Health recently wrote an article asking if CBD oil can relieve psoriasis symptoms. In recognition of Psoriasis Awareness Month, I consulted Adam Friedman, MD, FAAD, professor and interim chair of dermatology at the George Washington School of Medicine and Health Sciences. Dr. Friedman is also the residency program director, director of translational research and director of the Supportive Oncodermatology Clinic. In addition, Dr. Friedman serves as Medical Director for ODAC -Dermatology, Aesthetic & Surgical Conference. Can CBD help relieve psoriasis symptoms? We have only begun to scratch the surface of the unbridled potential of cannabinoids as therapeutic agents. Interestingly enough, psoriasis is one of the listed indications for medical cannabis in the great state of Connecticut, though little is really known on this and many other spaces in dermatology. Let’s take a step back and first talk about CBD. CBD stands for cannabidiol, one of about 120 different molecules that come from the cannabis plant. It’s the second most prevalent active ingredient in cannabis – tetrahydrocannabinol (THC) is the first. But unlike other cannabinoids – such as THC — CBD does not produce a euphoric “high” or psychoactive effect. That said, it has 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), regulating skin physiology by being anti-inflammatory, lipostatic and antiproliferative. Now back to the original question. Inflammatory skin conditions such as psoriasis result from a number of aberrant responses of the immune cells and immune signaling in the skin. Looking at psoriasis specifically, dysregulation of the skin immune system results in marked proliferation and keratinization of epidermal cells. Overactivation of Th1 and Th17 inflammatory responses in psoriasis produces cytokines like IL-17 and IL-22 that set off cascades of events resulting in increased keratinocyte proliferation, expression of keratins 6 and 16, and inflammatory cell infiltration. Because of its role in regulating the inflammatory response of keratinocytes and dermal immune cells, the endocannabinoid system offers potential targets for the management of many inflammatoryskin conditions, but the data to date is rather limited, mostly to cell bases, ex vivo and animal models. This is what we know:Activation of the endocannabinoid system in the skin reduces inflammation through a number of mechanisms, such as shifting the pro-inflammatory Th1 response to an anti-inflammatory Th2 response via CB2r activation (thank you, CBD). The endocannabinoid system also plays a role in regulating keratinocyte proliferation and differentiation, which are pathologically increased in 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 therapeutic effects of CBD in psoriasis also include activation of non-cannabinoid receptors such as GPR55, which reduces inflammation caused by nerve growth factor, and PPARα and PPARγ which reduces epidermal hyperplasia 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 agonism of CB2r is important for controlling the inflammatory response. CB2r agonism was also shown to block the endothelial adhesion and transmigration of human neutrophils in a CB2r- dependent manner. (FASEB J. 2019; 33: 6154–6167.) 3. CBD decreases IL-17 secretion in a dose-dependent manner(at 0.1-5 μM) from MOG-stimulated encephalitogenic T cells(Experimental Autoimmune Encephalitis when injected to mice) in the presence of spleen derived antigen presenting cells. Moreover, the mRNA and protein of IL-6, a key factor in Th17 induction, 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 psoriasis 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. How does CBD compare with other psoriasis treatments? Somewhat of an unfair comparison, but the million-mile high (wording purposeful) answer is that while biologics have very specific targets to both improve efficacy and limit side effects as compared to traditional immunosuppressants, CBD has multiple receptors with multiple biological actions. Short of that, it would be hard to compare. What types of psoriasis patients could benefit the most from CBD? I don’t foresee any one particular phenotype of psoriasis benefiting more from CBD over another. Identifying ideal routes of delivery will be key as a lipophilic topical carrier could be appropriate for limited disease whereas oral administration may be more appropriate for high BSA +/- PSA. How should dermatologists counsel their psoriasis patients when considering using CBD? So, we have years of research ahead of us to elucidate even some of the most basic of questions regarding CBD as a therapeutic agent including but not limited to ideal concentration, dosing, mode of delivery and vehicle for said delivery, and combination with synergistic cannabinoids, to name a few. Until we have said information, some basic rules apply when guiding your patients with the litany of over-the-counter as well as dispensary acquired products: Be open: Demonstrate a willingness to discuss. The fastest way to end the patient – physician relationship is dismissing their interest. Test it out first: Patients should choose a test site and check for irritant or allergic contact dermatitis before using on larger areas of the body. Check the label: Patients should make sure the amount of CBD in the product is clearly listed. Know thy CBD: Patients should make sure the product is actually cannabidiol, and not just hemp seed oil (which, in fact, contains very little cannabinoids such as CBD). Shop smart: Patients should look for reputable brands and sellers. Never be afraid to look for or ask for the certificate of analysis, which states that the product has been tested by a third-party vendor. The FDA has issued multiple warning letters to companies making inappropriate claims or lacking their actual contents (check here: https://www.fda.gov/news-events/public-health-focus/warning-letters-and-test-results-cannabidiol-related-products).