The utility of 2,5-dimethoxy-4-iodoamphetamine for the study of serotonin 2A and 2C receptors.
Lindsay P. Cameron, Alaina M Jaster, Raul A Ramos, Elijah Z. Ullman
Molecular Pharmacology 2026 DOI: 10.1016/j.molpha.2025.100093 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Serotonin |
| Keywords | Amphetamines Psychedelic Receptor pharmacology Research methods Serotonin receptors |
| Citations | 3 |
| Key findings | DOI has been a key pharmacological tool for studying 5-HT2A and 5-HT2C receptors in over 1,200 publications, but its potential scheduling may restrict future research, prompting the need for alternative compounds. |
Abstract
2,5-dimethoxy-4-iodoamphetamine (DOI) is a phenethylamine psychedelic with high affinity for 5-HT2 receptors. In 2022 and 2023, the US Drug Enforcement Administration proposed to place DOI, along with a similar compound, 2,5-dimethoxy-4-chloroamphetamine, in Schedule I of the Controlled Substances Act based on their psychoactivity and alleged abuse potential. Here, we describe the history of DOI, its utility in preclinical neuroscience research, and how it has significantly advanced the study of 5-HT2A and 5-HT2C receptors. Finally, we suggest alternative compounds for studying 5-HT2 receptors, should obtaining DOI for research become restricted. SIGNIFICANCE STATEMENT: 2,5-Dimethoxy-4-iodoamphetamine, the key pharmacological tool for studying 5-HT2A receptor function and localization, has been used in more 1200 publications across 5 decades. This review covers its utility, research barriers if the Drug Enforcement Administration schedules it, and alternatives for continued investigation of serotonin receptors.