Adam Friedman, MD, FAAD is Professor and Interim Chair of Dermatology and serves as Residency Program Director, Director of Translational Research, and Director of the Supportive Oncodermatology Program in the Department of Dermatology at The George Washington University School of Medicine & Health Sciences. Dr. Friedman is currently investigating novel nanotechnologies that allow for controlled and sustained delivery of a wide spectrum of physiologically and medicinally relevant molecules, such as cannabinoids, with an emphasis on treating infectious diseases, accelerating wound healing, immune modulation, and correcting vascular dysfunction.
He holds multiple patents derived from these investigations, and has published over 170 papers/chapters and 2 textbooks on both his research as well as a variety of clinical areas in dermatology with an emphasis on emerging medical therapies. He has received multiple awards such as the American Dermatologic Association Young Leader Award, the American Society for Dermatologic Surgery Cutting Edge Research Award, the 2017 Elle Beauty Genius Award, and has been on the Washingtonian Top Doctors list since 2017.
The CBD market has recently exploded, specifically after hemp was legalized in the annual Farm Bill last year. With that we have seen CBD marketed in an exponentially growing array of product types, such as oil drops, capsules, syrups, food products such as chocolate bars and gummy bears, and topical lotions and creams. Furthermore, the recent FDA approval of a CBD-based drug, Epidiolex, for treatment of two rare forms of severe epilepsy, added more fuel to the CBD craze. Unfortunately, the science, quality assurance, and regulation of these easily accessible CBD containing products has not remotely evolved at the same pace of the market and therefore there is a great need for standardized evaluation of said products to ensure the quality of production and resulting distribution. The FDA has voiced that it is working quickly to further clarify its regulatory approach for products containing cannabis and cannabis-derived compounds like CBD and will monitor the marketplace and take action against companies that violate the law in ways that raise public health concerns. The proclamation rings true with the recent issuing of 15 new warning letters to CBD based companies (12/2019), though they can not do it alone. This is why I am working with Trupotency to ensure that products containing CBD are held to a high standard, ensuring truthful labeling and claims.
I think CBD has tremendous potential in dermatology if used in an evidenced based fashion. It is important to note that CBD capitalizes on and works with systems already in place in our body, called the endocannabinoid system. Similar to our system of opioid receptors—the ones that respond to traditional painkillers—the endocannabinoid system is a network of specialized receptors that play a role in everything from sensations of pain and itch to mood, inflammation regulation, and wound healing. CBD tremendous biological reactivity through binding to a multitude of receptors, including the cannabinoid specific receptor, CB2r, which is expressed by practically every immune cell (as opposed to CB1r, which is most heavily expressed in the peripheral and central nervous system as mentioned above), regulating skin physiology by being anti-inflammatory, antiproliferative, and anti-sebum production.
This is what we know from an inflammation standpoint: Activation of the endocannabinoid system in the skin reduces inflammation through a number of mechanisms, such as shifting the pro-inflammatory response to an anti-inflammatory response via CB2r activation (thank you, CBD). The endocannabinoid system also plays a role in regulating keratinocyte (skin cell) proliferation and maturation, which are dysfunctional in aged skin and pathologically increased in diseases like psoriasis. For example, CB1r activation by cannabinoids such as anandamide (AEA) inhibits keratinocyte differentiation and decreases production of keratin K6, a marker of keratinocyte hyperproliferation. The potential anti-inflammatory effects of CBD may also also include activation of non-cannabinoid receptors such as GPR55, which reduces inflammation caused by nerve growth factor, and PPARα and PPARγ which reduces skin thickening via suppressed proliferation of keratinocytes.
Drawing from pre-clinical studies not directly related to dermatology, here’s what we know
1. CBD inhibits the Lipopolysaccharide-activated NF-κB and Interferon-β/STAT Proinflammatory Pathways in BV-2 Microglial Cells. (J. Biol. Chem. 2010, 285:1616-1626.)
2. CB2r deficiency in mice results in an exaggerated acute inflammatory response in a dorsal air pouch inflammation model, which is just a roundabout way of saying that CBD activation of CB2r is important for controlling the inflammatory response. CB2r activation was also shown to block important inflammatory cell called neutrophils from entering the skin in a CB2r- dependent manner. (FASEB J. 2019; 33: 6154–6167.)
3. CBD decreases interleukin-17 secretion ( a key inflammatory signal) in a dose-dependent manne. Moreover, the mRNA and protein of interleukin-6, a key factor in the activation of inflammation, were also decreased. (J Neuroimmune Pharmacol. 2013;8(5):1265-76.)
There is one “clinical” study (Clin Terr. 2019 170(2): e93-99), if you can even call it that, which looked at several inflammatory skin diseases, including psoriasis, and the impact of a specific product, Hemptouch organic skin care ointment (Hemptouch Ltd, Novo mesto, Slovenia), which contains CBD seed oil and natural ingredients, including Mangifera Indica, Calendula of cinalis, Lavendula of cinalis, Chamomile, Amyris Balsamifera, and butyrospermum (shea butter). This product was applied to active areas twice a day for three months in five patients with psoriasis. The topical ointment was significantly (p< 0.001) efficacious in improving PASI index score (excluding the head, which was not treated) at day 90. TEWL, skin elasticity, measured baseline and 90 days, with noted improvement. Yeaaaa ok. The authors even comment: “Main limitations of our study include the uncontrolled and retrospective design study and the small clinically heterogeneous cohort.”
So, what does it all mean? CBD clearly impacts targets important for inflammation based on solid pre-clinical work. However, clinical studies will be needed in order to optimize or even appreciate if this translates to the bedside.
I think we will see the emergence of CBD derived drugs targeting inflammatory diseases of the skin (acne, eczema, autoimmune diseases, etc) that will go through the FDA Investigational New Drug pathway of clinical trials. This work will provide us with an extraordinary amount of information and guide future development. We are already seeing this in Dermatology, not to mention the seizure medication noted above.
I think one area of great confusion is that not all cannabinoids are created equal. In fact, even physicians aren’t really sure all time, as a recent suvery study found that only 36% of participating dermatologosts know that CBD is not psychoactive (https://jddonline.com/
So lets dive in. The best-known and most-studied cannabinoids are tetrahydrocannabinol (THC) and cannabidiol (CBD), which are plant derived or “phyto” cannabinoids. While THC is best known for its mind-altering munchy causing properties, it was in fact the study of this illegal substance which led to the groundbreaking discovery of the humanendocannabinoid system I mentioned earlier (meaning, we make our very own cannabinoids and receptors for them)! Gold star for drugs?
THC and CBD have very different properties as they selectively go after each of the respective endocannabinoid receptors in the body, CB1 and CB2 respectively. CB1 is found throughout the central nervous system, which is why THC does its thing when smoked or eaten. Think of it this way however - cannabinoid receptors are present in pain circuits from the peripheral sensory nerve endings (finger tips) up to the brain thereby impacting the transmission of pain and itch. CB2 receptors, however, are found all throughout the immune system, making it a very favorable target for the management of inflammation and wound healing. CBD selectively goes after this receptor, which is why is has no psychoactive properties.