As with all drugs, the route, form, and/or dose of a substance administered or applied can play a defining role in its overall pharmacology and use as a therapeutic. This review will focus on these factors as they relate to the psychedelic N,N-dimethyltryptamine (DMT). It will examine the positive and negative aspects of different formulations and routes of administration of DMT and the observed effects from such administrations in the form of ayahuasca teas; oral "pharmahuasca"; injections by intravenous (IV) and intramuscular (IM) routes; inhalation, insufflation; and other routes; and high-dose, low-dose, and "micro-dose" effects. The review will consider possible oral route of administration alternatives that would not require concomitant use of a monoamine oxidase inhibitor. The review will then address the current research findings for DMT from in vivo and in vitro studies as well as the possibility that these findings may be revealing the role of endogenous DMT in normal brain function. Keywords: Dimethyltryptamine · Psychedelic therapeutics · Ayahuasca · Sigma-1 receptor · Monoamine oxidase inhibitor · Pharmahuasca · Deuterhuasca