Cannabidiol (CBD) is a very much talked about cannabinoid; but is it a cure-all? As has been often said, too much information makes information difficult to verify and is, therefore, useless.

Cannabinoids are components of cannabis, and cannabis is believed to perform wonders. It has been anecdotally reported to manage pain, enhance sexual pleasure, treat mild irritations, alleviate the symptoms of psoriasis, keep skin youthful, reduce inflammation and arthritis, heal burns faster, fight bacterial skin infections, all while being great for therapeutic massages. CBD, in particular, is offered as a skin care ingredient.

Yet, as late as mid-2018, the scientific literature summarized the status of knowledge in the field as follows: Cannabinoids have shown some initial promise as therapy for a variety of skin diseases. However, there is a requirement for thorough pre-clinical research and large-scale, randomized, controlled trials before cannabinoids can be considered safe and effective treatments for these conditions.¹
So much for cannabinoids in general. What about cannabidiol (CBD)?

Cannabidiol in Pharmacology

Epidiolex (a CBD-containing drug) has been approved by the U.S. Food and Drug Administration (FDA) for the treatment, via the general route, of seizures associated with tuberous sclerosis complex in patients one year of age and older. Epidiolex was previously approved for the treatment of seizures associated with two rare and severe forms of epilepsy, Lennox-Gastaut syndrome and Dravet syndrome. This is the only FDA-approved drug that contains a purified substance derived from cannabis.

CBD and the Skin

During the past couple of years, several papers were published that describe clinical effects of topical CBD. Xu et al² reported that 15 volunteers suffering from peripheral neuropathy of lower extremities (pain and cold and itch in the legs) were treated daily for four weeks with topical cannabidiol oil (2.5mg/ml), while another 14 volunteers were in the placebo group. At the end of the study the volunteers self-evaluated intense pain, sharp pain, cold and itchy sensations using the Neuropathic Pain Scale; volunteers in the treated group reported a statistically significant reduction in the four sensations.

Magfour et al³ published that 16 volunteers with self-reported eczema completed a Patient Oriented Eczema Measure questionnaire relative to the severity of eczema after two weeks of treatment with topical CBD seed oil. Two-thirds of the volunteers reported a decrease in itch and half of the volunteers perceived an improvement of the eczema by more than 60%.

Palmieri and coworkers⁴ observed that after three months of twice daily topical treatment with CBD-enriched ointments, 20 patients with psoriasis, Atopic Dermatitis (AD) or scars, observed an improvement in biophysical parameters (hydration, transepidermal water loss, elasticity), as well as clinical ones as assessed by the SCORAD and PASI (for AD and psoriasis, respectively) questionnaires. Regrettably, though, there was no placebo group and the quantitative composition of the ointment is not reported, so it is difficult to learn whether these effects are owed to cannabis seed oil or to the other ingredients such as Mangifera indica, Calendula officinalis, Lavandula officinalis, Chamomille or Amyris balsamifera.

Possible Mechanisms of Action

During the past few years, the mechanism of action of cannabinoids has been the subject of in vitro studies. Some papers tackled the mechanisms of the anti-inflammatory properties of CBD.
An active drug often exerts its activity by binding to receptors. There are receptors able to bind molecules produced in the brain (called endo-cannabinoids) as well as plant cannabinoids (called phyto-cannabinoids). The ones found in the brain, and also in the lungs, liver and kidney, are called CB1. The other ones, called CB2, can be found in some cells of the immune system, in hematopoietic cells, and on the endings of peripheral nerves. The “cosmetic” and “skin care” interest in CBD is justified by the fact that keratinocytes contain both types of cannabinoid receptors. Cultured keratinocytes from mice devoid of functional CB1 receptors release larger amounts of inflammatory chemokines, thus showing that functional CB1 receptors participate in the modulation of the secretion of pro-inflammatory cytokines and reduce the inflammation associated with contact allergy.⁵

Ruhaak et al⁶ measured the IC50, the concentration inhibiting 50% of the enzymatic activity of Cyclo-oxygenases COX-1/COX-2, two enzymes committed to the synthesis of prostaglandins. The cannabinoids tested were tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), CBD, cannabidiolic acid (CBDA), cannabigerol (CBG), and cannabigerolic acid (CBGA). They observed that the IC50 is between 0.2 mM and 2 mM for THCA, CBG, CBDA and CBGA, with CBDA inhibiting only COX-1. Surprisingly enough, THC increased both COX-1 and COX-2 and CBD increased COX-2 activity without inhibiting COX-1.

Formulating CBD

In preparation for a wider use of topical CBD, scientists are studying the best way to formulate it in order to enhance its penetration. It was interestingly found by Casiraghi and coworkers⁷ that a hydrophilic gel, mostly consisting of propylene glycol (79%, w/w), can be an optimal choice for the topical administration of CBD.

This should not be a surprise. Indeed, the partition coefficient of CBD is 6.5 and the one of propylene glycol is -0.91; the partition coefficient of the stratum corneum is well bracketed by these two values and one can easily grasp why propylene glycol “pushes” CBD in the horny layer. These results prepare us for topically administering CBD to the consumer in need of its properties. 


References

1. Lauren R M Eagleston, Nazanin Kuseh Kalani, Ravi R Patel, Hania K Flaten, Cory A Dunnick, Robert P Dellavalle (2018) Cannabinoids in dermatology: a scoping review. Dermatology online J 2018 June 15;24(6):13030/qt7pn8c0sb
2. Xu DH, Cullen BD, Tang M, Fang Y (2020) “The Effectiveness of Topical Cannabidiol Oil in Symptomatic Relief of Peripheral Neuropathy of the Lower Extremities”, Current Pharmaceutical Biotechnology (2020) 21: 390. https://doi.org/10.2174/1389201020666191202111534
3. Maghfour et al (2020) An Observational Study of the Application of a Topical Cannabinoid Gel on Sensitive Dry Skin. J Drugs Dermatol. 19 :1204-1208. doi:10.36849/JDD.2020.5464
4. Palmieri B, Laurino C, Vadalà M (2019) A therapeutic effect of CBD-enriched ointment in inflammatory skin diseases and cutaneous scars. Clin Ter 170 : e93-99. doi:10.7417/CT.2019.2126
5. Gaffal et al (2013) Cannabinoid I Receptors in keratinocytes Modulate Proinflammatory Chemokine Secretion and attenuate Contact Allergic Inflammation. J. Immunol 190 : 4929-4936
6. Ruhaak LR et al (2011) Evaluation of the cyclooxygenase inhibiting effects of six major cannabinoids isolated from Cannabis sativa. Biol Pharm Bull. 34 :774-8. doi: 10.1248/bpb.34.774.
7. Casiraghi A, Musazzi U, Centin G, Franzè S, Minghetti P (2020) Topical Administration of Cannabidiol: Influence of Vehicle-Related Aspects on Skin Permeation Process. Pharmaceuticals (Basel)13 : 337. doi: 10.3390/ph13110337.

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Paolo Giacomoni, PhD
Insight Analysis Consulting
paologiac@gmail.com
516-769-6904

Paolo Giacomoni acts as an independent consultant to the skin care industry. He served as executive director of research at Estée Lauder and was head of the department of biology with L’Oréal. He has built a record of achievements through research on DNA damage and metabolic impairment induced by UV radiation as well as on the positive effects of vitamins and antioxidants. He has authored more than 100 peer-reviewed publications and has more than 20 patents.