Magnesium–ibogaine therapy effects on cortical oscillations and neural complexity in veterans with traumatic brain injury

This analysis of an open-label observational study (n=30) found that magnesium-ibogaine therapy in combat veterans with traumatic brain injury (TBI) led to slower brain wave patterns and reduced neural complexity on EEG, which correlated with improvements in PTSD, anxiety, and cognitive function at one-month follow-up.

Abstract of Magnesium–ibogaine therapy effects on cortical oscillations and neural complexity in veterans with traumatic brain injury

“Traumatic brain injury can lead to chronic psychiatric and cognitive symptoms, coupled with changes to the nature of cortical oscillations and neural complexity. Treatment with magnesium–ibogaine was recently found to improve the sequelae of traumatic brain injury, yet the effects of ibogaine on human cortical oscillations and complexity are unknown. Resting-state electroencephalography was performed prospectively before, 3.5 days after and 1 month after magnesium–ibogaine therapy in an observational, open-label study of 30 combat veterans. We assessed the effects of ibogaine on cortical oscillations and complexity and how these neurophysiological effects relate to psychiatric and cognitive outcomes of ibogaine treatment. After treatment, slower oscillations (theta–alpha) increased in power, and power at higher frequencies (beta–gamma) decreased. Accordingly, the theta/beta ratio increased post-treatment, which correlated with improved cognitive inhibition. Peak alpha frequency and neural complexity were lower after treatment, which persisted at 1-month follow-up. These neurophysiological markers correlated with improved executive function, post-traumatic stress disorder and anxiety after ibogaine. Altogether, these findings suggest reduced spatiotemporal complexity of brain activity and ‘slowing’ of cortical oscillations in the brain at rest after magnesium–ibogaine therapy, which may relate to psychiatric and cognitive improvements after ibogaine, thus providing key insight into the effects of ibogaine on brain function in humans. Follow-up controlled clinical trials are needed to confirm the findings from this initial single-arm trial.“

Authors: Jennifer I. Lissemore, Anna Chaiken, Kirsten N. Cherian, Derrick Buchanan, Flint Espil, Jackob N. Keynan, Malvika Sridhar, Camarin E. Rolle, Manish Saggar, Corey J. Keller & Nolan R. Williams

Summary of Magnesium–ibogaine therapy effects on cortical oscillations and neural complexity in veterans with traumatic brain injury

Traumatic brain injury (TBI) often leaves enduring psychiatric and cognitive sequelae, such as post-traumatic stress disorder (PTSD), depression, anxiety and deficits in executive function. Conventional pharmacological and psychotherapeutic treatments fail many veterans, prompting the search for novel interventions. ibogaine—an oneirogenic alkaloid with a uniquely broad receptor profile—has shown rapid symptomatic relief in open-label studies, yet its effects on human brain function have remained largely unexplored. Cortical oscillations (rhythmic brain activity measurable with electroencephalography, EEG) and neural complexity (the diversity of spatiotemporal activity patterns across the cortex) are known to be disrupted after TBI and to track symptom severity. Lissemore and colleagues therefore set out to characterise how a single dose of magnesium-buffered ibogaine alters these neurophysiological indices in combat veterans and how such changes relate to clinical outcome. They hypothesised that (i) oscillatory power across the delta–gamma range and spatiotemporal complexity would shift in the days following treatment, (ii) these shifts would correlate with symptom improvement, and (iii) specific pretreatment EEG features would predict the magnitude of clinical benefit.

Results

Ibogaine enhances theta–alpha power and suppresses beta–gamma activity

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Magnesium–ibogaine therapy effects on cortical oscillations and neural complexity in veterans with traumatic brain injury

https://doi.org/10.1038/s44220-025-00463-x

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Cite this paper (APA)

Lissemore, J. I., Chaiken, A., Cherian, K. N., Buchanan, D., Espil, F., Keynan, J. N., ... & Williams, N. R. (2025). Magnesium–ibogaine therapy effects on cortical oscillations and neural complexity in veterans with traumatic brain injury. Nature Mental Health, 1-14.

Study details

Compounds studied
Ibogaine

Topics studied
Traumatic Brain Injury Neuroscience

Study characteristics
Original Re-analysis Open-Label Re-analysis Bio/Neuro

Participants
30 Humans

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Magnesium–ibogaine therapy in veterans with traumatic brain injuries
This observational study (n=30) evaluates ibogaine (up to 980mg/70kg) in combination with magnesium (1-2 hours before and 12 hours later) in male Special Operations Forces veterans with predominantly mild traumatic brain injury (mTBI). The study assessed changes in disability, PTSD, depression, and anxiety immediately and one month after treatment using various scales. Results show significant improvements in functioning and psychological symptoms with no serious adverse events.