BREAKING: Ibogaine Therapy Shows Promising Outcomes For Veterans With Trauma Brain Injury

Results of a first-in-class clinical trial on ibogaine-magnesium therapy for Special Operations Veterans (SOV) with repeated blast exposure have been published in the journal Nature. Although preliminary, outcomes have long been awaited as they provide evidence of ibogaine’s neuro-restorative effects.

Led by Stanford University’s Brain Stimulation Lab director Dr. Nolan Williams, the study is the first prospective clinician-rated ibogaine trial as compared to prior published studies on ibogaine, with results based on self-reports.

With an estimated completion date set in February 2024, ibogaine's administration took place at a clinic in Mexico, and nonprofit VETS helped with the treatment funding.

Context

Recent research suggests that ibogaine, a psychoactive derived from the Tabernanthe iboga shrub, may offer therapeutic benefits for people with traumatic brain injuries (TBIs) especially prompted by traditional treatment limitations and side effects.

Often termed the "signature injury" of the Iraq and Afghanistan conflicts, TBIs are a major cause of disability worldwide, and its effects can lead to severe consequences like functional impairments and comorbid psychiatric syndromes like PTSD, depression and an increased risk of suicide, particularly among veterans.

Ibogaine has a long history of use in African spiritual and healing practices. It was introduced in Europe in the 19th century and used as a stimulant and antidepressant until becoming illegal in the 1960s. In the U.S., ibogaine is to date a Schedule I drug, restricting clinical research.

Ibogaine’s potential in TBI treatment is linked to its impact on neuroplasticity and neuronal growth. It affects multiple neurotransmitters and increases levels of neurotrophic factors like GDNF, BDNF and NGF in the brain, which are crucial for neuron survival and differentiation. This suggests ibogaine could help reduce or prevent brain damage from blasts and explosions.

See Also: President Biden Approves Psychedelics Clinical Trials For Active Military Members

Stanford Trial

30 participants received ibogaine orally and magnesium sulfate intravenously, as a pre-med for ibogaine-related arrhythmia. While delivering a high dose of ibogaine is not novel, providing ibogaine and magnesium in a sole therapy is a unique combination of both mechanisms.

In an all-male cohort, fifteen participants met the criteria for Major Depressive Disorder, 14 for anxiety disorder and 23 for PTSD. 

Results 

• The primary outcome (change in the WHODAS-2.0 scale) showed a significant decrease from mild/moderate disability at baseline (30.2 ± 14.7) to borderline-no/mild disability (19.9 ± 16.3) at the immediate post-treatment evaluation. 

• This improvement was statistically significant across all subscales, the greatest effect size at the cognition domain. One month post-treatment, the results sustained with no disability (5.1 ± 8.1.)

• In terms of safety, there were no unexpected or serious treatment-emergent side effects and no instances of bradycardia (slower-than-normal heart rate) tachycardia, clinically meaningful Qt prolongation or blood flow (hemodynamic) instability. 

• All participants experienced signs like mild ataxia and intention tremor, which resolved within 24 hours. 12 participants were treated for headache, seven for nausea, three for anxiety, 2 for hypertension and one for insomnia.

• Changes in psychiatric symptoms as calculated by the mean percentage reduction [over all 30 participants], response and remission rates [over 29 participants] according to the CAPS-5, MADRS and HAM-A scales showed mean percentage reductions of 81%+, response rates of 93%+ and remission rates of 83%+.

• Suicidal ideation showed a statistically significant reduction from 47% at baseline to 0% and 7% at post-treatment and 1-month follow-up, respectively. 

• Cognitive effects: Results showed statistically significant improvements in processing speed (large effect sizes) and executive functioning including inhibition, cognitive flexibility, problem-solving, phonemic fluency and working memory (effects from small to large), both immediately post-treatment and at the 1-month follow-up. 

See full study preliminary results.

The study’s scientific breakthrough entails providing what is believed to be the first-ever evidence of a psychedelic’s neuro-restorative effects. 

“We were able to show that ibogaine appears to have a neuro-rehab effect, which is new and not known. We have to prove that definitively with future trials, but there's a really strong signal that that's true,” Williams told Benzinga.

The general idea of a substance being able to promote general rehab and reverse illnesses like TBI "is both useful and will expectedly trigger more interest," he said.

The key difference with other psychedelic compounds under study for psychiatric illnesses relies on the fact that this study shows the potential of treating brain deficits and disability. “So it's a completely different thing: we're trying to change neurological function.”

Though other researchers are working on the same problem with other psychedelics, Williams said this is the first evidence in the literature that “could be positive or negative.”

Further results will require a multi-site, randomized, controlled trial. Separately, additional EEG and neuroimaging work from the Stanford study is currently under review and will be published following suit.

Research Community Comments

For David Esselman, executive director of U.S. nonprofit BrainFutures, this research reveals much-needed information to advance access to psychedelic-assisted therapies for reaching the high-need communities and its credibility comes from "a very reputable institution," not industry or pharmacy-led.

Yet what he says is most encouraging is the potential for replicating the results in community mental health centers in the U.S., “which serve exactly the type of populations that we should be determining how we best treat mental illness, specifically PTSD, depression and anxiety.”

Dr. Martin Polanco, founder of Mexico-based veterans retreat clinic The Mission Within, is conducting replicate ibogaine research. Polanco sees ibogaine’s standout feature in its potential in neurology and psychiatry through its ability to increase the brain’s white matter and heal biological and psychiatric conditions. 

Though there is overlap and misdiagnosis of PTSD and TBI, Polanco told Benzinga, there is a pressing need for appropriate TBI treatment, especially due to neuroinflammation and hormone dysregulation.

Photo courtesy of DMTrott, originally in The Honest Drug Book.