5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a naturally occurring tryptamine that primarily acts as an agonist at the 5-HT1A and 5-HT2A receptors. Psychedelic effects following 5-MeO-DMT administration include distortions in auditory and time perception, amplification of emotional states, and feelings of ego dissolution that usually are short-lasting, depending on the route of administration. Observational studies and surveys have suggested that single exposure to 5-MeO-DMT can cause rapid and sustained reductions in symptoms of depression, anxiety, and stress. To date, clinical trials with synthetic formulations of 5-MeO-DMT have started to assess safety in healthy volunteers and safety and efficacy in patients with treatment resistant depression. These studies show that the drug is well tolerated when administered in single doses and in dose escalations steps. Patient data show a rapid decrease of depressive symptoms within 24 hours after receiving a 5-MeO-DMT formulation (GH001). In patients that received a single dose of GH001 (12 or 18mg), 3 out 8 patients achieved remission on day 7 after treatment, as assessed with the MADRS. In patients that received an individualized, incremental dosing regimen of a GH001, a remission of symptoms was observed in 7 out of 8 patients on day 7 after treatment. More clinical studies are underway to develop 5-MeO-DMT as an ultra-rapid, durable treatment of depression. Fundamental research will also be needed to increase understanding of the neural mechanisms that contribute to the potential clinical effects of 5-MeO-DMT.