The rising prevalence of New Psychoactive Substances (NPS), particularly synthetic cathinones and ketamine, is alarming. Synthetic cathinones are structurally diverse stimulants linked to multiorgan toxicity, while ketamine, often used as a racemic mixture, may exhibit enantiomer-specific pharmacodynamics, raising public health concerns due to their poorly characterized toxicological profiles. This project aims to characterize the organismal, cellular, and potentially transgenerational toxicity of prevalent synthetic cathinones [3-chloromethcathinone (3-CMC), 3-methylmethcathinone (3-MMC), 4-chloromethcathinone (4-CMC), ethcathinone, 4-chloroethcathinone (4-CEC), 4-chloro-α-pyrrolidinopropiophenone (4-Cl-α-PPP)] and ketamine [racemic mixture, and (R)- and (S)-ketamine], using Caenorhabditis elegans as a translational model organism. We will assess drug-induced effects on animal survival, development, locomotion and reproductive behaviours, and lifespan across different life stages. We expect to provide critical insights into age- and enantiomer-specific drug toxicity, addressing urgent knowledge gaps in NPS safety evaluation and offering translational relevance to human health.