Abstract
The endocannabinoid system (ECS) consists of endogenous cannabinoids, their receptors, and metabolic enzymes that play a critical homeostatic role in modulating polyunsaturated omega fatty acid (PUFA) signaling to maintain a balanced inflammatory and redox state. Whole food-based diets and dietary interventions linked to PUFAs of animal (fish, calamari, krill) or plant (hemp, flax, walnut, algae) origin, as well as full-spectrum hemp oils, are increasingly used to support the ECS tone, promote healthy metabolism, improve risk factors associated with cardiovascular disorders, encourage brain health and emotional well-being, and ameliorate inflammation. While hemp cannabinoids of THC and CBD groups show distinct but complementary actions through a variety of cannabinoid (CB1 and CB2), adenosine (A2A), and vanilloid (TRPV1) receptors, they also modulate PUFA metabolism within a wide variety of specialized lipid mediators that promote or resolve inflammation and oxidative stress. Clinical evidence reviewed in this study links PUFAs and cannabinoids to changes in ECS tone, immune function, metabolic and oxidative stress adaptation, and overall maintenance of a well-balanced systemic function of the body. Understanding how the body coordinates signals from the exogenous and endogenous ECS modulators is critical for discerning the underlying molecular mechanisms of the ECS tone in healthy and disease states. Nutritional and lifestyle interventions represent promising approaches to address chronic metabolic and inflammatory disorders that may overlap in the population at risk. Further investigation and validation of dietary interventions that modulate the ECS are required in order to devise clinically successful second-generation management strategies.
Highlights
The omega-3 series metabolites lead to formation of weakly anti-inflammatory groups of prostaglandins series 3 and leukotrienes series 5 [12], as well as less abundant classes of omega-3 derived endocannabinoids such as docosahexaenoylethanolamide (DHEA), eicosapentanoyl ethanolamide (EPEA), and related metabolites [13]. Both groups are further metabolized by the eicosanoid synthesizing enzymes: cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 epoxygenase (CYP450), to produce a variety of oxylipin metabolites including the specialized pro-resolving lipid mediators (SPM) that modulate the crosstalk between the endocannabinoid system (ECS) and immune systems of the body [14]
Prostaglandins derived from arachidonic acid serve as secondary messengers of hydrophilic bioactive molecules such as glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs), and statins to regulate blood cell aggregation, dilation of blood vessels, and vascular permeability, resulting in increased tissue edema, hyperemia, and fever to maintain the propagation of an inflammatory process
These effects can be counteracted with additional eicosapentaenoic 20:5(n-3) (EPA)/docosahexaenoic 22:6(n-3) (DHA) supplementation that changes the baseline levels of lipid mediators and decreases arachidonic acid derivatives [60], while reducing expression of cannabinoid receptors and the ECS
Summary
The omega-3 series metabolites lead to formation of weakly anti-inflammatory groups of prostaglandins series 3 and leukotrienes series 5 [12], as well as less abundant classes of omega-3 derived endocannabinoids such as docosahexaenoylethanolamide (DHEA), eicosapentanoyl ethanolamide (EPEA), and related metabolites [13] Both groups are further metabolized by the eicosanoid synthesizing enzymes: cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 epoxygenase (CYP450), to produce a variety of oxylipin metabolites including the specialized pro-resolving lipid mediators (SPM) that modulate the crosstalk between the ECS and immune systems of the body [14].
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