The human skin harbors a fully functional peripheral equivalent of the hypothalamic-pituitary-adrenal (HPA) axis documented over 25 years of research culminating in a 2025 Nature Reviews Endocrinology landmark review. This paper proposes JTDA™ (Janela Terapêutica de Dupla Ação / Dual-Action Therapeutic Window), a scoring framework identifying phytochemical compounds that act simultaneously at two windows: (A) the central HPA axis (systemic cortisol modulation) and (B) the peripheral cutaneous HPA axis (direct modulation of CRH-R1, CB2, NF-κB, and neuropeptide cascades in skin cells). Three candidates are characterized: Withania somnifera KSM-66 (JTDA-2), Rhodiola rosea SHR-5 (JTDA-2), and β-caryophyllene from Copaifera spp. (JTDA-3 — the first dietary CB2 agonist with direct cutaneous neuroendocrine action). JTDA™ integrates within the IDIBS™ architecture at 23% sub-index weight and drives the ACALMA™ protocol archetype. This paper represents the first formal operationalization of neuro-nutritional cosmeceutics within Phytodermonutrition™ science.
Willer de Souza (Wed,) studied this question.