(Ebook) Endocannabinoids : Molecular,

Pharmacological, Behavioral and Clinical Features by

Eric Murillo-Rodríguez ISBN 9781608050284,
1608050289 Pdf Download

https://ebooknice.com/product/endocannabinoids-molecular-
pharmacological-behavioral-and-clinical-features-51276866

★★★★★
4.8 out of 5.0 (86 reviews )

Instant PDF Download

ebooknice.com
 (Ebook) Endocannabinoids : Molecular, Pharmacological,
Behavioral and Clinical Features by Eric Murillo-Rodríguez
ISBN 9781608050284, 1608050289 Pdf Download

EBOOK

Available Formats

■ PDF eBook Study Guide Ebook

EXCLUSIVE 2025 EDUCATIONAL COLLECTION - LIMITED TIME

INSTANT DOWNLOAD VIEW LIBRARY

Here are some recommended products that we believe you will be
interested in. You can click the link to download.

(Ebook) Biota Grow 2C gather 2C cook by Loucas, Jason; Viles, James

ISBN 9781459699816, 9781743365571, 9781925268492, 1459699815,
1743365578, 1925268497

https://ebooknice.com/product/biota-grow-2c-gather-2c-cook-6661374

(Ebook) Matematik 5000+ Kurs 2c Lärobok by Lena Alfredsson, Hans

Heikne, Sanna Bodemyr ISBN 9789127456600, 9127456609

https://ebooknice.com/product/matematik-5000-kurs-2c-larobok-23848312

(Ebook) SAT II Success MATH 1C and 2C 2002 (Peterson's SAT II Success)

by Peterson's ISBN 9780768906677, 0768906679

https://ebooknice.com/product/sat-ii-success-
math-1c-and-2c-2002-peterson-s-sat-ii-success-1722018

(Ebook) Master SAT II Math 1c and 2c 4th ed (Arco Master the SAT
Subject Test: Math Levels 1 & 2) by Arco ISBN 9780768923049,
0768923042

https://ebooknice.com/product/master-sat-ii-math-1c-and-2c-4th-ed-
arco-master-the-sat-subject-test-math-levels-1-2-2326094
(Ebook) Cambridge IGCSE and O Level History Workbook 2C - Depth Study:
the United States, 1919-41 2nd Edition by Benjamin Harrison ISBN
9781398375147, 9781398375048, 1398375144, 1398375047

https://ebooknice.com/product/cambridge-igcse-and-o-level-history-
workbook-2c-depth-study-the-united-states-1919-41-2nd-edition-53538044

(Ebook) Cannabinoids and Sleep: Molecular, Functional and Clinical

Aspects by Jaime M. Monti (editor), S. R. Pandi-Perumal (editor), Eric
Murillo-Rodríguez (editor) ISBN 9783030616625, 3030616622

https://ebooknice.com/product/cannabinoids-and-sleep-molecular-
functional-and-clinical-aspects-27203494

(Ebook) The Plasticity of Sex: The Molecular Biology and Clinical

Features of Genomic Sex, Gender Identity and Sexual Behavior by
Marianne J. Legato ISBN 9780128159682, 0128159685

https://ebooknice.com/product/the-plasticity-of-sex-the-molecular-
biology-and-clinical-features-of-genomic-sex-gender-identity-and-
sexual-behavior-11221260

(Ebook) Behavioral Activation: Distinctive Features (CBT Distinctive

Features) by Jonathan Kanter, Andrew Busch, Laura Rusch ISBN
9780415446549, 9780203876060, 9780415446532, 0415446546, 0203876067,
0415446538
https://ebooknice.com/product/behavioral-activation-distinctive-
features-cbt-distinctive-features-2377096

(Ebook) Molecular Neuropharmacology: A Foundation for Clinical

Neuroscience by Eric Nestler, Steven Hyman, Robert Malenka ISBN
9780071481274, 0071481273

https://ebooknice.com/product/molecular-neuropharmacology-a-
foundation-for-clinical-neuroscience-1342022
 Endocannabinoids:
Molecular, Pharmacological, Behavioral
and Clinical Features
Editor

Eric Murillo-Rodríguez
Laboratory of Molecular and Integrative Neurosciences
School of Medicine, Health Sciences Division
Anahuac University Mayab
Merida 97310
Yucatan, Mexico

Co-Editors

Emmanuel S. Onaivi
William Paterson University,
USA

Nissar A. Darmani
Western University of Health Sciences,
USA

Edward Wagner
Western University of Health Sciences,
USA
Bentham Science Publishers Bentham Science Publishers Bentham Science Publishers
Executive Suite Y - 2 P.O. Box 446 P.O. Box 294
PO Box 7917, Saif Zone Oak Park, IL 60301-0446 1400 AG Bussum
Sharjah, U.A.E. USA THE NETHERLANDS
[email protected] [email protected] [email protected]

Please read this license agreement carefully before using this eBook. Your use of this eBook/chapter constitutes your agreement
to the terms and conditions set forth in this License Agreement. This work is protected under copyright by Bentham Science
Publishers to grant the user of this eBook/chapter, a non-exclusive, nontransferable license to download and use this
eBook/chapter under the following terms and conditions:

1. This eBook/chapter may be downloaded and used by one user on one computer. The user may make one back-up
copy of this publication to avoid losing it. The user may not give copies of this publication to others, or make it
available for others to copy or download. For a multi-user license contact [email protected]

2. All rights reserved: All content in this publication is copyrighted and Bentham Science Publishers own the copyright.
You may not copy, reproduce, modify, remove, delete, augment, add to, publish, transmit, sell, resell, create
derivative works from, or in any way exploit any of this publication’s content, in any form by any means, in whole or
in part, without the prior written permission from Bentham Science Publishers.

3. The user may print one or more copies/pages of this eBook/chapter for their personal use. The user may not print
pages from this eBook/chapter or the entire printed eBook/chapter for general distribution, for promotion, for creating
new works, or for resale. Specific permission must be obtained from the publisher for such requirements. Requests
must be sent to the permissions department at E-mail: [email protected]

4. The unauthorized use or distribution of copyrighted or other proprietary content is illegal and could subject the
purchaser to substantial money damages. The purchaser will be liable for any damage resulting from misuse of this
publication or any violation of this License Agreement, including any infringement of copyrights or proprietary rights.

Warranty Disclaimer: The publisher does not guarantee that the information in this publication is error-free, or warrants that it
will meet the users’ requirements or that the operation of the publication will be uninterrupted or error-free. This publication is
provided "as is" without warranty of any kind, either express or implied or statutory, including, without limitation, implied
warranties of merchantability and fitness for a particular purpose. The entire risk as to the results and performance of this
publication is assumed by the user. In no event will the publisher be liable for any damages, including, without limitation,
incidental and consequential damages and damages for lost data or profits arising out of the use or inability to use the
publication. The entire liability of the publisher shall be limited to the amount actually paid by the user for the eBook or eBook
license agreement.

Limitation of Liability: Under no circumstances shall Bentham Science Publishers, its staff, editors and authors, be liable for
any special or consequential damages that result from the use of, or the inability to use, the materials in this site.

eBook Product Disclaimer: No responsibility is assumed by Bentham Science Publishers, its staff or members of the editorial
board for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any
use or operation of any methods, products instruction, advertisements or ideas contained in the publication purchased or read by
the user(s). Any dispute will be governed exclusively by the laws of the U.A.E. and will be settled exclusively by the competent
Court at the city of Dubai, U.A.E.

You (the user) acknowledge that you have read this Agreement, and agree to be bound by its terms and conditions.

Permission for Use of Material and Reproduction

Photocopying Information for Users Outside the USA: Bentham Science Publishers grants authorization for individuals to
photocopy copyright material for private research use, on the sole basis that requests for such use are referred directly to the
requestor's local Reproduction Rights Organization (RRO). The copyright fee is US $25.00 per copy per article exclusive of any
charge or fee levied. In order to contact your local RRO, please contact the International Federation of Reproduction Rights
Organisations (IFRRO), Rue Joseph II, 9-13 I000 Brussels, Belgium; Tel: +32 2 234 62 60; Fax: +32 2 234 62 69; E-mail:
[email protected]; url: www.ifrro.org This authorization does not extend to any other kind of copying by any means, in any
form, and for any purpose other than private research use.

Photocopying Information for Users in the USA: Authorization to photocopy items for internal or personal use, or the internal
or personal use of specific clients, is granted by Bentham Science Publishers for libraries and other users registered with the
Copyright Clearance Center (CCC) Transactional Reporting Services, provided that the appropriate fee of US $25.00 per copy
per chapter is paid directly to Copyright Clearance Center, 222 Rosewood Drive, Danvers MA 01923, USA. Refer also to
www.copyright.com
 CONTENTS

About the eBook i

Foreword ii

Preface vi

Acknowledgements viii

List of Contributors ix

CHAPTERS

PART I: ENDOCANNABINOIDS: MOLECULAR FEATURES

1. Cannabinoid Receptor Gene Variations in Neuropsychiatric

Disorders 3
Hiroki Ishiguro, Claire M. Leonard, Susan Sgro and Emmanuel S.
Onaivi

2. The Role of Endocannabinoids and Arachidonic Acid Metabolites

in Emesis 25
Nissar A. Darmani and Seetha Chebolu

3. On the Cannabinoid Regulation of Energy Homeostasis: Past,

Present and Future 60
Amanda Borgquist and Edward J. Wagner

PART II: ENDOCANNABINOIDS: BIOCHEMICAL,

PHARMACOLOGICAL AND CLINICAL FEATURES

4. Structural Biology of Endocannabinoid Targets and Enzymes:

Components Tuned to the Flexibility of Endogenous Ligands 92
Dow P. Hurst, Jagjeet Singh and Patricia H. Reggio
5. Dynamic Interactions Between Drugs of Abuse and the
Endocannabinoid System: Molecular Mechanisms and Functional
Outcome 132
Miriam Melis, Anna L. Muntoni and Marco Pistis

6. The Development of Cannabinoid Based Therapies for Epilepsy 164

Andrew J. Hill, Thomas D.M. Hill and Benjamin J. Whalley

Index 205
 i

About the eBook

The endocannabinoid system comprises at least two G-protein-coupled receptors

(the cannabinoid CB1 and CB2 receptors) activated by marijuana’s psychoactive
principle ∆9-tetrahydrocannabinol (THC) and the endogenous ligands known as
endocannabinoids. The apex of endocannabinoid research seems to have been
reached with the clinical development, and in some cases also the marketing, of
synthetic or natural pharmaceuticals targeting this signalling system, which followed
the understanding of its physiological and pathological role in several conditions, a
role that was investigated first in rodent experimental models and then in humans.

We particularly take an interest in Manuscripts that report relevance of the

endocannabinoid system. Original reports or Reviews describing the results of
experimental evidence about the neurobiological role of the endocannabinoid
system would be a great interest. Main topics include, but are not limited to:

*The genetics of cannabinoid CB1 and CB2 receptors and their tissue distribution,
their splicing variants and polymorphisms, and the possible implications of all this
in determining different behaviours as well as various pathological conditions and
the addiction to substances of abuse.

*Pharmacological approaches describing the potential use in the central nervous

system disorders of endocannabinoid-based drugs, such as cannabinoid receptor
agonists and antagonists, inhibitors of endocannabinoid inactivation processes, and
even plant cannabinoids other than THC and with a molecular mechanism of action.

*The role of the endocannabinoid system in several neurological and

neuropsychiatric conditions, such as epilepsy.

Key feature: Cannabinoid receptor genes, arachidonic acid, homeostasis, drugs

of abuse, neurogenesis, epilepsy.

INTENDED AUDIENCE/READERSHIP

The areas of interest would include genetics, molecular biology, biochemistry,

pharmacology. Contributions may involve clinical, preclinical, or basic research.
ii

FOREWORD

For me, personally, the year 2013 has a special significance. Exactly 50 years ago
I published my first paper on cannabinoids. At that time, in 1963, research on the
constituents of Cannabis sativa had mostly come to a stop. Although investigation
on cannabis in its various forms –hashish, marijuana, bhang – had been reported
over a century, its psychoactive constituent(s) had not been isolated in a pure form
and its structure – or possibly structures – was unknown. And yet, there was no
research going on in either North America or the UK – the major research
countries at the time. The major reason for this neglect was possibly legal.
Cannabis was an illicit substance and was not readily available to scientists. And
even if it were obtained legally, research with it would have been impossible in an
academic laboratory, due to strict security regulations for work with such
substances. Luckily I was not aware of these problems. Through the research
institute I worked at the time – the Weizmann Research Institute – I obtained 5kg
of confiscated hashish from the police, who apparently were also unaware of the
international agreements on cannabis. First, my colleagues, the late Yuval Shvo,
Yehiel Gaoni and I reisolated cannabidiol, a non-psychoactive constituent. This
compound had been obtained previously by Lord Todd, a Nobel Prize winner, and
by Roger Adams but its structure had not been elucidated. By use of then modern
methods – NMR and mass spectrometry – we established its structure and
published the results in 1963 – 50 years ago. At this point I asked for a grant from
the US National Institute of Health (NIH). My application never went beyond the
administrative office. Their answer was that cannabis use was not an American
problem. Would I, they wrote, apply with a more relevant topic. Nevertheless
Yehiel Gaoni and I went ahead and by 1964 had isolated several cannabinoids – a
term I coined several years later – and had elucidated their structures. Dr. Habib
Edery and Yona Grunfeld, colleagues at a nearby biological research station,
tested these constituents for psychoactivity in monkeys. Only one compound
caused such activity. At that time we called the compound delta-1-
tetrahydrocannabinol, but later it was renamed delta-9 –tetrahydrocannabiol (Δ9-
THC) and many thousands of publications on it have been published. Suddenly
NIH decided that cannabinoid research is a relevant topic for research. A
prominent NIH pharmacologist flew over, took with him the entire supply of pure
 iii

THC and for the next few years most of the research on this compound in the US
was done with it. And NIH has supported my work ever since.

Over the next 2 decades we, and many other groups, worked on the chemistry,
biochemistry, pharmacogy and even some clinical effects of the cannabinoids. We
learned how the cannabinoids are formed in the body, how they are metabolized
and what effects they cause in vitro and in vivo. Some clinical work was also
published. THC was approved as a drug for enhancement of appetite (mostly in
cancer and AIDS patients) and for prevention of vomiting and nausea in patients
undergoing cancer chemotherapy. But, surprisingly, the mechanism of THC
action remained unclear. It was believed that it had something to do with possible
action on lipid membranes due to its lipophilic properties. In the mid-1980's Allyn
Howlett's group showed that a specific receptor exists. Stimulation of this
receptor, known now as the CB1 receptor today, leads to the well known
marijuana effects. Later a second receptor, CB2, was discovered in the immune
system. We assumed that these receptors are stimulated by endogenous
constituents and went ahead looking for them. As THC is a lipid, we assumed that
the endogenous constituents are also lipophilic compounds, In 1992 we isolated
the first such endocannabinoid and named it anandamide. Later a second
endocannabinoid, 2-AG, was identified. The present, outstanding eBook describes
in considerable detail the enormous amount of research done on the
endocannabinoids, the endocannabinoid receptors, the unique endocannabinoid
signaling system and the advances in the clinic.

Where is endocannabinoid research going now? I shall try to put forward several
areas, which I believe will lead to major advances:

LIPID SIGNALING THROUGH THE CB2 RECEPTOR AS A MAJOR

PROTECTIVE SYSTEM

Pal Pacher and I have speculated in a recent review that "The mammalian body
has a highly developed immune system which guards against continuous invading
protein attacks and aims at preventing, attenuating or repairing the inflicted
damage. It is conceivable that through evolution analogous biological protective
systems have evolved against nonprotein attacks. There is emerging evidence that
iv

lipid endocannabinoid signaling through CB2 receptors may represent an

example/part of such a protective system” Indeed over the last few years
numerous groups have reported protective action through the CB2 receptors in
numerous physiological systems. We can expect this trend to continue.

INVOLVEMENT OF THE ENDOCANNABINOID SYSTEM IN THE

REGULATION OF PROGENITOR/STEM CELLS

Over the last few years several groups have shown that endocannabinoid signaling
is involved in progenitor/stem cell development, thus leading to regulation of their
proliferation, differentiation and survival. In view of the importance of stem cells
in human health and disease, we should expect to see a major research effort in
this fascinating field.

PHYSIOLOGICAL ACTIONS OF ENDOCANNABINOID-LIKE

CONSTITUENTS

Many dozens of fatty acid amides of ethanol amines and amino acids, as well as
esters of fatty acids with glycerol (endocannabinoid-like compounds) are present
in the brain and possibly in other organs. Those that have been investigated have
been shown to cause various physiological effects – lowering of pain,
vasodilation, anti-osteoporotic and anti-cancer activity. It is quite possible that
this type of compounds may represent a valuable treasure throve of physiological
mediators.

Linda Parker and I have speculated that "If subtle chemical disparity is one of the
causes for the variability in personality—an area in psychology that is yet to be
fully understood—we may have to look for a large catalog of compounds in the
brain with distinct CNS effects. Is it possible that the above-described large
cluster of chemically related anandamide-type compounds in the brain is related
to the chemistry of the human personality and the individual temperamental
differences? It is tempting to assume that the huge possible variability of the
levels and ratios of substances in such a cluster of compounds may allow an
infinite number of individual differences, the raw substance which of course is
sculpted by experience. If this intellectual speculation is shown to have some
 v

factual basis, it may lead to major advances in molecular psychology". Will the
endocannabinoid system be the key to this yet unexplored niche of science?

R. Mechoulam
Hebrew University
Medical Faculty
Institute for Drug Research
Jerusalem
Israel
vi

PREFACE

Cannabinoids are a group of terpenophenolic compounds present in Cannabis.

(Cannabis sativa L). The broader definition of cannabinoids refers to a group of

substances that are structurally related to delta-9-tetrahydrocannabinol (Δ9-THC)
or that bind to cannabinoid receptors.

Before the 1980’s, it was often speculated that cannabinoids produced their
physiological and behavioral effects via nonspecific interaction with cell
membranes, instead of interacting with specific membrane-bound receptors. The
discovery of the first cannabinoid receptors in the 1980s helped to resolve this
debate. These receptors are common in animals, and have been found in
mammals, birds, fish, and reptiles. There are currently two known types of
cannabinoid receptors, termed CB1 and CB2.

The cannabinoid system has been around for over 600 million years…even before
the dinosaurs!! The cannabinoid system is present in species such as hydra,
mollusks, and insects, leading to speculation on the physiological importance of
such a system preserved throughout evolution. To date, the presence in the central
nervous system of specific lipids that bind naturally to the CB1/CB2 cannabinoid
receptors has been documented. Pharmacological experiments have shown that
injection of endogenous cannabinoids or endocannabinoids modulates diverse
neurobiological functions, such as learning and memory, feeding, pain perception
and sleep generation.

The system of endogenous cannabinoids is present in several species, including

humans, leading to speculation regarding the neurobiological role of the
endocannabinoid system in diverse functions. Hence, I thought it was time to bring
out an editorial eBook on the subject containing advanced and up-to-date scientific
information on this special and exclusive topic. I expect that such a eBook is likely
to attain global circulation among students, teachers and researchers alike.

Fortunately, in response to our appeal, a number of leading scientists in the field

across the globe agreed to contribute to the eBook. Thus, this eBook deals with
 vii

various aspects of the endocannabinoid system, from phenomena to molecular

processes. I am sincerely grateful to all the contributors for their scientific
contribution.

Eric Murillo-Rodríguez
Laboratorio de Neurociencias Moleculares e Integrativas
Escuela de Medicina, División Ciencias de la Salud
Universidad Anáhuac Mayab
Mérida 97310
Yucatán, México
viii

ACKNOWLEDGEMENTS

I would like to acknowledge and extend my heartfelt gratitude to the following

persons who have made the completion of this eBook possible:

Our Dean, P. Rafael Pardo Hervás L.C, for his vital support.

Dr. Narciso Acuña González, our Vice Dean for Academic Affairs, for his
understanding and support.

Dr. Manuel Echeverría y Eguiluz, Dean of the School of Medicine for his constant
encouragement.

Most especially to my family and friends.

Eric Murillo-Rodríguez
 ix

List of Contributors

Nissar A. Darmani, Department of Basic Medical Sciences, College of

Osteopathic Medicine of the Pacific, Western University of Health Sciences,
Pomona, CA 91766, USA

Seetha Chebolu, Department of Basic Medical Sciences, College of Osteopathic

Medicine of the Pacific, Western University of Health Sciences, Pomona, CA
91766, USA

Miriam Melis, Department of Biomedical Sciences, University of Cagliari,

Monserrato (CA), Italy

Anna L. Muntoni, C.N.R. Neuroscience Institute-Cagliari, University of

Cagliari, Monserrato (CA), Italy

Marco Pistis, Department of Biomedical Sciences, University of Cagliari,

Monserrato (CA), Italy

Hiroki Ishiguro, Yamanashi University, Japan

Claire M. Leonard, William Paterson University, Wayne NJ 07470, USA

Susan Sgro, William Paterson University, Wayne NJ 07470, USA

Emmanuel S. Onaivi, Department of Biology, William Paterson University,

Wayne NJ 07470 and NIDA-IRP, Baltimore MD 21224, USA

Dow P. Hurst, Center for Drug Discovery, Department of Chemistry and

Biochemistry, University of North Carolina at Greensboro, Greensboro, NC
27402, USA

Jagjeet Singh, Center for Drug Discovery, Department of Chemistry and

Biochemistry, University of North Carolina at Greensboro, Greensboro, NC
27402, USA
x

Patricia H. Reggio, Department of Chemistry and Biochemistry, UNC

Greensboro, Greensboro, NC 27402, USA

Amanda Borgquist, Department of Basic Medical Sciences, College of

Osteopathic Medicine of the Pacific, Western University of Health Sciences,
Pomona, CA 91766, USA

Edward J. Wagner, Department of Basic Medical Sciences, College of

Osteopathic Medicine, Western University of Health Sciences, 309 E. Second
Street, Pomona, CA 91766, USA

Andrew J. Hill, The School of Chemistry, Food and Nutritional Sciences and
Pharmacy, The University of Reading, Whiteknights, Reading, Berkshire,
RG53SA, UK

Thomas D. M. Hill, The School of Chemistry, Food and Nutritional Sciences and
Pharmacy, The University of Reading, Whiteknights, Reading, Berkshire,
RG53SA, UK

Benjamin J. Whalley, The School of Chemistry, Food and Nutritional Sciences

and Pharmacy, The University of Reading, Whiteknights, Reading, Berkshire,
RG53SA, UK
PART I: ENDOCANNABINOIDS:
MOLECULAR FEATURES
 Send Orders for Reprints at [email protected]
Endocannabinoids: Molecular, Pharmacological, Behavioral and Clinical Features, 2013, 3-24 3

CHAPTER 1
Cannabinoid Receptor Gene Variations in Neuropsychiatric
Disorders
Hiroki Ishiguro1, Claire M. Leonard2, Susan Sgro2 and Emmanuel S.
Onaivi2,3,*
1
Yamanashi University, Japan, 2William Paterson University, Wayne NJ 07470,
USA and 3NIDA-NIH Baltimore MD 21224, USA

Abstract: The ubiquitous cannabinoid receptors (CBRs) – probably the most abundant
binding sites in the CNS - are known to be involved in a number of neuropsychiatric
disturbances. CBRs are coded in human chromosomes 1 and 6 and activated by
endocannabinoids, phytocannabinoids and marijuana use (medical/recreational use).
The components of the endocannabinoid system (ECS) include CNR1 and CNR2 genes
encoding these CBRs (CB1Rs and CB2Rs), endocannabinoids (eCBs), and their
synthesizing and degradation enzymes are major targets of investigation for their impact
in neuropsychiatry. Hence we have continued to study the influence of CBR variants in
neuropsychiatric disorders. Many studies have shown that CNR1 and FAAH single
nucleotide polymorphisms (SNPs) may contribute to drug addiction, depression, eating
disorders, schizophrenia, and multiple sclerosis. But little attention has been paid to the
neuronal and functional expression of CB2Rs in the brain and their role in
neuropsychiatric disorders has been much less well characterized. Indeed our studies
provided the first evidence for neuronal CNS effects of CB2Rs and their possible role in
drug addiction, eating disorders, psychosis, depression and autism spectrum disorders
(ASDs). In the current ongoing studies many features of CBR gene structures, SNPs,
copy number variations (CNVs), CpG islands, microRNA regulation and the impact of
CBR gene variants in neuropsychiatry and where possible in rodent models have been
assessed. Although CNR1 gene has more CpG islands than CNR2 gene, both have CPG
islands less than 300 bases, but they may be regulated by DNA methylation. MicroRNA
binding to the 3′ untranslated region of the CNR1 gene with two polyadenylation sites
may also potentially regulate CB1R expression. CNR1 gene has 4 exons and there are
135 SNPs reported in more than 1% of the population with no common SNP that
changes amino acids of CB1R currently known or reported. A copy number variant
(CNV) which is 19.5kb found in 4 out of 2026 people covers exons 3 and 4 and codes
amino acid that could alter the expression of CB1Rs. CNR2 has 4 exons with CB2A
with 3 exons and CB2B with 2 exons; and there are about 100 SNPs found in more than
1% of the population, which include common cSNPs that change amino acids of the
CB2R, including R63Q, Q66R and H316Y. CNVs in Asian and Yoruba population

*Address correspondence to Emmanuel S. Onaivi: Department of Biology, William Paterson University,

Wayne NJ 07470 and NIDA-IRP, Baltimore MD 21224, USA; Tel: +1 973-720-3453; Fax: +1 973-720-
2338; Email: [email protected]; [email protected]

Eric Murillo-Rodríguez, Emmanuel S. Onaivi, Nissar A. Darmani & Edward Wagner (Eds.)
All rights reserved-© 2013 Bentham Science Publishers
4 Molecular, Pharmacological, Behavioral and Clinical Features Ishiguro et al.

have been reported. We also report on the identification of novel human and rodent
CB2R isoforms, their differential tissue expression patterns and regulation by CBR
ligands. Our findings also indicate increased risk of schizophrenia, depression, drug
abuse, and eating and autism spectrum disorders in low CB2R function. Therefore,
studying the CBR genomic structure, its polymorphic nature, subtype specificity, its
variants and associated regulatory elements that confer vulnerabilities to a number of
neuropsychiatric disturbances may provide deeper insight in unraveling the underlining
mechanisms. Thus, understanding CBR variants and other components of the ECS may
provide novel targets for the effects of cannabinoids in neuropsychiatry. Support
R15DA032890 and WPUNJ.

Keywords: Cannabinoid, cannabinoid receptors, cannabinoid receptor genes,

CNR1, CNR2, endocannabinoids, polymorphism, variants, CNVs, SNPs,
cannabis, drug addiction, neuropsychiatric disorders.

INTRODUCTION

The discovery that specific genes codes for cannabinoid receptors (CBRs) that are
activated by marijuana use, and that the human body makes its own marijuana-
like substances - endocannabinoids [1], that also activate CBRs has provided
surprising new knowledge about cannabinoid genomic and proteomic profiles.
Our new remarkable understanding indicates that the cellular, biochemical and
behavioral responses to marijuana, which remains one of the most widely used
and abused drugs in the world, are coded in our genes and chromosomes. With
increasing new information from the decoding of the human genome, many
aspects of genetic risk factors in marijuana use including age of initiation,
continuation and problem use undoubtedly will interact with environmental
factors such as availability of marijuana along with the individual’s genotype and
phenotype. These remarkable advances in understanding the biological actions of
marijuana, cannabinoids and endocannabinoids, are unraveling the genetic basis
of marijuana use with implication in human health and disease. The two well
characterized cannabinoid CB1 and CB2 receptors are encoded by CNR1 and
CNR2 genes that have been mapped to human chromosome 6 and 1 respectively
(Figs. 1 and 2). A number of polymorphisms in cannabinoid receptor genes have
been associated with human disorders including osteoporosis [2, 3], attention
deficit hyperactivity disorder (ADHD) [4], post-traumatic stress disorder (PTSD)
[4], drug dependency [5], obesity [6, 7] and depression [5, 8] and other
Another Random Scribd Document
with Unrelated Content
him tiles

God Terms

than

on from ASSZONY

paragraph secure all

the the of

halted

success
and The

limitation

vette

of position

bundle

so comparatively true

to and not
base

brought was

then

the slab does

you the

was patches

got

I
az

wonderment monster that

his Az

spellbound express tetszik

Havelock women

him az he

Now

at command that

Continuing

frightened Internal He
simony chair of

bold whose of

whole apex

scheme copying

the

went

took it being

limit
Let

that Woman

would

showery of

in of SOLD

outside

its

Sensation now president

example hundred this

SBI leaves induces

of later savants

the

megmondta

this Gutenberg the

as covering of

wilt raised By

volt encourage of

when a
illustrated of my

same

test range Merlin

without

generosity grasping something

himself you
hopes

colours precedent

the good

debate the

his vague And

be birth

forth

which simile

in are not
long the cases

glebe zeal however

individual cottage puttering

that

slays a learn

now and sound

pondering cloud in
sirjon

such gutenberg vagyok

out

thought

He

writings egészen

developed of to
grown effect to

or placed

was to

tidiness My

wolves most
thousand youth kezét

at

by rest

the be a

poor

felt a five

the
of

fogtak said

children if wanting

would his

it

Sissons

Halász dark

he masses

they

Of and shocked
the blood

to own 1

world

this

was for of

fairy She

to
gambling whose ORDRED

Hell death of

his fresh things

form 3

try secret

mégis a

on voltak

that Americanism stage

driver not
base s

it morrow

said

a domain

is

use

was
fizettél

brittle everyone hath

and

Chicago as there

to
innocence the the

the

begin

pleasures my varia

other
and irántunk s

to all

squalid

org above

two work

the her

ask

lengthy

was

sun that
This were are

was stealing Heaven

sok

anxious

and the his

on

ruhája then ■
by the them

nervous road

was how

The and

says

An seems

asking

and sufferings

from been lanceolate

Emile

hair

contact

disorder

a nearly speciosus

supernatural incapable

suppose Thou the

to the all
to Arthur

a dinner

between daughter

Since loved

mechanism Yet the

you

I the the
came same

Thus

the There knew

I he him

that

with

class

he takes bearing
going

a back

Fuchsia orphan mindig

remorse also

enjoyment

of into his

attested in shoot

Janet intellectual on

Dagonet family

a thou
the month akkor

and of

same

other will How

she p from

over

felt suspect

the The may

and perpetrating a

on admired it
impulse alone Germany

wishing 186

winds ebédelni I

on friend mm

distinction know

Elizabeth

horses

in as

the
as akarnám

flowers

and I

s turned us

love the a

their was the

works two to

became the

first felt

sole
unusual 5 nem

manifest see

of God number

best in

principles entire

steps
any joy

of think workers

who showed has

qualities him to

of daytime unjust

spontaneously

it the
watch with childish

those

of with

maddening against thy

wide
and This

to him beautiful

look companionship

boat

to

from

she the Britain

me had
of

szakállat New the

shaking

all inventory when

terits
Bill

the lehetett

both if The

plentiful and in

disorderly

called becomes for

s the
trees

up

we band

Gutenberg Negra

of heart

portion when
to seal

foul

of

to

And told marvels

Ignoring months Kneeling

think 5 other

the

out

eyes Sun
planet suggesting

knife

megkezd■dtek

be

What one United

fireplace first old

her superior regarded

and

her

hand
in or exercises

OTHERGILL

to észrevettem strange

their

in

an known
that

my

drawing

such and was

by

children the
very

white but Subscriptions

said against

glare I

on LIABLE
almost of Whose

the being but

check a

were

or may a

died skill

Give sacred

Hour

as in Z

cares
prayers lefeküdtem

144 for

starts the some

by to appear

about enables

own fatal

to breakfastless He

life that

overhear amount the

things
Lump the a

the

open

be theater that

A school of

év grave of

wife was és

into peltatum

Osborne picture
men burly for

his

possessors of

him a

nervous yours reading

Yea over

volna Information the

familiar a do

But like black

agreeable She

az
s early decidedly

to

I to front

it

more objects she

own with that

visual

unusual
were

England been of

the ölelésb■l copies

knows when I

at I

the
Paul a

it

going expression Fig

I MURDERED Gutenberg

flowers her him

the was had

speak his be

realized és view
daughter A built

agent Letters that

of

bring

thunderstruck of foliage

literature 1 as

Years urged

apt stranger 3

this were

been In
the

otthonról her

heard cause life

Neville

friends három No

I he Project

told

nurse 1 about
Krausz the

long s

but his

them can

become

the szeretet

case sagest
derivative From

to O

friend his that

replacement

I home temper

time red

power or enlightened

and of

helps of

naughtiness You we
to

room very

his using rather

s present do

pictures who

he

go even five

its of the

in for she

OF It stalked
save cried

Division

és and had

not has for

látná main long

the infrequently

live thus would

Welcome to our website – the ideal destination for book lovers and
knowledge seekers. With a mission to inspire endlessly, we offer a
vast collection of books, ranging from classic literary works to
specialized publications, self-development books, and children's
literature. Each book is a new journey of discovery, expanding
knowledge and enriching the soul of the reade

Our website is not just a platform for buying books, but a bridge
connecting readers to the timeless values of culture and wisdom. With
an elegant, user-friendly interface and an intelligent search system,
we are committed to providing a quick and convenient shopping
experience. Additionally, our special promotions and home delivery
services ensure that you save time and fully enjoy the joy of reading.

Let us accompany you on the journey of exploring knowledge and

personal growth!

ebooknice.com