Endocannabinoid System Controls Key Circuits

Endocannabinoid System Controls Key Circuits
Posted by CN Staff on August 16, 2006 at 14:54:42 PT
Medical Research News 
Source: News-Medical.Net
Germany -- The same brain machinery that responds to the active substance in marijuana provides a central "on-demand" protection against seizures, researchers have found. They said their discoveries suggest that the "endocannabinoid" system might constitute a prime target for drugs against seizures of epilepsy and other neurodegenerative diseases.The findings were published by Beat Lutz and Giovanni Marsicano, of Max Planck Institute of Psychiatry and Johannes Gutenberg University in Mainz, and colleagues in the August 17, 2006, issue of the journal Neuron, published by Cell Press.
The endocannabinoid system--which includes the receptors, the natural cannabinoid compounds that trigger them, as well as the machinery for regulating the process--was already known to modulate the excitation of neuronal transmission, noted the researchers. However, it had not been established that such modulation might affect neurons in the hippocampus responsible for the "excitotoxicity" that underlies the uncontrolled activity of seizures.Thus, Lutz, Marsicano, and his colleagues used genetic techniques to pinpoint the role of the endocannabinoid system on these neurons and on seizure activity. They used mice as their animal model and induced seizures in these mice with the chemical kainic acid (KA).In particular, they wanted to explore the role played by the endocannabinoid system in hippocampal neurons that are responsive to the neurotransmitter glutamine. These neurons are known to play a central role in seizure activity. The endocannabinoid regulatory system is also active in another type of neuron triggered by the neurotransmitter gamma-aminobutyric acid (GABA).Thus, the researchers conducted experiments in which they genetically knocked out the endocannabinoid receptor CB1 and analyzed the effects on seizure sensitivity. They found that, indeed, when they knocked out CB1 in glutamatergic, but not GABAergic neurons, the chemically induced seizures increased in the mice. In fact, their experiments all but ruled out the role of GABAergic neurons in the seizure-protection function, they concluded."Altogether, these results confirm that physiological endocannabinoid-dependent control of GABAergic transmission depends on intact CB1 signaling in GABAergic interneurons and suggest that the endocannabinoid system does not influence GABAergic transmission during the development of KA-induced seizures," they concluded. "Therefore, direct modulation of glutamatergic transmission by CB1 receptors expressed on cortical glutamatergic neurons appears to be the major mechanism of endocannabinoid-mediated protection against KA-induced seizures."Furthermore, the researchers' experiments established that endocannabinoid receptors were also present in the same glutamatergic neurons in areas of the hippocampus known to be central to seizure generation. The researchers wrote that this finding "represents a novel step in understanding the progression of acute excitotoxic seizures and the development of epileptic states."And significantly, when the researchers used a targeted virus to knock out the CB1 gene for the endocannabinoid receptor specifically in the glutamatergic neurons of the hippocampus, the mice also showed strong worsening of chemically induced seizures in comparison to mice still expressing CB1."Altogether, these observations support a hypothetical scenario in which acute KA-induced excitotoxic seizures would activate the endocannabinoid system in respect to its ability to inhibit only 'harmful' glutamatergic transmission, but not 'protective' GABAergic release," concluded Lutz, Marsicano, and colleagues."In conclusion, our study reveals a mechanism through which the endocannabinoid system is able to provide on-demand protection against acute behavioral seizures. CB1 expression on hippocampal glutamatergic circuits accounts for this protection and might represent a suitable target for the treatment of neurological disorders associated with excessive neuronal excitation," they wrote.Complete Title: The Endocannabinoid System Controls Key Epileptogenic Circuits In The Hippocampus URL: Source: News-Medical.Net (Australia) Published: August 16, 2006Copyright: 2006 News-Medical.Net  Contact: editorial news-medical.netWebsite: Medical Marijuana Archives
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Comment #7 posted by paulpeterson on August 17, 2006 at 08:43:08 PT
Good point, newshawk, and thanks for keeping your brain online-Ethan Russo already noted a few years ago that "Accompli", that CB1 blocker, touted to be, in fact, a blockbuster when the FDA approves it right around the proverbial corner, will probably cause people to get noticeably more fidgety and have an increase in anxiety and depression-and boom-that is what news reports report as to some of the major "side effects" of this blockbuster already.Major increase in stroke risk? Maybe, in older people, but the most IMPORTANT risk factor would probably be for people that have just HAD a stroke-to trigger secondary strokes on and on until death-Les Grinspoon actually noted in an article in 1999 (remember that year? when IOM 99 came online?) that if you have a stroke you have two choices-wait about 15 years for the FDA to tell you that you should have copped a smoke-or go cop a smoke real quick and save your life and your brain (sorry to Les, I put my own words on it, just taking your idea and making it my own, if you get my drift, and hats off to Les for all his wonderful contributions to marijuana research and publishing over about 30 years so far, kudos).Now we have a cascading river of proof being added to the pudding as to just how powerful this group of drugs can be and how many people have already started on the road to neurodegerative protection-gentlemen, start your engines and "engage" and that's an order, sir.Marijuana-"not just the for breakfast drink anymore-don't leave home without it" because you never know when a stroke may strike after all-and we all want to get back home after all, don't we, Wally?PAUL PETERSON, from deep behind enemy lines.
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Comment #6 posted by whig on August 16, 2006 at 22:01:55 PT
You're right, if they could scare enough people in the non-free states they could try to make it into a civil war. They don't even have to scare a majority, if they have the majority of the media owners and they can fix the votes electronically. That is the point we have to remember to always stay peaceful and never ever allow them to dictate the terms of this disagreement.In retrospect, it is a civil war already and has been for some time. I've been too sheltered by half to know the worst of it, and I have no desire to put myself or anyone in unnecessary harm's way to see how bad it really is. I suppose it's not as bad as Iraq, but is that saying very much?
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Comment #5 posted by Wayne on August 16, 2006 at 21:33:41 PT
My theory is this: They're already waging war on people in California. If Colorado passes it, they'll start in on them too. But soon, Nevada and Arizona and other states will start following suit, and eventually the feds will crack. They could try to fight a couple states, but not all of them. I still have a little faith left in the American people, and I think they will catch on before too long.
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Comment #4 posted by bdimebag on August 16, 2006 at 17:07:29 PT:
ok lets say that in november the people of Colorado vote to legalize or decrim marijuana (can somebody fill me in on which one it is) what do you think will go down? will the feds rage war upon the people of CO or will the people finally have their freedom (maybe it will start a chain reaction to other states?)
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Comment #3 posted by hempity on August 16, 2006 at 16:25:30 PT
Ok how about this one?
August 16, 2006CONTACT:
Patrick Goggin
415-312-0084Tom Murphy
207-542-4998Adam Eidinger
adam votehemp.comCalifornia Industrial Hemp Farming Act Passes Final Senate Vote
Groundbreaking Bill Expected to Go to Governor's DeskSACRAMENTO, CA - AB 1147, The California Industrial Hemp Farming Act, 
passed in the Senate today by a vote of 26-13. The bill now heads to 
the Assembly for a final concurrence vote and will then be sent to 
Governor Arnold Schwarzenegger's desk for his signature. Since 
passing out of the Assembly in January of this year, AB 1147 has 
gained momentum as legislators learned that California businesses 
spend millions of dollars each year importing hemp from Canada, China 
and Europe. Demand for hemp products such as clothing, food, body 
care, paper and even auto parts has been growing rapidly in recent 
years with the U.S. hemp market now exceeding $270 million in 
estimated annual retail sales. The new law would give farmers the 
ability to legally supply U.S. manufacturers with hemp seed, oil and 
fiber and would not weaken anti-drug laws."We thank legislators from both parties that listened to the facts 
about industrial hemp and made a historic decision to bring back the 
crop," says Vote Hemp President Eric Steenstra. "Passage in the 
California Legislature is a major accomplishment for the authors and 
sponsors of the bill as well as thousands of ecology conscious 
people, farmers, and businesses that wrote California legislators," 
says Steenstra.The California Industrial Hemp Farming Act was introduced in February 
of 2005 by Democratic Assemblyman Mark Leno. This year, the bill was 
amended, and Republican Assemblyman Chuck Devore joined as a 
co-author. In the bipartisan spirit of the legislation the bill was 
managed on the floor of the Senate by Republican Tom McClintock and 
received support from Senator Able Maldonado, a farmer and Republican 
member of the Agriculture Committee. Another influential Republican 
Senator who supported the bill was Sam Aanestad who is Vice Chair of 
the Senate Appropriations Committee.AB 1147 has been carefully crafted to comply with federal law and 
minimize impact to law enforcement. It includes tough regulations 
without placing an undue burden on farmers. The bill only permits 
cultivation of ultra-low THC industrial hemp when grown as an 
agricultural field crop or in a research setting. Backyard or 
horticultural cultivation is prohibited. Any clandestine grove of 
Cannabis will be considered a controlled substance regardless of its 
THC content.California's AB 1147 has already passed a series of committee votes 
and a floor vote in the Assembly. The final passage in the Assembly 
is expected by the end of August. Vote Hemp believes the new law 
would withstand federal scrutiny in the form of legal challenges and 
ultimately will result in commercial hemp farming in California. No 
industrial hemp is grown in the United States today even though seven 
states have passed hemp farming and research bills in recent years. 
More details on industrial hemp legislation can be found at .Final passage of AB 1147 could revitalize commercial industrial hemp 
farming, which occurred in California until shortly after World War 
II. "It appears the hemp seed and oil we currently import soon will 
be grown and produced right here in California," says David Bronner, 
Chair of the HIA's Food and Oil Committee and President of 
Alpsnack/Dr. Bronner's Magic Soaps. "The Hemp Industries 
Association's member companies are urging Governor Schwarzenegger to 
promote sustainable growth for the California economy by signing the 
industrial hemp bill.  Increasing double digit sales growth over the 
last few years in the hemp food and body care sector indicates strong 
consumer demand for hemp products that will sustain high prices for 
farmers for years to come," said Bronner.More information about hemp legislation and the crop's many uses can 
be found at BETA SP and DVD Video News 
Release featuring footage of hemp farming in other countries is 
available upon request by contacting
Adam Eidinger at 202-744-2671.
grow yer own
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Comment #2 posted by OverwhelmSam on August 16, 2006 at 15:40:23 PT
"This thing stinks to high heaven," Mr. Bonner said. "I am outraged and at a loss to explain why there were so many irregularities in this case. The only thing that is clear is that the prosecutors pointed their guns at the wrong guys, the good guys, and they let the bad guy walk. Now they want to send these agents to prison for doing their job. Oh! So it's okay to bust peaceful pot consumers, but when law enforcement get's busted for being jerks, you want to cry like a little baby. Sucks doesn't it! It's just collateral damage to the drug war mongers in Washington. Legalize marijuana for adult use, and this all goes away.
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Comment #1 posted by laduncon on August 16, 2006 at 15:39:26 PT
Rimonobant Anyone?
So I suppose that a major effect of Rimonobant (new weight-loss and smoking cessation drug), which blocks the CB1 receptor in order to "work", would be highly increased risk of seizures.Nice one, big Pharma! Sadly, many people will probably choose to make this unfortunate tradeoff.
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