Abstract
Recently, cannabis, or its major constituent cannabidiol (CBD), has emerged as an attractive cosmetic ingredient. Initiated as a basic investigation of the physiological roles of cannabinoid receptors and their endogenous ligands, endocannabinoids’ diverse potential benefits have been proposed for using cannabinoid receptor modulating compounds in skin health. Improvement in skin barrier functions, alleviating inflammatory responses, and the relief of itching sensations are some commonly expected therapeutic benefits, which have been supported by many in vitro, in vivo, and clinical studies. While hemp seed oils or hemp extracts might be used for the cosmetic formulation, the potential for contamination with a psychoactive cannabinoid, such as 9-THC, should be carefully checked. Instead of using hemp-derived ingredients, the use of cannabinomimetics, synthetic ligands on cannabinoid receptors, or entourage compounds (which modulate intracellular synthesis and the degradation of endocannabinoids), have been tried. In this review, a brief introduction of the epidermal endocannabinoid system (EES) and its physiological roles will be followed by a review of the cosmetic and dermatologic application of cannabinomimetics and entourage compounds. The practical application of newly developed endocannabinomimetics will be discussed as well.
Highlights
Cannabis, or its major constituent cannabidiol (CBD), has emerged as an attractive cosmetic ingredient
Intracellular transport and uptake of endocannabinoids have been reported as having modulatory activity on endocannabinoid system (ECS) tones, which has emerged as a new potential target for ECS activity modulation [3]
Cannabinoid receptor-1 (CB1R) and cannabinoid receptor-2 (CB2R), have been identified and cloned from mammalian tissue. Both receptors belong to the seven-transmembrane G-protein-coupled receptor (GPCR), coupled to Gi-Go heterotrimeric G proteins [5]
Summary
As a Gi-coupled GPCR, the binding of an agonistic ligand on a cannabinoid receptor (CBR). CBRsAEA and catalyzes the cellular synthesis of AEA, stimulation of cellular uptake of AEA by a specific further induce cellular responses This kind of indirect activation of CBRs through the modulation membrane transporter (AMT), or inhibition of AEA-hydrolyzing enzyme fatty acid amide hydrolase of related can enzymes or transporter activity called an “entourage [20]. While the “entourage effect” was first used for describing the modulating ability to interfere with the degradation of biologically active (target receptor binding) compounds, or to increase the affinity of active compounds on the target receptor [21] This indirect modulation of CBRs underlies, at least in part, the mode of action for the current use of palmitoylethanolamine (PEA) as a topical anti-inflammatory and anti-pruritic ingredient [22,23]. It can be suggested that, even with a CBR agonist with lower efficacy, a combination of FAAH inhibitors or other entourage compounds can provide sufficient therapeutic efficacy [24]
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