THC: moderation during implantation

Piomelli, Daniele

doi:10.1038/nm0104-19

Cited by 15 publications

(9 citation statements)

References 11 publications

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“…In addition, the highest FAAH activity and the lowest AEA concentrations in peripheral T-cells are reported on day 21 of gestation [116], a period that temporally coincides with the putative window of implantation in humans. Taken together, these data strengthen the hypothesis that high FAAH activity and low AEA levels are among the factors that determine the success of implantation, raising concerns about marijuana use in pregnant women [117]. In keeping with this view, FAAH activity and expression are under control of wellknown regulators of fertility.…”

Section: Therapeutic Potential Of Enhancers Of Faah Activity and Exprsupporting

confidence: 75%

Fatty Acid Amide Hydrolase: A Potential Target for Next Generation Therapeutics

Maccarrone

2006

CPD

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Endocannabinoids are amides, esters and ethers of long chain polyunsaturated fatty acids, which act as new lipid mediators. Anandamide (N-arachidonoylethanolamine; AEA) and 2-arachidonoylglycerol are the main endogenous agonists of cannabinoid receptors, able to mimic several pharmacological effects of Delta(9)-tetrahydrocannabinol, the active principle of Cannabis sativa preparations like hashish and marijuana. The activity of AEA at its receptors is limited by cellular uptake through a specific membrane transporter, followed by intracellular degradation by a fatty acid amide hydrolase (FAAH). Growing evidence demonstrates that FAAH is the critical regulator of the endogenous levels of AEA, suggesting that it may serve as an attractive therapeutic target for the treatment of human disorders. In particular, FAAH inhibitors may be next generation therapeutic drugs of potential value for the treatment of pathologies in the central nervous system and in the periphery. Here, the potential applications of these inhibitors for human disease will be reviewed, with an emphasis on the properties of hydro(pero)xy-anandamides. In fact, these oxygenated derivatives of AEA are the most powerful inhibitors of FAAH of natural origin as yet discovered. In addition, new insights into the promoter region of FAAH gene will be presented, and the therapeutic potential of mimetics of transcription factors of this gene in the management of human infertility will be discussed.

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Section: Therapeutic Potential Of Enhancers Of Faah Activity and Exprsupporting

confidence: 75%

Fatty Acid Amide Hydrolase: A Potential Target for Next Generation Therapeutics

Maccarrone

2006

CPD

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“…Anandamide (N-arachidonoylethanolamine, AEA) is an endogenously produced cannabinoid-like lipid mediator [7] that mimics several actions of the natural Cannabis sativa component Δ 9 -tetrahydrocannabinol, which accounts for the majority of the reproductive hazards in marijuana users [8], [9]. AEA binds to and activates two classical G protein (Gi/o)–coupled cell-surface cannabinoid receptors, cannabinoid receptor type 1 (CB1) and type 2 (CB2) [10], [11].…”

Section: Introductionmentioning

confidence: 99%

The Effect of Anandamide on Uterine Nitric Oxide Synthase Activity Depends on the Presence of the Blastocyst

et al. 2011

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Nitric oxide production, catalyzed by nitric oxide synthase (NOS), should be strictly regulated to allow embryo implantation. Thus, our first aim was to study NOS activity during peri-implantation in the rat uterus. Day 6 inter-implantation sites showed lower NOS activity (0.19±0.01 pmoles L-citrulline mg prot−1 h−1) compared to days 4 (0.34±0.03) and 5 (0.35±0.02) of pregnancy and to day 6 implantation sites (0.33±0.01). This regulation was not observed in pseudopregnancy. Both dormant and active blastocysts maintained NOS activity at similar levels. Anandamide (AEA), an endocannabinoid, binds to cannabinoid receptors type 1 (CB1) and type 2 (CB2), and high concentrations are toxic for implantation and embryo development. Previously, we observed that AEA synthesis presents an inverted pattern compared to NOS activity described here. We adopted a pharmacological approach using AEA, URB-597 (a selective inhibitor of fatty acid amide hydrolase, the enzyme that degrades AEA) and receptor selective antagonists to investigate the effect of AEA on uterine NOS activity in vitro in rat models of implantation. While AEA (0.70±0.02 vs 0.40±0.04) and URB-597 (1.08±0.09 vs 0.83±0.06) inhibited NOS activity in the absence of a blastocyst (pseudopregnancy) through CB2 receptors, AEA did not modulate NOS on day 5 pregnant uterus. Once implantation begins, URB-597 decreased NOS activity on day 6 implantation sites via CB1 receptors (0.25±0.04 vs 0.40±0.05). While a CB1 antagonist augmented NOS activity on day 6 inter-implantation sites (0.17±0.02 vs 0.27±0.02), a CB2 antagonist decreased it (0.17±0.02 vs 0.12±0.01). Finally, we described the expression and localization of cannabinoid receptors during implantation. In conclusion, AEA levels close to and at implantation sites seems to modulate NOS activity and thus nitric oxide production, fundamental for implantation, via cannabinoid receptors. This modulation depends on the presence of the blastocyst. These data establish cannabinoid receptors as an interesting target for the treatment of implantation deficiencies.

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“…Studies in mouse models demonstrate that under normal physiological conditions, endocannabinoid signaling through CB 1 is crucial to development of embryos and their oviductal transport, as well as their homing and implantation in the receptive uterus. This figure is adapted from Piomelli (2004) since there is evidence that women with elevated peripheral AEA levels have spontaneous pregnancy loss (Maccarrone et al 2000. A considerable amount of early pregnancy loss occurs due to either preimplantation embryonic death or implantation failure resulting from asynchronous embryonic development and failure of the uterus to differentiate to the receptive stage (Wilcox et al 1988).…”

Section: Resultsmentioning

confidence: 99%

Behavioral Neurobiology of the Endocannabinoid System

2009

Current Topics in Behavioral Neurosciences

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About this seriesCurrent Topics in Behavioral Neurosciences provides critical and comprehensive discussions of the most significant areas of behavioral neuroscience research, written by leading international authorities. Each volume offers an informative and contemporary account of its subject, making it an unrivalled reference source. Titles in this series are available in both print and electronic formats.With the development of new methodologies for brain imaging, genetic and genomic analyses, molecular engineering of mutant animals, novel routes for drug delivery, and sophisticated cross-species behavioral assessments, it is now possible to study behavior relevant to psychiatric and neurological diseases and disorders on the physiological level. The Behavioral Neurosciences series focuses on ''translational medicine'' and cutting-edge technologies. Preclinical and clinical trials for the development of new diagnostics and therapeutics as well as prevention efforts are covered whenever possible. This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilm or in any other way, and storage in data banks. Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September 9, 1965, in its current version, and permission for use must always be obtained from Springer. Violations are liable to prosecution under the German Copyright Law. The use of general descriptive names, registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Cover illustration: Artistic representation of oscillatory synchrony and timing of neurons in networks by Gyorgy BuzsakiCover design: WMXDesign GmbH, Heidelberg, GermanyPrinted on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com) PrefaceIt is abundantly clear that the endocannabinoid signalling system is ubiquitously expressed throughout the animal kingdom from simple invertebrates to man, and that it is represented in almost every cell type.The components of the system in relation to the synthesis and metabolism of the endocannabinoids and their biological targets are beginning to be unravelled, but the degree of complexity involved is enormous. This is particularly true for endocannabinoid signalling in the central nervous system, which is the subject of this volume.In the book, a variety of authors, who are all very active researchers in the field, provide current accounts of the roles of the endocannabinoid system in normal brain physiology in relation to the neurobiology of essential behaviors and in a number of central disease states.The first part provides a background and "tool box", detailing what is known about the endocannabinoids them...

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THC: moderation during implantation

Cited by 15 publications

References 11 publications

Fatty Acid Amide Hydrolase: A Potential Target for Next Generation Therapeutics

Fatty Acid Amide Hydrolase: A Potential Target for Next Generation Therapeutics

The Effect of Anandamide on Uterine Nitric Oxide Synthase Activity Depends on the Presence of the Blastocyst

Behavioral Neurobiology of the Endocannabinoid System

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