Nolan Williams, now a psychiatrist and a neurologist at Stanford University, first developed an interest in the psychedelic drug ibogaine during his residency at the Medical University of South Carolina. He was blown away by accounts he read about a single dose of the powerful drug, derived from a Central African plant, being able to free some people from substance use disorders. This was back in 2010, however, “way before the psychedelic renaissance,” Williams says. Given that ibogaine is a strictly banned substance in the U.S., “I pretty much convinced myself that it was unstudiable.”
Williams’s interest in ibogaine was reignited in 2018 when he met with Marcus Capone, a medically retired Navy SEAL, and his wife, Amber Capone. After multiple combat deployments, Marcus Capone had been diagnosed with post-traumatic stress disorder (PTSD) and traumatic brain injury (TBI). He was one of more than 480,000 U.S. service members—many of whom had been deployed to Iraq and Afghanistan and were exposed to repeated blasts—who were diagnosed with TBI between 2000 and the first quarter of 2023. TBI frequently co-occurs with PTSD, and together they can cause a suite of symptoms, including depression, anxiety, irritability, fatigue, impulsivity, headaches, insomnia, nightmares, and poor concentration, attention and processing speed. Conventional treatments do not work for everyone, and many veterans turn to alcohol or drugs in an attempt to self-medicate. An estimated 17 to 24 veterans commit suicide per day.
Marcus Capone suffered from many of these symptoms, he and his wife told Williams, and it got to the point that he was struggling to perform even simple tasks such as brushing his teeth or taking a shower. Williams says he was perplexed, though, because “the guy I was talking to was seemingly completely normal, without any of those problems.”
Williams learned that Marcus Capone had taken ibogaine at a specialized clinic in Mexico and that the experience had healed him. The Capones wanted Williams to start researching ibogaine’s ability to help veterans like Marcus in the hopes of eventually seeking Food and Drug Administration approval for the drug.
Williams agreed, and the first of those studies, conducted with 30 male U.S. special operations forces veterans who received ibogaine treatment in Mexico, was published this week in Nature Medicine. Immediately following treatment, all of the participants experienced significant reductions in measures of TBI-associated disability, PTSD, depression and anxiety. And one month later most participants’ scores had improved even more. None of the participants experienced serious side effects, the authors report.
For veterans, the new study is “a message of hope,” Williams says. For scientists, it indicates that “we have some work to do.”
Williams and his colleagues recruited the participants after they had already signed up to receive ibogaine treatment at a specialized clinic in Mexico that is part of the Vancouver-based company Ambio Life Sciences. All of the participants had also received a grant to support their treatment from Veterans Exploring Treatment Solutions (VETS), a nonprofit organization that the Capones founded in 2019 to help veterans receive psychedelic-assisted therapy in places outside of the U.S. where it’s legal.
The fact that the veterans were “essentially self-recruited” helped Williams and his colleagues secure permission to do the study from Stanford’s institutional review board (IRB), a process that took more than a year. “Most IRBs wouldn’t have even done it, so I do give them credit,” Williams says. “They’d see ibogaine as too much of a risk.”
Ibogaine is a more potentially dangerous substance than most other psychedelics and has been known to cause fatal cardiac arrhythmias. From 1990 to 2008 at least 19 people died after taking the drug. In a 2018 study on ibogaine use for opioid dependence that was conducted in New Zealand, one of the 15 participants died during treatment.
A key challenge Williams and his colleagues faced in moving forward with their study was figuring out how to mitigate this risk. Intravenous magnesium used as a prophylaxis turned out to be the answer. Ambio Life Sciences began giving magnesium to all of its clients in 2014, and of the 1,000 veterans who have taken ibogaine at the clinic since then, none have experienced a serious arrhythmia. None of the 30 study participants experienced arrhythmias, either.
Williams and his colleagues performed a full battery of clinician-administered psychological and cognitive tests on participants prior to their ibogaine treatment and then did so again a few days and one month afterward. The participants’ scores across all TBI-related disability, PTSD, anxiety and depression significantly decreased immediately after treatment and continued to improve over time. At the one-month mark, suicidal ideation, for example, had decreased from 47 percent to 7 percent. The continued improvement suggests that ibogaine’s effects are likely to be real rather than placebo-driven, Williams says, because the placebo effect tends to peak immediately after treatment and degrade over time.
The new findings add to the “mounting evidence [supporting] the importance of studying this treatment in rigorous clinical trials in the U.S.,” says Alan Davis, a clinical psychologist at the Ohio State University, who was not involved in the work. In 2020 Davis and his colleagues conducted a retrospective survey of 51 veterans after they received treatment with ibogaine and the psychedelic compound 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) in Mexico. They found similar reductions in the participants’ self-reported suicidal ideation, cognitive impairment, depression, anxiety and symptoms of PTSD.
Stephen Xenakis, executive director of the American Psychedelic Practitioners Association and a retired U.S. Army brigadier general, who also was not involved in the study, says that the findings show promise for ibogaine’s ability to help veterans with multiple problems and to improve cognition. “With such a high suicide rate among veterans, having another option for treatment is vitally important,” he says.
Xenakis adds, though, that he would like to see further evidence that ibogaine specifically reduced problems associated with TBI among the broad array of other disabilities and impairments the participants were suffering from. “Advanced neuroimaging, as well as quantitative electroencephalography, offer better tools to assess changes in the brain following treatment interventions,” he says.
Williams says that he and his colleagues did perform neuroimaging of the participants before and after treatment and that they are planning to publish those results in a follow-up study. They are also working on another follow-up study that will measure the durability of ibogaine’s effects beyond the one-month mark. “As a generality, it looks like it lasts a very long time,” Williams says.
The new Nature Medicine study’s participants received preparation from therapists before taking ibogaine and also met with them afterward to discuss their experience and how to integrate what they learned into their daily lives. Unlike other psychedelics that are paired with therapy, though, the ibogaine trip itself is essentially internal and self-directed. People often experience a life review that appears in their mind almost like a slideshow, Williams says. “It somehow drives a particular sort of psychological phenomenon that you don’t achieve through guidance,” he adds.
Researchers are still working out how ibogaine and other psychedelics can have such a powerful therapeutic effect, but Williams suspects that it has to do with their “profound ability to increase plasticity in the brain” by “bringing it back to a more juvenile state where reorganization can occur.”
Gül Dölen, a neuroscientist at the University of California, Berkeley, who was not involved in the research, agrees that the new study “provides further evidence that psychedelics as a class of drugs, which includes ibogaine, have remarkable therapeutic potential for the treatment of neuropsychiatric disease.” Last year Dölen and her colleagues published a study in Nature showing that ibogaine, among other psychedelics, can reopen critical periods for social learning in mice. Williams and his colleagues’ results, she says, “are consistent with our findings identifying a common neurobiological mechanism underlying these effects.”
Only a handful of trials have ever been conducted on ibogaine’s therapeutic use, and just one, a small 2014 study of ibogaine's effects on cocaine use, has included double-blind placebo controls. Williams and his colleagues hope that the data they produced in Mexico will help make a compelling case to the FDA that ibogaine should move forward with such trials in the U.S. There are already signs of interest in the drug from some U.S. officials, including a proposal in Kentucky to allocate $42 million of the state’s $842-million opioid lawsuit settlements for ibogaine research. The National Defense Authorization Act, signed by President Joe Biden last December, also authorizes any member of the military diagnosed with PTSD or TBI to take part in clinical studies of certain psychedelics, including ibogaine.
“It’s all really timely,” Williams says. “From my perspective, we should have some traction to make a strong argument that the risk-benefit is right.”
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