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US: Marijuana-like compounds are crucial for stress-induced pain relief Philip Lee Williams University of Georgia Press Release Thursday 23 Jun 2005 Scientists at UGA and UC, Irvine discover that the body's own marijuana-like compounds are crucial for stress-induced pain relief Athens, Ga. - A new study shows, for the first time, that the release of the body's own marijuana-like compounds is crucial to stress-induced analgesia - the body's way of initially shielding pain after a serious injury. The work, led by scientists at the University of Georgia and the University= =20 of California, Irvine, may yield a target for new drug therapies that will= =20 completely bypass the current arguments over the use of medical marijuana.= =20 In theory, the new research makes it possible to design a pill that will=20 have the same pain relieving effects as smoked marijuana, but through an=20 indirect mechanism that could also reduce unwanted psychoactive side=20 effects and not have the same political baggage. =93There is no prescription or over the counter drug that allows us to=20 manipulate the level of the brain=92s marijuana-like compounds,=94 said= Andrea=20 Hohmann, a neuroscientist in the department of psychology at the University= =20 of Georgia and co-author of the paper. =93This is the first time anyone has= =20 shown that one of the body=92s naturally occurring cannabinoids, a compound= =20 known as 2-AG, has anything to do with pain regulation under natural=20 conditions.=94 The study was published today in the journal Nature. Hohmann=92s co-author, Daniele Piomelli at the University of=20 California-Irvine, is the discoverer of a compound that blocks the=20 breakdown of this marijuana-like compound called 2-AG, and it is that=20 blocking compound, patented by UC-Irvine, that could become the new drug of= =20 choice for those suffering from pain or stress conditions. Importantly, it= =20 would not require people to smoke marijuana to obtain relief or wrestle=20 with the legal issues surrounding the drug. Others from UGA involved in the study include faculty members Philip Holmes= =20 and Jonathon Crystal and students Richard Suplita, Nathan Bolton and Mark=20 Neely. Authors from UC-Irvine include Darren Fegley and Regina Mangieri, in=20 addition to Piomelli. Other co-authors are Jocelyn Krey and Michael Walker= =20 from Brown University; Andrea Duranti, Giorgio Tarzia and Andrea Tontini=20 from the University of Urbino Carlo Bo in Italy; and Marco Mor from the=20 University of Parma, also in Italy. All were crucial in designing and=20 synthesizing the enzyme inhibitor. Scientists have long known that injured athletes or even gunshot victims=20 have a period of time in which the body=92s pain reaction is delayed. This= =20 effect is called =93stress-induced analgesia.=94 By the mid-1990s,= researchers=20 had targeted the sites of action of the brain=92s naturally occurring=20 marijuana-like compounds as having a crucial role in blocking pain, but no= =20 one understood the conditions in which these compounds were released to=20 block pain. Researchers along the way found out there are two kinds of stress-induced=20 analgesia mechanisms, opioid and nonopioid (or =93opioid independent=94).=20 Hohmann and colleagues discovered that the opioid-independent form was=20 produced by release of the brain=92s own marijuana-like compounds. =93We showed that cannabinoid receptors were involved in this remarkable=20 phenomenon,=94 said Hohmann, =93because blocking the receptors where= marijuana=20 acts virtually erased this opioid-independent form of stress analgesia.=94 If this is true, was there a compound that could also prolong the action of= =20 these compounds, making them work better? The answer lay in Piomelli=92s=20 pioneering work on inhibitors that break down the brain=92s own=20 marijuana-like compounds. =93If we design chemicals that tweak the levels of these transmitter=20 substances in the brain,=94 said Piomelli, =93we might be able to boost= their=20 normal effects.=94 When rats used in Hohmann=92s study were given the compound developed by=20 Piomelli and his collaborators at the University of Urbino Carlo Bo and the= =20 University of Parma, it increased stress-induced analgesia dramatically,=20 proving the connection between pain suppression and the release of these=20 marijuana-like compounds. The enzyme that inhibits the formation of the naturally occurring=20 marijuana-like compound 2-AG is called monoacylglycerol lipase, and it is=20 this enzyme that could be a target for therapeutic drug intervention to=20 help those in pain. A new drug increasing the body=92s own marijuana-like compounds could work= =20 similar to something like Prozac, which blocks the body=92s reuptake of the= =20 compound serotonin, causing it to be active longer, Hohmann said. Apparently, several parts of the brain are involved in the effect, most=20 notably a structure in the midbrain known as the periaqueductal gray. In=20 this region, stress causes the release of the naturally occurring=20 marijuana-like compounds in the brain. A drug derived from the new research would likely be more effective and=20 specific than smoked marijuana, said Hohmann.
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