Written by Chrystal Moulton, Science Writer. We will explore the composition and value of the endocannabinoid system, as well as the natural products eliciting their therapeutic benefits through this system.

The endocannabinoid system (ECS) is a complex chemical signaling pathway that affects development and progression of various chronic ailments both neurological and metabolic. Omega-3 is known for its anti-inflammatory effects and ability to improve lipid profile. However, understanding the effect of both omega-3s and the endocannabinoid system (ECS) on overall health and well-being could support decision-making around strategies to counteract negative effects of the Western diet and the development of chronic syndromes. In this paper, we will understand what the endocannabinoid system (ECS) is, the role the ECS plays in disease, and the effect of omega-3 supplementation on the ECS.

What is the ECS?

The endocannabinoid system is comprised of receptors, enzymes, and ligands. It plays an integral role in all other systems within the body.^1-3 The respective components of the endocannabinoid system are detailed in the table below.

Table 1. Components of the Endocannabinoid System^1,2

The CB1 receptors are primarily located in the central nervous system and throughout the peripheral nervous system, as well as in the reproductive, cardiovascular, digestive, pulmonary, and immune systems.^1,2 However, they cannot be found in the brain stem and medulla oblongata, which operate the autonomic nervous system.¹ CB2 receptors are found mainly in the immune system. Together, both receptors are essential to metabolic regulation, inflammation, pain, anxiety, neuroplasticity, immune function, and bone growth.^1-3 The endogenous ligands, also known as endocannabinoids, most studied to affect biological processes are 2-arachidonoylglycerol (2-AG) and arachidonoyl ethanolamide (AEA) [also referred to as anandamide]. Both ligands can bind to either receptor.^1,2 CB1 and 2, like other G-coupled protein receptors (GPR), function via tonic signaling and phasic signaling.^1,3 Essentially, a constant basal signal is sent from cells that utilize the GPR pathway. This basal signal is referred to as the tone (or tonic signal) and regarded as the baseline. This baseline signal is maintained because ligand or endocannabinoid is kept at a specific concentration within cell. A change in cellular action potential is triggered by an increase or decrease in endocannabinoid concentration. Signals sent because of a change in endocannabinoid concentration is referred to as phasic signaling, which occurs in response to various internal or external events. The downstream effects can prove either negative or positive depending on the initial event triggering the change in tonic signaling. It is this downstream effect that interests researchers as they discover the role the endocannabinoid system (ECS) plays in overall health and disease progression.^1-3

Since the discovery of the effect of endocannabinoids in various biological systems, G-coupled receptors (GPR) within the ECS have been targeted by most pharmacological therapies.^1,2 Ongoing research on the ECS has also demonstrated that certain active components of Cannabis sativa, including beta-caryophyllene and cannabidiol, elicit therapeutic effects at the G-coupled receptors (GPR) similar to pharmaceutical drugs.^1-4

Endocannabinoids were initially discovered in the brain and thus implicated in healthy brain function.⁴ Researchers have found that dysregulation in the ECS contributes to neurodegenerative diseases such as Alzheimer’s, Huntington’s, multiple sclerosis, amyotrophic lateral sclerosis (ALS), and Parkinson’s disease.⁴(4) Furthermore, ECS dysfunction is related to cardiometabolic diseases, metabolic syndrome, and obesity.^1,5,6 Therefore existing research recommends ongoing investigation to determine how to support the ECS, more importantly, how to support this system with natural products.

Supplements Leveraging the ECS

Omega-3

Omega-3 fatty acids have been touted for its anti-inflammatory effects for decades. Omega-3 fatty acids EPA and DHA can selectively bind to CB1 receptors triggering the anti-inflammatory effects downstream. When EPA and DHA bind to the CB1 receptor, eicosopentaenoyl ethanolamide (EPEA) and docosahexaenoyl ethanolamide (DHEA), respectively, are created. These components eliminate radical oxygen species and other pro-inflammatory molecules responsible for low-grade chronic inflammation evident in most disease states.^6,7 In a comprehensive review of omega-3s’ effect with respect to the ECS, researchers found that omega-3 competes with arachidonic acid for activation at the CB receptor. The downstream effect of EPA and DHA displacing arachidonic acid is reduced endocannabinoid tone, which is associated with improvements in insulin sensitivity, blood pressure, appetite signaling, reduced lipid storage in adipose tissue and overall oxidative stress.⁶ With regard to obesity, studies showed that omega-3 intake was associated with a significant decrease in fat mass and adipocyte diameter, as well as a healthy BMI, hip and waist circumference.⁷ Researchers also found that omega-3 fatty acids leverage the ECS to improve cognitive functioning⁸ and even reverse damage caused by excessive drinking.⁹

Curcumin

Curcumin, like omega-3’s, is well-known for reducing inflammation.^10,11 Curcumin modulates the ECS to elicit its anti-inflammatory effects.¹⁰ Research has also demonstrated that curcumin exhibits anti-nociceptive effects.¹² However, it is hypothesized that curcumin doesn’t bind directly to CB receptors but rather encourages release of endogenous opioid and cannabinoids to induce its painkilling effect.¹² Curcumin is also neuroprotective and has demonstrated significant improvement in inflammatory markers as well as neurological symptom frequency in human trials.^10,11 Additional research on the form, frequency, and therapeutic dosing of curcumin is still ongoing along with the mechanism of action specific to the ECS. Nonetheless, results so far are promising.  Furthermore, research into cannabidiol and PEA have also demonstrated positive effects may be elicited via the ECS.^13,14 See Table 2 for natural products that support ECS and their respective doses.

Table 2. Supplements utilizing the ECS to provide physiological benefits

In all, the ECS is a remarkable discovery revealing an important pathway for healing and homeostatic restoration during chronic illness or disease. Leveraging this pathway could be the most effective form of treatment in therapeutics and support a healthy lifestyle.

Chrystal is a 2008 graduate of the University of Illinois at Chicago. She graduated with a bachelor’s in psychology with a focus on premedical studies and is a licensed project manager. She currently resides in Chicago.

References:

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