Psoriasis is a chronic inflammatory skin disease that is characterized by the differentiation of keratinocyte dysregulation, but oxidative stress also plays an important role in the pathogenesis of this disease. The occurrence of psoriasis is affected by several factors, such as hereditary predisposition, environmental factors, endocrine hormones, stress and immunological factors.
Psoriasis is an autoimmune disease that affects 2-3% of the world's population and can markedly reduce quality of life. The pathophysiology of psoriasis is complex and dynamic, involving skin cells and immune system cells. A wealth of evidence has defined a role for the immune system and its interactive network of leukocytes and cytokines in the pathogenesis of psoriasis.
This disease is usually manifested by the presence of many erythematous, well-demarcated, elevated oval plaques with adherent silvery scales. The scales represent the result of a hyperproliferative epidermis with premature maturation of keratinocytes and an incomplete cornification with retention of nuclei in the stratum corneum (parakeratosis).
People who are affected by the disease of psoriasis have lesions that usually occur in places where there is trauma to the epidermis, such as the elbows and knees, but the lesions can appear anywhere on the body. Furthermore, it is becoming increasingly clear that psoriasis is not just superficial. For example, the frequency of seronegative arthritis in individuals with psoriasis has been estimated to be approximately 7 to 8% of the population with psoriasis, but can be as high as 30%. Other comorbidities seen in individuals with psoriasis can include cardiovascular disease, diabetes mellitus (specially type 2), metabolic syndromes, obesity, impaired quality of life, and depression.
Early studies on the pathogenesis of chronic inflammatory diseases, including rheumatoid arthritis, psoriasis and inflammatory bowel disease, led to the identification of TNF-α as a key trigger of innate inflammatory pathways. Although TNF-α blockers successfully treated rheumatoid arthritis for the first time, they were also rapidly extended to psoriasis and psoriatic arthritis. The inhibitory effects of TNF-α in psoriasis and psoriatic arthritis are complex, because the therapeutic benefits likely result from indirect adaptive immune effects on the IL-23 / IL-17A axis.
The pathogenesis and etiology of psoriasis is complex and our understanding is incomplete, but in summary, psoriasis can be characterized by hyperproliferation of epidermal keratinocytes, accompanied by the infiltration and increase of pro-inflammatory mediators in the skin. The most important mediators involved are those that are associated with a dominant Th1 cytokine profile.
The endocannabinoid system (ECS) is a complex, evolutionarily conserved homeostatic signaling network. It comprises endogenous ligands - endocannabinoids (eCB), for example, anandamide (AEA) - receptors responsive to eCB (for example, cannabinoid receptors CB1 and CB2) and a complex apparatus of enzymes and transporters.
Depending on their concentrations, endocannabinoids (eCBs) and phytocannabinoids (pCBs) are able to notably activate/antagonize/inhibit a wide variety of cellular targets, including several metabotropics (e.g., CB1 or CB2 receptors), ionotropics, as certain transient receptor potential ion channels (TRP) and nuclear receptors, which are activated by peroxisome receptor proliferators (PPARs), various enzymes and transporters. More importantly, each ligand can be characterized by a unique molecular fingerprint and, in some cases, they can even exert opposite biological actions on the same target molecule.
Cannabinoids are known to play a critical role in suppressing and inhibiting angiogenesis and inflammation. Cannabinoids can inhibit TNF-α, INF-γ and IL-2 and IL-8, which are considered to be key elements of both angiogenesis and inflammation in the disease of psoriasis.
Some studies suggest that cannabinoids and their receptors constitute a new clinically relevant control element for the expression of K6 and K16 human keratinocytes. Therefore, cannabimimetic agents may be relevant for the treatment of several skin diseases related to the important expression of K6/K16, such as psoriasis and wound healing. Furthermore, skin organ culture may be a physiologically relevant system model to investigate the effect of specific CB1 agonists/antagonists on human skin.
The beneficial effects of phytocannabinoids Δ-9-Tetrahydrocannabinol (THC), Cannabidiol (CBD) and Cannabinol (CBN) in psoriasis are the conversion of the pro-inflammatory Th1 profile into an anti-inflammatory expressed as being of the Th2 type, in addition to the antiproliferative properties in keratinocytes. However, these effects seem to be mediated predominantly through gamma-type peroxisome proliferator-activated receptors - PPARγ, independent of endocannabinoid receptors - CBs, demonstrated by robust results in CB1 and CB2 blockade in human papilloma virus (HPV) - 16 E6/E7 in cultures of transformed human skin keratinocytes.
Another important function of cannabinoid signaling is to control local immune responses in the skin. Several lines of evidence demonstrate that both eCBs and pCBs can modulate immune functions, and are generally considered anti-inflammatory agents. Importantly, the immunological effects of cannabinoids are not only exerted on immune cells, but also on cells that do not belong to the immune system (e.g., keratinocytes, sebocytes).
Despite solid clinical and experimental evidence proving that CBD is capable of antagonizing CB1, it is very important to emphasize that it can also behave in a context-dependent manner as a functional CB1 activator. In fact, by inhibiting fatty acid amide hydrolase (FAAH) and/or endocannabinoid membrane transporters (EMT), their administration can lead to an elevation of the local eCB and therefore indirectly to an increase in CB1 activity in certain systems.
Genetic and epigenetic abnormalities, as well as changes in skin microbiota, pH, or, more importantly, IL-17 signaling are known to be involved in the development of psoriasis as well as non-cutaneous symptoms (e.g., arthritis). It is, of course, accompanied by a disturbance in the dynamic cross-talk between epidermal keratinocytes and professional skin immune cells. This inadequate communication then leads to pathological inflammatory processes and a disturbance in the proliferation/differentiation balance of epidermal keratinocytes. Since, as discussed above, the proliferation/differentiation as well as the immunological activity of epidermal keratinocytes are under strict control of eCB signaling.
The oxidative stress observed in the keratinocytes of patients with psoriasis is a critical element of the immune response to this pathology, which is further intensified by ultraviolet radiation. Metabolic modifications, especially in the phospholipid/protein membrane, can lead to excessive apoptosis or modulation of cell signaling dependent on phospholipid derivatives, which are partially responsible for the modulation of oxidative stress. Therefore, treatment with CBD, which leads to accumulation of CBD, mainly in keratinocyte membranes, particularly in UV-irradiated psoriasis cells, reduces phospholipid oxidative modifications and their consequences. At the same time, CBD, by increasing the level of palmitoylethanolamide (PEA), can help reduce inflammation. The observed changes may indicate the cellular mechanism of action of CBD in psoriasis and in the case of ultraviolet radiation on the patient's skin.
Palmitoylethanolamide (PEA) is an endogenous fatty acid amide belonging to the class of nuclear factor agonists.
The anti-inflammatory properties of some cannabinoids, particularly CBD, suggest that it may have therapeutic application against inflammatory dermatological diseases. Inflammation in general plays an important role in autoimmune diseases, including psoriasis, as well as in the pathogenesis of many cancers. In addition to other anticancer/antineoplastic properties of cannabinoids, it is suggested that phytocannabinoids may also play a role in regulating, or at least inhibiting, cutaneous carcinogenesis. In addition to anti-inflammatory effects, cannabinoids interact with the skin's ECS components to produce anti-pruritic, anti-aging, anti-cancer and anti-nociceptive effects. Furthermore, it is important to note that solar UV radiation also induces skin inflammation and carcinogenesis via activation of CB1 and CB2 receptors.
In one of the studies linking psoriasis with Cannabis sativa, it was observed that the phytocannabinoids THC, CBD, CBN and Cannabigerol (CBG) can neutralize the proliferation of human keratinocytes transformed with human papillomavirus 16 (HPV 16). The effect was independent of the transient receptor potential channel TRPV 1 CB1/CB2 agonism and was slightly superior for non-psychotropic cannabinoids.
The objective of Piauhy Labs is to carry out studies with cannabinoids, terpenes and other substances present in the Cannabis sativa plant through in-vitro assays, such as cell and tissue cultures (cellular models of target diseases). At the same time, Piauhy intends to use the results and conclusions of its findings to establish key partnerships with Portuguese and international universities and clinical institutions, in order to create academic synergies and potentially lead to the future development of clinical trials together with other institutions.
At a later stage, the objective of Piauhy Labs will be to use the substances that show the greatest potential in in-vitro tests in investigations with animal models (in vivo research). The start of this phase of the project will be pending authorization from the General Directorate of Food and Veterinary Medicine. The research and development activity carried out by Piauhy Labs also aims to characterize and identify methods and substances of interest that can present a safety profile and adequate quality to be included in medicines.
In a final phase, Piauhy Labs intends to obtain a Certification of compliance with Good Laboratory Practices, in accordance with the principles of the OECD, for the pharmaceutical area so that the results obtained from its research are properly used for the granting of licenses or for registration of pharmaceutical products, including medicines for human use and similar products.
As a result of the research processes mentioned above in the therapeutic and medical application, Piauhy Labs intends to create patents and originate intellectual property, with the ultimate objective of producing innovative medicines that improve the health of the population, in particular, medicines that improve the quality of life of patients with the autoimmune disease psoriasis.
Elmo Resende, Ph.D
Director of R&D
Piauhy Labs
References
Benhadou, F.; Mintoff, D.; Schnebert, B. and Thio, H. B. Psoriasis and Microbiota: A Systematic Review. Diseases 6, 47, 2018.
Bigliardi, P. L. Role of Skin pH in Psoriasis. Curr. Probl. Dermatol. 54, 108–114, 2018.
Blauvelt, A. and Chiricozzi, A. The Immunologic Role of IL-17 in Psoriasis and Psoriatic Arthritis Pathogenesis. Clinical Reviews in Allergy & Immunology Dec;55(3):379-390, 2018.
Giulia Martinelli, G.; Andrea Magnavacca, A.; Fumagalli, M.; DellʼAgli, M.; Piazza, S. and Sangiovanni, E. Cannabis sativa and Skin Health: Dissecting the Role of Phytocannabinoids. Planta Med. 2021, published online. DOI 10.1055/a-1420-5780.
Jarocka-Karpowicz, I.; Biernacki, M.; Wronski, A.; Gegotek, A. and Skrzydlewska, E. Cannabidiol Effects on Phospholipid Metabolism in Keratinocytes from Patients with Psoriasis Vulgaris. Biomolecules 10(3), 367, 2020.
Johnson-Huang, L. M.; Lowes, M. A. and Krueger, J. G. Putting together the psoriasis puzzle: an update on developing targeted therapies. Disease Models & Mechanisms, 5(4), 423–433, 2012.
Lin, X. and Huang, T. Oxidative stress in psoriasis and potential therapeutic use of antioxidants. Free Radical Research, Jun;50(6):585-95, 2016.
Lowe, H.; Toyang, N.; Steele, B.; Bryant, J. and Ngwa, W. The Endocannabinoid System: A Potential Target for the Treatment of Various Diseases. Int. J. Mol. Sci. 22, 9472, 2021.
Nestle, F. O.; Kaplan, D. H. and Barker, J. Psoriasis. New England Journal of Medicine, 361(5), 496–509, 2009.
Norooznezhad, A. H.; Norooznezhad, F. Cannabinoids: Possible Agents for Treatment of Psoriasis via Suppression of Angiogenesis and Inflammation, Medical Hypotheses Feb;99:15-18, 2017.
Ogawa, E.; Sato, Y.; Minagawa, A. and Okuyama, R. Pathogenesis of psoriasis and development of treatment. The Journal of Dermatology, Mar;45(3):264-272, 2018.
Ramot, Y.; Sugawara, K.; Zákány, N.; Tóth, B. I.; Bíró, T. and Paus, R. A novel control of human keratin expression: cannabinoid receptor 1-mediated signaling downregulates the expression of keratins K6 and K16 in human keratinocytes in vitro and in situ. PeerJ. 1:e40, 2013.
Shao, K.; Stewart, C. and Grant-Kels, J. M. (2021). Cannabis and the skin. Clinics in Dermatology. Available online 14 May 2021. DOI:10.1016/j.clindermatol.
Scheau, C.; Badarau, I. A.; Mihai, L. G. et al. Cannabinoids in the Pathophysiology of Skin Inflammation. Molecules 25(3), 2020.
Singh, S.; Pradhan, D.; Puri, P.; Ramesh, V.; Aggarwal, S.; Nayek, A. and Jain, A. K. Genomic alterations driving psoriasis pathogenesis. Gene 683, 61–71, 2019.
Timis, T. L. and Orasan, R. I. Understanding psoriasis: Role of miRNAs. Biomed. Rep. 9, 367–374, 2018.
Tóth, F. K.; Ádám, D.; Tamás, B. and Attila, O. Cannabinoid Signaling in the Skin: Therapeutic Potential of the “C(ut)annabinoid” System. Molecules, 24(5), 918, 2019.
Wilkinson, J. D. and Williamson, E. M. 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, 87-92, 2007.
Zhang, X.; Wang, J. F.; Kunos, G. and Groopman, J. E. Cannabinoid modulation of Kaposi's sarcoma-associated herpesvirus infection and transformation. Cancer Res. 67(15):7230-7237, 2007.
Psoriasis is a chronic inflammatory skin disease that is characterized by the differentiation of keratinocyte dysregulation, but oxidative stress also plays an important role in the pathogenesis of this disease. The occurrence of psoriasis is affected by several factors, such as hereditary predisposition, environmental factors, endocrine hormones, stress and immunological factors.
Psoriasis is an autoimmune disease that affects 2-3% of the world's population and can markedly reduce quality of life. The pathophysiology of psoriasis is complex and dynamic, involving skin cells and immune system cells. A wealth of evidence has defined a role for the immune system and its interactive network of leukocytes and cytokines in the pathogenesis of psoriasis.
This disease is usually manifested by the presence of many erythematous, well-demarcated, elevated oval plaques with adherent silvery scales. The scales represent the result of a hyperproliferative epidermis with premature maturation of keratinocytes and an incomplete cornification with retention of nuclei in the stratum corneum (parakeratosis).
People who are affected by the disease of psoriasis have lesions that usually occur in places where there is trauma to the epidermis, such as the elbows and knees, but the lesions can appear anywhere on the body. Furthermore, it is becoming increasingly clear that psoriasis is not just superficial. For example, the frequency of seronegative arthritis in individuals with psoriasis has been estimated to be approximately 7 to 8% of the population with psoriasis, but can be as high as 30%. Other comorbidities seen in individuals with psoriasis can include cardiovascular disease, diabetes mellitus (specially type 2), metabolic syndromes, obesity, impaired quality of life, and depression.
Early studies on the pathogenesis of chronic inflammatory diseases, including rheumatoid arthritis, psoriasis and inflammatory bowel disease, led to the identification of TNF-α as a key trigger of innate inflammatory pathways. Although TNF-α blockers successfully treated rheumatoid arthritis for the first time, they were also rapidly extended to psoriasis and psoriatic arthritis. The inhibitory effects of TNF-α in psoriasis and psoriatic arthritis are complex, because the therapeutic benefits likely result from indirect adaptive immune effects on the IL-23 / IL-17A axis.
The pathogenesis and etiology of psoriasis is complex and our understanding is incomplete, but in summary, psoriasis can be characterized by hyperproliferation of epidermal keratinocytes, accompanied by the infiltration and increase of pro-inflammatory mediators in the skin. The most important mediators involved are those that are associated with a dominant Th1 cytokine profile.
The endocannabinoid system (ECS) is a complex, evolutionarily conserved homeostatic signaling network. It comprises endogenous ligands - endocannabinoids (eCB), for example, anandamide (AEA) - receptors responsive to eCB (for example, cannabinoid receptors CB1 and CB2) and a complex apparatus of enzymes and transporters.
Depending on their concentrations, endocannabinoids (eCBs) and phytocannabinoids (pCBs) are able to notably activate/antagonize/inhibit a wide variety of cellular targets, including several metabotropics (e.g., CB1 or CB2 receptors), ionotropics, as certain transient receptor potential ion channels (TRP) and nuclear receptors, which are activated by peroxisome receptor proliferators (PPARs), various enzymes and transporters. More importantly, each ligand can be characterized by a unique molecular fingerprint and, in some cases, they can even exert opposite biological actions on the same target molecule.
Cannabinoids are known to play a critical role in suppressing and inhibiting angiogenesis and inflammation. Cannabinoids can inhibit TNF-α, INF-γ and IL-2 and IL-8, which are considered to be key elements of both angiogenesis and inflammation in the disease of psoriasis.
Some studies suggest that cannabinoids and their receptors constitute a new clinically relevant control element for the expression of K6 and K16 human keratinocytes. Therefore, cannabimimetic agents may be relevant for the treatment of several skin diseases related to the important expression of K6/K16, such as psoriasis and wound healing. Furthermore, skin organ culture may be a physiologically relevant system model to investigate the effect of specific CB1 agonists/antagonists on human skin.
The beneficial effects of phytocannabinoids Δ-9-Tetrahydrocannabinol (THC), Cannabidiol (CBD) and Cannabinol (CBN) in psoriasis are the conversion of the pro-inflammatory Th1 profile into an anti-inflammatory expressed as being of the Th2 type, in addition to the antiproliferative properties in keratinocytes. However, these effects seem to be mediated predominantly through gamma-type peroxisome proliferator-activated receptors - PPARγ, independent of endocannabinoid receptors - CBs, demonstrated by robust results in CB1 and CB2 blockade in human papilloma virus (HPV) - 16 E6/E7 in cultures of transformed human skin keratinocytes.
Another important function of cannabinoid signaling is to control local immune responses in the skin. Several lines of evidence demonstrate that both eCBs and pCBs can modulate immune functions, and are generally considered anti-inflammatory agents. Importantly, the immunological effects of cannabinoids are not only exerted on immune cells, but also on cells that do not belong to the immune system (e.g., keratinocytes, sebocytes).
Despite solid clinical and experimental evidence proving that CBD is capable of antagonizing CB1, it is very important to emphasize that it can also behave in a context-dependent manner as a functional CB1 activator. In fact, by inhibiting fatty acid amide hydrolase (FAAH) and/or endocannabinoid membrane transporters (EMT), their administration can lead to an elevation of the local eCB and therefore indirectly to an increase in CB1 activity in certain systems.
Genetic and epigenetic abnormalities, as well as changes in skin microbiota, pH, or, more importantly, IL-17 signaling are known to be involved in the development of psoriasis as well as non-cutaneous symptoms (e.g., arthritis). It is, of course, accompanied by a disturbance in the dynamic cross-talk between epidermal keratinocytes and professional skin immune cells. This inadequate communication then leads to pathological inflammatory processes and a disturbance in the proliferation/differentiation balance of epidermal keratinocytes. Since, as discussed above, the proliferation/differentiation as well as the immunological activity of epidermal keratinocytes are under strict control of eCB signaling.
The oxidative stress observed in the keratinocytes of patients with psoriasis is a critical element of the immune response to this pathology, which is further intensified by ultraviolet radiation. Metabolic modifications, especially in the phospholipid/protein membrane, can lead to excessive apoptosis or modulation of cell signaling dependent on phospholipid derivatives, which are partially responsible for the modulation of oxidative stress. Therefore, treatment with CBD, which leads to accumulation of CBD, mainly in keratinocyte membranes, particularly in UV-irradiated psoriasis cells, reduces phospholipid oxidative modifications and their consequences. At the same time, CBD, by increasing the level of palmitoylethanolamide (PEA), can help reduce inflammation. The observed changes may indicate the cellular mechanism of action of CBD in psoriasis and in the case of ultraviolet radiation on the patient's skin.
Palmitoylethanolamide (PEA) is an endogenous fatty acid amide belonging to the class of nuclear factor agonists.
The anti-inflammatory properties of some cannabinoids, particularly CBD, suggest that it may have therapeutic application against inflammatory dermatological diseases. Inflammation in general plays an important role in autoimmune diseases, including psoriasis, as well as in the pathogenesis of many cancers. In addition to other anticancer/antineoplastic properties of cannabinoids, it is suggested that phytocannabinoids may also play a role in regulating, or at least inhibiting, cutaneous carcinogenesis. In addition to anti-inflammatory effects, cannabinoids interact with the skin's ECS components to produce anti-pruritic, anti-aging, anti-cancer and anti-nociceptive effects. Furthermore, it is important to note that solar UV radiation also induces skin inflammation and carcinogenesis via activation of CB1 and CB2 receptors.
In one of the studies linking psoriasis with Cannabis sativa, it was observed that the phytocannabinoids THC, CBD, CBN and Cannabigerol (CBG) can neutralize the proliferation of human keratinocytes transformed with human papillomavirus 16 (HPV 16). The effect was independent of the transient receptor potential channel TRPV 1 CB1/CB2 agonism and was slightly superior for non-psychotropic cannabinoids.
The objective of Piauhy Labs is to carry out studies with cannabinoids, terpenes and other substances present in the Cannabis sativa plant through in-vitro assays, such as cell and tissue cultures (cellular models of target diseases). At the same time, Piauhy intends to use the results and conclusions of its findings to establish key partnerships with Portuguese and international universities and clinical institutions, in order to create academic synergies and potentially lead to the future development of clinical trials together with other institutions.
At a later stage, the objective of Piauhy Labs will be to use the substances that show the greatest potential in in-vitro tests in investigations with animal models (in vivo research). The start of this phase of the project will be pending authorization from the General Directorate of Food and Veterinary Medicine. The research and development activity carried out by Piauhy Labs also aims to characterize and identify methods and substances of interest that can present a safety profile and adequate quality to be included in medicines.
In a final phase, Piauhy Labs intends to obtain a Certification of compliance with Good Laboratory Practices, in accordance with the principles of the OECD, for the pharmaceutical area so that the results obtained from its research are properly used for the granting of licenses or for registration of pharmaceutical products, including medicines for human use and similar products.
As a result of the research processes mentioned above in the therapeutic and medical application, Piauhy Labs intends to create patents and originate intellectual property, with the ultimate objective of producing innovative medicines that improve the health of the population, in particular, medicines that improve the quality of life of patients with the autoimmune disease psoriasis.
Elmo Resende, Ph.D
Director of R&D
Piauhy Labs
References
Benhadou, F.; Mintoff, D.; Schnebert, B. and Thio, H. B. Psoriasis and Microbiota: A Systematic Review. Diseases 6, 47, 2018.
Bigliardi, P. L. Role of Skin pH in Psoriasis. Curr. Probl. Dermatol. 54, 108–114, 2018.
Blauvelt, A. and Chiricozzi, A. The Immunologic Role of IL-17 in Psoriasis and Psoriatic Arthritis Pathogenesis. Clinical Reviews in Allergy & Immunology Dec;55(3):379-390, 2018.
Giulia Martinelli, G.; Andrea Magnavacca, A.; Fumagalli, M.; DellʼAgli, M.; Piazza, S. and Sangiovanni, E. Cannabis sativa and Skin Health: Dissecting the Role of Phytocannabinoids. Planta Med. 2021, published online. DOI 10.1055/a-1420-5780.
Jarocka-Karpowicz, I.; Biernacki, M.; Wronski, A.; Gegotek, A. and Skrzydlewska, E. Cannabidiol Effects on Phospholipid Metabolism in Keratinocytes from Patients with Psoriasis Vulgaris. Biomolecules 10(3), 367, 2020.
Johnson-Huang, L. M.; Lowes, M. A. and Krueger, J. G. Putting together the psoriasis puzzle: an update on developing targeted therapies. Disease Models & Mechanisms, 5(4), 423–433, 2012.
Lin, X. and Huang, T. Oxidative stress in psoriasis and potential therapeutic use of antioxidants. Free Radical Research, Jun;50(6):585-95, 2016.
Lowe, H.; Toyang, N.; Steele, B.; Bryant, J. and Ngwa, W. The Endocannabinoid System: A Potential Target for the Treatment of Various Diseases. Int. J. Mol. Sci. 22, 9472, 2021.
Nestle, F. O.; Kaplan, D. H. and Barker, J. Psoriasis. New England Journal of Medicine, 361(5), 496–509, 2009.
Norooznezhad, A. H.; Norooznezhad, F. Cannabinoids: Possible Agents for Treatment of Psoriasis via Suppression of Angiogenesis and Inflammation, Medical Hypotheses Feb;99:15-18, 2017.
Ogawa, E.; Sato, Y.; Minagawa, A. and Okuyama, R. Pathogenesis of psoriasis and development of treatment. The Journal of Dermatology, Mar;45(3):264-272, 2018.
Ramot, Y.; Sugawara, K.; Zákány, N.; Tóth, B. I.; Bíró, T. and Paus, R. A novel control of human keratin expression: cannabinoid receptor 1-mediated signaling downregulates the expression of keratins K6 and K16 in human keratinocytes in vitro and in situ. PeerJ. 1:e40, 2013.
Shao, K.; Stewart, C. and Grant-Kels, J. M. (2021). Cannabis and the skin. Clinics in Dermatology. Available online 14 May 2021. DOI:10.1016/j.clindermatol.
Scheau, C.; Badarau, I. A.; Mihai, L. G. et al. Cannabinoids in the Pathophysiology of Skin Inflammation. Molecules 25(3), 2020.
Singh, S.; Pradhan, D.; Puri, P.; Ramesh, V.; Aggarwal, S.; Nayek, A. and Jain, A. K. Genomic alterations driving psoriasis pathogenesis. Gene 683, 61–71, 2019.
Timis, T. L. and Orasan, R. I. Understanding psoriasis: Role of miRNAs. Biomed. Rep. 9, 367–374, 2018.
Tóth, F. K.; Ádám, D.; Tamás, B. and Attila, O. Cannabinoid Signaling in the Skin: Therapeutic Potential of the “C(ut)annabinoid” System. Molecules, 24(5), 918, 2019.
Wilkinson, J. D. and Williamson, E. M. 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, 87-92, 2007.
Zhang, X.; Wang, J. F.; Kunos, G. and Groopman, J. E. Cannabinoid modulation of Kaposi's sarcoma-associated herpesvirus infection and transformation. Cancer Res. 67(15):7230-7237, 2007.