Recent evidence reveals that several psychotropic compounds exert significant biological effects on the skin through neurochemical and immunomodulatory pathways. Cannabinoids such as tetrahydrocannabinol (THC) show potent anti-inflammatory, antipruritic, and anti-aging properties when applied topically, and may hold therapeutic potential. Antidepressants, particularly fluoxetine (Prozac), have been shown to regulate the expression of pro-inflammatory cytokines in keratinocytes, suggesting benefits applied in allergic pathologies. Additionally, fluoxetine promotes wound healing and cell regeneration, indicating broader dermatological applications. Psychedelics, acting as serotonin receptor agonists (5-HTR), may influence cellular aging and immune modulation via the serotonergic system. Studies report that 5-HT receptor agonists can prevent UV-induced photocarcinogenesis, while psilocybin has been observed to reduce aging markers in human fibroblasts. Furthermore, recent data suggests that psilocin may alleviate acute itch involving the kynurenine pathway. These findings highlight the emerging relevance of psychoactive compounds in cutaneous biology, bridging neuropharmacology and dermatology toward novel therapeutic strategies.