By Melissa Patrick
Kentucky Health News
The Kentucky Opioid Abatement Advisory Commission held its first public hearing Monday, July 17, to discuss funding development of an opioid-use disorder treatment using the psychedelic drug ibogaine with some of the money the state is getting from settlements with drug makers and distributors.
The commission heard from five experts, all in favor of the idea, and two people who have successfully used ibogaine in other countries to recover from their opioid addictions. The drug is illegal in the U.S. but has been anecdotally reported to stop the withdrawal symptoms of opioid dependence.
Juliana Mulligan, a psychotherapist and ibogaine treatment specialist in New York, told the story of her opioid addiction and the seven years she spent in and out of treatment and jail. With the support of her parents, she traveled to an ibogaine clinic in Mexico, and that experience involved a “plethora of mistakes” that landed her in the hospital with cardiac issues that resulted in a heart attack.
Ibogaine’s effects on the heart are a major obstacle to its use, and the commission discussed that with another expert. But Mulligan called her experience with the drug “nothing short of miraculous” and said she has not used an opioid or had a craving since November 2011.
“Despite the dramatic hospital story, the medicine did its job for me,” she said. “I remember suddenly feeling with total certainty that ibogaine is the future of opioid-disorder treatment. . . . Of course, ibogaine isn’t magic and it isn’t a cure, but it is hands-down the best door open to the path of healing that myself and many other could find.”
Jessica Blackburn of Floyd County talked about her success with ibogaine in 2008 for opioid-use disorder after many attempts at recovery. Blackburn said she relapsed, but in August will have gone eight years without using any drugs.
Blackburn said she would not be alive today “without the use of iboga,” the African shrub from which the drug is produced. “No Kentuckian should have to leave the country to receive this life-saving treatment.”
Drug developer calls for ‘Manhattan Project’
Dr. Deborah Mash, founder and CEO of DemeRx, which wants to develop ibogaine as an addiction treatment, told the commissioners that if clinical trials are approved for it, her company would look to demonstrate that ibogaine could be used for relapse prevention.
“This class of molecules, ibogaine in particular, opens plasticity in the brain, and this is, we believe, why we will be able to prove — in effective and well-designed clinical trials — that this drug is transformative,” said Mash, an emeritus professor of neurology at the University of Miami.
Plasticity is the brain’s ability to alter its connections and rewire itself to function in a way that differs from how it previously functioned.
“What we want to be able to demonstrate, working in a public-private partnership, is that this drug [will] help break the cycle of addiction and promote that transition to abstinence-based treatments,” Mash said, adding later that it needs to be “a Manhattan Project,” like the one that developed nuclear weapons.
“I think we need the best scientists, the best people who know how to do clinical trials, our academic colleagues together (with) public-private partnership, to accelerate the pace of this,” she said.
Mash said she has studied ibogaine for 30 years and her initial published research was done on the West Indies island of St. Kitts, with permission from its government, and published in 2018 in Frontiers in Pharmacology.
She said that research of treating hard-core drug users with ibogaine “demonstrated . . . not only that it benefited people, but we also demonstrated that it could be administered safely under full medical monitor.”
Dr. Kenneth Alper, a neuropsychiatrist and visiting scientist at the Nathan Kline Institute for Psychiatric Research in Orangebrg, N.Y., said his research has found that the drug’s “action is novel, which suggests that ibogaine could provide a basis for the development of fundamentally innovative pharmacotherapy.”
This is important, Alper said, because while effective medications are available for addiction, “The need for innovation in the treatment of opioid-use disorder is clear” because “only a fraction of those with OUD access medication-assisted therapy, and when they do, a third or more will drop out within eight months.”
He said 20% to 60% of people in medication-assisted treatment use illicit opioids, “completion of detoxification fails one-third to one-half of the time,” and even if treatment is successful, it “is followed by relapse within four to six weeks 75% to 80% of the time.”
Dr. Nolan Williams, an associate professor at Stanford University, told the commissioners that his study of veterans who have suffered from traumatic brain injury, which is under peer review for publication, is “the most comprehensive evaluation ever done” on people who have received ibogaine treatment.
He said that while the results won’t be available for about six weeks, he’s let other professionals look at the data and they have said “the findings are shocking and that they’ve never seen a drug do this before.”
State Rep. Danny Bentley, R-Russell, a pharmacist, asked about ibogaine’s effect on the heart. Williams said that risk could be mitigated by an additional layer of controls to protect patients, such as careful screening.
Williams said some people who take ibogaine display an electrocardiogram change called “QT prolongation” associated with a particular type of dysrhythmia that can progress into ventricular fibrillation and death. But “If you’re in a supervised medical setting, there’s a lot you can do about it.”
He said the deaths associated with ibogaine treatment have largely occurred in hotel rooms in other countries, and in an appropriately monitored setting, the threat would be dealt with in the same way “a lot of drugs that have QT prolongation,” he said.
Mash said there have been 33 deaths from ibogaine in the published peer review literature over 20 years.
Alper said his work in forensic toxicology, aimed at informing efforts to make ibogaine safer, found that ibogaine-related deaths often involved pre-existing medical conditions, particularly cardiac conditions. Other factors include the use of ibogaine of uncertain or impure composition or co-ingestion of substances of abuse.
“I believe that many of these deaths were likely preventable,” he said. “This highlights the need for adequate medical supervision during ibogaine treatment, minimally including cardiac monitoring.”
Federal approval process
Bryan Hubbard, chair and executive director of the commission, has asked it to consider committing $42 million of the settlement money from drug companies to help get ibogaine through the FDA approval process in the next six years.
Hubbard works for Attorney General Daniel Cameron, the Republican nominee for governor. Democratic Gov. Andy Beshear’s appointees on the commission, Health Secretary Eric Friedlander and Office of Drug Control Policy Director Van Ingram, asked how long it takes to get a drug through the FDA process.
Dr. Srinivas Rao, co-founder and chief scientific officer of Atai Life Sciences, a German company. said the estimates are around 10 years at a cost of between $600 million and $800 million. Mash said it can go faster.
“I believe the open-label data, the observational data, supports this. I believe that the regulators are going to be supportive of this,” Mash said. “And certainly when you see these initiatives, these types of public-private initiatives, this will not be lost on other partners that will come. So the leadership today, even having this meeting, is really groundbreaking.”
Mash said it is time for a “pivotal, Phase II study” to demonstrate safety and efficacy of the drug. She said there have been no controlled trials but there is an abundance of observational data that show ibogaine treatments have resulted in patients having remission from addiction.
Mash said the trials would be done in a monitored, in-patient setting after the person had been screened to make sure they would be a good candidate. She said the drug would be given by tablet, and in about 45 minutes the patient would enter a deep phase of cognitive introspection for four to eight hours. She said the patient would be required to stay overnight and be released the next day.
Why $42 million?
Friedlander asked Hubbard why he is asking the commission for $42 million and exactly what the state would get from it.
Hubbard said the legislature gave the same amount to Senate Bill 90, a criminal-justice reform initiative related to addiction and recovery, and noted that it is 5% of the more than $900 million in settlement money that will come to the state. The commission handles half and local governments the other half.
“If this commission can pay for a highly consequential criminal-justice reform initiative in 11 counties to the tune of $42 million over four years,” he said, “then perhaps we can explore devoting $42 million, which would be matched by the participating clinical research entity for a total of $84 million over the next six years, to potentially revolutionize how we treat opioid use disorder for the people of this state, for the people of this country, and for the people of this world.”
Williams said, “It’s an important point that maybe something like this wouldn’t fund all of it, but if you could get some momentum going, then that’s very helpful to getting other parties involved.”
The second public hearing about ibogaine will be held from 9 a.m. to 3:30 p.m. Sept. 15 in Conference Room A-125 at the Administrative Office of the Courts building, 1001 Vandalay Drive, Frankfort.