RationaleMicrodosing psychedelics—the regular consumption of small amounts of psychedelic substances such as LSD or psilocybin—is a growing trend in popular culture. Recent studies on full-dose psychedelic psychotherapy reveal promising benefits for mental well-being, especially for depression and end-of-life anxiety. While full-dose therapies include perception-distorting properties, microdosing mayprovide complementary clinical benefits using lower-risk, non-hallucinogenic doses.ObjectivesThis pre-registered study aimed to investigate whether microdosing psychedelics is related to differences in personality, mental health, and creativity.MethodsIn this observational study, respondents recruited from online forums self-reported their microdosing behaviors and completed questionnaires concerning dysfunctional attitudes, wisdom, negative emotionality, open-mindedness, and mood. Respondents also performed the Unusual Uses Task to assess their creativity.ResultsCurrent and former microdosers scored lower on measures of dysfunctional attitudes (p < 0.001, r = − 0.92) and negative emotionality (p = 0.009, r = − 0.85) and higher on wisdom (p < 0.001, r = 0.88), openmindedness(p = 0.027, r = 0.67), and creativity (p < 0.001, r = 0.15) when compared to non-microdosing controls.ConclusionsThese findings provide promising initial evidence that warrants controlled experimental research to directly test safety and clinical efficacy. As microdoses are easier to administer than full-doses, this new paradigm has the exciting potential to shape future psychedelic research.