This study aims to understand how ibogaine treatment may change brain activity and symptoms in people with moderate-severe opioid use disorder (OUD), as defined by the DSM-5. Ibogaine is a plant-derived compound that some studies suggest can reduce opioid cravings and withdrawal. Participants in this study will already be independently scheduled to receive legal ibogaine treatment at a licensed clinic outside of the U.S. The University of California, Irvine (UCI) research team will not provide the treatment but will conduct brain imaging, administer psychometric questionnaires, and obtain urine samples throughout the course of this study. UCI does not sponsor or financially support the ibogaine treatment in any way; all treatment costs are the sole responsibility of the participant.

The main goal is to see if ibogaine changes brain function as assessed with magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and electroencephalography (EEG). MRI/MRS will measure brain activity when participants view opioid-related images, brain connectivity at rest, and levels of brain chemicals involved in craving and substance use. EEG will measure brain wave activity. MRI/MRS/EEG will be administered across 3 study time points. In addition, participants will complete psychometric surveys related to opioid craving, withdrawal symptoms, mood, anxiety, pain, and quality of life, along with urine tests to monitor substance use and screen for pregnancy.

The investigators hypothesize that after ibogaine treatment, participants will show reduced brain responses to opioid cues, changes in brain connectivity and chemistry, and improvements in self-reported cravings and other symptoms. This information may help researchers better understand how ibogaine works in the brain and whether it could play a role in future treatments for OUD.

Primary Hypothesis:

3-5 days and 1-month after ibogaine treatment (compared to baseline), participants will show reduced brain responses to opioid-related images on task fMRI and reduced resting-state connectivity within reward circuitry. The brain areas expected to be affected include the basal ganglia, cingulate cortex, hippocampus, and amygdala. Post-ibogaine spectroscopy will also show lower glutamate + glutamine (Glx) levels within the insula and nucleus accumbens.

Exploratory Hypotheses:

The magnitude of MRI/MRS changes (including activation/connectivity in the cingulate, hippocampus, and amygdala) will correlate with improvements in opioid craving and related symptoms measured by validated questionnaires (e.g., VAS craving, SOWS, CEQ).

EEG will show relative decreases in alpha power, relative decreases in gamma power, and decreases in frontal alpha frequency and signal complexity, which will track with reductions in craving and withdrawal.

Inclusion Criteria:

• Adults aged 21-70 with confirmed moderate to severe OUD as assessed by equal or greater than 4 symptoms using DSM-5 criteria.
• Independently scheduled to receive ibogaine treatment at Ambio Life Sciences in Tijuana, Mexico.
• Able to undergo MRI and EEG procedures at UC Irvine at Visit 1 (baseline), Visit 4, and Visit 5, totaling three sessions.
• Able to complete psychometric surveys at each study time point.
• Able to provide urine samples at all three scanning sessions at UCI.
• Able to provide urine samples at a local external lab for 3- and 6-month follow-ups.
• Capable of giving written informed consent.
• Proficient ability to speak, read, and write in English.

Exclusion Criteria:

• Presence of known past procedures, devices in the body, claustrophobia, or other contraindications for MRI.
• Use of any psychedelic substances within 3 months prior to screening.
• Diagnosis of schizophrenia, bipolar disorder (type I or II), or borderline personality disorder.
• Use of ibogaine within 6 months prior to screening.
• Pregnant or nursing. Participants who become pregnant during the study will be withdrawn from further participation.
• Diagnosis of epilepsy or history of seizures.
• Other contraindications to MRI/EEG methods. These may include but are not limited to: brain surgical clips and surgical staples, metal implants in the brain, and certain metallic dental material.
• Inability to complete MRI/EEG sessions or follow-up visits.
• Inability or unwillingness of an individual to give written informed consent.

Note: UCI does not sponsor or financially support the ibogaine treatment in any way; all treatment costs are the sole responsibility of the participant.

Adults ages 21 to 70 with a confirmed diagnosis of moderate to severe opioid use disorder (OUD), defined as meeting four or more symptoms according to DSM-5 criteria. Participants must be independently scheduled to receive ibogaine treatment at a licensed clinic outside the United States.