Changes in Brain Structure and Age in Veterans with TBI Following Treatment with Magnesium-ibogaine

Research Objectives: TBI is common among Veterans of US conflicts and can lead to accelerated brain aging. Ibogaine, a psychoactive alkaloid, has demonstrated neurotrophic properties. This may help remodel neural circuitry and improve cognitive function and emotional regulation.

Design: Participants arrived at Stanford University two to three days before their treatment. During this period, they underwent in-person assessments encompassing self-report measures, clinical and neuropsychological evaluations, and MR imaging. Following the evaluations, participants underwent ibogaine treatment, involving approximately 13 mg/kg of oral ibogaine after an intravenous infusion of magnesium. Subsequently, participants returned to Stanford for a follow-up evaluation four to five days post-treatment, with an additional assessment conducted one month later.

Setting: MRI Scans were collected at the Center for Cognitive and Neurobiological Imaging at Stanford University.

Participants: 30 Veterans with multiple blast TBI (mbTBI) and complex clinical problems were enrolled. They were from special forces.

Interventions: 30 participants received supervised ibogaine treatment (up to 21mg/kg) over several hours, preceded and followed by days of preparation and integration. At baseline, immediate post, and 1 month timepoints, we performed clinical assessments and MRI scans.

Main Outcome Measures: Cortical thickness, volumetric MRI and brain aging in structural MRI.

Results: Wald Χ2 test of regional LME models revealed a sig. (pFDR < 0.05) main effect of study visit on CT in 13 ROIs. Post-hoc pairwise t-tests demonstrated sig. (pholm < 0.05) increases in CT immediately following ibogaine therapy (~7 days) relative to baseline visit in 11 regions. No sig. changes were found between immediate post and 1 month post visits, suggesting sustained increase in CT across the study period. For subcortical volume, Wald Χ2 test of subcortical LME models revealed a sig. (pFDR < 0.05) main effect of study visit on the log-jacobian determinant in the Right Ventral Diencephalon which was sustained at the 1 month time point. Estimated marginal mean predicted brain age for each timepoint was M(SE): baseline 39.7(1.73), immediate post 39.1(1.73), 1-month 38.1(1.74). Wald Χ2 test of the LME, revealed a sig. change across timepoints [Χ2(2) = 10.64, p = 0.0049]. Post-hoc paired sample t-tests revealed a sig. (pholm < 0.05) reduction of 1.60 years in predicted brain age relative to baseline 1 month after ibogaine treatment (t = 3.18, p = 0.0082, d = 1.035).

Conclusions: This is the first evidence of morphometric brain changes in humans following ibogaine therapy, suggesting ibogaine may reduce accelerated brain aging in Veterans with mbTBI.

Author(s) Disclosures: Dr. Adamson is presenting and does not have any disclosures.