Inhalable Psychedelic 5-MeO-DMT Shows Promise in Treatment-Resistant Depression

Treatment-resistant depression (TRD) is defined as the failure to achieve a clinically significant improvement in major depressive disorder (MDD) despite treatment with at least two different standard antidepressants administered at adequate doses duration.1 TRD significantly impairs daily functioning and imposes a considerable economic burden in the United States. 2 Given the limited number of FDA-approved medications currently available for the treatment of TRD, 3 there remains an urgent unmet need for safer and more effective therapies.Recently, the U.S. Food and Drug Administration (FDA) granted a fast-track review designation for psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) as a treatment for MDD and TRD, highlighting the therapeutic potential of psychedelic compounds.4 In addition, 5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine; 1; Figure 1A) and DMT (N,Ndimethyltryptamine; 4; Figure 2) demonstrated promise in rapidly alleviating symptoms of TRD.5-7 5-MeO-DMT is a rapidly acting atypical psychedelic that occurs naturally in various plants and in the venom of the Colorado River toad (Incilius alvarius).8