Tauopathies are characterized by neurotoxic tau accumulation and alterations in autophagy. Previous studies suggest that cannabidiol (CBD) can induce autophagy in cell culture models. Here, we used N2a neuroblastoma cells and Drosophila melanogaster to evaluate the impact of cannabinoids on autophagy and tau-induced neurodegeneration. Our initial screening in N2a cells involved CBD, CBDA, THCA, and THC. Our results show that CBD consistently induced autophagy, and THCA exhibited a potential autophagy-inducing effect. Conversely, CBDA inhibited autophagy, while THC had no detectable effect. Consequently, we chose CBD as the primary candidate for further investigation into its efficacy against tau neurotoxicity. We are assessing if CBD-induced autophagy reduces tau neurotoxicity. To this end, we evaluated in N2a clones that stably express human tau whether CBD treatment reduces its accumulation. In parallel, in a Drosophila model, we expressed human tau in neurons and eyes to evaluate neurodegeneration phenotypes. We optimized methods for quantifying the rough eye phenotype, assessing locomotor function and detecting tau and phosphorylated tau via Western blot. Additionally, a bioinformatic analysis is underway to identify potential molecular targets of cannabinoids in the autophagy pathway. Our results provide evidence for CBD's role as a selective modulator of autophagy, supporting its further exploration as a therapeutic strategy for tau-related neurodegenerative diseases