{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T15:22:47Z","timestamp":1790608967041,"version":"4.1.0"},"reference-count":169,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"KAU Endowment (WAQF) at King Abdulaziz University"},{"name":"Deanship of Scientific Research"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Chronic inflammatory skin disorders, including atopic dermatitis, psoriasis, acne, and chronic wounds, affect nearly two billion people worldwide, impose substantial morbidity and economic burden, and remain only partially controlled by existing therapies. The cutaneous endocannabinoid system (ECS), comprising cannabinoid receptors, endocannabinoids, and their metabolic enzymes, regulates inflammation, pruritus, barrier integrity, and tissue repair; cannabinoid receptor type 2 (CB2) has emerged as a particularly relevant target. \u03b2-Caryophyllene (BCP), a dietary sesquiterpene and highly selective CB2 agonist with favorable safety and pharmacokinetic attributes, has attracted attention as a promising topical candidate. Methods: We systematically searched PubMed, Embase, and Web of Science (inception\u201330 July 2025) for studies on \u201c\u03b2-caryophyllene\u201d and dermatological outcomes, prioritizing purified BCP and analytically characterized BCP-rich fractions. Quantitative parameters, including tested concentration ranges (0.5 \u00b5M\u201310%) and principal mechanistic outcomes, were extracted to provide a translational context. Results: BCP penetrates the stratum corneum, suppresses NF-\u03baB\/MAPK and IL-4\/TSLP pathways, enhances Nrf2-driven antioxidant defenses, and accelerates re-epithelialization and collagen remodeling. Across in vitro, in vivo, and formulation studies, BCP produced consistent anti-inflammatory and barrier-restorative effects within this concentration range. CB2 antagonism attenuated these responses, confirming receptor specificity. BCP\u2019s volatility and autoxidation to \u03b2-caryophyllene oxide (BCPO) necessitate stability-by-design strategies using antioxidants, low-oxygen processing, and protective packaging. Human evidence, limited to BCP-rich botanicals such as Copaifera oleoresins, suggests benefits for scars, wounds, and acne but lacks compound-specific validation. Conclusions: BCP exhibits coherent CB2-mediated anti-inflammatory, antipruritic, antioxidant, and reparative actions with a favorable safety profile. Dose-defined, oxidation-controlled clinical trials of purified BCP are warranted to establish its potential as a steroid-sparing topical therapy.<\/jats:p>","DOI":"10.3390\/ph18111605","type":"journal-article","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:47:36Z","timestamp":1761266856000},"page":"1605","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Topical \u03b2-Caryophyllene for Dermatologic Disorders: Mechanisms, Human Evidence, and Clinical Translation"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1850-5686","authenticated-orcid":false,"given":"Amina M.","family":"Bagher","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Yakupu, A., Aimaier, R., Yuan, B., Chen, B., Cheng, J., Zhao, Y., Peng, Y., Dong, J., and Lu, S. (2023). The Burden of Skin and Subcutaneous Diseases: Findings from the Global Burden of Disease Study 2019. Front. Public Health, 11.","DOI":"10.3389\/fpubh.2023.1145513"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"623","DOI":"10.2147\/CCID.S315846","article-title":"The Impact of Acne, Atopic Dermatitis, Skin Toxicities and Scars on Quality of Life and the Importance of a Holistic Treatment Approach","volume":"14","author":"Dreno","year":"2021","journal-title":"Clin. Cosmet. Investig. Dermatol."},{"key":"ref_3","first-page":"e71293","article-title":"Prevalence of Acne Vulgaris in Adolescents and Young Adults in Al-Baha Region, Saudi Arabia","volume":"16","author":"Alsohaimi","year":"2024","journal-title":"Cureus"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1080\/13696998.2022.2152234","article-title":"The Humanistic and Economic Burden of Atopic Dermatitis among Adults and Adolescents in Saudi Arabia","volume":"25","author":"Elezbawy","year":"2022","journal-title":"J. Med. Econ."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Mahmoud, O., Yosipovitch, G., and Attia, E. (2023). Burden of Disease and Unmet Needs in the Diagnosis and Management of Atopic Dermatitis in the Arabic Population of the Middle East. J. Clin. Med., 12.","DOI":"10.3390\/jcm12144675"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jaad.2005.01.010","article-title":"Adverse Effects of Topical Glucocorticosteroids","volume":"54","author":"Hengge","year":"2006","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.jaad.2019.08.049","article-title":"Joint American Academy of Dermatology\u2013National Psoriasis Foundation Guidelines of Care for the Management and Treatment of Psoriasis in Pediatric Patients","volume":"82","author":"Menter","year":"2020","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"460","DOI":"10.5114\/ada.2021.108445","article-title":"Treatments in Psoriasis: From Standard Pharmacotherapy to Nanotechnology Therapy","volume":"39","author":"Zhu","year":"2022","journal-title":"Postepy Dermatol. Alergol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1111\/pme.12654","article-title":"Novel Use of Pharmacogenetic Testing in the Identification of CYP2C9 Polymorphisms Related to NSAID-Induced Gastropathy","volume":"16","author":"Gupta","year":"2015","journal-title":"Pain Med."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Schick, M.A., and Schlegel, N. (2022). Clinical Implication of Phosphodiesterase-4-Inhibition. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031209"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1124\/pr.54.2.161","article-title":"International Union of Pharmacology. XXVII. Classification of Cannabinoid Receptors","volume":"54","author":"Howlett","year":"2002","journal-title":"Pharmacol. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"T\u00f3th, K.F., \u00c1d\u00e1m, D., B\u00edr\u00f3, T., and Ol\u00e1h, A. (2019). Cannabinoid Signaling in the Skin: Therapeutic Potential of the \u201cC(Ut)Annabinoid\u201d System. Molecules, 24.","DOI":"10.3390\/molecules24050918"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.tips.2009.05.004","article-title":"The Endocannabinoid System of the Skin in Health and Disease: Novel Perspectives and Therapeutic Opportunities","volume":"30","author":"Paus","year":"2009","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s12950-018-0201-z","article-title":"Cannabinoid 2 Receptor Attenuates Inflammation during Skin Wound Healing by Inhibiting M1 Macrophages Rather than Activating M2 Macrophages","volume":"15","author":"Du","year":"2018","journal-title":"J. Inflamm."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Yoo, E.H., and Lee, J.H. (2023). Cannabinoids and Their Receptors in Skin Diseases. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242216523"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/j.jaad.2024.06.088","article-title":"Topical Nanoencapsulated Cannabidiol Cream as an Innovative Strategy Combating UV-A\u2013Induced Nuclear and Mitochondrial DNA Injury: A Pilot Randomized Clinical Study","volume":"91","author":"McCormick","year":"2024","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1007\/s11101-023-09860-5","article-title":"Skin Applications of Cannabidiol: Sources, Effects, Delivery Systems, Marketed Formulations and Safety","volume":"22","author":"Ferreira","year":"2023","journal-title":"Phytochem. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e64","DOI":"10.1097\/itx.0000000000000064","article-title":"Therapeutics in Chronic Pruritus of Unknown Origin","volume":"8","author":"Ju","year":"2023","journal-title":"Itch"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"S13","DOI":"10.1038\/sj.ijo.0803272","article-title":"The Pharmacology of Cannabinoid Receptors and Their Ligands: An Overview","volume":"30","author":"Pertwee","year":"2006","journal-title":"Int. J. Obes."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1038\/sj.bjp.0705666","article-title":"The Endocannabinoid System: A General View and Latest Additions","volume":"141","author":"Petrocellis","year":"2004","journal-title":"Br. J. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"9099","DOI":"10.1073\/pnas.0803601105","article-title":"Beta-Caryophyllene Is a Dietary Cannabinoid","volume":"105","author":"Gertsch","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/j.euroneuro.2013.10.008","article-title":"The Cannabinoid CB2 Receptor-Selective Phytocannabinoid Beta-Caryophyllene Exerts Analgesic Effects in Mouse Models of Inflammatory and Neuropathic Pain","volume":"24","author":"Klauke","year":"2014","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3007","DOI":"10.1002\/cam4.816","article-title":"\u03b2-caryophyllene and \u03b2-caryophyllene Oxide\u2014Natural Compounds of Anticancer and Analgesic Properties","volume":"5","author":"Fidyt","year":"2016","journal-title":"Cancer Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.jdermsci.2005.01.007","article-title":"Distribution of Cannabinoid Receptor 1 (CB1) and 2 (CB2) on Sensory Nerve Fibers and Adnexal Structures in Human Skin","volume":"38","author":"Schmelz","year":"2005","journal-title":"J. Dermatol. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Bagher, A.M. (2025). Intraplantar \u03b2-Caryophyllene Alleviates Pain and Inflammation in STZ-Induced Diabetic Peripheral Neuropathy via CB2 Receptor Activation. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26094430"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Rakotoarivelo, V., Mayer, T.Z., Simard, M., Flamand, N., and Di Marzo, V. (2024). The Impact of the CB2 Cannabinoid Receptor in Inflammatory Diseases: An Update. Molecules, 29.","DOI":"10.3390\/molecules29143381"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1111\/j.1476-5381.2011.01238.x","article-title":"Taming THC: Potential Cannabis Synergy and Phytocannabinoid-Terpenoid Entourage Effects","volume":"163","author":"Russo","year":"2011","journal-title":"Br. J. Pharmacol."},{"key":"ref_28","unstructured":"U.S. Food and Drug Administration, Center for Food Safety and Applied Nutrition (2025, August 14). Substances Added to Food (Formerly EAFUS), Available online: https:\/\/www.hfpappexternal.fda.gov\/scripts\/fdcc\/index.cfm?set=FoodSubstances&sort=Used_for_Technical_Effect&utm_source=chatgpt.com."},{"key":"ref_29","unstructured":"Flavor and Extract Manufacturers Association of the United States (FEMA) (2025, August 14). BETA-CARYOPHYLLENE. Available online: https:\/\/www.femaflavor.org\/flavor-library\/beta-caryophyllene?utm_source=chatgpt.com."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Ahn, S.S., Yeo, H., Jung, E., Ou, S., Lee, Y.H., Lim, Y., and Shin, S.Y. (2022). \u03b2-Caryophyllene Ameliorates 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis through the Downregulation of Mitogen-Activated Protein Kinase\/EGR1\/TSLP Signaling Axis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232314861"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"155726","DOI":"10.1016\/j.phymed.2024.155726","article-title":"\u03b2-Caryophyllene Promotes the Survival of Random Skin Flaps by Upregulating the PI3K\/AKT Signaling Pathway","volume":"130","author":"Deng","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"9004014","DOI":"10.1155\/2022\/9004014","article-title":"Beta-Caryophyllene as an Antioxidant, Anti-Inflammatory and Re-Epithelialization Activities in a Rat Skin Wound Excision Model","volume":"2022","author":"Gushiken","year":"2022","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Koyama, S., Purk, A., Kaur, M., Soini, H.A., Novotny, M.V., Davis, K., Kao, C.C., Matsunami, H., and Mescher, A. (2019). Beta-Caryophyllene Enhances Wound Healing through Multiple Routes. PLoS ONE, 14.","DOI":"10.1101\/611046"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Scandiffio, R., Bonzano, S., Cottone, E., Shrestha, S., Bossi, S., De Marchis, S., Maffei, M.E., and Bovolin, P. (2023). Beta-Caryophyllene Modifies Intracellular Lipid Composition in a Cell Model of Hepatic Steatosis by Acting through CB2 and PPAR Receptors. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24076060"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"112476","DOI":"10.1016\/j.jep.2019.112476","article-title":"Copaiba Oleoresin Has Topical Antinociceptive Activity in a UVB Radiation-Induced Skin-Burn Model in Mice","volume":"250","author":"Becker","year":"2020","journal-title":"J. Ethnopharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Inan, S., Ward, S.J., Baltazar, C.T., Peruggia, G.A., Javed, E., and Nayak, A.P. (2023). Epicutaneous Sensitization to the Phytocannabinoid \u03b2-Caryophyllene Induces Pruritic Inflammation. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241814328"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3685","DOI":"10.1096\/fj.07-104877","article-title":"Endocannabinoids Enhance Lipid Synthesis and Apoptosis of Human Sebocytes via Cannabinoid Receptor-2-Mediated Signaling","volume":"22","author":"Dobrosi","year":"2008","journal-title":"FASEB J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"112707","DOI":"10.1016\/j.fct.2021.112707","article-title":"RIFM Fragrance Ingredient Safety Assessment, \u03b2-Caryophyllene, CAS Registry Number 87-44-5","volume":"159","author":"Api","year":"2022","journal-title":"Food Chem. Toxicol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"111102","DOI":"10.1016\/j.fct.2019.111102","article-title":"RIFM Fragrance Ingredient Safety Assessment, Caryophyllene Oxide, CAS Registry Number 1139-30-6","volume":"138","author":"Api","year":"2020","journal-title":"Food Chem. Toxicol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1016\/j.fct.2005.08.028","article-title":"The Fragrance Chemical Beta-Caryophyllene-Air Oxidation and Skin Sensitization","volume":"44","author":"Karlberg","year":"2006","journal-title":"Food Chem. Toxicol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"5298","DOI":"10.1074\/jbc.M306642200","article-title":"Molecular Characterization of a Phospholipase D Generating Anandamide and Its Congeners","volume":"279","author":"Okamoto","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1083\/jcb.200305129","article-title":"Cloning of the First Sn1-DAG Lipases Points to the Spatial and Temporal Regulation of Endocannabinoid Signaling in the Brain","volume":"163","author":"Bisogno","year":"2003","journal-title":"J. Cell Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/384083a0","article-title":"Molecular Characterization of an Enzyme That Degrades Neuromodulatory Fatty-Acid Amides","volume":"384","author":"Cravatt","year":"1996","journal-title":"Nature"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"10819","DOI":"10.1073\/pnas.152334899","article-title":"Brain Monoglyceride Lipase Participating in Endocannabinoid Inactivation","volume":"99","author":"Dinh","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1016\/j.chembiol.2007.11.006","article-title":"A Comprehensive Profile of Brain Enzymes That Hydrolyze the Endocannabinoid 2-Arachidonoylglycerol","volume":"14","author":"Blankman","year":"2007","journal-title":"Chem. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"6375","DOI":"10.1073\/pnas.0901515106","article-title":"Identification of Intracellular Carriers for the Endocannabinoid Anandamide","volume":"106","author":"Kaczocha","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.2174\/092986710790980078","article-title":"Endocannabinoids as Regulators of Transient Receptor Potential (TRP)Channels: A Further Opportunity to Develop New Endocannabinoid-Based Therapeutic Drugs","volume":"17","author":"Marzo","year":"2010","journal-title":"Curr. Med. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/S0092-8674(02)00652-9","article-title":"A TRP Channel That Senses Cold Stimuli and Menthol","volume":"108","author":"Peier","year":"2002","journal-title":"Cell"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1038\/22761","article-title":"Vanilloid Receptors on Sensory Nerves Mediate the Vasodilator Action of Anandamide","volume":"400","author":"Zygmunt","year":"1999","journal-title":"Nature"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Caterina, M., and Pang, Z. (2016). TRP Channels in Skin Biology and Pathophysiology. Pharmaceuticals, 9.","DOI":"10.3390\/ph9040077"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1038\/sj.jid.5700590","article-title":"Effects of Skin Surface Temperature on Epidermal Permeability Barrier Homeostasis","volume":"127","author":"Denda","year":"2007","journal-title":"J. Investig. Dermatol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1007\/s00424-012-1081-3","article-title":"Importance of Transient Receptor Potential Vanilloid 4 (TRPV4) in Epidermal Barrier Function in Human Skin Keratinocytes","volume":"463","author":"Kida","year":"2012","journal-title":"Pflugers Arch.-Eur. J. Physiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"18749","DOI":"10.1074\/jbc.M110.103606","article-title":"The TRPV4 Channel Contributes to Intercellular Junction Formation in Keratinocytes","volume":"285","author":"Sokabe","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1146\/annurev-pharmtox-010818-021441","article-title":"Beyond THC and Endocannabinoids","volume":"60","author":"Pacher","year":"2020","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"100095","DOI":"10.1016\/j.xjidi.2022.100095","article-title":"Cannabinoids for the Treatment of Dermatologic Conditions","volume":"2","author":"Sivesind","year":"2022","journal-title":"JID Innov."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"927","DOI":"10.2147\/CCID.S286411","article-title":"Therapeutic Potential of Cannabidiol (CBD) for Skin Health and Disorders","volume":"13","author":"Baswan","year":"2020","journal-title":"Clin. Cosmet. Investig. Dermatol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e40","DOI":"10.7717\/peerj.40","article-title":"A Novel Control of Human Keratin Expression: Cannabinoid Receptor 1-Mediated Signaling down-Regulates the Expression of Keratins K6 and K16 in Human Keratinocytes In Vitro and In Situ","volume":"1","author":"Ramot","year":"2013","journal-title":"PeerJ"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2534","DOI":"10.1038\/onc.2012.278","article-title":"The Orphan Receptor GPR55 Drives Skin Carcinogenesis and Is Upregulated in Human Squamous Cell Carcinomas","volume":"32","author":"Andradas","year":"2013","journal-title":"Oncogene"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Bagood, M.D., and Isseroff, R.R. (2021). TRPV1: Role in Skin and Skin Diseases and Potential Target for Improving Wound Healing. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22116135"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"P\u00e9nzes, Z., Horv\u00e1th, D., Moln\u00e1r, P., Fekete, T., P\u00e1zm\u00e1ndi, K., B\u00e1csi, A., and Sz\u00f6ll\u0151si, A.G. (2024). Anandamide Modulation of Monocyte-Derived Langerhans Cells: Implications for Immune Homeostasis and Skin Inflammation. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1423776"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.neuron.2005.11.027","article-title":"The Endocannabinoid Anandamide Protects Neurons during CNS Inflammation by Induction of MKP-1 in Microglial Cells","volume":"49","author":"Eljaschewitsch","year":"2006","journal-title":"Neuron"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/1742-2094-2-29","article-title":"Stimulation of Cannabinoid Receptor 2 (CB2) Suppresses Microglial Activation","volume":"2","author":"Ehrhart","year":"2005","journal-title":"J. Neuroinflamm."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1016\/j.jaci.2011.11.009","article-title":"Endocannabinoids Limit Excessive Mast Cell Maturation and Activation in Human Skin","volume":"129","author":"Sugawara","year":"2012","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3534","DOI":"10.1096\/fj.06-7689com","article-title":"Inhibition of Human Hair Follicle Growth by Endo- and Exocannabinoids","volume":"21","author":"Telek","year":"2007","journal-title":"FASEB J."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1007\/s00011-003-1162-z","article-title":"Histamine Induced Responses Are Attenuated by a Cannabinoid Receptor Agonist in Human Skin","volume":"52","author":"Dvorak","year":"2003","journal-title":"Inflamm. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1744","DOI":"10.1523\/JNEUROSCI.4298-03.2004","article-title":"Differential Effects of CB1 and Opioid Agonists on Two Populations of Adult Rat Dorsal Root Ganglion Neurons","volume":"24","author":"Khasabova","year":"2004","journal-title":"J. Neurosci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"E693","DOI":"10.1208\/aapsj080479","article-title":"Endocannabinoid Mechanisms of Pain Modulation","volume":"8","author":"Hohmann","year":"2006","journal-title":"AAPS J."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1967","DOI":"10.1038\/jid.2012.118","article-title":"Endocannabinoids Regulate Growth and Survival of Human Eccrine Sweat Gland-Derived Epithelial Cells","volume":"132","author":"Czifra","year":"2012","journal-title":"J. Investig. Dermatol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2568","DOI":"10.1111\/bph.12569","article-title":"TRP Channels in the Skin","volume":"171","year":"2014","journal-title":"Br. J. Pharmacol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.cell.2010.03.013","article-title":"TRP Channel Regulates EGFR Signaling in Hair Morphogenesis and Skin Barrier Formation","volume":"141","author":"Cheng","year":"2010","journal-title":"Cell"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1016\/j.jid.2018.02.022","article-title":"Endocannabinoid Tone Regulates Human Sebocyte Biology","volume":"138","author":"Markovics","year":"2018","journal-title":"J. Investig. Dermatol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1111\/bph.12309","article-title":"Epigenetic Control of Skin Differentiation Genes by Phytocannabinoids","volume":"170","author":"Pucci","year":"2013","journal-title":"Br. J. Pharmacol."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Gerasymchuk, M., Robinson, G.I., Groves, A., Haselhorst, L., Nandakumar, S., Stahl, C., Kovalchuk, O., and Kovalchuk, I. (2022). Phytocannabinoids Stimulate Rejuvenation and Prevent Cellular Senescence in Human Dermal Fibroblasts. Cells, 11.","DOI":"10.3390\/cells11233939"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"16511","DOI":"10.1073\/pnas.0902743106","article-title":"The Putative Cannabinoid Receptor GPR55 Affects Osteoclast Function in Vitro and Bone Mass in Vivo","volume":"106","author":"Whyte","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1042\/bj3460835","article-title":"Functional CB1 Cannabinoid Receptors in Human Vascular Endothelial Cells","volume":"346","author":"Liu","year":"2000","journal-title":"Biochem. J."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Hartmannsgruber, V., Heyken, W.-T., Kacik, M., Kaistha, A., Grgic, I., Harteneck, C., Liedtke, W., Hoyer, J., and K\u00f6hler, R. (2007). Arterial Response to Shear Stress Critically Depends on Endothelial TRPV4 Expression. PLoS ONE, 2.","DOI":"10.1371\/journal.pone.0000827"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1111\/exd.13336","article-title":"Systemic Immune Mechanisms in Atopic Dermatitis and Psoriasis with Implications for Treatment","volume":"27","author":"Krueger","year":"2018","journal-title":"Exp. Dermatol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1016\/S0140-6736(15)00149-X","article-title":"Atopic Dermatitis","volume":"387","author":"Weidinger","year":"2016","journal-title":"Lancet"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1126\/science.1142265","article-title":"Attenuation of Allergic Contact Dermatitis through the Endocannabinoid System","volume":"316","author":"Karsak","year":"2007","journal-title":"Science"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"8796","DOI":"10.4049\/jimmunol.177.12.8796","article-title":"Involvement of the Cannabinoid CB2 Receptor and Its Endogenous Ligand 2-Arachidonoylglycerol in Oxazolone-Induced Contact Dermatitis in Mice","volume":"177","author":"Oka","year":"2006","journal-title":"J. Immunol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1016\/S0140-6736(14)61909-7","article-title":"Psoriasis","volume":"386","author":"Boehncke","year":"2015","journal-title":"Lancet"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1146\/annurev-immunol-032713-120225","article-title":"Immunology of Psoriasis","volume":"32","author":"Lowes","year":"2014","journal-title":"Annu. Rev. Immunol."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Li, L., Liu, X., Ge, W., Chen, C., Huang, Y., Jin, Z., Zhan, M., Duan, X., Liu, X., and Kong, Y. (2022). CB2R Deficiency Exacerbates Imiquimod-Induced Psoriasiform Dermatitis and Itch Through the Neuro-Immune Pathway. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.790712"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"33896","DOI":"10.1074\/jbc.M303994200","article-title":"The Endocannabinoid System in Human Keratinocytes. Evidence That Anandamide Inhibits Epidermal Differentiation through CB1 Receptor-Dependent Inhibition of Protein Kinase C, Activation Protein-1, and Transglutaminase","volume":"278","author":"Maccarrone","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/jdv.15043","article-title":"Cutibacterium acnes (Propionibacterium acnes) and Acne Vulgaris: A Brief Look at the Latest Updates","volume":"32","author":"Corvec","year":"2018","journal-title":"Acad. Dermatol. Venereol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1111\/j.1600-0625.2009.00890.x","article-title":"New Developments in Our Understanding of Acne Pathogenesis and Treatment","volume":"18","author":"Kurokawa","year":"2009","journal-title":"Exp. Dermatol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"265sr6","DOI":"10.1126\/scitranslmed.3009337","article-title":"Wound Repair and Regeneration: Mechanisms, Signaling, and Translation","volume":"6","author":"Eming","year":"2014","journal-title":"Sci. Transl. Med."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Wilkinson, H.N., and Hardman, M.J. (2020). Wound Healing: Cellular Mechanisms and Pathological Outcomes. Open Biol., 10.","DOI":"10.1098\/rsob.200223"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Filipiuc, S.-I., Neagu, A.-N., Uritu, C.M., Tamba, B.-I., Filipiuc, L.-E., Tudorancea, I.M., Boca, A.N., H\u00e2ncu, M.F., Porumb, V., and Bild, W. (2023). The Skin and Natural Cannabinoids-Topical and Transdermal Applications. Pharmaceuticals, 16.","DOI":"10.3390\/ph16071049"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.4102\/safp.v64i1.5493","article-title":"Topical Cannabidiol (CBD) in Skin Pathology\u2014A Comprehensive Review and Prospects for New Therapeutic Opportunities","volume":"64","author":"Makhakhe","year":"2022","journal-title":"S. Afr. Fam. Pract."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Bizarro, A.F., Schmidt, V.M., Fernandes, B., Pinto, M., Pereira, H., Marto, J., and Louren\u00e7o, A.M. (2025). The Potential of Cannabidiol for Treating Canine Atopic Dermatitis. Vet. Sci., 12.","DOI":"10.3390\/vetsci12020159"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s42238-025-00317-4","article-title":"Therapeutic Potential of Cannabinoids for Treating Atopic Dermatitis","volume":"7","author":"Stoco","year":"2025","journal-title":"J. Cannabis Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"4449","DOI":"10.1007\/s00018-016-2300-4","article-title":"The CB2 Receptor and Its Role as a Regulator of Inflammation","volume":"73","author":"Turcotte","year":"2016","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"22","DOI":"10.5021\/ad.2016.28.1.22","article-title":"Selective Cannabinoid Receptor-1 Agonists Regulate Mast Cell Activation in an Oxazolone-Induced Atopic Dermatitis Model","volume":"28","author":"Nam","year":"2016","journal-title":"Ann. Dermatol."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Baser, K.H.C., and Buchbauer, G. (2020). Handbook of Essential Oils: Science, Technology, and Applications, CRC Press. [3rd ed.].","DOI":"10.1201\/9781351246460"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Katerina, V., Klara, U., Samnang, N., and Ladislav, K. (2023). Chemical Composition of Essential Oils and Supercritical Carbon Dioxide Extracts from Amomum Kravanh, Citrus Hystrix and Piper Nigrum \u201cKampot\u201d. Molecules, 28.","DOI":"10.3390\/molecules28237748"},{"key":"ref_97","unstructured":"PubChem (2025, August 09). (+)-Beta-Caryophyllene, Available online: https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/20831623."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.1111\/j.1476-5381.2012.02059.x","article-title":"The Antinociceptive Triterpene \u0392-amyrin Inhibits 2-arachidonoylglycerol (2-AG) Hydrolysis without Directly Targeting Cannabinoid Receptors","volume":"167","author":"Chicca","year":"2012","journal-title":"Br. J. Pharmacol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.1211\/jpp.59.12.0005","article-title":"Potentiating Effect of \u03b2-Caryophyllene on Anticancer Activity of \u03b1-Humulene, Isocaryophyllene and Paclitaxel","volume":"59","author":"Legault","year":"2007","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.supflu.2006.03.020","article-title":"Supercritical Fluid Extraction and Fractionation of Natural Matter","volume":"38","author":"Reverchon","year":"2006","journal-title":"J. Supercrit. Fluids"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1208\/s12249-015-0383-0","article-title":"Microemulsion-Based Topical Hydrogels of Tenoxicam for Treatment of Arthritis","volume":"17","author":"Goindi","year":"2016","journal-title":"AAPS PharmSciTech"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"124252","DOI":"10.1016\/j.ijpharm.2024.124252","article-title":"Development of Ophthalmic Nanoemulsions of \u03b2-Caryophyllene for the Treatment of Acanthamoeba Keratitis","volume":"659","author":"Conte","year":"2024","journal-title":"Int. J. Pharm."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Weimer, P., Kreutz, T., Limberger, R.P., Rossi, R.C., De Lima, \u00c1.A.N., Veiga, V.F., De Ara\u00fajo, B.V., and Koester, L.S. (2022). Correlation between the Skin Permeation Profile of the Synthetic Sesquiterpene Compounds, Beta-Caryophyllene and Caryophyllene Oxide, and the Antiedematogenic Activity by Topical Application of Nanoemulgels. Biomolecules, 12.","DOI":"10.3390\/biom12081102"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/bs.apha.2017.03.004","article-title":"Cannabis Pharmacology: The Usual Suspects and a Few Promising Leads","volume":"Volume 80","author":"Russo","year":"2017","journal-title":"Advances in Pharmacology"},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Di Sotto, A., Irannejad, H., Eufemi, M., Mancinelli, R., Abete, L., Mammola, C.L., Altieri, F., Mazzanti, G., and Di Giacomo, S. (2020). Potentiation of Low-Dose Doxorubicin Cytotoxicity by Affecting P-Glycoprotein through Caryophyllane Sesquiterpenes in HepG2 Cells: An in Vitro and in Silico Study. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21020633"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.cbi.2017.10.021","article-title":"The Inhibitory Effects of \u03b2-Caryophyllene, \u03b2-Caryophyllene Oxide and \u03b1-Humulene on the Activities of the Main Drug-Metabolizing Enzymes in Rat and Human Liver in Vitro","volume":"278","author":"Nguyen","year":"2017","journal-title":"Chem. Biol. Interact."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Francomano, F., Caruso, A., Barbarossa, A., Fazio, A., La Torre, C., Ceramella, J., Mallamaci, R., Saturnino, C., Iacopetta, D., and Sinicropi, M.S. (2019). \u03b2-Caryophyllene: A Sesquiterpene with Countless Biological Properties. Appl. Sci., 9.","DOI":"10.3390\/app9245420"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"130","DOI":"10.4161\/derm.15025","article-title":"Peroxisome Proliferator-Activated Receptors (PPARs) in Dermatology: Challenge and Promise","volume":"3","author":"Sertznig","year":"2011","journal-title":"Dermato-Endocrinology"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1016\/j.jpain.2013.03.012","article-title":"Induction of Monocyte Chemoattractant Protein-1 (MCP-1) and Its Receptor CCR2 in Primary Sensory Neurons Contributes to Paclitaxel-Induced Peripheral Neuropathy","volume":"14","author":"Zhang","year":"2013","journal-title":"J. Pain"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"7697699","DOI":"10.1155\/2023\/7697699","article-title":"The Role of TSLP in Atopic Dermatitis: From Pathogenetic Molecule to Therapeutical Target","volume":"2023","author":"Luo","year":"2023","journal-title":"Mediators Inflamm."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1038\/ni805","article-title":"Human Epithelial Cells Trigger Dendritic Cell\u2013Mediated Allergic Inflammation by Producing TSLP","volume":"3","author":"Soumelis","year":"2002","journal-title":"Nat. Immunol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"3221","DOI":"10.1007\/s00018-016-2223-0","article-title":"Role of Nrf2\/HO-1 System in Development, Oxidative Stress Response and Diseases: An Evolutionarily Conserved Mechanism","volume":"73","author":"Loboda","year":"2016","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1080\/03602530600971974","article-title":"Mechanistic Studies of the Nrf2-Keap1 Signaling Pathway","volume":"38","author":"Zhang","year":"2006","journal-title":"Drug Metab. Rev."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.redox.2012.10.001","article-title":"The Keap1-Nrf2 Pathway: Mechanisms of Activation and Dysregulation in Cancer","volume":"1","author":"Kansanen","year":"2013","journal-title":"Redox Biol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1021\/acsptsci.3c00027","article-title":"\u03b2-Caryophyllene, a Dietary Phytocannabinoid, Alleviates Diabetic Cardiomyopathy in Mice by Inhibiting Oxidative Stress and Inflammation Activating Cannabinoid Type-2 Receptors","volume":"6","author":"Sheikh","year":"2023","journal-title":"ACS Pharmacol. Transl. Sci."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1007\/s00403-015-1554-2","article-title":"The Role of Transcription Factor Nrf2 in Skin Cells Metabolism","volume":"307","author":"Skrzydlewska","year":"2015","journal-title":"Arch. Dermatol. Res."},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Furue, M. (2020). Regulation of Filaggrin, Loricrin, and Involucrin by IL-4, IL-13, IL-17A, IL-22, AHR, and NRF2: Pathogenic Implications in Atopic Dermatitis. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21155382"},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Che-Wen, Y., Lin, F.-L., Chen, K.-H., Cheng, Y.-P., Cheng, Y.-C., and Guo, J.-W. (2025). Transcriptional Dysregulation of Skin Barrier Genes in Atopic Dermatitis and Psoriasis: Mechanistic Insights and Emerging Therapeutic Strategies. Biomed. Pharmacother., 191.","DOI":"10.1016\/j.biopha.2025.118508"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1093\/carcin\/bgv076","article-title":"\u03b2-Caryophyllene Potently Inhibits Solid Tumor Growth and Lymph Node Metastasis of B16F10 Melanoma Cells in High-Fat Diet\u2013Induced Obese C57BL\/6N Mice","volume":"36","author":"Jung","year":"2015","journal-title":"Carcinogenesis"},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Del R\u00edo, C., Navarrete, C., Collado, J.A., Bellido, M.L., G\u00f3mez-Ca\u00f1as, M., Pazos, M.R., Fern\u00e1ndez-Ruiz, J., Pollastro, F., Appendino, G., and Calzado, M.A. (2016). The Cannabinoid Quinol VCE-004.8 Alleviates Bleomycin-Induced Scleroderma and Exerts Potent Antifibrotic Effects through Peroxisome Proliferator-Activated Receptor-\u03b3 and CB2 Pathways. Sci. Rep., 6.","DOI":"10.1038\/srep21703"},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Seminotti, B., Grings, M., Gl\u00e4nzel, N.M., Vockley, J., and Leipnitz, G. (2023). Peroxisome Proliferator-Activated Receptor (PPAR) Agonists as a Potential Therapy for Inherited Metabolic Disorders. Biochem. Pharmacol., 209.","DOI":"10.1016\/j.bcp.2023.115433"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"3093","DOI":"10.1073\/pnas.0409888102","article-title":"CB2 Cannabinoid Receptor Activation Produces Antinociception by Stimulating Peripheral Release of Endogenous Opioids","volume":"102","author":"Ibrahim","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Xu, X., Yu, C., Xu, L., and Xu, J. (2022). Emerging Roles of Keratinocytes in Nociceptive Transduction and Regulation. Front. Mol. Neurosci., 15.","DOI":"10.3389\/fnmol.2022.982202"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.neuroscience.2013.12.030","article-title":"Involvement of Cannabinoid Receptors in Peripheral and Spinal Morphine Analgesia","volume":"261","author":"Desroches","year":"2014","journal-title":"Neuroscience"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"b2700","DOI":"10.1136\/bmj.b2700","article-title":"The PRISMA Statement for Reporting Systematic Reviews and Meta-Analyses of Studies That Evaluate Healthcare Interventions: Explanation and Elaboration","volume":"339","author":"Liberati","year":"2009","journal-title":"BMJ"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 Statement: An Updated Guideline for Reporting Systematic Reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Percie du Sert, N., Hurst, V., Ahluwalia, A., Alam, S., Avey, M.T., Baker, M., Browne, W.J., Clark, A., Cuthill, I.C., and Dirnagl, U. (2020). The ARRIVE Guidelines 2.0: Updated Guidelines for Reporting Animal Research. PLoS Biol., 18.","DOI":"10.1371\/journal.pbio.3000410"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"l4898","DOI":"10.1136\/bmj.l4898","article-title":"RoB 2: A Revised Tool for Assessing Risk of Bias in Randomised Trials","volume":"366","author":"Sterne","year":"2019","journal-title":"BMJ"},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Mazzantini, C., El Bourji, Z., Parisio, C., Davolio, P.L., Cocchi, A., Pellegrini-Giampietro, D.E., and Landucci, E. (2024). Anti-Inflammatory Properties of Cannabidiol and Beta-Caryophyllene Alone or Combined in an In Vitro Inflammation Model. Pharmaceuticals, 17.","DOI":"10.3390\/ph17040467"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"100018","DOI":"10.1016\/j.xjidi.2021.100018","article-title":"Characterization of Human Keratinocyte Cell Lines for Barrier Studies","volume":"1","author":"Moran","year":"2021","journal-title":"JID Innov."},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Gull\u00ec, M., Percaccio, E., Di Giacomo, S., and Di Sotto, A. (2022). Novel Insights into the Immunomodulatory Effects of Caryophyllane Sesquiterpenes: A Systematic Review of Preclinical Studies. Appl. Sci., 12.","DOI":"10.3390\/app12052292"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"3713","DOI":"10.1172\/JCI64628","article-title":"Cannabidiol Exerts Sebostatic and Antiinflammatory Effects on Human Sebocytes","volume":"124","author":"Sugawara","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"110216","DOI":"10.1016\/j.neuropharm.2024.110216","article-title":"The Synthetic Cannabinoid Agonist WIN 55,212-2 Reduces Experimental Pruritus via CB2 Receptor Activation","volume":"264","author":"Reck","year":"2025","journal-title":"Neuropharmacology"},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"da Trindade, R., da Silva, J.K., and Setzer, W.N. (2018). Copaifera of the Neotropics: A Review of the Phytochemistry and Pharmacology. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19051511"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1007\/s13555-021-00634-5","article-title":"Prospective, Randomized, Double-Blind, Placebo-Controlled Study on Efficacy of Copaiba Oil in Silicone-Based Gel to Reduce Scar Formation","volume":"11","author":"Waibel","year":"2021","journal-title":"Dermatol. Ther."},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Cardinelli, C.C., Passos, J.T.G., Veiga-Junior, V.F., de Oliveira, B.G.R.B., Santos, E.P.d., Neto, G.G., Di Piero, K.C., and de Freitas, Z.M.F. (2024). Skin Tear Treatment with Copaifera Multijuga Hayne in Polymeric Hydrogel: A Randomized Clinical Trial. Pharmaceuticals, 17.","DOI":"10.3390\/ph17121691"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"e22045","DOI":"10.12707\/RVI22045","article-title":"Cicatriza\u00e7\u00e3o de feridas cr\u00f3nicas tratadas com oleorresina de copa\u00edba","volume":"6","author":"Leite","year":"2023","journal-title":"Rev. Enf. Ref."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1097\/FBP.0000000000000422","article-title":"Anti-NGF Treatment Can Reduce Chronic Neuropathic Pain by Changing Peripheral Mediators and Brain Activity in Rats","volume":"30","author":"Evangelista","year":"2019","journal-title":"Behav. Pharmacol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1002\/ansa.202000158","article-title":"Recent Trends in the Chromatographic Analysis of Volatile Flavor and Fragrance Compounds: Annual Review 2020","volume":"2","author":"Louw","year":"2021","journal-title":"Anal. Sci. Adv."},{"key":"ref_140","unstructured":"U.S. Food and Drug Administration (2025). Product-Specific Guidances for Generic Drug Development."},{"key":"ref_141","unstructured":"Tietje, C., and Brouder, A. (2010). International Conference On Harmonisation Of Technical Requirements For Registration Of Pharmaceuticals For Human Use. Handbook of Transnational Economic Governance Regimes, Brill|Nijhoff."},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"Alharthi, S., Ziora, Z.M., Mustafa, G., Chaubey, P., El Kirdasy, A.F., and Alotaibi, G. (2023). \u03b2-Caryophyllene-Loaded Microemulsion-Based Topical Hydrogel: A Promising Carrier to Enhance the Analgesic and Anti-Inflammatory Outcomes. Gels, 9.","DOI":"10.3390\/gels9080634"},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Ghazwani, M., Hani, U., Alqarni, M.H., and Alam, A. (2023). Beta Caryophyllene-Loaded Nanostructured Lipid Carriers for Topical Management of Skin Disorders: Statistical Optimization, In Vitro and Dermatokinetic Evaluation. Gels, 9.","DOI":"10.3390\/gels9070550"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"24045","DOI":"10.1021\/acsomega.0c03456","article-title":"Preparation and Characterization of Liposomal \u03b2-Caryophyllene (Rephyll) by Nanofiber Weaving Technology and Its Effects on Delayed Onset Muscle Soreness (DOMS) in Humans: A Randomized, Double-Blinded, Crossover-Designed, and Placebo-Controlled Study","volume":"5","author":"Amalraj","year":"2020","journal-title":"ACS Omega"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"106401","DOI":"10.1016\/j.ejps.2023.106401","article-title":"Investigation of \u03b2-Caryophyllene as Terpene Penetration Enhancer: Role of Stratum Corneum Retention","volume":"183","author":"Tang","year":"2023","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/S0928-0987(01)00167-1","article-title":"Novel Mechanisms and Devices to Enable Successful Transdermal Drug Delivery","volume":"14","author":"Barry","year":"2001","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.ejpb.2006.10.019","article-title":"Nanoparticles--an Efficient Carrier for Drug Delivery into the Hair Follicles","volume":"66","author":"Lademann","year":"2007","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"3335","DOI":"10.1080\/14786419.2024.2317887","article-title":"Association Effect of the Phytocannabinoid Beta-Caryophyllene and Indomethacin Carried in Topical Nanoemulgels: An Evaluation by in Vivo Anti-Inflammatory Model","volume":"39","author":"Weimer","year":"2025","journal-title":"Nat. Prod. Res."},{"key":"ref_149","doi-asserted-by":"crossref","unstructured":"Oliveira Ribeiro, S., Fontaine, V., Mathieu, V., Abdesselam, Z., Dominique, B., Caroline, S., and Florence, S. (2021). Antibacterial Activities of Homemade Matrices Miming Essential Oils Compared to Commercial Ones. Antibiotics, 10.","DOI":"10.3390\/antibiotics10050584"},{"key":"ref_150","unstructured":"European Commission (2025, September 25). Cosmetic Ingredient Database. Available online: https:\/\/single-market-economy.ec.europa.eu\/sectors\/cosmetics\/cosmetic-ingredient-database_en."},{"key":"ref_151","unstructured":"European Commission (2025, August 15). CosIng\u2014Cosmetics Ingredients: Function\u2014Skin Conditioning. Available online: https:\/\/ec.europa.eu\/growth\/tools-databases\/cosing\/reference\/functions\/list\/SKIN%20CONDITIONING?utm_source=chatgpt.com."},{"key":"ref_152","unstructured":"U.S. Food and Drug Administration (FDA) (2025, August 15). FDA Authority Over Cosmetics: How Cosmetics Are Not FDA-Approved, but Are FDA-Regulated, Available online: https:\/\/www.fda.gov\/cosmetics\/cosmetics-laws-regulations\/fda-authority-over-cosmetics-how-cosmetics-are-not-fda-approved-are-fda-regulated."},{"key":"ref_153","unstructured":"Panag Pharma Inc (2025, September 17). Randomized, Double Blind, Placebo Controlled Crossover Trial with Open Label Extension of Topical 20% Beta Caryophyllene Alone and in Combination with 0.025% Capsaicin in The Treatment of Pain Caused by Osteoarthritis of The Knee, Available online: https:\/\/clinicaltrials.gov\/study\/NCT03152578."},{"key":"ref_154","unstructured":"Sinai, A., Turner, Z., and Baruch, Y. (2018). Cannabis-Based Extracts and Topical Formulations for Use in Skin Disorders. (2018\/0042890 A1), U.S. Patent."},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Ofir, R., Rachmilevich, S., Amiel, E., Dudai, N., and Rabinski, T. (2012). Compositions Comprising Beta-Caryophyllene and Methods of Utilizing the Same. (WO2012104845A1).","DOI":"10.1155\/2012\/872394"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1016\/j.jpainsymman.2017.06.005","article-title":"Topical Medical Cannabis: A New Treatment for Wound Pain\u2014Three Cases of Pyoderma Gangrenosum","volume":"54","author":"Maida","year":"2017","journal-title":"J. Pain Symptom Manag."},{"key":"ref_157","unstructured":"Mata, J.E. (2021). Multifunctional Topical Cream Comprising Beta-Caryophyllene, Essential Oils, in a Phospholipid and Triglyceride Base. (2020\/0030252 A1), U.S. Patent."},{"key":"ref_158","doi-asserted-by":"crossref","unstructured":"Niyangoda, D., Muayad, M., Tesfaye, W., Bushell, M., Ahmad, D., Samarawickrema, I., Sinclair, J., Kebriti, S., Maida, V., and Thomas, J. (2024). Cannabinoids in Integumentary Wound Care: A Systematic Review of Emerging Preclinical and Clinical Evidence. Pharmaceutics, 16.","DOI":"10.3390\/pharmaceutics16081081"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1080\/15569520902938032","article-title":"The Human Repeated Insult Patch Test in the 21st Century: A Commentary","volume":"28","author":"Basketter","year":"2009","journal-title":"Cutan. Ocul. Toxicol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1097\/DER.0000000000000684","article-title":"Fragrance Skin Sensitization Evaluation and Human Testing: 30-Year Experience","volume":"32","author":"Na","year":"2021","journal-title":"Dermatitis"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1111\/j.0105-1873.2005.00605.x","article-title":"Selected Oxidized Fragrance Terpenes Are Common Contact Allergens","volume":"52","author":"Matura","year":"2005","journal-title":"Contact Dermat."},{"key":"ref_162","unstructured":"European Commission (2009). Regulation (EC) No 1223\/2009 of the European Parliament and of the Council of 30 November 2009 on Cosmetic Products (Recast), European Commission."},{"key":"ref_163","unstructured":"U.S. Food and Drug Administration (FDA) (2025, August 15). Modernization of Cosmetics Regulation Act of 2022 (MoCRA), Available online: https:\/\/www.fda.gov\/cosmetics\/cosmetics-laws-regulations\/modernization-cosmetics-regulation-act-2022-mocra."},{"key":"ref_164","unstructured":"Scientific Committee on Consumer Safety (SCCS) (2025, September 18). SCCS Notes of Guidance for the Testing of Cosmetic Ingredients and Their Safety Evaluation\u201412th Revision. Available online: https:\/\/health.ec.europa.eu\/publications\/sccs-notes-guidance-testing-cosmetic-ingredients-and-their-safety-evaluation-12th-revision_en."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"104","DOI":"10.18433\/J3201Z","article-title":"The Tape-Stripping Technique as a Method for Drug Quantification in Skin","volume":"11","year":"2008","journal-title":"J. Pharm. Pharm. Sci."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"978","DOI":"10.2340\/00015555-2433","article-title":"Itch Assessment with Visual Analogue Scale and Numerical Rating Scale: Determination of Minimal Clinically Important Difference in Chronic Itch","volume":"96","author":"Reich","year":"2016","journal-title":"Acta Dermato-Venereol."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1111\/j.1398-9995.2011.02719.x","article-title":"EASI, (Objective) SCORAD and POEM for Atopic Eczema: Responsiveness and Minimal Clinically Important Difference","volume":"67","author":"Schram","year":"2012","journal-title":"Allergy"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1111\/jdv.13301","article-title":"The Effect of Environmental Humidity and Temperature on Skin Barrier Function and Dermatitis","volume":"30","author":"Engebretsen","year":"2016","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_169","first-page":"1215","article-title":"Racial Disparities in Dermatology","volume":"315","author":"Narla","year":"2023","journal-title":"Arch. Dermatol. Res."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/11\/1605\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T04:38:06Z","timestamp":1761367086000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/11\/1605"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,23]]},"references-count":169,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["ph18111605"],"URL":"https:\/\/doi.org\/10.3390\/ph18111605","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,23]]}}}