Fear and Loathing about Ibogaine

Figure: ibogaine, opioids, PTSD, brain injury psychoactive alkaloid, Tabernanthe Iboga, nausea, ataxia, cardiotoxicity, methadone detoxification, alcoholism, withdrawal, tachycardia, torsades des pointes, potassium channels, QTc, QT syndrome, hypokalemia, atherosclerosis, cardiomegaly, hypomagnesemiaFigure“Not much has been written about The Ibogaine Effect as a serious factor in the Presidential Campaign, but toward the end of the Wisconsin primary race—about a week before the vote—word leaked out that some of Muskie's top advisors had called in a Brazilian doctor who was said to be treating the candidate with ‘some kind of strange drug’ that nobody in the press corps had ever heard of. ... I immediately recognized The Ibogaine Effect...” —Hunter S. Thompson, Fear and Loathing: On the Campaign Trail ‘72 Reading Hunter S. Thompson's dispatches from the 1972 Democratic primary race in Rolling Stone was the first time I learned about a mysterious drug called ibogaine. I never believed that Edmund Muskie was taking a psychedelic substance on the hustings. Mr. Thompson later admitted that he made up the entire story and was flabbergasted when people believed it. Even so, Frank Mankiewicz, the campaign manager for eventual Democratic nominee George McGovern, later called Thompson's coverage the “least factual, most accurate account” of the 1972 presidential contest. (New York Times. July 4, 2008; https://tinyurl.com/y979fau5.) It was that crazy of an election year. I hadn't thought much about ibogaine again until this year when stories about the drug started appearing in the New York Times, the Washington Post, and other publications. The Times reported that “[a]ccording to a number of small studies, between a third and two-thirds of the people who were addicted to opioids or crack cocaine and were treated with [ibogaine] in a therapeutic setting were effectively cured of their habits, many after just a single session.” (March 5, 2024; https://tinyurl.com/2kt63xak.) The Post noted that some physicians thought ibogaine may also be helpful in treating PTSD and the after-effects of traumatic brain injury. (March 14, 2024; https://tinyurl.com/bdzfamrx.) Anecdotal reports and animal studies have suggested that ibogaine may be useful in treating these conditions as well as nicotine and alcohol dependence, depression, and anxiety. But no convincing studies have confirmed that ibogaine is safe and effective for these indications. Research into these questions, which started in the 1960s, stalled when ibogaine was classified as a Schedule I drug with the passage of the Controlled Substances Act in 1970. Ibogaine is firmly back in the news and generating considerable interest. It's time to take a new look at this fascinating drug. What is Ibogaine? Ibogaine is the most prominent psychoactive alkaloid found in the root bark of the African shrub Tabernanthe iboga. Scrapings from the bark have been used for centuries by people in Gabon, Cameroon, and the Congo as a stimulant to fight fatigue, hunger, and thirst on long hunting expeditions. Ibogaine at higher doses is used as a hallucinogenic in religious and initiation ceremonies. Ibogaine never achieved popularity as a recreational drug because it can cause severe nausea and ataxia as well as intense, harrowing hallucinogenic episodes lasting 24 hours or longer. Opioid Treatment Ibogaine has effects at a wide range of neurotransmitter receptors. It acts as an antagonist at certain nicotinic acetylcholine receptors as well as NMDA receptors. Crucially, it blocks cardiac potassium channels, delaying repolarization and prolonging the QTc interval. The half-life of ibogaine in humans is about seven hours, but it has an active metabolite—noribogaine—that has a prolonged half-life of 24 to 48 hours. A large amount of anecdotal evidence and a number of animal studies suggest that a single ibogaine session can in many cases dramatically suppress opioid cravings and withdrawal symptoms for weeks, months, or even longer. University of Miami neurologist Deborah Mash, PhD, said in a New York Times article, “Ibogaine is not a silver bullet, and it won't work for everybody, but it's the most powerful addiction interrupter I've ever seen.” (March 5, 2024; https://tinyurl.com/2kt63xak.) Ibogaine has unfortunately not yet been the subject of extensive human research because of its classification as a Schedule I substance, but that may be changing. The website clinicaltrials.gov lists four current projects studying ibogaine for methadone detoxification, opioid withdrawal, alcoholism, and traumatic brain injury. (https://tinyurl.com/mr38yecw.) Reports of Death Ibogaine can be dangerous, the primary concern being cardiotoxicity. Ibogaine use has been associated with intermittent ventricular tachycardia and torsades de pointes because it blocks potassium channels and prolongs the QTc interval. (N Engl J Med. 2009;360[3]:308; https://tinyurl.com/2vyz796a.) Risk factors for ibogaine cardiotoxicity include hereditary long QT syndrome, concomitant use of drugs that prolong the QT interval, existing cardiac disease such as atherosclerosis and cardiomegaly, and hypokalemia or hypomagnesemia. Conditions or drugs that inhibit the activity of the enzyme CYP2D6 can increase ibogaine levels. (See table.) Ibogaine has also been associated with clinically significant bradycardia. Several dozen reports of deaths have been temporally associated with exposure to ibogaine since the 1960s. The safe use of ibogaine will no doubt incorporate strict protocols including careful patient selection, screening for medical or psychiatric conditions that increase risk, avoiding drugs that interact with ibogaine, continuous ECG monitoring during sessions, and possibly magnesium supplementation and infusion. Ibogaine is unregulated in much of the world, including Canada and Mexico, and it is scheduled and illegal except for research purposes in the United States. The key take-home point is that EPs should think QT prolongation, torsades de pointes, and bradycardia when they think of ibogaine. A handful of deaths attributed to ibogaine toxicity have been reported over the past half-century, but I suspect that many of these also involved exposure to one or more other drugs, pre-existing high-risk conditions, or use by unlicensed, unregulated practitioners who did not provide proper medical screening and monitoring. I predict that emergency physicians and toxicologists will see more patients who present after being exposed to ibogaine in the coming years. We should all be aware of its basic clinical effects and drug-drug interactions. A useful resource is the website crediblemeds.com, which lists drugs that prolong the QT interval and can interact with ibogaine. (https://tinyurl.com/3e5sa28u.) A call to the regional poison center can provide up-to-date support in managing ibogaine toxicity. DR. GUSSOW is a voluntary attending physician at the John H. Stroger Hospital of Cook County in Chicago, an assistant professor of emergency medicine at Rush Medical College, a consultant to the Illinois Poison Center, and a lecturer in emergency medicine at the University of Illinois Medical Center in Chicago. Follow him on X @poisonreview, and read his past columns at http://tinyurl.com/EMN-Gussow. Share this article on X and Facebook. Access the links in EMN by reading this on our website: www.EM-News.com. Comments? Write to us at [email protected].

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