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Cannabis sativa, or marijuana, has a long history of human use. The earliest evidence of the use of marijuana as an herbal medicine dates back to 500 B.C. in ancient China. Some ancient cultures cultivated the plant for its psychoactive properties to use in religious ceremonies. The plant maintains popularity to this day—for both medicinal and recreational use.
The molecule that is primarily responsible for the mind-altering effects of marijuana was first isolated in the early 1950s. Named tetrahydrocannabinol (THC), this molecule became the subject of further scientific study.
Researchers eventually discovered that humans have receptors for THC in the brain as well as other parts of the body. The receptors that THC binds to in the human body are called cannabinoid (CB) receptors and are numbered CB1 and CB2. CB1 receptors are found mainly in the brain and central nervous system. CB2 receptors are primarily found on immune cells.
Once CB receptors were discovered in the human body, the next logical question to ask was—why? Were those receptors there for some other purpose than achieving a high? This question led researchers in the 1990s to discover endogenously produced molecules that bind to CB1 and CB2 receptors. They called them endocannabinoids.
The most recent development in our understanding of endocannabinoids has revealed a fascinating link to nutrition and nutrition therapy. Some of these signaling molecules that bind to the same receptors as compounds present in marijuana are derived from dietary fats. More specifically, they are derived from omega-3 fatty acids.
In this article, we delve into the endocannabinoid system, the omega-3 cannabinoids, and the practical implications of the latest endocannabinoid science to nutrition therapy.
The Endocannabinoid system
The endocannabinoid system is a term that has emerged as the science of CB receptors and signaling molecules has unraveled. Whereas some body systems are defined by physical organs (like the digestive system or urinary system), others are defined by their function (like the immune system or endocrine system). The endocannabinoid system is similar to the immune and endocrine systems, in that it is defined by receptors and signaling molecules in cells throughout many organs of the body.
The endocannabinoid system includes these four parts:
- CB receptors (CB1 in the brain and CB2 in the rest of the body)
- Endocannabinoids (which bind to CB receptors)
- Enzymes that synthesize endocannabinoids
- Enzymes that break down endocannabinoids
The first endocannabinoids to be discovered were two molecules that were found to activate CB1 receptors. They were called anandamide (AEA) AND 2-arachidonoylglycerol (2-AG). AEA and 2-AG are signaling molecules that are synthesized from omega-6 polyunsaturated fatty acids and arachidonic acid.
For many years, AEA and 2-AG were the only known endogenous molecules to activate the same receptors as Cannabis in the human body. There was a growing interest in how these molecules interact with the brain and the immune system. Research also began to explore how these molecules might influence the risk of diseases like obesity, Multiple Sclerosis, and Parkinson’s Disease.
With increasing interest inside the nutrition therapy and research communities, scientists began to explore whether omega-3 fatty acids also served as building blocks for endocannabinoid molecules. The answer turned out to be yes.
In 2017, a team of researchers at the University of Illinois was the first to discover a biosynthetic pathway in humans to produce omega-3-derived endocannabinoids. These endocannabinoids were derived from both docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA).
There are now four endocannabinoid molecules that are known to be derived from omega-3 fatty acids: DHA ethanolamide, EPA ethanolamide, DHA glycerol, and EPA glycerol. Each of these molecules may have their own physiologic effects (which are not well understood), but they are also converted into more potent bioactive molecules.
The conversion of omega-3 endocannabinoids into more bioactive compounds occurs via pathways that are similar to the conversion of essential fatty acids into eicosanoids (leukotrienes and prostaglandins).
Metabolites of Omega-3-Endocannabinoids
Omega-3 endocannabinoids enter metabolic pathways that involve cyclooxygenase (COX) enzymes, lipoxygenase (LOX) enzymes, and cytochrome P450 epoxygenase (CYP450). Studies suggest that the resulting metabolites might significantly modulate inflammation and platelet aggregation.
Although not directly derived from endocannabinoids, there are additional endogenous molecules that researchers think are similar to the omega-3 endocannabinoids. These are compounds that form when EPA or DHA combine with neurotransmitters: EPA-serotonin, DHA-serotonin, EPA-dopamine, and DHA-dopamine.
Physiologic Effects of Omega-3 Endocannabinoids
Initial studies of omega-3 endocannabinoids were conducted in animals and in cell cultures. These studies suggest that omega-3 endocannabinoids enhance the formation of nerves and synapses in the brain, reduce inflammation, block the growth of cancer cells, and modify the pain response.
In humans, omega-3 endocannabinoids have been detected in breast milk. They have been shown to increase significantly in the human bloodstream after exercise. People who ate a diet high in omega-3s and low in omega-6s were shown to have higher levels of DHA-ethanolamide in circulation. The details of the physiologic effects of these molecules are yet to be determined.
The Relevance of Omega-3 Endocannabinoids to Nutrition Therapy
The study of omega-3 endocannabinoids is brand new. Do we know enough to be able to apply what we know to nutrition therapy? One thing we know for sure is that eating more omega-3 fats increases the levels of endogenous omega-3 endocannabinoids.
What happens next is still up for debate. Preclinical studies suggest that these molecules may explain part of the reason that omega-3 fatty acids have anti-inflammatory effects. Animal studies also indicate that these molecules have beneficial effects on platelet aggregation and immune function.
Traditional cultures ate far more omega-3 fatty acids in their diets than we do in modern times. Numerous studies provide evidence for the health benefits of omega-3s. The new knowledge that omega-3s feed into the endocannabinoid system may be one more compelling argument for why we should eat more nuts, flaxseeds, and fish.
About the Author
Sarah Cook, ND, is an instructor at the Nutrition Therapy Institute. She is also the owner of ND Pen, providing branding, copywriting, and website design services for integrative healthcare practitioners. Connect with Sarah at www.ndpen.com.
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