How CBD Supports the Skin Endocannabinoid System

Medically reviewed by Stefan Kuprowsky, ND

As the largest organ in the body, the skin is constantly being challenged by myriad environmental and cosmetic compounds, climate conditions, internal stress and diet.

Most people tend to view their skin as a means of attraction; clean, youthful and hydrated skin is the goal to enhance visual appeal. However, most people don’t know that their skin has a more pertinent role in health and well-being, as the barrier that both protects against the elements and releases irrelevant compounds or toxins through the pores.

The skin’s dual functionality is controlled in part by dermal immune cells that protect it from pathogens, sebocytes that release sebum, the viscous substance coating the skin as a protectant, and sensory neurons that alert to sensations touching or wafting by the skin.

The skin also features a self-contained endocannabinoid system (ECS) that acts to help regulate all functions of the skin; this ECS is integrated into the larger ECS in the body. The skin ECS functions autonomously, producing endocannabinoids, notably anandamide (AEA), and 2-AG. These endocannabinoids are generated as needed to manage a physiological response in the skin, after which they are quickly degraded. Anandamide is a fatty acid neurotransmitter that plays a significant role in homeostasis and was, incidentally, the first endocannabinoid to be discovered, in 1992. A few years later in 1995, 2-AG or endogenous 2-monoglyceride, was identified.

In addition, research has revealed that the skin contains a widespread distribution of cannabinoid receptor type 1(CB1) and cannabinoid receptor type 2(CB2). In 2005, researchers discovered CB1 and CB2 were found in epidermal keratinocytes, hair follicle and sebaceous glands. They further discovered that the placement of the cannabinoid receptors on the skin’s nerve fibers and mast cells suggested that they participated in regulating inflammatory response.

The skin ECS has also been shown to have regulatory roles in varied dermal cells; roles include growth, proliferation, differentiation, and apoptosis in the hair follicles and sebaceous glands in the skin’s landscape. Further, it is theorized that disruption of the regulatory balance may result in the pathogenesis of skin conditions such as seborrhea, scleroderma allergic dermatitis, acne, itching, hair growth disorders and psoriasis.

The Roles of CBD in Skin Health

Cannabidiol has been widely reported anecdotally to be therapeutic in alleviating skin conditions and reducing skin symptoms. Research began investigating the activity and efficacy of CBD through skin in animal models in 2003.

CBD was (and continues to be) studied for effects in barrier function/protection, atopic dermatitis, pruritis, wound healing, and seborrhea/acne.

Sun exposure generates oxidative stress in keratinocytes, a process that causes inflammation. NRF2 and PPARy, which play significant roles in the antioxidant defense response in skin cells, help protect against reactive oxygen species (ROS), created by sun and other harmful exposures to the skin. Among the evidence is one study on human keratinocytes, where CBD was shown to facilitate expression of genes targeted by NRF2, such as the stress-associated hemeoxyenase1 (HMOX1).  

Severe itching that defines pruritis and is also a symptom of psoriasis is a condition that research shows has approximately 18,000 genes commonly expressed. Findings of a study suggest that endocannabinoid-degrading enzymes FAAH (fatty acid amide hydrolase) and MAGL (monoacylglycerol lipase) are implicated in the cascade of pruritis, and therefore agents that inhibit FAAH and/or MAGL may have promising antipruritic effects. Supporting endocannabinoid activity through inhibiting FAAH and MAGL is believed to help reduce pruritus.

A more intense chronic condition is atopic dermatitis (or eczema) that is often triggered by environmental agents. In one study CBD was able to exert anti-inflammatory properties through activating CB2 receptors.

Acne vulgaris, generated by hyperproduction of sebum through sebocyte proliferation and concurrent inflammation, may be partially caused by a dysfunction in the skin ECS, notably the endocannabinoid AEA, which stimulates the production of lipids in sebocytes. Research has shown that CBD acts as an effective suppressor of sebocyte proliferation. The authors of the study were staunch in their conclusion that CBD has promising therapeutic potential for managing acne.

What Ingredients Synergize with CBD for Topical Use?

CBD and other synergistic ingredients provide a new approach to dealing with dermatological conditions. With CBD and other co-factors, we can influence the dermatological ECS through its receptors to mitigate abnormal skin conditions.

Hemp and botanical-derived terpenes contribute to and amplify the therapeutic effects of CBD. Linalool is the calming, anti-inflammatory and analgesic active ingredient in lavender, while pinene from pine is likewise anti-inflammatory as well as anti-microbial. Beta-caryophyllene, a dietary cannabinoid found in black pepper and cloves, acts as an anti-bacterial, analgesic and anti-inflammatory.

Palmitoylethanolamide (PEA) is a potent, multi-functional compound that also acts as an analgesic and anti-inflammatory. This endogenous fatty acid, found in every cell of the body, functions as a parallel endocannabinoid. It is auto-generated as needed to help with regulation of pain and inflammation. In addition, there is evidence that PEA may help alleviate inflammation in cases of pruritus, as well as in neuropathic discomfort.

The potential applications for topical CBD are numerous. They include easing physical discomfort, modulating inflammation, and easing itching, burns and breakouts, as well as potentially enhancing moisturization.

CBD as an effective key ingredient for topical formulas is an exciting area for researchers and for product formulators, and you will assuredly see much more in this area that can help you help your patients support their skin health.

References

A.T. Peana, et al. Anti-inflammatory activity of linalool and linalyl acetate constituents of essential oils, Phytomedicine, Volume 9, Issue 8, 2002, Pages 721-726, ISSN 0944-7113

Baswan SM, et al. Therapeutic Potential of Cannabidiol for Skin Health and Disorders. Clin Cosmet Investig Dermatol. 2020;13:927-942.

Bíró T, et al. The endocannabinoid system of the skin in health and disease: novel perspectives and therapeutic opportunities. Trends Pharmacol Sci. 2009 Aug;30(8):411-20. doi: 10.1016/j.tips.2009.05.004. Epub 2009 Jul 14.

Casares L, et al. Cannabidiol induces antioxidant pathways in keratinocytes by targeting BACH1. Redox Biol. 2020 Jan;28:101321. doi: 10.1016/j.redox.2019.101321. Epub 2019 Sep 5. PMID: 31518892; PMCID: PMC6742916.

Devane WA, et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science. 1992 Dec 18;258(5090):1946-9.

Dobrosi N, et al. Endocannabinoids enhance lipid synthesis and apoptosis of human sebocytes via cannabinoid receptor-2-mediated signaling. FASEB J. 2008 Oct;22(10):3685-95. Epub 2008 Jul 2.

Gertsch, Jurg, et al. “Beta-Caryophyllene Is a Dietary Cannabinoid.” Proceedings of the National Academy of Sciences, vol. 105, no. 26, 1 July 2008, pp. 9099–9104.

Lee C. Collaborative Power of Nrf2 and PPARγ Activators against Metabolic and Drug-Induced Oxidative Injury. Oxid Med Cell Longev. 2017;2017:1378175. Epub 2017 Aug 27.

Mechoulam R, et al. Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem Pharmacol. 1995 Jun 29;50(1):83-90.

Nattkemper LA, et al. The Genetics of Chronic Itch: Gene Expression in the Skin of Patients with Atopic Dermatitis and Psoriasis with Severe Itch. J Invest Dermatol. 2018 Jun;138(6):1311-1317. Epub 2018 Jan 6.

Oláh A, et al. Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes. J Clin Invest. 2014 Sep;124(9):3713-24. doi: 10.1172/JCI64628. Epub 2014 Jul 25. PMID: 25061872; PMCID: PMC4151231.

Petrosino S, et al. Anti-inflammatory Properties of Cannabidiol, a Nonpsychotropic Cannabinoid, in Experimental Allergic Contact Dermatitis. J Pharmacol Exp Ther. 2018 Jun;365(3):652-663. Epub 2018 Apr 9. 

Re G, et al. Palmitoylethanolamide, endocannabinoids and related cannabimimetic compounds in protection against tissue inflammation and pain: potential use in companion animals. Vet J. 2007 Jan;173(1):21-30. doi: 10.1016/j.tvjl.2005.10.003. Epub 2005 Dec 1.

Silva, A.C.R.d, et al. Biological Activities of a-Pinene and β-Pinene Enantiomers. Molecules 201217, 6305-6316.

Ständer S, et al. Distribution of cannabinoid receptor 1 (CB1) and 2 (CB2) on sensory nerve fibers and adnexal structures in human skin. J Dermatol Sci. 2005 Jun;38(3):177-88.

Tosun NC, et al. Attenuation of serotonin-induced itch responses by inhibition of endocannabinoid degradative enzymes, fatty acid amide hydrolase and monoacylglycerol lipase. J Neural Transm (Vienna). 2015 Mar;122(3):363-7. Epub 2014 Jun 11.

Yesilyurt O, et al. Systemic and spinal administration of FAAH, MAGL inhibitors and dual FAAH/MAGL inhibitors produce antipruritic effect in mice. Arch Dermatol Res. 2016 Jul;308(5):335-45. Epub 2016 Apr 28.