The endogenous cannabinoid system and the treatment of marijuana dependence

Piomelli, Daniele

doi:10.1016/j.neuropharm.2004.07.018

Cited by 39 publications

(36 citation statements)

References 62 publications

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“…O 2-AG é agonista total CB 1 /CB 2 24,26,27,29 ; a anandamida é agonista parcial CB 1 /CB 2 e agonista total (com baixa afinidade) TRPV1 24,26,27,29 . Embora tenha menor afinidade para os receptores canabinoides 29 , dada a concentração elevada de 2-AG (concentrações 200x superiores à anandamida), este parece ser o principal endocanabinoide [23][24][25]29,38,42,45 . Os endocanabinoides são uma das exceções à lei da polarização dinâmica, proposta por Ramon e Cajal em 1891, que postula que a comunicação interneural procede dos terminais axonais pré-sinápticos para dendritos pós--sinápticos 28,46,47 ; diferentemente dos neurotransmissores clássicos, funcionam como mensageiros retrógados extracelulares, sendo liberados do neurônio pós-sináptico para atuar nos CB 1 pré-sinápticos de forma autócrina e parácri-na 7,24,25,28,38 .…”

Section: Endocanabinoidesunclassified

“…A principal via de síntese de anandamida é a "transacilação-fosfodiesterase": a N-aciltransferase (NAT) converte fosfatidiletanolamina e fosfatidilcolina em N-araquidonilfosfatidiletanolamina (NAPE) 23,[25][26][27]41,42,45 -a N-acilação da fosfatidiletanolamina constitui o passo limitante 26,42 ; segue-se a hidrólise do NAPE pela N-araquidonil-fosfatidil-etanolamina--fosfolipase-D (NAPE-FLD), gerando anandamida 23,[25][26][27]41,42,45 (Figura 1).…”

Section: Sínteseunclassified

“…A NAT é regulada pelo Ca 2+ (necessário para a sua ativação) (Figura 1) e AMPc/PKA (atividade enzimática aumentada pela fosforilação) 25,42,45 . A NAPE-FLD está constitutivamente ativa, localizando-se, sobretudo, no retículo endoplasmáti-co dos neurônios pré-sinápticos 23,42 , mas também em pós--sinápticos 39,42,48 .…”

Section: Sínteseunclassified

“…Essa via também é Ca 2+ -dependente 26 (Figura 2). Vias alternativas envolvem: fosfolipase A 1 /FLC-liso-inositolfosfato-específica, lipase hormonossensível e uma fosfatase de lipídeos 23,42,45 . A ativação de TRPV1 pós-sinápticos pela anandamida poderá constituir um mecanismo de feedback regulatório, inibindo a DAGLα e diminuindo a produção de 2-AG 23,40 .…”

Section: Sínteseunclassified

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Neurobiologia da Cannabis: do sistema endocanabinoide aos transtornos por uso de Cannabis

Costa

Maia

Orlandi-Mattos

et al. 2011

J. bras. psiquiatr.

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rESUMo objetivos: Diante das lacunas na efetividade das terapêuticas para transtornos por uso de Cannabis, a droga ilícita mais consumida no mundo, este trabalho propõe-se a rever os conhecimentos sobre o substrato neuroanatômico, biomolecular e celular do sistema endocanabinoide, descrever os mecanismos de neuroplasticidade dependente dos canabinoides e relacioná-los com a neurobiologia dos transtornos por uso de Cannabis (abuso e dependên-cia). Métodos: Recorreu-se às bases de dados Medline, Scopus e ISI Web of Knowledge; as palavras-chave pesquisadas foram "Cannabis", "neurobiology", "endocannabinoid system", "endocannabinoids", "receptors, cannabinoid", "neuronal plasticity", "long-term synaptic depression", "long-term potentiation", "marijuana abuse" e "tetrahydrocannabinol". Foram incluídos 80 trabalhos nesta revisão. Discussão: A distribuição neuroanatômica, celular e biomolecular do sistema endocanabinoide adequa-se perfeitamente às suas funções de neuromodulação (via neuroplasticidade e metaplasticidade), nomeadamente em vias relacionadas aos transtornos por uso de substâncias. Os canabinoides exógenos perturbam essas funções. Conclusão: O sistema endocanabinoide contribui para a definição de setpoints em diversas vias neuronais, incluindo vias cruciais na instalação de transtornos por uso de substâncias; com o uso de Cannabis, esses setpoints tornar-se-ão mais permissivos, facilitando os transtornos por uso de Cannabis. Os avanços no entendimento da neurobiologia da Cannabis abrem uma janela de oportunidades para novas estratégias terapêuticas nos transtornos por uso de Cannabis. aBStraCt objectives: Given the challenges arising from the poor effectiveness of therapies for

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Section: Endocanabinoidesunclassified

Section: Sínteseunclassified

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Neurobiologia da Cannabis: do sistema endocanabinoide aos transtornos por uso de Cannabis

Costa

Maia

Orlandi-Mattos

et al. 2011

J. bras. psiquiatr.

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“…Both are endogenous ligands of cannabinoid (CB) receptors, thus mimicking several actions of the natural Cannabis sativa component delta-9-tetrahydrocannabinol (THC), which accounts for the majority of the reproductive hazards in marijuana users (Piomelli, 2004). Two are the cannabinoid receptors that respond to THC and that have been identified and cloned.…”

Section: The Endocannabinoid Systemmentioning

confidence: 99%

Regulation of male fertility by the endocannabinoid system

Battista¹,

Rapino²,

Tommaso³

et al. 2008

Molecular and Cellular Endocrinology

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Please cite this article as: Battista, N., Rapino, C., Di Tommaso, M., Bari, M., Pasquariello, N., Maccarrone, M., Regulation of male fertility by the endocannabinoid system, Molecular and Cellular Endocrinology (2007Endocrinology ( ), doi:10.1016Endocrinology ( /j.mce.2008 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Page 1 of 35A c c e p t e d M a n u s c r i p t A c c e p t e d M a n u s c r i p t 2 AbstractMammalian conception is a complex process regulated by both sexual behavior and reproductive performance. Alcohol, marijuana and tobacco are among the main factors which affect negatively fertility in women and men. Several studies have demonstrated that marijuana impairs the male copulatory activity, and that smokers of this illegal drug show reduced fertility due, for instance, to decrease in sperm concentration, defective sperm function or alteration of sperm morphology.The discovery of endocannabinoids and all components responsible for their metabolism has allowed to collect valuable information on the effects of these endogenous lipids, able to mimic the actions of delta-9-tetrahydrocannabinol (THC), in reproductive functions.The purpose of this review is to describe the actions of cannabinoids and endocannabinoids on the control of procreation and hormonal release during the fertilization process in males.Page 3 The endocannabinoid systemThe best characterized endocannabinoids are N-arachidonoylethanolamine (anandamide, AEA) and 2-arachidonoylglycerol (2-AG). Both are endogenous ligands of cannabinoid (CB) receptors, thus mimicking several actions of the natural Cannabis sativa component delta-9-tetrahydrocannabinol (THC), which accounts for the majority of the reproductive hazards in marijuana users (Piomelli, 2004). Two are the cannabinoid receptors that respond to THC and that have been identified and cloned. These receptors, indicated as CB1 and CB2, belong to the superfamily of G-protein coupled receptors (Matsuda et al., 1990;Munro et al., 1993). CB1 has been found mainly in the central nervous system, but it is also present in ovary, uterine endometrium, testis, vas deferens, urinary bladder, and other peripheral endocrine and neurological tissues (McPartland, 1999;McPartland and Pruitt, 1999). CB2 receptors have been identified mainly in immune cells (Munro et al., 1993) but are expressed also in brainstem (Van Sickle et al., 2005).Biochemical studies have revealed that AEA is produced by a transacylasephosphodiesterase-mediated synthesis, starting from the precursor Narachidonoylphosphatidylethanolamine (NArPE) through the action of N-archidonylphosphatidylethanolamine (NAPE) h...

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New vistas for treatment of obesity and diabetes? Endocannabinoid signalling and metabolism in the modulation of energy balance

et al. 2012

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Growing evidence suggests that pathological overactivation of the endocannabinoid system (ECS) is associated with dyslipidemia, obesity and diabetes. Indeed, this signalling system acting through cannabinoid receptors has been shown to function both centrally and peripherally to regulate feeding behaviour as well as energy expenditure and metabolism. Consequently, modulation of these receptors can promote significant alterations in body weight and associated metabolic profile. Importantly, blocking cannabinoid receptor type 1 function has been found to prevent obesity and metabolic dysfunction in various murine models and in humans. Here we provide a detailed account of the known physiological role of the ECS in energy balance, and explore how recent studies have delivered novel insights into the potential targeting of this system as a therapeutic means for treating obesity and related metabolic disorders.

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The endogenous cannabinoid system and the treatment of marijuana dependence

Cited by 39 publications

References 62 publications

Neurobiologia da Cannabis: do sistema endocanabinoide aos transtornos por uso de Cannabis

Neurobiologia da Cannabis: do sistema endocanabinoide aos transtornos por uso de Cannabis

Regulation of male fertility by the endocannabinoid system

New vistas for treatment of obesity and diabetes? Endocannabinoid signalling and metabolism in the modulation of energy balance

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