To the Editor: Kong et al1Kong H.E. Pollack B.P. Blalock T.W. Cannabinoids in dermatologic surgery.J Am Acad Dermatol. 2021; 85: 1565-1570Abstract Full Text Full Text PDF Scopus (3) Google Scholar comprehensively reviewed the impact of cannabinoids on inflammation, proliferation, fibrosis, pain management, and wound healing, with a focus on implications for dermatologic surgery. We would like to extend this thorough discussion to include the effect of cannabinoids on tissue perfusion and chronic wound healing as well as the potential concerns with the modes of administration of cannabinoids.Studies examining the impact of cannabinoids on tissue perfusion have reported mixed results. In a study of 18 patients, the administration of HU210, a synthetic cannabinoid receptor agonist, was shown to decrease blood flow, as measured using laser Doppler.2Dvorak M. Watkinson A. McGlone F. Rukwied R. Histamine-induced responses are attenuated by a cannabinoid receptor agonist in human skin.Inflamm Res. 2003; 52: 238-245Crossref PubMed Scopus (126) Google Scholar However, a recent systematic review outlined the literature on the vasodilatory and vasoconstrictive effects of cannabinoids.3Richter J.S. Quenardelle V. Rouyer O. et al.A systematic review of the complex effects of cannabinoids on cerebral and peripheral circulation in animal models.Front Physiol. 2018; 9: 622Crossref PubMed Scopus (23) Google Scholar In this review, it was suggested that the vascular effects of endocannabinoids depend on the dose, time since administration, use of anesthesia, and baseline arterial pressure. Although currently, there is limited and poor-quality evidence to definitively conclude how cannabinoids affect postoperative tissue perfusion and chronic wound healing, it is an important area of future study.The anti-inflammatory and analgesic effects of cannabinoids may positively impact chronic wound healing. Although the exact mechanisms are unclear, it has been postulated that cannabinoids decrease the levels of tumor necrosis factor α, reactive oxygen species, and lipoxygenases, resulting in beneficial effects on periwound tissues and improved wound healing.4Maida V. Shi R.B. Fazzari F.G. Zomparelli L. Topical cannabis-based medicines - A novel paradigm and treatment for non-uremic calciphylaxis leg ulcers: an open label trial.Int Wound J. 2020; 17: 1508-1516Crossref PubMed Scopus (21) Google Scholar Although the current data suggesting that cannabinoid use is beneficial for wound healing are limited to a few case reports, several higher-quality studies are underway. An ongoing open-label clinical trial of 35 patients is examining the effect of topical cannabis-based medicine, which includes a mixture of cannabinoids, terpenes, and flavonoids, on chronic wound healing and wound-related pain (ISRCTN16488940). The preliminary results of 2 elderly female patients with recalcitrant nonuremic calciphylaxis leg ulcers demonstrated complete wound closure after a mean of 76 days, with no adverse effects.4Maida V. Shi R.B. Fazzari F.G. Zomparelli L. Topical cannabis-based medicines - A novel paradigm and treatment for non-uremic calciphylaxis leg ulcers: an open label trial.Int Wound J. 2020; 17: 1508-1516Crossref PubMed Scopus (21) Google Scholar The results of the ongoing and future larger clinical trials will help establish whether topical cannabinoids may be an effective and safe treatment for chronic wounds.Finally, the method of cannabis administration and the type of vehicle are important considerations for the efficacy of wound healing, given the numerous systemic formulations available (smoking, vaping, edibles, patches, as well as topical formulations with oils, creams, and sprays). Patients who smoke cannabis are more likely to smoke tobacco than patients who do not and may not disclose that tobacco is rolled in with the marijuana. Mechanistically, heated tobacco, nicotine, and gaseous byproducts cause tissue hypoxia via vasoconstriction and increased blood viscosity. This ultimately leads to poor wound healing5McDaniel J.C. Browning K.K. Smoking, chronic wound healing, and implications for evidence-based practice.J Wound Ostomy Continence Nurs. 2014; 41: 415-423Crossref PubMed Scopus (82) Google Scholar and is an important confounder to consider clinically. Given this potential risk, a restriction on smoking both cannabis and tobacco preoperatively may be warranted.In summary, considering the factors affecting tissue perfusion, their role in wound healing, and the method of administration is substantial for the evaluation of the safety and efficacy of cannabinoids in relation to medical and surgical dermatology. High-quality clinical trials are warranted to help establish future recommendations and guidelines. To the Editor: Kong et al1Kong H.E. Pollack B.P. Blalock T.W. Cannabinoids in dermatologic surgery.J Am Acad Dermatol. 2021; 85: 1565-1570Abstract Full Text Full Text PDF Scopus (3) Google Scholar comprehensively reviewed the impact of cannabinoids on inflammation, proliferation, fibrosis, pain management, and wound healing, with a focus on implications for dermatologic surgery. We would like to extend this thorough discussion to include the effect of cannabinoids on tissue perfusion and chronic wound healing as well as the potential concerns with the modes of administration of cannabinoids. Studies examining the impact of cannabinoids on tissue perfusion have reported mixed results. In a study of 18 patients, the administration of HU210, a synthetic cannabinoid receptor agonist, was shown to decrease blood flow, as measured using laser Doppler.2Dvorak M. Watkinson A. McGlone F. Rukwied R. Histamine-induced responses are attenuated by a cannabinoid receptor agonist in human skin.Inflamm Res. 2003; 52: 238-245Crossref PubMed Scopus (126) Google Scholar However, a recent systematic review outlined the literature on the vasodilatory and vasoconstrictive effects of cannabinoids.3Richter J.S. Quenardelle V. Rouyer O. et al.A systematic review of the complex effects of cannabinoids on cerebral and peripheral circulation in animal models.Front Physiol. 2018; 9: 622Crossref PubMed Scopus (23) Google Scholar In this review, it was suggested that the vascular effects of endocannabinoids depend on the dose, time since administration, use of anesthesia, and baseline arterial pressure. Although currently, there is limited and poor-quality evidence to definitively conclude how cannabinoids affect postoperative tissue perfusion and chronic wound healing, it is an important area of future study. The anti-inflammatory and analgesic effects of cannabinoids may positively impact chronic wound healing. Although the exact mechanisms are unclear, it has been postulated that cannabinoids decrease the levels of tumor necrosis factor α, reactive oxygen species, and lipoxygenases, resulting in beneficial effects on periwound tissues and improved wound healing.4Maida V. Shi R.B. Fazzari F.G. Zomparelli L. Topical cannabis-based medicines - A novel paradigm and treatment for non-uremic calciphylaxis leg ulcers: an open label trial.Int Wound J. 2020; 17: 1508-1516Crossref PubMed Scopus (21) Google Scholar Although the current data suggesting that cannabinoid use is beneficial for wound healing are limited to a few case reports, several higher-quality studies are underway. An ongoing open-label clinical trial of 35 patients is examining the effect of topical cannabis-based medicine, which includes a mixture of cannabinoids, terpenes, and flavonoids, on chronic wound healing and wound-related pain (ISRCTN16488940). The preliminary results of 2 elderly female patients with recalcitrant nonuremic calciphylaxis leg ulcers demonstrated complete wound closure after a mean of 76 days, with no adverse effects.4Maida V. Shi R.B. Fazzari F.G. Zomparelli L. Topical cannabis-based medicines - A novel paradigm and treatment for non-uremic calciphylaxis leg ulcers: an open label trial.Int Wound J. 2020; 17: 1508-1516Crossref PubMed Scopus (21) Google Scholar The results of the ongoing and future larger clinical trials will help establish whether topical cannabinoids may be an effective and safe treatment for chronic wounds. Finally, the method of cannabis administration and the type of vehicle are important considerations for the efficacy of wound healing, given the numerous systemic formulations available (smoking, vaping, edibles, patches, as well as topical formulations with oils, creams, and sprays). Patients who smoke cannabis are more likely to smoke tobacco than patients who do not and may not disclose that tobacco is rolled in with the marijuana. Mechanistically, heated tobacco, nicotine, and gaseous byproducts cause tissue hypoxia via vasoconstriction and increased blood viscosity. This ultimately leads to poor wound healing5McDaniel J.C. Browning K.K. Smoking, chronic wound healing, and implications for evidence-based practice.J Wound Ostomy Continence Nurs. 2014; 41: 415-423Crossref PubMed Scopus (82) Google Scholar and is an important confounder to consider clinically. Given this potential risk, a restriction on smoking both cannabis and tobacco preoperatively may be warranted. In summary, considering the factors affecting tissue perfusion, their role in wound healing, and the method of administration is substantial for the evaluation of the safety and efficacy of cannabinoids in relation to medical and surgical dermatology. High-quality clinical trials are warranted to help establish future recommendations and guidelines. None disclosed. Cannabinoids in dermatologic surgeryJournal of the American Academy of DermatologyVol. 85Issue 6PreviewThough known as a medicinal herb for centuries, the recent legalization of cannabinoids across many states has ushered in a new era where cannabinoids have become a popular treatment option among clinicians and patients alike. Cannabinoids have demonstrated efficacy in wound healing, reducing inflammation, ameliorating pain, and have shown potential as an antitumor agent. As a result, cannabinoids have been rapidly woven into the fabric of modern medicine. However, the utility of cannabinoids in dermatologic surgery has not been explored to date. Full-Text PDF
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