In a country where 100,000 people die from drug overdoses each year—the majority of deaths caused by illicitly made fentanyl—Americans need more ways to treat addiction.
Massachusetts-based Delix Therapeutics, a startup trying to turn non-psychedelic analogs of powerful hallucinogens into medicines to treat psychiatric and neurological conditions, will be working with the National Institute on Drug Abuse (NIDA) to test its patented version of ibogaine as a potential treatment for a range of substance-use disorders.
“The therapeutic potential for ibogaine is huge,” says David Olson, the co-founder of Delix. “There are some indications that a single dose can keep people with opioid use disorder drug-free for months.”
Ibogaine is a powerful psychedelic substance. Derived from the iboga shrub native to West Africa, it has a history as a spiritual sacrament in the Bwiti religion in the country of Gabon. But it has also been found—anecdotally and through a slate of studies—to help people get off heroin and other opioids. Ibogaine is not the ideal addiction-treatment drug; it can cause cardiac arrhythmia (an irregular heartbeat) and its intense psychedelic experience is not for everyone.
Olson, who is a professor and runs his own lab at the University of California at Davis, modified the ibogaine molecule and patented it. His ibogaine analog, which he has dubbed Delix-7, is not psychedelic. Delix-7 also does not cause cardiac arrhythmia like its psychedelic version does.
“We started with the ibogaine structure because of its fantastic efficacy, and we whittled it down to its essential feature,” says Olson, describing how he modified ibogaine to remove the psychedelic-inducing properties. “By cutting it down, we got rid of these undesired side effects.”
A lab contracted by Nida’s Addiction Treatment Discovery Program will conduct preclinical tests on Delix’s compound to evaluate its pharmacological, pharmacokinetic and toxicological properties. If the preclinical data and animal studies shows that the experimental drug could be a safe and potentially effective treatment for people with substance abuse disorders, Delix will apply to the U.S. Food and Drug Administration to launch human clinical trials.
Nida would not comment on the preclinical testing of Delix-7, but a spokesperson said that the federal agency is interested in the therapeutic potential for psychedelics in general. Research into these substances is being conducted across the National Institutes of Health, including Nida, in a range of projects to identify potential medicines. All testing is conducted under blinded conditions and all data is confidential.
“Our focus historically has, of course, been the misuse and problems associated with these substances,” says Dr. Wilson Compton, the deputy director of Nida. “But we're very aware of the potential therapeutic advantages of many abusable substances.”
Right now, Compton says that the therapeutic potential of psychedelics is “theoretical” as there have been no proven treatments yet. But Nida is funding studies and giving grants to researchers in the space because “we will take advances wherever they come from” if based on rigorous science.
“We're particularly excited about this as a possibility,” says Compton. “But it remains very speculative and a possibility, not a reality.”
The psychedelic renaissance has been resurrected, thanks to a slate of studies showing that when combined with psychotherapy, psychedelic drugs like psilocybin (the active ingredient in magic mushrooms), MDMA (also known as the party drug “Molly”) and LSD show enormous potential to treat a range of conditions and mental illnesses. The studies, and a good dose of psychedelic hype, has convinced investors to pour billions into companies racing to develop the first FDA-approved psychedelic medicines.
Companies like Compass Pathways and nonprofits like the Multidisciplinary Association for Psychedelic Studies are pursuing FDA approval for psilocybin-assisted therapy to treat certain types of depression and MDMA-assisted therapy to treat PTSD, respectively.
But Olson is party to a camp in the industry that believes the psychedelic experience might not be necessary at all. Olson doesn’t think the therapeutic benefits of psychedelic drugs is due to the ego-melting trip, but rather due to what these drugs trigger in the brain.
The reason psychedelic drugs have been found to alleviate symptoms of depression and PTSD in clinical trials, it is thought, is due the signaling of the 5-HT-2A receptor, which sparks what’s called neuroplasticity. Neuroplasticity helps the brain form new neural connections, which is believed to generate rapid and sustained positive mood effects. In studies, psilocybin-assisted psychotherapy has provided almost immediate reductions in depressive symptoms after a single high dose and antidepressant effects that last as long as six months in some participants.
Olson says that the root of many neuropsychiatric conditions, including addiction, is the atrophy of neurons in the prefrontal cortex. But drugs that trigger neuroplasticity are like Miracle-Gro, helping the brain rewire healthy neural pathways.
Olson has discovered 1,000 novel compounds—all nonpsychedelic but based on psychedelic molecules and still trigger neuroplasticity. Olson calls his molecules “psychoplastogens,” a term he coined, to differentiate between drugs with similar structures that produce a psychedelic experience and ones that don’t. Another lead compound Delix is trying to develop is DLX-1, a patented molecule that has a similar structure to MDMA but lacks Molly’s rolling waves of euphoria.
Drugs currently on the market that are used to treat opioid use disorder, like naltrexone and buprenorphine, bind to opioid receptors in the brain. This reduces cravings, prevents withdrawal and prevents patients from getting high if they use. But both are daily pills. Psychedelic drugs or drugs based on psychedelic compounds act differently. Studies have found that a single dose of a psychedelic can have lasting positive effects.
“I think one of the limitations [for current drugs on the market] is that a drug has to be on board to have the effect, whereas what we’ll hopefully see in our compounds is that you don’t have to take it every day,” says Retsina Meyer, Delix’s head of strategic partnerships who is working with Nida.
Delix hopes that Delix-7 will work to treat a range of substance abuse disorders, including stimulants like cocaine and methamphetamine. Currently, there is no FDA-approved medicine that helps people addicted to these substances.
Olson says if Delix-7 is found to be safe and effective, it could become a blockbuster drug one day. When asked why Delix Therapeutics is targeting substance use disorder, he says because it’s personal.
“It’s personal to you, and everyone else: One in five people will suffer from a neuropsychiatric disease at some point in their lifetime,” says Olson. “We all know five people, we’ve all been touched by this, and we’ve all been affected by it.”
This piece was originally published in Forbes here: https://www.forbes.com/sites/willyakowicz/2021/12/07/us-government-will-test-ibogaine-as-an-addiction-treatment/?sh=3dba96114c4e