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Molecular Mechanism Found That Controls Marijuana-Like Substance In Body

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Molecular mechanism found that controls marijuana-like substance in body

August 9, 2010

A newly discovered molecular mechanism helps control the amount and effectiveness of a substance that mimics an active ingredient in marijuana, but that is produced by the body’s own nerve cells.


The results were reported in the latest Nature Neuroscience. The lead author on the study is William R. Marrs of the Neurobiology and Behavior program at the University of Washington (UW). The senior author is Dr. Nephi Stella, UW professor of pharmacology and psychiatry.


In previous papers, Stella and other scientists have noted that the body manufactures several cell signals called endocannabinoids that mimic the actions of marijuana-derived chemicals. They hope their future work encourages the design of therapies to modulate these molecular communications. Specifically targeted treatments, for example, might give cancer and AIDS patients the same medicinal benefits as marijuana without its mind-altering properties.


Because cannabinoid signaling systems are common throughout the body and affect a variety of functions, therapies aimed at these systems might be more wide-ranging than simply a better substitute for medicinal marijuana. Stella is especially interested in the potential for helping people with conditions for which even symptomatic treatment is limited or non-existent, such as multiple sclerosis, brain tumors, Huntington’s disease and other autoimmune or neurological disorders.


Controlling cannabinoid receptors to control pain, anxiety, and brain inflammation


Earlier Stella’s group discovered a key endocannabinoid, called 2-AG, that carries a type of messaging between brain cells. 2-AG is also implicated in brain cell migration and brain tissue inflammation. It does this by activating one type of cannabinoid receptor on neurons, and another type of cannabinoid receptor on microglia, the tiny cells that clean up debris, like damaged nerve cells and plaque, in the brain and spinal cord. As the brain’s first line of defense against infection, microglia are attune to the most subtle clues suggesting an attack.


Stella’s team further investigated 2-AG nerve cell signaling in the study just published in Nature Neuroscience. They looked at an enzyme called ABHD6, newly identified by other scientists using advanced protein profiling technology, also known as proteomics. ABHD6 is present in nerve cells in the brain.


Stella’s team observed that this enzyme degrades the 2-AG nerve signaling substance by splitting it with water. This happens near the cell receptor for the 2-AG signal.


Breaking apart 2-AG reduced its accumulation and decreased its ability to prod other cells to action. In this case, the broken down 2-AG was less effective in stimulating the microglia — the brain defenders — to get moving.


The results provided by their study, the authors said, suggest that the enzyme ABDH6 “is a bona fide member of the endocannabinoid signaling system.”


“The enzymatic steps that control the production and inactivation of endocannabinoids constitute promising molecular targets for indirectly modulating the activity of cannabinoid receptors,” the authors noted. Designing treatments that manage the production and inactivation of important enzymes like ABHD6 could thereby control such conditions as brain inflammation or overactive brain signals. Other enzymes are involved in controlling the accumulation of different endocannabinoids.


Each of these enzymes, the researchers pointed out, provides a unique therapeutic opportunity. Inhibiting distinct enzymes would allow for the fine-tuned direction of endocannabinoid signaling. For example, blocking a specific enzyme to heighten a certain signal might ameliorate pain and also act as anti-anxiety and antidepressant therapy, the authors explained. Drugs that reduce the activity of the ABDH6 enzyme might prevent brain damage from an overactive response to a virus.



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we are standing at the edge-


with the advance of medical marijuana usage becoming more prevalent every day, the amount of studies is going to skyrocket. modern medicine has shied away from cannabis, all the while virtually all other known compounds studied extensively. i think researchers are itching to catch up.


it's my opinion that marijuana is going to provide amazing medical properties and discoveries. in the near future at that.


the fact that we have receptors in our cells, ONLY for cannabinoids, that control some very important and basic physiological functions, and where only recently discovered, is amazing in itself.


the truth is out there :)LOL

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Thanks AKenewell, much appreciated. It seems there is an increase in studies of the effects of various cannabinoids, which should be good news for all of us.


I thought the following paragraph was interesting. This is actually from another paper that AKenewell posted today, in this thread:


The main obstacle for the use of CB1 ligands lies in their psychotropic side effects, such as highs, hallucinations, depression or anxiety. From targeting the CB1 receptor, we learned that both agonists and antagonists result in serious side effects and strategies bypassing or minimizing central involvement of CB ligands are urgently needed. One strategy is to target the ECS at sites distinct of the CB1 receptor and, thus, characterization of all structures in the ECS, including the novel cannabinoid receptors – GPR55 and GPR119 – are wanted. Another strategy would be to modify cannabinoid drugs to stop them from traversing the blood–brain barrier or to diminish their psychoactivity. This will dominate cannabinoid research in the pharmaceutical industry in the near future. Furthermore, for most of the synthetic cannabinoid drugs, oral bioavailability will also have to be addressed as well.


That sounds to me like it's been well established (even for these conservative researchers) that there are definite benefits and medical uses for various cannabinoids. Hopefully this makes FDA's position and cannabis' Schedule 1 status look more ridiculous that it already does.

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Yeah...just realizing the "Dr. Bob" that posted here is not your doctor Bob


...yet another Dr. Bob


Yeah as I was telling him in the thread that confusion is why we started going by Dr.Bix, people were confused. We have received many call's with people wondering but didn't officially know who he was, just he was Dr.Bob and he was traveling, which originally kind of upset us that our patients were going huh, BUT He is posting here now though and was unaware of my Dr. bob and he seems very nice, and it seems he is doing great things for our community as well....so glad to have him on here and that confusion cleared up!

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