The Epidemiology of Recreational Use and Availability of DOC and DOI in the United States

The U.S. Drug Enforcement Administration (DEA) proposed a rule in which they intend to place the psychedelic phenethylamines 2,5-dimethoxy-4-chloroamphetamine (DOC) and 2,5-dimethoxy-4-iodoamphetamine (DOI) into Schedule I of the Controlled Substances Act. We investigated the epidemiology of use and availability of these substances. We investigated national trends in seizures of these compounds (which indicate availability) using DEA National Forensic Laboratory Information System (NFLIS) and High Intensity Drug Trafficking Areas (HIDTA) data. We also examined the prevalence of self-reported use on the National Survey of Drug Use and Health (NSDUH), a nationally representative sample of noninstitutionalized individuals aged ≥12 in the United States. The scientific literature was also systematically searched for reports of poisonings linked to use. Between 2005 and 2024, NFLIS received 795 submissions of drugs testing positive for DOC, with a peak of 152 in 2012. There was then a decrease through 2024, with only two submissions containing DOC in 2023-2024. Forty submissions contained DOI, with no submissions testing positive in 2019-2024. Three DOC seizures were recorded by HIDTA in 2017-2021, with none in 2022-2024. HIDTA had no recorded seizures of DOI. Between 2005 and 2023, there were 37 and 10 type-in mentions of lifetime DOC and DOI use, respectively, in NSDUH responses, suggesting a lifetime prevalence of < 0.01% among the noninstitutionalized U.S. population. We located three reports of poisonings linked to DOC use (in 2008-2024) and none linked to DOI use. Availability, recreational use, and poisoning related to the use of DOC and especially DOI appear to be rare.