Psychedelics such as psilocybin and methylenedioxymethamphetamine are powerful psychoactive substances with overlap in both their behavioral pharmacology and molecular pharmacology. Research on these drugs is currently undergoing a renaissance. Recent studies have shown impressive efficacy in the treatment of a variety of mood and substance-use disorders. Despite these groundbreaking results, much work remains to elucidate the precise mechanisms underlying the therapeutic effects of psychedelics. Moreover, the development of new psychedelic medications that maximize therapeutic benefits, while minimizing adverse effects, is a major research goal. In this symposium, we will discuss recent findings from preclinical studies addressing these important research topics.