A new study published in Nature Mental Health provides initial evidence that the psychedelic compound ibogaine may alter brain activity and improve psychiatric symptoms in individuals with a history of traumatic brain injury. In a group of combat veterans, researchers found that magnesium-ibogaine therapy was associated with changes in cortical oscillations and neural complexity, which were linked to improvements in cognitive functioning, post-traumatic stress, and anxiety. These findings offer a rare look at the neural effects of ibogaine in humans and suggest that altered brain rhythms may play a role in its therapeutic potential.
Ibogaine is a psychoactive alkaloid derived from the root bark of the Tabernanthe iboga shrub, native to Central Africa. Traditionally used in spiritual ceremonies, ibogaine has gained attention in recent years for its possible therapeutic properties, particularly in treating substance use disorders. More recently, anecdotal reports and small studies have suggested that it might help with symptoms related to traumatic brain injury, or TBI, such as anxiety, depression, cognitive dysfunction, and post-traumatic stress.
Unlike classic psychedelic compounds such as psilocybin or LSD, ibogaine is categorized as oneirogenic—it tends to produce immersive, dream-like states accompanied by extended periods of self-reflection. Its effects are long-lasting and pharmacologically complex. Ibogaine interacts with a wide array of targets in the brain, including serotonin and dopamine transporters, opioid receptors, and the N-methyl-D-aspartate system. Despite this pharmacological breadth, little is known about how ibogaine alters human brain function.
To address this gap, researchers Jennifer I. Lissemore, Corey J. Keller, Nolan R. Williams, and their colleagues at Stanford University conducted a prospective study to explore how a single session of magnesium-ibogaine therapy might affect brain activity. They focused on two neural features commonly altered by brain injury: cortical oscillations, which refer to rhythmic patterns of neural activity, and neural complexity, which reflects how variable or stable brain signals are over time.
“Many veterans have independently sought out ibogaine treatment based on anecdotal reports, despite the lack of safety data or scientific validation in this population,” explained Lissemore, a postdoctoral scholar affiliated with the Brain Stimulation Lab.
“We saw a critical need to rigorously study ibogaine in a controlled setting – both to evaluate its therapeutic potential and to better understand its impact on brain function. This study was designed to address that gap and provide the first clinical and neurophysiological evidence to inform policy, clinical practice, and future trials. This study was also motivated by our overarching interest as researchers in developing new, rapid-acting treatment options in psychiatry.”
The study involved 30 male veterans who had previously served in Special Operations Forces and had documented histories of traumatic brain injury from combat, blast exposure, or head trauma. Most of the participants reported psychiatric diagnoses at baseline, including post-traumatic stress, depression, anxiety, and alcohol use disorder. On average, participants had experienced nearly 39 TBIs across their lifetimes, most of which were classified as mild.
Before undergoing ibogaine treatment, participants stopped taking medications that could interfere with the compound. They then traveled independently to a treatment facility in Mexico, where they received oral ibogaine combined with intravenous magnesium sulfate—a formulation known as magnesium-ibogaine. The magnesium was added to reduce potential cardiovascular risks associated with ibogaine, such as disruptions to heart rhythms. No psychotherapy was delivered during the experience, although preparatory and integration coaching were offered.
To assess changes in brain function, participants underwent high-density electroencephalography (EEG) scans at three time points: before treatment, roughly three and a half days afterward, and again one month later. During the EEG recordings, participants were asked to keep their eyes open and remain awake while letting their minds wander. EEG data were analyzed to examine both frequency-specific brain rhythms (e.g., theta, alpha, beta, gamma) and measures of neural complexity.
After ibogaine treatment, participants showed changes in the rhythms of their brain activity. Specifically, the power of slower oscillations—particularly those in the theta (4–8 Hz) and alpha (8–13 Hz) ranges—increased, while faster oscillations in the beta (13–30 Hz) and gamma (30–50 Hz) bands decreased. This shift toward slower activity was reflected in a higher ratio of theta to beta power, which correlated with improvements in executive functioning, particularly in tasks requiring cognitive inhibition.
Another key finding was a reduction in peak alpha frequency—essentially a slowing of the brain’s dominant rhythm. This effect was most prominent in posterior brain regions and persisted even one month after treatment. Lower peak alpha frequency after ibogaine was associated with reductions in post-traumatic stress and anxiety symptoms.
Neural complexity, as measured by Lempel–Ziv complexity (a statistical index of signal variability), also decreased after treatment. Lower complexity suggests that brain signals became more stable and less random over time. This reduction in complexity was linked to improvements in executive functioning, and individuals who had lower complexity at baseline tended to experience greater cognitive gains after treatment.
Some of the effects on brain rhythms and complexity were still present one month after treatment, suggesting that ibogaine may lead to lasting changes in how the brain organizes its activity at rest.
Several of the observed changes in EEG measures were tied to clinical improvements. For example, participants who showed greater increases in the theta/beta ratio also demonstrated larger gains in cognitive inhibition, a form of executive control. Similarly, those with more pronounced decreases in peak alpha frequency experienced greater reductions in post-traumatic stress symptoms, particularly in the arousal and reactivity domain.
“A single treatment led to large and lasting improvements in symptoms like PTSD, anxiety, and difficulties with thinking,” Lissemore told PsyPost. “Brain recordings (EEG) showed that these improvements were accompanied by changes in brain activity – ibogaine shifted brain activity toward slower, calmer rhythms and made brain signals more predictable. These changes suggest that ibogaine may help the brain move into a more stable state that is potentially less reactive to stress – something especially important for recovery from TBI and PTSD.”
At baseline, individuals with lower peak alpha frequency and lower neural complexity were more likely to benefit from treatment. These findings suggest that EEG patterns recorded before treatment might help predict who is most likely to respond to ibogaine.
The authors note that slower brain rhythms, especially in the theta range, have been linked in previous studies to neuroplasticity and long-term learning. It is possible that the observed increase in theta power after ibogaine reflects a brain state more conducive to change, especially in people recovering from trauma.
“Clinically, the extent of improvement in symptoms after ibogaine treatment was surprising,” Lissemore said. “Neurobiologically, the changes in brain function that we saw after a single treatment with ibogaine were a lot like the changes we see in the brain after long-term meditation practice.”
Although the results are promising, it is important to note that the study was not a randomized controlled trial. All participants received the same treatment, and there was no placebo group for comparison. This makes it difficult to rule out the influence of expectancy, coaching, or other factors unrelated to the pharmacological effects of ibogaine. The sample was also highly specific—male Special Operations veterans with high TBI exposure—and may not generalize to broader clinical populations. Still, the magnitude and persistence of the observed brain and behavioral changes provide a strong rationale for follow-up trials using more rigorous designs.
“The results need to be confirmed in larger, controlled trials,” Lissemore said. “That said, this is the first study to show how ibogaine affects brain activity in humans, and it provides an important first step toward developing magnesium-ibogaine as a potential treatment for veterans with traumatic brain injury.”
“While not yet ready for routine use, these findings offer a potential new path forward for treating complex post-TBI symptoms in veterans, particularly when other therapies have failed. The results may encourage federal physicians to support further research and consider enrollment of patients into future clinical trials.”
“Ibogaine is a powerful compound that should not be used outside of medically supervised settings,” Lissemore added. “Clinicians should view these findings as promising early evidence that a therapeutic shift in brain state may be achievable in a single ibogaine session, but further research and regulatory steps are needed before clinical use.”
The study, “Magnesium–ibogaine therapy effects on cortical oscillations and neural complexity in veterans with traumatic brain injury,” was authored by 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, and Nolan R. Williams.
