Using the Endocannabinoid System for Better Skin Health Sponsored by CV Sciences

By Joseph Maroon Maroon, MD, FACS

December 10, 2019

Why are we hearing so much about CBD and skincare? It’s because our skin—the largest of our organs—contains a vast amount of cannabinoid receptors and endocannabinoid machinery. A number of excellent review papers1-3 show how endocannabinoids, along with the phytocannabinoids that work with them, affect everything from skin homeostasis and wound repair4 to skin permeability and the differentiation of skin stem cells.

We’ve seen increasing research on the endocannabinoid system (ECS) since it was discovered in the early 90s. The existence of the first two cannabinoid receptors—CB1 and CB2—suggested the presence of endocannabinoid neurotransmitters that work to bind them. Although we now know of six such neurotransmitters, the two that have been most closely studied are anandamide (AEA) and 2-AG. And in the field of dermatology, we’ve also seen considerable research on the anti-inflammation effects of the endocannabinoid palmitoylethanolamide (PEA).

To be discussed here are the specific effects of endocannabinoids on the four main skin cell types: keratinocytes, mast cells, melanocytes, and sebocytes.


Professor and author Dr. Mauro Maccarrone wrote a paper on the accumulating evidence that AEA controls the differentiation of keratinocytes,5 the primary cell of the epidermis and the producers of the keratin that makes up the outermost layer of our skin. It surprised researchers to find that endocannannoids may be the primary regulators of this vital process. One known effect of CBD is lowering the activity of the FAAH enzyme responsible for degrading AEA; therefore, the ability of CBD to raise the AEA levels controlling skin differentiation may be one of the reasons for its effectiveness in skin products.

Additional research has shown that the activation of the CB1 receptor in keratinocytes lessens allergic inflammation via the modulation of proinflammatory chemokines.6 Furthermore, the activation of the CB2 receptor in keratinocytes releases endorphins that lessen pain transmission,7 and because CBD induces antioxidant pathways in keratinocytes,8 it may be helpful in atopic dermatitis. Research also points to how electroacupuncture increases CB2 expression on keratinocyte membranes.9

Mast cells

Our skin’s mast cells also contain both CB1 and CB2 receptors. Mast cells are generally known for being carriers of the histamine underlying allergic reactions - but they are also involved in wound healing, pathogenic immune responses, and angiogenesis (blood vessel formation). Research from the Endocannabinoid Research Group in Naples, Italy, shows that “mast cells act as surveillance antennae against different types of injury and can undergo activation, thereby regulating both innate and adaptive immune reactions through the release of several preformed and newly synthesized mediators. Mast cells are now viewed as key players in orchestrating several disorders including both acute and chronic inflammatory processes, and have a role in angiogenesis and hyperalgesia.”10 PEA helps to modulate mast cells via a complex modulation of receptors, AEA causes them to produce fewer proinflammatory molecules.11 Because of the tight regulation of the skin by endocannabinoids, the activation of CB1 receptors show promise for skin allergies and other mast cell-dependent skin diseases.12


A third important skin cell type found to contain the full complement of endocannabinoid machinery are melanocytes, which produce the dark pigment melanin that protects the skin from UV radiation. Activation by AEA induces melanogenesis in these cells,13 and when the skin is insulted by UV light, cannabinoid receptors play a role in mediating the damage.14 When melanocytes start to divide uncontrollably, they become one of the deadliest forms of cancer: melanoma. Recent work has suggested the activation of cannabinoid receptors is a way to slow tumor growth15 and to cause apoptosis of cancerous cells.16


Lastly, sebocytes are the highly specialized cells that produce the sebum (oil) that protects the outer layer of our skin. If overactive, the excess oil leads to acne. CBD shows potential as an acne treatment because it suppresses sebocyte proliferation while also exerting anti-inflammatory effects.17 In addition, the transient receptor potential vanilloid-1 channels (TRPV1) regulates human sebocytes, and anandamide is a known activator of these TRPV channels.18 In fact, several of the cannabinoids from the plant have shown effectiveness in the treatment for both dry skin and acne.19

This article summarizes only a small portion of our knowledge on the relationship of the endocannabinoid system to the skin and does not explore the efficacy of cannabinoids on disease states. Yet it serves to show the exciting and ever-increasing science that supports the popularity of CBD and full-spectrum hemp extracts for dermatological use.

About the Author

Joseph Maroon, MD, FACS is a board-certified neurosurgeon and Heindl Scholar in neurosciences. He is regarded as a premier specialist in the surgical treatment of injuries and diseases of the brain and spine, particularly with microscopic and minimally invasive procedures. He has published over 270 papers and is on numerous editorial boards. He is consistently listed in America’s Best Doctors and has an international patient clientele. He is the co-developer of ImPACT™ (Immediate Post-Concussion Assessment and Cognitive Testing). Maroon is also a health and fitness expert and Ironman triathlete. He has written six books including Fish Oil: The Natural Anti-Inflammatory and The Longevity Factor: How Resveratrol and Red Wine Activate Genes for a Longer and Healthier Life. He is president of Inflammation Solutions, LLC, and serves as senior vice-president of the American Academy of Anti-Aging Medicine.


  1. Cannabinoid Signaling in the Skin: Therapeutic Potential of the "C(ut)annabinoid" System
  2. Cannabinoids in dermatology: a scoping review
  3. The Therapeutic Potential of Cannabinoids in Dermatology
  4. Cannabinoid CB2 receptors are involved in the regulation of fibrogenesis during skin wound repair in mice
  5. Regulation of gene transcription and keratinocyte differentiation by anandamide
  6. Cannabinoid 1 receptors in keratinocytes modulate proinflammatory chemokine secretion and attenuate contact allergic inflammation
  7. Signaling Mechanism of Cannabinoid Receptor-2 Activation-Induced β-Endorphin Release
  8. Cannabidiol induces antioxidant pathways in keratinocytes by targeting BACH1
  9. Electroacupuncture increases CB2 receptor expression on keratinocytes and infiltrating inflammatory cells in inflamed skin tissues of rat
  10. New insights in mast cell modulation by palmitoylethanolamide
  11. Anandamide inhibits FcεRI-dependent degranulation and cytokine synthesis in mast cells through CB2 and GPR55 receptor activation. Possible involvement of CB2-GPR55 heteromers
  12. Endocannabinoids limit excessive mast cell maturation and activation in human skin
  13. Endocannabinoids stimulate human melanogenesis via type-1 cannabinoid receptor
  14. Inhibition of basal and ultraviolet B-induced melanogenesis by cannabinoid CB(1) receptors: A keratinocyte-dependent effect
  15. Ligands for cannabinoid receptors, promising anticancer agents
  16. Exploiting cannabinoid-induced cytotoxic autophagy to drive melanoma cell death
  17. Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes
  18. Transient receptor potential vanilloid-1 signaling as a regulator of human sebocyte biology
  19. Differential effectiveness of selected non-psychotropic phytocannabinoids on human sebocyte functions implicates their introduction in dry/seborrhoeic skin and acne treatment