KY commission weighing investment in psychedelic to treat addiction hears from detractors

Deliberation over a proposal to invest state money in clinical research of a psychedelic drug as a potential treatment for opioid addiction is intensifying.

After the Kentucky Opioid Abatement Advisory Commission heard from dozens of ibogaine proponents at two public hearings over the summer, commission members heard for the first time from opponents last week, who warned of ibogaine’s potentially harmful impacts on the heart — a reality that may compromise the U.S. Food and Drug Administration’s willingness to give an initial green light for clinical trials.

“My opinion is ibogaine is not safe, its efficacy is unproven, and the cost to Kentucky would be unsupportable,” said Dr. Mark Haigney. He’s a professor of Medicine and Pharmacology and director of Cardiology and Military Cardiovascular Outcomes Research at Walter Reed National Military Medical Center in Maryland.

Commission Chair Bryan Hubbard first floated the idea of investing $42 million from Kentucky’s share of opioid lawsuit settlement money – a pot whose total sum verges on $1 billion – into clinical research of ibogaine as an opioid use disorder therapeutic in late May.

An alkaloid derived from the root bark of an iboga shrub native to West Central Africa, ibogaine is an illicit hallucinogenic Schedule 1 drug in the U.S. The nation’s first clinical trial for ibogaine was approved in 1993, but after the National Institute on Drug Abuse revoked its funding to test the drug on humans, the plug was pulled on the trials in 1995.

Hubbard and his allies’ plan is grand and would be historic: Cultivate public and private partnerships to match the commission’s share of $42 million and, over the next six years, begin the process of testing ibogaine’s efficacy on people .

Their hope: Eventually earning full approval from the FDA to distribute the psychedelic widely as another means of treating opioid dependency. Currently there are three primarily used FDA-approved drugs used to treat opioid use disorder: naltrexone, methadone and buprenorphine, or Suboxone. Each has a slightly different effect on the brain, but all work to suppress withdrawal symptoms and cravings.

Proposed as an alternative to already on-the-market drugs to treat substance use, Hubbard’s proposal drew near-immediate resistance from some commission members and addiction researchers, partly because of the risks ibogaine poses to cardiac activity, partly because of how the proposal was introduced.

Hubbard unveiled his proposal publicly at a May 2023 event attended by Republican Attorney General Daniel Cameron, before it was formally presented to the commission. Cameron lauded ibogaine’s potential and vowed to help Kentucky explore a “new approach” to help curb opioid use.

The decision whether to invest Kentucky’s initial lawsuit settlement funds ultimately falls to commission members, who’ve hosted three public hearings on Hubbard’s proposal since July. The first two featured dozens of ibogaine proponents, including people who’ve personally taken ibogaine to treat their opioid addiction and attested to its benefits, and others that have researched the psychedelic’s potential to treat not only addiction, but post-traumatic stress disorder.

Nearly all of the individuals who spoke were invited to speak by Hubbard, himself, or other ibogaine proponents. Before the Oct. 17 hearing, the only people who addressed the commission were in favor of ibogaine.

Dr. Patricia Freeman, a commission member and professor in the College of Pharmacy at the University of Kentucky, introduced two individuals who raised concerns about ibogaine at the hearing.

Freeman, the commission’s newest member, filled a vacancy left by Dr. Sharon Walsh, who resigned from the commission in the summer. Walsh is the director of UK’s Center on Drug and Alcohol Research. Both Freeman and Walsh are involved in the $87 million National Institutes of Health grant-funded HEALing Communities Study.

The goal of the grant is to build a model with community partners to reduce opioid overdoses by 40% in 16 Kentucky counties using evidence-based methods. If successful, that model would be applied to the rest of the state.

As the Herald-Leader has previously reported, it’s ibogaine’s impact on cardiac activity that gives some health care providers and addiction researchers, including Walsh, pause.

The drug blocks the hERG potassium channels in the heart, which help to regulate a heartbeat, and increases what’s called a QT interval – essentially the time it takes for a heart to relax between beats.

Drug-induced prolongation of a heartbeat in this way can cause an irregular heartbeat (an arrhythmia), even death. Ibogaine has caused documented cases of both, according to medical literature.

While there are currently FDA-approved drugs to help curb opioid misuse, “You have to take them every day, often for life,” said Haigney, who called himself an “expert in drug-induced sudden death.”

Many people who’ve addressed the commission and personally taken ibogaine have taken only one dose.

“It does have a certain attractiveness to think if you could give a single dose of a drug, that could give a lifetime cure,” he said. But “this would be attractive only if the drug is safe in the immediate term, effective in the long term, FDA approved and affordable for the huge number of Kentuckians with opioid use disorder.”

Bringing a new drug through the FDA approval process and to market is a protracted and expensive process, estimated to cost close to $2 billion, according to one recent study.

“The finding of a QT interval prolongation is the most common reason for removal of a drug from further development” by the FDA, Haigney said. Ibogaine is “associated with an unprecedented degree of cardiac toxicity, it prolongs the QT interval 20-times more than buprenorphine and 20-times above the FDA threshold.”

Administering a drug with this potential side effect can be done safely in a hospital setting with specialized providers standing by, but it would be “incredibly resource demanding,” he said.

Robert Walsh, a retired chief of Regulatory Affairs Branch in the Division of Therapeutics and Medical Consequences at the National Institute on Drug Abuse, enumerated many of the technical challenges that would likely surface during clinical trials using ibogaine, repeating several of the points made by Haigney.

For example, the health risks associated with ibogaine could limit the potential patient pool, or cause the trials to last longer, increasing the overall cost, he said. Walsh worked for NIDA when the FDA approved the first clinical trial of ibogaine in the early 1990s.

Beyond the cost of bringing a drug to market, Walsh and Haigney said the known risks would mean a greater use of health care resources in order to monitor trial participants for adverse cardiac events. And seeing as Kentucky already has a critical nursing shortage, Haigney said, adding to this strain would only further exacerbate that crisis.

“This is a treatment for wealthy individuals who can pay for hospitalization with intensive monitoring and is not going to help the 2.7 million Kentuckians who struggle with opioid dependency,” Haigney said.

Not everyone agreed.

Ibogaine does include documented risks, most of the speakers at the hearing agreed. But the most pressing and realistic risk facing Kentuckians living with opioid addiction is the threat of overdosing on a daily basis.

It’s because of the acuteness of this crisis that Rick Doblin, executive director at the Multidisciplinary Association for Psychedelic Studies, said would perhaps push the FDA would “look at this in terms of a risk-benefit analysis.”

“I think, because it’s such a national crisis, the FDA is interested in trying to expedite the national research,” Doblin said.

Commission member Vic Brown said the first clinical trials using ibogaine ended before the full brunt of the opioid crisis began choking the nation.

“Now, 20 years later, we are still living with (roughly) 100,000 folks a year dying of overdose deaths,” Brown said.

“You mentioned that there’s other drugs available to combat that use, but obviously something more is needed if we’re still losing 100,000 individuals a year,” he continued. “So, wouldn’t you think that it would be proper to continue the study of (ibogaine)?”

Walsh didn’t say no.

“To be honest, I think all (treatments) should be examined,” Walsh said. “But I do think, too, we have to move cautiously. When we know about certain side effects or risks for patients, that it’s important as we’re developing that drug we keep a very close handle on.”

Walsh said his main concern is that, when there are known risks with a drug like ibogaine, developing that drug for human use is likely to be more expensive, “because it requires more studies and measures to be taken.”

“That doesn’t mean it can’t happen,” Walsh said. But the thinking behind a potential treatment like this should be, “what might have the greatest chance of success (and) reach most of your patients in the quickest time possible.”

The commission does not have a date set to take a final vote on the proposal. Its next regularly scheduled meeting will be held Nov. 15.