2,5-Dimethoxy-4-iodoamphetamine

2,5-Dimethoxy-4-iodoamphetamine (DOI) is a psychedelic drug of the amphetamine and 4-substituted-2,5-dimethoxyamphetamine (DOx) families. It is relatively little-used as a recreational drug but is frequently used in scientific research in the study of psychedelics and serotonin receptors.

DOI acts as a potent serotonin 5-HT₂ receptor agonist, including of the serotonin 5-HT_2A and 5-HT_2C receptors. The compound has a stereocenter, and R-(−)-DOI is the more active stereoisomer. [¹²⁵I]-R-(−)-DOI is used as a radioligand and indicator of the presence of serotonin 5-HT_2A receptors in studies.

DOI's effects have been compared to LSD, although there are differences that experienced users can distinguish. Besides the longer duration of DOI compared to LSD, the trip tends to be more energetic than an LSD trip, with more body load and a different subjective visual experience. The after effects include residual stimulation and difficulty sleeping, which, depending on the dose, may persist for days. While rare, DOI has sometimes been sold as a substitute for LSD, or even sold falsely as LSD, which may be dangerous because DOI does not have the same established safety profile as LSD. Owing to their very long durations, which users tend to find disagreeable however, DOI and other DOx psychedelics have seen very little recreational use.

DOI was first synthesized in 1973, by Coutts and Malicky. Unlike many other psychedelic drugs, DOI is not an explicitly controlled substance in the United States. However, it could be considered a controlled substance under the Federal Analog Act. In any case, its non-controlled status has made DOI usefully accessible for use in scientific research, which has contributed to its popularity for such uses. In December 2023, the Drug Enforcement Agency (DEA) proposed making DOI a schedule I controlled substance. This proposal has been opposed by psychedelic researchers and the DEA has consequently delayed its June 2024 hearing on the proposal.