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A primer on cannabis for cosmeceuticals: Research and treatments for particular skin conditions
The relatively recent discovery of the endogenous cannabinoid system and the quickly evolving, yet still convoluted, legal status of cannabis in the United States has spurred excitement over expanded research opportunities. Despite its checkered legal history, marijuana – derived from Cannabis sativa and Cannabis indica – has long been used for medical purposes and is one of the most widely used drugs throughout the world.1 Modern medicine has deployed this dynamic plant to treat chronic pain, glaucoma, and nausea, and continues to investigate its application in a broad array of conditions: anorexia, spasticity, atherosclerosis, autoimmune disorders, inflammatory bowel disease, multiple sclerosis, spasticity, tumorigenesis, and multiple cutaneous disorders, including acne, eczematous disorders, lichen simplex, melanoma and nonmelanoma skin cancer, melasma, prurigo, pruritus, psoriasis, scleroderma and systemic sclerosis, and seborrheic dermatitis.1-4 This .
Acne
Oláh et al. have demonstrated that the nonpsychotropic phytocannabinoid ((-)-cannabidiol [CBD]) imparts anti-acne benefits by diminishing sebaceous lipid synthesis, decreasing proliferation, and easing inflammation in human SZ95 sebocytes.5 In additional investigations of nonpsychotropic phytocannabinoids and their effects on human sebocyte function, they reported in 2016 that the phytocannabinoids (-)-cannabigerol [CBG] and (-)-cannabigerovarin (CBGV) appear to exhibit promise in treating xerotic and seborrheic skin, and ((-)-cannabichromene [CBC], (-)-cannabidivarin [CBDV], and (-)-delta9-tetrahydrocannabivarin [THCV], in particular, display notable potential as anti-acne ingredients. The investigators added that these compounds, due to their substantial anti-inflammatory effects, warrant consideration for use in treating skin inflammation.5 Previously, Ali and Akhtar conducted a single-blinded, 12-week comparative study in healthy male volunteers to evaluate the effects of twice-daily application of 3% cannabis seed extract cream on human cheek skin. The researchers found the base with 3% cannabis seed extract to be safe and effective, with skin sebum and erythema content on the treated side reduced significantly compared with the side treated only with the control base. They concluded that this well-tolerated formulation could be indicated for the treatment of acne and seborrhea to enhance facial appearance.6
Psoriasis
The endocannabinoid system itself is thought to play a potentially important role in the treatment of psoriasis, as interactions between the immune and nervous systems via cholinergic anti-inflammatory pathways are considered to be key in psoriasis etiology and the endocannabinoid system interacts with both systems through the cannabinoid (CB) receptors CB1 and CB2.7 Compared with normal human skin, psoriatic skin is characterized by fewer CB receptors.8
In 2007, Wilkinson and Williamson used a keratinocyte proliferation assay to study the phytocannabinoids delta9-tetrahydrocannabinol (THC), CBD, CBG, and cannabinol (CNB) to assess their capacity to halt the growth of a hyper-proliferating human keratinocyte cell line with an eye toward potential use in treating psoriasis. CB1 and CB2 receptors were confirmed present by Western blot and RT-PCR analyses. All cannabinoids investigated concentration-dependently hindered keratinocyte proliferation, as the authors concluded that these compounds show potential for use in psoriasis treatment.9
In 2013, Ramot et al. found that treating human skin culture with the CB1-specific agonist arachidonoyl-chloro-ethanolamide reduced the expression of keratins K6 and K16 in vitro and in situ, which may have implications for psoriasis treatment as K6 and K16 are upregulated in that disorder.10 The same team has also recently shown that the CB1 agonist arachidonyl-2’-chloroethylamide upregulated K10 protein expression in human epidermis and reduced K1 in human skin culture thus suggesting its potential as a treatment for epidermolytic ichthyosis.11
Notably, the synthetic cannabinoid JWH-133, known for its potent antiangiogenic and anti-inflammatory properties, has been shown in vivo and in vitro to suppress various inflammatory cytokines and angiogenic growth factors involved in psoriasis pathogenesis, including hypoxia inducible factor-1 alpha (HIF-1 alpha), vascular endothelial growth factor (VEGF), matrix metalloproteinases, basic fibroblast growth factor (bFGF), angiopoietin-2, interleukin-8 (IL-8), IL-17, and IL-2. While more research is necessary to determine the safety and efficacy of this product, it appears promising as an anti-psoriatic agent.12
Pruritus
Stimulation of the CB1 receptor has been demonstrated to inhibit histamine-induced pruritus.8
In 2005, Szepietowski et al. conducted a preliminary study to ascertain the efficacy and tolerance of a cream with structured physiological lipids and endogenous cannabinoids in managing pruritus in 21 patients on maintenance dialysis. For 3 weeks, the patients with uremic pruritus applied the test cream twice daily, with eight patients experiencing full eradication of pruritus at the end of this period. Further, xerosis was completely eliminated in 17 patients after the study, and significantly decreased during the 3-week period. The investigators suggested that while more research was needed, the well-tolerated product is thought to have been enhanced by the addition of endocannabinoids.13
A year later, Ständer et al. assessed the effects of the use of the topical cannabinoid agonist N-palmitoyl ethanolamine (PEA), which stimulates the endocannabinoid arachidonoyl ethanolamide (AEA) to activate CB1, in an open application study with 22 patients with prurigo, lichen simplex, and pruritus. Antipruritic benefits were seen in 14 patients, with an average decrease in itch of 86.4%. The treatment was reported to be well tolerated, as no patients complained of adverse effects such as contact dermatitis or a burning sensation.14
Eczematic dermatoses
Atopic dermatitis
In a small pilot study on pediatric atopic dermatitis in 2007, Pulvirenti et al. evaluated the safety and efficacy of the twice-daily application of a topical emulsion containing a synthetic aliamide (adelmidrol 2%), comparable to its parent substance PEA, in the treatment of 11 males and 9 females with atopic dermatitis (AD), whose mean age was 8 years. Among the 20 pediatric patients, 16 experienced complete resolution of symptoms after 4 weeks of treatment and had no relapses at the 8-week follow-up assessment. No improvement was noted in the six patches of AD in six patients with several untreated lesions that served as controls.15 Also in 2007, Del Rosso reported on a trial in which a PEA-containing nonsteroidal cream significantly lowered the mean time between flares in pediatric and adult AD patients.16
One year later, Eberlein et al. evaluated an emollient containing PEA in AD patients, finding that itch severity and sleep loss were improved by an average of 60%, with 38% of participants stopping oral antihistamines, 33.6% discontinuing topical steroid regimens, and 20% ending their use of topical immunomodulators as the study concluded.4,17
In 2018, Río et al. suggested that targeted manipulation of the endocannabinoid system at various AD stages might rein in the inflammatory and immune responses and ensuing alterations in keratinocytes, thus helping to preserve epidermal barrier function.18 As Trusler et al. noted, though, no control groups were used in the latter two studies, so it is unknown what effect the application of the vehicle alone would have had on the pruritus in these patients.19
Allergic contact dermatitis
In 2007, Karsak et al. demonstrated that mice lacking CB1/2 receptors exhibited aggravated contact hypersensitivity, whereas mice with higher levels of AEA evinced lower cutaneous allergic responses.20
Recently, Petrosino et al. provided the first evidence that the nonpsychotropic cannabinoid cannabidiol conferred anti-inflammatory activity in an experimental in vitro model of allergic contact dermatitis.21
Dermatomyositis
Robinson et al. have found that treating blood samples of patients with dermatomyositis with the nonpsychoactive cannabinoid ajulemic acid appears to limit the production of pathogenic cytokines. They suggest that oral administration of this cannabinoid merits consideration for dermatomyositis.22
Skin cancer
In 2015, Glodde et al. used a mouse model to investigate the role of cannabinoids in skin cancer pathogenesis. They considered THC, which binds to CB1 and CB2, and the endogenous cannabinoid system. The researchers found that in a CB receptor-dependent fashion THC significantly hindered the tumor growth of HCmel12 melanomas in vivo, verifying the merit of exogenous cannabinoids in melanoma treatment. They did not identify a role of the endogenous cannabinoid system in skin cancer pathogenesis.23
Additional studies suggest that endocannabinoids, phytocannabinoids, and synthetic cannabinoids diminish skin cancer growth (melanoma and nonmelanoma) in vitro and in vivo through CB receptor-dependent and -independent pathways, though in vivo human studies have not yet been conducted.8,24
Epidermolysis bullosa
In a promising observational study in 2018, Chelliah et al. reported on three cases of self-initiated topical cannabidiol use in patients with epidermolysis bullosa. Each patient experienced more rapid wound healing, less blistering, and reduced pain as a result of cannabidiol treatment, and one was able to discontinue oral opioids. The authors were encouraged by such findings, but cautioned that randomized, double-blind clinical trials are needed to establish cannabidiol as an effective therapy.25
This seems particularly important given the climate of expanding legalization of medical and recreational cannabis use, as well as the increasing use of topical cannabinoids among dermatology patients.26 Nevertheless, it is important to be cognizant of one’s own state laws as topical cannabinoids may be restricted; these products are marketed for pain and pruritus on the Internet but are unavailable by prescription unless the physician has a special license.4
Attitudes about cannabinoid use in dermatology
In an intriguing study last year about the knowledge, cognizance, and perceptions of cannabinoids among dermatologists, Robinson et al. created a 20-question online survey that netted a response rate of 21% (n = 531). In terms of awareness, 29% of respondents did not know that THC is psychoactive and a significant majority (64%) did not know that CBD is not psychoactive. Nevertheless, the majority thought that cannabinoids should be legal for medical treatment (86%), and even more (94%) support researching dermatologic applications of cannabinoids. More responders (86%) would prescribe a Food and Drug Administration–approved cannabinoid-containing topical formulation than an oral product (71%). In also noting that 55% revealed at least one conversation about cannabinoids initiated by a patient in the previous year, while 48% expressed concern about a possible stigma associated with suggesting cannabinoid treatments to patients, Robinson et al. call for further education about the benefits and risks of cutaneous cannabinoids for dermatologists.27
Conclusion
It is important that we educate ourselves as to the effects of orally administered and topical products containing cannabis so that we are prepared for questions from patients. Data on psoriasis, pruritus, eczema, and acne warrant optimism and much additional research. Now that the FDA is allowing research sites to enroll for a special license to investigate schedule I drugs, we stand to learn much more about the various effects on the health benefits of cannabis. Despite the longstanding traditional use of C. sativa and C. indica, we are in the early stages of research on the impact of phytocannabinoids and synthetic cannabinoids on human health and the role that the endocannabinoid system plays. The extant findings provide reasons to consider the endocannabinoid system as a target for therapeutic intervention for various cutaneous disorders as research continues.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and “Cosmeceuticals and Cosmetic Ingredients” (New York: McGraw-Hill, 2014), and a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems LLC. She has no relevant disclosures related to this column. Write to her at [email protected].
References
1. Russo EB. Chem Biodivers. 2007 Aug;4(8):1614-48.
2. Goldenberg M et al. Drug Alcohol Depend. 2017 May 1;174:80-90.
3. Mounessa JS et al. J Am Acad Dermatol. 2017 Jul;77(1):188-90.
4. Shalaby M et al. Pract Dermatol. 2018;68-70.
5. Oláh A et al. Exp Dermatol. 2016 Sep;25(9):701-7.
6. Ali A et al. Pak J Pharm Sci. 2015 Jul;28(4):1389-95.
7. Derakhshan N et al. Curr Clin Pharmacol. 2016;11(2):146-7.
8. Singh D et al. Clin Dermatol. 2018 May-Jun;36(3):399-419.
9. Wilkinson JD et al. J Dermatol Sci. 2007 Feb;45(2):87-92.
10. Ramot Y et al. PeerJ. 2013 Feb 19;1:e40.
11. Ramot Y et al. Br J Dermatol. 2018 Jun;178(6):1469.
12. Norooznezhad AH et al. Med Hypotheses. 2017 Feb;99:15-18.
13. Szepietowski JC et al. Acta Dermatovenerol Croat. 2005;13(2):97-103.
14. Ständer S et al. Hautarzt. 2006 Sep;57(9):801-7.
15. Pulvirenti N et al. Acta Dermatovenerol Croat. 2007;15(2):80-3.
16. Del Rosso JQ. Cosmetic Dermatol. 2007 Apr; 20(4):208-211.
17. Eberlein B et al. J Eur Acad Dermatol Venereol. 2008 Jan;22(1):73-82.
18. Del Río CD et al. Biochem Pharmacol. 2018 Nov;157:122-133.
19. Trusler AR et al. Dermatitis. 2017 Jan/Feb;28(1):22-32.
20. Karsak M et al. Science. 2007 Jun 8;316(5830):1494-7.
21. Petrosino S et al. J Pharmacol Exp Ther. 2018 Jun;365(3):652-63.
22. Robinson ES et al. J Invest Dermatol. 2017 Nov;137(11):2445-7.
23. Glodde N et al. Life Sci. 2015 Oct 1;138:35-40.
24. Soliman E. et al. J Dermatol Clin Res. 2016;4(2):1069-76.
25. Chelliah MP et al. Pediatr Dermatol. 2018 Jul;35(4):e224-e227.
26. Hashim PW et al. Cutis. 2017 Jul;100(1):50-52.
27. Robinson E et al. J Drugs Dermatol. 2018 Dec 1;17(12):1273-8.
The relatively recent discovery of the endogenous cannabinoid system and the quickly evolving, yet still convoluted, legal status of cannabis in the United States has spurred excitement over expanded research opportunities. Despite its checkered legal history, marijuana – derived from Cannabis sativa and Cannabis indica – has long been used for medical purposes and is one of the most widely used drugs throughout the world.1 Modern medicine has deployed this dynamic plant to treat chronic pain, glaucoma, and nausea, and continues to investigate its application in a broad array of conditions: anorexia, spasticity, atherosclerosis, autoimmune disorders, inflammatory bowel disease, multiple sclerosis, spasticity, tumorigenesis, and multiple cutaneous disorders, including acne, eczematous disorders, lichen simplex, melanoma and nonmelanoma skin cancer, melasma, prurigo, pruritus, psoriasis, scleroderma and systemic sclerosis, and seborrheic dermatitis.1-4 This .
Acne
Oláh et al. have demonstrated that the nonpsychotropic phytocannabinoid ((-)-cannabidiol [CBD]) imparts anti-acne benefits by diminishing sebaceous lipid synthesis, decreasing proliferation, and easing inflammation in human SZ95 sebocytes.5 In additional investigations of nonpsychotropic phytocannabinoids and their effects on human sebocyte function, they reported in 2016 that the phytocannabinoids (-)-cannabigerol [CBG] and (-)-cannabigerovarin (CBGV) appear to exhibit promise in treating xerotic and seborrheic skin, and ((-)-cannabichromene [CBC], (-)-cannabidivarin [CBDV], and (-)-delta9-tetrahydrocannabivarin [THCV], in particular, display notable potential as anti-acne ingredients. The investigators added that these compounds, due to their substantial anti-inflammatory effects, warrant consideration for use in treating skin inflammation.5 Previously, Ali and Akhtar conducted a single-blinded, 12-week comparative study in healthy male volunteers to evaluate the effects of twice-daily application of 3% cannabis seed extract cream on human cheek skin. The researchers found the base with 3% cannabis seed extract to be safe and effective, with skin sebum and erythema content on the treated side reduced significantly compared with the side treated only with the control base. They concluded that this well-tolerated formulation could be indicated for the treatment of acne and seborrhea to enhance facial appearance.6
Psoriasis
The endocannabinoid system itself is thought to play a potentially important role in the treatment of psoriasis, as interactions between the immune and nervous systems via cholinergic anti-inflammatory pathways are considered to be key in psoriasis etiology and the endocannabinoid system interacts with both systems through the cannabinoid (CB) receptors CB1 and CB2.7 Compared with normal human skin, psoriatic skin is characterized by fewer CB receptors.8
In 2007, Wilkinson and Williamson used a keratinocyte proliferation assay to study the phytocannabinoids delta9-tetrahydrocannabinol (THC), CBD, CBG, and cannabinol (CNB) to assess their capacity to halt the growth of a hyper-proliferating human keratinocyte cell line with an eye toward potential use in treating psoriasis. CB1 and CB2 receptors were confirmed present by Western blot and RT-PCR analyses. All cannabinoids investigated concentration-dependently hindered keratinocyte proliferation, as the authors concluded that these compounds show potential for use in psoriasis treatment.9
In 2013, Ramot et al. found that treating human skin culture with the CB1-specific agonist arachidonoyl-chloro-ethanolamide reduced the expression of keratins K6 and K16 in vitro and in situ, which may have implications for psoriasis treatment as K6 and K16 are upregulated in that disorder.10 The same team has also recently shown that the CB1 agonist arachidonyl-2’-chloroethylamide upregulated K10 protein expression in human epidermis and reduced K1 in human skin culture thus suggesting its potential as a treatment for epidermolytic ichthyosis.11
Notably, the synthetic cannabinoid JWH-133, known for its potent antiangiogenic and anti-inflammatory properties, has been shown in vivo and in vitro to suppress various inflammatory cytokines and angiogenic growth factors involved in psoriasis pathogenesis, including hypoxia inducible factor-1 alpha (HIF-1 alpha), vascular endothelial growth factor (VEGF), matrix metalloproteinases, basic fibroblast growth factor (bFGF), angiopoietin-2, interleukin-8 (IL-8), IL-17, and IL-2. While more research is necessary to determine the safety and efficacy of this product, it appears promising as an anti-psoriatic agent.12
Pruritus
Stimulation of the CB1 receptor has been demonstrated to inhibit histamine-induced pruritus.8
In 2005, Szepietowski et al. conducted a preliminary study to ascertain the efficacy and tolerance of a cream with structured physiological lipids and endogenous cannabinoids in managing pruritus in 21 patients on maintenance dialysis. For 3 weeks, the patients with uremic pruritus applied the test cream twice daily, with eight patients experiencing full eradication of pruritus at the end of this period. Further, xerosis was completely eliminated in 17 patients after the study, and significantly decreased during the 3-week period. The investigators suggested that while more research was needed, the well-tolerated product is thought to have been enhanced by the addition of endocannabinoids.13
A year later, Ständer et al. assessed the effects of the use of the topical cannabinoid agonist N-palmitoyl ethanolamine (PEA), which stimulates the endocannabinoid arachidonoyl ethanolamide (AEA) to activate CB1, in an open application study with 22 patients with prurigo, lichen simplex, and pruritus. Antipruritic benefits were seen in 14 patients, with an average decrease in itch of 86.4%. The treatment was reported to be well tolerated, as no patients complained of adverse effects such as contact dermatitis or a burning sensation.14
Eczematic dermatoses
Atopic dermatitis
In a small pilot study on pediatric atopic dermatitis in 2007, Pulvirenti et al. evaluated the safety and efficacy of the twice-daily application of a topical emulsion containing a synthetic aliamide (adelmidrol 2%), comparable to its parent substance PEA, in the treatment of 11 males and 9 females with atopic dermatitis (AD), whose mean age was 8 years. Among the 20 pediatric patients, 16 experienced complete resolution of symptoms after 4 weeks of treatment and had no relapses at the 8-week follow-up assessment. No improvement was noted in the six patches of AD in six patients with several untreated lesions that served as controls.15 Also in 2007, Del Rosso reported on a trial in which a PEA-containing nonsteroidal cream significantly lowered the mean time between flares in pediatric and adult AD patients.16
One year later, Eberlein et al. evaluated an emollient containing PEA in AD patients, finding that itch severity and sleep loss were improved by an average of 60%, with 38% of participants stopping oral antihistamines, 33.6% discontinuing topical steroid regimens, and 20% ending their use of topical immunomodulators as the study concluded.4,17
In 2018, Río et al. suggested that targeted manipulation of the endocannabinoid system at various AD stages might rein in the inflammatory and immune responses and ensuing alterations in keratinocytes, thus helping to preserve epidermal barrier function.18 As Trusler et al. noted, though, no control groups were used in the latter two studies, so it is unknown what effect the application of the vehicle alone would have had on the pruritus in these patients.19
Allergic contact dermatitis
In 2007, Karsak et al. demonstrated that mice lacking CB1/2 receptors exhibited aggravated contact hypersensitivity, whereas mice with higher levels of AEA evinced lower cutaneous allergic responses.20
Recently, Petrosino et al. provided the first evidence that the nonpsychotropic cannabinoid cannabidiol conferred anti-inflammatory activity in an experimental in vitro model of allergic contact dermatitis.21
Dermatomyositis
Robinson et al. have found that treating blood samples of patients with dermatomyositis with the nonpsychoactive cannabinoid ajulemic acid appears to limit the production of pathogenic cytokines. They suggest that oral administration of this cannabinoid merits consideration for dermatomyositis.22
Skin cancer
In 2015, Glodde et al. used a mouse model to investigate the role of cannabinoids in skin cancer pathogenesis. They considered THC, which binds to CB1 and CB2, and the endogenous cannabinoid system. The researchers found that in a CB receptor-dependent fashion THC significantly hindered the tumor growth of HCmel12 melanomas in vivo, verifying the merit of exogenous cannabinoids in melanoma treatment. They did not identify a role of the endogenous cannabinoid system in skin cancer pathogenesis.23
Additional studies suggest that endocannabinoids, phytocannabinoids, and synthetic cannabinoids diminish skin cancer growth (melanoma and nonmelanoma) in vitro and in vivo through CB receptor-dependent and -independent pathways, though in vivo human studies have not yet been conducted.8,24
Epidermolysis bullosa
In a promising observational study in 2018, Chelliah et al. reported on three cases of self-initiated topical cannabidiol use in patients with epidermolysis bullosa. Each patient experienced more rapid wound healing, less blistering, and reduced pain as a result of cannabidiol treatment, and one was able to discontinue oral opioids. The authors were encouraged by such findings, but cautioned that randomized, double-blind clinical trials are needed to establish cannabidiol as an effective therapy.25
This seems particularly important given the climate of expanding legalization of medical and recreational cannabis use, as well as the increasing use of topical cannabinoids among dermatology patients.26 Nevertheless, it is important to be cognizant of one’s own state laws as topical cannabinoids may be restricted; these products are marketed for pain and pruritus on the Internet but are unavailable by prescription unless the physician has a special license.4
Attitudes about cannabinoid use in dermatology
In an intriguing study last year about the knowledge, cognizance, and perceptions of cannabinoids among dermatologists, Robinson et al. created a 20-question online survey that netted a response rate of 21% (n = 531). In terms of awareness, 29% of respondents did not know that THC is psychoactive and a significant majority (64%) did not know that CBD is not psychoactive. Nevertheless, the majority thought that cannabinoids should be legal for medical treatment (86%), and even more (94%) support researching dermatologic applications of cannabinoids. More responders (86%) would prescribe a Food and Drug Administration–approved cannabinoid-containing topical formulation than an oral product (71%). In also noting that 55% revealed at least one conversation about cannabinoids initiated by a patient in the previous year, while 48% expressed concern about a possible stigma associated with suggesting cannabinoid treatments to patients, Robinson et al. call for further education about the benefits and risks of cutaneous cannabinoids for dermatologists.27
Conclusion
It is important that we educate ourselves as to the effects of orally administered and topical products containing cannabis so that we are prepared for questions from patients. Data on psoriasis, pruritus, eczema, and acne warrant optimism and much additional research. Now that the FDA is allowing research sites to enroll for a special license to investigate schedule I drugs, we stand to learn much more about the various effects on the health benefits of cannabis. Despite the longstanding traditional use of C. sativa and C. indica, we are in the early stages of research on the impact of phytocannabinoids and synthetic cannabinoids on human health and the role that the endocannabinoid system plays. The extant findings provide reasons to consider the endocannabinoid system as a target for therapeutic intervention for various cutaneous disorders as research continues.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and “Cosmeceuticals and Cosmetic Ingredients” (New York: McGraw-Hill, 2014), and a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems LLC. She has no relevant disclosures related to this column. Write to her at [email protected].
References
1. Russo EB. Chem Biodivers. 2007 Aug;4(8):1614-48.
2. Goldenberg M et al. Drug Alcohol Depend. 2017 May 1;174:80-90.
3. Mounessa JS et al. J Am Acad Dermatol. 2017 Jul;77(1):188-90.
4. Shalaby M et al. Pract Dermatol. 2018;68-70.
5. Oláh A et al. Exp Dermatol. 2016 Sep;25(9):701-7.
6. Ali A et al. Pak J Pharm Sci. 2015 Jul;28(4):1389-95.
7. Derakhshan N et al. Curr Clin Pharmacol. 2016;11(2):146-7.
8. Singh D et al. Clin Dermatol. 2018 May-Jun;36(3):399-419.
9. Wilkinson JD et al. J Dermatol Sci. 2007 Feb;45(2):87-92.
10. Ramot Y et al. PeerJ. 2013 Feb 19;1:e40.
11. Ramot Y et al. Br J Dermatol. 2018 Jun;178(6):1469.
12. Norooznezhad AH et al. Med Hypotheses. 2017 Feb;99:15-18.
13. Szepietowski JC et al. Acta Dermatovenerol Croat. 2005;13(2):97-103.
14. Ständer S et al. Hautarzt. 2006 Sep;57(9):801-7.
15. Pulvirenti N et al. Acta Dermatovenerol Croat. 2007;15(2):80-3.
16. Del Rosso JQ. Cosmetic Dermatol. 2007 Apr; 20(4):208-211.
17. Eberlein B et al. J Eur Acad Dermatol Venereol. 2008 Jan;22(1):73-82.
18. Del Río CD et al. Biochem Pharmacol. 2018 Nov;157:122-133.
19. Trusler AR et al. Dermatitis. 2017 Jan/Feb;28(1):22-32.
20. Karsak M et al. Science. 2007 Jun 8;316(5830):1494-7.
21. Petrosino S et al. J Pharmacol Exp Ther. 2018 Jun;365(3):652-63.
22. Robinson ES et al. J Invest Dermatol. 2017 Nov;137(11):2445-7.
23. Glodde N et al. Life Sci. 2015 Oct 1;138:35-40.
24. Soliman E. et al. J Dermatol Clin Res. 2016;4(2):1069-76.
25. Chelliah MP et al. Pediatr Dermatol. 2018 Jul;35(4):e224-e227.
26. Hashim PW et al. Cutis. 2017 Jul;100(1):50-52.
27. Robinson E et al. J Drugs Dermatol. 2018 Dec 1;17(12):1273-8.
The relatively recent discovery of the endogenous cannabinoid system and the quickly evolving, yet still convoluted, legal status of cannabis in the United States has spurred excitement over expanded research opportunities. Despite its checkered legal history, marijuana – derived from Cannabis sativa and Cannabis indica – has long been used for medical purposes and is one of the most widely used drugs throughout the world.1 Modern medicine has deployed this dynamic plant to treat chronic pain, glaucoma, and nausea, and continues to investigate its application in a broad array of conditions: anorexia, spasticity, atherosclerosis, autoimmune disorders, inflammatory bowel disease, multiple sclerosis, spasticity, tumorigenesis, and multiple cutaneous disorders, including acne, eczematous disorders, lichen simplex, melanoma and nonmelanoma skin cancer, melasma, prurigo, pruritus, psoriasis, scleroderma and systemic sclerosis, and seborrheic dermatitis.1-4 This .
Acne
Oláh et al. have demonstrated that the nonpsychotropic phytocannabinoid ((-)-cannabidiol [CBD]) imparts anti-acne benefits by diminishing sebaceous lipid synthesis, decreasing proliferation, and easing inflammation in human SZ95 sebocytes.5 In additional investigations of nonpsychotropic phytocannabinoids and their effects on human sebocyte function, they reported in 2016 that the phytocannabinoids (-)-cannabigerol [CBG] and (-)-cannabigerovarin (CBGV) appear to exhibit promise in treating xerotic and seborrheic skin, and ((-)-cannabichromene [CBC], (-)-cannabidivarin [CBDV], and (-)-delta9-tetrahydrocannabivarin [THCV], in particular, display notable potential as anti-acne ingredients. The investigators added that these compounds, due to their substantial anti-inflammatory effects, warrant consideration for use in treating skin inflammation.5 Previously, Ali and Akhtar conducted a single-blinded, 12-week comparative study in healthy male volunteers to evaluate the effects of twice-daily application of 3% cannabis seed extract cream on human cheek skin. The researchers found the base with 3% cannabis seed extract to be safe and effective, with skin sebum and erythema content on the treated side reduced significantly compared with the side treated only with the control base. They concluded that this well-tolerated formulation could be indicated for the treatment of acne and seborrhea to enhance facial appearance.6
Psoriasis
The endocannabinoid system itself is thought to play a potentially important role in the treatment of psoriasis, as interactions between the immune and nervous systems via cholinergic anti-inflammatory pathways are considered to be key in psoriasis etiology and the endocannabinoid system interacts with both systems through the cannabinoid (CB) receptors CB1 and CB2.7 Compared with normal human skin, psoriatic skin is characterized by fewer CB receptors.8
In 2007, Wilkinson and Williamson used a keratinocyte proliferation assay to study the phytocannabinoids delta9-tetrahydrocannabinol (THC), CBD, CBG, and cannabinol (CNB) to assess their capacity to halt the growth of a hyper-proliferating human keratinocyte cell line with an eye toward potential use in treating psoriasis. CB1 and CB2 receptors were confirmed present by Western blot and RT-PCR analyses. All cannabinoids investigated concentration-dependently hindered keratinocyte proliferation, as the authors concluded that these compounds show potential for use in psoriasis treatment.9
In 2013, Ramot et al. found that treating human skin culture with the CB1-specific agonist arachidonoyl-chloro-ethanolamide reduced the expression of keratins K6 and K16 in vitro and in situ, which may have implications for psoriasis treatment as K6 and K16 are upregulated in that disorder.10 The same team has also recently shown that the CB1 agonist arachidonyl-2’-chloroethylamide upregulated K10 protein expression in human epidermis and reduced K1 in human skin culture thus suggesting its potential as a treatment for epidermolytic ichthyosis.11
Notably, the synthetic cannabinoid JWH-133, known for its potent antiangiogenic and anti-inflammatory properties, has been shown in vivo and in vitro to suppress various inflammatory cytokines and angiogenic growth factors involved in psoriasis pathogenesis, including hypoxia inducible factor-1 alpha (HIF-1 alpha), vascular endothelial growth factor (VEGF), matrix metalloproteinases, basic fibroblast growth factor (bFGF), angiopoietin-2, interleukin-8 (IL-8), IL-17, and IL-2. While more research is necessary to determine the safety and efficacy of this product, it appears promising as an anti-psoriatic agent.12
Pruritus
Stimulation of the CB1 receptor has been demonstrated to inhibit histamine-induced pruritus.8
In 2005, Szepietowski et al. conducted a preliminary study to ascertain the efficacy and tolerance of a cream with structured physiological lipids and endogenous cannabinoids in managing pruritus in 21 patients on maintenance dialysis. For 3 weeks, the patients with uremic pruritus applied the test cream twice daily, with eight patients experiencing full eradication of pruritus at the end of this period. Further, xerosis was completely eliminated in 17 patients after the study, and significantly decreased during the 3-week period. The investigators suggested that while more research was needed, the well-tolerated product is thought to have been enhanced by the addition of endocannabinoids.13
A year later, Ständer et al. assessed the effects of the use of the topical cannabinoid agonist N-palmitoyl ethanolamine (PEA), which stimulates the endocannabinoid arachidonoyl ethanolamide (AEA) to activate CB1, in an open application study with 22 patients with prurigo, lichen simplex, and pruritus. Antipruritic benefits were seen in 14 patients, with an average decrease in itch of 86.4%. The treatment was reported to be well tolerated, as no patients complained of adverse effects such as contact dermatitis or a burning sensation.14
Eczematic dermatoses
Atopic dermatitis
In a small pilot study on pediatric atopic dermatitis in 2007, Pulvirenti et al. evaluated the safety and efficacy of the twice-daily application of a topical emulsion containing a synthetic aliamide (adelmidrol 2%), comparable to its parent substance PEA, in the treatment of 11 males and 9 females with atopic dermatitis (AD), whose mean age was 8 years. Among the 20 pediatric patients, 16 experienced complete resolution of symptoms after 4 weeks of treatment and had no relapses at the 8-week follow-up assessment. No improvement was noted in the six patches of AD in six patients with several untreated lesions that served as controls.15 Also in 2007, Del Rosso reported on a trial in which a PEA-containing nonsteroidal cream significantly lowered the mean time between flares in pediatric and adult AD patients.16
One year later, Eberlein et al. evaluated an emollient containing PEA in AD patients, finding that itch severity and sleep loss were improved by an average of 60%, with 38% of participants stopping oral antihistamines, 33.6% discontinuing topical steroid regimens, and 20% ending their use of topical immunomodulators as the study concluded.4,17
In 2018, Río et al. suggested that targeted manipulation of the endocannabinoid system at various AD stages might rein in the inflammatory and immune responses and ensuing alterations in keratinocytes, thus helping to preserve epidermal barrier function.18 As Trusler et al. noted, though, no control groups were used in the latter two studies, so it is unknown what effect the application of the vehicle alone would have had on the pruritus in these patients.19
Allergic contact dermatitis
In 2007, Karsak et al. demonstrated that mice lacking CB1/2 receptors exhibited aggravated contact hypersensitivity, whereas mice with higher levels of AEA evinced lower cutaneous allergic responses.20
Recently, Petrosino et al. provided the first evidence that the nonpsychotropic cannabinoid cannabidiol conferred anti-inflammatory activity in an experimental in vitro model of allergic contact dermatitis.21
Dermatomyositis
Robinson et al. have found that treating blood samples of patients with dermatomyositis with the nonpsychoactive cannabinoid ajulemic acid appears to limit the production of pathogenic cytokines. They suggest that oral administration of this cannabinoid merits consideration for dermatomyositis.22
Skin cancer
In 2015, Glodde et al. used a mouse model to investigate the role of cannabinoids in skin cancer pathogenesis. They considered THC, which binds to CB1 and CB2, and the endogenous cannabinoid system. The researchers found that in a CB receptor-dependent fashion THC significantly hindered the tumor growth of HCmel12 melanomas in vivo, verifying the merit of exogenous cannabinoids in melanoma treatment. They did not identify a role of the endogenous cannabinoid system in skin cancer pathogenesis.23
Additional studies suggest that endocannabinoids, phytocannabinoids, and synthetic cannabinoids diminish skin cancer growth (melanoma and nonmelanoma) in vitro and in vivo through CB receptor-dependent and -independent pathways, though in vivo human studies have not yet been conducted.8,24
Epidermolysis bullosa
In a promising observational study in 2018, Chelliah et al. reported on three cases of self-initiated topical cannabidiol use in patients with epidermolysis bullosa. Each patient experienced more rapid wound healing, less blistering, and reduced pain as a result of cannabidiol treatment, and one was able to discontinue oral opioids. The authors were encouraged by such findings, but cautioned that randomized, double-blind clinical trials are needed to establish cannabidiol as an effective therapy.25
This seems particularly important given the climate of expanding legalization of medical and recreational cannabis use, as well as the increasing use of topical cannabinoids among dermatology patients.26 Nevertheless, it is important to be cognizant of one’s own state laws as topical cannabinoids may be restricted; these products are marketed for pain and pruritus on the Internet but are unavailable by prescription unless the physician has a special license.4
Attitudes about cannabinoid use in dermatology
In an intriguing study last year about the knowledge, cognizance, and perceptions of cannabinoids among dermatologists, Robinson et al. created a 20-question online survey that netted a response rate of 21% (n = 531). In terms of awareness, 29% of respondents did not know that THC is psychoactive and a significant majority (64%) did not know that CBD is not psychoactive. Nevertheless, the majority thought that cannabinoids should be legal for medical treatment (86%), and even more (94%) support researching dermatologic applications of cannabinoids. More responders (86%) would prescribe a Food and Drug Administration–approved cannabinoid-containing topical formulation than an oral product (71%). In also noting that 55% revealed at least one conversation about cannabinoids initiated by a patient in the previous year, while 48% expressed concern about a possible stigma associated with suggesting cannabinoid treatments to patients, Robinson et al. call for further education about the benefits and risks of cutaneous cannabinoids for dermatologists.27
Conclusion
It is important that we educate ourselves as to the effects of orally administered and topical products containing cannabis so that we are prepared for questions from patients. Data on psoriasis, pruritus, eczema, and acne warrant optimism and much additional research. Now that the FDA is allowing research sites to enroll for a special license to investigate schedule I drugs, we stand to learn much more about the various effects on the health benefits of cannabis. Despite the longstanding traditional use of C. sativa and C. indica, we are in the early stages of research on the impact of phytocannabinoids and synthetic cannabinoids on human health and the role that the endocannabinoid system plays. The extant findings provide reasons to consider the endocannabinoid system as a target for therapeutic intervention for various cutaneous disorders as research continues.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and “Cosmeceuticals and Cosmetic Ingredients” (New York: McGraw-Hill, 2014), and a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems LLC. She has no relevant disclosures related to this column. Write to her at [email protected].
References
1. Russo EB. Chem Biodivers. 2007 Aug;4(8):1614-48.
2. Goldenberg M et al. Drug Alcohol Depend. 2017 May 1;174:80-90.
3. Mounessa JS et al. J Am Acad Dermatol. 2017 Jul;77(1):188-90.
4. Shalaby M et al. Pract Dermatol. 2018;68-70.
5. Oláh A et al. Exp Dermatol. 2016 Sep;25(9):701-7.
6. Ali A et al. Pak J Pharm Sci. 2015 Jul;28(4):1389-95.
7. Derakhshan N et al. Curr Clin Pharmacol. 2016;11(2):146-7.
8. Singh D et al. Clin Dermatol. 2018 May-Jun;36(3):399-419.
9. Wilkinson JD et al. J Dermatol Sci. 2007 Feb;45(2):87-92.
10. Ramot Y et al. PeerJ. 2013 Feb 19;1:e40.
11. Ramot Y et al. Br J Dermatol. 2018 Jun;178(6):1469.
12. Norooznezhad AH et al. Med Hypotheses. 2017 Feb;99:15-18.
13. Szepietowski JC et al. Acta Dermatovenerol Croat. 2005;13(2):97-103.
14. Ständer S et al. Hautarzt. 2006 Sep;57(9):801-7.
15. Pulvirenti N et al. Acta Dermatovenerol Croat. 2007;15(2):80-3.
16. Del Rosso JQ. Cosmetic Dermatol. 2007 Apr; 20(4):208-211.
17. Eberlein B et al. J Eur Acad Dermatol Venereol. 2008 Jan;22(1):73-82.
18. Del Río CD et al. Biochem Pharmacol. 2018 Nov;157:122-133.
19. Trusler AR et al. Dermatitis. 2017 Jan/Feb;28(1):22-32.
20. Karsak M et al. Science. 2007 Jun 8;316(5830):1494-7.
21. Petrosino S et al. J Pharmacol Exp Ther. 2018 Jun;365(3):652-63.
22. Robinson ES et al. J Invest Dermatol. 2017 Nov;137(11):2445-7.
23. Glodde N et al. Life Sci. 2015 Oct 1;138:35-40.
24. Soliman E. et al. J Dermatol Clin Res. 2016;4(2):1069-76.
25. Chelliah MP et al. Pediatr Dermatol. 2018 Jul;35(4):e224-e227.
26. Hashim PW et al. Cutis. 2017 Jul;100(1):50-52.
27. Robinson E et al. J Drugs Dermatol. 2018 Dec 1;17(12):1273-8.
Infographic: Hyperhidrosis Survey Results
Hyperhidrosis: Survey of the Cutis Editorial Board
To improve patient care and outcomes, leading dermatologists from the Cutis Editorial Board answered 5 questions on hyperhidrosis. Here’s what we found.
In which areas do patients report hyperhidrosis most frequently?
Nearly 70% of dermatologists see patients with hyperhidrosis of the axillae, followed by the palms and soles (27%). Only 4% of dermatologists indicated that they see hyperhidrosis all over the body.
Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)
Hyperhidrosis affects up to 5% of the US population and may remarkably affect quality of life. Primary hyperhidrosis accounts for 93% of cases. Before puberty, hyperhidrosis affects the palms and soles in up to 90% of patients. In adults, the axillae are most commonly affected (51%), followed by plantar (30%), palmar (24%), and facial (10%) areas (Strutton et al).
Next page: Topical treatment
Approximately what percentage of patients are satisfied with topical treatments for hyperhidrosis?
The majority of dermatologists (88%) reported that less than half of their patients are satisfied with topical treatments for hyperhidrosis. Only 12% indicated that 51% to 70% of their patients were satisfied, and none of the respondents indicated that >70% were satisfied.
Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)
There is clearly a need for safe and effective treatments for hyperhidrosis. Treatment of hyperhidrosis should include lifestyle and behavioral modifications. It is helpful to try to avoid hot crowded rooms when feasible, as well as stress, tight clothing, occlusive shoes, alcohol, and spicy foods. Patients should be instructed on proper use of medications, as well as the need to continue therapy for maintenance. Patients should be encouraged to follow up for alternative treatment options in cases of therapy failure.
Next page: Botulinum toxin
On average, how long do the effects of botulinum toxin last in your axillary hyperhidrosis patients?
The effects of botulinum toxin last at least 4 months and up to 6 months in most patients, according to 58% of dermatologists surveyed. Thirty percent reported 2 to 4 months, and 13% reported more than 6 months.
Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)
OnabotulinumtoxinA is approved by the US Food and Drug Administration for severe primary axillary hyperhidrosis. Injections are ideally placed at the dermal-subcutaneous junction, with 1 unit placed every 1 to 2 cm. Dosing is 50 to 100 U per axilla with higher dosing required for the palms and soles (off label). Reported efficacy for axillary hyperhidrosis is 82% to 87%; however, 50% of patients with plantar hyperhidrosis are dissatisfied with the treatment. Sweat reduction is most apparent after 2 weeks and typically persists 6 to 8 months in clinical trials (Botox package insert).
Next page: Systemic anticholinergics
When prescribing systemic anticholinergics for hyperhidrosis, what side effect is most common among your patients?
More than three-quarters of dermatologists (81%) reported that dry mouth is the most common side effect of systemic anticholinergics. Dry eyes is the second most common side effect (15%).
Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)
Systemic anticholinergics are commonly used off label for the treatment of hyperhidrosis. Adverse effects include dry mouth, blurred vision, dry eyes, orthostatic hypotension, gastrointestinal, urinary retention, tachycardia, and drowsiness. Unfortunately, these side effects cause one-third of patients to discontinue treatment (Bajaj and Langtry). A slow escalation of the dose may increase tolerability and reduce these side effects. These anticholinergics should not be taken with other medications with anticholinergic activity to avoid exacerbating these side effects.
Next page: Surgical treatment
What percentage of patients require surgery for treatment of hyperhidrosis after topical, injectable, systemic options and devices have failed?
According to 62% of dermatologists, 10% or less of patients require surgery for treatment of hyperhidrosis after other therapies have failed. Almost one-third indicated that none of their patients require surgical treatment. None of the dermatologists surveyed reported that more than 60% of patients need surgery.
Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)
Surgery is an option to treat hyperhidrosis when conservative methods have failed. Surgical therapies include curettage, liposuction, and excision. A last resort is considered sympathectomy. Endoscopic thoracic sympathectomy is employed for palmar, facial, and axillary hyperhidrosis, while endoscopic lumbar sympathectomy is indicated for plantar hyperhidrosis.
Next page: More tips from derms
More Tips From Dermatologists
The dermatologists we polled had the following advice for their peers:
Patients with focal idiopathic hyperhidrosis of the axillae as well as palms/soles report that this condition interferes with the quality of life in major ways, from social interactions to professional interactions. They often don't even know they have a problem and internalize that they must be overly anxious about things. I have patients that buy 3 of the same shirts and change a few times a day, costing a great deal of money (plus cleaning bills for 3 shirts as well) and costing a great deal of wasted time when they could be doing something more productive. It's great that not only botulinum toxins can be helpful for the underarms but also even less-invasive topical anticholinergics (easy to use, no discomfort, predictable, and helping make treatment for axillary hyperhidrosis much more on the radar).—Joel L. Cohen, MD (Denver, Colorado)
More and more patients are presenting to request relief from hyperhidrosis, and increasingly in nontraditional areas (ie, areas other than the axilla and forehead). These include the palms and scalp most commonly, and then the breast, chest, and back. Patients with hyperhidrosis of the feet often present requesting help for their malodorous or smelly feet and shoes.—Fran E. Cook-Bolden, MD (New York, New York)
I have found that systemic hyperhidrosis has usually been responsive to oral glycopyrrolate. But localized hyperhidrosis is more difficult to treat. Glycopyrronium has made life so much easier for my axillary hyperhidrosis patients. Now I am waiting for some game changer for palms and soles.—Lawrence J. Green, MD (Washington, DC)
About This Survey
The survey was fielded electronically to Cutis Editorial Board Members within the United States from March 11, 2019, to April 8, 2019. A total of 26 usable responses were received.
Bajaj V, Langtry JA. Use of oral glycopyrronium bromide in hyperhidrosis. Br J Dermatol. 2007;157:118-121.
Botox [package insert]. Madison, NJ: Allergan, Inc; 2018.
Strutton DR, Kowalski JW, Glaser DA, et al. US prevalence of hyperhidrosis and impact on individuals with axillary hyperhidrosis: Results from a national survey. J Am Acad Dermatol. 2004;51:241-248.
To improve patient care and outcomes, leading dermatologists from the Cutis Editorial Board answered 5 questions on hyperhidrosis. Here’s what we found.
In which areas do patients report hyperhidrosis most frequently?
Nearly 70% of dermatologists see patients with hyperhidrosis of the axillae, followed by the palms and soles (27%). Only 4% of dermatologists indicated that they see hyperhidrosis all over the body.
Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)
Hyperhidrosis affects up to 5% of the US population and may remarkably affect quality of life. Primary hyperhidrosis accounts for 93% of cases. Before puberty, hyperhidrosis affects the palms and soles in up to 90% of patients. In adults, the axillae are most commonly affected (51%), followed by plantar (30%), palmar (24%), and facial (10%) areas (Strutton et al).
Next page: Topical treatment
Approximately what percentage of patients are satisfied with topical treatments for hyperhidrosis?
The majority of dermatologists (88%) reported that less than half of their patients are satisfied with topical treatments for hyperhidrosis. Only 12% indicated that 51% to 70% of their patients were satisfied, and none of the respondents indicated that >70% were satisfied.
Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)
There is clearly a need for safe and effective treatments for hyperhidrosis. Treatment of hyperhidrosis should include lifestyle and behavioral modifications. It is helpful to try to avoid hot crowded rooms when feasible, as well as stress, tight clothing, occlusive shoes, alcohol, and spicy foods. Patients should be instructed on proper use of medications, as well as the need to continue therapy for maintenance. Patients should be encouraged to follow up for alternative treatment options in cases of therapy failure.
Next page: Botulinum toxin
On average, how long do the effects of botulinum toxin last in your axillary hyperhidrosis patients?
The effects of botulinum toxin last at least 4 months and up to 6 months in most patients, according to 58% of dermatologists surveyed. Thirty percent reported 2 to 4 months, and 13% reported more than 6 months.
Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)
OnabotulinumtoxinA is approved by the US Food and Drug Administration for severe primary axillary hyperhidrosis. Injections are ideally placed at the dermal-subcutaneous junction, with 1 unit placed every 1 to 2 cm. Dosing is 50 to 100 U per axilla with higher dosing required for the palms and soles (off label). Reported efficacy for axillary hyperhidrosis is 82% to 87%; however, 50% of patients with plantar hyperhidrosis are dissatisfied with the treatment. Sweat reduction is most apparent after 2 weeks and typically persists 6 to 8 months in clinical trials (Botox package insert).
Next page: Systemic anticholinergics
When prescribing systemic anticholinergics for hyperhidrosis, what side effect is most common among your patients?
More than three-quarters of dermatologists (81%) reported that dry mouth is the most common side effect of systemic anticholinergics. Dry eyes is the second most common side effect (15%).
Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)
Systemic anticholinergics are commonly used off label for the treatment of hyperhidrosis. Adverse effects include dry mouth, blurred vision, dry eyes, orthostatic hypotension, gastrointestinal, urinary retention, tachycardia, and drowsiness. Unfortunately, these side effects cause one-third of patients to discontinue treatment (Bajaj and Langtry). A slow escalation of the dose may increase tolerability and reduce these side effects. These anticholinergics should not be taken with other medications with anticholinergic activity to avoid exacerbating these side effects.
Next page: Surgical treatment
What percentage of patients require surgery for treatment of hyperhidrosis after topical, injectable, systemic options and devices have failed?
According to 62% of dermatologists, 10% or less of patients require surgery for treatment of hyperhidrosis after other therapies have failed. Almost one-third indicated that none of their patients require surgical treatment. None of the dermatologists surveyed reported that more than 60% of patients need surgery.
Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)
Surgery is an option to treat hyperhidrosis when conservative methods have failed. Surgical therapies include curettage, liposuction, and excision. A last resort is considered sympathectomy. Endoscopic thoracic sympathectomy is employed for palmar, facial, and axillary hyperhidrosis, while endoscopic lumbar sympathectomy is indicated for plantar hyperhidrosis.
Next page: More tips from derms
More Tips From Dermatologists
The dermatologists we polled had the following advice for their peers:
Patients with focal idiopathic hyperhidrosis of the axillae as well as palms/soles report that this condition interferes with the quality of life in major ways, from social interactions to professional interactions. They often don't even know they have a problem and internalize that they must be overly anxious about things. I have patients that buy 3 of the same shirts and change a few times a day, costing a great deal of money (plus cleaning bills for 3 shirts as well) and costing a great deal of wasted time when they could be doing something more productive. It's great that not only botulinum toxins can be helpful for the underarms but also even less-invasive topical anticholinergics (easy to use, no discomfort, predictable, and helping make treatment for axillary hyperhidrosis much more on the radar).—Joel L. Cohen, MD (Denver, Colorado)
More and more patients are presenting to request relief from hyperhidrosis, and increasingly in nontraditional areas (ie, areas other than the axilla and forehead). These include the palms and scalp most commonly, and then the breast, chest, and back. Patients with hyperhidrosis of the feet often present requesting help for their malodorous or smelly feet and shoes.—Fran E. Cook-Bolden, MD (New York, New York)
I have found that systemic hyperhidrosis has usually been responsive to oral glycopyrrolate. But localized hyperhidrosis is more difficult to treat. Glycopyrronium has made life so much easier for my axillary hyperhidrosis patients. Now I am waiting for some game changer for palms and soles.—Lawrence J. Green, MD (Washington, DC)
About This Survey
The survey was fielded electronically to Cutis Editorial Board Members within the United States from March 11, 2019, to April 8, 2019. A total of 26 usable responses were received.
To improve patient care and outcomes, leading dermatologists from the Cutis Editorial Board answered 5 questions on hyperhidrosis. Here’s what we found.
In which areas do patients report hyperhidrosis most frequently?
Nearly 70% of dermatologists see patients with hyperhidrosis of the axillae, followed by the palms and soles (27%). Only 4% of dermatologists indicated that they see hyperhidrosis all over the body.
Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)
Hyperhidrosis affects up to 5% of the US population and may remarkably affect quality of life. Primary hyperhidrosis accounts for 93% of cases. Before puberty, hyperhidrosis affects the palms and soles in up to 90% of patients. In adults, the axillae are most commonly affected (51%), followed by plantar (30%), palmar (24%), and facial (10%) areas (Strutton et al).
Next page: Topical treatment
Approximately what percentage of patients are satisfied with topical treatments for hyperhidrosis?
The majority of dermatologists (88%) reported that less than half of their patients are satisfied with topical treatments for hyperhidrosis. Only 12% indicated that 51% to 70% of their patients were satisfied, and none of the respondents indicated that >70% were satisfied.
Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)
There is clearly a need for safe and effective treatments for hyperhidrosis. Treatment of hyperhidrosis should include lifestyle and behavioral modifications. It is helpful to try to avoid hot crowded rooms when feasible, as well as stress, tight clothing, occlusive shoes, alcohol, and spicy foods. Patients should be instructed on proper use of medications, as well as the need to continue therapy for maintenance. Patients should be encouraged to follow up for alternative treatment options in cases of therapy failure.
Next page: Botulinum toxin
On average, how long do the effects of botulinum toxin last in your axillary hyperhidrosis patients?
The effects of botulinum toxin last at least 4 months and up to 6 months in most patients, according to 58% of dermatologists surveyed. Thirty percent reported 2 to 4 months, and 13% reported more than 6 months.
Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)
OnabotulinumtoxinA is approved by the US Food and Drug Administration for severe primary axillary hyperhidrosis. Injections are ideally placed at the dermal-subcutaneous junction, with 1 unit placed every 1 to 2 cm. Dosing is 50 to 100 U per axilla with higher dosing required for the palms and soles (off label). Reported efficacy for axillary hyperhidrosis is 82% to 87%; however, 50% of patients with plantar hyperhidrosis are dissatisfied with the treatment. Sweat reduction is most apparent after 2 weeks and typically persists 6 to 8 months in clinical trials (Botox package insert).
Next page: Systemic anticholinergics
When prescribing systemic anticholinergics for hyperhidrosis, what side effect is most common among your patients?
More than three-quarters of dermatologists (81%) reported that dry mouth is the most common side effect of systemic anticholinergics. Dry eyes is the second most common side effect (15%).
Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)
Systemic anticholinergics are commonly used off label for the treatment of hyperhidrosis. Adverse effects include dry mouth, blurred vision, dry eyes, orthostatic hypotension, gastrointestinal, urinary retention, tachycardia, and drowsiness. Unfortunately, these side effects cause one-third of patients to discontinue treatment (Bajaj and Langtry). A slow escalation of the dose may increase tolerability and reduce these side effects. These anticholinergics should not be taken with other medications with anticholinergic activity to avoid exacerbating these side effects.
Next page: Surgical treatment
What percentage of patients require surgery for treatment of hyperhidrosis after topical, injectable, systemic options and devices have failed?
According to 62% of dermatologists, 10% or less of patients require surgery for treatment of hyperhidrosis after other therapies have failed. Almost one-third indicated that none of their patients require surgical treatment. None of the dermatologists surveyed reported that more than 60% of patients need surgery.
Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)
Surgery is an option to treat hyperhidrosis when conservative methods have failed. Surgical therapies include curettage, liposuction, and excision. A last resort is considered sympathectomy. Endoscopic thoracic sympathectomy is employed for palmar, facial, and axillary hyperhidrosis, while endoscopic lumbar sympathectomy is indicated for plantar hyperhidrosis.
Next page: More tips from derms
More Tips From Dermatologists
The dermatologists we polled had the following advice for their peers:
Patients with focal idiopathic hyperhidrosis of the axillae as well as palms/soles report that this condition interferes with the quality of life in major ways, from social interactions to professional interactions. They often don't even know they have a problem and internalize that they must be overly anxious about things. I have patients that buy 3 of the same shirts and change a few times a day, costing a great deal of money (plus cleaning bills for 3 shirts as well) and costing a great deal of wasted time when they could be doing something more productive. It's great that not only botulinum toxins can be helpful for the underarms but also even less-invasive topical anticholinergics (easy to use, no discomfort, predictable, and helping make treatment for axillary hyperhidrosis much more on the radar).—Joel L. Cohen, MD (Denver, Colorado)
More and more patients are presenting to request relief from hyperhidrosis, and increasingly in nontraditional areas (ie, areas other than the axilla and forehead). These include the palms and scalp most commonly, and then the breast, chest, and back. Patients with hyperhidrosis of the feet often present requesting help for their malodorous or smelly feet and shoes.—Fran E. Cook-Bolden, MD (New York, New York)
I have found that systemic hyperhidrosis has usually been responsive to oral glycopyrrolate. But localized hyperhidrosis is more difficult to treat. Glycopyrronium has made life so much easier for my axillary hyperhidrosis patients. Now I am waiting for some game changer for palms and soles.—Lawrence J. Green, MD (Washington, DC)
About This Survey
The survey was fielded electronically to Cutis Editorial Board Members within the United States from March 11, 2019, to April 8, 2019. A total of 26 usable responses were received.
Bajaj V, Langtry JA. Use of oral glycopyrronium bromide in hyperhidrosis. Br J Dermatol. 2007;157:118-121.
Botox [package insert]. Madison, NJ: Allergan, Inc; 2018.
Strutton DR, Kowalski JW, Glaser DA, et al. US prevalence of hyperhidrosis and impact on individuals with axillary hyperhidrosis: Results from a national survey. J Am Acad Dermatol. 2004;51:241-248.
Bajaj V, Langtry JA. Use of oral glycopyrronium bromide in hyperhidrosis. Br J Dermatol. 2007;157:118-121.
Botox [package insert]. Madison, NJ: Allergan, Inc; 2018.
Strutton DR, Kowalski JW, Glaser DA, et al. US prevalence of hyperhidrosis and impact on individuals with axillary hyperhidrosis: Results from a national survey. J Am Acad Dermatol. 2004;51:241-248.
Tips for preventing complications in resurfacing skin of color
DENVER – In the opinion of
“You have to have the right patients and the right indication,” Dr. Brauer said at the annual conference of the American Society for Laser Medicine and Surgery. “What are they coming in for? Are they asking for what they really need?”
Taking a thorough medical history during consultations and follow-up visits is also key. “What medical or surgical problems do they have?” he asked. “Do they have a history of keloid formation? Are they on isotretinoin? What allergies do they have? What are their expectations, and are they realistic? For example, do they believe that you are going to erase all of their acne scars? On physical exam, be sure that what you’re looking at is what they’re concerned about, so that you agree upon what can and can’t be effectively treated.”
Above all else, stay true to your gut. “If you perceive that someone is not a suitable candidate for resurfacing or has unrealistic expectations, and they are insistent, it is important to stand your ground, and even find a way to politely walk away,” said Dr. Brauer of the department of dermatology at New York University.
Most complications from laser resurfacing are not unique to skin of color, he continued. A review of the topic revealed that mild complications may include prolonged erythema, acne and milia, delayed purpura, superficial erosions, contact dermatitis, and recall phenomenon (Dermatol Surg. 2010;36[3]:299-306). Moderate complications may include infection, pigmentary alteration, anesthesia toxicity, and eruptive keratoacanthomas, while severe complications may include hypertrophic scarring, ectropion formation, and disseminated infection.
An earlier analysis of fractional laser treatment found that patients with darker skin types had a significantly higher proportion of certain side effects, namely postinflammatory hyperpigmentation (Dermatol Surg. 2008;34[3]:301-7). “Additionally, the researchers found that this presented both later and lasted longer than in individuals with lighter skin types,” said Dr. Brauer, who was not involved with the study.
He listed pigmentary alterations and hypertrophic scarring/keloid formation as the potential complications from resurfacing to be most concerned about in skin of color patients. “In addition to appropriate device selection, the correct device parameters are key,” he said. “You have to make sure you use appropriate energy, but you can use higher energies with lower densities to minimize the risk of postinflammatory pigmentation. You also want to protect the epidermis by use of epidermal cooling, avoid bulk heating, and perform sessions at prolonged treatment intervals, to safely achieve optimal results.”
Dr. Brauer reported having received honoraria or being a member of the medical advisory board for Cutera, Cynosure/Hologic, and Merz.
DENVER – In the opinion of
“You have to have the right patients and the right indication,” Dr. Brauer said at the annual conference of the American Society for Laser Medicine and Surgery. “What are they coming in for? Are they asking for what they really need?”
Taking a thorough medical history during consultations and follow-up visits is also key. “What medical or surgical problems do they have?” he asked. “Do they have a history of keloid formation? Are they on isotretinoin? What allergies do they have? What are their expectations, and are they realistic? For example, do they believe that you are going to erase all of their acne scars? On physical exam, be sure that what you’re looking at is what they’re concerned about, so that you agree upon what can and can’t be effectively treated.”
Above all else, stay true to your gut. “If you perceive that someone is not a suitable candidate for resurfacing or has unrealistic expectations, and they are insistent, it is important to stand your ground, and even find a way to politely walk away,” said Dr. Brauer of the department of dermatology at New York University.
Most complications from laser resurfacing are not unique to skin of color, he continued. A review of the topic revealed that mild complications may include prolonged erythema, acne and milia, delayed purpura, superficial erosions, contact dermatitis, and recall phenomenon (Dermatol Surg. 2010;36[3]:299-306). Moderate complications may include infection, pigmentary alteration, anesthesia toxicity, and eruptive keratoacanthomas, while severe complications may include hypertrophic scarring, ectropion formation, and disseminated infection.
An earlier analysis of fractional laser treatment found that patients with darker skin types had a significantly higher proportion of certain side effects, namely postinflammatory hyperpigmentation (Dermatol Surg. 2008;34[3]:301-7). “Additionally, the researchers found that this presented both later and lasted longer than in individuals with lighter skin types,” said Dr. Brauer, who was not involved with the study.
He listed pigmentary alterations and hypertrophic scarring/keloid formation as the potential complications from resurfacing to be most concerned about in skin of color patients. “In addition to appropriate device selection, the correct device parameters are key,” he said. “You have to make sure you use appropriate energy, but you can use higher energies with lower densities to minimize the risk of postinflammatory pigmentation. You also want to protect the epidermis by use of epidermal cooling, avoid bulk heating, and perform sessions at prolonged treatment intervals, to safely achieve optimal results.”
Dr. Brauer reported having received honoraria or being a member of the medical advisory board for Cutera, Cynosure/Hologic, and Merz.
DENVER – In the opinion of
“You have to have the right patients and the right indication,” Dr. Brauer said at the annual conference of the American Society for Laser Medicine and Surgery. “What are they coming in for? Are they asking for what they really need?”
Taking a thorough medical history during consultations and follow-up visits is also key. “What medical or surgical problems do they have?” he asked. “Do they have a history of keloid formation? Are they on isotretinoin? What allergies do they have? What are their expectations, and are they realistic? For example, do they believe that you are going to erase all of their acne scars? On physical exam, be sure that what you’re looking at is what they’re concerned about, so that you agree upon what can and can’t be effectively treated.”
Above all else, stay true to your gut. “If you perceive that someone is not a suitable candidate for resurfacing or has unrealistic expectations, and they are insistent, it is important to stand your ground, and even find a way to politely walk away,” said Dr. Brauer of the department of dermatology at New York University.
Most complications from laser resurfacing are not unique to skin of color, he continued. A review of the topic revealed that mild complications may include prolonged erythema, acne and milia, delayed purpura, superficial erosions, contact dermatitis, and recall phenomenon (Dermatol Surg. 2010;36[3]:299-306). Moderate complications may include infection, pigmentary alteration, anesthesia toxicity, and eruptive keratoacanthomas, while severe complications may include hypertrophic scarring, ectropion formation, and disseminated infection.
An earlier analysis of fractional laser treatment found that patients with darker skin types had a significantly higher proportion of certain side effects, namely postinflammatory hyperpigmentation (Dermatol Surg. 2008;34[3]:301-7). “Additionally, the researchers found that this presented both later and lasted longer than in individuals with lighter skin types,” said Dr. Brauer, who was not involved with the study.
He listed pigmentary alterations and hypertrophic scarring/keloid formation as the potential complications from resurfacing to be most concerned about in skin of color patients. “In addition to appropriate device selection, the correct device parameters are key,” he said. “You have to make sure you use appropriate energy, but you can use higher energies with lower densities to minimize the risk of postinflammatory pigmentation. You also want to protect the epidermis by use of epidermal cooling, avoid bulk heating, and perform sessions at prolonged treatment intervals, to safely achieve optimal results.”
Dr. Brauer reported having received honoraria or being a member of the medical advisory board for Cutera, Cynosure/Hologic, and Merz.
EXPERT ANALYSIS FROM ASLMS 2019
Split-face trial compares outcomes of two different lasers on photoaging
DENVER – The fractionated picosecond Nd:YAG laser and fractionated thulium fiber laser can be equally effective for facial rejuvenation, results from a small split-face trial showed. However, the fractionated picosecond Nd:YAG laser may result in significantly less postoperative downtime, compared with the fractionated thulium fiber laser.
The findings from the prospective, evaluator-blinded trial were presented by Douglas C. Wu, MD, PhD, at the annual conference of the American Society for Laser Medicine and Surgery. Dr. Wu, of San Diego–based Cosmetic Laser Dermatology, and his colleague, Mitchel P. Goldman, MD, enrolled 20 subjects with at least moderate photoaging who randomly received three treatments with either the 1064/532-nm fractionated picosecond Nd:YAG laser or with the 1927-nm fractionated thulium fiber laser on each side of the face, 4 weeks apart. The primary endpoint was the degree of rhytids, laxity, dyschromia, erythema-telangiectasia, keratoses, and texture rated on a four-point scale and performed by a blinded evaluator at baseline, and 12, 20, and 30 weeks from baseline. Secondary endpoints were the global aesthetic improvement score, investigator satisfaction questionnaire, and a subject satisfaction questionnaire administered at weeks 12, 20, and 30. Recovery time and adverse events were assessed through a 14-day subject diary administered after each treatment.
All but 1 of the 20 patients were female and their mean age was 57 years. Six had Fitzpatrick skin type II, seven had type III, six had type IV, and one had type V. The device settings were on medium for both devices. The researchers observed significant improvements in elastosis, erythema, dyschromia, and texture at all treatment follow-up time points (P less than .01 for all endpoints).
There were no differences between the two lasers in terms of efficacy. “Clinically, the efficacy was rated to be the same,” Dr. Wu said. “However, when we analyzed the patient diaries, we found some very interesting results. In terms of redness, at days 3 and 4, there was a consistently increased amount of redness on the side treated with the fractionated thulium fiber laser, with swelling also being significantly increased at day 5.” Similarly, he said, the side treated with the fractionated picosecond laser experienced significantly less crusting on posttreatment days 1 through 9, less peeling on days 3 through 5, and less itching on day 4. Posttreatment pain was minimal on both sides and did not differ significantly.
Dr. Wu disclosed having numerous financial ties to pharmaceutical and device companies.
DENVER – The fractionated picosecond Nd:YAG laser and fractionated thulium fiber laser can be equally effective for facial rejuvenation, results from a small split-face trial showed. However, the fractionated picosecond Nd:YAG laser may result in significantly less postoperative downtime, compared with the fractionated thulium fiber laser.
The findings from the prospective, evaluator-blinded trial were presented by Douglas C. Wu, MD, PhD, at the annual conference of the American Society for Laser Medicine and Surgery. Dr. Wu, of San Diego–based Cosmetic Laser Dermatology, and his colleague, Mitchel P. Goldman, MD, enrolled 20 subjects with at least moderate photoaging who randomly received three treatments with either the 1064/532-nm fractionated picosecond Nd:YAG laser or with the 1927-nm fractionated thulium fiber laser on each side of the face, 4 weeks apart. The primary endpoint was the degree of rhytids, laxity, dyschromia, erythema-telangiectasia, keratoses, and texture rated on a four-point scale and performed by a blinded evaluator at baseline, and 12, 20, and 30 weeks from baseline. Secondary endpoints were the global aesthetic improvement score, investigator satisfaction questionnaire, and a subject satisfaction questionnaire administered at weeks 12, 20, and 30. Recovery time and adverse events were assessed through a 14-day subject diary administered after each treatment.
All but 1 of the 20 patients were female and their mean age was 57 years. Six had Fitzpatrick skin type II, seven had type III, six had type IV, and one had type V. The device settings were on medium for both devices. The researchers observed significant improvements in elastosis, erythema, dyschromia, and texture at all treatment follow-up time points (P less than .01 for all endpoints).
There were no differences between the two lasers in terms of efficacy. “Clinically, the efficacy was rated to be the same,” Dr. Wu said. “However, when we analyzed the patient diaries, we found some very interesting results. In terms of redness, at days 3 and 4, there was a consistently increased amount of redness on the side treated with the fractionated thulium fiber laser, with swelling also being significantly increased at day 5.” Similarly, he said, the side treated with the fractionated picosecond laser experienced significantly less crusting on posttreatment days 1 through 9, less peeling on days 3 through 5, and less itching on day 4. Posttreatment pain was minimal on both sides and did not differ significantly.
Dr. Wu disclosed having numerous financial ties to pharmaceutical and device companies.
DENVER – The fractionated picosecond Nd:YAG laser and fractionated thulium fiber laser can be equally effective for facial rejuvenation, results from a small split-face trial showed. However, the fractionated picosecond Nd:YAG laser may result in significantly less postoperative downtime, compared with the fractionated thulium fiber laser.
The findings from the prospective, evaluator-blinded trial were presented by Douglas C. Wu, MD, PhD, at the annual conference of the American Society for Laser Medicine and Surgery. Dr. Wu, of San Diego–based Cosmetic Laser Dermatology, and his colleague, Mitchel P. Goldman, MD, enrolled 20 subjects with at least moderate photoaging who randomly received three treatments with either the 1064/532-nm fractionated picosecond Nd:YAG laser or with the 1927-nm fractionated thulium fiber laser on each side of the face, 4 weeks apart. The primary endpoint was the degree of rhytids, laxity, dyschromia, erythema-telangiectasia, keratoses, and texture rated on a four-point scale and performed by a blinded evaluator at baseline, and 12, 20, and 30 weeks from baseline. Secondary endpoints were the global aesthetic improvement score, investigator satisfaction questionnaire, and a subject satisfaction questionnaire administered at weeks 12, 20, and 30. Recovery time and adverse events were assessed through a 14-day subject diary administered after each treatment.
All but 1 of the 20 patients were female and their mean age was 57 years. Six had Fitzpatrick skin type II, seven had type III, six had type IV, and one had type V. The device settings were on medium for both devices. The researchers observed significant improvements in elastosis, erythema, dyschromia, and texture at all treatment follow-up time points (P less than .01 for all endpoints).
There were no differences between the two lasers in terms of efficacy. “Clinically, the efficacy was rated to be the same,” Dr. Wu said. “However, when we analyzed the patient diaries, we found some very interesting results. In terms of redness, at days 3 and 4, there was a consistently increased amount of redness on the side treated with the fractionated thulium fiber laser, with swelling also being significantly increased at day 5.” Similarly, he said, the side treated with the fractionated picosecond laser experienced significantly less crusting on posttreatment days 1 through 9, less peeling on days 3 through 5, and less itching on day 4. Posttreatment pain was minimal on both sides and did not differ significantly.
Dr. Wu disclosed having numerous financial ties to pharmaceutical and device companies.
REPORTING FROM ASLMS 2019
A primer on cannabis for cosmeceuticals: The endocannabinoid system
In the United States, 31 states, the District of Columbia, Puerto Rico, and Guam have legalized medical marijuana, which is also permitted for recreational use in 9 states, as well as in the District of Columbia. However, marijuana, derived from Cannabis sativa and Cannabis indica, is regulated as a schedule I drug in the United States at the federal level. (Some believe that the federal status may change in the coming year as a result of the Democratic Party’s takeover in the House of Representatives.1)
Cannabis species contain hundreds of various substances, of which the cannabinoids are the most studied. More than 113 biologically active chemical compounds are found within the class of cannabinoids and their derivatives,2 which have been used for centuries in natural medicine.3 The legal status of marijuana has long hampered scientific research of cannabinoids. Nevertheless, the number of studies focusing on the therapeutic potential of these compounds has steadily risen as the legal landscape of marijuana has evolved.
Findings over the last 20 years have shown that cannabinoids present in C. sativa exhibit anti-inflammatory activity and suppress the proliferation of multiple tumorigenic cell lines, some of which are moderated through cannabinoid (CB) receptors.4 In addition to anti-inflammatory properties, .3 Recent research has demonstrated that CB receptors are present in human skin.4
The endocannabinoid system has emerged as an intriguing area of research, as we’ve come to learn about its convoluted role in human anatomy and health. It features a pervasive network of endogenous ligands, enzymes, and receptors, which exogenous substances (including phytocannabinoids and synthetic cannabinoids) can activate.5 Data from recent studies indicate that the endocannabinoid system plays a significant role in cutaneous homeostasis, as it regulates proliferation, differentiation, and inflammatory mediator release.5 Further, psoriasis, atopic dermatitis, pruritus, and wound healing have been identified in recent research as cutaneous concerns in which the use of cannabinoids may be of benefit.6,7 We must also consider reports that cannabinoids can slow human hair growth and that some constituents may spur the synthesis of pro-inflammatory cytokines.8,9This column will briefly address potential confusion over the psychoactive aspects of cannabis, which are related to particular constituents of cannabis and specific CB receptors, and focus on the endocannabinoid system.
Psychoactive or not?
C. sativa confers biological activity through its influence on the G-protein-coupled receptor types CB1 and CB2,10 which pervade human skin epithelium.11 CB1 receptors are found in greatest supply in the central nervous system, especially the basal ganglia, cerebellum, hippocampus, and prefrontal cortex, where their activation yields psychoactivity.2,5,12,13 Stimulation of CB1 receptors in the skin – where they are present in differentiated keratinocytes, hair follicle cells, immune cells, sebaceous glands, and sensory neurons14 – diminishes pain and pruritus, controls keratinocyte differentiation and proliferation, inhibits hair follicle growth, and regulates the release of damage-induced keratins and inflammatory mediators to maintain cutaneous homeostasis.11,14,15
CB2 receptors are expressed in the immune system, particularly monocytes, macrophages, as well as B and T cells, and in peripheral tissues including the spleen, tonsils, thymus gland, bone, and, notably, the skin.2,16 Stimulation of CB2 receptors in the skin – where they are found in keratinocytes, immune cells, sebaceous glands, and sensory neurons – fosters sebum production, regulates pain sensation, hinders keratinocyte differentiation and proliferation, and suppresses cutaneous inflammatory responses.14,15
The best known, or most notorious, component of exogenous cannabinoids is delta9-tetrahydrocannabinol (delta9-THC or simply THC), which is a natural psychoactive constituent in marijuana.3 In fact, of the five primary cannabinoids derived from marijuana, including cannabidiol (CBD), cannabichromene (CBC), cannabigerol (CBG), cannabinol (CBN), and THC, only THC imparts psychoactive effects.17
CBD is thought to exhibit anti-inflammatory and analgesic activities.18 THC has been found to have the capacity to induce cancer cell apoptosis and block angiogenesis,19 and is thought to have immunomodulatory potential, partly acting through the G-protein-coupled CB1 and CB2 receptors but also yielding effects not related to these receptors.20In a 2014 survey of medical cannabis users, a statistically significant preference for C. indica (which contains higher CBD and lower THC levels) was observed for pain management, sedation, and sleep, while C. sativa was associated with euphoria and improving energy.21
The endocannabinoid system and skin health
The endogenous cannabinoid or endocannabinoid system includes cannabinoid receptors, associated endogenous ligands (such as arachidonoyl ethanolamide [anandamide or AEA], 2-arachidonoyl glycerol [2-AG], and N-palmitoylethanolamide [PEA], a fatty acid amide that enhances AEA activity),2 and enzymes involved in endocannabinoid production and decay.11,15,22,23 Research in recent years appears to support the notion that the endocannabinoid system plays an important role in skin health, as its dysregulation has been linked to atopic dermatitis, psoriasis, scleroderma, and skin cancer. Data indicate that exogenous and endogenous cannabinoids influence the endocannabinoid system through cannabinoid receptors, transient receptor potential channels (TRPs), and peroxisome proliferator–activated receptors (PPARs). Río et al. suggest that the dynamism of the endocannabinoid system buttresses the targeting of multiple endpoints for therapeutic success with cannabinoids rather than the one-disease-one-target approach.24 Endogenous cannabinoids, such as arachidonoyl ethanolamide and 2-arachidonoylglycerol, are now thought to be significant mediators in the skin.3 Further, endocannabinoids have been shown to deliver analgesia to the skin, at the spinal and supraspinal levels.25
Anti-inflammatory activity
In 2010, Tubaro et al. used the Croton oil mouse ear dermatitis assay to study the in vivo topical anti-inflammatory effects of seven phytocannabinoids and their related cannabivarins (nonpsychoactive cannabinoids). They found that anti-inflammatory activity was derived from the involvement of the cannabinoid receptors as well as the inflammatory endpoints that the phytocannabinoids targeted.26
In 2013, Gaffal et al. explored the anti-inflammatory activity of topical THC in dinitrofluorobenzene-mediated allergic contact dermatitis independent of CB1/2 receptors by using wild-type and CB1/2 receptor-deficient mice. The researchers found that topically applied THC reduced contact allergic ear edema and myeloid immune cell infiltration in both groups of mice. They concluded that such a decline in inflammation resulted from mitigating the keratinocyte-derived proinflammatory mediators that direct myeloid immune cell infiltration independent of CB1/2 receptors, and positions cannabinoids well for future use in treating inflammatory cutaneous conditions.20
Literature reviews
In a 2018 literature review on the uses of cannabinoids for cutaneous disorders, Eagleston et al. determined that preclinical data on cannabinoids reveal the potential to treat acne, allergic contact dermatitis, asteatotic dermatitis, atopic dermatitis, hidradenitis suppurativa, Kaposi sarcoma, pruritus, psoriasis, skin cancer, and the skin symptoms of systemic sclerosis. They caution, though, that more preclinical work is necessary along with randomized, controlled trials with sufficiently large sample sizes to establish the safety and efficacy of cannabinoids to treat skin conditions.27
A literature review by Marks and Friedman published later that year on the therapeutic potential of phytocannabinoids, endocannabinoids, and synthetic cannabinoids in managing skin disorders revealed the same findings regarding the cutaneous conditions associated with these compounds. The authors noted, though, that while the preponderance of articles highlight the efficacy of cannabinoids in treating inflammatory and neoplastic cutaneous conditions, some reports indicate proinflammatory and proneoplastic activities of cannabinoids. Like Eagleston et al., they call for additional studies.28
Conclusion
As in many botanical agents that I cover in this column, cannabis is associated with numerous medical benefits. I am encouraged to see expanding legalization of medical marijuana and increased research into its reputedly broad potential to improve human health. Anecdotally, I have heard stunning reports from patients about amelioration of joint and back pain as well as relief from other inflammatory symptoms. Discovery and elucidation of the endogenous cannabinoid system is a recent development. Research on its functions and roles in cutaneous health has followed suit and is steadily increasing. Particular skin conditions for which cannabis and cannabinoids may be indicated will be the focus of the next column.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and “Cosmeceuticals and Cosmetic Ingredients” (New York: McGraw-Hill, 2014), and a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems LLC. Write to her at [email protected]
References
1. Higdon J. Why 2019 could be marijuana’s biggest year yet. Politico Magazine. Jan 21, 2019.
2. Singh D et al. Clin Dermatol. 2018 May-Jun;36(3):399-419.
3. Kupczyk P et al. Exp Dermatol. 2009 Aug;18(8):669-79.
4. Wilkinson JD et al. J Dermatol Sci. 2007 Feb;45(2):87-92.
5. Milando R et al. Am J Clin Dermatol. 2019 April;20(2):167-80.
6. Robinson E et al. J Drugs Dermatol. 2018 Dec 1;17(12):1273-8.
7. Mounessa JS et al. J Am Acad Dermatol. 2017 Jul;77(1):188-90.
8. Liszewski W et al. J Am Acad Dermatol. 2017 Sep;77(3):e87-e88.
9. Telek A et al. FASEB J. 2007 Nov;21(13):3534-41.
10. Wollenberg A et al. Br J Dermatol. 2014 Jul;170 Suppl 1:7-11.
11. Ramot Y et al. PeerJ. 2013 Feb 19;1:e40.
12. Schlicker E et al. Trends Pharmacol Sci. 2001 Nov;22(11):565-72.
13. Christie MJ et al. Nature. 2001 Mar 29;410(6828):527-30.
14. Ibid.
15. Bíró T et al. Trends Pharmacol Sci. 2009 Aug;30(8):411-20.
16. Pacher P et al. Pharmacol Rev. 2006 Sep;58(3):389-462.
17. Shalaby M et al. Pract Dermatol. 2018 Jan;68-70.
18. Chelliah MP et al. Pediatr Dermatol. 2018 Jul;35(4):e224-e227.
19. Glodde N et al. Life Sci. 2015 Oct 1;138:35-40.
20. Gaffal E et al. Allergy. 2013 Aug;68(8):994-1000.
21. Pearce DD et al. J Altern Complement Med. 2014 Oct;20(10):787:91.
22. Leonti M et al. Biochem Pharmacol. 2010 Jun 15;79(12):1815-26.
23. Trusler AR et al. Dermatitis. 2017 Jan/Feb;28(1):22-32.
24. Río CD et al. Biochem Pharmacol. 2018 Nov;157:122-133.
25. Chuquilin M et al. J Am Acad Dermatol. 2016 Feb;74(2):197-212.
26. Tubaro A et al. Fitoterapia. 2010 Oct;81(7):816-9.
27. Eagleston LRM et al. Dermatol Online J. 2018 Jun 15;24(6).
28. Marks DH et al. Skin Therapy Lett. 2018 Nov;23(6):1-5.
In the United States, 31 states, the District of Columbia, Puerto Rico, and Guam have legalized medical marijuana, which is also permitted for recreational use in 9 states, as well as in the District of Columbia. However, marijuana, derived from Cannabis sativa and Cannabis indica, is regulated as a schedule I drug in the United States at the federal level. (Some believe that the federal status may change in the coming year as a result of the Democratic Party’s takeover in the House of Representatives.1)
Cannabis species contain hundreds of various substances, of which the cannabinoids are the most studied. More than 113 biologically active chemical compounds are found within the class of cannabinoids and their derivatives,2 which have been used for centuries in natural medicine.3 The legal status of marijuana has long hampered scientific research of cannabinoids. Nevertheless, the number of studies focusing on the therapeutic potential of these compounds has steadily risen as the legal landscape of marijuana has evolved.
Findings over the last 20 years have shown that cannabinoids present in C. sativa exhibit anti-inflammatory activity and suppress the proliferation of multiple tumorigenic cell lines, some of which are moderated through cannabinoid (CB) receptors.4 In addition to anti-inflammatory properties, .3 Recent research has demonstrated that CB receptors are present in human skin.4
The endocannabinoid system has emerged as an intriguing area of research, as we’ve come to learn about its convoluted role in human anatomy and health. It features a pervasive network of endogenous ligands, enzymes, and receptors, which exogenous substances (including phytocannabinoids and synthetic cannabinoids) can activate.5 Data from recent studies indicate that the endocannabinoid system plays a significant role in cutaneous homeostasis, as it regulates proliferation, differentiation, and inflammatory mediator release.5 Further, psoriasis, atopic dermatitis, pruritus, and wound healing have been identified in recent research as cutaneous concerns in which the use of cannabinoids may be of benefit.6,7 We must also consider reports that cannabinoids can slow human hair growth and that some constituents may spur the synthesis of pro-inflammatory cytokines.8,9This column will briefly address potential confusion over the psychoactive aspects of cannabis, which are related to particular constituents of cannabis and specific CB receptors, and focus on the endocannabinoid system.
Psychoactive or not?
C. sativa confers biological activity through its influence on the G-protein-coupled receptor types CB1 and CB2,10 which pervade human skin epithelium.11 CB1 receptors are found in greatest supply in the central nervous system, especially the basal ganglia, cerebellum, hippocampus, and prefrontal cortex, where their activation yields psychoactivity.2,5,12,13 Stimulation of CB1 receptors in the skin – where they are present in differentiated keratinocytes, hair follicle cells, immune cells, sebaceous glands, and sensory neurons14 – diminishes pain and pruritus, controls keratinocyte differentiation and proliferation, inhibits hair follicle growth, and regulates the release of damage-induced keratins and inflammatory mediators to maintain cutaneous homeostasis.11,14,15
CB2 receptors are expressed in the immune system, particularly monocytes, macrophages, as well as B and T cells, and in peripheral tissues including the spleen, tonsils, thymus gland, bone, and, notably, the skin.2,16 Stimulation of CB2 receptors in the skin – where they are found in keratinocytes, immune cells, sebaceous glands, and sensory neurons – fosters sebum production, regulates pain sensation, hinders keratinocyte differentiation and proliferation, and suppresses cutaneous inflammatory responses.14,15
The best known, or most notorious, component of exogenous cannabinoids is delta9-tetrahydrocannabinol (delta9-THC or simply THC), which is a natural psychoactive constituent in marijuana.3 In fact, of the five primary cannabinoids derived from marijuana, including cannabidiol (CBD), cannabichromene (CBC), cannabigerol (CBG), cannabinol (CBN), and THC, only THC imparts psychoactive effects.17
CBD is thought to exhibit anti-inflammatory and analgesic activities.18 THC has been found to have the capacity to induce cancer cell apoptosis and block angiogenesis,19 and is thought to have immunomodulatory potential, partly acting through the G-protein-coupled CB1 and CB2 receptors but also yielding effects not related to these receptors.20In a 2014 survey of medical cannabis users, a statistically significant preference for C. indica (which contains higher CBD and lower THC levels) was observed for pain management, sedation, and sleep, while C. sativa was associated with euphoria and improving energy.21
The endocannabinoid system and skin health
The endogenous cannabinoid or endocannabinoid system includes cannabinoid receptors, associated endogenous ligands (such as arachidonoyl ethanolamide [anandamide or AEA], 2-arachidonoyl glycerol [2-AG], and N-palmitoylethanolamide [PEA], a fatty acid amide that enhances AEA activity),2 and enzymes involved in endocannabinoid production and decay.11,15,22,23 Research in recent years appears to support the notion that the endocannabinoid system plays an important role in skin health, as its dysregulation has been linked to atopic dermatitis, psoriasis, scleroderma, and skin cancer. Data indicate that exogenous and endogenous cannabinoids influence the endocannabinoid system through cannabinoid receptors, transient receptor potential channels (TRPs), and peroxisome proliferator–activated receptors (PPARs). Río et al. suggest that the dynamism of the endocannabinoid system buttresses the targeting of multiple endpoints for therapeutic success with cannabinoids rather than the one-disease-one-target approach.24 Endogenous cannabinoids, such as arachidonoyl ethanolamide and 2-arachidonoylglycerol, are now thought to be significant mediators in the skin.3 Further, endocannabinoids have been shown to deliver analgesia to the skin, at the spinal and supraspinal levels.25
Anti-inflammatory activity
In 2010, Tubaro et al. used the Croton oil mouse ear dermatitis assay to study the in vivo topical anti-inflammatory effects of seven phytocannabinoids and their related cannabivarins (nonpsychoactive cannabinoids). They found that anti-inflammatory activity was derived from the involvement of the cannabinoid receptors as well as the inflammatory endpoints that the phytocannabinoids targeted.26
In 2013, Gaffal et al. explored the anti-inflammatory activity of topical THC in dinitrofluorobenzene-mediated allergic contact dermatitis independent of CB1/2 receptors by using wild-type and CB1/2 receptor-deficient mice. The researchers found that topically applied THC reduced contact allergic ear edema and myeloid immune cell infiltration in both groups of mice. They concluded that such a decline in inflammation resulted from mitigating the keratinocyte-derived proinflammatory mediators that direct myeloid immune cell infiltration independent of CB1/2 receptors, and positions cannabinoids well for future use in treating inflammatory cutaneous conditions.20
Literature reviews
In a 2018 literature review on the uses of cannabinoids for cutaneous disorders, Eagleston et al. determined that preclinical data on cannabinoids reveal the potential to treat acne, allergic contact dermatitis, asteatotic dermatitis, atopic dermatitis, hidradenitis suppurativa, Kaposi sarcoma, pruritus, psoriasis, skin cancer, and the skin symptoms of systemic sclerosis. They caution, though, that more preclinical work is necessary along with randomized, controlled trials with sufficiently large sample sizes to establish the safety and efficacy of cannabinoids to treat skin conditions.27
A literature review by Marks and Friedman published later that year on the therapeutic potential of phytocannabinoids, endocannabinoids, and synthetic cannabinoids in managing skin disorders revealed the same findings regarding the cutaneous conditions associated with these compounds. The authors noted, though, that while the preponderance of articles highlight the efficacy of cannabinoids in treating inflammatory and neoplastic cutaneous conditions, some reports indicate proinflammatory and proneoplastic activities of cannabinoids. Like Eagleston et al., they call for additional studies.28
Conclusion
As in many botanical agents that I cover in this column, cannabis is associated with numerous medical benefits. I am encouraged to see expanding legalization of medical marijuana and increased research into its reputedly broad potential to improve human health. Anecdotally, I have heard stunning reports from patients about amelioration of joint and back pain as well as relief from other inflammatory symptoms. Discovery and elucidation of the endogenous cannabinoid system is a recent development. Research on its functions and roles in cutaneous health has followed suit and is steadily increasing. Particular skin conditions for which cannabis and cannabinoids may be indicated will be the focus of the next column.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and “Cosmeceuticals and Cosmetic Ingredients” (New York: McGraw-Hill, 2014), and a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems LLC. Write to her at [email protected]
References
1. Higdon J. Why 2019 could be marijuana’s biggest year yet. Politico Magazine. Jan 21, 2019.
2. Singh D et al. Clin Dermatol. 2018 May-Jun;36(3):399-419.
3. Kupczyk P et al. Exp Dermatol. 2009 Aug;18(8):669-79.
4. Wilkinson JD et al. J Dermatol Sci. 2007 Feb;45(2):87-92.
5. Milando R et al. Am J Clin Dermatol. 2019 April;20(2):167-80.
6. Robinson E et al. J Drugs Dermatol. 2018 Dec 1;17(12):1273-8.
7. Mounessa JS et al. J Am Acad Dermatol. 2017 Jul;77(1):188-90.
8. Liszewski W et al. J Am Acad Dermatol. 2017 Sep;77(3):e87-e88.
9. Telek A et al. FASEB J. 2007 Nov;21(13):3534-41.
10. Wollenberg A et al. Br J Dermatol. 2014 Jul;170 Suppl 1:7-11.
11. Ramot Y et al. PeerJ. 2013 Feb 19;1:e40.
12. Schlicker E et al. Trends Pharmacol Sci. 2001 Nov;22(11):565-72.
13. Christie MJ et al. Nature. 2001 Mar 29;410(6828):527-30.
14. Ibid.
15. Bíró T et al. Trends Pharmacol Sci. 2009 Aug;30(8):411-20.
16. Pacher P et al. Pharmacol Rev. 2006 Sep;58(3):389-462.
17. Shalaby M et al. Pract Dermatol. 2018 Jan;68-70.
18. Chelliah MP et al. Pediatr Dermatol. 2018 Jul;35(4):e224-e227.
19. Glodde N et al. Life Sci. 2015 Oct 1;138:35-40.
20. Gaffal E et al. Allergy. 2013 Aug;68(8):994-1000.
21. Pearce DD et al. J Altern Complement Med. 2014 Oct;20(10):787:91.
22. Leonti M et al. Biochem Pharmacol. 2010 Jun 15;79(12):1815-26.
23. Trusler AR et al. Dermatitis. 2017 Jan/Feb;28(1):22-32.
24. Río CD et al. Biochem Pharmacol. 2018 Nov;157:122-133.
25. Chuquilin M et al. J Am Acad Dermatol. 2016 Feb;74(2):197-212.
26. Tubaro A et al. Fitoterapia. 2010 Oct;81(7):816-9.
27. Eagleston LRM et al. Dermatol Online J. 2018 Jun 15;24(6).
28. Marks DH et al. Skin Therapy Lett. 2018 Nov;23(6):1-5.
In the United States, 31 states, the District of Columbia, Puerto Rico, and Guam have legalized medical marijuana, which is also permitted for recreational use in 9 states, as well as in the District of Columbia. However, marijuana, derived from Cannabis sativa and Cannabis indica, is regulated as a schedule I drug in the United States at the federal level. (Some believe that the federal status may change in the coming year as a result of the Democratic Party’s takeover in the House of Representatives.1)
Cannabis species contain hundreds of various substances, of which the cannabinoids are the most studied. More than 113 biologically active chemical compounds are found within the class of cannabinoids and their derivatives,2 which have been used for centuries in natural medicine.3 The legal status of marijuana has long hampered scientific research of cannabinoids. Nevertheless, the number of studies focusing on the therapeutic potential of these compounds has steadily risen as the legal landscape of marijuana has evolved.
Findings over the last 20 years have shown that cannabinoids present in C. sativa exhibit anti-inflammatory activity and suppress the proliferation of multiple tumorigenic cell lines, some of which are moderated through cannabinoid (CB) receptors.4 In addition to anti-inflammatory properties, .3 Recent research has demonstrated that CB receptors are present in human skin.4
The endocannabinoid system has emerged as an intriguing area of research, as we’ve come to learn about its convoluted role in human anatomy and health. It features a pervasive network of endogenous ligands, enzymes, and receptors, which exogenous substances (including phytocannabinoids and synthetic cannabinoids) can activate.5 Data from recent studies indicate that the endocannabinoid system plays a significant role in cutaneous homeostasis, as it regulates proliferation, differentiation, and inflammatory mediator release.5 Further, psoriasis, atopic dermatitis, pruritus, and wound healing have been identified in recent research as cutaneous concerns in which the use of cannabinoids may be of benefit.6,7 We must also consider reports that cannabinoids can slow human hair growth and that some constituents may spur the synthesis of pro-inflammatory cytokines.8,9This column will briefly address potential confusion over the psychoactive aspects of cannabis, which are related to particular constituents of cannabis and specific CB receptors, and focus on the endocannabinoid system.
Psychoactive or not?
C. sativa confers biological activity through its influence on the G-protein-coupled receptor types CB1 and CB2,10 which pervade human skin epithelium.11 CB1 receptors are found in greatest supply in the central nervous system, especially the basal ganglia, cerebellum, hippocampus, and prefrontal cortex, where their activation yields psychoactivity.2,5,12,13 Stimulation of CB1 receptors in the skin – where they are present in differentiated keratinocytes, hair follicle cells, immune cells, sebaceous glands, and sensory neurons14 – diminishes pain and pruritus, controls keratinocyte differentiation and proliferation, inhibits hair follicle growth, and regulates the release of damage-induced keratins and inflammatory mediators to maintain cutaneous homeostasis.11,14,15
CB2 receptors are expressed in the immune system, particularly monocytes, macrophages, as well as B and T cells, and in peripheral tissues including the spleen, tonsils, thymus gland, bone, and, notably, the skin.2,16 Stimulation of CB2 receptors in the skin – where they are found in keratinocytes, immune cells, sebaceous glands, and sensory neurons – fosters sebum production, regulates pain sensation, hinders keratinocyte differentiation and proliferation, and suppresses cutaneous inflammatory responses.14,15
The best known, or most notorious, component of exogenous cannabinoids is delta9-tetrahydrocannabinol (delta9-THC or simply THC), which is a natural psychoactive constituent in marijuana.3 In fact, of the five primary cannabinoids derived from marijuana, including cannabidiol (CBD), cannabichromene (CBC), cannabigerol (CBG), cannabinol (CBN), and THC, only THC imparts psychoactive effects.17
CBD is thought to exhibit anti-inflammatory and analgesic activities.18 THC has been found to have the capacity to induce cancer cell apoptosis and block angiogenesis,19 and is thought to have immunomodulatory potential, partly acting through the G-protein-coupled CB1 and CB2 receptors but also yielding effects not related to these receptors.20In a 2014 survey of medical cannabis users, a statistically significant preference for C. indica (which contains higher CBD and lower THC levels) was observed for pain management, sedation, and sleep, while C. sativa was associated with euphoria and improving energy.21
The endocannabinoid system and skin health
The endogenous cannabinoid or endocannabinoid system includes cannabinoid receptors, associated endogenous ligands (such as arachidonoyl ethanolamide [anandamide or AEA], 2-arachidonoyl glycerol [2-AG], and N-palmitoylethanolamide [PEA], a fatty acid amide that enhances AEA activity),2 and enzymes involved in endocannabinoid production and decay.11,15,22,23 Research in recent years appears to support the notion that the endocannabinoid system plays an important role in skin health, as its dysregulation has been linked to atopic dermatitis, psoriasis, scleroderma, and skin cancer. Data indicate that exogenous and endogenous cannabinoids influence the endocannabinoid system through cannabinoid receptors, transient receptor potential channels (TRPs), and peroxisome proliferator–activated receptors (PPARs). Río et al. suggest that the dynamism of the endocannabinoid system buttresses the targeting of multiple endpoints for therapeutic success with cannabinoids rather than the one-disease-one-target approach.24 Endogenous cannabinoids, such as arachidonoyl ethanolamide and 2-arachidonoylglycerol, are now thought to be significant mediators in the skin.3 Further, endocannabinoids have been shown to deliver analgesia to the skin, at the spinal and supraspinal levels.25
Anti-inflammatory activity
In 2010, Tubaro et al. used the Croton oil mouse ear dermatitis assay to study the in vivo topical anti-inflammatory effects of seven phytocannabinoids and their related cannabivarins (nonpsychoactive cannabinoids). They found that anti-inflammatory activity was derived from the involvement of the cannabinoid receptors as well as the inflammatory endpoints that the phytocannabinoids targeted.26
In 2013, Gaffal et al. explored the anti-inflammatory activity of topical THC in dinitrofluorobenzene-mediated allergic contact dermatitis independent of CB1/2 receptors by using wild-type and CB1/2 receptor-deficient mice. The researchers found that topically applied THC reduced contact allergic ear edema and myeloid immune cell infiltration in both groups of mice. They concluded that such a decline in inflammation resulted from mitigating the keratinocyte-derived proinflammatory mediators that direct myeloid immune cell infiltration independent of CB1/2 receptors, and positions cannabinoids well for future use in treating inflammatory cutaneous conditions.20
Literature reviews
In a 2018 literature review on the uses of cannabinoids for cutaneous disorders, Eagleston et al. determined that preclinical data on cannabinoids reveal the potential to treat acne, allergic contact dermatitis, asteatotic dermatitis, atopic dermatitis, hidradenitis suppurativa, Kaposi sarcoma, pruritus, psoriasis, skin cancer, and the skin symptoms of systemic sclerosis. They caution, though, that more preclinical work is necessary along with randomized, controlled trials with sufficiently large sample sizes to establish the safety and efficacy of cannabinoids to treat skin conditions.27
A literature review by Marks and Friedman published later that year on the therapeutic potential of phytocannabinoids, endocannabinoids, and synthetic cannabinoids in managing skin disorders revealed the same findings regarding the cutaneous conditions associated with these compounds. The authors noted, though, that while the preponderance of articles highlight the efficacy of cannabinoids in treating inflammatory and neoplastic cutaneous conditions, some reports indicate proinflammatory and proneoplastic activities of cannabinoids. Like Eagleston et al., they call for additional studies.28
Conclusion
As in many botanical agents that I cover in this column, cannabis is associated with numerous medical benefits. I am encouraged to see expanding legalization of medical marijuana and increased research into its reputedly broad potential to improve human health. Anecdotally, I have heard stunning reports from patients about amelioration of joint and back pain as well as relief from other inflammatory symptoms. Discovery and elucidation of the endogenous cannabinoid system is a recent development. Research on its functions and roles in cutaneous health has followed suit and is steadily increasing. Particular skin conditions for which cannabis and cannabinoids may be indicated will be the focus of the next column.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and “Cosmeceuticals and Cosmetic Ingredients” (New York: McGraw-Hill, 2014), and a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems LLC. Write to her at [email protected]
References
1. Higdon J. Why 2019 could be marijuana’s biggest year yet. Politico Magazine. Jan 21, 2019.
2. Singh D et al. Clin Dermatol. 2018 May-Jun;36(3):399-419.
3. Kupczyk P et al. Exp Dermatol. 2009 Aug;18(8):669-79.
4. Wilkinson JD et al. J Dermatol Sci. 2007 Feb;45(2):87-92.
5. Milando R et al. Am J Clin Dermatol. 2019 April;20(2):167-80.
6. Robinson E et al. J Drugs Dermatol. 2018 Dec 1;17(12):1273-8.
7. Mounessa JS et al. J Am Acad Dermatol. 2017 Jul;77(1):188-90.
8. Liszewski W et al. J Am Acad Dermatol. 2017 Sep;77(3):e87-e88.
9. Telek A et al. FASEB J. 2007 Nov;21(13):3534-41.
10. Wollenberg A et al. Br J Dermatol. 2014 Jul;170 Suppl 1:7-11.
11. Ramot Y et al. PeerJ. 2013 Feb 19;1:e40.
12. Schlicker E et al. Trends Pharmacol Sci. 2001 Nov;22(11):565-72.
13. Christie MJ et al. Nature. 2001 Mar 29;410(6828):527-30.
14. Ibid.
15. Bíró T et al. Trends Pharmacol Sci. 2009 Aug;30(8):411-20.
16. Pacher P et al. Pharmacol Rev. 2006 Sep;58(3):389-462.
17. Shalaby M et al. Pract Dermatol. 2018 Jan;68-70.
18. Chelliah MP et al. Pediatr Dermatol. 2018 Jul;35(4):e224-e227.
19. Glodde N et al. Life Sci. 2015 Oct 1;138:35-40.
20. Gaffal E et al. Allergy. 2013 Aug;68(8):994-1000.
21. Pearce DD et al. J Altern Complement Med. 2014 Oct;20(10):787:91.
22. Leonti M et al. Biochem Pharmacol. 2010 Jun 15;79(12):1815-26.
23. Trusler AR et al. Dermatitis. 2017 Jan/Feb;28(1):22-32.
24. Río CD et al. Biochem Pharmacol. 2018 Nov;157:122-133.
25. Chuquilin M et al. J Am Acad Dermatol. 2016 Feb;74(2):197-212.
26. Tubaro A et al. Fitoterapia. 2010 Oct;81(7):816-9.
27. Eagleston LRM et al. Dermatol Online J. 2018 Jun 15;24(6).
28. Marks DH et al. Skin Therapy Lett. 2018 Nov;23(6):1-5.
Nitrous oxide in dermatology
. When used properly, with meticulous patient monitoring, it is safe and effective. In my practice, I have used it for procedures as simple as a skin biopsy. While we have excellent topical numbing options for pain control, nitrous oxide works well as an anxiolytic and can help calm the patient who is nervous or has a fear of needles.
Nitrous oxide is a tasteless gas synthesized and released by cells. Inhalational nitrous oxide is absorbed from the lungs and diffuses into plasma, where it acts on the central nervous system as an anxiolytic and analgesic by blocking the NMDA receptor. It has a quick onset of action and short duration, is easily titrated, and has a low side effect profile.
Initially used to provide pain relief during labor in the late 1800s, nitrous oxide is now rarely used in the United States as inhalational analgesia during surgery or labor; however, use in dentistry and pediatrics is common. In a recent review of PubMed and Cochrane databases by Brotzman et al., eight studies on the use of nitrous oxide in dermatology were identified. Studies reported favorable safety and efficacy of nitrous oxide in providing analgesia during dermatologic procedures, which included facial rejuvenation, hair transplantation, and pediatric procedures. Several other studies also discussed the use of nitrous oxide in combination with tumescent anesthesia for venous ablation and liposuction. All adverse effects were limited to the time of inhalation and included euphoria, laughter, nausea, dizziness, and vertigo. There are no studies reviewing the risk of nitrous oxide used during CO2 resurfacing procedures.
In five of the eight studies, vital signs and oxygen saturation were recorded during the period of inhalation. Almost all patients maintained adequate oxygen saturation and vitals also remained stable in these five studies, except for a slight increase in systolic and diastolic arterial pressure after ulcer debridement. In four of the eight studies, a 50% nitrous oxide/50% oxygen mixture delivered through an on-demand valve activated by a patient’s inspired breaths was used to minimize the risk of oversedation and to prevent hypoxia.
Contraindications for using nitrous oxide are pregnancy (in patients, health care providers, and assistants). Relative contraindications include nasal obstruction, chronic obstructive pulmonary disease, active cystic fibrosis, recent tympanic membrane surgery, and claustrophobia. According to the National Institute for Occupational Safety and Health, occupational exposure to nitrous oxide can lead to adverse effects that include reduced fertility and spontaneous abortion, as well as neurologic, renal, and hepatic diseases. The consensus of the majority of the studies in the PubMed/Cochrane review is that nitrous oxide provided a significant reduction in pain during dermatologic procedures, with mild and transient adverse effects. The effects dissipated quickly and thus patients could drive themselves home. But studies remain limited, and more well designed, randomized clinical trials are needed to provide clinical guidelines, safety monitoring protocols, and evidence for the use of nitrous oxide in dermatology. In my opinion, when more data are available, it will become one of the mainstays of analgesia in dermatologic procedures, particularly for pediatric, Mohs, and facial rejuvenation procedures.
Dr. Talakoub Dr. Wesley and are cocontributors to this column. Dr. Talakoub is in private practice in McLean, Va. Dr. Wesley practices dermatology in Beverly Hills, Calif. This month’s column is by Dr. Talakoub. Write to them at [email protected]. They had no relevant disclosures.
Sources
Brotzman EA et al. Dermatol Surg. 2018 May;44(5):661-9.
“Controlling Exposures to Nitrous Oxide During Anesthetic Administration,” National Institute for Occupational Safety and Health (https://www.cdc.gov/niosh/docs/94-100/default.html).
. When used properly, with meticulous patient monitoring, it is safe and effective. In my practice, I have used it for procedures as simple as a skin biopsy. While we have excellent topical numbing options for pain control, nitrous oxide works well as an anxiolytic and can help calm the patient who is nervous or has a fear of needles.
Nitrous oxide is a tasteless gas synthesized and released by cells. Inhalational nitrous oxide is absorbed from the lungs and diffuses into plasma, where it acts on the central nervous system as an anxiolytic and analgesic by blocking the NMDA receptor. It has a quick onset of action and short duration, is easily titrated, and has a low side effect profile.
Initially used to provide pain relief during labor in the late 1800s, nitrous oxide is now rarely used in the United States as inhalational analgesia during surgery or labor; however, use in dentistry and pediatrics is common. In a recent review of PubMed and Cochrane databases by Brotzman et al., eight studies on the use of nitrous oxide in dermatology were identified. Studies reported favorable safety and efficacy of nitrous oxide in providing analgesia during dermatologic procedures, which included facial rejuvenation, hair transplantation, and pediatric procedures. Several other studies also discussed the use of nitrous oxide in combination with tumescent anesthesia for venous ablation and liposuction. All adverse effects were limited to the time of inhalation and included euphoria, laughter, nausea, dizziness, and vertigo. There are no studies reviewing the risk of nitrous oxide used during CO2 resurfacing procedures.
In five of the eight studies, vital signs and oxygen saturation were recorded during the period of inhalation. Almost all patients maintained adequate oxygen saturation and vitals also remained stable in these five studies, except for a slight increase in systolic and diastolic arterial pressure after ulcer debridement. In four of the eight studies, a 50% nitrous oxide/50% oxygen mixture delivered through an on-demand valve activated by a patient’s inspired breaths was used to minimize the risk of oversedation and to prevent hypoxia.
Contraindications for using nitrous oxide are pregnancy (in patients, health care providers, and assistants). Relative contraindications include nasal obstruction, chronic obstructive pulmonary disease, active cystic fibrosis, recent tympanic membrane surgery, and claustrophobia. According to the National Institute for Occupational Safety and Health, occupational exposure to nitrous oxide can lead to adverse effects that include reduced fertility and spontaneous abortion, as well as neurologic, renal, and hepatic diseases. The consensus of the majority of the studies in the PubMed/Cochrane review is that nitrous oxide provided a significant reduction in pain during dermatologic procedures, with mild and transient adverse effects. The effects dissipated quickly and thus patients could drive themselves home. But studies remain limited, and more well designed, randomized clinical trials are needed to provide clinical guidelines, safety monitoring protocols, and evidence for the use of nitrous oxide in dermatology. In my opinion, when more data are available, it will become one of the mainstays of analgesia in dermatologic procedures, particularly for pediatric, Mohs, and facial rejuvenation procedures.
Dr. Talakoub Dr. Wesley and are cocontributors to this column. Dr. Talakoub is in private practice in McLean, Va. Dr. Wesley practices dermatology in Beverly Hills, Calif. This month’s column is by Dr. Talakoub. Write to them at [email protected]. They had no relevant disclosures.
Sources
Brotzman EA et al. Dermatol Surg. 2018 May;44(5):661-9.
“Controlling Exposures to Nitrous Oxide During Anesthetic Administration,” National Institute for Occupational Safety and Health (https://www.cdc.gov/niosh/docs/94-100/default.html).
. When used properly, with meticulous patient monitoring, it is safe and effective. In my practice, I have used it for procedures as simple as a skin biopsy. While we have excellent topical numbing options for pain control, nitrous oxide works well as an anxiolytic and can help calm the patient who is nervous or has a fear of needles.
Nitrous oxide is a tasteless gas synthesized and released by cells. Inhalational nitrous oxide is absorbed from the lungs and diffuses into plasma, where it acts on the central nervous system as an anxiolytic and analgesic by blocking the NMDA receptor. It has a quick onset of action and short duration, is easily titrated, and has a low side effect profile.
Initially used to provide pain relief during labor in the late 1800s, nitrous oxide is now rarely used in the United States as inhalational analgesia during surgery or labor; however, use in dentistry and pediatrics is common. In a recent review of PubMed and Cochrane databases by Brotzman et al., eight studies on the use of nitrous oxide in dermatology were identified. Studies reported favorable safety and efficacy of nitrous oxide in providing analgesia during dermatologic procedures, which included facial rejuvenation, hair transplantation, and pediatric procedures. Several other studies also discussed the use of nitrous oxide in combination with tumescent anesthesia for venous ablation and liposuction. All adverse effects were limited to the time of inhalation and included euphoria, laughter, nausea, dizziness, and vertigo. There are no studies reviewing the risk of nitrous oxide used during CO2 resurfacing procedures.
In five of the eight studies, vital signs and oxygen saturation were recorded during the period of inhalation. Almost all patients maintained adequate oxygen saturation and vitals also remained stable in these five studies, except for a slight increase in systolic and diastolic arterial pressure after ulcer debridement. In four of the eight studies, a 50% nitrous oxide/50% oxygen mixture delivered through an on-demand valve activated by a patient’s inspired breaths was used to minimize the risk of oversedation and to prevent hypoxia.
Contraindications for using nitrous oxide are pregnancy (in patients, health care providers, and assistants). Relative contraindications include nasal obstruction, chronic obstructive pulmonary disease, active cystic fibrosis, recent tympanic membrane surgery, and claustrophobia. According to the National Institute for Occupational Safety and Health, occupational exposure to nitrous oxide can lead to adverse effects that include reduced fertility and spontaneous abortion, as well as neurologic, renal, and hepatic diseases. The consensus of the majority of the studies in the PubMed/Cochrane review is that nitrous oxide provided a significant reduction in pain during dermatologic procedures, with mild and transient adverse effects. The effects dissipated quickly and thus patients could drive themselves home. But studies remain limited, and more well designed, randomized clinical trials are needed to provide clinical guidelines, safety monitoring protocols, and evidence for the use of nitrous oxide in dermatology. In my opinion, when more data are available, it will become one of the mainstays of analgesia in dermatologic procedures, particularly for pediatric, Mohs, and facial rejuvenation procedures.
Dr. Talakoub Dr. Wesley and are cocontributors to this column. Dr. Talakoub is in private practice in McLean, Va. Dr. Wesley practices dermatology in Beverly Hills, Calif. This month’s column is by Dr. Talakoub. Write to them at [email protected]. They had no relevant disclosures.
Sources
Brotzman EA et al. Dermatol Surg. 2018 May;44(5):661-9.
“Controlling Exposures to Nitrous Oxide During Anesthetic Administration,” National Institute for Occupational Safety and Health (https://www.cdc.gov/niosh/docs/94-100/default.html).
Novel body contouring device targets muscle, not fat
DENVER –
The device, known as CoolTone, is being developed by Allergan and uses high-powered coil electromagnetic stimulation applicators to induce eddy currents in the muscle tissue. CoolTone is pending Food and Drug Administration clearance and is not yet commercially available.
“Fat reduction is just one part of body contouring,” Mathew M. Avram, MD, said at the annual conference of the American Society for Laser Medicine and Surgery. “You have skin, fat, and muscle. More and more we’re targeting all three areas for patients’ best body contouring outcomes.”
According to Dr. Avram, director of the Massachusetts General Hospital Dermatology Laser & Cosmetic Center, Boston, CoolTone provides high-frequency electromagnetic muscle stimulation that triggers muscle contractions that cannot be achieved by normal exercise to increase muscle mass and strength. “You’re doing super physiological amounts of contractions with this stimulation – the equivalent of doing thousands of sit-ups, if you’re treating the abdomen,” he said. “It strengthens, tones, and firms muscles in abdomen, buttocks, arms, and legs. There is a history of this type of technology for athletes and other indications in physical therapy.”
The current FDA clearance for a predicate electromagnetic stimulation system for muscle conditioning is for the abdomen, buttocks, thighs, and arms. “This is for improvement of abdominal tone, strengthening of the abdominal muscles, and development of a firmer abdomen,” said Dr. Avram, who also is director of dermatologic surgery at Mass General. “It’s for strengthening, toning, and firming of buttocks and thighs, and for improvement of muscle tone and firmness, and for strengthening muscle in arms.”
The electrical current induced by the CoolTone device flows readily into muscle and not into fat, he continued. This brings the current to nearby motor nerve structures that stimulate contraction once the action potential is reached. “You’re getting maximal contractions that are extreme for a full range of muscle fibers,” explained Dr. Avram, who is the immediate past president of the ASLMS. “This requires an external electrical stimulus; it’s not something you do with normal exercise. With mild exercise, only the slow-twitch muscle fibers are activated, not the fast-twitch muscle fibers. Also, the pulsing sequences are designed to preferentially excite motor nerves rather than sensory nerves. So it’s really going after the ability for you to contract your muscles as much as possible.”
Dr. Avram has received consulting fees from Merz and Alastin and holds ownership interests with ZALEA, InMode, and Cytrellis. He has served on the advisory boards for ZELTIQ Aesthetics, Soliton, Sciton, and Sienna Biopharmaceuticals, and he has intellectual property rights with Cytrellis.
DENVER –
The device, known as CoolTone, is being developed by Allergan and uses high-powered coil electromagnetic stimulation applicators to induce eddy currents in the muscle tissue. CoolTone is pending Food and Drug Administration clearance and is not yet commercially available.
“Fat reduction is just one part of body contouring,” Mathew M. Avram, MD, said at the annual conference of the American Society for Laser Medicine and Surgery. “You have skin, fat, and muscle. More and more we’re targeting all three areas for patients’ best body contouring outcomes.”
According to Dr. Avram, director of the Massachusetts General Hospital Dermatology Laser & Cosmetic Center, Boston, CoolTone provides high-frequency electromagnetic muscle stimulation that triggers muscle contractions that cannot be achieved by normal exercise to increase muscle mass and strength. “You’re doing super physiological amounts of contractions with this stimulation – the equivalent of doing thousands of sit-ups, if you’re treating the abdomen,” he said. “It strengthens, tones, and firms muscles in abdomen, buttocks, arms, and legs. There is a history of this type of technology for athletes and other indications in physical therapy.”
The current FDA clearance for a predicate electromagnetic stimulation system for muscle conditioning is for the abdomen, buttocks, thighs, and arms. “This is for improvement of abdominal tone, strengthening of the abdominal muscles, and development of a firmer abdomen,” said Dr. Avram, who also is director of dermatologic surgery at Mass General. “It’s for strengthening, toning, and firming of buttocks and thighs, and for improvement of muscle tone and firmness, and for strengthening muscle in arms.”
The electrical current induced by the CoolTone device flows readily into muscle and not into fat, he continued. This brings the current to nearby motor nerve structures that stimulate contraction once the action potential is reached. “You’re getting maximal contractions that are extreme for a full range of muscle fibers,” explained Dr. Avram, who is the immediate past president of the ASLMS. “This requires an external electrical stimulus; it’s not something you do with normal exercise. With mild exercise, only the slow-twitch muscle fibers are activated, not the fast-twitch muscle fibers. Also, the pulsing sequences are designed to preferentially excite motor nerves rather than sensory nerves. So it’s really going after the ability for you to contract your muscles as much as possible.”
Dr. Avram has received consulting fees from Merz and Alastin and holds ownership interests with ZALEA, InMode, and Cytrellis. He has served on the advisory boards for ZELTIQ Aesthetics, Soliton, Sciton, and Sienna Biopharmaceuticals, and he has intellectual property rights with Cytrellis.
DENVER –
The device, known as CoolTone, is being developed by Allergan and uses high-powered coil electromagnetic stimulation applicators to induce eddy currents in the muscle tissue. CoolTone is pending Food and Drug Administration clearance and is not yet commercially available.
“Fat reduction is just one part of body contouring,” Mathew M. Avram, MD, said at the annual conference of the American Society for Laser Medicine and Surgery. “You have skin, fat, and muscle. More and more we’re targeting all three areas for patients’ best body contouring outcomes.”
According to Dr. Avram, director of the Massachusetts General Hospital Dermatology Laser & Cosmetic Center, Boston, CoolTone provides high-frequency electromagnetic muscle stimulation that triggers muscle contractions that cannot be achieved by normal exercise to increase muscle mass and strength. “You’re doing super physiological amounts of contractions with this stimulation – the equivalent of doing thousands of sit-ups, if you’re treating the abdomen,” he said. “It strengthens, tones, and firms muscles in abdomen, buttocks, arms, and legs. There is a history of this type of technology for athletes and other indications in physical therapy.”
The current FDA clearance for a predicate electromagnetic stimulation system for muscle conditioning is for the abdomen, buttocks, thighs, and arms. “This is for improvement of abdominal tone, strengthening of the abdominal muscles, and development of a firmer abdomen,” said Dr. Avram, who also is director of dermatologic surgery at Mass General. “It’s for strengthening, toning, and firming of buttocks and thighs, and for improvement of muscle tone and firmness, and for strengthening muscle in arms.”
The electrical current induced by the CoolTone device flows readily into muscle and not into fat, he continued. This brings the current to nearby motor nerve structures that stimulate contraction once the action potential is reached. “You’re getting maximal contractions that are extreme for a full range of muscle fibers,” explained Dr. Avram, who is the immediate past president of the ASLMS. “This requires an external electrical stimulus; it’s not something you do with normal exercise. With mild exercise, only the slow-twitch muscle fibers are activated, not the fast-twitch muscle fibers. Also, the pulsing sequences are designed to preferentially excite motor nerves rather than sensory nerves. So it’s really going after the ability for you to contract your muscles as much as possible.”
Dr. Avram has received consulting fees from Merz and Alastin and holds ownership interests with ZALEA, InMode, and Cytrellis. He has served on the advisory boards for ZELTIQ Aesthetics, Soliton, Sciton, and Sienna Biopharmaceuticals, and he has intellectual property rights with Cytrellis.
EXPERT ANALYSIS FROM ASLMS 2019
Energy-based devices for vaginal rejuvenation described in FDA adverse event reports
The use of was implicated in nearly four dozen adverse event reports found in the agency’s medical device adverse event reporting database, researchers report.
The 45 unique event reports, submitted to the FDA during October 2015–January 2019, described 46 patients in total, of whom 33 reported long-term effects including pain, numbness, and burning, said the researchers, led by Jusleen Ahluwalia, MD, of the department of dermatology at the University of California, San Diego, and her coauthors. They included 31 that were reported by the patients, 8 reported by the manufacturer; 4 reported by the distributor, and 2 not specified.
These findings emphasize the need for clinical trials to evaluate the safety and efficacy of the lasers and radiofrequency devices that have been marketed and used for so-called vaginal rejuvenation procedures, they wrote in Lasers in Surgery and Medicine. The coauthors are Arisa Ortiz, MD, also with the University of California, San Diego, and Mathew M. Avram, MD, director of the Massachusetts General Hospital Dermatology Laser & Cosmetic Center, Boston. “Randomized studies are necessary to compare these therapies with standard modalities and to establish the safety of these devices,” they wrote.
In July 2018, the FDA issued a safety communication alerting patients and health care providers that the safety and effectiveness of energy-based devices has not been established for procedures described as “vaginal rejuvenation.” Scott Gottlieb, MD, FDA commissioner at the time, issued a statement decrying “deceptive health claims and significant risks” related to devices marketed for those medical procedures. In a November 2018 update, the FDA said they contacted some device manufacturers to express concerns that the devices were being marketed inappropriately and that manufacturers they had contacted so far “responded with adequate corrections.”
In their report, Dr. Ahluwalia and her associates noted that “vaginal rejuvenation” is an ill-defined term that may encompass a variety of procedures related to tightening; dyspareunia; dysuria; urinary incontinence; vulvar issues including irritation, dryness, and atrophy; and orgasmic dysfunction.
They found a total of 58 records in their review of the Manufacturer and User Facility Device Experience database, of which 25 were reported prior to the FDA’s July 2018 statement. Of 45 unique event descriptions found in those records, 39 were categorized as patient-related injuries, while 2 were operator-related injuries, 2 were device malfunctions, and 2 were not specified.
Pain was the most commonly adverse event, accounting for 19 reports in their analysis, while 11 patients reported numbness or burning.
Among the laser- and energy-based devices specifically described in the 39 patient-report injuries, the MonaLisa Touch had the highest number of adverse event reports (16), the data show. “However, this may be reflective of length of time bias as it is one of the first devices utilized to promote vaginal rejuvenation,” the authors pointed out.
In light of these findings, the authors advised clinicians to ask patients about their reasons for seeking vaginal rejuvenation procedures. “Normal variety of female genital appearances should also be reviewed when patients express cosmetic concerns,” they added. Concerns about related to genitourinary syndrome of menopause “or optimizing sexual function may be alleviated by exploring nonprocedural, conservative approaches, such as hormonal creams, if not contraindicated, and/or counseling,” they noted.
The authors provided conflict of interest disclosures related to Zalea, Inmode, Cytrellis, Zeltiq Aesthetics, Soliton, Sciton, Allergan, and Sienna Biopharmaceuticals, among others.
Adverse events related to devices and drugs can be reported to the FDA’s Medwatch program.
SOURCE: Ahluwalia J et al. Lasers Surg Med. 2019 Mar 29. doi: 10.1002/lsm.23084.
The use of was implicated in nearly four dozen adverse event reports found in the agency’s medical device adverse event reporting database, researchers report.
The 45 unique event reports, submitted to the FDA during October 2015–January 2019, described 46 patients in total, of whom 33 reported long-term effects including pain, numbness, and burning, said the researchers, led by Jusleen Ahluwalia, MD, of the department of dermatology at the University of California, San Diego, and her coauthors. They included 31 that were reported by the patients, 8 reported by the manufacturer; 4 reported by the distributor, and 2 not specified.
These findings emphasize the need for clinical trials to evaluate the safety and efficacy of the lasers and radiofrequency devices that have been marketed and used for so-called vaginal rejuvenation procedures, they wrote in Lasers in Surgery and Medicine. The coauthors are Arisa Ortiz, MD, also with the University of California, San Diego, and Mathew M. Avram, MD, director of the Massachusetts General Hospital Dermatology Laser & Cosmetic Center, Boston. “Randomized studies are necessary to compare these therapies with standard modalities and to establish the safety of these devices,” they wrote.
In July 2018, the FDA issued a safety communication alerting patients and health care providers that the safety and effectiveness of energy-based devices has not been established for procedures described as “vaginal rejuvenation.” Scott Gottlieb, MD, FDA commissioner at the time, issued a statement decrying “deceptive health claims and significant risks” related to devices marketed for those medical procedures. In a November 2018 update, the FDA said they contacted some device manufacturers to express concerns that the devices were being marketed inappropriately and that manufacturers they had contacted so far “responded with adequate corrections.”
In their report, Dr. Ahluwalia and her associates noted that “vaginal rejuvenation” is an ill-defined term that may encompass a variety of procedures related to tightening; dyspareunia; dysuria; urinary incontinence; vulvar issues including irritation, dryness, and atrophy; and orgasmic dysfunction.
They found a total of 58 records in their review of the Manufacturer and User Facility Device Experience database, of which 25 were reported prior to the FDA’s July 2018 statement. Of 45 unique event descriptions found in those records, 39 were categorized as patient-related injuries, while 2 were operator-related injuries, 2 were device malfunctions, and 2 were not specified.
Pain was the most commonly adverse event, accounting for 19 reports in their analysis, while 11 patients reported numbness or burning.
Among the laser- and energy-based devices specifically described in the 39 patient-report injuries, the MonaLisa Touch had the highest number of adverse event reports (16), the data show. “However, this may be reflective of length of time bias as it is one of the first devices utilized to promote vaginal rejuvenation,” the authors pointed out.
In light of these findings, the authors advised clinicians to ask patients about their reasons for seeking vaginal rejuvenation procedures. “Normal variety of female genital appearances should also be reviewed when patients express cosmetic concerns,” they added. Concerns about related to genitourinary syndrome of menopause “or optimizing sexual function may be alleviated by exploring nonprocedural, conservative approaches, such as hormonal creams, if not contraindicated, and/or counseling,” they noted.
The authors provided conflict of interest disclosures related to Zalea, Inmode, Cytrellis, Zeltiq Aesthetics, Soliton, Sciton, Allergan, and Sienna Biopharmaceuticals, among others.
Adverse events related to devices and drugs can be reported to the FDA’s Medwatch program.
SOURCE: Ahluwalia J et al. Lasers Surg Med. 2019 Mar 29. doi: 10.1002/lsm.23084.
The use of was implicated in nearly four dozen adverse event reports found in the agency’s medical device adverse event reporting database, researchers report.
The 45 unique event reports, submitted to the FDA during October 2015–January 2019, described 46 patients in total, of whom 33 reported long-term effects including pain, numbness, and burning, said the researchers, led by Jusleen Ahluwalia, MD, of the department of dermatology at the University of California, San Diego, and her coauthors. They included 31 that were reported by the patients, 8 reported by the manufacturer; 4 reported by the distributor, and 2 not specified.
These findings emphasize the need for clinical trials to evaluate the safety and efficacy of the lasers and radiofrequency devices that have been marketed and used for so-called vaginal rejuvenation procedures, they wrote in Lasers in Surgery and Medicine. The coauthors are Arisa Ortiz, MD, also with the University of California, San Diego, and Mathew M. Avram, MD, director of the Massachusetts General Hospital Dermatology Laser & Cosmetic Center, Boston. “Randomized studies are necessary to compare these therapies with standard modalities and to establish the safety of these devices,” they wrote.
In July 2018, the FDA issued a safety communication alerting patients and health care providers that the safety and effectiveness of energy-based devices has not been established for procedures described as “vaginal rejuvenation.” Scott Gottlieb, MD, FDA commissioner at the time, issued a statement decrying “deceptive health claims and significant risks” related to devices marketed for those medical procedures. In a November 2018 update, the FDA said they contacted some device manufacturers to express concerns that the devices were being marketed inappropriately and that manufacturers they had contacted so far “responded with adequate corrections.”
In their report, Dr. Ahluwalia and her associates noted that “vaginal rejuvenation” is an ill-defined term that may encompass a variety of procedures related to tightening; dyspareunia; dysuria; urinary incontinence; vulvar issues including irritation, dryness, and atrophy; and orgasmic dysfunction.
They found a total of 58 records in their review of the Manufacturer and User Facility Device Experience database, of which 25 were reported prior to the FDA’s July 2018 statement. Of 45 unique event descriptions found in those records, 39 were categorized as patient-related injuries, while 2 were operator-related injuries, 2 were device malfunctions, and 2 were not specified.
Pain was the most commonly adverse event, accounting for 19 reports in their analysis, while 11 patients reported numbness or burning.
Among the laser- and energy-based devices specifically described in the 39 patient-report injuries, the MonaLisa Touch had the highest number of adverse event reports (16), the data show. “However, this may be reflective of length of time bias as it is one of the first devices utilized to promote vaginal rejuvenation,” the authors pointed out.
In light of these findings, the authors advised clinicians to ask patients about their reasons for seeking vaginal rejuvenation procedures. “Normal variety of female genital appearances should also be reviewed when patients express cosmetic concerns,” they added. Concerns about related to genitourinary syndrome of menopause “or optimizing sexual function may be alleviated by exploring nonprocedural, conservative approaches, such as hormonal creams, if not contraindicated, and/or counseling,” they noted.
The authors provided conflict of interest disclosures related to Zalea, Inmode, Cytrellis, Zeltiq Aesthetics, Soliton, Sciton, Allergan, and Sienna Biopharmaceuticals, among others.
Adverse events related to devices and drugs can be reported to the FDA’s Medwatch program.
SOURCE: Ahluwalia J et al. Lasers Surg Med. 2019 Mar 29. doi: 10.1002/lsm.23084.
FROM LASERS IN SURGERY AND MEDICINE
Key clinical point: Nearly four dozen distinct adverse event reports related to energy-based devices used for vaginal rejuvenation were found in an analysis of an FDA database.
Major finding: The 45 unique event reports, disclosed to FDA during October 2015–January 2019, described 46 patients in total, of whom 33 reported long-term effects including pain, numbness, and burning.
Study details: Cross-sectional analysis of records in the Manufacturer and User Facility Device Experience database entered during October 2015–January 2019.
Disclosures: Authors provided conflict of interest disclosures related to ZALEA, InMode, Cytrellis, Zeltiq Aesthetics, Soliton, Sciton, Allergan, and Sienna Biopharmaceuticals, among others.
Source: Ahluwalia J et al. Lasers Surg Med. 2019 Mar 29. doi: 10.1002/lsm.23084.
Survey finds high rate of complications from laser tattoo removal in non-clinic settings
DENVER – A survey from a dermatology practice in Houston found that among patients seeking corrective treatment for laser tattoo removal, 79% had complications from previous removal attempts and 63% were treated in non-clinic facilities by a non-physician provider without physician supervision.
The findings come from a single-center study that sought to identify the type, burden, and frequency of complications from laser tattoo removal, a procedure offered by both physician and non-physician facilities. “Laser tattoo removal is increasing in popularity,” lead study author Amanda K. Suggs, MD, said at the annual conference of the American Society for Laser Medicine and Surgery.
Dr. Suggs and Paul M. Friedman, MD, of Houston-based Dermatology and Laser Surgery, have observed an increase in patients seeking corrective tattoo removal after complications from and lack of efficacy of prior treatments provided predominantly at non-clinic facilities, including medical spas and tattoo removal clinics –so they decided to interview 19 patients who presented to their practice seeking corrective laser tattoo removal. The majority (84%) were female, their mean age was 34 years old, and 53% had Fitzpatrick skin types IV or higher. Nearly three-quarters of tattoos (74%) consisted of multiple colors, which are known to be more difficult to treat. Of the patients seeking corrective treatment, 42% were seeking removal of more than one tattoo.
Prior to coming to their office, the patients had undergone an average of seven prior tattoo removal treatments and 72% of patients were treated by a non-physician provider at some point. Nearly two-thirds of patients (63%) were treated in non-clinic facilities. “All patients were unsatisfied with the degree of improvement, and 79% had at least one complication from their prior treatments,” said Dr. Suggs, who is a fellow at the practice.
Of the 15 patients with prior treatment complications, 64% were treated by a non-physician provider. The most common complication was scarring (53%), followed by dyspigmentation (47%), blistering (20%) and paradoxical darkening (20%). Six patients (40%) had more than one complication. Patients with Fitzpatrick skin types IV or higher had a higher proportion of scarring and dyspigmentation (63% and 71%, respectively) compared with those with other skin types. “This suggests that we should use caution when treating tattoos in patients with higher Fitzpatrick skin types, and use appropriate settings and endpoints when treating these patients,” Dr. Suggs said.
When she and Dr. Friedman interviewed the patients about their prior treatment experience elsewhere, all said they experienced excessive pain, only 33% received topical anesthesia, and none reported receiving an injectable anesthesia.
At the Dermatology and Laser Surgery Center, the protocol for corrective laser tattoo removal involves injectable anesthesia, Dr. Suggs said. They use a picosecond laser, a perfluorodecalin patch, and, if needed, nonablative fractional resurfacing at 1550 nm for scarring. The wavelength used for the picosecond laser (1064nm, 785nm or 532nm) is chosen based on patient characteristics and tattoo color or colors.
In a subset analysis, the investigators interviewed eight patients again after undergoing laser tattoo removal at their practice. All underwent treatment with a picosecond laser, perfluorodecalin patch, and injectable anesthesia. All reported minimal to no pain during the procedure and an optimal experience. No complications were noted.
Dr. Friedman and Dr. Suggs emphasized that consumers should be aware of the risks and potential for complications from laser tattoo removal. They recommend that all consumers – especially those at higher risk for complications such as higher Fitzpatrick skin type patients and those with multicolored tattoos – choose a provider with extensive training in the procedure, such as a board-certified dermatologist or plastic surgeon.
Dr. Suggs disclosed that she is an ambassador for Tri Sirena sun protective athletic apparel. Dr. Friedman disclosed that he is a member of the advisory board for Allergan, Solta Medical, Syneron-Candela, and Sienna Biopharmaceuticals. He is also a research investigator for Syneron-Candela and has received a research grant from Sienna.
DENVER – A survey from a dermatology practice in Houston found that among patients seeking corrective treatment for laser tattoo removal, 79% had complications from previous removal attempts and 63% were treated in non-clinic facilities by a non-physician provider without physician supervision.
The findings come from a single-center study that sought to identify the type, burden, and frequency of complications from laser tattoo removal, a procedure offered by both physician and non-physician facilities. “Laser tattoo removal is increasing in popularity,” lead study author Amanda K. Suggs, MD, said at the annual conference of the American Society for Laser Medicine and Surgery.
Dr. Suggs and Paul M. Friedman, MD, of Houston-based Dermatology and Laser Surgery, have observed an increase in patients seeking corrective tattoo removal after complications from and lack of efficacy of prior treatments provided predominantly at non-clinic facilities, including medical spas and tattoo removal clinics –so they decided to interview 19 patients who presented to their practice seeking corrective laser tattoo removal. The majority (84%) were female, their mean age was 34 years old, and 53% had Fitzpatrick skin types IV or higher. Nearly three-quarters of tattoos (74%) consisted of multiple colors, which are known to be more difficult to treat. Of the patients seeking corrective treatment, 42% were seeking removal of more than one tattoo.
Prior to coming to their office, the patients had undergone an average of seven prior tattoo removal treatments and 72% of patients were treated by a non-physician provider at some point. Nearly two-thirds of patients (63%) were treated in non-clinic facilities. “All patients were unsatisfied with the degree of improvement, and 79% had at least one complication from their prior treatments,” said Dr. Suggs, who is a fellow at the practice.
Of the 15 patients with prior treatment complications, 64% were treated by a non-physician provider. The most common complication was scarring (53%), followed by dyspigmentation (47%), blistering (20%) and paradoxical darkening (20%). Six patients (40%) had more than one complication. Patients with Fitzpatrick skin types IV or higher had a higher proportion of scarring and dyspigmentation (63% and 71%, respectively) compared with those with other skin types. “This suggests that we should use caution when treating tattoos in patients with higher Fitzpatrick skin types, and use appropriate settings and endpoints when treating these patients,” Dr. Suggs said.
When she and Dr. Friedman interviewed the patients about their prior treatment experience elsewhere, all said they experienced excessive pain, only 33% received topical anesthesia, and none reported receiving an injectable anesthesia.
At the Dermatology and Laser Surgery Center, the protocol for corrective laser tattoo removal involves injectable anesthesia, Dr. Suggs said. They use a picosecond laser, a perfluorodecalin patch, and, if needed, nonablative fractional resurfacing at 1550 nm for scarring. The wavelength used for the picosecond laser (1064nm, 785nm or 532nm) is chosen based on patient characteristics and tattoo color or colors.
In a subset analysis, the investigators interviewed eight patients again after undergoing laser tattoo removal at their practice. All underwent treatment with a picosecond laser, perfluorodecalin patch, and injectable anesthesia. All reported minimal to no pain during the procedure and an optimal experience. No complications were noted.
Dr. Friedman and Dr. Suggs emphasized that consumers should be aware of the risks and potential for complications from laser tattoo removal. They recommend that all consumers – especially those at higher risk for complications such as higher Fitzpatrick skin type patients and those with multicolored tattoos – choose a provider with extensive training in the procedure, such as a board-certified dermatologist or plastic surgeon.
Dr. Suggs disclosed that she is an ambassador for Tri Sirena sun protective athletic apparel. Dr. Friedman disclosed that he is a member of the advisory board for Allergan, Solta Medical, Syneron-Candela, and Sienna Biopharmaceuticals. He is also a research investigator for Syneron-Candela and has received a research grant from Sienna.
DENVER – A survey from a dermatology practice in Houston found that among patients seeking corrective treatment for laser tattoo removal, 79% had complications from previous removal attempts and 63% were treated in non-clinic facilities by a non-physician provider without physician supervision.
The findings come from a single-center study that sought to identify the type, burden, and frequency of complications from laser tattoo removal, a procedure offered by both physician and non-physician facilities. “Laser tattoo removal is increasing in popularity,” lead study author Amanda K. Suggs, MD, said at the annual conference of the American Society for Laser Medicine and Surgery.
Dr. Suggs and Paul M. Friedman, MD, of Houston-based Dermatology and Laser Surgery, have observed an increase in patients seeking corrective tattoo removal after complications from and lack of efficacy of prior treatments provided predominantly at non-clinic facilities, including medical spas and tattoo removal clinics –so they decided to interview 19 patients who presented to their practice seeking corrective laser tattoo removal. The majority (84%) were female, their mean age was 34 years old, and 53% had Fitzpatrick skin types IV or higher. Nearly three-quarters of tattoos (74%) consisted of multiple colors, which are known to be more difficult to treat. Of the patients seeking corrective treatment, 42% were seeking removal of more than one tattoo.
Prior to coming to their office, the patients had undergone an average of seven prior tattoo removal treatments and 72% of patients were treated by a non-physician provider at some point. Nearly two-thirds of patients (63%) were treated in non-clinic facilities. “All patients were unsatisfied with the degree of improvement, and 79% had at least one complication from their prior treatments,” said Dr. Suggs, who is a fellow at the practice.
Of the 15 patients with prior treatment complications, 64% were treated by a non-physician provider. The most common complication was scarring (53%), followed by dyspigmentation (47%), blistering (20%) and paradoxical darkening (20%). Six patients (40%) had more than one complication. Patients with Fitzpatrick skin types IV or higher had a higher proportion of scarring and dyspigmentation (63% and 71%, respectively) compared with those with other skin types. “This suggests that we should use caution when treating tattoos in patients with higher Fitzpatrick skin types, and use appropriate settings and endpoints when treating these patients,” Dr. Suggs said.
When she and Dr. Friedman interviewed the patients about their prior treatment experience elsewhere, all said they experienced excessive pain, only 33% received topical anesthesia, and none reported receiving an injectable anesthesia.
At the Dermatology and Laser Surgery Center, the protocol for corrective laser tattoo removal involves injectable anesthesia, Dr. Suggs said. They use a picosecond laser, a perfluorodecalin patch, and, if needed, nonablative fractional resurfacing at 1550 nm for scarring. The wavelength used for the picosecond laser (1064nm, 785nm or 532nm) is chosen based on patient characteristics and tattoo color or colors.
In a subset analysis, the investigators interviewed eight patients again after undergoing laser tattoo removal at their practice. All underwent treatment with a picosecond laser, perfluorodecalin patch, and injectable anesthesia. All reported minimal to no pain during the procedure and an optimal experience. No complications were noted.
Dr. Friedman and Dr. Suggs emphasized that consumers should be aware of the risks and potential for complications from laser tattoo removal. They recommend that all consumers – especially those at higher risk for complications such as higher Fitzpatrick skin type patients and those with multicolored tattoos – choose a provider with extensive training in the procedure, such as a board-certified dermatologist or plastic surgeon.
Dr. Suggs disclosed that she is an ambassador for Tri Sirena sun protective athletic apparel. Dr. Friedman disclosed that he is a member of the advisory board for Allergan, Solta Medical, Syneron-Candela, and Sienna Biopharmaceuticals. He is also a research investigator for Syneron-Candela and has received a research grant from Sienna.
REPORTING FROM ASLMS 2019