Are Cannabinoids the Future of Dermatology?

Medical Cannabinoids

Currently, there are only 4 FDA-approved synesthetic and phytocannabinoid medications available in the United States. These are approved for neurologic conditions or adverse effects associated with chemotherapies for cancers:

  • Dronabinol (Marinol)
  • Nabilone
  • Nabiximols (Sativex)
  • Cannabidiol (Epidiolex)

In dermatology, preclinical and a few clinical trials are showing the efficacy of cannabinoids for various skin conditions (Table),3,5 including atopic dermatitis, psoriasis, acne, scleroderma, skin cancers, neutrophil diseases, dermatomyositis, and cutaneous lupus erythematosus (CLE).3,6-8 Cannabinoids also have potential for the treatment of hidradenitis suppurativa, lichen simplex chronicus, prurigo nodularis, among other inflammatory conditions. 

table

Two studies found evidence suggesting that cannabinoids could be used to target acne. Oláh et al showed that CBD inhibited sebocytes and inflammation in immune cells.6 Similarly, Ali et al found that cannabis 3% extract improved acne symptoms among participants.7 More trials are needed to examine cannabis’ full potential as a topical acne treatment.

In autoimmune diseases, phase 3 trials are investigating the efficacy of synesthetic AJA at treating refractory skin-predominant dermatomyotisis8 and cutaneous systemic sclerosis,9 with results showing efficacy for both conditions. Preclinical data also demonstrated efficacy of topical 4% AEA, administered with nanoparticles, at reducing symptoms of CLE in mice.10 

These studies and further explorations into the ECS’ role in skin care show the limitless potential for harnessing cannabinoids for the treatment of various skin conditions, including ones with few other therapeutic options.

Areas for Consideration 

Although several forms of cannabinoids are under investigation, many questions regarding best practices for selecting the type or ratio, such as TCH to CBD, administration, and dosage remain unanswered. Patients recommended cannabis by a provider predominately receive the products from dispensaries, limiting the ability of providers and patients to determine which type of cannabis and which ratio of cannabinoids are effective for their condition. In addition, routes of administration for various conditions are still under investigation, with the focus being on oral and topical forms due to negative stigma around inhalable cannabis.

For topical therapies, investigations into the best delivery method are underway. Topical delivery of cannabinoids, in particular, is problematic due to the highly lipophilic nature of the compounds, which have poor penetration outside of fatty environments. One possible solution is using nanoparticles, which slowly delivers cannabinoids into the skin for maximum penetration and benefit to patients. Mouse models of CLE showed the efficacy of using nanoparticles for delivering cannabinoids into the skin and improving symptoms.10

In addition to drug development, there is a need to educate providers. Survey data of 531 dermatologists and allied health professionals suggests that the majority of providers are open to the exploration of cannabinoids for the treatment of various skin diseases (94%) and were willing to prescribe topical cannabinoids to patients (91%).11 Nearly half of providers (47.5%), particularly those younger than 35 years, reported concerns about the negative perception of prescribing cannabinoids. 

One concerning finding from the survey was 64% of responders were not aware that CBD is not psychoactive and 29% did not know THC is psychoactive. Providers recommending cannabis will need some form of education on the benefits, harms, and risks associated with cannabinoids, like other therapies, to ensure that patients are aware of all potential outcomes and can be informed when selecting cannabinoid-based products at dispensaries.11 

Prescribing Cannabis

With the exception of the 4 FDA-approved cannabinoids, cannabis cannot be prescribed. Providers can recommend or refer cannabis to patients based on their state’s requirements. As more state laws change in favor of medical cannabis, providers should be prepared for patients to ask about the potential of these therapies. At the time of the above-mentioned survey in 2018, 55% of dermatologists reported a patient asking about it.11 This number will likely rise over the next few years as cannabis use for medical purposes becomes more legally and culturally acceptable.

Prior to recommending cannabis, providers should be aware of all processes required by their states that must be completed, such as online registration or formal letters, and know their state’s allowable indications. All states that allow the use of medical cannabis (Figure) permit referrals for pain management. Illinois, Michigan, Maine, New Hampshire, and Connecticut have allowable indications for 4 dermatologic conditions: CLE (IL, NH), nail-patella syndrome (IL, MI, ME), neurofibromatosis (IL), and psoriasis (CT). 

cannabinoids map

Figure. Cannabis Programs by State. Adapted from reference 12.

Similar to other therapies, physicians and patients should discuss risks, benefits, and adverse effects of cannabinoids and cannabis use. When recommending cannabinoids, providers should take steps to avoid blindly handing out referrals to patients and becoming a “marijuana mill.” Organizations including the Canadian Consortium for the Investigation of Cannabinoids (http://www.ccic.net) and the University of Washington’s Alcohol and Drug Abuse Institute (http://adai.uw.edu/mcacp/toolkit.htm) offer online toolkits with printable forms to help walk you through steps for recommending cannabis. Other general tips:

  • Follow a medical cannabis checklist (you can find these in online toolkits such as those mentioned above)  
  • Use validated quality-of-life measures to record patients’ progress
  • Create a signed, written contract with the patient (also in online toolkits)
  • Use the following mantra: “start low, go slow, stay low” (use low concentrations to achieve maximum benefit without adverse effects)

Looking Ahead 

Paradigm shifts are slow, even in medicine. In 1910, germ theory was considered a controversial topic and remained as such until changes in technology and studies on microorganisms shifted public opinion. Cannabinoids as a medical treatment are facing similar opposition, but research is doing its best to slowly address the gaps caused by social and legal controversies. In the midst of this major paradigm shift, dermatology needs to be at the forefront of current research endeavors on the benefits of cannabinoids for autoimmune and inflammatory conditions, which can then be taught to peers in other fields. It is vital for us to play an active role in bolstering research and improving our understanding of cannabinoids and the ECS, not just be spectators waiting for other fields to discover all the possibilities. 

Dr Friedman is a professor of dermatology, residency program director, director of translational research, and director of supportive oncodermatology at George Washington School of Medicine and Health Sciences in Washington, DC.

 

Disclosures: Dr Friedman was a consultant and/ or worked on the ad board for Loreal, La Roche Posay, Galderma, Aveeno, Valeant, Microcures, Biogen, Pfizer, G&W, Laboratories, Novartis, Sonoma Pharmaceuticals, Intraderm, Encore, Exeltis, Menlo, Lilly, Aclaris, Dermira, Berg, Allergan, Zylo Therapeutics. He was a speaker for Janssen, Regeneron, and AbbVie, as well as received grants from Aclaris and CPN.

References

1. Castillo PE, Younts TJ, Chávez AE, Hashimotodani Y. Endocannabinoid signaling and synaptic function. Neuron. 2012;76(1):70-81. doi:10.1016/j.neuron.2012.09.020

2. Chiurchiù V, Battistini L, Maccarrone M. Endocannabinoid signalling in innate and adaptive immunity. Immunology. 2015;144(3):352-364. doi:10.1111/imm.12441

3. Milando R, Friedman A. Cannabinoids: Potential role in inflammatory and neoplastic skin diseases [published online December 12, 2018]. Am J Clin Dermatol. doi:10.1007/s40257-018-0410-5

4. Bridgeman MB, Abazia DT. Medicinal cannabis: History, pharmacology, and implications for the acute care setting. P T. 2017;42(3):180-188. 

5. Bíró T, Tóth BI, Haskó G, Paus R, Pacher P. The endocannabinoid system of the skin in health and disease: novel perspectives and therapeutic opportunities. Trends Pharmacol Sci. 2009;30(8):411-420. doi:10.1016/j.tips.2009.05.004

6. Oláh A, Tóth BI, Borbíró I, et al. Cannabidiol exerts sebostatic and anti-inflammatory effects on human sebocytes. J Clin Invest. 2014;124(9):3713-3724. doi:10.1172/JCI64628 

7. Ali A, Akhtar N. The safety and efficacy of 3% Cannabis seeds extract cream for reduction of human cheek skin sebum and erythema content. Pak J Pharm Sci. 2015;28(4):1389-1395.

8. Werth VP, Hejazi E, Pena SM, et al. A phase 2 study of safety and efficacy of anabasum (JBT-101), a cannabinoid receptor type 2 agonist, in refractory skin-predominant dermatomyositis. Presented at: 2017 American College of Rheumatology Annual Meeting; November 3-8, 2017; San Diego, CA. 

9. Spiera RF, Hummers LK, Chung L, et al. A phase 2 study of safety and efficacy of anabasum (JBT-101), a cannabinoid receptor type 2 agonist, in diffuse cutaneous systemic sclerosis. Presented at: 2017 American College of Rheumatology Annual Meeting; November 3-8, 2017; San Diego, CA.

10. Chalmers S, Garcia S, Draganski A, et al. Topical endocannabinoid administration protects MRL-Lpr/Lpr mice from cutaneous lupus erythematosus. Presented at: 2018 American College of Rheumatology Annual meeting; October 19-24, 2018; Chicago, IL.

11. Robinson ES, Murphy EC, Friedman AJ. Knowledge, perception, and attitudes of cannabinoids in the dermatology community. J Drugs Dermatol. 2018;17(12):1273-1278.

12. State medical marijuana laws. National Conference of State Legislatures website.http://www.ncsl.org/research/health/state-medical-marijuana-laws.aspx. Published November 11, 2018. Accessed January 11, 2019.



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