University of California Irvine pharmacology professor Daniele Piomelli and his colleagues found a way to breed mice who had naturally low levels of the endocannabinoid 2-AG, reports Dennis Romero at LA Weekly. "These modified mice ate more and moved less than typical mice, but did not gain any weight, even when they were fed a high-fat diet," the researchers noted.
Now, while that may sound as if a cannabinoid-blocking pill would allow you to eat all the junk food you want, not exercise, and still not gain any weight, you might wanna hold off just a minute before stocking your freezer with Klondike bars.
Previous research has found that endocannabinoids play an important role in regulating energy metabolism, reports Jennifer Walsh at the Huffington Post.
A previous study by Piomelli found that these compounds make us crave fat, so he decided to see if lowering the levels of cannabinoids could have the opposite effect. He bred mice to produce only low levels of the compound, then compared their behavior and health with that of normal mice.
The modified stayed skinny even on a high-fat diet. They also had normal blood pressure and no increased risk of heart disease and diabetes that usually come with such a diet.
The researchers determined that the brown fat of the modified mice was overactive -- it was being turned into heat much quicker than in normal mice. Brown fat is a type of fat that keeps mammals warm, burning off excess energy.
"We discovered that these mice were resistant to obesity because they burned fat calories much more efficiently that normal mice do," Piomelli said. "We had know that endocannabinoids play a critical role in cell energy regulation, but this is the first time we found a target where this occurs."
But Wait A Minute...
While the study's results may have you thinking wonderful thoughts like "effortless dieting," there are a couple of snakes (aren't there always?) in this dietary Garden of Eden.
For starters, as we already pointed out, the mice in the study, which was published in the March issue of Cell Metabolism, were bred to have low levels of the endocannabinoid 2-AG; a drug to actually block the effects of 2-AG in humans would take years to develop.
"To produce the desired effects, we would need to create a drug that blocks 2-AG production in the brain, something we're not yet able to do," Piomelli noted.
"So don't cancel that gym membership just yet," Piomelli said. "But as you hit the treadmill, think about the added health benefits if you could train your brain to make fewer endocannabinoids."
Secondly -- and this is important to point out, especially since apparently all of the mainstream media overlooked it -- cannabinoid blockers in the past have shown themselves to be quite dangerous, and in fact have resulted in suicidal behavior.
When the endocannabinoids have shown themselves to be crucial in the regulation of higher cognition, learning, memory, stress, pain, and appetite, to muck about in the brain willy-nilly by blocking their receptors seems a foolhardy premise indeed, akin to a bull in a china shop.
All the effects of endocannabinoids are not limited to the central nervous system -- peripheral tissues have receptors and are affected as well. Not all of these effects are known or understood, points out Corpus Callosum, therefore there are many potential adverse effects.
The infamous CB1 receptor blocker Rimonabant -- brand name Accomplia -- was the first selective cannabinoid receptor to be approved for use. After just two years of use (2006-2008), it was concluded by the European Medicines Agency (EMEA) that "the benefits of Accomplia no longer outweighed the risks, and subsequently recommended the product be suspended from the UK market."
Rimonabant was used for obesity and for smoking cessation (it also blocks the psychoactive effects of marijuana), with sales in the UK starting up in July 2006. It only took just over two years, until October 2008, for the EMEA to recommend that doctors not prescribe the drug "due to the risk of serious psychiatric problems and even suicide."
Shortly after its market introduction, press reports and independent studies suggested side effects occurred more intensely and more commonly than claimed by the manufacturer, the French pharma firm Sanofi-Aventis, in their clinical studies. Rimonabant's blocking of the CB1 cannabinoid receptors in the brain frequently resulted in severe depression and suicidal thoughts.
Additionally, research which was released late last year suggests that deficits in endocannabinoids may contribute to anorexia nervosa and bulimia.
In that study, scientists measured the status of the endocannabinoid system indirectly by finding whether there was an increase or decrease in the density of CB1 endocannabinoid receptors. They compared these densities in women with anorexia or bulimia with those of healthy women.
Researchers found evidence of deficits in endocannabinoid levels or reduced CB1 receptor function in the brains of women with anorexia nervosa. CB1 receptor availability in the insula (a region that integrates body perception, reward and emotion, functions known to be disturbed in these patients) was affected in both anorexia and bulimia patients.
Researchers hope those findings lead to a new target for developing drugs to treat eating disorders, a practice currently being investigated with animal test subjects.