Marijuana-like Brain Chemicals Work as Antidepressant
November 7, 2007
Science Daily/University of California - Irvine
American and Italian researchers have found that boosting the amounts of a marijuana-like brain transmitter called anandamide produces antidepressant effects in test rats.
Led by Daniele Piomelli, the Louise Turner Arnold Chair in Neurosciences and director of the Center for Drug Discovery at the University of California, Irvine, the researchers used a drug they created, called URB597, which blocks anandamide degradation in the brain, thereby increasing the levels of this chemical.
“These findings raise the hope that the mood-elevating properties of marijuana can be harnessed to treat depression,” Piomelli said. “Marijuana itself has shown no clinical use for depression. However, specific drugs that amplify the actions of natural marijuana-like transmitters in the brain are showing great promise.”
The researchers administered URB597 to chronically stressed rats which showed behaviors similar to those seen in depressed human patients. After five weeks of treatment, the stressed rats treated with the drug were behaving similarly to a comparison group of unstressed animals.
URB597 works by inhibiting FAAH, an enzyme in the body that breaks down anandamide. Dubbed “the bliss molecule” for its similarities to the active ingredient in marijuana, anandamide is a neurotransmitter that is part of the brain’s endocannabinoid system and it has been shown in studies by Piomelli and others to play analgesic, anti-anxiety and antidepressant roles. It also is involved in regulating feeding and obesity. Blocking FAAH activity boosts the effects of anandamide without producing the “high” seen with marijuana.
Piomelli and colleagues at the Universities of Urbino and Parma in Italy created URB597. A patent was issued in 2007. The European pharmaceutical company Organon holds the license to the patent and will begin clinical studies on the drug in 2008, according to Piomelli.
Marco Bortolato, Regina Mangieri, Jin Fu, Janet Kim and Oliver Arguello of UC Irvine; Andrea Duranti, Andrea Tontini and Giorgio Tarzia of the University of Urbino; and Marco Mor of the University of Parma also participated in the study. It was supported by the National Institute on Drug Abuse, the University of California Discovery Program and the National Alliance for Research on Schizophrenia and Depression.
https://www.sciencedaily.com/releases/2007/11/071105120556.htm
New Antidepressant Drug Increases 'Brain's Own Cannabis'
December 13, 2005
Science Daily/McGill University
Researchers have discovered a new drug that raises the level of endocannabinoids -- the 'brain's own cannabis' -- providing anti-depressant effects. The new research published in this week's Proceedings of the National Academy of Sciences (PNAS), suggests the new drug, called URB597, could represent a safer alternative to cannabis for the treatment of pain and depression, and open the door to new and improved treatments for clinical depression--a condition that affects around 20% of Canadians.
In preclinical laboratory tests researchers found that URB597 increased the production of endocannabinoids by blocking their degradation, resulting in measurable antidepressant effects. "This is the first time it has been shown that a drug that increases endocannabinoids in the brain can improve your mood," says the lead investigator Dr. Gabriella Gobbi, an MUHC and Université de Montréal researcher.
Endocannabinoids are chemicals released by the brain under certain conditions, like exercise; they stimulate specific brain receptors that can trigger feelings of well-being. The researchers, which included scientists from the University of California at Irvine, were able to measure serotonin and noradrenaline activity as a result of the increased endocannabinoids, and also conducted standard experiments to gauge the 'mood' of their subjects and confirm their findings.
"The results were similar to the effect we might expect from the use of commonly prescribed antidepressants, which are effective on only around 30% of the population," explains Dr. Gobbi. "Our discovery strengthens the case for URB597 as a safer, non-addictive, non-psychotropic alternative to cannabis for the treatment of pain and depression and provides hope for the development of an alternate line of antidepressants, with a wider range of effectiveness."
Cannabis has been known for its anti-depressant and pain-relief effects for many years, but the addictive nature and general health concerns of cannabis use make this drug far from ideal as a medical treatment. The active ingredient in cannabis--THC (Tetrahydrocannabinol)--stimulates cannabinoid receptors.
Funding for this study was provided by the Fonds de la Recherche en Santé du Québec (FRSQ), the Canadian Psychiatric Research Foundation (CPRF), the National Institute on Drug Abuse (NIDA) and an MUHC fellowship.
https://www.sciencedaily.com/releases/2005/12/051213172852.htm