It would be very stupid of the DEA to schedule DOI and DOC.
In attempting to place DOI and DOC in Schedule 1, the DEA would be kneecapping psychedelic neuroscience at a time when the field is flourishing, and for no discernible reason.
On December 13th, 2023, the Drug Enforcement Administration (DEA) announced that it intended to place two obscure psychedelic drugs into the Schedule 1 category, which is reserved for compounds with a high potential for abuse and no accepted medical use (although the continued placement of cannabis in Schedule 1 suggests that the DEA may not be entirely trustworthy when it comes to making that decision). These two drugs, 2,5-dimethoxy-4-iodoamphetamine (DOI) and 2,5-dimethoxy-4-chloroamphetamine (DOC), are probably not going to top anyone’s list of “most culturally significant psychedelics”. There are no great jam bands inspired by the DOC experience, and there are no clinical trials of DOI for depression, anxiety, or anything else. As far as I can tell, there’s not even that much recreational interest in them (with most people preferring the classic standbys of LSD, psilocybin, and mescaline, all of which are easily available to anyone who knows how to grow mushrooms or has even a modicum of internet savvy). That doesn’t mean that the attempt to ban DOI and DOC isn’t significant, however: DOI and DOC are, in some ways, uniquely important drugs.
As some of the last psychedelics that are not already banned by the DEA, they are indispensable tools for scientists who study how psychedelic drugs and the serotonin system more broadly, work. A quick Google Scholar search for “DOC, serotonin” and “DOI, serotonin” returns tens of thousands of scientific papers exploring everything from cross-talk between the serotonin and dopamine systems, to whether activation of serotonin receptors is protective against brain cancers. Very little sets these papers apart from the millions of other highly technical studies published every year on how some specific ligand/receptor interaction modulates activity in some piece of biological machinery. Except, of course, that these particular receptor/ligand interactions were deemed politically inconvenient by Nixon and friends in the mid-20th century, and all of the tools that could be used to do science were locked behind regulatory doors.
Except for DOI, DOC, and a small handful of other compounds, that is.
This is not the first time in recent memory that the DEA has attempted to schedule DOI and DOC. They tried in 2022, although the proposal was withdrawn with no explanation given. At the time, I thought that perhaps the outcry from scientists had prompted the agency to change its mind, but it doesn’t seem that that’s the case (if it was, why attempt again so soon again?). It seems like someone has a bee in their bonnet about these drugs and would like to see them banned, and they don’t apparently care about the knock-on effects on scientific research in the United States.
This is a subject on which I can speak with some professional authority. As a neuroscientist interested in the ways that the serotonin system helps regulate brain dynamics and behavior, psychedelic drugs are one of many tools that I (and others in the field) have used to study the mechanistic foundations of brain activity. This is basic science: no mysticism or anything that might get derisively written off as “woo-woo”, and is just as integral a part of the project of neuroscience as any of the other million ways neuroscientists explore the brain. No one is spending hard-won grant money buying drugs to personally get high with.
However, if you happen to ask the wrong scientific question, you can find your progress blocked by a mountain of bureaucratic red tape required even get permission to have the compounds in your lab. Working with something like N,N-dimethyltryptamine (N,N-DMT) requires getting a Schedule 1 drug license from the DEA, which can take significant time and requires filling out forms, purchasing special storage facilities for the drugs, implementing complex handling protocols, and of course, paying fees. And of course the licenses are only valid for a fixed term and must be continually re-applied for, so this is a commitment to years of often Kafkaesque bureaucratic hassle. If you want to take a look at all the regulations involved with merely ordering a Schedule 1 or Schedule 2 drug, look here, although be warned; it’s eye-watering stuff full of terrifying words like “triplicate” and worryingly detailed instructions on how to dispose of unused paperwork.
Getting around the regulations.
When I approached my PhD mentors about the possibility of exploring how psychedelic drugs influenced the information processing dynamics of neural networks they were both enthusiastic, but we immediately ran into the problem that none of us had a Schedule 1 license, and none of us had funding to make all the changes required to bring the lab up to snuff. Even if we did, purchasing scheduled drugs from a chemical supply company like Sigma-Aldrich is generally quite expensive (manufacturing highly controlled molecules is expensive, and that cost is passed onto scientists). By the time we had 1) gotten a grant that could cover the material requirements and 2) applied for and received the license, I’d have been long gone. The whole project was very nearly dead-on-arrival, due entirely to the regulatory constraints on doing this kind of research. The project itself was scientifically sound: we had the technology and expertise to record neural activity organotypic cultures, we had validated the statistical measures in a variety of other studies, and there were compelling theoretical reasons to believe that the results would be of interest to the broader scientific community. It’s everything you want in a PhD project, but again, the regulations very nearly stymied us from the get-go.
I say “very nearly” because we were, actually, able to do the project, but only by finding a psychedelic drug, of the class I was interested in (tryptamine analogs of serotonin), that was not scheduled by the DEA or the state of Indiana. Enter: N,N-dipropyltryptamine (DPT). DPT is a very close structural analogue of the highly-illegal darling of online psychonauts N,N-dimethyltryptamine (DMT). The only difference is the addition of four extra carbon atoms on the tails, and it is known to be quite psychedelic in humans. There’s even a “temple” (cult?) in New York City that uses DPT it as a religious sacrament. Since it is unscheduled, we were able to buy the necessary quantities from a reputable chemical supply company, dose our brain slices with them, and complete the project in time for me to graduate. The resulting paper (currently available on the arXiv) is under review at a peer-reviewed journal and I am confident that it will be a worthy contribution to the scientific literature.
None of this would have been possible if we hadn’t known about DPT, and this same story plays out every day in neuroscience labs all over the country.
There are, of course, plenty of labs doing good, basic science on scheduled drugs. In general though, those labs have made these drugs their primary area of focus. For example, I’m a huge fan of the work by the Gonzalez-Maeso lab, which has been churning out papers on the biology of psychedelic drugs at least since I was in college. If you are a scientist who has chosen to make a career out of studying this class of compounds, then it absolutely makes sense to deal with all the regulatory hurdles (and I think most people would agree that, if a lab is keeping large quantities of LSD around, someone should be keeping an eye on that). This is not the kind of work that will be kneecapped by the DEA’s attempts to schedule DOI and DOC.
Instead, it will be projects like mine: the labs I worked in were not “psychedelic science” labs. We had our own, non-psychedelic research interests that, in one case, intersected with psychedelic science and inspired the study. However, if we hadn’t had access to DPT (or DOI/DOC) it wouldn’t have made sense for us to get a Schedule 1 license just to do my project.
The science just wouldn’t have gotten done.
Maybe I would have used a different drug less relevant to the question I was asking, or maybe I’d have just gone and done something else.
These are the kinds of studies that the DEA is proposing to make even harder: interdisciplinary bridge-building between different areas of biology, neuroscience, and preclinical research. One of the cases I am most concerned about is the nascent line of research related psychedelic drugs to inflammatory processes, and neuroinflammation in particular. It turns out that psychedelic drugs are weirdly powerful anti-inflammatory agents, and this discovery has already begun to spin off into a whole new line of clinical research investigating what psychedelics might tell us about diseases like fibromyaliga (a complex, chronic pain disorder which, on the surface, seems like it would have very little to do with psychedelics). I myself suffer from a chronic pain condition that psychedelics might prove amenable to (migraines), and so this is of particular personal interest to me as well. There are dozens, maybe hundreds of immunology labs around the country for whom this discovery may be relevant to their own work. Some may bite the bullet and fight through the regulatory red tape, but my guess is that most won’t. Time is limited, grant dollars are even more limited, and there is no question so interesting that it can’t be ignored in favor of another one (especially if the alternative is cheaper, faster, and less of an administrative headache). As long as drugs like DOI, DOC, and DPT exist, researchers won’t have to make that choice: if they find that questions about the serotonin-2A receptor intersect with their own immunological research then they can just hop onto Sigma-Aldrich, or Cayman Chemical and buy the tool they need just like any other. But if conservative organizations like the DEA get their way, that will get harder and harder. As we learn more and more about how widespread inflammation is, and the role it plays in diseases like Alzheimer's, Long COVID, and chronic, disabling conditions like ME/CFS, it makes me both saddened and angry to think that the Government would do anything to slow this research, for something as stupid as left-over, Reagan-era “Just Say No” paranoia.
Which brings me to my final thought about all of this ;which is that it really highlights how totally out of step the DEA is with...basically everything at this point. The agency seems trapped in a kind of groundhog day where every year is 1980. Pretty much everyone has heard the idea that we are in a “psychedelic renaissance”, and the deep freeze on psychedelic science that began with the passage of the Controlled Substances Act in 1971 has pretty thoroughly thawed out. This has even reached some dimensions of the Federal Government itself. The FDA has granted “breakthrough” designation to two Schedule 1 drugs: MDMA and psilocybin as treatments for PTSD and depression, and states are beginning to legalize certain psychedelic drugs on their own. My own town of Northampton, Massachusetts recently decriminalized psilocybin mushrooms, Ayahuasca, and iboga, as have a number of other cities, and the states of Oregon and Colorado. Psychedelic pharmaceutical companies are traded on the New York Stock Exchange and are worth millions of dollars.
So I’d be lying if I said that, in addition to the frustration and anxiety I feel about the DEA’s action, there’s also a fair amount of exasperated incredulity. The arrow of the zeitgeist is clearly pointing in one direction, and here is the DEA standing athwart the tracks of his history yelling “STOP!” For no discernible reason, either. There has been no rash of recent deaths or hospitalizations related to either drug, there’s no evidence that they are an emerging threat to public health. They don’t even appear to be that popular with recreational drug users, and the news coverage I can find related to these drugs is all from the 2000s or very early 2010s. There is no compelling reason to advance this regulation now, unless you are so consumed by the vision of a bureaucratic state that you feel like everything not mandatory must be forbidden.
It is clear, at this point, that the DEA is basically a kind of shambling golem: driven, not by any coherent scientific or even policy vision, but by the accumulated momentum of decades of conservative bureaucracy. It is out of step, not just with the scientific establishment it helps regulate (which is hardly news), but even with other arms of the Federal Government. And that’s to say nothing of the ever-widening rift between Federal drug policy and State policies on everything from cannabis to psilocybin. I have no idea what they hope to accomplish with this action and, to be frank, I’m not entirely sure it even makes sense to talk of the agency as having “goals” at this point, beyond mindlessly repeating warmed-over Reagan-era anti-drug propaganda.
It hardly matters either way though. The attempt to further kneecap an accelerating and promising field of science, for no apparent reason other than the inertia, reveals that, whatever the motivation, the DEA as an institution is a relic we no longer need. Forget about stopping them from scheduling DOI and DOC – the entire organization should just be dissolved.