This study examined the ability of Delta-9 tetrahydrocannabinol, cannabidiol, cannabinol, and cannabigerol to suppress human keratinocyte proliferation and elucidate cannabinoid receptor involvement.
The results showed that human keratinocyte proliferation was suppressed by all tested cannabinoids in a concentration-dependent manner. Only partial suppression was achieved by the selective CB2 receptor agonists JWH015 and BML190, and a concentration-dependent response was produced by the non-selective CB agonist HU210. CB1/CB2 antagonists did not block the activity of these agonists.
These findings demonstrate that CB receptors may be circumstantially involved in human keratinocyte proliferation, meaning that they do not play a significant role in this process. On the other hand, human keratinocyte proliferation is suppressed by cannabinoids, suggesting that cannabinoids could be possibly used for treating psoriasis (Wilkinson and Williamson, 2007).1
It was found that keratinocyte proliferation was strongly inhibited by the endocannabinoid anandamide, via activation of CB1 and TRPV1, proposing that keratinocyte proliferation is normally regulated by the endocannabinoid system (Tóth et al., 2011).2
Keratins K6 and K16 which play a role in wound healing can be downregulated by stimulating CB1 in human keratinocytes (Ramot et al., 2013)3, highlighting the relevance of the cannabinoid system in therapeutic treatment of psoriasis.
Cutaneous cannabinoid (“c[ut]annabinoid”) signaling plays a crucial role in barrier formation and regeneration, and in keeping skin homeostasis. Also, its dysregulation may lead to several diseases and disorders, including atopic dermatitis, psoriasis, scleroderma, acne, hair growth, and pigmentation disorders, keratin diseases, various tumors, and itch.
This review focuses on the skin-relevant endo- and phytocannabinoid scientific literature centered on the presumed translational potential, promising future research directions and challenges.
In a study, skin biopsies from 25 psoriasis patients were evaluated using RNAseq and this was compared to region-matched skin of healthy individuals with several essential “cannabinoid-relevant” genes being differentially expressed. Also, it was demonstrated that the expression of adenosine A1, A2A, A2B, A3 receptors, CB1, CB2, PPARα, and PPARγ was decreased, while the expression of FAAH1, TRIB3, TRPV1, and TRPV3 was increased in itchy lesional skin of psoriasis patients. Overall, changes in the ECS can be seen in patients suffering from psoriasis, pointing out that certain cannabinoids may play a potential role in treating such disease (Tóth et al., 2019).4
Cannabidiol (CBD) is a cannabinoid compound derived from Cannabis Sativa that does not possess a high affinity for either the CB1 or CB2 cannabinoid receptors. Similar to other cannabinoids, it demonstrated that CBD suppressed attacks from the immune system (psoriasis and rheumatoid arthritis). The data of this study suggest that CBD suppresses T cell function and that CB1 and/or CB2 play a critical role in the magnitude of the in vitro anti-SRBC IgM AFC response (Kaplan et al., 2008).5
In vivo studies aimed to evaluate nasal and transdermal permeation using rats and guinea pigs, respectively. Intranasal delivery of CBD showed a bioavailability of 34-46% with CBD being absorbed within 10 minutes. Polyethylene glycol formulation in rats showed a bioavailability of 100% and the use of enhancers did not improve bioavailability. Transdermal gel application in guinea pigs showed that the steady-state plasma concentration of CBD was sufficiently high for this administration route for CBD to be considered beneficial for treating chronic pain. Furthermore, it was demonstrated that with the use of enhancers, the steady-state concentration of CBD was increased by 3.7-fold. This shows that CBD could be successfully administered intranasally or transdermally (Paudel et al., 2010).6
1. Wilkinson, Jonathan D., and Elizabeth M. Williamson. “Cannabinoids inhibit human keratinocyte proliferation through a non-CB1/CB2 mechanism and have a potential therapeutic value in the treatment of psoriasis.” Journal of dermatological science 45.2 (2007): 87-92.
2. Tóth, Balázs I., et al. “Endocannabinoids modulate human epidermal keratinocyte proliferation and survival via the sequential engagement of cannabinoid receptor-1 and transient receptor potential vanilloid-1.” Journal of Investigative Dermatology 131.5 (2011): 1095-1104.
3. Ramot, Yuval, et al. “A novel control of human keratin expression: cannabinoid receptor 1-mediated signaling down-regulates the expression of keratins K6 and K16 in human keratinocytes in vitro and in situ.” PeerJ 1 (2013): e40
4. Tóth, Kinga Fanni, et al. “Cannabinoid Signaling in the Skin: Therapeutic Potential of the “C (ut) annabinoid” System.” Molecules 24.5 (2019): 918.
5. Kaplan, Barbara LF, Alison EB Springs, and Norbert E. Kaminski. “The profile of immune modulation by cannabidiol (CBD) involves deregulation of nuclear factor of activated T cells (NFAT).” Biochemical pharmacology 76.6 (2008): 726-737.
6. Paudel, Kalpana S., et al. “Cannabidiol bioavailability after nasal and transdermal application: effect of permeation enhancers.” Drug development and industrial pharmacy 36.9 (2010): 1088-1097.