The Endocannabinoids: Functional Roles 

The Endocannabinoids: Functional Roles 
Posted by CN Staff on October 14, 2007 at 09:05:45 PT
Press Release
Source: EurekAlert
Washington, DC -- Cannabis (marijuana) is the most widely produced plant-based illicit drug worldwide and the illegal drug most frequently used in Europe. Its use increased in almost all EU countries during the 1990s, in particular among young people, including school students. Cannabis use is highest among 15- to 24-year-olds, with lifetime prevalence ranging for most countries from 20–40% (EMCDDA 2006). Recently there has been a new surge in the level of concern about potential social and health outcomes of cannabis use, although the available evidence still does not provide a clear-cut understanding of the issues.
Intensive cannabis use is correlated with non-drug-specific mental problems, but the question of co-morbidity is intertwined with the questions of cause and effect (EMCDDA 2006). Prevention is of importance in adolescents, which is underlined by evidence that early-onset cannabis-users (pre- to mid-adolescence) have a significantly higher risk of developing drug problems, including dependence (Von Sydow et al., 2002; Chen et al., 2005). The illegal status and wide-spread use of cannabis made basic and clinical cannabis research difficult in the past decades; on the other hand, it has stimulated efforts to identify the psychoactive constituents of cannabis. As a consequence, the endocannabinoid system was discovered, which was shown to be involved in most physiological systems – the nervous, the cardiovascular, the reproductive, the immune system, to mention a few. One of the main roles of endocannabinoids is neuroprotection, but over the last decade they have been found to affect a long list of processes, from anxiety, depression, cancer development, vasodilatation to bone formation and even pregnancy (Panikashvili et al., 2001; Pachter et al., 2006). Cannabinoids and endocannabinoids are supposed to represent a medicinal treasure trove which waits to be discovered.  What is The Endocannabinoid System? In the 1960s the constituent of the cannabis plant was discovered – named tetrahydrocannabinol, or THC – which causes the 'high' produced by it (Gaoni & Mechoulam, 1964). Thousands of publications have since appeared on THC. Today it is even used as a therapeutic drug against nausea and for enhancing appetite, and, surprisingly, has not become an illicit drug – apparently cannabis users prefer the plant-based marijuana and hashish. Two decades later it was found that THC binds to specific receptors in the brain and the periphery and this interaction initiates a cascade of biological processes leading to the well known marijuana effects. It was assumed that a cannabinoid receptor is not formed for the sake of a plant constituent (that by a strange quirk of nature binds to it), but for endogenous brain constituents and that these putative 'signaling' constituents together with the cannabinoid receptors are part of a new biochemical system in the human body, which may affect various physiological actions. In trying to identify these unknown putative signaling molecules, our research group in the 1990s was successful in isolating 2 such endogenous 'cannabinoid' components – one from the brain, named anandamide (from the word ´ananda, meaning ´supreme joy´ in Sanscrit), and another one from the intestines named 2-arachidonoyl glycerol (2-AG) (Devane et al., 1992; Mechoulam et al., 1995).  Neuroprotection The major endocannabinoid (2-AG) has been identified both in the central nervous system and in the periphery. Stressful stimuli – traumatic brain injury (TBI) for example – enhance brain 2-AG levels in mice. 2-AG, both of endogenous and exogenous origin, has been shown to be neuroprotective in closed head injury, ischemia and excitotoxicity in mice. These effects may derive from the ability of cannabinoids to act through a variety of biochemical mechanisms. 2-AG also helps repair the blood brain barrier after TBI. The endocannabinoids act via specific cannabinoid receptors, of which the CB1 receptors are most abundant in the central nervous system. Mice whose CB1 receptors are knocked out display slower functional recovery after TBI and do not respond to treatment with 2-AG. Over the last few years several groups have noted that CB2 receptors are also formed in the brain, particularly as a reaction to numerous neurological diseases, and are apparently activated by the endocannabinoids as a protective mechanism.Through evolution the mammalian body has developed various systems to guard against damage that may be caused by external attacks. Thus, it has an immune system, whose main role is to protect against protein attacks (microbes, parasites for example) and to reduce the damage caused by them. Analogous biological protective systems have also been developed against non-protein attacks, although they are much less well known than the immune system. Over the last few years the research group of Esther Shohami in collaboration with our group showed that the endocannabinoid system, through various biological routes, lowers the damage caused by brain trauma. Thus, it helps to attenuate the brain edema and the neurological injuries caused by it (Panikashvili et al., 2001; Panikashvili et al., 2006). Clinical Importance Furthermore it is assumed that the endocannabinoid system may be involved in the pathogenesis of hepatic encephalopathy, a neuropsychiatric syndrome induced by fulminant hepatic failure. Indeed in an animal model the brain levels of 2-AG were found to be elevated. Administration of 2-AG improved a neurological score, activity and cognitive function (Avraham et al., 2006). Activation of the CB2 receptor by a selective agonist also improved the neurological score. The authors concluded that the endocannabinoid system may play an important role in the pathogenesis of hepatic encephalopathy. Modulation of this system either by exogenous agonists specific for the CB2 receptors or possibly also by antagonists to the CB1 receptors may have therapeutic potential. The endocannabinoid system generally is involved in the protective reaction of the mammalian body to a long list of neurological diseases such as multiple sclerosis, Alzheimer's and Parkinson's disease. Thus, there is hope for novel therapeutic opportunities.Numerous additional endocannabinoids – especially various fatty acid ethanolamides and glycerol esters – are known today and regarded as members of a large ´endocannabinoid family´. Endogenous cannabinoids, the cannabinoid receptors and various enzymes that are involved in their syntheses and degradations comprise the endocannabinoid system. The endocannabinoid system acts as a guardian against various attacks on the mammalian body. Conclusion The above described research concerning the endocannabinoid-system is of importance in both basic science and in therapeutics:The discovery of the cannabis plant active constituent has helped advance our understanding of cannabis use and its effects.The discovery of the endocannabinoids has been of central importance in establishing the existence of a new biochemical system and its physiological roles – in particular in neuroprotection.These discoveries have opened the door for the development of novel types of drugs, such as THC for the treatment of nausea and for enhancing appetite in cachectic patients.The endocannabinoid system is involved in the protective reaction of the mammalian body to a long list of neurological diseases such as multiple sclerosis, Alzheimer's and Parkinson's disease which raises hope for novel therapeutic opportunities for these diseases. References Avraham Y, Israeli E, Gabbay E, et al. Endocannabinoids affect neurological and cognitive function in thioacetamide-induced hepatic encephalopathy in mice. Neurobiology of Disease 2006;21:237-245Chen CY, O´Brien MS, Anthony JC. Who becomes cannabis dependent soon after onset of use" Epidemiological evidence from the United States: 2000-2001. Drug and alcohol dependence 2005;79:11-22Devane WA, Hanus L, Breuer A, et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 1992;258:1946-1949[EMCDDA 2006] European Monitoring Centre for Drugs and Drug Addiction. The state of the drugs problem in Europe. Annual Report 2006 ( Y, Mechoulam R. Isolation, structure and partial synthesis of an active constituent of hashish. J Amer Chem Soc 1964;86:1646-1647Journal Interview 85: Conversation with Raphael Mechoulam. Addiction 2007;102:887-893Mechoulam R, Ben-Shabat S, Hanus L, et al. Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem Pharmacol 1995;50:83-90Mechoulam R, Panikashvili D, Shohami E. Cannabinoids and brain injury. Trends Mol Med 2002;8:58-61Pachter P, Batkai S, Kunos G. The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev 2006;58:389-462Panikashvili D, Simeonidou C, Ben-Shabat S, et al. An endogenous cannabinoid (2-AG) is neuroprotective after brain injury. Nature 2001;413:527-531Panikashvili D, Shein NA, Mechoulam R, et al. The endocannabinoid 2-AG protects the blood brain barrier after closed head injury and inhibits mRNA expression of proinflammatory cytokines. Neurobiol Disease 2006;22:257-264Von Sydow K, Lieb R, Pfister H, et al. What predicts incident use of cannabis and progression to abuse and dependence" A 4-year prospective examination of risk factors in a community sample of adolescents and young adults. Drug and alcohol dependence 2002;68:49-64Complete Title: The Endocannabinoids: Functional Roles and Therapeutic OpportunitiesContact: Professor Raphael Mechoulam: mechou College of Neuropsychopharmacology Source: EurekAlert (DC)Published: October 14, 2007Copyright: 2007 by AAAS, The Science SocietyContact: mechou Medical Marijuana Archives
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Comment #15 posted by aolbites on October 17, 2007 at 13:58:38 PT
heres a direct link since I sense Censorship [a search for Endocannabinoid on eurekalert won't pull up this article] Can find it with cannabinoid as the search term... Thats a bit odd don't you think?
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Comment #14 posted by whig on October 16, 2007 at 17:19:45 PT
Boiron 30C pellets
This is the formulation I got of Mezereum. Five tablets under my tongue at noon on October 1, repeated once twelve hours later at midnight, and it has continued to have effectiveness and improvement even now.
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Comment #13 posted by whig on October 16, 2007 at 17:15:30 PT
What this is, is metallic gold, which is triturated and then diluted with shaking many times, so that none of the original gold atoms remain in the solution. This solution is water or alcohol which contains some kind of ability to trigger a psychedelic sensation of the original gold even though it is virtually absent. Believe it or not, and if it doesn't do anything at all for you it's just a harmless placebo in that case. The psychic reaction then causes a psychosomatic response which can treat both emotional and physical illness. But this is my hypothesis, you would have to decide for yourself.
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Comment #12 posted by whig on October 16, 2007 at 04:12:31 PT
Whenever you find your closest match, you don't have to say what it is if you don't care to. I picked the one I did because you made some statements that are bold in this description which means it usually applies in those cases, even if some of the unbolded symptoms don't seem to match.I found 30C potency of Mezerium to be helpful, for my own sinus headache.
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Comment #11 posted by whig on October 16, 2007 at 03:13:58 PT
Something to compare your symptoms to. it doesn't seem like a good match, see if you can find a better one. I've deduced a mechanism but I can only hypothesize now, yet I think this can be an effective way to treat illness.
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Comment #10 posted by Hope on October 15, 2007 at 18:20:24 PT
Please hang in there, MBC. I feel the same way about hope. Hope is the opposite of despair and futility, for sure. Many times I've found myself praying for hope. Nothing more than hope. I just felt I needed some even tiny essence of hope just to keep going.You hear about people who are sick or injured and about how some of them seem to have an amazing "will to live"...I think that's the hope we are talking about. Some people have it naturally more than others. But I believe, I hope, that we can train ourselves, like athletes sort of be hope athletes. We may not be naturally hopeful, but practicing and practicing and forcing ourselves and exercising hope, surely works like it does in athletics, exercise, skill honing, and learning anything, and so many other aspects of life. Find it, recall the feeling of it. Remember it. Make yourself feel it...acting...if even for a split second. Keep doing it. It helps. You can remember the feeling and make yourself feel it. Really. Perhaps not as easily and readily as when you have cannabis...but you can remember the feeling and recall it and use it.Hopelessness is dangerous. You've got to fight it. You've got to step back from that dark void that it is and can be. But you know that and you've likely spent your life fighting it...and that's how you discovered that cannabis can be so helpful, I would guess.I understand what you mean about how using cannabis can help you find that sense of hope that seems impossible to find sometimes. It's one of the blessings that can be in using the herb for some people. I've experienced it myself. But please, remember, the element of it, hope, is always still there within you, always. There is no doubt that the right cannabis can serve as a powerful catalyst to that hope and serve as a powerful natural antidepressant...regardless of the fact that it's known as a depressant. It can certainly depress that sense of futility, that's for sure. Remember the study done on mice that their tails were taped to a bar? The mice given cannabis kept fighting to get loose longer than the mice who didn't have cannabis. It can strengthen some part of the spirit and the soul somehow, I'm sure of it. It's a powerful and good medicine, I have no doubt. Those mice had more hope of getting loose...and they were made stronger longer because of it. I know it's like a super food. It can do wonders, just like food can when you're hungry and weak and tired. Even at those times when you can't get the help that the plant can bring...hope for it and the powerful hope stimulation it can bring. I believe you. We believe you. That's got to help a little. That little smile that can come, that little being believed...that too can spark hope.
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Comment #9 posted by Max Flowers on October 15, 2007 at 12:17:58 PT
I want to get some help to you, if you would like that. We just have to figure out a safe way to get your address to me again (I should have kept it last time but didn't)I'm working on getting a new untraceable email address today which I'll pass along to you. Hang in there.
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Comment #8 posted by FoM on October 15, 2007 at 08:59:27 PT
I am sorry about how hard it is for you. It's wrong that you and others are denied a medicinal herb that can help. Life can be very hard sometimes but never forget life can be good sometimes too. We love and appreciate you here on CNews.When life is really hard I remember this.All things will pass.That means good times go away and that is sad but it also means bad times go away too and that's a good thing.
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Comment #7 posted by mai_bong_city on October 15, 2007 at 08:43:03 PT
endocannabinoids and me
i just want to mention something that i have found about my own endocannabinoid system....i have both physical and mental illnesses, which i treat solely with cannabis and advil on occasion.
they recently discovered a possible genetic anomaly that may be responsible for suicide - for a person's predispensity for the act, and as to who might be unduly affected by treatment with anti-depressants.
my bipolar and suicidal ideation have been very effectively remitted with cannabis therapy - when nothing else had any benefit at all - or worse side-effects. 
when i do not have my medicine, the physical problems are of course severe - but they're severe most of the time anyway - what happens is that my mind is able to weather-through whereas, without cannabis, i have no.....hope, i guess.
i think that, certainly in my case, cannabis prevents suicide.
unfortunately, every effort to get access to medicine and change laws and every sacrifice still......i'm expected somehow to survive, hang in there, etc.....
i simply can not. cannabis saves lives. 
without it, i'm dead. and that just should not happen. my life is not worth a few ounces of plant material from the earth?
people should not have to claw their way across the ground for a few morsels of kindness, and of peace.
someday, maybe they will find the correlation. and the thing they've never found before - along with many other cures that cannabis offers - the cure - to prevent suicide - is in this plant they've killed over.
with all this insanity, i don't see the point in staying in such a world, anyway.
i know the one truth. i can not stop the tears for the many they've harmed.....destroyed....brutalized.
i can not stop the tears for what this world has become, and what we are doing to each other in the name of....what, exactly?peace be with you.mbc 
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Comment #6 posted by Toker00 on October 15, 2007 at 03:39:51 PT
Cannabis. The Anti-abuse Drug.
You know, I ABUSED alcohol for twenty-five years and it abused me back. I ABUSED tobacco for thirty years and it abused me back. I've USED cannabis for thirty-seven years and it has never once ABUSED me. It has merely AMUSED me and ENTHUSED me. It has never ever USED me.Now tell me why they want to jail me just because I USE it,When in all of thirty-seven years I never once ABUSED it?Toke. 
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Comment #5 posted by aolbites on October 14, 2007 at 14:02:47 PT
Stop yelling please
It seems Every time you post its gotta be all caps.. whats your deal?STOP YELLING!
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Comment #4 posted by Hope on October 14, 2007 at 13:47:46 PT
Researchers that don't say it
remind me of some of the words of the old Steely Dan tune, Reeling in the Years.They "wouldn't even know a diamond if" they "held it in their hand."The lyrics, with the lover words excluded, so it would be directly to all of them."You wouldn't know a diamond
If you held it in your hand
The things you think are precious
I can't understandAre you gathering up the tears?
Have you had enough of mine?You been telling me you're a genius
Since you were seventeenThe things that pass for knowledge
I can't understandThe things you think are useless
I can't understand"
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Comment #3 posted by Hope on October 14, 2007 at 13:26:07 PT
Something that irks me...terribly.
Is that these studies don't say what they should. They should say, "Stop the persecution of people who use this plant! Immediately! The plant is good for you. You don't have to use it, but stop persecuting the people who wish too! Now!"What's wrong with them? Why won't they say it?Stop punishing people and prohibiting people from using and consuming the plant, cannabis!That should be of great importance. Instead, as though in some sort of fear or shyness or belonging to the pharmaceutical industry...they excitedly say that their research opens the door to more opportunities to create more synthetic drugs based on cannabinoids.What in the world is wrong with them?Say it! Say it! For God's sake, say it!Cannabis does more good than harm. It's healthy.It's good for you in so many ways. Legalize it! Stop depriving and harming people because of idiotic superstitious type beliefs and old wives' tales. Stop the idiocy and cruelty! Legalize it and stop persecuting the people who know what is good for them and helps them. These researchers should be demanding it as a matter of conscience.
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Comment #2 posted by Toker00 on October 14, 2007 at 12:51:08 PT
Richard, that is the reason the Government had to allow medical cannabis patients access in the first place. The fact that any SANE human being would use cannabis even if it is illegal, if it helped them to not go blind, was a legitimate enough excuse for the program. Illness suffered from Dental Malpractice or unsafe materials permanently embedded in your teeth through no fault of your own, and if the poison is treatable with cannabis, would be an even more Sane reason to use cannabis, as for Life preservation, in MHO. Sight preservation is important enough reason but I guess Life preservation isn't. Go figure.Toke.
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Comment #1 posted by Richard Zuckerman on October 14, 2007 at 09:39:49 PT:
DOES ENDOGENOUS CANNABINOIDS PROTECT NERVE AND BRAIN DAMAGES CAUSED BY MERCURY? LESS THAN A WEEK AGO, I RECEIVED FOR THE FIRST TIME A NEWSLETTER ENTITLED "DENTAL TRUTH", ABOUT THE CUMULATIVE MEDICAL DANGERS CAUSED BY MERCURY AMALGAM DENTAL "SILVER" FILLINGS. THE NEWSLETTER IS PUBLISHED BY DAMS, Intl., 1079 Summit Avenue, St. Paul, MN, 55105, (toll free telephone number)(800) 311-6265, (telephone number)(651) 222-6760, dams Upon my telephone calls to Congresswoman Diane Watson, I learned that she is about to sponsor a Congressional legislative Bill which would ban Mercury Amalgam "Silver" dental fillings. I told her that the United States Veteran's Administration hospital in East Orange, New Jersey, have refused to even give me a body test for Mercury comtamination!!! Congresswoman Watson switched me to "Mr. Henderson" of her Washington, D.C., office who promised to e-mail me the Bill when it is ready. I'm still waiting to receive the e-mail, so I can print it out and send it to the local Congressman and State legislators for similar support in State legislation!! IF ENDOGENOUS CANNABIS CAN PROTECT NERVE AND BRAIN DAMAGE FROM MERCURY, THEN, DAMN THE TORPEDOES!, I'LL USE CANNABIS "MARIJUANA" DESPITE ITS ILLEGALITY!!!!
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