a Centre Laser Palaiseau, Palaiseau, France; b Phillip Frost Department of Dermatology, University of Miami Miller School of Medicine, Miami, FL, USA; c Department of Dermatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan; d Singapore Immunology Network (SIgN) & Institute of Medical Biology (IMB), Agency for Science, Technology and Research (A∗STAR), Singapore; e INSERM, CNRS, Immunology and New Concepts in ImmunoTherapy (INCIT), Nantes Université, Nantes, France

The skin is not merely a passive physical barrier but a highly complex sensory organ with rich innervation and immunological activity, housing an intrinsic neuroendocrine system. Keratinocytes, melanocytes, and other cutaneous cells can produce and respond to neuromediators (e.g., β-endorphins, dopamine, serotonin), forming the skin-brain axis (neurocutaneous system) that enables bidirectional communication with the central nervous system (CNS). Disruptions to this axis caused by emotional stress, neuroinflammation, and microbial dysbiosis are implicated in the pathophysiology of dermatological conditions such as atopic dermatitis, psoriasis, and rosacea.

Neurocosmetics is defined as a transdisciplinary field that develops topical agents acting on the skin’s neurosensory system to modulate psychophysiological responses, thereby improving cutaneous function and emotional well-being. Distinct from psychodermatology, which addresses psychiatric comorbidities secondary to skin diseases, neurocosmetics adopts a proactive, integrative approach—using topicals to regulate mood, mitigate stress-related cutaneous reactions, and maintain neurocutaneous homeostasis.

The skin expresses a diverse array of neurotransmitter receptors and neuromediators. Topical application of specific active ingredients targets this system for therapeutic and cosmetic effects: acetyl hexapeptide-8 mimics botulinum toxin to inhibit neurotransmitter release and reduce muscle contraction/wrinkles; cannabinoid receptor agonists alleviate pruritus, inflammation, and modulate mood perception; sensory modulators act on cutaneous mechanoreceptors and transient receptor potential (TRP) channels, and when combined with olfactory/tactile stimuli, achieve emotional coregulation. Common active ingredients and their mechanisms are categorized by their functional roles (e.g., neuropeptides, neurotransmitter modulators, plant adaptogens).

Skin microbial diversity influences barrier integrity and inflammatory status, and modulates emotional states indirectly through the gut-skin-brain axis. Dysbiosis of the gut or skin microbiome activates systemic inflammatory pathways and hypothalamic-pituitary-adrenal (HPA) axis responses, exacerbating mood disorders and cutaneous inflammation. Commensal-derived postbiotics and short-chain fatty acids (SCFAs) from the skin microbiota regulate neuroinflammation and psychological stress, while stress itself alters skin microbial composition—creating a feedback loop that amplifies dermatological and emotional symptoms. Topical postbiotics and microbiome-targeted skincare thus represent a promising adjunct for managing skin sensitivity and stress-induced flare-ups (note: current research in this area remains preclinical/correlative, with causal links yet to be validated).

AI and digital diagnostics are revolutionizing personalized skincare by moving beyond image-based skin type analysis. Novel AI models detect emotional biomarkers via facial micro-expressions, thermal imaging, and skin tone fluctuations associated with stress/fatigue, enabling the development of emotion-responsive skincare regimens. For example, AI can identify early signs of emotional dysregulation in patients with stress-exacerbated skin conditions, guiding targeted application of neuroactive topicals during high-stress periods.

Wearable sensors and mobile apps integrate emotion tracking, circadian rhythm analysis, and skin conductance measurements to tailor the timing and type of neurocosmetic application—an approach that aligns with chronodermatology and incorporates real-time mood feedback. This fusion of neuroscience, dermatology, and data science shifts the paradigm from static skincare routines to dynamic, neuro-responsive interventions that stabilize both the skin and psyche.

The modulation of emotional states via topical neurocosmetic agents raises critical questions regarding safety, transparency, and long-term psychoneurobiological effects. Potential risks include off-target effects and psychological dependency, necessitating rigorous clinical evaluation. For AI-guided neurocosmetic tools, ensuring data privacy, algorithmic fairness, and informed patient consent is essential. Interdisciplinary collaboration between dermatologists, neuroscientists, psychologists, ethicists, and regulatory bodies is required to establish responsible frameworks for the field’s development.

Most neurocosmetic formulations remain in preclinical or early clinical stages, with a lack of standardized outcome measures. Current findings are largely based on in vitro/animal models, and human trials rely heavily on subjective assessments (e.g., self-reported mood, stress perception). The subjectivity of emotional responses, combined with strong placebo effects in cosmetic trials, hinders the establishment of causal links between neurocosmetic actives and psychophysiological outcomes. Additionally, individual variability in neurocutaneous signaling, skin type, and microbiome composition limits the generalizability of results. Objective emotional biomarkers (e.g., salivary cortisol, heart rate variability) are rarely integrated into dermatological research, and unified regulatory guidelines for psychodermatologic endpoints are absent.

Future research must translate the conceptual promise of neurocosmetics into validated clinical applications, including the development of standardized protocols to assess the effects of neuroactive topicals on cutaneous neuromediator levels and psychological outcomes. Longitudinal, well-designed human trials with multimodal assessments (combining dermatological metrics and psychometric tools) are urgently needed to confirm efficacy and safety. Digital diagnostics and wearable biosensors will further enable real-time, personalized interventions based on stress/emotional biomarkers, with psychophysiological endpoints (e.g., heart rate variability, salivary cortisol) becoming key for evaluating neurocosmetic efficacy.

Neurocosmetics represents a paradigm shift in dermatology and cosmetic science, embracing the skin as a dynamic neurobiological interface between the body, brain, and environment. By targeting both somatic and emotional pathways, it provides a science-based approach to integrative, psychophysiologically aware skincare, meeting the growing demand for holistic skin health solutions. As the field matures, it will evolve into a distinct area of translational research—bridging neurocutaneous mechanisms, sensorial pharmacology, and digital health—to redefine skin health as an interplay of structure, function, and affect.

Declaration of Competing Interest: The authors declare no financial or commercial conflicts of interest related to this work, and no funding was received for the study.