The plant-based psychoactive compound ibogaine, combined with magnesium to protect the heart, is linked to improvement in severe psychiatric symptoms including depression, anxiety, and functioning in veterans with traumatic brain injury (TBI), early results from a small study showed.
"The most unique findings we observed are the improvements in disability and cognition. At the start of the study, participants had mild to moderate levels of disability. However, a month after treatment, their average disability rating indicated no disability and cognitive testing indicated improvements in concentration and memory," study investigator Nolan Williams, MD, Stanford University, Palo Alto, California, told Medscape Medical News.
Also noteworthy were improvements across all participants in posttraumatic stress disorder (PTSD), depression, and anxiety — effects that lasted for at least 1 month after treatment, he said.
"These results are remarkable and exceeded our expectations. There is no drug today that can broadly relieve functional and neuropsychiatric symptoms of TBI as we observed with ibogaine," Nolan added.
The study was published online on January 5, 2024, in Nature Medicine.
'The Storm Lifted'
Ibogaine is derived from the root bark of the Tabernanthe iboga shrub and related plants and is traditionally used in African spiritual and healing ceremonies.
It is known to interact with multiple neurotransmitter systems and has been studied primarily as a treatment of substance use disorders (SUDs). Some studies of ibogaine for SUDs have also noted improvements in self-reported measures of mood.
In the United States, ibogaine is classified as a Schedule I substance, but legal ibogaine treatments are offered in clinics in Canada and Mexico.
Nolan noted that a handful of US veterans who went to Mexico for ibogaine treatment anecdotally reported improvements a variety of aspects of their lives.
The goal of the current study was to characterize those improvements with structured clinical and neurobiological assessments.
Participants included 30 US Special Operations Forces veterans (SOVs) with predominantly mild TBI from combat/blast exposures and psychiatric symptoms and functional limitations. All of them had independently scheduled themselves for treatment with magnesium and ibogaine at a clinic in Mexico.
Before treatment, the veterans had an average disability rating of 30.2 on the World Health Organization Disability Assessment Scale 2.0, equivalent to mild to moderate disability. One month after ibogaine treatment, that rating improved to 5.1, indicating no disability, the researchers reported.
One month after treatment, participants also experienced average reductions of 88% in PTSD symptoms, 87% in depression symptoms, and 81% in anxiety symptoms relative to before treatment.
Neuropsychological testing revealed improved concentration, information processing, memory, and impulsivity. There was also a substantial reduction in suicidal ideation.
"Before the treatment, I was living life in a blizzard with zero visibility and a cold, hopeless, listless feeling. After ibogaine, the storm lifted," Sean, a 51-year-old veteran from Arizona with six combat deployments who participated in the study, said in a Stanford news release.
There were no serious side effects of ibogaine, and no instances of heart problems associated with the treatment.
Although the study findings are promising, additional research is needed to address some clear limitations, the researchers noted.
"Most importantly, the study was not controlled and so the relative contribution of any therapeutic benefits from non-ibogaine elements of the experience, such as complementary treatments, group activities, coaching, international travel, expectancy, or other nonspecific effects, cannot be determined," they wrote.
In addition, follow-up was limited to 1 month, and longer-term data are needed to determine durability of the effects.
"We plan to study this compound further, as well as launch future studies to continue to understand how this drug can be used to treat TBI and possibly as a broader neuro-rehab drug. We will work towards a US-based set of trials to confirm efficacy with a multisite design," said Nolan.
Promising, but Very Preliminary
Commenting on the study for Medscape Medical News, Ramon Diaz-Arrastia, MD, PhD, professor of neurology and director of the Clinical TBI Research Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, said the results are "promising, but very preliminary."
Diaz-Arrastia noted that this was an open-label, nonrandomized study, early phase 2a study with "highly subjective outcome measures and the likelihood of it being a placebo effect is very high."
Nonetheless, "there is a lot of interest in these 'psychedelic' alkaloids, and ibogaine is a good candidate for further study," Diaz-Arrastia said.
Also providing perspective, Alan K. Davis, PhD, director of the Center for Psychedelic Drug Research and Education, Ohio State University, Columbus, said "mounting evidence supports the importance of studying this treatment in rigorous clinical trials in the US."
Davis and colleagues recently observed that treatment with two naturally occurring psychedelics — ibogaine and 5-MeO-DMT — was associated with reduced depressive and anxiety symptoms in trauma-exposed SOVs, as previously reported by Medscape Medical News.
This new study "basically is a replication of what we've already published on this topic, and we published data from much larger samples and longer follow up," said Davis.
Davis said it's "important for the public to know that there are important and serious risks associated with ibogaine therapy, including the possibility of cardiac problems and death. These risks are compounded when people are in clinics or settings where proper screening and medical oversight are not completed."
"Furthermore, the long-term effectiveness of this treatment is not well established. It may only help in the short term for most people. For many, ongoing clinical aftercare therapy and other forms of treatment may be needed," Davis noted.
The study was independently funded by philanthropic gifts from Steve and Genevieve Jurvetson and another anonymous donor. Williams is an inventor on a patent application related to the safety of MISTIC administration as described in the paper and a separate patent related to the use of ibogaine to treat disorders associated with brain aging. Davis is a board member at Source Resource Foundation and a lead trainer at Fluence. Diaz-Arrastia has no relevant disclosures.
