Neurocosmetics and Aromatherapy Through Neurocutaneous Receptors and Their Functional Implications in Cosmetics

Abstract

There is little scientific evidence for many of the medical benefits attributed to aromatherapy and neurocosmetics; however, they have been shown to be useful in the management of symptoms such as pain, nausea, general well-being, anxiety, depression, stress, and insomnia through various mechanisms, including the olfactory pathway and activation of TRPV and CBD receptors. This review therefore aims to compile the most relevant literature on active ingredients proven effective in neurocosmetics and aromatherapy, as well as the mechanisms responsible for their function, in order to highlight how they can be synergistically integrated into a new generation of multifunctional formulations forming the basis of neuro-functional skin care.

1. Introduction

Aesthetic beauty is the holistic interrelation of mind and body. Over the past few decades, the concept of beauty has taken a new course in which focus on physical appearance has given way to the notion of greater emotional well-being. This developing vision recognizes that the essence of beauty and skin health in the individual also depends upon emotional, neuropsychological, and sensory parameters [1,2,3].

Within this framework, neurocosmetics are defined as products capable of modulating the activity of the neuro-immuno-cutaneous system at the epidermal level. These products have gained increasing relevance as a transdisciplinary field of study, focused on the complex and dynamic biochemistry of skin–nerve interactions, and are establishing themselves as a cutting-edge area within current cosmetic science [4].

From a neurophysiological perspective, the skin is viewed as a very specialized neuroendocrine and immunological organ, closely linked with the central nervous system through a sophisticated network of sensory receptors, nerve endings, neuropeptides, and neurotransmitters.

This subtle system lets some active ingredients—such as biomimetic peptides, botanical extracts, or volatile compounds—target molecular pathways that not only modulate the key processes at work in the skin (such as inflammation, aging, and tissue renewal) but also affect emotional states by either calming stress and anxiety or fostering a general sense of well-being. In parallel, aromatherapy has attracted renewed interest from the scientific community, as it has the power to modulate the limbic system through odors [5,6,7,8].

The olfactory pathway has a unique anatomical connection to the limbic system, unlike other sensory systems that require prior relay through the thalamus. This distinctive feature allows olfactory stimuli—such as essential oils used in aromatherapy—to trigger immediate emotional and physiological responses (Figure 1). Structurally, this sensory pathway begins in the olfactory epithelium of the nasal cavity, where aromatic molecules bind to specific receptor proteins on olfactory neurons. These signals are transmitted via the olfactory nerve to the olfactory bulb and then through the olfactory tract to key brain regions within the limbic system, including the amygdala, piriform cortex, and entorhinal cortex. This intimate connection between smell, emotion, and memory explains why certain scents can evoke vivid recollections or elicit strong emotional states [8].

Several studies have shown that aromatherapy not only modulates brain activity but also exerts beneficial effects on mental health. For instance, a clinical trial conducted at the Jeju National University Hospital evaluated the impact of an essential oil massage program on neurobiological and psychological variables in women who were caregivers of children with attention-deficit/hyperactivity disorder (ADHD). Participants were randomly assigned to either an experimental group (n = 13), which received a 40 min massage with lavender and geranium essential oils twice a week for four weeks, or a control group with no treatment (n = 12). The results revealed a significant reduction in levels of anxiety, depression, and stress, accompanied by a decrease in salivary cortisol and an increase in plasma levels of brain-derived neurotrophic factor (BDNF). These findings suggest that the intervention exerted a regulatory effect on the hypothalamic–pituitary–adrenal (HPA) axis, as well as a potential neuroprotective mechanism mediated by olfactory stimulation with essential oils [9].

Olfactory stimulation has also been shown to influence various brain functions, particularly those related to cognition and mental flexibility. In a recent study, the effects of inhaling lavender essential oil on brain activity dynamics and cognitive performance were assessed in 20 healthy adults. Participants completed a set-shifting task under two conditions: without aromatic stimulation and with olfactory exposure to lavender oil. Using electroencephalographic (EEG) recordings and normalized power spectral density (PSD) analysis across five frequency bands, researchers observed that lavender inhalation significantly increased theta, alpha, and beta wave activity—associated with relaxation, focus, and cognitive agility—while delta wave activity, linked to unconscious states, was reduced. Behaviorally, participants demonstrated greater response accuracy and shorter reaction times, suggesting improved cognitive flexibility. These findings provide neurophysiological evidence for the potential of aromatherapy as a non-invasive strategy to enhance mental performance in contexts requiring adaptability and sustained attention [10,11].

Table 1. Some essential oils used in aromatherapy, their main functions, and their active compounds.

Entry	Essential Oil	Main Function in Aromatherapy	Some of the Main Active Compounds	References
1	Lavender	Relaxing, anti-anxiety	Linalool, Linalyl acetate	[12,13,14,15,16]
2	Tea Tree	Antiseptic, immune support	Terpinen-4-ol, α-Terpinene	[17,18]
3	Peppermint	Stimulating, decongestant, neuroprotective effect	Menthol, Menthone	[19,20,21,22,23,24]
4	Eucalyptus	Respiratory relief, antibacterial, central nervous system	1,8-Cineole, α-Pinene	[25,26,27,28]
5	Lemon	Uplifting, refreshing, stress-related disorders/mood disorders	Limonene, Citral	[29,30,31]
6	Sweet Orange	Mood enhancer, calming, pain and anxiety	Limonene, Linalol, Myrcene	[32,33,34,35,36,37]
7	Chamomile	Anti-inflammatory, soothing, anxiety	Chamazulene, Bisabolol, Matricine	[38,39,40,41,42,43]
8	Rosemary	Mental clarity, energizing	1,8-Cineole, Camphor, α-Pinene	[44,45,46,47,48]
9	Frankincense	Grounding, stress relief	α-Pinene, Incensole acetate	[6,49]
10	Ylang-Ylang	Balancing, mood enhancing	Linalool, Geranyl acetate	[50,51,52,53,54]
11	Cedarwood	Calming, sedative	Cedrol, Thujopsene	[55,56]
12	Bergamot	Stress reduction, mood enhancer	Linalyl acetate, Limonene	[57,58,59]
13	Geranium	Balancing hormones, skincare	Geraniol, Citronellol	[60,61,62]
14	Clary Sage	Hormonal balance, antidepressant	Linalyl acetate, Sclareol	[6,63,64,65]
15	Lemongrass	Detoxifying, purifying	Citral, Geraniol	[66,67,68,69]
16	Patchouli	Earthy, aphrodisiac	Patchoulol, Norpatchoulenol	[70,71,72]
17	Jasmine	Euphoric, soothing	Benzyl acetate, Jasmonates	[73,74,75]
18	Sandalwood	Grounding, meditative	Santalol, β-Santalene	[76,77,78,79]
19	Basil	Mental alertness, fatigue	Linalool, Methyl chavicol	[80,81,82]
20	Cypress	Circulation booster, calming	α-Pinene, Limonene	[83,84]
21	Marjoram	Muscle relaxation, sleep aid	Terpinen-4-ol, Sabinene	[85,86,87]
22	Thyme	Immune support, purifying	Thymol, Carvacrol	[88,89,90]
23	Oregano	Antiviral, immune booster	Carvacrol, Thymol	[91,92]
24	Ginger	Warming, anti-nausea	Zingiberene, β-Bisabolene	[93,94]
25	Fennel	Digestive aid, calming	Anethole, Fenchone	[95,96,97]
26	Spearmint	Mental clarity, digestive support	Carvone, Limonene	[97,98,99]
27	Cinnamon	Stimulant, warming, mental clarity	Cinnamaldehyde, Eugenol	[100,101,102]
28	Myrrh	Soothing, skincare	Furanosesquiterpenoids, Curzerene	[103,104,105]
29	Neroli	Nervous tension, uplifting, anxiety	Nerolidol, Linalool	[102,106,107,108]
30	Helichrysum	Skin regeneration, wound healing	Italidione, Geranyl acetate, α-Cedrene	[109,110]
31	Pine	Respiratory support, energizing	α-Pinene, β-Pinene	[84,111,112]
32	Tangerine	Cheering, emotional balance	Limonene, γ-Terpinene	[113]
33	Petitgrain	Nervous system calming	Linalyl acetate, Geraniol	[114,115,116]
34	Juniper Berry	Reduce stress and instill calm	α-Pinene, β-Myrcene	[117,118,119]
35	Black Pepper	Pain relief, neuroprotective, anxiolytic	Piperine, Piperlonguminine	[120,121,122]
36	Melissa (Lemon Balm)	Calming, antidepressant	Citral, β-Caryophyllene	[123,124,125,126]
37	Bay Laurel	Respiratory and lymphatic support	1,8-Cineole, Sabinene, Linalool	[127,128]
38	Turmeric	Mental disorders, including depression	Curcumin, Turmerone	[129,130,131]
39	Citronella	Mood states and brain activities	Citronellal, Geraniol	[132,133,134]
40	Wintergreen	Analgesic, anti-inflammatory	Methyl salicylate	[135,136]
41	Copaiba	Reducing anxiety	β-Caryophyllene, α-Humulene	[137,138]
42	Valerian	Reduction in stress and sleep problems	Valerenic acid, Bornyl acetate	[139,140,141,142]

summarizes some essential oils used in aromatherapy, highlighting their main therapeutic functions, relevant active compounds, and corresponding references. This compilation reveals the remarkable diversity of chemical profiles and associated sensory and physiological effects of essential oils, supporting their increasing integration into neurocosmetic formulations.

Essential oils such as lavender (Entry 1), bergamot (Entry 12), ylang-ylang (Entry 10), neroli (Entry 29), and melissa (Entry 36) share anxiolytic and relaxing activity, generally attributed to the presence of monoterpenes such as linalool, linalyl acetate, or citral. These compounds have been shown to modulate central nervous system activity by acting on GABAergic and serotonergic receptors, which justifies their use for inducing calm, improving sleep, and reducing stress. In contrast, oils like peppermint (Entry 3), rosemary (Entry 8), basil (Entry 19), or cinnamon (Entry 27) exhibit stimulating and mentally clarifying effects due to components such as menthol, 1,8-cineole, or methyl chavicol. These molecules can enhance alertness, focus, and cognitive performance through noradrenergic and dopaminergic pathways.

Several oils present dual cutaneous and emotional functions, making them particularly attractive for neurocosmetic development. For example, jasmine (Entry 17) and rose (not listed in the table but commonly cited with geraniol and citronellol) not only induce euphoria and well-being but also possess anti-inflammatory and skin-regenerative properties mediated by compounds such as benzyl acetate or geraniol. Similarly, helichrysum (Entry 30) promotes skin regeneration, while turmeric (Entry 38) and ginger (Entry 24) have been explored for their neuroprotective potential, linked to their systemic antioxidant and anti-inflammatory effects.

It is important to highlight that several of these oils—such as thyme (Entry 22), oregano (Entry 23), tea tree (Entry 2), and cinnamon (Entry 27)—possess immunomodulatory or antimicrobial properties, enabling their use in cosmetics with protective or purifying functions. The synergy between sensory (olfactory) impact and topical activity reinforces the skin–brain axis hypothesis as a therapeutic target in modern neurocosmetics.

Finally, some oils, such as valerian (Entry 42), vetiver (not included in this table), or wintergreen (Entry 40), show specific applications in the management of pain, inflammation, or sleep disorders, extending their utility beyond the cosmetic realm and positioning them as potential adjuvants in the treatment of psychophysiological conditions.

Altogether, the functional and chemical diversity of essential oils supports their potential as multifunctional ingredients in neurocosmetic formulations—aimed not only at improving the skin’s physical appearance but also at eliciting positive emotional states through sensory and neurocutaneous pathways.

This multidimensional action of essential oils—combining emotional modulation with cutaneous effects—aligns with the growing understanding of the skin as more than a passive barrier. Instead, it functions as an active neuro-immuno-endocrine interface capable of perceiving, responding to, and even generating biochemical signals that influence both local and systemic physiology. This conceptual framework forms the foundation of neurocosmetics, where the interaction between the skin and the nervous system is leveraged to promote not only dermatological health but also emotional well-being through targeted sensory pathways.

1.1. The Skin as a Neuroendocrine–Sensory Organ: Functional Basis

The skin is not only a physical barrier, but it is a specialized neuroendocrine and immune organ with complex signaling to the central nervous system [143,144]. This network consists of peripheral nerve fibers and their endings, free nerve endings, and immunocompetent cells, together with molecular receptors for the transduction and detection of internal and external stimuli. Furthermore, several (epidermal) cell types, i.e., keratinocytes, melanocytes, and Langerhans cells, have the ability to synthesize and release neuromediators and neurohormones, like substance P, β-endorphin, gamma-aminobutyric acid (GABA), and melatonin. These compounds are integral to the maintenance of local balance in vital humoral reactions such as inflammation, tissue repair, pigmentation, nociception, and cutaneous comfort sensation [145,146,147].

1.2. Neurocutaneous Receptors and Their Functional Implications

The skin’s neuroactive functionality is supported by the expression of a wide range of specialized receptors that mediate responses to physicochemical and neurosensory stimuli. Among the most relevant are the following:

Transient Receptor Potential (TRP) Channels [148,149]: Transient Receptor Potential (TRP) channels are sensory ion channels in the skin that respond to physical and chemical stimuli like heat, cold, pH changes, and irritants. Found in keratinocytes, sensory neurons, melanocytes, and immune cells, they help regulate pain, itch, inflammation, pigmentation, and wound healing. Dysfunctions in these channels are linked to skin conditions such as dermatitis, vitiligo, alopecia, and chronic itch. Key TRP types include TRPV1 (heat, capsaicin), TRPA1 (cold, oxidative stress), TRPM8 (cold sensing), and TRPM1 (pigmentation). As mediators between environmental stimuli and skin responses, TRP channels are promising targets for dermatological and neurocosmetic treatments (Figure 2).

Cannabinoid Receptors (CB1 and CB2) [150,151,152]: Involved in skin homeostasis, these receptors modulate crucial functions such as inflammation, nociception, sebum production, and immune regulation. Activation of these receptors by both phytocannabinoids and endogenous ligands has stimulated interest in the clinical use of cosmeceuticals.

Cannabinoid receptors CB1 and CB2 are the primary receptor components of the endocannabinoid system and belong to the family of G protein-coupled receptors (GPCRs), characterized by the presence of seven transmembrane domains. These receptors can be activated by both phytocannabinoids (such as Δ⁹-tetrahydrocannabinol [THC] and cannabidiol [CBD]) and endogenous ligands (anandamide and 2-arachidonoylglycerol [2-AG]), which has driven extensive research into their therapeutic potential, including applications in the field of cosmeceuticals.

CB1 receptors are mainly expressed in the central nervous system, although they have also been identified in peripheral tissues. Their activation is directly associated with the psychoactive effects of THC and is involved in the regulation of various physiological processes, including nociception, stress response, appetite, lipogenesis, and immune modulation. However, CB1 stimulation can also lead to adverse effects such as cognitive impairment, anxiety, and the potential for dependency.

In contrast, CB2 receptors are predominantly expressed in immune cells, including B lymphocytes, macrophages, NK cells, and microglia. Their activation significantly modulates inflammatory and immune responses without inducing psychotropic effects, making them an attractive therapeutic target for autoimmune diseases, neuroinflammatory disorders, and transplant rejection prevention.

In the skin, both receptors have been shown to play an active role in maintaining cutaneous homeostasis by modulating key processes such as inflammation, peripheral nociception, sebum production, and local immune responses. The functional presence of these receptors in skin cells has sparked growing interest in developing cosmeceutical formulations that leverage their regulatory effects for the treatment of dermatological conditions and the promotion of skin health.

Figure 3 presents a schematic comparison of CB1 and CB2 cannabinoid receptors, highlighting their cellular localization and key physiological functions. The CB1 receptor is primarily located in the central and peripheral nervous systems, including the skin, where it mediates the psychoactive effects of THC and regulates pain, stress, inflammation, nociceptive perception, and sebum production. Conversely, the CB2 receptor is predominantly expressed in immune cells such as B lymphocytes, NK cells, macrophages, and microglia, where it contributes to immune response modulation, inflammation control, and physiological processes related to transplant response.

This differential distribution suggests complementary roles for both receptors in neuroimmune-cutaneous homeostasis, positioning the endocannabinoid system as a relevant therapeutic target in both dermatology and immunomodulation.

Serotonergic and Dopaminergic Receptors [153,154,155]: Both expressed in keratinocytes and melanocytes, it is speculated that they could be involved in cell proliferation, pigmentation, and mood regulation by the use of the same signaling cascades used by the nervous system.

In recent years, an integrative view of the skin has emerged, recognizing it as a highly specialized neuro-immuno-endocrine organ, capable of perceiving, processing, and responding to environmental stimuli through a complex network of cellular communication. Within this network, melanocytes are no longer regarded solely as pigment-producing cells but rather as multifunctional neuroectodermal sensors. These cells not only synthesize melanin for photoprotection but also secrete neurotransmitters, neuropeptides, and hormones and express ectopic sensory systems similar to those found in the retina and olfactory mucosa. Through these capabilities, melanocytes actively participate in light detection, local circadian rhythm regulation, inflammation, wound healing, and epidermal immune responses [153].

In parallel, a functional intrinsic serotoninergic/melatoninergic system has been identified in the skin, operating independently of the central axis, with the capacity to synthesize and metabolize these neuromodulators locally. Key enzymes such as TPH1, AANAT, and HIOMT have been detected in melanocytes, keratinocytes, fibroblasts, and cutaneous tumor cells. Moreover, the presence of specific receptors for serotonin (5-HT1A, 2A, 2B, 7) and melatonin (MT1) in various skin layers suggests a complex signaling system that regulates proliferation, pigmentation, inflammation, and oxidative stress. Functional evidence from cell and animal models has demonstrated that these compounds modulate the hair cycle, skin homeostasis, and the response to environmental stressors, consolidating their relevance as promising targets for new therapeutic and cosmetic interventions [154].

Simultaneously, dopamine—classically known for its role in central neurotransmission—has emerged as a significant immunomodulator in both the central nervous system and peripheral tissues, including the skin. Various immune cells express dopaminergic receptors and enzymes involved in dopamine synthesis, degradation, and transport, enabling them to respond through autocrine and paracrine mechanisms. Depending on the receptor subtype activated, dopamine may either promote or inhibit inflammatory processes, influencing functions such as phagocytosis, cytokine secretion, and cell migration. These context-dependent actions position dopamine as a key regulator at the neuroimmune interface, and its dysregulation may contribute to inflammatory, neurodegenerative, and autoimmune diseases. Investigating its role in the cutaneous environment represents an emerging avenue for understanding skin pathophysiology and developing novel therapeutic strategies [156].

Cutaneous Olfactory Receptors [5,157,158,159,160]: Recently found on epidermal cells, these receptors allow the perception of volatile molecules applied to the skin; the process is uncoupled from the nasal olfactory system. Activation of these channels elicits intracellular responses that may modulate regeneration, inflammation, and sensation.

Taken together, the skin emerges as a bona fide peripheral sensory organ that participates in emotional cognition of and reaction to the environment. This physiological model forms the scientific basis for the effect of neuroactive actives in high-tech cosmetics.

Olfactory systems in animals have evolved a sophisticated architecture to detect, discriminate, and interpret a vast diversity of chemical signals that are fundamental to survival and social behavior. In both insects and mammals, olfactory receptor neurons (ORNs)—which typically express one or a few specific receptors—project their axons toward highly organized glomeruli within structures such as the antennal lobe or olfactory bulb, where sensory processing begins through mechanisms such as lateral inhibition, non-linear amplification, and interneuron-mediated modulation [161]. This processing results in spatiotemporal neural representations that are decoded by higher brain centers, including the piriform cortex and mushroom bodies, enabling an efficient combinatorial coding that integrates memory, emotion, and behavior. In parallel, the concept of “olfactory spaces” has been proposed to link the chemical structure of odorants with their neural and perceptual correlates, opening new avenues for modeling and predicting olfactory perception.

Complementarily, recent studies have revealed that olfactory receptors (ORs), beyond their traditional sensory function, are ectopically expressed in non-olfactory tissues such as the skin, gut, immune system, and central nervous system (CNS), where they fulfill specific physiological roles [159]. In the CNS, ORs have been detected in neurons, astrocytes, and microglia within neurogenic niches like the dentate gyrus of the hippocampus and the subventricular zone, where they may modulate neuronal differentiation, synaptic plasticity, and cell survival. In vitro assays using odorants such as β-ionone and sandalore have shown activation of specific ORs, such as OR2AT4, leading to enhanced cell proliferation, migration, and differentiation.

Furthermore, olfactory ensheathing glia (OEG)—which naturally support regeneration of the olfactory epithelium—have demonstrated the ability to promote axonal growth, angiogenesis, and remyelination in spinal cord injury models.

It has also been proposed that ectopic ORs can be activated by a broad range of endogenous ligands, including short-chain fatty acids, microbiota-derived metabolites, and steroid hormones, expanding their role as functional sensors in diverse physiopathological contexts [158]. The interaction of ORs with other signaling proteins, such as β-adrenergic receptors, suggests a complex network of intracellular regulation with potential therapeutic applications.

Collectively, current evidence supports the study of ectopic olfactory receptors as key elements in neuroregenerative processes and highlights their potential as molecular targets for the treatment of neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and spinal cord injuries.

1.3. Neuroactive Ingredients

Neurocosmetic actives act on specific receptors present on the skin, modifying sensory and physiological responses. These bioactive chemicals can act on pathways associated with inflammation, neurosensory perception, sebum production, pigmentation, and tissue repair. Their effect is not just limited to the skin, since they participate in the modulation of emotional states via skin–brain communication [162].

In recent years, the development of neurocosmetics has transformed the traditional concept of skin care, promoting an integrative approach that considers both cutaneous physiology and the individual’s emotional state. This emerging category of cosmetic products arises from the recognition that the skin is not merely a physical barrier but a highly sensory neuroendocrine and immunological organ, capable of perceiving, processing, and responding to environmental stimuli. Its common embryological origin with the nervous system explains the complex bidirectional communication network between the skin and the brain, known as the skin–brain axis.

The skin contains numerous neurosensory receptors, including TRPV1, serotoninergic, dopaminergic, and melatoninergic receptors, as well as POMC-derived peptides such as ACTH, α-MSH, and β-endorphins. These systems play crucial roles in regulating processes such as inflammation, pigmentation, itching, sensitivity, and stress response [163]. When these pathways are disrupted—such as during chronic stress, aging, or persistent inflammation—visible skin dysfunctions may occur. Neurocosmetic strategies aim to restore this balance through specific molecular mechanisms.

One of the most relevant targets is the TRPV1 channel, which is involved in neurosensory sensitivity, inflammation, and thermally induced aging. Its modulation helps soothe sensitive skin and reduce redness. Another key target is the enzyme 11β-HSD1, which converts cortisone into cortisol and contributes to structural skin damage. Inhibiting 11β-HSD1 reduces local cortisol overload, improving skin firmness and elasticity.

Recent advances in skin biology have highlighted the importance of neuroendocrine signaling and longevity-associated pathways in maintaining skin homeostasis and delaying visible aging. Among the central molecular regulators, FOXO (Forkhead box O) and KLOTHO have emerged as critical players in cellular repair, oxidative stress resistance, and tissue longevity. FOXO transcription factors promote DNA repair and antioxidant defense, while KLOTHO exerts anti-inflammatory, anti-senescent, and metabolic effects. Together, they contribute synergistically to skin resilience and healthy aging [164].

Simultaneously, the activation of the POMC (proopiomelanocortin) pathway has gained recognition for its role in the neurocutaneous axis. Stimulation of this pathway induces the release of β-endorphins, endogenous opioids that bind to skin receptors and enhance the perception of comfort and well-being. This dual mechanism—structural protection via FOXO/KLOTHO and sensory modulation via β-endorphins—underscores the integrative potential of neurocosmetics, which aim to address both the physiological and emotional dimensions of skin health.

A wide variety of active ingredients have demonstrated efficacy through in vitro, ex vivo, and even clinical studies, consolidating the scientific foundation of this new generation of multifunctional topical products.

Table 2 presents representative examples of ingredients used in neurocosmetics, along with their molecular targets, physiological effects on the skin, and their perceived sensory or emotional impact. These actives range from biotechnological compounds and biomimetic peptides to essential oils and natural molecules, all capable of modulating specific receptors in the skin or the peripheral nervous system. This interaction results not only in objective skin improvements—such as reduced inflammation, regulated sebum production, enhanced microcirculation, or a strengthened epidermal barrier—but also in measurable subjective sensory effects, including relaxation, freshness, comfort, or mood enhancement. This multidimensional approach reflects the emerging paradigm of functional neurocosmetics, which aims to act simultaneously on the skin–brain–emotion axis to promote holistic well-being.

The table offers an integrated view of how different neuroactive ingredients act on well-characterized molecular receptors. For instance, palmitoyl tetrapeptide-7 targets inflammatory pathways, reducing the expression of proinflammatory cytokines, which improves skin firmness and induces a sense of relief and comfort. Similarly, niacinamide interacts with receptors such as GPR109A and immunological pathways, enhancing the skin barrier, decreasing hyperpigmentation, and alleviating discomfort in sensitive skin.

Another notable example is cannabidiol (CBD), which binds to CB1 and CB2 cannabinoid receptors to regulate sebum production, reduce inflammation, and produce emotionally relaxing effects. Menthol, through the activation of TRPM8 ion channels, generates an immediate sensation of freshness and local relief, while capsaicin, acting on TRPV1, stimulates microcirculation and produces a warming, revitalizing effect.

Botulinum-like peptides, designed to mimic botulinum toxin’s action at neuromuscular junctions, visibly reduce expression lines and induce a subjective sensation of facial relaxation—highly valued in anti-aging treatments.

Likewise, natural ingredients such as ylang-ylang and lavender essential oils act via the olfactory pathway, modulating the limbic system: the former with antioxidant and toning properties, and the latter promoting deep relaxation and improved sleep quality through GABA receptor interactions.

Citral-rich compounds, found in lemon or verbena essential oils, also act on olfactory receptors associated with the limbic system, evoking sensations of optimism, vitality, and freshness, while providing toning and revitalizing effects on the skin. Lastly, enkephalins—small endogenous opioid peptides—bind to cutaneous opioid receptors, delivering pain relief, increased comfort, and a pleasant sensory experience that fosters emotional well-being.

Together, these examples illustrate the wide array of mechanisms by which neurocosmetic actives can modulate both skin functions and neurosensory responses. This biological-perceptual synergy forms the foundation of modern neurocosmetics, capable of addressing both physical and emotional well-being through innovative topical formulations.

The use of these functional ingredients has enabled the development of neurocosmetics indicated for sensitive, aging, inflamed, or pigmented skin. Notably, clinical and preclinical studies have demonstrated benefits such as reduction in signs of cutaneous stress, restoration of barrier function, increased sensory resilience, improved skin texture and tone, and enhanced subjective perceptions of comfort and well-being.

However, this innovative approach also poses significant regulatory challenges. According to European Regulation (EC) No. 1223/2009, a cosmetic product must be intended for application to the external parts of the human body, and its effects must remain limited to surface-level actions, without significantly altering physiological functions [165]. Nevertheless, many neurocosmetics interact with molecular pathways that could be interpreted as pharmacological, creating ambiguity regarding their classification. As a result, the category of “borderline products” has emerged—those whose nature may fall between cosmetic, medicinal, or medical device, depending on application site, absorption route, active ingredient concentration, and mechanism of action [166].

To address this issue, the European Commission has published the Borderline Products Manual, a guiding document to help determine on a case-by-case basis whether a product qualifies as a cosmetic. It relies on three criteria: type of product, site of application, and intended cosmetic purpose. For example, an anti-wrinkle product will be considered a cosmetic if it acts on external appearance, but not if it significantly alters physiological functions like collagen synthesis through pharmacological pathways. In the case of neurocosmetics, this distinction is especially relevant, as many ingredients act at the dermal or neurosensory level, requiring detailed evaluation and strong scientific evidence to support their claims.

Moreover, international regulation remains heterogeneous: while Europe has clear regulatory frameworks, in other markets such as the United States or China, classification of these products is still uncertain, which limits their global positioning.

Table 2. Examples of neurocosmetic actives and their cutaneous/sensory effects.

Entry	Neurocosmetic Active	Receptor/Target	Cutaneous Effect	Emotional/Sensory Effect	References
1	Palmitoyl tetrapeptide-7	Cytokine/pro-inflammatory receptors	Reduces inflammation, improves firmness	Sensation of relief and comfort	[167]
2	Niacinamide	GPR109A, immune receptors	Enhances skin barrier, reduces hyperpigmentation	Decreases discomfort in sensitive skin	[168]
3	Cannabidiol (CBD)	Cannabinoid receptors CB1, CB2	Regulates sebum, anti-inflammatory	Promotes relaxation, reduces anxiety	[169]
4	Menthol	TRPM8 ion channels	Cooling, soothing effect	Induces freshness, immediate local relief	[170]
5	Capsaicin	TRPV1 ion channels	Stimulates microcirculation, enhances skin tone	Mild warming sensation, invigorating effect	[171,172,173]
6	Botulinum-like peptides	Neuronal receptors at neuromuscular junction	Smoothes expression lines	Sensation of facial relaxation and skin smoothing	[162,174,175]
7	Ylang-ylang essential oil	Limbic system via olfactory route	Antioxidant, skin toning properties	Promotes relaxation, stress relief	[53,176,177]
8	Lavender essential oil	GABA receptors/limbic system	Calms irritation, improves sleep quality	Deep relaxation, anxiety reduction	[178,179,180]
9	Citral compounds	Olfactory/limbic receptors	Brightens and revitalizes skin	Enhances mood, induces optimistic and energizing sensations	[181,182,183]
10	Enkephalins	Cutaneous opioid receptors	Pain relief, increases skin comfort	Pleasant sensation, supports general emotional well-being	[184,185,186,187]

Table 2. Examples of neurocosmetic actives and their cutaneous/sensory effects.

Entry	Neurocosmetic Active	Receptor/Target	Cutaneous Effect	Emotional/Sensory Effect	References
1	Palmitoyl tetrapeptide-7	Cytokine/pro-inflammatory receptors	Reduces inflammation, improves firmness	Sensation of relief and comfort	[167]
2	Niacinamide	GPR109A, immune receptors	Enhances skin barrier, reduces hyperpigmentation	Decreases discomfort in sensitive skin	[168]
3	Cannabidiol (CBD)	Cannabinoid receptors CB1, CB2	Regulates sebum, anti-inflammatory	Promotes relaxation, reduces anxiety	[169]
4	Menthol	TRPM8 ion channels	Cooling, soothing effect	Induces freshness, immediate local relief	[170]
5	Capsaicin	TRPV1 ion channels	Stimulates microcirculation, enhances skin tone	Mild warming sensation, invigorating effect	[171,172,173]
6	Botulinum-like peptides	Neuronal receptors at neuromuscular junction	Smoothes expression lines	Sensation of facial relaxation and skin smoothing	[162,174,175]
7	Ylang-ylang essential oil	Limbic system via olfactory route	Antioxidant, skin toning properties	Promotes relaxation, stress relief	[53,176,177]
8	Lavender essential oil	GABA receptors/limbic system	Calms irritation, improves sleep quality	Deep relaxation, anxiety reduction	[178,179,180]
9	Citral compounds	Olfactory/limbic receptors	Brightens and revitalizes skin	Enhances mood, induces optimistic and energizing sensations	[181,182,183]
10	Enkephalins	Cutaneous opioid receptors	Pain relief, increases skin comfort	Pleasant sensation, supports general emotional well-being	[184,185,186,187]

These neuroactive ingredients serve as a model for which state-of-the-art cosmetic compositions can address cutaneous health and emotional status for functional, sensorially driven skin care. In this context, their potential to act via topical-/olfactory-mediated administration also broadens their utility in holistic formulations that aim to moderate the skin–brain axis.

1.4. Biomimetic Peptides: An Advanced Molecular Strategy in Neurocosmetics

This review will focus, among other relevant actives of neurocosmetics, on biomimetic peptides, which can modulate in an anodyne way the crucial cellular processes, imitating properly the natural function of the growth factor [167,188,189,190]. These synthetic oligopeptides, usually 10–15 amino acids in length, possess several advantages over natural peptides, such as increased chemical stability, low molecular weight, superior skin penetration, low toxicity, and lower cost of production.

In cosmetic dermatology, biomimetic peptides find broad use in anti-aging, depigmenting, hair-growth-stimulating, and anti-inflammatory formulations [191,192]. They work by fighting against the degradation of the extracellular matrix, which is caused by intrinsic (e.g., oxidative stress and cellular metabolism) and extrinsic factors (e.g., UV radiation and air pollution).

Biomimetic peptides can be functionally divided into four main groups (Figure 1):

• Signaling peptides: Encourage the production of collagen and elastin and other extracellular matrix (ECM) proteins.
• Carrier peptides: Enhance the penetration of vital trace elements (copper and manganese).
• Enzyme inhibitory peptides: Inhibit enzymes that break down the extracellular matrix.
• Neurotransmitter-inhibiting peptides: Reduce the action of facial muscle contraction, also helping to diminish dynamic wrinkles.

The latter group (neurotransmitter-inhibiting peptides) includes compounds such as acetyl hexapeptide-3 (also known as Argireline^®) and acetyl octapeptide-3 (also known as Snap-8), since they block acetylcholine release by hindering the formation of the SNARE complex and therefore all work at the same mechanism of botulinum toxins but with a better safety profile [188,193]. Others, like Vialox^® or Syn-Ake^® [194], act through antagonizing the postsynaptic receptors, whereas opioid-like peptides like Leuphasyl^® [195] and Peptilift^® [192] induce muscle relaxation through stimulation of cutaneous opioid receptors.

Altogether, biomimetic peptides are bridging a critical gap in the cosmetic industry, enabling the rational design of next-generation products with targeted activity at both structural and neurosensory levels. However, some of these compounds still require independent clinical validation to confirm their individual efficacy within complex, multi-ingredient formulations.

Table 3. Bioactive peptides used in cosmetic formulations and their neurocosmetic potential.

Entry	Commercial Name	Peptide Name	Amino Acid Sequence	Target Receptor/Pathway	Emotional/Sensory Effect	References
1	Argireline®	Acetyl Hexapeptide-8	Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2	SNARE complex	Reduces muscle contraction signals	[196,197,198]
2	Matrixyl® 3000	Palmitoyl Tetrapeptide-7 + Palmitoyl Oligopeptide	Gly-Gln-Pro-Arg + Pal-Gly-Gly-Gly	TGF-β pathway	Supports cell communication and repair	[199,200]
3	Syn®-Ake	Dipeptide Diaminobutyroyl Benzylamide Diacetate	H-D-Ala-D-But-OH derivative	Nicotinic acetylcholine receptor	Neuromuscular modulation	[193,201]
4	Syn®-Coll	Palmitoyl Tripeptide-5	Pal-Lys-Val-Lys	TGF-β receptor	Improves dermal matrix via signal transduction	[202,203]
5	Snap-8	Acetyl Octapeptide-3	Ac-Glu-Glu-Met-Gln-Arg-Arg-Glu-Lys	SNAP-25 cascade	Inhibits facial tension	[204,205]
6	Leuphasyl®	Pentapeptide-18	Tyr-D-Ala-Gly-Phe-Leu	SNARE complex	Modulates synaptic contraction	[195,206]
7	Progeline™	Trifluoroacetyl Tripeptide-2	TFA-Val-Tyr-Val	MMPs and progerin	Improves firmness by reducing cell aging	[207,208]
8	Thymulen™	Acetyl Tetrapeptide-2	Ac-Tyr-Arg-Lys-Lys-NH2	ECM regulation	Improves firmness and elasticity	[209,210,211]
9	Decorinyl®	Decorin-mimetic peptide	Not disclosed	Decorin interaction	Strengthens skin via ECM support	[212,213]
10	Idealift™	Acetyl dipeptide-1 cetyl ester	Ac-Tyr-Arg-NH2 (with cetyl ester)	Elastic fiber proteins	Improves tone by elastic fiber reinforcement	[167,214]
11	Melitane™	Acetyl Hexapeptide-1	Ac-Tyr-Arg-Ser-Arg-Lys-NH2	MC1-R receptor	Stimulates melanin and mood-linked peptides	[215]
12	Ac-SDKP	N-acetyl-seryl-aspartyl-lysyl-proline	Ac-Ser-Asp-Lys-Pro	Angiotensin II/TGF-β signaling modulation	Promotes cutaneous comfort and relaxation	[216,217,218]
13	GHK-Cu	Copper Tripeptide-1	Gly-His-Lys + Cu2+ ion	Copper transporters	Promotes healing via neurotrophic pathways	[219,220]
14	SpecPed® PT1P	Palmitoyl Tripeptide-1	Pal-Gly-His-Lys	Collagen biosynthesis enzymes	Stimulates collagen linked to nerve stimulation	[167,192,221]
15	Rigin™	Palmitoyl Tetrapeptide-7	Pal-Gly-Gln-Pro-Arg	Cytokine receptors	Reduces inflammation mediated by neuropeptides	[203,219,222]
16	Neutrazen™	Palmitoyl Tripeptide-8	Pal-Gly-Gln-Pro-Arg	Inflammatory neuropeptide receptors	Calms via neuroimmune modulation	[167]

compiles a representative selection of cosmetic peptides currently used in commercial formulations, highlighting their INCI names, amino acid sequences (when available), molecular targets, and associated emotional or sensory effects. These peptides act primarily through modulation of neuroreceptors, cellular signaling pathways, and extracellular matrix (ECM) components, contributing not only to anti-aging and skin repair effects but also to neurocosmetic outcomes such as relaxation, comfort, or muscle relaxation. Their mechanisms of action include SNARE complex interference (Entries 1, 5, 6), TGF-β signaling (Entries 2, 4, 12), neuromodulation of acetylcholine or neuropeptides (Entries 3, 15, 16), and interaction with ECM-related proteins (Entries 7–10). Some peptides, such as Ac-SDKP (Entry 12) and Copper Tripeptide-1 (Entry 13), also demonstrate anti-inflammatory or neurotrophic activity, reinforcing their dual functionality in both cutaneous and emotional modulation. This convergence of dermatological efficacy and sensory perception modulation supports the growing relevance of peptides in neurocosmetic science.

The versatility of these biomimetic peptides positions them as key elements in modern cosmetic innovation. Their high molecular specificity, efficacy at low concentrations, and excellent skin tolerance make them especially valuable in formulations for sensitive, aging, or neuroreactive skin. Moreover, their capacity to function as peripheral neuromodulators or sensory messengers opens the door to a new generation of functional cosmetic products—ones that aim not only to enhance external appearance but also to promote emotional and sensory balance.

Thus, biomimetic peptides represent an advanced tool for designing integrative cosmetic treatments that combine science, perception, and well-being.

1.5. Challenges of Neurocosmetics and Essential Oils

These findings support the emergence of neurocosmetics and aromatherapy as pioneering therapeutic strategies that simultaneously target skin health and emotional balance through the modulation of the skin–brain axis. Both approaches interact with neurocutaneous and neurosensory receptors, although through distinct routes: neurocosmetic actives act topically via cutaneous receptors—such as TRP channels, cannabinoid receptors, and serotonergic pathways—whereas aromatic compounds exert their effects through the olfactory system, ultimately modulating central structures like the limbic system (Figure 4).

However, despite their appeal as an emerging field aimed at modulating both emotional and cutaneous responses via topically applied neuroactive ingredients, neurocosmetics still face significant scientific, technological, and clinical limitations that hinder their full integration into evidence-based dermatology.

Firstly, most neurocosmetic formulations remain at the preclinical or early clinical trial stage, with limited validation in human subjects through robust methodologies. Much of the current evidence is derived from in vitro models or animal studies, restricting translational applicability. Additionally, human clinical trials frequently rely on subjective outcome measures such as self-reported mood, stress perception, or quality-of-life indices, introducing variability and complicating the establishment of clear causal links between active ingredients and psychophysiological effects.

Moreover, the inherently subjective nature of emotional responses, combined with the pronounced placebo effect commonly observed in cosmetic studies, further complicates result interpretation. Interindividual variability in neurocutaneous signaling, skin type, microbiome composition, emotional baseline, and sensory sensitivity also challenges the generalizability of findings across diverse populations.

From a methodological perspective, a notable gap exists in the integration of objective biomarkers of emotional state—such as salivary cortisol, heart rate variability, or functional neuroimaging—into neurocosmetic research. The absence of unified regulatory frameworks and international consensus guidelines for evaluating psychodermatological outcomes contributes to inconsistencies in validation and commercialization standards.

Finally, the effective transdermal delivery of neuroactive ingredients remains a critical formulation challenge, as many compounds possess physicochemical properties that limit epidermal penetration. Innovations such as controlled-release systems, nanocarriers, or lipid-based delivery vehicles are needed to ensure adequate bioavailability at neurocutaneous receptor sites.

From a safety standpoint, although fatal outcomes from dermal absorption of essential oils have not been documented to date, cases of non-fatal systemic toxicity have been reported. The most common adverse effects are photosensitization and contact dermatitis. Given the uncertain true incidence of these reactions and the wide variability in published estimates, essential oils should be used cautiously, adhering to safe concentration ranges and minimizing cumulative exposure [223,224,225].

Altogether, these limitations underscore the urgent need for longitudinal, multicenter studies employing rigorous methodological designs and incorporating multimodal assessments and validated psychophysiological biomarkers. Only then will it be possible to definitively establish the efficacy, safety, and therapeutic relevance of neurocosmetics in modern dermatological practice and neuroscience-based functional skincare.

2. Conclusions

The convergence of neurocosmetics and aromatherapy represents a promising frontier in functional skincare, offering a dual approach that targets both the physiological and emotional dimensions of cutaneous health. As scientific understanding of the skin–brain axis deepens, it becomes increasingly evident that the skin is not only a sensory interface but also an active participant in neuroendocrine and immune signaling. By leveraging bioactive compounds—whether topically applied or olfactorily delivered—formulations can modulate neurosensory pathways, promote homeostasis, and evoke perceptible emotional benefits such as relaxation, comfort, and improved mood.

This review underscores the potential of neuroactive ingredients, including biomimetic peptides, essential oils, cannabinoids, and neurotransmitter modulators, to influence skin structure, sensory perception, and emotional well-being through defined molecular targets such as TRP channels, CB1/CB2, serotonin and dopamine receptors, and cutaneous opioid systems. Furthermore, the integration of aromatherapeutic compounds via olfactory-limbic stimulation offers a complementary mechanism for enhancing psychodermatological outcomes.

Table 4. Short glossary of key terms.

Term	Definition
Neurocosmetics	Topical products that modulate the skin’s neuro-immuno-endocrine system to influence cutaneous function and emotional states.
Neurocosmetic Active	A functional ingredient (e.g., biomimetic peptide, TRP modulator, cannabinoid ligand, ectopic olfactory receptor ligand) that alters neurocutaneous signaling to produce measurable skin and/or neurosensory effects.
Neurocosmetic Formulation	A topical product designed to deliver one or more neurocosmetic actives at safe, effective levels using suitable delivery systems, sensory/olfactory design, and evidence-based claims within cosmetic regulations.
Aromatherapy	Use of volatile compounds (essential oils) via the olfactory route to modulate limbic activity and psychophysiological responses.
Skin–Brain Axis	Bidirectional communication between skin and CNS through neuroendocrine, immune, and sensory pathways.
TRP Channels (e.g., TRPV1, TRPM8, TRPA1)	Sensory ion channels responding to heat/cold/irritants; regulate pain, itch, inflammation, and pigmentation—key neurocosmetic targets.
Cannabinoid Receptors (CB1/CB2)	GPCRs in skin and immune cells that modulate inflammation, nociception, and sebum; CB1 is more neuronal, CB2 is more immune-linked.
Cutaneous Serotonergic/Dopaminergic Receptors	Neuroreceptors in skin cells implicated in proliferation, pigmentation, inflammation, and sensory comfort.
Ectopic Olfactory Receptors (e.g., OR2AT4)	Olfactory receptors expressed in skin and other tissues; activation can influence regeneration, inflammation, and cell migration.
Limbic System	Brain network (e.g., amygdala, piriform/entorhinal cortex) mediating emotion and memory; activated by olfactory inputs.
HPA Axis	Hypothalamic–pituitary–adrenal stress pathway; commonly monitored via salivary cortisol in psychoderm studies.
BDNF	Brain-derived neurotrophic factor; supports neuroplasticity and can change with olfactory/aromatherapy interventions.
Psychophysiological Biomarkers	Objective measures (e.g., cortisol, HRV, EEG/neuroimaging) used to validate neurocosmetic effects.
EEG/Power Spectral Density (PSD)	Electrophysiological methods quantifying brain activity across frequency bands to assess arousal/attention states.
HRV (Heart Rate Variability)	Autonomic biomarker of stress and emotional regulation; useful in cosmetic/psychoderm endpoints.
Transdermal Delivery	Penetration of actives across the epidermal barrier; a central challenge for efficacy in neurocosmetics.
Advanced Delivery Systems	Technologies (e.g., nanocarriers, lipid vehicles, controlled release) that enhance penetration, targeting, and bioavailability.
Placebo and Subjective Outcomes	Expectation effects and self-reported endpoints that add variability; motivate inclusion of objective measures.
Borderline Products (EU Reg. 1223/2009)	Products at the cosmetic–drug/device interface; classification depends on site, mechanism, and intended purpose.
Photosensitization	Light-triggered adverse reaction (common with some essential oils) leading to erythema or hyperpigmentation.

provides a concise glossary of the key terms.

However, despite encouraging preclinical and emerging clinical evidence, significant challenges remain—particularly regarding standardized methodologies, objective biomarker validation, and regulatory classification. Future progress will depend on robust interdisciplinary research, longitudinal human trials, and the development of advanced delivery systems that ensure efficacy and safety.

Ultimately, neurocosmetics and aromatherapy embody a shift toward a more holistic, evidence-based paradigm in cosmetics—one that embraces not only the aesthetic and structural integrity of the skin but also the subjective and emotional experience of the user. This integrative approach holds great promise for the development of next-generation cosmetic formulations that promote both skin health and emotional resilience.