The Public Record · Exhibit B
A decade of research. A company. Human trials. Now — Schedule I.
01 — The Science
This is peer-reviewed, published science — not industry talking points.
Starting around 2014, a team at Columbia University led by chemist Dalibor Sames and his former student Andrew Kruegel, working with pharmacologist Susruta Majumdar, began systematically mapping the pharmacology of kratom's alkaloids. Two publications became foundational.
In 2016, the team published in the Journal of the American Chemical Society, identifying mitragynine as an "atypical" mu-opioid scaffold — one that activates pain-relief pathways while behaving differently from classical opioids in receptor-signaling assays. In 2019, a follow-up in ACS Central Science confirmed that 7-hydroxymitragynine (7-OH) is the key active metabolite — the compound the body produces from mitragynine that drives most of the analgesic effect.
The scientific draw was specific: these alkaloids appear to be "biased" mu-opioid agonists that do not strongly recruit β-arrestin-2, a signaling pathway associated with opioid side effects including tolerance, constipation, and — critically — respiratory depression. In animal studies they showed slower tolerance than morphine and meaningfully limited respiratory suppression compared to classical opioids.
Why respiratory depression matters: it is the mechanism by which opioid overdoses kill people. A compound that relieves pain without triggering it is not a minor refinement — it is the central unsolved problem in the field.
Mitragynine, kratom's primary alkaloid, activates mu-opioid receptors through a signaling pathway that differs from morphine, codeine, and fentanyl. Its metabolite 7-OH is the more potent active form.
By not recruiting β-arrestin-2, these compounds may separate analgesia from the side-effect profile — tolerance, dependence, constipation, and respiratory depression — that makes existing opioids so dangerous at scale.
02 — The Pipeline
This research didn't stay in journals — it became a funded company in clinical trials.
Kruegel, Sames, and Majumdar establish mitragynine as an atypical opioid scaffold with potential to separate analgesia from classical opioid side effects. Kruegel tells PBS the compounds "alone may already be superior to codeine and oxycodone" — but only "if the research were able to legally continue."
ACS Central Science establishes that the body converts mitragynine into 7-OH, and that 7-OH is responsible for the majority of kratom's analgesic effect — making it a direct drug-discovery target.
atai — a publicly traded mental-health and addiction biotech — acquires Kures, a Columbia spinout co-founded by Andrew Kruegel, and takes on an exclusive license to the Sames laboratory's mitragyna alkaloid patents. The stated goal: develop novel opioid-use-disorder and pain treatments.
KUR-101 — a deuterated (chemically stabilized) form of mitragynine, not 7-OH itself — enters Phase 1 for acute pain and opioid use disorder. This is the first kratom-derived compound to reach human clinical trials.
Kures reports dose-dependent pain relief in human subjects. Crucially, effects on respiration were comparable to placebo — the hypothesis from animal studies held in humans. That is the result the entire field has been trying to produce for years.
03 — The Honest Qualifier
The drug in human trials, KUR-101, is a mitragynine derivative. The DEA's Notice of Intent targets concentrated and synthetic 7-OH plus three specific lab-made derivatives: MP, MGM-15, and MGM-16.
The DEA is placing the 7-OH chemical family — the same scaffold a decade of academic research and a funded, clinical-stage company have been mining for safer pain medicine — into Schedule I. One of the three named derivatives, MGM-15, was itself studied as a potential analgesic lead: literature describes its higher μ/δ receptor affinity and antinociceptive potency in rodents as what "initially motivated its exploration as a potential analgesic lead."
Schedule I classification raises the legal and regulatory barrier to work on the entire class. In 2016, when the DEA tried to schedule kratom's alkaloids outright, Kruegel told PBS that the compounds could "save thousands of lives" — but only "if the research were able to legally continue." That quote was written for a different scheduling attempt. It describes the same stakes.
04 — The Irony
The FDA's July 2025 scientific assessment of 7-OH — the document supporting the scheduling recommendation — draws on the same Columbia and WashU body of research that established 7-OH as a potent analgesic candidate. The science that argued "this compound has real pain-relief potential" is being cited to argue "this compound is a dangerous opioid."
Both readings come from the same data set. The question isn't whether the research is real — it plainly is. The question is what follows from it:
7-OH is a potent mu-opioid agonist with opioid-like effects — the same potency that makes it a drug-discovery target makes it an abuse and safety concern at high concentrations without a physician.
That same potency, combined with the atypical signaling profile, is exactly why it reached clinical trials. Schedule I status closes the research pathway — the one the government's own scientific record helped build the case for.
The Bottom Line
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