LSD contains stereogenic centers at the C5- and C8-positions that are susceptible to epimerization and the active form, (+)-LSD, has the absolute configuration 5R, 8R.

The C5 isomers of lysergamides do not exist in nature and are not formed during the synthesis of (+)-LSD. However, the C8 center rapidly interconverts in the presence of base. The C8 isomer, (+)-iso-LSD, is not active and can be separated by chromatography and isomerized to give (+)-LSD.