As their name implies, the bodily compounds called endocannabinoids resemble the cannabinoids that give marijuana (cannabis sativa/indica) its psychoactive properties.
Two key endocannabinoids – anandamide and 2-AG – act as neurotransmitters and metabolic agents in human organs, including the brain and fatty (adipose) tissue.
Endocannabinoids (ECs) help regulate pain and inflammatory pain signals, and are needed for appetite regulation and for “working” memory.
Starting several years ago, researchers began to find and detail unhealthful “dysregulation” (abnormal activity) of key ECs in overweight/obese animals and humans.
Overstimulation of the body’s EC receptors can lead to weight gain, with cannabis smokers often experiencing mild hunger pangs known as “the munchies”.
Endocannabinoid-blocking drug proves unsafe
The revelation that obese people show abnormal activity in their EC systems led to a rush to develop synthetic, EC-like anti-obesity drugs.
A drug called Rimonabant (Acomplia) – which works by blocking EC cell receptors – was the first to reach the FDA review process.
But Rimonabant’s slight beneficial effects on appetite and weight gain were outweighed by its adverse psychological effects … as might have been predicted with use of a “blunt instrument” drug that interferes, clumsily, with a complex, delicately balanced neurological system.
Synthetic cannabinoid-receptor blockers like Rimonabant interfere with neural connectivity in rodents’ brains … a characteristic of depression in humans. In fact, Rimonabant causes depression, suicidal thoughts, and anxiety and may hinder infants’ neurological development.
Knowledge that people who are overweight show abnormal activity in their EC systems has led to hunt for natural or synthetic ways to normalize it.
So far, the synthetic drug approach hasn’t worked well or safely: see our sidebar, “Endocannabinoid-blocking drug proves unsafe”.
Conversely, a new study in rodents suggests that seafood-source omega-3s – particularly the phospholipid-bound omega-3s in krill oil – may be real alternatives.
Krill oil normalized EC activity in rodents fed fatty diets
University and private researchers from Australia, Norway, and Italy report encouraging results with regard to krill oil’s potential benefit in appetite regulation.
In their study, supplemental krill oil partially reversed adverse EC-system changes seen in mice fed a high-fat, obesity-inducing diet.
The high fat diet, rich in pro-inflammatory omega-6 fatty acids, was associated with an increase in levels of ECs in all tissues except the liver and subcutaneous (under-skin) adipose tissue.
Feeding these overstuffed mice krill oil for eight weeks reduced the levels of both ECs associated with weight gain (anandamide and/or 2-AG), in all tissues except the liver.
Importantly, these beneficial effects usually occurred in a dose-dependent manner, which strengthens the case that krill oil was responsible.
Levels of both ECs’ chemical precursors were also generally reduced, indicating that krill oil curbs the body’s supply of the raw materials it needs to make ECs.
The authors expressed an optimistic conclusion, saying “Our data suggest that KO may promote therapeutic benefit by reducing endocannabinoid precursor availability and hence endocannabinoid biosynthesis.”
In other words, rather than acting as a blind, blunt instrument, it appears that krill oil’s phospholipid-bound omega-3s help the body return to balance naturally and safely.
As the authors wrote, “… these data might suggest that KO [krill oil] can potentially produce beneficial metabolic effects against dys-metabolism and inflammation in obesity”. (Piscitelli F et al. 2011)
Kjetil Berge, Ph.D., of krill oil harvester/supplier Aker Biomarine led the study, and made two key points:
“[Our findings] support previous animal and clinical studies performed with krill oil that is characterized by a high content of omega-3 phospholipids. Hence krill oil has a high potential to alleviate metabolic dysfunctions associated with obesity and other metabolic disorders.”
Batetta B, Griinari M, Carta G, Murru E, Ligresti A, Cordeddu L, Giordano E, Sanna F, Bisogno T, Uda S, Collu M, Bruheim I, Di Marzo V, Banni S. Endocannabinoids may mediate the ability of (n-3) fatty acids to reduce ectopic fat and inflammatory mediators in obese Zucker rats.J Nutr. 2009 Aug;139(8):1495-501. Epub 2009 Jun 23.
Matias I, Carta G, Murru E, Petrosino S, Banni S, Di Marzo V. Effect of polyunsaturated fatty acids on endocannabinoid and N-acyl-ethanolamine levels in mouse adipocytes. Biochim Biophys Acta. 2008 Jan-Feb;1781(1-2):52-60. Epub 2007 Nov 17.
Patti ME. Rehashing endocannabinoid antagonists: can we selectively target the periphery to safely treat obesity and type 2 diabetes? J Clin Invest. 2010 Aug 2;120(8):2646-8. doi: 10.1172/JCI44099. Epub 2010 Jul 26.
Piscitelli F, Carta G, Bisogno T, Murru E, Cordeddu L, Berge K, Tandy S, Cohn JS, Griinari M, Banni S, Di Marzo V. Effect of dietary krill oil supplementation on the endocannabinoidome of metabolically relevant tissues from high fat-fed mice. Nutr Metab (Lond). 2011 Jul 13;8(1):51. [Epub ahead of print]
Starowicz KM, Cristino L, Matias I, Capasso R, Racioppi A, Izzo AA, Di Marzo V. Endocannabinoid dysregulation in the pancreas and adipose tissue of mice fed with a high-fat diet. Obesity (Silver Spring). 2008 Mar;16(3):553-65. Epub 2008 Jan 17.
Tam J, Vemuri VK, Liu J, Bátkai S, Mukhopadhyay B, Godlewski G, Osei-Hyiaman D, Ohnuma S, Ambudkar SV, Pickel J, Makriyannis A, Kunos G. Peripheral CB1 cannabinoid receptor blockade improves cardiometabolic risk in mouse models of obesity. J Clin Invest. 2010 Aug 2;120(8):2953-66. doi: 10.1172/JCI42551. Epub 2010 Jul 26. Erratum in: J Clin Invest. 2010 Oct 1;120(10):3735.