Researchers at Stanford University have reported remarkable improvements in veterans suffering from traumatic brain injuries (TBIs) using a novel treatment protocol. The study, which involved a combination of magnesium and ibogaine, a naturally occurring psychedelic substance, showed significant reductions in disability and psychiatric symptoms, including post-traumatic stress disorder, depression, and anxiety. The findings have been published in the journal Nature Medicine.
The motivation behind this pivotal research stems from the urgent need to address the complex health challenges faced by veterans, particularly those with a history of TBIs, commonly resulting from military combat and blast exposures. These injuries often lead to debilitating neuropsychiatric symptoms, for which existing treatments are typically less effective. The Stanford team, understanding the gravity of these conditions, aimed to explore alternative and more effective treatment options.
Ibogaine is a naturally occurring psychedelic substance found in the root bark of the Tabernanthe iboga shrub, traditionally used in African spiritual and healing ceremonies. It has attracted scientific interest due to its unique pharmacological properties, exhibiting moderate to weak affinity for various neurotransmitter receptors and increasing the transcription of neurotrophic factors, which are crucial for brain health.
“The Stanford Brain Stimulation Lab is interested in research and innovation in novel treatment models, including psychedelics, to improve outcomes for populations who are not effectively treated through currently available interventions,” said study author Kirsten Cherian, a postdoctoral research fellow at Stanford Medicine.
“As a neuropsychologist, I am particularly interested in interventions with high efficacy and safety for people who are struggling with impairments in cognition, mood, and function as a result of neuropsychiatric conditions and TBI.”
“Members of our study population, Special Forces Veterans, have been living with TBI in addition to other challenges to healthy functioning, including PTSD, depression, anxiety, substance use disorders, suicidality, and other medical sequelae of repeated blast and combat exposures. Currently, available treatments can be less effective for individuals with this kind of presentation of multiple and multifaceted conditions.”
“Some veterans have been crossing the border to access ibogaine treatments not currently legal in the United States. Although ibogaine is currently being accessed therapeutically, the field is early in investigating its treatment potential and safety profile. We were first to provide prospective clinician assessed data about ibogaine treatment efficacy, mechanisms, and safety for TBI and other sequelae of repeated exposure to blasts and combat.”
To conduct this study, the researchers engaged 30 male veterans, all of whom had a history of mild TBIs and repeated blast exposures. These participants were experiencing severe psychiatric symptoms and functional disabilities at the time of the study. The treatment involved administering a specific dosage of oral ibogaine, followed by a thorough evaluation of its effects.
Following the initial assessments at Stanford, the participants traveled to a clinic in Mexico run by Ambio Life Sciences. There, under careful medical monitoring, they received oral ibogaine combined with magnesium. The magnesium was added to help prevent potential heart complications associated with ibogaine use. After receiving the treatment, the veterans returned to Stanford for post-treatment assessments.
“The study protocol included rigorous screening and magnesium co-administered with ibogaine as a cardioprotective agent,” Cherian explained. “Treatment providers ensured participants were well prepared, both from medical and psychiatric perspectives, and monitored the participants closely throughout treatment in order to optimize safety and reduce risk for treatment recipients.”
At the beginning of the study, the participants were experiencing clinically significant levels of disability. This was measured using the World Health Organization Disability Assessment Scale 2.0, which assesses disability across six functional domains: cognition, mobility, self-care, getting along, life activities, and community participation. The scale of the participants’ challenges was evident: 23 met the criteria for post-traumatic stress disorder, 14 for an anxiety disorder, and 15 for alcohol use disorder. Additionally, 19 participants had experienced suicidal thoughts in their lifetimes, and seven had attempted suicide.
The primary measure was the World Health Organization Disability Assessment Schedule, which gauges the level of disability. Additionally, standardized scales like the Clinician-Administered PTSD Scale for DSM-5, the Montgomery–Åsberg Depression Rating Scale, and the Hamilton Anxiety Rating Scale were employed to assess changes in PTSD, depression, and anxiety symptoms. These assessments were conducted at baseline, immediately after treatment, and one month following the treatment.
The researchers observed a significant decrease in the disability scores, indicating a substantial reduction in the severity of the participants’ conditions. Remarkably, this improvement persisted and was even more pronounced one month after the treatment. In terms of psychiatric symptoms, there were notable reductions in the severity of PTSD, depression, and anxiety, with the improvements remaining consistent over time. Moreover, neuropsychological tests revealed enhancements in cognitive functions, particularly in processing speed and executive functioning, without any negative impacts on other cognitive areas.
“Ibogaine is a powerful psychoactive medicine and has real potential as a treatment for trauma, both physical (repeated TBI) and psychological (repeated combat exposure). We saw rapid and durable (up to at least one month) treatment effects on function, symptoms of PTSD, depression, and anxiety, and cognition,” Cherian told PsyPost.
“Approval of ibogaine as a legal focus of research in the United States would allow us to study ibogaine and other psychedelic medicines more rigorously, in order to better delineate treatment efficacy and safety for those most in need. This study’s findings support such further research.”
In terms of safety, the study reported no serious or unexpected side effects. While some participants experienced mild side effects like ataxia, headache, and nausea, these were transient and resolved within 24 hours. This aspect is particularly important, as it suggests the treatment is not only effective but also safe for use in this vulnerable population.
“I was surprised at how rapid and durable the effects of ibogaine were for the majority in the study (ie. up to one-month post-treatment),” Cherian said. “I could feel a powerful difference in the room with individual participants when comparing my assessments with them prior to treatment to assessments only one week later, after they had undertaken one dose of ibogaine treatment.”
“Currently, available treatments often require individuals to undertake months, if not years, of sometimes expensive and often emotionally difficult treatment (for example, exposure therapy for PTSD). Ibogaine demonstrated strong effects within days after treatment for most participants.”
“Some participants had been extremely limited by the issues they were living with,” Cherian added. “Most participants felt they were impaired in their function in life. We saw Veterans who had not been able to continue working, who wouldn’t leave their homes, and who withdrew from family and other social connections.”
“Some were notably struggling with suicidal ideation and many had ready access to means for suicide. Some veterans shared with complete certainty that they felt that ibogaine saved their lives. The effects of ibogaine were not only healing from a psychological perspective, but also appear to have contributed to improvements in cognition and significant reductions in suicidality.”
Despite these promising results, the study is not without its limitations. One significant limitation is that it was not a randomized controlled trial (RCT), which is considered the gold standard in medical research. This means that the possibility of placebo effects or other biases cannot be entirely ruled out. Additionally, the participants in this study self-selected for the treatment and traveled to Mexico for it, which may have influenced the outcomes due to expectancy or other factors associated with the treatment setting.
Looking to the future, the researchers emphasize the need for further studies, particularly placebo-controlled RCTs, to solidify these findings. Such studies would help to establish the true efficacy of this treatment protocol, free from the potential biases of expectancy or self-selection.
The study, “Magnesium–ibogaine therapy in veterans with traumatic brain injuries“, was authored by Kirsten N. Cherian, Jackob N. Keynan, Lauren Anker, Afik Faerman, Randi E. Brown, Ahmed Shamma, Or Keynan, John P. Coetzee, Jean-Marie Batail, Angela Phillips, Nicholas J. Bassano, Gregory L. Sahlem, Jose Inzunza, Trevor Millar, Jonathan Dickinson, C. E. Rolle, Jennifer Keller, Maheen Adamson, Ian H. Kratter, and Nolan R. Williams.
