DEA Revives Bid to Place Five Tryptamines in Schedule I, Clashing With FDA Psychedelic Push
核心洞察
The DEA published a proposed rule to place five tryptamines, including 4-OH-DiPT (搜索) and 5-MeO-MiPT, in Schedule I, with a 30-day public comment period.
The filing marks DEA's second attempt at scheduling the same compounds after withdrawing an identical 2022 proposal following public and legal pushback.
Reunion Neuroscience (搜索)'s 4-OH-DiPT (搜索) prodrug luvesilocin (搜索) holds FDA Breakthrough Therapy Designation for postpartum depression (搜索), and Mindstate Design Labs (搜索) has studied 5-MeO-MiPT.
The U.S. Drug Enforcement Administration (搜索) has formally published a proposed rule to place five hallucinogenic tryptamines in Schedule I of the Controlled Substances Act, reviving a scheduling effort the agency abandoned in 2022 and drawing immediate objections from researchers, attorneys and mental health advocates.
The compounds named in the notice of proposed rulemaking are 4-Hydroxy-N,N-Diisopropyltryptamine (4-OH-DiPT (搜索)), 5-Methoxy-alpha-Methyltryptamine (5-MeO-AMT (搜索)), 5-Methoxy-N-Methyl-N-Isopropyltryptamine (5-MeO-MiPT), 5-Methoxy-N,N-Diethyltryptamine (5-MeO-DET (搜索)) and N,N-Diisopropyltryptamine (DiPT (搜索)). All five are currently unscheduled under federal law. Schedule I is reserved for substances the government considers to have no accepted medical use and high abuse potential. The public has 30 days from the proposal's publication date to comment.
In the notice, DEA officials wrote that "based on available pharmacology information the five tryptamines are expected to have significant overlap in effects with schedule I hallucinogenic substances such as DMT, psilocybin, and others." The agency also stated: "There are no well-controlled clinical studies showing safety or efficacy for these substances. In addition, there is no evidence by qualified experts that 4-OH-DiPT (搜索), 5-MeO-AMT (搜索), 5-MeO-MiPT, 5-MeO-DET (搜索), and DiPT (搜索) are accepted as having therapeutic uses."
A Second Attempt, Four Years Later
This is not the first time the five compounds have approached rescheduling. DEA proposed placing the same substances in Schedule I in 2022, citing "reports of abuse and trafficking" that led the Department of Health and Human Services (搜索) to evaluate the drugs for scientific and medical use and issue scheduling recommendations in 2012. At the time, the agency asserted the tryptamines "pose a risk to public health due to their hallucinogenic properties."
That proposal was withdrawn after public pushback, including comments from the pharmatech company Tactogen (搜索), which argued DEA was encumbering psychedelics research with restrictions and making decisions not based on current science. In its notice withdrawing the proposal, DEA said it was requesting an updated HHS scientific and medical evaluation of the five compounds.
According to the latest rule proposal, that request was submitted in 2023, and on April 2, 2026, HHS provided its updated evaluation and recommendations. DEA then updated its own analysis in May 2026 and reached the same conclusion as HHS: the five hallucinogens and their respective salts should be rescheduled due to abuse potential and lack of medical merit.
Evidence Cited, and Its Limits
DEA's justification rests on enforcement and poison center data that critics say does not establish a significant public health threat. The agency's filing cites "a cumulative total of 518 encounters of these tryptamines by United States law enforcement in several states and the District of Columbia," without specifying the timeframe over which those encounters were recorded.
DEA also cited data from America's Poison Centers' National Poison Data System showing 65 exposure cases involving one or more of the five tryptamines over an 18-year period, from January 1, 2003, to December 31, 2021. The filing acknowledges that "no single-substance exposure cases involving the five tryptamines resulted in death." It further notes that, per HHS's report on the substances, "FDA is not aware of any diversion from research or legitimate manufacturing activities."
Clinical Programs Caught in the Middle
The scheduling push intersects with active drug development around at least two of the compounds. Philadelphia-based Reunion Neuroscience (搜索) has received Breakthrough Therapy Designation from the FDA for its proprietary 4-OH-DiPT (搜索) prodrug, luvesilocin (搜索), in the treatment of postpartum depression (搜索). A prodrug is an inactive or less active compound that is converted to the active drug by the body. 4-OH-DiPT is a synthetic analog of psilocin, the metabolite of psilocybin, and is known to be faster acting and shorter lasting than psilocybin. A trial at UMass Chan Medical School has also tested 4-OH-DiPT in treating symptoms of adjustment disorder (搜索).
San Francisco-based Mindstate Design Labs (搜索) has led studies of 5-MeO-MiPT. Dillan DiNardo, the company's CEO and co-founder, said his team expected the announcement. "To my knowledge, Mindstate has perhaps generated more extensive data around 5-MeO-MiPT, and maybe some of the other molecules in question, than any other institution," DiNardo said. "So we're just evaluating now how we can best contribute scientific evidence and expertise to the process."
DiNardo also described the regulatory difficulty the agency faces. "They're charged with protecting public health, but they're being asked to apply a 20th-century category system to a 21st-century measurement problem," he said. "Compounds like 5-MeO-MiPT don't fit into legacy boxes like 'psychedelic' or 'hallucinogen' or 'stimulant.'"
Researchers and Attorneys Push Back
Psychedelic patent attorney Graham Pechenik challenged the agency's reasoning and its treatment of the earlier proceedings. "Four years ago DEA withdrew this same proposal after experts across the field made an enormous effort to demonstrate why these compounds have no place on Schedule I. Yet DEA is now trying again, relying on a new HHS review that still fails to show abuse or risk to public health, and claiming there is 'no evidence by qualified experts' for therapeutic use, while citing nothing from the earlier proceedings," Pechenik said. "Just as before, the real impact of DEA's action would be to impede research."
Robert Rush, founder of the Rights and Reason Project, framed the move as consistent with the agency's broader posture. "Schedule I has become the default for the DEA for any substance that is not FDA-approved and has any sort of psychoactive qualities," Rush said. "Many people mistakenly believe that the DEA has a different attitude regarding psychedelics versus other drugs. The actions of the DEA to once again move to schedule these five tryptamines, which have important research potential and are involved in active research, reflect the true position of the agency."
Rush pointed to the agency's position in prior litigation. "The DEA has been very explicit, though they do not consider research harm in decision-making. During our DOI/DOC scheduling challenge in 2024, they argued that harm to the research is irrelevant."
He also highlighted the divergence between the two federal agencies. "This is particularly poignant with this example now because one of the compounds, 4-OH-DiPT (搜索), the prodrug, is currently in development for postpartum depression (搜索) and has been granted breakthrough status from the FDA," he said. "We have the FDA attempting to move forward a promising new treatment while the DEA is doing everything they can to obstruct its development. One foot steps on the gas while the other steps on the brake, and the taxpayers are left to pay for this whole mess."
Rush noted the timing relative to a recent FDA hearing on psychedelics. "It is also interesting that after four years, the DEA decided to drop its previous scheduling attempt then decided to revisit it less than two weeks after a very positive FDA hearing on psychedelics," he said. "The DEA believes in the prohibition of all drugs unless they're coming from a pharmaceutical company, and even then, they are willing to put roadblocks in the way of promising compounds to address the mental health needs of Americans."
"We still have a crisis of mental health issues and deaths of despair in this country, yet the DEA seems to think that research to address these issues is irrelevant and not a public health issue," Rush said. "The Rights and Reason Project thinks this use of taxpayer-funded resources harms public health and scientific research, and we will be fighting this to the greatest extent possible."
The renewed scheduling effort follows a historic public hearing on the future utility of psychedelic drugs held at FDA headquarters in Silver Spring, Maryland, one week before the DEA filing. The two actions point to differing positions within the federal government on the therapeutic viability of psychedelic substances, with DEA pursuing prohibition while FDA increasingly supports clinical exploration.