New way to boost potency of natural pain relief chemical in body
November 21, 2011
Science Daily/University of California - Irvine
UC Irvine and Italian researchers have discovered a new means of enhancing the effects of anandamide -- a natural, marijuana-like chemical in the body that provides pain relief.
Led by Daniele Piomelli, UCI's Louise Turner Arnold Chair in the Neurosciences, the team identified an "escort" protein in brain cells that transports anandamide to sites within the cell where enzymes break it down. They found that blocking this protein -- called FLAT -- increases anandamide's potency.
Previous work by the researchers indicates that compounds boosting anandamide's natural abilities could form the basis of pain medications that don't produce sedation, addiction or other central nervous system side effects common with existing painkillers, such as opiates.
"These findings raise hope that the analgesic properties of marijuana can be harnessed for new, safe drugs," said Piomelli, a professor of pharmacology. "Specific drug compounds we are creating that amplify the actions of natural, marijuana-like chemicals are showing great promise."
For the study, which appears in the Nov. 20 online version of Nature Neuroscience, he and his colleagues used computational methods to understand how FLAT binds with anandamide and escorts it to cell sites to be degraded by fatty acid amide hydrolase (FAAH) enzymes.
Anandamide has been dubbed "the bliss molecule" for its similarities to the active ingredient in marijuana. A neurotransmitter that's part of the body's endocannabinoid system, it's been shown in studies by Piomelli and others to play analgesic, antianxiety and antidepressant roles. It's also important in regulating food consumption. Blocking FAAH activity enhances several effects of anandamide without generating the "high" seen with marijuana.
Piomelli and his collaborators speculate that inhibiting FLAT (FAAH-like anandamide transporters) might be particularly useful in controlling certain forms of pain -- that caused by damage to the central nervous system, for example -- and curbing addiction to such drugs as nicotine and cocaine.
Researchers from UCI, Italy's University of Parma and University of Bologna, and the Italian Institute of Technology participated in the study, which was supported by grants from the U.S. National Institute on Drug Abuse, the U.S. National Institute on Alcohol Abuse & Alcoholism, and the U.S. National Institute of General Medical Sciences.
https://www.sciencedaily.com/releases/2011/11/111121142501.htm
Compound boosts marijuana-like chemical in the body to relieve pain at injury site
September 21, 2010
Science Daily/University of California -- Irvine
American and Italian researchers have found that a novel drug allows anandamide -- a marijuana-like chemical in the body -- to effectively control pain at the site of an injury.
Led by Daniele Piomelli, the Louise Turner Arnold Chair in Neurosciences and director of the Center for Drug Discovery at UC Irvine, the study suggests that such compounds could form the basis of pain medications that don't produce sedation, addiction or other central nervous system side effects common with existing painkillers, such as opiates.
"These findings raise hope that the analgesic properties of marijuana can be harnessed to curb pain," Piomelli said. "Marijuana itself is sometimes used in clinical settings for pain relief but causes many unwanted effects. However, specific drugs that amplify the actions of natural, marijuana-like chemicals are showing great promise."
For the study, which appears in the Sept. 19 online version of Nature Neuroscience, rats and mice were given a drug created by Piomelli and colleagues at the Italian universities of Urbino and Parma. The researchers discovered that the compound, URB937, did not enter the central nervous system but simply boosted the levels of anandamide in peripheral tissues. Still, it produced a profound analgesic effect for both acute and chronic pain. This was surprising, since anandamide had been thought to only work in the brain.
The synthetic drug inhibits FAAH, an enzyme in the body that breaks down anandamide, dubbed "the bliss molecule" for its similarities to the active ingredient in marijuana. A neurotransmitter that's part of the endocannabinoid system, anandamide has been shown in studies by Piomelli and others to play analgesic, antianxiety and antidepressant roles. It's also important in regulating food consumption. Blocking FAAH activity enhances the effects of anandamide without generating the "high" seen with marijuana.
Piomelli and his team are now collaborating with drug discovery specialists at the Italian Institute of Technology, in Genoa, to develop the new compound -- which is protected by a patent application -- into a clinically useful medication.
Researchers from UCI, the University of Georgia, the University of Naples, the University of Parma, the University of Urbino and the Italian Institute of Technology participated in the study, which was supported by the National Institute on Drug Abuse and the Italian Ministry of Public Education.
https://www.sciencedaily.com/releases/2010/09/100920131140.htm