In a recent puzzling move, the Drug Enforcement Agency announced it will oppose the surging tide of widespread support for psychedelic research and proposed adding five more tryptamine drugs to Schedule 1. The most restrictive category of controlled substances, drugs in that class are identified as “having the greatest potential for abuse and no known medical value.” An example of one such tryptamine currently confined in Schedule 1 is psilocybin, even as clinical data from the Food and Drug Administration confirmed the medical value of psilocybin therapy by designating it a “breakthrough therapy” for severe depression.
The proposed tryptamine compounds the DEA is considering changing to Schedule 1 include 4-Hydroxy-N,N-diisopropyltryptamine (4-OH-DiPT), 5-Methoxy-alphamethyltryptamine (5-MeO-AMT), N-Isopropyl-5-Methoxy-N-Methyltryptamine (5-MeO-MiPT), N,N-Diethyl-5-methoxytryptamine (5-MeO-DET), and N,N-Diisopropyltryptamine (DiPT).
In a published document by the DEA on the Federal Register, the agency cites a 2012 review by the Department of Health & Human Services of “hospital emergency room admissions related to the abuse of 5-MeO-AMT and 5-MeO-MiPT,” reads the document. “One confirmed death was reported in 2004 from the abuse of 5-MeO-AMT, taken in combination with alcohol and the antidepressant bupropion. However, it is unclear what role 5-MeO-AMT played in the death.”
Concerned scientists say that the proposal will make more than just those five substances discussed by the DEA illegal for manufacture and possession. It will also inevitably hamper vital research of nearly 100 related compounds.
The move is particularly egregious to researchers like neuroscientist Matthew Baggott, co-founder and CEO at Tactogen, a pharmatech startup developing the next generation of MDMA-like medicines. Baggott explains while all five of the compounds in question are currently regulated under the Federal Analogue Act — meaning they are legal to possess but illegal for humans to ingest — the new proposal would make the compounds unlawful to possess, even for research purposes, without a license obtained from the agency.
“This will greatly hinder research into not just these compounds, but many closely related ones,” says Baggott. “That is because when the DEA makes a compound Schedule I, it automatically also makes it illegal to possess structurally related compounds called positional isomers.”
Though the DEA has discussed making only five tryptamine-containing compounds illegal, he says, the underlying message is that those positional isomers effectively ensnare another roughly 100 chemically adjacent compounds.
Baggott says his team regularly uses one of the compounds on the list in his lab. “When my team synthesizes and characterizes a new compound, we need to compare it to compounds with known effects. We use 5-MeO-MiPT as one of these known comparison compounds,” he says. “It is scientifically interesting to my team because, although it has classical psychedelic effects at higher doses, it has some MDMA-like effects at low doses.”
Because Tactogen is seeking to develop gentler, more sustainable analogues of MDMA, compounds like 5-MeO-MIPT can offer important clues. From experience, he knows that when a drug is placed in Schedule 1, research teams will then be required to jump through onerous DEA hoops to attain licensing for studies. Particularly when running multiple projects.
“A key consideration is that researchers will need a separate permit to study 5-MeO-MiPT for every research location and, often, every project,” says Baggott. He notes that modern biotech companies are collaborative enterprises relying on contract research organizations and academic labs to run specialized analyses. “So that might mean applying for five or more permits for 5-MeO-MiPT,” he says. “Many research sites can be unwilling to jump through the bureaucratic hoops for small projects, so we might lose some collaborators and need to find new ones.”
He adds, the DEA approval process is slow, with consent often taking around six months. For a lot of researchers that lag time could mean a domino effect of stalled studies and missed deadlines.
“In short,” says Baggott, “if 5-MeO-MiPT is made illegal, we will likely stop studying it.”
The period to comment to the DEA on the proposal is open until February 14, 2022.