Psychiatric Times: NIH Phase 1 Trial of Mitragynine for Opioid Use Disorder Cleared to Proceed

Why it matters

FDA acceptance of an IND for mitragynine marks the first time a kratom alkaloid will undergo a rigorous U.S. government-sponsored phase 1 safety trial, a critical step toward potential approval as an opioid use disorder treatment. This happens simultaneously with the DEA moving to schedule 7-OH — a metabolite of mitragynine — illustrating the tension between kratom's harms and potential benefits.

The big picture

The NIH HEAL Initiative's phase 1 trial will evaluate MG001, an oral mitragynine formulation developed by NIH and University of Florida researchers. Mitragynine works as a partial opioid mu-receptor agonist and antagonist at kappa and delta receptors, with additional adrenergic and serotonergic activity. A prior European phase 1 study found low doses produced stimulant-like effects while a 40 mg dose produced mild psychopathological symptoms. Importantly, the DEA's 7-OH scheduling does not affect the trial, because the mitragynine dose levels produce 7-OH concentrations well below the DEA threshold.

Key findings

• FDA accepted an IND for MG001, an oral mitragynine formulation, for a phase 1 opioid use disorder trial
• Approximately 32 healthy volunteers will receive single doses of 25, 50, 75, or 100 mg or placebo
• Participants will be monitored for 4 days inpatient plus a day 7 follow-up visit
• Safety monitoring includes vital signs, ECG/QTc, pupil constriction, sedation scores, and full pharmacokinetic sampling
• DEA scheduling of 7-OH does not affect this trial — peak 7-OH from whole-plant kratom or MG001 stays below DEA thresholds
• A previous European phase 1 study found minimal effects at 5-20 mg and stimulant-like changes at the lowest (5 mg) dose

What they say

"We have seen the potential of mitragynine in the lab, and now we are finally able to examine its potential in people," stated Joni Rutter, PhD, director of the National Center for Advancing Translational Sciences at NIH. "Hopefully, this work will lead to a new treatment option for people with opioid use disorder and support a path to recovery."

Bottom line

The NIH's first human phase 1 trial of mitragynine for opioid use disorder has been cleared to begin — a scientific milestone that unfolds in direct tension with the DEA's simultaneous move to schedule 7-OH, a metabolite produced when mitragynine is metabolized in the body.