What is Actually Known About CBD's Effects on Skin

The Science-based Facts About CBD Effects on the Skin: Data From the Library of Medicine

CBD products have exploded onto the marketplace as a result of the farm bill that legalized hemp agriculture. Both oral and topical products are now being widely sold in states that allow CBD sales. Accompanying the hundreds of products now on the market are a multitude of therapeutic “claims” that these products can treat a wide variety of medical problems, including pain, arthritis, psoriasis, aging and even cancer. Given all of the claims for benefits of using CBD products, it is important to understand what the real science and clinical evidence is regarding CBD’s effects both orally and topically.

First of all, evidence that cannabinoids occur naturally in the body dates back over 60 years. Since that time, the Endocannabinoid System (ECS) has been studied in depth. The ECS is made up of:

1. the endocannabinoids (like CBD) that interact with the receptors of the ECS
2. the main receptors for cannabinoids, CB1 and CB2, which are found in the central and peripheral nervous system as well as on skin cells
3. various specific enzymes that either synthesize cannabinoids or degrade them. The body actually makes its own cannabinoids and these are called endocannabinoids

However, the cannabinoids that have received all the attention lately are the phytocannabinoids that are derived from plants, like cannabis and hemp.

The Take Home Lesson

For those that don’t wish to read the full report below regarding what is really known about CBD effects on the skin when applied topically, the take-home message is:

• As of April, 2021, there are NO peer-reviewed publications of controlled clinical studies that describe any benefit of CBD to the skin when applied topically. There are three non-controlled “anecdotal” human studies, several mice and rat studies, and many studies of CBD effects on cultured skin cells. So, at present, we simply don’t know if topically applied CBD products provide ANY benefits.

Although there has been a lot of research regarding cannabinoids, the only in depth clinical studies that have been conducted have looked at effects of cannabinoids after either ingesting, inhaling or injecting the cannabinoids. There have been essentially no published controlled clinical studies on the effects of topically applied cannabinoids. This is surprising in light of the numerous claims showing up on the internet about all the wonderful things cannabinoids can do. If one wants to know what “claims” that show up on the internet are true and which are false, the ONLY way to accurately assess truth from fiction is to do your research on the Library of Medicine’s database. Pubmed (https://www.ncbi.nlm.nih.gov/pubmed), the Library of Medicine’s online searchable database lists every peer-reviewed scientific publication related to a given subject.

A search of the Pubmed database using the search words cannabidiol (CBD) turned up over 3000 publications that have appeared over the years, with most dealing with the oral use of CBD to either treat epilepsy (the only FDA approved CBD medicine is Epidiolex) or to reduce pain. Many other published studies have focused on analyzing CBD content in various cannabis extracts. When the term “cannabidiol” was combined with “skin”, only 62 publications were found. Of these 62, there were only THREE clinical studies on the topical effect of cannabinoids on skin, and these were carried out with very small numbers of patients, which does not provide any statistically significant results. As a result these studies are considered “anecdotal” and not controlled studies. A quick summary of all the results of peer reviewed scientific articles on cannabinoids is listed below.

1. Although there have been a few mice and rat studies on topically applied cannabinoids, there have been only three published reports of clinical studies on the topical use of cannabidiol.
   1. In one study patients with mild to moderate scalp psoriasis or seborrheic dermatitis were given a shampoo containing cannabidiol. After 14 days of use, the level of itching and redness had decreased in the patients.
   2. In a second very small study of 16 patients, they were asked to evaluate the effect of a topical cannabidiol lotion on their eczema. After 2 weeks of use, the patients “self-reported” an modest improvement in the severity of their eczema.
   3. In a third small study, patients treated topically with 8% CBD reported having less nerve pain.
   4. NOTE: in addition to the above studies, a non-clinical study with only  3 individuals suffering from a rare skin blistering disease, epidermolysis bullosa, applied a topical CBD oil to their skin and all 3 reported less blistering.
2. In regard to animal studies using mice or rats, cannabidiol has been shown to have the following effects:
   1. A topical preparation of CBD was shown to reduce inflammation and swelling in the foot of a mouse injected with an irritant.
   2. Rats treated topically with CBD and then exposed to a UVB lamp showed protection of keratinocytes from apoptosis (cell death caused by UV radiation). Whether or not CBD was simply acting as a sunscreen was not determined.
   3. Mice treated on the ears with a tumor promoter to trigger inflammation showed less ear edema (swelling) in the ear treated with CBD.
   4. Changes in the proteome profile of UVB treated fibroblasts.
3. Many studies have looked at CBD effects on skin cells that were grown in tissue culture flasks. The types of skin cells studied included keratinocytes, fibroblasts and melanocytes.
   1. CBD induces the expression of antioxidant enzyme genes in keratinocytes treated with UVR.
   2. CBD blocks the NF-kB pathway that leads to the activation of inflammatory genes in UVR stimulated keratinocytes.
   3. CBD reduces keratinocyte proliferation, which may be useful for treating psoriasis but may not be good for normal skin turnover.
   4. CBD reduces free radical (ROS) levels in keratinocytes.
   5. CBD is a gene suppressor and can lower keratin levels in keratinocytes
   6. CBD stimulates melanogenesis (pigmentation) in human melanocytes.
   7. Hemp extract protects keratinocytes and fibroblasts from hydrogen peroxide toxicitiy by blocking ROS (free radicals) and by inhibiting the inflammatory mediator, PGE-2.
   8. CBD reduces sebum production in cultured sebocytes, which might be useful for acne.
   9. CBD increases activity of NRF-2 and this leads to increased antioxidant (superoxide dismutase). CBD also prevented cells damaged by UVB from undergoing apoptosis (cell death). Note: the value of keeping potentially mutated cells alive may not be a good thing.
   10. CBD may lower ROS levels.
   11. Flax extract inhibited inflammation but stimulated MMPs in a wound healing model, which may be good for wound healing but bad for maintenance of the dermal matrix.
4. CBD is anti-microbial.

As you can see, research on CBD is in its infancy and there is almost NO clinical data showing any beneficial effects of topical CBD on human skin. Given the available data, what effect on the skin might we expect to see if we applied CBD topically?

1. CBD and keratinocyte growth: The keratinocytes in our skin are dividing all the time at the basal layer of the epidermis and from there they migrate to the skin’s surface to replace those dead, cornified keratinocytes that make up the stratum corneum. The stratum corneum is a critically important protective barrier that protects us against environmental damage by pathogenic bacteria, fungi, parasites, viruses, UV radiation and water loss. We know that in a young person, the epidermis “turns over” about every 40-45 days (recent studies suggest that the complete turnover of the epidermis takes longer than the 30 day time period that has been used for years). We also know that this “turnover rate” decreases as you get older, due, in large part, to a reduction in the proliferation rate of keratinocytes at the basal layer of the epidermis (age can cause up to a 50% reduction in keratinocyte mitosis). Thus, fewer keratinocytes migrate to the surface and the skin becomes thinner as we age. An article in the Journal of Dermatological Science (Wilkinson and Williamson (2007), J.Dermatol Sci: 45: 87-92) describes the inhibition of keratinocyte proliferation/growth by cannabinoids. In addition, a more recent research study has shown that cannabidiol, as well as other cannabinoids, inhibit the expression of genes that code for important keratinocyte proteins (Pucci, M. et al (2013); Br.J. Pharmacol. 170: 581-591). These proteins, including Keratin 1 and 10, and involucrin, are important structural components of the epidermis. Since these proteins are critical for the normal development, strength and barrier properties of the stratum corneum, inhibiting their production and lowering their levels in the skin, weakens the skin’s barrier.

So, although the use of CBD in slowing the proliferation of keratinocytes might be helpful in reducing psoriatic plaques caused by rapidly growing keratinocytes, and might even help treat skin cancer, there is no data at present that its use in normal skin care and “anti-aging” products will provide any benefits. And based on the available data, topical CBD might cause skin thinning and a loss of barrier function.

2. CBD Effects on Inflammation: At the present time there is no scientifically published human data on any anti-inflammatory effect of topically applied A few studies with cell cultures have shown that CBD can lower the level of the inflammatory mediator, TNF-alpha, in leukocytes, block IL-6 and IL-8 production in human monocytes and macrophages, lower COX-2 (PGE-2) expression in macrophages, and block inflammatory cytokines in keratinocytes (Pellati, F; et al; (2018) Biomed Res. Intl. ID. 1691428). Finally, a recent publication has shown that Flax Fiber (which contains several chemicals, including CBD) might be useful as a wound dressing to accelerate healing. Recently, a derivative of CBD, VCE-004, was found to INHIBIT collagen production in human dermal fibroblasts (Del Rio, C., et al., 2018, Br.J.Pharmacol. 175:3813). For a very recent review on what is known about CBD effects on inflammation see Baswan, S.M et al. (2020) Clinical, Cosmetic and Investigational Dermatology. 13:927-942. So although cell culture studies suggest that CBD may provide anti-inflammatory benefits, at present, there are no clinical studies that demonstrate any anti-aging or anti-inflammatory effects of CBD when applied topically to the skin.

3. CBD Stimulates Pigmentation A recent study on human melanocytes grown in culture found that CBD can stimulate melanogenesis in these cells by increasing tyrosinase activity and by activating a number of melanogenic specific genes ( Hwang, YS. Et al (2017) Chem. Biol. Interact. 273: 107-114). Given this finding, while topical CBD might be useful as a “tanning stimulator” it may aggravate an existing hyperpigmentation (age spot) condition.

4. CBD Inhibits Sebum Production One of the potentially beneficial uses of a topical CBD product might be for controlling acne breakouts. A recent publication has shown that CBD can reduce sebum production in human sebocytes (Olah, A et al. (2016), Exp. Dermatol. 25:701-707. While retinoic acid also inhibits sebum production, and improves acne, further research might find that CBD provides the same benefit without the redness, and drying seen with the use of topical retinoic acid.

5. CBD Reduces Neuropathy Pain. One recent study (Xu, DH. et al. 2019, Curr.Pharm.Biotechnol.) conducted with a small group of patients (29) showed that an 8% topical solution of CBD could reduce pain caused by neuropathy.

6. CBD Inhibits Growth of Cancer Cells One of the more promising effects of CBD is its ability to slow the growth rate of cancer cells, including breast cancer. The mechanism of action of CBD likely involves an antagonism of one or both of the endocannabinoid receptors, CB1 and CB2. Both of these receptors play a role in tumor progression, with CB2 playing the greater role in stimulating breast cancer growth and tumor aggressiveness. By blocking the activity of these receptors, CBD lower cancer cell prolilferatoin and also causes cancer cell apoptosis (cell death). For an excellent review on CBD and breast cancer, see Kiskova, T. et al. (2019) Intl. J. Molec.Sci. 20: 1673-1694.

In summary, there is considerable peer-reviewed scientifically credible research that shows positive effects of oral CBD on anxiety, stress, and aggressiveness, and on preventing epileptic seizures. In fact, the only FDA approved CBD drug for epilepsy is Epidiolex, a drug that is effective in reducing the frequency of seizures. In addition, there is growing evidence that CBD may be useful in reducing the growth rates of some cancers.

Conclusion

At present there have been only 3 published, very small clinical studies on the effectiveness of topical CBD in treating any skin problem; one on the use of CBD for treating scalp psoriasis/seborrheic dermatitis, one that involved only patient “self- evaluation” on the benefit of topical CBD for eczema, and finally, one small study where patients used a topical CBD lotion to reduce nerve pain. Research on human cells grown in culture suggests that CBD does have some anti-inflammatory effects. Finally, there is currently no published data that topical CBD provides any benefits for normal skin, and no data showing any anti-aging benefits.