α-Ethyltryptamine: A Ratiocinatory Review of a Forgotten Antidepressant.

α-Ethyltryptamine (AET) is quite an interesting, but perhaps long-forgotten, centrally acting agent. Known for more than 75 years, AET was once clinically available as an antidepressant but was withdrawn shortly after its introduction. AET was subsequently controlled as a U.S. Schedule I substance due to its perceived abuse liability and/or toxicity but remains an agent of interest. Hallucinogenic tryptamines (that is, serotonergic psychedelic agents) are now in vogue as novel and exciting chemotherapeutics for the treatment of various neuropsychiatric disorders, including treatment-resistant depression and anxiety. Does AET represent a serotonergic psychedelic agent? Does AET (or its analogs) deserve further investigation? Here, the history of AET is critically reviewed in detail, and an argument is made that AET might have been an agent well ahead of its time. It possesses many of the hallmarks of an antidepressant, suggesting that AET derivatives and particularly their optical isomers are deserving of further investigation.