Köfalvi.E. - Cannabinoids and the Brain.pdf - ANGIELSKIE - mikke2

Cannabinoids and the Brain

Attila Köfalvi

Editor

Cannabinoids and the Brain

Editorial and Chapters 1, 9, 14, 22 were proofed

by Zsóﬁ a Gombár

With 44 illustrations and 16 tables

Attila Köfalvi

Center for Neurosciences of Coimbra

Faculty of Medicine

University of Coimbra

Coimbra, 3000-045 Portugal

ISBN-13: 978-0-387-74348-6

e-ISBN-13: 978-0-387-74349-3

Library of Congress Control Number: 2007933065

permission of the publisher (Springer Science+Business Media, LLC, 233 Spring Street, New York, NY

10013, USA), except for brief excerpts in connection with reviews or scholarly analysis. Use in connection

with any form of information storage and retrieval, electronic adaptation, computer software, or by similar

or dissimilar methodology now known or hereafter developed is forbidden.

The use in this publication of trade names, trademarks, service marks, and similar terms, even if they are

not identified as such, is not to be taken as an expression of opinion as to whether or not they are subject

to proprietary rights.

Printed on acid-free paper

9 8 7 6 5 4 3 2 1

springer.com

Editorial

Did you know that if you take aspirin or some other type of painkillers, you simply

upregulate your endocannabinoid system against your endovanilloid system? If it

happens to be a completely new piece of information to you, then this book is for

you! Seriously speaking, the first part of the book you are holding in your hands is

an exhaustive source of scientific reviews on the molecular biology, pharmacology,

anatomy, and physiology of the endocannabinoid and related lipid mediator sys-

tems. The second part of the book, however, covers the involvement of these signal-

ing systems in metabolic, neurological, and psychiatric disorders, and gives an

overview on clinical trials and on recent advances in cannabinoid-based medicine.

Therefore, the target audience for this book are (a) physicians, especially endo-

crinologists, neurologists, psychiatrists, and neuroscientists who want to update

their knowledge about metabolism, basic brain physiology, molecular biology, and

pathology and about novel therapeutic opportunities; (b) graduate and undergradu-

ate students who also wish to broaden their knowledge about endocrinology, neuro-

science, neurology, and psychiatry, or may need orientation to determine their future

scientific goals; (c) politicians and health care employers who hesitate whether

marijuana or cannabinoid-based medications should be legalized; and last but not

least, (d) journalists who can help the scientists to convey their message to a larger

audience. All the authors of the present volume are world’s leading neuroscientists

and physicians, who are also regarded to be pioneers in the cannabinoid research

area. Here I would like to gratefully thank them for all their altruistic contributions,

and for sparing their precious time on this work.

The very first idea of writing this book occurred to me in 2005 when I had an

interesting conversation with a neurologist professor from the USA, after his excit-

ing lecture about the impact of adenosine receptors on epilepsy. I asked him

whether he would be interested in the role of cannabinoid receptors also besides

adenosine receptors. I noticed a faint note of indignation in his answer when he

said: “No, I do not treat drug addicts, but epilepsy patients.” He was apparently

unaware of those facts which are extensively reviewed in this book, especially the

CB 1 receptor that is believed to have the highest density among metabotropic recep-

tors in the nervous tissue, and, together with its endogenous agonists, they represent

a unique signaling system, which seems to be a goldmine of therapeutic targets

against many neuropsychiatric disorders. The reaction of the professor may be

Editorial

excusable, since the body’s own cannabinoid system as well as the body’s opioid

system or the nicotinic receptors were discovered in the quest to find the specific

targets for drugs of abuse, such as marijuana, morphine, heroin, and tobacco’s nico-

tine. Importantly, the last 16 years of constant research has discovered a much

broader role for endocannabinoids than for the opioid or nicotinic acetylcholine

signaling. Nevertheless, this role does not seem to receive sufficient recognition by

those who otherwise should find it important in their professional activity. At

present, I have the growing belief that the endocannabinoid system and related sys-

tems of lipid mediators, such as eicosanoids and endovanilloids, constitute a major

modulator/messenger supersystem, which is at least as important as the monoam-

inergic, purinergic, and cholinergic systems. Furthermore, these modulator systems

work hand in hand, and thus they cannot be viewed as solitary therapeutic targets.

The borders between classical pharmacological areas are likely to be forgotten.

Therefore we, the authors, consider ourselves extremely fortunate to make this

book happen and to disseminate challenging up-to-date reviews on the role of can-

nabinoids in the brain.

Now I would like to take the opportunity of addressing a few challenging ideas

to the cannabinoid research area. There are some minor and major problems can-

nabinoid researchers normally encounter, which could be easily alleviated. For

instance, it seems to be ironic and even ridiculous to some extent that permission is

required for using certain cannabinoid research tools, such as

∆

9 -THC and for what purpose.

Absurdly enough, at that point of time, I still had not received the shipment of the

compound from the pharmaceutical company due to permission issues. It is no

more than pure hypocrisy, knowing that there are several other even more selective,

potent, and efficacious cannabinoid ligands available, causing even more expressed

effects than

∆

9 -THC requires permis-

sion, it being the major constituent of marijuana. Nonetheless, the price of

∆

9 -THC in animals. It is understandable that

∆

9 -THC

and HU-210 appears to be so high, especially considering the remarkably little buy-

able amounts, that selling these products for research purposes without permission

would not represent a gross criminal risk.

Normalization of chemical names would also be desirable. For instance,

researchers may face a considerable challenge to find all the articles of the popular

nonselective potent cannabinoid agonist WIN55212-2 in searchable databases,

since the ligand is variously termed WIN-55,212-2, WIN 55212-2, WIN 55,212-2,

WIN-2 or R-(+)-WIN55212, R-WIN55212, R-WIN 55212, R-WIN 55,212, etc.

with all possible permutations. The same is true for other compounds, such as the

popular CB 1 receptor antagonist AM251. It is frequently used as AM 251, and a

search for the terms AM and 251 in a database may result in a lot of additional

unrelated articles. Thus, combining two or more ligands in one search is definitely

a vain idea. The problem could be solved with only a slight common effort to stand-

ardize chemical names. It is also unfortunate that several old-fashioned journals

still force the authors to use the long cumbersome chemical names of cannabinoid

∆

9 -THC and its potent

derivative HU-210. More importantly, their experimental usage is further hindered

by other rules in certain places. I will never forget the incident when the police

appeared in my lab, inquiring how I had used

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