Changes in brain structure and age in Veterans with TBI following treatment with Magnesium-Ibogaine
Poster No:
317
Submission Type:
Abstract Submission
Authors:
Andrew Geoly1, John Coetzee1,2, Wiebke Struckmann1, Derrick Buchanan1, Azeezat Azeez1, Bora Kim1, Kirsten Cherian1, Nimrod Keynan1, Maheen Adamson2,3,4, Nolan Williams1
Institutions:
1Department of Psychiatry and Behavioral Sciences, Stanford School of Medicine, Stanford, CA, 2Rehabilitation Service, VA Palo Alto Health Care System, Palo Alto, CA, 3WRIISC-Women, VA Palo Alto Health Care System, Palo Alto, CA, 4Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, United States
First Author:
Andrew Geoly
Department of Psychiatry and Behavioral Sciences, Stanford School of Medicine
Stanford, CA
Department of Psychiatry and Behavioral Sciences, Stanford School of Medicine
Stanford, CA
Co-Author(s):
John Coetzee, PhD
Department of Psychiatry and Behavioral Sciences, Stanford School of Medicine|Rehabilitation Service, VA Palo Alto Health Care System
Stanford, CA|Palo Alto, CA
Department of Psychiatry and Behavioral Sciences, Stanford School of Medicine|Rehabilitation Service, VA Palo Alto Health Care System
Stanford, CA|Palo Alto, CA
Wiebke Struckmann
Department of Psychiatry and Behavioral Sciences, Stanford School of Medicine
Stanford, CA
Department of Psychiatry and Behavioral Sciences, Stanford School of Medicine
Stanford, CA
Derrick Buchanan, PhD
Department of Psychiatry and Behavioral Sciences, Stanford School of Medicine
Stanford, CA
Department of Psychiatry and Behavioral Sciences, Stanford School of Medicine
Stanford, CA
Azeezat Azeez
Department of Psychiatry and Behavioral Sciences, Stanford School of Medicine
Stanford, CA
Department of Psychiatry and Behavioral Sciences, Stanford School of Medicine
Stanford, CA
Kirsten Cherian, PhD
Department of Psychiatry and Behavioral Sciences, Stanford School of Medicine
Stanford, CA
Department of Psychiatry and Behavioral Sciences, Stanford School of Medicine
Stanford, CA
Nimrod Keynan, PhD
Department of Psychiatry and Behavioral Sciences, Stanford School of Medicine
Stanford, CA
Department of Psychiatry and Behavioral Sciences, Stanford School of Medicine
Stanford, CA
Maheen Adamson, PhD
Rehabilitation Service, VA Palo Alto Health Care System|WRIISC-Women, VA Palo Alto Health Care System|Department of Neurosurgery, Stanford University School of Medicine
Palo Alto, CA|Palo Alto, CA|Stanford, CA, United States
Rehabilitation Service, VA Palo Alto Health Care System|WRIISC-Women, VA Palo Alto Health Care System|Department of Neurosurgery, Stanford University School of Medicine
Palo Alto, CA|Palo Alto, CA|Stanford, CA, United States
Nolan Williams
Department of Psychiatry and Behavioral Sciences, Stanford School of Medicine
Stanford, CA
Department of Psychiatry and Behavioral Sciences, Stanford School of Medicine
Stanford, CA
Introduction:
Introduction: Traumatic brain injury (TBI) is common among Veterans of recent US conflicts.1 TBI may lead to a range of neuropsychiatric symptoms,2 and may also be associated with accelerated brain aging,3 increasing the risk for dementia and other neurodegenerative diseases.4
Ibogaine, a naturally-occurring psychoactive alkaloid, has demonstrated neuroplasticity promoting properties, including increased neurogenesis and enhanced synaptic plasticity via the release of neurotrophic factors, such as brain-derived neurotrophic factor (BDNF) and GDNF (glial cell-derived neurotrophic factor).5 This may help remodel neural circuitry and improve cognitive function, emotional regulation, and physical well-being in Veterans with TBI.
Ibogaine, a naturally-occurring psychoactive alkaloid, has demonstrated neuroplasticity promoting properties, including increased neurogenesis and enhanced synaptic plasticity via the release of neurotrophic factors, such as brain-derived neurotrophic factor (BDNF) and GDNF (glial cell-derived neurotrophic factor).5 This may help remodel neural circuitry and improve cognitive function, emotional regulation, and physical well-being in Veterans with TBI.
Methods:
Methods: We conducted an observational study with 30 Veterans with multiple blast TBI (mbTBI) and complex clinical problems who received supervised ibogaine treatment (up to 21mg/kg) over a period of several hours, preceded and followed by multiple days of preparation and integration. At the baseline, immediate post, and 1-month time points, we performed clinical assessments and structural magnetic resonance imaging (MRI) scans. We derived cortical thickness measures for our participants with the Advanced Normalization Tools (ANTs) longitudinal cortical thickness pipeline, and evaluated thickness and volumetric statistics in cortical and subcortical gray matter and cerebellar regions of interest (ROIs), respectively. To evaluate longitudinal changes in cortical thickness and volume across the ROIs, we employed linear mixed effects (LME) models. We used the algorithm described by Cole et al. (2015)6 to determine brain age using T1s.
Results:
Results: Wald Χ2 test of regional LME models revealed a significant (pFDR < 0.05) main effect of study visit on cortical thickness in 13 ROIs. Subsequent post-hoc pairwise t-tests demonstrated significant (pholm < 0.05) increases in cortical thickness immediately following ibogaine therapy (~7 days) relative to the baseline visit in 11 regions. No significant changes were found between immediate-post and 1-month post visits, suggesting a likely sustained increase in cortical thickness across the study period following treatment. For subcortical volume, Wald Χ2 test of the subcortical LME models revealed a significant (pFDR < 0.05) main effect of study visit on the log-jacobian determinant in the Right Ventral Diencephalon which was sustained at the one month time point. Estimated marginal mean predicted brain age for each timepoint was as follows 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 significant change across timepoints [Χ2(2) = 10.64, p = 0.0049]. Post-hoc paired sample t-tests revealed a significant (pholm < 0.05) reduction of 1.60 years in predicted brain age relative to baseline one month after ibogaine treatment (t = 3.18, p = 0.0082, d = 1.035).
Conclusions:
Conclusions: This work provides the first evidence of measurable brain morphometric changes in humans following ibogaine therapy, suggesting that ibogaine therapy may reduce signs of accelerated brain aging in Veterans with mbTBI. Given the heightened risk of dementia associated with TBI, this has important implications for the treatment of this underserved patient group. However, more research is needed to fully understand the therapeutic mechanisms by which ibogaine works and to determine the long-term impact on cortical structure.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 1
Psychiatric (eg. Depression, Anxiety, Schizophrenia)
Lifespan Development:
Aging
Novel Imaging Acquisition Methods:
Anatomical MRI 2
Keywords:
Aging
Plasticity
Psychiatric Disorders
STRUCTURAL MRI
Trauma
1|2Indicates the priority used for review
Provide references using author date format
1. Hayward, P. Traumatic brain injury: the signature of modern conflicts. Lancet Neurol. 7, 200–201 (2008).
2. Rickels, E. et al. The Long-Term Sequelae of Traumatic Brain Injury Over 10 Years of Follow-Up—A Matched Cohort Study Based on Routine Data of a Statutory Health Insurance Carrier. Dtsch. Arzteblatt Int. 120, 271–276 (2023).
3. Gan, S. et al. Accelerated Brain Aging in Mild Traumatic Brain Injury: Longitudinal Pattern Recognition with White Matter Integrity. J. Neurotrauma 38, 2549–2559 (2021).
4. Weiner, M. W. et al. Effects of traumatic brain injury and posttraumatic stress disorder on development of Alzheimer’s disease in Vietnam Veterans using the Alzheimer’s Disease Neuroimaging Initiative: Preliminary report. Alzheimers Dement. Transl. Res. Clin. Interv. 3, 177–188 (2017).
5. Marton, S. et al. Ibogaine Administration Modifies GDNF and BDNF Expression in Brain Regions Involved in Mesocorticolimbic and Nigral Dopaminergic Circuits. Front. Pharmacol. 10, 193 (2019).
6. Cole, J. H., Leech, R., Sharp, D. J. & Initiative, for the A. D. N. Prediction of brain age suggests accelerated atrophy after traumatic brain injury. Ann. Neurol. 77, 571–581 (2015).