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Clinical trials using full doses of psychedelics have provided preliminary evidence supporting their safety and efficacy in treating a variety of physical and psychological conditions. Anecdotal reports indicate that even very small amounts of these substances may provide therapeutic benefits, though robust clinical studies are still needed. This chapter reviews the current experimental studies in humans using psychedelics in small doses to better understand their therapeutic potential. Research in both neurotypical individuals (n = 18 studies) and patients (n = 3) suggests that small doses of LSD and psilocybin produce subtle, acute, effects on neural connectivity, brain electrophysiology, blood pressure, sleep duration, pain perception, temporal processing, and mood; and show reductions in symptoms of depression and obsessive-compulsive behavior in patient samples. The chapter also discusses the influence of extra-pharmacological factors, such as the baseline subjective state, expectations, and individual differences in drug metabolism, on treatment outcomes. Overall, controlled microdosing studies suggest the potential therapeutic applications of small psychedelic doses, warranting further exploration through large-scale trials in clinical populations.