By Melissa Patrick
Kentucky Health News
In a session focused on challenges of getting the psychedelic drug ibogaine approved by the Food and Drug Administration for treating addiction with help of the state's opioid settlement funds, a cardiologist said it couldn't be done in a reasonable time and the drug is unsafe.
"My opinion is that ibogaine is not safe, the efficacy is unproven, it's unlikely to be approved by the FDA in a reasonable time period, and the cost to Kentucky would be unsupportable," said Dr. Mark Haigney, a board-certified cardiologist and electrophysiologist, and an attending physician at the Walter Reed National Military Medical Center.
Haigney was invited to a special Kentucky Opioid Abatement Advisory Commission meeting on Oct. 17 by commission member Patricia Freeman, a pharmacy professor at the University of Kentucky. The meeting also saw the head of the commission discuss a "rough" plan for funding ibogaine research.
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Patricia Freeman
(Photos by Melissa Patrick) |
After two hearings that focused on ibogaine development and personal testimonies favoring the drug, she asked to invite experts in regulatory drug development to testify about the challenges of navigating ibogaine through the FDA process, given its potential for damage to the heart and its current classification as a Schedule I drug with no medical use.
Freeman said she had concerns that people at one hearing thought there would be quick access to ibogaine with the $42 million investment and felt compelled to ensure they understand that this would be a multi-year endeavor with no guarantee of success.
"I felt this was important as it would help make sure that at large, our commission would be as fully informed as possible prior to making a decision on proposed ibogaine funding," Freeman said.
The proposal comes from Bryan Hubbard, chair and executive director of the commission, which operates in the office of Attorney General Daniel Cameron, the Republican nominee for governor. Ibogaine is illegal everywhere but Mexico and New Zealand, but has been anecdotally reported to stop drug-withdrawal symptoms.
Haigney, who described himself as an "expert in drug-induced sudden death and drug-induced loss of consciousness," said that while he recognized the attractiveness of a single-dose drug like ibogaine to treat opioid-use disorder, such a drug must be "safe in the immediate term, effective in the long term, FDA-approved, and affordable for the huge number of Kentuckians with opioid-use disorder."
He said ibogaine isn't safe because it is known to cause cardiac arrhythmias and sudden death. In detail, he explained that this happens because ibogaine causes a "prolonged QT interval," which is one of the measurements taken by a standard electrocardiogram.
A prolonged QT interval occurs when the heart muscle takes longer to contract and relax than usual, which can affect heart rhythms and lead to sudden cardiac arrest.
Haigney said the FDA requires all drugs to undergo cardiac testing and that "the finding of QT interval prolongation is the most common reason for removal of a drug from further development."
He added that a prolonged QT interval can happen when a drug blocks the cardiac potassium channels to the heart and that ibogaine is a "potent blocker" of this channel, even with normal therapeutic doses.
"So this means that most if not all subjects would experience some significant degree of blocking the channel," he said. "And this is a very poor prognostic finding for a drug."
Haigney pointed to a study of 14 hospitalized patients who received a "relatively low dose" of ibogaine. The average increase in QT interval was 95 milliseconds. He said the FDA's published guidelines say it is concerned when a drug prolongs the QT interval by 5 milliseconds or more.
"I've never seen a drug prolong the QT interval so profoundly," he said, adding later, "This degree of QT prolongation would be expected, associated with increased risk of fatal events."
He then asked rhetorically, "Can this drug be given safely?" His answer, "Yes, in the hospital. We do a lot of dangerous things in the hospital with a lot of technology," adding that this would be "an incredibly resource-demanding" drug to administer.
"The likelihood that this drug with this safety profile will be approved by the FDA in less than 10 years, in my opinion, is remote and the effort will require at least a billion dollars," Haigney said. "The administration of ibogaine would strain hospital resources at a time when bed shortages are severe. This is a treatment for wealthy individuals who can pay for hospitalization with intensive monitoring," so it would not help most Kentuckians "who struggle with opioid dependence."
Freeman also invited Robert Walsh, recently retired from working in the National Institute on Drug Abuse for 36 years, where he headed NIDA's Regulatory Affairs Branch.
Walsh spoke to the regulatory challenges of ibogaine development, including cardiac safety, ensuring enough supply of a plant-based drug from another country, creating a plant-based drug with the same dose in each pill, and the challenges of working with a Schedule I drug in laboratories and clinical settings.
Dr. Sidney Peykar, a cardiac electrophysiologist and medical director at the Cardiac Arrhythmia Institute, said the drug could be given safely in a hospital setting and said he has expanded the protocol for how to administer ibogaine safely at the Beyond Ibogaine Treatment Center in Cancun, Mexico.
"Most if not all of these deaths could be mitigated or completely prevented through safety protocols," he said.
Dr. Javier Muniz, the FDA's supervisory general-health scientist for controlled-substances initiatives, was asked if FDA would definitely not approve ibogaine. He said that without all of the information in front of him, "I have no idea."
Asked by Freeman if a 95-millisecond QT prolongation would disqualify ibogaine from being approved, he said it's important to remember that when the FDA is considering the approval of a drug, the agency looks at a drug holistically and considers both risks and benefits.
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Bryan Hubbard, right, and
Carlos Cameron, commission
member. |
Hubbard was asked after the meeting if any speaker had caused him to change his mind about his ibogaine plan. He said, "Dr. Haigney was brought in here to oppose this initiative and he articulated all of the talking points that the opponents of this initiative have already parlayed at public remarks. So there was nothing that was either surprising, nor persuasive about his remarks, and insofar as what he has articulated, are already widely publicly disseminated talking points of opposition."
He said Haigney was "thoroughly debunked [by] individuals who serve, respectively, on an FDA advisory board for psychopharmacology, as well as the science journal for the FDA's research arm related to controlled substances."
At the end of the meeting, Hubbard gave the commission a "very rough draft" of a plan with a list of requirements that would have to be met before the commission would commit $42 million to the project. He did not release the plan, but told Kentucky Health News after the meeting that it contains these points:
- "Viable research proposals from qualified research entities" that will match the state's $42 million
- The state would have ownership of any patentable intellectual property that is generated
- Clinical trials would be held in the West End of Louisville and in Wast Kentucky, "in a way that ensures social, racial, and economic equity of access to the treatment,"
- An approved drug-investigation application from the FDA "with secured clinical-trial sites and a diverse group of qualified clinical-trial participants before the first dollar is ever matched by the commission,"
"This will have to be a viable, go project before any commission resources are put on the table," Hubbard said,. Nothing like this has ever been done. So all of this is breaking ground." He cited "the competing interests, the areas of concern, the nature of this money, the necessity of protecting it, the necessity of making sure that the Commonwealth of Kentucky has a leadership position that is protected and recognized, and consideration of risk that we are taking by making this bet."
When it comes time for the commission to vote, he said, "Theoretically, the vote will be to legally authorize a $42 million match from the commission for our clinical research team that is ready to conduct clinical trials with ibogaine in Kentucky."
Hubbard said it is imperative that no vote be taken until Dr. Nolan Williams' peer-reviewed research of veterans who have suffered from traumatic brain injury and received ibogaine is published and they hear from him about his findings. Williams is an associate professor at Stanford University.
At the commission's first public hearing, Williams said he had let other professionals look at the data from his study and they said "the findings are shocking and that they've never seen a drug do this before."
Before the eight guests spoke, Hubbard took about five minutes to address how he and the commission came to explore ibogaine and its potential therapeutic uses. He said as far back as 2018, he became aware of emerging science on therapeutic psychedelics and an author who at the time wrote about the topic and led him to other sources of information. Her newsletter The Journey is published on Substack. She wrote under the pen name of Julia Blum now uses the name Julia Christina.
Hubbard was responding to an Oct. 9
Daily Beast story, excerpted in Kentucky Health News, which reported that about the time Cameron implicitly endorsed his plan at a public event, a major national political contributor
increased its investment in ibogaine research and later gave Cameron's campaign a political boost. He is running against Democratic Gov. Andy Beshear, who has objected to Hubbard's ibogaine plan.
Hubbard said, "It's important to set the record straight in full public view, lest the fictitious narrative of a smoke-and-mirror smear job generated by a third-rate, agenda-driven political tabloid prevail in the public arena against the integrity and sincerity of all who have offered their time, expertise and visceral lived experiences for all the world to see on behalf of all Kentuckians."
The commission's next regular business meeting is scheduled for 1 p.m. Nov. 14 at 1024 Capital Center Dr., Suite 200, Frankfort.
