Cannabinoids in Dermatology

Studies on cannabinoid treatment for skin conditions are promising.1 Although more research is needed, some initial studies show that enhancing the endocannabinoid system (ECS) in the skin with topical CBD and other cannabinoids can contribute to treatment for acne, skin cancer, effects of aging, atopic dermatitis, psoriasis, wound healing, and itching. Legalizing medical cannabis would in some states create more opportunities to study cannabinoids and their effects on the skin.

“There is clinical research supporting CBD’s ability to systematically lower cortisol and inflammation in the body. CBD may help manage and prevent flare-ups of inflammatory skin conditions including acne, psoriasis, and eczema,” says Deanne Mraz Robinson, MD, FAAD, cofounder of Modern Dermatology in Westport, Connecticut, and an assistant clinical professor of dermatology at Yale School of Medicine. “Endocannabinoid molecules are synthesized by several cell types in the epidermis, hair follicles, and sebaceous glands.”

Adam Friedman, MD, FAAD, chair of the department of dermatology at the George Washington University School of Medicine and Health Sciences, and two other researchers—Elizabeth S. Robinson, MD, and Emily C. Murphy, BS—conducted a 20-question online survey to gain an understanding of dermatology providers’ knowledge, attitude, and perceptions of cannabinoids.2 The questionnaire answers provided by 531 dermatologists and allied health professionals suggest that most of those providers believe the use of cannabinoids to treat various skin diseases should be investigated (94%) and were willing to prescribe FDA-approved topical cannabinoids to patients (86%). Nearly one-half of providers (48%), particularly those younger than 35 years, reported concerns about the negative perception of prescribing cannabinoids. Friedman says that one primary concern from the study is how much education is needed. “One concerning finding from the survey: 64% of responders were not aware that CBD is not intoxicating, and 29% did not know THC is psychoactive,” Friedman says.

Janice Newell Bissex, MS, RDN, FAND, is a holistic cannabis practitioner, co–program director of Cannabinoid Medical Sciences at John Patrick University School of Integrative and Functional Medicine, creator of the Jannabis Wellness product line, and author of the new book Simple Guide to CBD. She says that while double-blind human studies are lacking, evidence in animals has suggested that cannabinoids may help with a wide variety of skin conditions. “One mouse study showed that the terpene limonene, found in cannabis, decreased inflammation, inhibited oxidative stress, and induced apoptosis of cancer cells,”3 she says. “I have clients who have seen improvements in psoriasis, hives, basal cell carcinoma, and wound healing using topical CBD.”

How Do They Work? Endocannabinoid Receptors Found in the Skin
According to research published in the Journal of Clinical Investigation, the ECS governs several physiological mechanisms, including cutaneous cell growth and differentiation.4 Researchers unequivocally agree that humans have receptors which can bind and recognize 21 carbon phenolic compounds, called phytocannabinoids, from cannabis.5 The ECS is a complex cell-signaling network that’s active in the body whether cannabis is used or not. Endocannabinoids or endogenous cannabinoids are molecules made by the body, similar to phytocannabinoids, which are molecules made by plants.6 A 2009 study published in Trends in Pharmacological Sciences indicates that there is a “functional ECS in the skin” that helps control and support well-balanced skin functions such as regulating skin cell proliferation, differentiation, growth, and survival, and has an effect on the immunity and tolerance of skin cells, as well as hormone production.7 Researchers continue to look for ways to target the cutaneous ECS in skin for the treatment for skin diseases.

Promising Results: Cannabinoids May Replace Some Traditional Treatments
Cannabinoids hold promise as a treatment for a number of dermatological conditions.

Acne
Acne is the most common skin disease in the United States. The American Academy of Dermatology Association reports that although 85% of people who experience at least one form of minor acne are between the ages of 12 and 24, acne prevalence in adults has been increasing in recent years, affecting up to 15% of women.8

Jeanette Jacknin, MD, a board-certified dermatologist and author of Smart Medicine for Your Skin, one of the first books to explore integrative dermatology and holistic treatment, says that although CDB oil is well known, other nonpsychotropic phytocannabinoids have shown anti-acne effects. Jacknin refers to a Hungarian-supported study published in Experimental Dermatology in 2016. Several cannabis compounds helped normalize the elevated sebum production and inflammation characteristic of acne. Findings showed highly efficient antiacne agents in CBC (cannabichromene), CBDV (cannabidivarin), and THCV (tetrahydrocannabivarin). Additionally, CBC, CBDV, and THCV significantly reduced arachidonic acid–induced “acnelike” lipogenesis.9 A 2019 study also suggests that CBD may be beneficial for treating the appearance of acne scars.10

According to Friedman, we now have some clinical data using different cannabinoids for dermatologic disease, including acne and atopic dermatitis. “What we need is evidence-based guidance, and that requires data,” he says.

Skin Cancer
Skin cancer is the most common cancer in the United States, with 1 in 5 Americans developing it in their lifetime. “The American Cancer Society is calling for more scientific research for cannabis and cancer,” Bissex says. “They’ve reported early clinical trials showing the potential of cannabinoid therapy to mitigate the side effects of cancer and its treatment.”

Leslie Apgar, MD, is an OB/GYN, coauthor of High Heals: How Two Women Found Their Footing in the Medical Cannabis Industry, founder of PuraVida Medspa & Cosmetic Laser Center, and cofounder of Blissiva, a female-focused cannabis line. She says a peer-reviewed in vitro study in the British Journal of Pharmacology revealed that cannabigerol and CBD were able to down-regulate genes involved in both cell proliferation and differentiation of select epidermal cells.11

There’s is a considerable amount of cell and animal data suggesting that cannabinoids could potentially lead to managing nonmelanoma and melanoma skin cancer; however, human data are lacking, Friedman says. “Unfortunately,” he adds, “This has not stopped opportunists from trying to sell cannabis-based products, most notably Rick Simpson, without any supportive data and therefore causing harm.”

Friedman cites a study by Glodde and colleagues that found THC exerts antagonistic effects on the proinflammatory microenvironment of a mouse model with transplanted melanoma cells.12 “THC antagonizes infiltration of immune cells like macrophages and neutrophils into the melanoma microenvironment, which have been known to promote growth of the neoplasm,” Friedman says, highlighting the fact that THC’s role in reducing melanoma growth only occurred in vivo and not in vitro, indicating the role that the microenvironment might play in this pathway. “This might point to reasons why there have previously been contradictory studies about the role of cannabinoids in neoplasms,” he says.

Questions remain as to what types of cannabis treatments may help skin cancer in terms of topical, oral, or other administration; choice of cannabinoids; and dosage. Topical delivery, Friedman says, is problematic because the cannabinoid compounds require a fatty environment for penetration, so nanoparticles may be an effective way of delivering cannabinoids into the skin. “We honestly don’t know,” he says. “The preclinical studies have covered both topical and systemic administration of plant-derived, human-derived, and even synthetic cannabinoids. It’s really too early to say.”

Antiaging
Cannabis-based antiaging products are beginning to enter the mainstream market, according to Jacknin. Consultants at Prohibition Partners, a data company for government bodies, investors, and brands, estimates that the global CBD skin care market will reach $959 million by 2024 and include products created to be used in dermatologists’ offices and offered as medical retail.13 Jacknin says studies have shown that affecting the ECS with CBD can help skin look youthful.14

One of the critical characteristics of aging skin is a reduction in the amount of collagen. Research has shown CBD acts as a powerful antioxidant, helping to slow collagen loss and aid the skin in retaining firmness.14,15

Apgar shares her anecdotal experience, saying that cannabinoid products have worked well. Her med-spa offers a facial “featuring a powerhouse of CBD extracts,” which she says counteracts visible signs of aging, resulting in a hydrated, radiant appearance.

Dermatitis, Pruritus, and Psoriasis
“Cannabinoids possess anti-inflammatory, antimicrobial, and anti-itch properties,” Bissex says. One study, she adds, “showed a 60% improvement in itch and loss of sleep in atopic dermatitis sufferers.16 In another study, mice given THC showed a reduction in allergic swelling and inflammatory cells and compounds in the skin.”17

Pruritus, or itching, is associated with many skin diseases and appears as a secondary symptom of many serious conditions such as renal failure, diabetes, HIV, and liver disease. In 2002, the American Journal of Gastroenterology reported that three patients with cholestatic liver disease were seemingly out of options as the standard medications for pruritus no longer provided relief. They were treated with 5 mg of THC and experienced a decrease in itching and improved sleep, enabling all three to return to work.18

The Journal of the American Academy of Dermatology published a review of cannabinoids for the treatment of chronic pruritus in 2020, observing that numerous studies in vitro and using animals seem to indicate that the mechanism of neuronal modulation of peripheral itch fibers and centrally acting cannabinoid receptors has the strongest evidence of cannabinoid modulation on pruritus. Second, the review of human studies showed that some cannabinoids reduced symptoms in chronic pruritus. Finally, the review included studies that demonstrated a reduction in pruritus in both dermatologic and systemic diseases, suggesting that cannabinoid formulations are worthy of consideration in areas where they’re legal to use.19

In 2021, JAMA Dermatology reported that a patient with a 10-year history of pruritus unresponsive to topical corticosteroids and other antipruritic therapies improved over 20 months using only botanical cannabis and cannabis-based tinctures.20 The team of Johns Hopkins University researchers following the subject reported that the patient’s Dermatology Life Quality score began at 17 and fell to 1 during the period cannabinoids were used, with few adverse effects.

“One area that I’ve found most promising is in treating psoriasis,” Mraz Robinson says. She references a 2007 Journal of Dermatological Science study that showed cannabinoids might have the ability to inhibit keratinocyte proliferation, concluding that anti-inflammatory cannabinoids may have an important role in the treatment of psoriasis.21 This chronic autoimmune condition presents on the skin, Mraz Robinson says, but can also occur with joint pain (psoriatic arthritis). “Because of the multifaceted patient discomfort, it’s an area where I hope to see CBD continue to help,” she adds.

Apgar treats some patients with a CBD facial and she’s seen it bring improvement for psoriasis, acne, rosacea, and eczema. She says the benefits of the facial include regulated sebum production and a reduction in inflammation. “We also do muscle rubs on eczema, which work well,” Apgar adds. “Additionally, my mother has gotten cannabis-based treatment for lesions on her face, and she’s enjoyed great results.”

Conclusion
Paradigm shifts are slow in medicine. “In a perfect world, health professionals are open to suggesting CBD and cannabis for skin diseases and conditions,” Bissex says, “and everyone has easy access to affordable, high-quality cannabis products.”

Mraz Robinson says, “I think it’s important as health care providers that we coach our patients to be their own best advocates and encourage them to seek out CBD products with third-party testing behind them. I also advise patients to always read product labels to identify accompanying ingredients that may not be compatible with their skin.”

“In order to be current, I think physicians and other health care providers need to educate themselves about cannabinoids,” Jacknin says. She confirms that although research has slowed due to legal issues, there is still much research to back up the claims that cannabis and cannabinoids such as CBD have great potential for treating many diseases. “There are many well conducted, double-blind studies,” she says. “Some date back to the early 2000s and are relevant now.”

Friedman believes dermatologists are well positioned to be pioneers in the use of cannabinoids, and research is progressing to slowly address the gaps in our understanding of the benefits of cannabinoids for autoimmune and inflammatory conditions. “I think the future is very bright for cannabinoids in dermatology,” Friedman says. “But we can’t be overzealous and jump over the much-needed scientific journey and exploration.”

About the best way for most clinicians to move forward with adding cannabis to their dermatology practice, Apgar says that education is vital. She’s seen excellent results. “We have these cannabis solutions [for our patients]. I think it’s sad that so many [physicians] are closed-minded to them. It’s so exciting to be on the precipice of this new therapy. The future for cannabinoid use is bright, and, personally, I’m grateful to be on the forefront.”

— Michele Deppe is a freelance writer based in South Carolina.

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