I-LSD yaqala ukudityaniswa ngusokhemisti waseSwitzerland u-Albert Hofmann ngo-1938 ukusuka kwi-lysergic acid kusetyenziswa umngundo wengqolowa kwiinzame zokuphuhlisa i-analeptic entsha. UHofmann wafumanisa iziphumo zayo ezibi emva kokuba ethe engaqondanga wafunxa isixa esikhulu ngolusu lwakhe. Emva koko, i-LSD yaphakamisa umdla okhethekileyo kwi-psychiatry ngeminyaka yee-1950s nakwi-1960s yokuqala, kunye ne-Sandoz eyisasaza kubaphandi ngelinge lokufumana ukusetyenziswa okuthengiswayo.
Unyango lwengqondo oluncediswa yiLSD lwaluqhutywa ngeminyaka yee-1950 kunye nee-1960 ngoogqirha bengqondo abaneziphumo ezithembisayo ekunyangeni iimeko ezinjengokunxila. I-LSD kunye nezinye ii-psychedelics ziye zahamba ngendlela efanayo kunye nentshukumo ye-counterculture eyakhokelela ekubeni i-LSD ijongwe njengesoyikiso kulawulo lwaseMelika, kwaye emva koko yabizwa ngokuba yinto yeShedyuli I ngo-1968.
