CBD: Potential or placebo?

By Emily Margosian, assistant editor

This recent Mother’s Day holiday, shoppers may have observed a different type of product among the typical mugs, greeting cards, and candles. “Get your mom the tools she needs to de-stress and treat herself,” wrote an ad for a popular craft and greeting card chain. Featured items included CBD-infused oils, exfoliants, sheet masks, and patches. While moms and marijuana might not seem a likely combination, as medical and recreational use have become widely available, consumer interest in cannabinoids has risen sharply. Cannabidiol, or CBD, has found its way into a variety of products, many of which claim dermatologic applications. “Recent years have brought an assortment of cannabinoid-containing topicals such as oils, lotions, emollients, creams, and patches specifically advertised for use on the skin,” observed a recent JAAD article (https://doi.org/10.1016/j.jaad.2020.01.036).

However, despite the explosion in popularity of these products, many questions remain regarding the efficacy and long-term effects of CBD use. This month, Dermatology World investigates the research currently available regarding CBD’s effects, its potential dermatologic uses, and what regulators are doing to ensure the safety and quality of CBD products available on the market. >>

What is CBD?

While many consumers have likely seen the letters “CBD” applied to a product, they may not necessarily know what it is, or how it is distinguished from other cannabis-derived components. In a recent Q&A with DW physician editor Kathryn Schwarzenberger, MD, (May 2020), Mark Bechtel, MD, professor and division director of dermatology at the Ohio State University Wexner Medical Center, described the differences between the many variants derived from cannabis. “Phytocannabinoids derived from the marijuana plant, Cannabis sativa, include: Δ (9) – tetrahydrocannabinol (THC) and cannabidiol (CBD),” Dr. Bechtel explained. “Medical marijuana contains THC, which produces the psychoactive effects, while CBD oil does not contain THC and has no psychoactive stimulation. Hemp is a strain of the Cannabis sativa plant species, which has been used in the past for industrial purposes. Hemp oil has only traces of CBD and THC. Because it contains high quantities of omega 3 and omega 6 fatty acids, it can be used as an emollient.”

Currently, CBD has become a popular ingredient in an expanding variety of products including soft chews, oils, pet food, and sparkling water. Although CBD is generally ingested, it has also become a common presence in topical products such as lotions and balms.

CBD also has a wide range of alleged benefits, not limited to: relief from seizures, pain, depression, anxiety, insomnia, inflammatory bowel disease (IBD), migraines, and nausea, although most CBD products are marketed for general relaxation purposes.

What does the evidence show regarding its effects?

Research regarding the effects of CBD is ongoing. To date, CBD has been found to effectively treat certain types of epilepsy in clinical trials, and in June 2018, the FDA approved the first drug containing CBD (Epidiolex) for the treatment of seizures associated with two rare and severe forms of epilepsy, Lennox-Gastaut syndrome and Dravet syndrome, in patients two years of age and older.

Beyond treatment for epilepsy however, there is a lack of strong evidence on the therapeutic benefit of CBD for any particular medical condition, and there are mostly negative reports regarding the effectiveness of CBD compared to placebo. A 2018 report submitted by the World Health Organization’s Expert Committee on Drug Dependence cited limited evidence that CBD may help with opioid, cocaine, and tobacco addiction; however, it reiterated that more research is needed (www.who.int/medicines/access/controlled-substances/CannabidiolCriticalReview.pdf).

What about CBD and dermatology?

Recent studies have examined the use of cannabinoids in dermatology for the treatment of psoriasis, atopic dermatitis, dermatomyositis, wound healing, and melanoma. However, current research shows the most promise for cannabinoids in the treatment of itch. A recent 2020 study in JAAD suggests that topical application and oral administration of cannabinoids may be effective at treating chronic pruritus related to several conditions, including neurogenic itch, atopic dermatitis, asteatotic eczema, allergic contact dermatitis, prurigo nodularis, uremic pruritus, and cholestatic pruritus (https://doi.org/10.1016/j.jaad.2020.01.036). Dr. Bechtel, who co-authored the paper, notes in his conversation with Dr. Schwarzenberger that, “Cannabinoids, based on their pharmacodynamics, have the potential to be a significant part of our anti-itch therapeutics. The delivery method for cannabinoids, which are highly lipophilic, determines efficacy due to different bioavailability.” The study reports that to date, the anti-pruritic effects of cannabinoids have been mainly observed in non-THC containing cannabinoids, such as CBD and PEA, “eliminating the concern for undesired psychoactive effects” (https://doi.org/10.1016/j.jaad.2020.01.036).

According to Robert Dellavalle, MD, PhD, MSPH, professor of dermatology and public health at the University of Colorado Medicine, topical cannabinoids are a promising alternative for patients wary of traditional therapies. “Dermatologists are always looking for additional therapies for treating itch — a symptom they hear a lot about from their patients. At the same time, many patients are actively seeking nonsteroidal therapies for skin disease,” he said. “Topical cannabinoids are promising new anti-itch, anti-inflammatory skin therapy, and given recent changes in U.S. law, topical CBD is now widely available.”

According to Dr. Dellavalle, cannabinoids may also show promise in the treatment of serious dermatologic conditions, although more research is needed. “I was impressed by photography of chronic wound healing following topical cannabinoid application, which was presented at a recent CannX cannabinoid conference in Lisbon, Portugal,” said Dr. Dellavalle, who receives stock options and expense reimbursement as a medical consultant for Altus Labs. “I am waiting to see those results in the peer-reviewed academic literature. Cannabinoids can clearly help treat pain. Currently, DEBRA UK is funding a randomized controlled trial of oral CBD for the treatment of pain and itch in epidermolysis bullosa patients, and I’m looking forward to seeing the results of that trial as well.”

What do dermatologists think about cannabinoids?

As the regulatory landscape and cultural stigmas surrounding cannabis use loosen, physicians are increasingly likely to encounter cannabinoids in practice or even in their personal lives. A 2019 JAAD survey examined dermatology workforce perspectives on the use and benefits of cannabinoids, as well as their general knowledge of cannabis. While nearly all of survey respondents (94%) thought it was worthwhile to research dermatologic uses of cannabinoids, almost half (48%) were concerned about negative stigma when proposing cannabinoid therapy.

Interestingly, younger respondents (35 years or younger) were more likely to be concerned about this stigma than their older counterparts. See the graphic below for a further breakdown of the survey’s findings regarding the dermatology community’s perceptions and attitudes regarding cannabinoid use.

90% think cannabinoids have benefits beyond pain and nausea
86% think cannabinoids should be legal for medical treatment
86% are willing to prescribe cannabinoids as a topical treatment
81% were uncomfortable with their knowledge of cannabinoid biology
71% are willing to prescribe oral forms
64% did not know that CBD is not psychoactive
55% reported at least one patient-initiated discussion of cannabis last year
29% did not know that THC is psychoactive

Source: https://doi.org/10.1016/j.jaad.2019.06.337.

What are the risks?

While CBD holds promise, given the lack of available research regarding its effects and current regulatory status, physicians and their patients should be aware of the potential risks. CBD must contain no more than 0.3% THC to be considered legal at the federal level. However, given CBD’s current lack of FDA regulation, retailers may not adequately disclose the amount of THC in their products, potentially resulting in a positive drug screen several days or even weeks after consumption. Likewise, CBD products are widely available for purchase online with little consumer safety oversight and can contain unknown and potentially hazardous elements.

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“The FDA exercised limited enforcement for CBD,” says Natasha Pattanshetti, JD, MPH, AADA manager of regulatory policy. “This has to do primarily with enforcement resources, if the CBD product has medical claims or is intended to treat a medical condition, and the risk posed by the CBD product.” Pattanshetti notes that while many CBD products fall under the FDA’s definition of what constitutes a drug (“a substance intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease,” or “a substance (other than food) intended to affect the structure or any function of the body”) — and would necessitate some sort of approval by the agency, many CBD products meeting this criteria have not received FDA approval.

In a November 2019 statement, FDA Principal Deputy Commissioner Amy Abernethy, MD, PhD, said, “We remain concerned that some people wrongly think that the myriad of CBD products on the market, many of which are illegal, have been evaluated by the FDA and determined to be safe, or that trying CBD ‘can’t hurt.’ Aside from one prescription drug approved to treat two pediatric epilepsy disorders, these products have not been approved by the FDA and we want to be clear that a number of questions remain regarding CBD’s safety — including reports of products containing contaminants, such as pesticides and heavy metals — and there are real risks that need to be considered. We recognize the significant public interest in CBD, and we must work together with stakeholders and industry to fill in the knowledge gaps about the science, safety, and quality of many of these products.”

Legally speaking, all 50 states have laws legalizing CBD with varying levels of restriction. Presently, the federal government still considers CBD in the same class as marijuana but doesn’t typically enforce against it (see map for more on cannabis legality by state).

Peering through the haze of medical marijuana laws

Read more about the legal landscape regarding medical marijuana at staging.aad.org/dw/monthly/2019/july/peering-through-the-haze-of-medical-marijuana-laws.

In terms of side effects, limited adverse events have been reported. In a revised consumer update released in March 2020, the FDA cautioned that CBD has the potential to cause liver injury, affect the performance of other drugs, and potentially damage fertility in males. FDA guidance also indicates changes in alertness, gastrointestinal distress, and changes in mood as potential side effects. In an attempt to gather more insights into the long-term effects of CBD, the FDA also recently reopened its public docket in March 2020 to collect safety data on CBD, available at the FDA. The need for additional research into cannabinoids and their current federal status has created a frustrating Catch 22 scenario, according to Dr. Dellavalle, who notes that despite increasing interest in cannabinoids in medicine, their legal classification has proved a tough hurdle to overcome. “It’s hard to research medications that are in the same drug class as heroin. U.S. federal regulations need to be relaxed to facilitate topical cannabinoid research for skin disease.”

In the DW article, Dr. Bechtel agrees that research into medical marijuana has been limited due to state and federal regulations, despite ongoing questions regarding its treatment potential. “The legal prescribing of medical marijuana varies widely from state to state. Many academic institutions have concerns about research or prescribing medical marijuana. As a result, there are very limited double-blinded, controlled clinical trials evaluating medical marijuana.”

According to Pattanshetti, the AADA is closely monitoring activity on the regulation, safety, and quality of CBD products, and has been in touch with the Collaborative for CBD Sciences and Safety. “Their position is that CBD products on the market should be required to undergo the FDA-approval process,” says Pattanshetti, who notes that while the AADA does not have a position statement on CBD at this time due to lack of evidence, “given that CBD has been used and is being explored for dermatologic conditions, we are continuing to monitor the situation.”