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 January 1, 2026 Peer reviewed DOI: 10.1016/j.molpha.2025.100093 via PubMed
Summary
2,5-Dimethoxy-4-iodoamphetamine (DOI) is a psychedelic compound with a strong affinity for 5-HT2 receptors, used in over 1200 publications to advance the understanding of these receptors. The US Drug Enforcement Administration has proposed to classify DOI as a Schedule I substance due to its psychoactivity and potential for abuse. This review discusses DOI's history, its importance in neuroscience research, and potential alternatives for studying serotonin receptors if access to DOI is restricted.
Study at a glance
| Design | review |
|---|---|
| Key finding | DOI has been a key pharmacological tool for studying 5-HT2A receptor function and localization, utilized in more than 1200 publications. |
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.