New research suggests that omega-3 fatty acids can enhance endocannabinoid synthesis. Fish oil (FO) and phytocannabinoids have received considerable attention for their intestinal anti-inflammatory effects. We investigated whether the combination of FO with cannabigerol (CBG) and cannabidiol (CBD) or a combination of all three treatments results in a more pronounced intestinal antiin …
CBD And Fish Oil
Chances are, you’ve probably heard about CBD, and how the many molecules it contains (cannabinoids) can benefit health and wellness. In fact, according to the most recent national poll, 1 in 7 of you reading this article are already using phytocannabinoids (cannabinoids derived from plants) for their various physiological effects and functions. 1
But do you understand how cannabinoids “work” within the body? And did you know that simple adjustments to your diet can promote your body’s natural production of molecules called endocannabinoids? Read on to discover how you can support your endocannabinoid system with or without external sources of cannabinoids.
The Endocannabinoid System: Nature’s Balancing Act
Over the past thirty years, studies exploring the physiological effects of cannabis have led to the discovery of a complex cell signaling network called the endocannabinoid system. 2 – 4 This is a network of lipid (fat)-based signaling molecules called endocannabinoids and the cells that detect them. Importantly, the endocannabinoid system plays an integral role in maintaining balance throughout the body—a vital process called homeostasis. 5
Homeostasis is the ability to maintain a relatively stable internal state despite changes in the external environment. Common examples of homeostatic processes include regulation of body temperature, blood sugar, and blood pressure.
Essentially, whenever an internal function becomes irregular due to injury, insult or illness, a well-functioning endocannabinoid system will respond by synthesizing chemical messengers called endocannabinoids in the brain, organs, connective tissue, glands, and immune cells. 5 These endocannabinoids will then bind with cannabinoid receptors in the central nervous system and immune system to set into motion a variety of cellular responses aimed at restoring balance to the irregular function. 5
Cannabinoid Receptors and Functions
To date, two primary cannabinoid receptors have been identified: CB1 and CB2. Whereas CB1 receptors are found primarily on the surface of cells in the brain and spinal cord, CB2 receptors are largely found on cells in the immune system. 6 Importantly, because these receptors are widely distributed throughout the body, the endocannabinoid system can help regulate the body’s:
- inflammatory response, 7
- perception of pain, 8
- reproductive function, 9
- sleep/wake cycle, 10
- stress response, 11
- mood and anxiety, 12
- immune system, 13 and more. 14
Types of Cannabinoids: Endocannabinoids and Phytocannabinoids
The human body produces a variety of endocannabinoids, some of which are derived from omega-6s, and some of which are derived from omega-3s. The two most well-researched endocannabinoids are anandamide and 2-AG, which come from the omega-6 fatty acid, arachidonic acid. Unlike endocannabinoids, which are synthesized within the body (endo- meaning “within”), THC and CBD are phytocannibinoids—a type of cannabinoid derived from plants (phyto- meaning “relating to plants”). 15 Although there are more than 85 different types of phytocannabinoids known to date, CBD and THC are by far the most well-known and well-researched. 16
THC is considered the mimetic phytocannabinoid of the endocannabinoid anandamide, and similar to anandamide, binds directly to CB1 receptors. 17 Along a similar vein, CBD is considered the mimetic phytocannabinoid of the endocannabinoid 2-AG, and like 2-AG, interacts with both CB1 and CB2 receptors. However, unlike 2-AG, anandamide, and THC—which bind directly to cannabinoid receptors—CBD affects cannabinoid receptors indirectly. 17
Cannabinoids Promote Homeostasis by Influencing Neuronal Communication
The most well-researched homeostatic process that the endocannabinoid system regulates is the speed of communication between cells of the nervous system called neurons. Similar to other neurotransmitters such as dopamine and serotonin, cannabinoids “talk” to neurons in the brain through the release of chemicals. 6
The communication actually occurs when one neuron sends a chemical messenger, or neurotransmitter, to another neuron across a gap called the synapse. Every time a neurotransmitter is sent, this is called neuron firing or transmission. The rate of neuron firing determines the speed that the brain and body can react to various stimuli, but too little or too much firing prevents us from functioning normally. 18 In essence, the endocannabinoid system helps maintain the balance of neuronal transmission by slowing down the rate of neuron firing. Now here comes the really interesting part.
Whereas in most neurotransmitter systems, the sending neuron (pre-synaptic neuron) releases excitatory or inhibitory chemicals across the synapse to the receiving neuron (post-synaptic neuron), in order to slow down neuronal transmission, endocannabinoids are sent in the reverse order—from post-synaptic neuron to pre-synaptic neuron. 6 Then, when endocannabinoids bind to receptors on the pre-synaptic neuron, they inhibit the firing of that neuron. 18 In effect, the endocannabinoid system promotes homeostasis by putting the brakes on neuronal speed by limiting the release of neurotransmitters.
Role of Omega-3 and Omega-6 fats in Endocannabinoid Synthesis and Function
Consuming EPA and DHA can provide many of the same benefits as cannabinoids
Intriguingly, the past fifty years of research on omega-3 fatty acids suggest that consuming an adequate amount of EPA and DHA can provide many of the same benefits as cannabinoids. 19 In truth, this really isn’t that surprising, given that endocannabinoids are lipid-based signaling molecules that are synthesized internally from omega-6 and omega-3 fatty acids. What’s more, research shows that the effects of endocannabinoids can be significantly influenced by the type of fatty acids consumed. 20 , 21 More specifically, their effects can be influenced by the ratios of omega-3 and omega-6 fatty acids consumed.
For example, new research suggests that the consumption of omega-3 fatty acids actually shifts the balance of endocannabinoids towards a higher proportion of omega-3 endocannabinoids (e.g., DHEA, EPEA) as well as endocannabinoid-like molecules that form when omega-3s combine with neurotransmitters like dopamine and serotonin (e.g., DHA-serotonin, EPA-dopamine). 20 Importantly, these omega-3 endocannabinoid and endocannabinoid-like molecules are believed to control vital physiological processes in the body—such as the body’s inflammatory response, pain, and more. 20 , 21
Research also suggests that a diet high in omega-3s can positively influence the neurological functions of the endocannabinoid system. In a study looking at the links between diet, brain functioning, and the endocannabinoid system, researchers fed mice a diet modeled after the Standard American diet—one high in omega-6 fatty acids, and low in omega-3s. Importantly, the omega-3-deficient mice displayed altered brain function and cannabinoid receptor activity in brain areas related to emotional behavior and mood disorders. 22 Put more simply, mice that were deprived of omega-3 fatty acids showed reduced cannabinoid receptor activity and increased depressive behaviors, while these effects were not observed in the mice fed a balanced diet rich in omega-3s.
In light of the reduced endocannabinoid binding and neurological functioning observed in the omega-3-deficient mice, these results suggest that a western diet may have serious implications for neurological health and overall well-being. 22 The good news, however, is that eating a diet with approximately equal ratios of omega-6 and omega-3 fatty acids can help preserve a healthy endocannabinoid system.
Promote Your Health Naturally
Regardless of how you feel about taking external cannabinoids, it is difficult to dispute the benefits of the endocannabinoid system, and its unique ability to restore homeostasis when physiological functions go awry. The fact that research suggests a diet low in omega-3s can disturb cannabinoid function and synthesis, while a diet rich in omega-3 fatty acids can help promote the synthesis of omega-3 endocannabinoids, suggests that simple changes to your diet and/or the addition of omega-3 fish or algae oil can greatly (and naturally!) enhance your health.
Gina Jaeger, PhD is a Developmental Specialist and Lead Research Writer for Nordic Naturals. She holds a doctorate in Human Development, and has published several research articles on children’s cognitive development. Gina enjoys studying and educating others on strategies for optimizing health and wellness throughout the lifespan.
Anandamide and 2-AG: The main two endocannabinoids and are synthesized from omega-6 and omega-3 fatty acids.
Cannabinoids: Molecules derived from fatty acids that binds to cannabinoid receptors.
Cannabis: Any plant of the Cannabis species; does not indicate the presence or absence of the hallucinogenic phytocannabinoid THC.
CB1 and CB2: The two main receptors of the endocannabinoid system, and widely distributed throughout the body. CB1 receptors are primarily found on the surface of cells in the brain and spinal cord, while CB2 receptors are largely found on cells in the immune system.
CBD: Cannabidiol, a phytocannibinoid that acts indirectly on cannabinoid receptors to help restore homeostasis.
Cannabinoid receptors: Cell membrane receptors involved in a variety of physiological processes.
Endocannabinoid System (ECS): Consists of cannabinoid receptors, endocannabinoids, and the metabolic enzymes that synthesize and break endocannabinoids down.
Endocannabinoids: Chemical messengers synthesized by the endocannabinoid system to restore physiological functions.
Homeostasis: Any self-regulating process by which biological systems tend to maintain stability; state of steady internal physical and chemical conditions while adjusting to conditions that are optimal for survival.
Phytocannabinoids: Cannabinoids derived from plants; the most prevalent types are CBD (cannabidiol) and THC (tetrahydrocannabinol).
Pre-synaptic neuron: A nerve cell that sends a chemical messenger, or neurotransmitter, across the synapse.
Post-synaptic neuron: A nerve cell that receives a chemical messenger, or neurotransmitter, after it has crossed the synapse.
Synapse: The site of transmission between a neuron sending a chemical or electric signal to the neuron receiving it.
Efficacy of combined therapy with fish oil and phytocannabinoids in murine intestinal inflammation
Fish oil (FO) and phytocannabinoids have received considerable attention for their intestinal anti-inflammatory effects. We investigated whether the combination of FO with cannabigerol (CBG) and cannabidiol (CBD) or a combination of all three treatments results in a more pronounced intestinal antiinflammatory action compared to the effects achieved separately. Colitis was induced in mice by 2,4-dinitrobenzenesulfonic acid (DNBS). CBD and CBG levels were detected and quantified by liquid chromatography coupled with time of flight mass spectrometry and ion trap mass spectrometry (LC-MS-IT-TOF). Endocannabinoids and related mediators were assessed by LC-MS. DNBS increased colon weight/colon length ratio, myeloperoxidase activity, interleukin-1β, and intestinal permeability. CBG, but not CBD, given by oral gavage, ameliorated DNBS-induced colonic inflammation. FO pretreatment (at the inactive dose) increased the antiinflammatory action of CBG and rendered oral CBD effective while reducing endocannabinoid levels. Furthermore, the combination of FO, CBD, and a per se inactive dose of CBG resulted in intestinal anti-inflammatory effects. Finally, FO did not alter phytocannabinoid levels in the serum and in the colon. By highlighting the apparent additivity between phytocannabinoids and FO, our preclinical data support a novel strategy of combining these substances for the potential development of a treatment of inflammatory bowel disease.
Keywords: cannabidiol; cannabigerol; fish oil; inflammatory bowel disease; phytocannabinoids.
© 2020 John Wiley & Sons Ltd.
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