Methods and compositions are described that comprise pyrone analogs such as flavonoids and cyclodextrins including quercetin and quercetin derivatives and sulfoalkyl ether cyclodextrins. In some cases the compounds of the invention are administered with a therapeutic agent such as an analgesic. In some cases, treatment with the compositions of the invention can result in the modulation of central nervous system and/or fetal effects of substances. Methods and compositions are described for the modulation of efflux transporter activity to increase the efflux of drugs and other compositions out of a physiological compartment and into an external environment. In particular, the methods and compositions disclosed herein provide for the increase of efflux transporter activity at blood-brain, blood-CSF and placental-maternal barriers to increase the efflux of drugs and other compositions from physiological compartments, including central nervous system and fetal compartments.