Aboriginals of Latin America have used DMT (N,N-dimethyltryptamine) in ritualistic ceremonies for centuries. Nevertheless, there are limited data on web users’ interest concerning DMT. We aim to review the literature and explore the spatial–temporal mapping of online search behavior concerning DMT, 5-MeO-DMT, and the Colorado River toad via Google Trends over the past 10 years (2012–2022) while using 5 search terms: “N,N-dimethyltryptamine”, “5-methoxy-N,N-dimethyltryptamine”, “5-MeO-DMT”, “Colorado River toad”, and “Sonoran Desert toad”. Literature analysis conveyed novel information concerning DMT’s past shamanic and present-day illicit uses, showcased experimental trials on DMT uses for neurotic disorders, and highlighted potential uses in modern medicine. DMT’s geographic mapping signals originated mainly from Eastern Europe, the Middle East, and Far East Asia. In contrast, 5-MeO-DMT signals prevailed in Western Europe, Indo-China, and Australasia. Signals concerning the toad originated from the Americas, Australia, India, the Philippines, and Europe. Web users searched the most for “N,N-dimethyltryptamine” and “5-MeO-DMT”. Three terms exhibited significant upgoing linear temporal trends: “5-MeO-DMT” (β = 0.37,p< 0.001), “Sonoran Desert toad” (β = 0.23,p< 0.001), and “Colorado River toad” (β = 0.17,p< 0.001). The literature and Infoedemiology data provided crucial information concerning DMT’s legal status, risks and benefits, and potential for abuse. Nonetheless, we opine that in the upcoming decades, physicians might use DMT to manage neurotic disorders pending a change in its legal status.