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AET was once clinically available as an antidepressant but was withdrawn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.