Improved processes for the extraction of quassinoids such as quassin and neoquassin from natural substances containing these compounds are described. The process uses compounds that are Generally Recognized As Safe by the U.S. Food and Drug Administration. In a first embodiment, the process includes a sonication method using water and no organic solvent. The process is highly efficient and comprises fewer steps than other processes known in the art. In a second embodiment, a method of extracting quassinoids from natural substance comprising bark of a plant of the plant family Simaroubaceae is also disclosed. In a third embodiment, indirect sonication of quassinoids is described using a mixture of polar and non-polar organic solvents.