“Cannabinoid receptor type 1 (CB1) is an important modulator of many key physiological functions and thus a compelling molecular target. However, safe CB1 targeting is a non-trivial task. In recent years, there has been a surge of data indicating that drugs successfully used in the clinic for years (e.g. paracetamol) show CB1 activity. Moreover, there is a lot of promise in finding CB1 ligands in plants other than Cannabis sativa. In this study, we searched for possible CB1 activity among already existing drugs, their metabolites, phytochemicals, and natural-like molecules. We conducted two iterations of virtual screening, verifying the results with in vitro binding and functional assays. The in silico procedure consisted of a wide range of structure- and ligand-based methods, including docking, molecular dynamics, and quantitative structure-activity relationship (QSAR). As a result, we identified travoprost and ginkgetin as CB1 ligands, which provides a starting point for future research on the impact of their metabolites or preparations on the endocannabinoid system. Moreover, we found five natural-like compounds with submicromolar or low micromolar affinity to CB1, including one mixed partial agonist/antagonist viable for hit-to-lead phase. Finally, the computational procedure established in this work will be of use for future screening campaigns for novel CB1 ligands.”