The discovery of a skin endocannabinoid system and its role in maintaining skin homeostasis has raised interest in the use of cannabinoids for the treatment of different skin conditions.
The disturbances of the endocannabinoid system and its regular actions can contribute to the development of pathological skin disorders, so cannabinoids might be the answer to certain diseases like acne, eczema, dermatitis, and psoriasis.
In the skin, CB1 and CB2 receptors have been found in numerous types of cells — epidermal keratinocytes, melanocytes, dermal cells, mast cells, sweat glands, hair follicles, and cutaneous nerve fibers. All of these areas present potential targets for future topical drugs or cosmetics based on CBD formulations.
Unfortunately, even with the growing enthusiasm in the industry and among the consumers, and with the proven anti-inflammatory effects of CBD, there is still not much clinical evidence on the benefits of CBD in the potential treatment of numerous skin disorders, and some research is financed by the industry itself.
CBD and skin: CBD might help with acne
One such example is a 2019 phase 2 clinical study on 368 patients with moderate to severe acne. The trial lasting 12 weeks found that CBD showed a strong impact on inflammatory lesions and an even stronger effect on non-inflammatory lesion reduction. This research is adding more weight to the claim that CBD could effectively treat acne, although more research is needed to confirm the results.
A phase 1 study in 23 volunteers aged 18 to 65 years with moderate to severe acne showed that a 5% formulation of CBD when applied twice daily for four weeks to the entire face brings a considerate promise to a novel use of CBD in the treatment of the skin.
These findings might point in a similar direction as small previous research on 11 patients, which found that 3% cannabis seeds extract cream was significantly effective in the reduction of skin sebum and erythema. (The skin sebum is an oily substance produced by the sebaceous glands, and erythema is a skin rash caused by inflamed blood capillaries.)
Similar to the aforementioned research, where Cannabis Sativa seeds extract cream has been used, in a study on 20 patients with atopic dermatitis, skin dryness and itchiness significantly improved after intake of dietary hempseed oil for 20 weeks. However, the patients in this trial used the hempseed oil orally and not topically, and there is a difference in bioavailability in the different forms of cannabinoid intake. Also, in modern cannabinoid formulations, hempseed oil is mostly used as base oil, and not the active ingredient. Nevertheless, it is another human study showing promising results of cannabis products in treating atopic dermatitis.
However rare the studies on topically administrated CBD are, they are not nonexistent. The effect of CBD on dermal nerve fibers was confirmed in a study on 18 participants with an experimentally induced itch that was significantly reduced by applying CBD-containing skin patches.
CBD might help with eczema, dermatitis and psoriasis
An observational study looking into the effects of CBD on individuals with self-reported eczema also showed promising results — out of 16 patients applying CBD gel for two weeks, 67% reported a decrease in itch and 50% perceived an improvement in their eczema by more than 60%. Moreover, the patients noted a reduction in the psychosocial and emotional burden of eczema.
Another trial confirmed that the topical administration of CBD ointment is a safe and effective alternative for the improvement of the quality of life in patients with the most common skin diseases. The spontaneous, anecdotal, retrospective study investigated changes in 20 patients with psoriasis, atopic dermatitis, and resulting outcome scars. The patients were instructed to administer topical CBD-enriched ointment to lesioned skin areas twice daily for three months of treatment. As a result, skin elasticity and hydration improved, while blemishes and scars were reduced. The topical product also improved the severity of itches as well as the consequent loss of sleep in patients with atopic dermatitis. The product used in this study contained CBD seed oil and natural ingredients, including Mangifera Indica, Calendula officinalis, Lavendula officinalis, Chamomile, Amyris Balsamifera, and Shea butter.
Furthermore, scientists found that replacing current shampooing practices with a broad-spectrum CBD-containing shampoo significantly reduces the severity and symptoms of scalp inflammation within two weeks of use. A study on 50 people aged 18-61 years with mild or moderate cases of scalp psoriasis and seborrheic dermatitis showed that CBD could be highly effective in reducing symptoms of both diseases. Apart from the broad-spectrum CBD, the shampoo ingredients have included ketoconazole and numerous ingredients that promote hair growth. After two weeks, scalp inflammation (arborizing vessels, twisted capillaries, and scales), as well as the symptoms of erythema and scaling, itching, and burning were reduced in all participants.
CBD could help with rare and painful diseases
There are records of the use of topical CBD to treat a rare and painful skin condition in children, epidermolysis bullosa. One of them is the case of a six-month-old boy who suffered from blisters on the lower part of his body and whose parents self-initiated the treatment with CBD spray containing CBD tincture two to three times a day. From the start of the treatment, the parents noticed a reduction in blisters and faster healing of chronic wounds. Also, there was no more need for morphine before the dressing changes.
The second case is of a three-year-old girl whose mother began using a blend of emu oil and CBD oil to treat blisters on her face, trunk, and extremities at least twice daily, after which she had fewer blisters, and the healing time for facial blisters was reduced by approximately half. The application of CBD also reduced pain, allowing the child to walk longer distances.
In the third case, the child treated with CBD was a 10-year-old boy in whom blistering around the neckline had first been noticed at one month of age, and blisters on the palms and soles progressed at approximately 13 months of age when he began walking. His parents self-initiated CBD oil and cream topically to his blisters and noted a significant reduction in blisters. There was also a reduction in pain, leading to less wheelchair use, and he was able to discontinue the previous therapy.
The photographs accompanying these reports witness the dramatic improvement in the state of children’s skin health.
CBD and skin: CBD could help with wound closure
There is scientific evidence that CBD could help with wound closure in previously non-healing or recurring wounds. Patients who experience such conditions are, for example, patients with calciphylaxis. It is a rare disease in which calcium accumulates in small blood vessels of the fat and skin tissues and causes blood clots, painful skin ulcers, and may cause serious infections that can lead to death. In a multicohort open-label trial, 32 participants with calciphylaxis, received topical CBD (3.75 mg/ml) and minimal Δ9-THC (<1 mg per day), which was applied to wound beds and peri-wound tissues. Wound closure was achieved in 90% of cases after one year of treatment.
CBD was also found to have great potential in rapid wound closure of previously non-healing venous leg ulcers. In a prospective open-label cohort trial on 11 patients, a formulation containing CBD 3.8 mg/ml, THC <1 mg/ml, Quercetin 31.3 mg/ml, Diosmin 25.3 mg/ml, Hesperidin 2.5 mg/ml and Beta-Caryophyllene 152.7 mg/ml in the base carrier containing Hyaluronic acid + Aloe Vera Gel (1/1 v/v) led to complete wound closure in 79% of the patients and 81% of the wounds within 34 days.
In healthy volunteers, hemp extract was found to promote the hydration of the skin, suggesting that cannabinoids in cosmetics might act as natural moisturizers. After treating skin with a substance that causes it to dry substantially, scientists applied hydrogels containing 0.5%, 1%, and 5% of hemp extract. After five hours, the treated skin returned to its normal state, with the moisturizing effects rising with the higher extract percentage. The addition of hemp extracts in the formulation of hydrogels has shown an influence on the restoring of the hydrolipid balance and the rebuilding of the hydrolipid barrier of the skin. Scientists have concluded that hemp extracts can be a valuable source of biologically active substances that reduce oxidative stress, inhibit skin aging processes and positively affect the viability of skin cells.
CBD regulates 163 genes in the skin
A study examining the mechanisms of action of topical application of CBD showed that CBD regulates a number of genes in the skin. Genemarkers, a company specializing in clinical genomics testing and genomics research services has conducted an in vitro study on a skin model containing keratinocytes and fibroblasts with an ex vivo skin tissue system. Observing the biological efficacy of CBD extracts and cosmetic formulas containing them, they found that CBD regulates 163 genes:
14 related to wound healing and growth factors;
7 connected with skin hydration;
15 related to skin barrier integrity;
17 relevant to pigmentation;
23 linked to inflammation and immune response;
13 involved in extracellular matrix breakdown and barrier integrity;
7 relevant for acne regulation;
6 connected with anti-aging functions;
15 linked to antioxidant and stress responses;
11 related to cell renewal and regeneration;
8 related to regulating the circadian rhythm;
2 related to the endocannabinoid system, and
25 involved in epidermal barrier formation.
They determined that the changes in gene expression in response to CBD occur over time, with fewer changes at early time points of three and six hours, and with 24 or 48 hours as the most relevant time points for identifying changes.
At the molecular level, in keratinocytes, CBD targets a protein called BACH1 that regulates the expression of antioxidant and anti-inflammatory genes. The same protein is a therapeutic target for lung and breast cancer.
CBD and skin: The potential of PEA
Some thorough reviews on the effects of cannabis-based products on the skin include human studies that used palmitoylethanolamide (PEA). PEA is an endocannabinoid-like lipid mediator with anti-inflammatory, analgesic, and neuroprotective properties. It has a multi-modal mechanism of action, primarily activating the nuclear receptor PPAR-α and potentially working through the endocannabinoid system (ECS). Since it targets similar pathways as CBD, it is interesting to look into its benefits for the skin. For example, PEA was found to improve the symptoms of eczema, decrease the use of topical steroids in atopic dermatitis, eliminate itching in full in 38% of cases of chronic pruritus, and reduce the dryness of the skin in 81% of patients.
The anti-inflammatory effects of CBD are mediated through direct modulation of the immune system, while PEA enhances endogenous cannabinoids. The presence of PEA in topical CBD did not show any signs of skin irritation or sensitization with the concentrations of CBD from 0.1% up to 10% in healthy humans. Mild phototoxic reactions were found with a cream product featuring hemp seed oil, containing little to no detectable CBD or PEA. This peculiar finding is puzzling because essential oils have been shown to be phototoxic, but fatty acids from hemp seed oil have not been demonstrated to be phototoxic in either animals or humans, so found phototoxicity could be due to other ingredients in the formulation in question.
Protective action of CBD against UV radiation
UV radiation decreases the level of endocannabinoids in skin cells and enhances the expression of membrane endocannabinoid receptors CB1, CB2, and TRPV1, influencing the cytoprotective and proinflammatory properties of these cells. For that reason, CBD might be a promising agent for protecting skin cells against UV radiation.
A study analyzing the effects of CBD on keratinocytes exposed to UVA and UVB radiation in a 3D system found that CBD shows a series of positive actions that stimulate skin cells to prevent the harmful effects of such radiation. These include antioxidant and anti-inflammatory activity, regulation of protein biosynthesis and degradation, and control of enzyme activity by structural modification. However, further research is required to elucidate its long-term use in epidermal cells.
In rats, it is found that topical application of CBD to the skin, when exposed to UV radiation, helps normalize the expression of keratinocyte proteins. As UV therapy is a part of the treatment of skin diseases like psoriasis, CBD might be useful as a protective factor to reduce the metabolic changes in keratinocytes caused by UV radiation. After the beneficial effect of CBD on psoriasis-induced skin lesions has been confirmed, this could be another reason for more research in this field.
So far, it has been found that CBD treatment intensifies some changes, like phospholipid content and membrane charge, caused by the radiation of psoriatic cells, while it prevents these changes in the cells of healthy people.
CBD and skin: The double effect of CBD on pigmentation and melanoma
Another compelling research area is the effects of CBD on pigmentation and skin cancer. The pigmentation comes as a manifestation of the synthesis of dark pigment, melanin. The involvement of ECS pathways in melanin-producing cells melanocytes is found to be complex, with somewhat controversial results in so far conducted preclinical trials.
CBD was found to have a double effect on human melanocytes. At low concentrations, through CB1 receptors, it induces the process for the production of melanin, and at high concentrations, through TRPV1 receptors, it induces cell death, which could be useful in treating skin cancer.
CBD might be beneficial for hair growth
The analysis of human skin revealed the presence of CB1 and CB2 receptors within the hair follicle. CB1 was detected in portions of the infundibulum and the inner root sheath, and CB2 was found in the outer root sheath and hair bulb.
The discovery led to research on the potential of CBD in promoting hair growth. The enthusiasm was further fueled by the results of a trial on obese mice, when orally administered synthetic antagonist of CB1 promoted hair growth in that rodent model.
However, different studies point to the conclusion that hair growth induced by CBD is strictly dose-dependent. Promising results came from a case study on 35 people using topical hemp extract with 3-4 mg of CBD once daily. The results have shown a 93.5% increase in hair growth after six months. The topical extract in question has been made of high CBD cannabis Sativa flower ultra-pulverized into a fine powder containing 10.78% CBD, and 0.21% THC.