Mapping Ibogaine Neural Dynamics in Opioid Use Disorder

Brock Pluimer and colleagues, University of California, Irvine and Ambio Life Sciences

Researchers at the Susan Samueli Integrative Health Institute at the University of California, Irvine are studying how the brain changes after ibogaine treatment in people with moderate to severe opioid use disorder. The project is called Mapping Ibogaine Neural Dynamics in Opioid Use Disorder, or MIND OUD, and is registered as NCT07226570.

The UCI team is not administering the treatment. Participants are already scheduled to receive legal treatment at Ambio Life Sciences in Mexico. The researchers measure them before and after treatment using MRI, magnetic resonance spectroscopy, EEG, questionnaires, and urine testing. The goal is to look at several different parts of the same problem at once: how strongly the brain responds to opioid cues, how reward-related regions communicate at rest, changes in glutamate and glutamine, changes in brain wave activity, and changes in craving, withdrawal, mood, pain, and substance use. The full study is designed to enroll 20 participants.

The first poster reports preliminary results from five participants. All five tested negative for opioids after treatment. Craving and withdrawal decreased, participants met fewer DSM 5 opioid use disorder criteria, and confidence in refusing drugs increased. The EEG recordings also showed a reduction in resting alpha power. During the MRI drug cue task, activation in the basal ganglia decreased when participants were shown opioid related images.

That last finding is directly related to my work on reward system recovery. My 2025 paper proposed that ibogaine may do more than suppress withdrawal. Part of the longer-term effect may involve changing the way reward systems respond to drug-related information. If an opioid cue produces a weaker response in the basal ganglia after treatment, one possibility is that the cue no longer carries the same motivational weight that it did before treatment.

There are important limits to what can be said from five people. The Ambio protocol also includes 5 MeO DMT after ibogaine, which means these results cannot yet be assigned specifically to ibogaine. The researchers acknowledge both problems. These are descriptive findings from an observational, unblinded study without a placebo control; formal statistical testing is planned after enrollment reaches the target sample size.

The larger study should tell us much more. I would eventually like to see the same approach expanded beyond opioid cues. Reward, threat, salience, craving, interoception, and cognitive control can all be tested directly. Pairing those tasks with resting EEG and imaging would tell us not only whether the brain changed, but whether the systems involved actually respond differently when they are challenged.

My hope is that this will provide empirical support for reward system restoration. Reduced cue reactivity alone would not establish that broader claim.