Raoul Jenni, Carina Ferrari, Maurizio Pompili, Rolf Gruetter, Kim Q Do, Philippe Conus
RATIONALE: Recent studies have shown that cannabis may disrupt glutamate (Glu) signaling depressing Glu tone in frequent users. Current evidence have also consistently reported lower Glu-levels in various brain regions, particularly in the medial prefrontal cortex (mPFC) of chronic schizophrenia patients, while findings in early psychosis (EP) are not conclusive. Since cannabis may alter Glu synaptic plasticity and its use is a known risk factor for psychosis, studies focusing on Glu signaling in EP with or without a concomitant cannabis-usage seem crucial...
January 2018: Psychopharmacology
J O Owolabi, S Y Olatunji, A J Olanrewaju
BACKGROUND: Caffeine and cannabis are globally consumed and abused psychoactive substances. While caffeine is legally used in various forms, including in tea and coffee as beverages, it is also consumed in soda and energy drinks as additives. Cannabis, on the other hand, is considered illegal in most countries; albeit, it is being consumed globally particularly by adolescents. PURPOSE: The adolescent stage marks a critical stage of brain development and maturation...
May 2017: Annals of Neurosciences
Erica Zamberletti, Marina Gabaglio, Massimo Grilli, Pamela Prini, Alberto Catanese, Anna Pittaluga, Mario Marchi, Tiziana Rubino, Daniela Parolaro
Cannabis use has been frequently associated with sex-dependent effects on brain and behavior. We previously demonstrated that adult female rats exposed to delta-9-tetrahydrocannabinol (THC) during adolescence develop long-term alterations in cognitive performances and emotional reactivity, whereas preliminary evidence suggests the presence of a different phenotype in male rats. To thoroughly depict the behavioral phenotype induced by adolescent THC exposure in male rats, we treated adolescent animals with increasing doses of THC twice a day (PND 35-45) and, at adulthood, we performed a battery of behavioral tests to measure affective- and psychotic-like symptoms as well as cognition...
September 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Marco Colizzi, Philip McGuire, Roger G Pertwee, Sagnik Bhattacharyya
Use of cannabis or delta-9-tetrahydrocannabinol (Δ9-THC), its main psychoactive ingredient, is associated with psychotic symptoms or disorder. However, the neurochemical mechanism that may underlie this psychotomimetic effect is poorly understood. Although dopaminergic dysfunction is generally recognized as the final common pathway in psychosis, evidence of the effects of Δ9-THC or cannabis use on dopaminergic measures in the brain is equivocal. In fact, it is thought that cannabis or Δ9-THC may not act on dopamine firing directly but indirectly by altering glutamate neurotransmission...
May 2016: Neuroscience and Biobehavioral Reviews
Peter S Freestone, Xi Hau Wu, Gabriel de Guzman, Janusz Lipski
Endocannabinoids (eCBs) are cannabis-like substances produced in the brain where their primary function is to regulate synaptic transmission by inhibiting neurotransmitter release in a retrograde fashion. We have recently demonstrated a novel mechanism regulating GABAergic transmission from neurons in the Substantia Nigra pars reticulata (SNr) to dopaminergic neurons in the Substantia Nigra pars compacta (SNc) mediated by eCBs. Production of eCBs was initiated by spillover of glutamate, yet the source of the glutamate was not determined (Freestone et al...
November 15, 2015: European Journal of Pharmacology
Tiziana Rubino, Daniela Parolaro
The regular use of cannabis during adolescence is of particular concern because use by this age group seems to be associated with an increased likelihood of deleterious consequences, as reported by several epidemiologic studies. However, despite their unquestionable value, epidemiologic data are inconclusive. Modeling the adolescent phase in animals appears to be a useful approach to investigate the impact of cannabis use on the adolescent brain. In these models, adolescent cannabinoid exposure has been reported to cause long-term impairment in specific components of learning and memory and to have differential effects on anxiety, social behavior, and depressive-like signs...
April 1, 2016: Biological Psychiatry
Mathieu Caudron, Benjamin Rolland, Sylvie Deheul, Pierre Alexis Geoffroy, Pierre Thomas, Ali Amad
BACKGROUND: Catatonia is a severe motor syndrome found in approximately 10% of all acute psychiatric hospital admissions. It can occur in various psychiatric diseases. The authors report the first case report of catatonia during cannabis withdrawal. CASE PRESENTATION: Mr. A, a 32-year-old man, reported to have smoked approximately 20 g of cannabis daily since the age of 11. Mr. A was incarcerated and was reported 3 weeks later to the medical department for having completely ceased talking and eating...
2016: Substance Abuse
Deepmala, John Slattery, Nihit Kumar, Leanna Delhey, Michael Berk, Olivia Dean, Charles Spielholz, Richard Frye
N-acetylcysteine (NAC) is recognized for its role in acetaminophen overdose and as a mucolytic. Over the past decade, there has been growing evidence for the use of NAC in treating psychiatric and neurological disorders, considering its role in attenuating pathophysiological processes associated with these disorders, including oxidative stress, apoptosis, mitochondrial dysfunction, neuroinflammation and glutamate and dopamine dysregulation. In this systematic review we find favorable evidence for the use of NAC in several psychiatric and neurological disorders, particularly autism, Alzheimer's disease, cocaine and cannabis addiction, bipolar disorder, depression, trichotillomania, nail biting, skin picking, obsessive-compulsive disorder, schizophrenia, drug-induced neuropathy and progressive myoclonic epilepsy...
August 2015: Neuroscience and Biobehavioral Reviews
Felipe V Gomes, Ana Carolina Issy, Frederico R Ferreira, Maria-Paz Viveros, Elaine A Del Bel, Francisco S Guimarães
BACKGROUND: Preclinical and clinical data suggest that cannabidiol (CBD), a major non-psychotomimetic compound from Cannabis sativa, induces antipsychotic-like effects. However, the antipsychotic properties of repeated CBD treatment have been poorly investigated. Behavioral changes induced by repeated treatment with glutamate N-methyl-D-aspartate receptor (NMDAR) antagonists have been proposed as an animal model of schizophrenia-like signs. In the present study, we evaluated if repeated treatment with CBD would attenuate the behavioral and molecular modifications induced by chronic administration of one of these antagonists, MK-801...
March 2015: International Journal of Neuropsychopharmacology
Anna Chiarlone, Luigi Bellocchio, Cristina Blázquez, Eva Resel, Edgar Soria-Gómez, Astrid Cannich, José J Ferrero, Onintza Sagredo, Cristina Benito, Julián Romero, José Sánchez-Prieto, Beat Lutz, Javier Fernández-Ruiz, Ismael Galve-Roperh, Manuel Guzmán
The CB1 cannabinoid receptor, the main molecular target of endocannabinoids and cannabis active components, is the most abundant G protein-coupled receptor in the mammalian brain. Of note, CB1 receptors are expressed at the synapses of two opposing (i.e., GABAergic/inhibitory and glutamatergic/excitatory) neuronal populations, so the activation of one and/or another receptor population may conceivably evoke different effects. Despite the widely reported neuroprotective activity of the CB1 receptor in animal models, the precise pathophysiological relevance of those two CB1 receptor pools in neurodegenerative processes is unknown...
June 3, 2014: Proceedings of the National Academy of Sciences of the United States of America
Trinidad M M Saez, María P Aronne, Laura Caltana, Alicia H Brusco
The endocannabinoid system, composed of cannabinoid receptors, endocannabinoids, and synthesis and degradation enzymes, is present since early stages of brain development. During this period, the endocannabinoid system is involved in the regulation of neural progenitor proliferation and specification as well as the migration and differentiation of pyramidal neurons and interneurons. Marijuana consumption during pregnancy represents a serious risk in relation to the fetal brain development since Δ(9) -tetrahidrocannabinol, the main active compound of cannabis, can reach the fetus through placenta and hemato-encephalic barrier...
May 2014: Journal of Neurochemistry
Rongqing Chen, Jian Zhang, Ni Fan, Zhao-Qian Teng, Yan Wu, Hongwei Yang, Ya-Ping Tang, Hao Sun, Yunping Song, Chu Chen
Marijuana has been used for thousands of years as a treatment for medical conditions. However, untoward side effects limit its medical value. Here, we show that synaptic and cognitive impairments following repeated exposure to Δ(9)-tetrahydrocannabinol (Δ(9)-THC) are associated with the induction of cyclooxygenase-2 (COX-2), an inducible enzyme that converts arachidonic acid to prostanoids in the brain. COX-2 induction by Δ(9)-THC is mediated via CB1 receptor-coupled G protein βγ subunits. Pharmacological or genetic inhibition of COX-2 blocks downregulation and internalization of glutamate receptor subunits and alterations of the dendritic spine density of hippocampal neurons induced by repeated Δ(9)-THC exposures...
November 21, 2013: Cell
Erica Zamberletti, Sarah Beggiato, Luca Steardo, Pamela Prini, Tiziana Antonelli, Luca Ferraro, Tiziana Rubino, Daniela Parolaro
Although several findings indicate an association between adolescent cannabis abuse and the risk to develop schizophrenia later in life, the evidence for a causal relationship is still inconclusive. In the present study, we investigated the emergence of psychotic-like behavior in adult female rats chronically exposed to delta-9-tetrahydrocannabinol (THC) during adolescence. To this aim, female Sprague-Dawley rats were treated with THC during adolescence (PND 35-45) and, in adulthood (PND 75), a series of behavioral tests and biochemical assays were performed in order to investigate the long-term effects of adolescent THC exposure...
March 2014: Neurobiology of Disease
Sergiy Sylantyev, Thomas P Jensen, Ruth A Ross, Dmitri A Rusakov
G protein-coupled receptor (GPR) 55 is sensitive to certain cannabinoids, it is expressed in the brain and, in cell cultures, it triggers mobilization of intracellular Ca(2+). However, the adaptive neurobiological significance of GPR55 remains unknown. Here, we use acute hippocampal slices and combine two-photon excitation Ca(2+) imaging in presynaptic axonal boutons with optical quantal analysis in postsynaptic dendritic spines to find that GPR55 activation transiently increases release probability at individual CA3-CA1 synapses...
March 26, 2013: Proceedings of the National Academy of Sciences of the United States of America
K A Gleason, S G Birnbaum, A Shukla, S Ghose
Clinical studies report associations between cannabis use during adolescence and later onset of schizophrenia. We examined the causal relationship between developmental cannabinoid administration and long-term behavioral and molecular alterations in mice. Mice were administered either WIN 55,212-2 (WIN), a cannabinoid receptor 1 (CB1) agonist or vehicle (Veh) during adolescence (postnatal day 30-35) or early adulthood (postnatal day 63-70). Behavioral testing was conducted after postnatal day 120 followed by biochemical assays...
November 27, 2012: Translational Psychiatry
Anand Gururajan, Elizabeth E Manning, Maren Klug, Maarten van den Buuse
OBJECTIVE: There is considerable evidence to suggest that the abuse of illicit drugs, particularly cannabis and methamphetamine, has aetiological roles in the pathogenesis of psychosis and schizophrenia. Factors that may increase susceptibility to the propsychotic effects of these drugs include the age at which the abuse starts as well as family history of genetic polymorphisms relevant to the pathophysiology of this disorder. However, the neurobiological mechanisms involved in drug abuse-associated psychosis remain largely unclear...
December 2012: Australian and New Zealand Journal of Psychiatry
Nina B L Urban, Diana Martinez
Neuroimaging studies have been crucial in understanding changes in the various neurotransmitter systems implicated in addiction in the living human brain. Predominantly reduced striatal dopamine transmission appears to play an important role in psychostimulant, alcohol and heroin addiction, while addiction to cannabis may be mediated primarily by the endocannabinoid system. However, the study of other neurotransmitter systems likely involved in addiction, for example glutamate, has been limited by the number and quality of available radiotracers, and data on changes in these systems in the most common addictions are emerging only now...
June 2012: Psychiatric Clinics of North America
Jing Han, Philip Kesner, Mathilde Metna-Laurent, Tingting Duan, Lin Xu, Francois Georges, Muriel Koehl, Djoher Nora Abrous, Juan Mendizabal-Zubiaga, Pedro Grandes, Qingsong Liu, Guang Bai, Wei Wang, Lize Xiong, Wei Ren, Giovanni Marsicano, Xia Zhang
Impairment of working memory is one of the most important deleterious effects of marijuana intoxication in humans, but its underlying mechanisms are presently unknown. Here, we demonstrate that the impairment of spatial working memory (SWM) and in vivo long-term depression (LTD) of synaptic strength at hippocampal CA3-CA1 synapses, induced by an acute exposure of exogenous cannabinoids, is fully abolished in conditional mutant mice lacking type-1 cannabinoid receptors (CB(1)R) in brain astroglial cells but is conserved in mice lacking CB(1)R in glutamatergic or GABAergic neurons...
March 2, 2012: Cell
Iain S McGregor, Michael T Bowen
Drug use typically occurs within a social context, and social factors play an important role in the initiation, maintenance and recovery from addictions. There is now accumulating evidence of an interaction between the neural substrates of affiliative behavior and those of drug reward, with a role for brain oxytocin systems in modulating acute and long-term drug effects. Early research in this field indicated that exogenous oxytocin administration can prevent development of tolerance to ethanol and opiates, the induction of stereotyped, hyperactive behavior by stimulants, and the withdrawal symptoms associated with sudden abstinence from drugs and alcohol...
March 2012: Hormones and Behavior
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