The psychedelic drug ibogaine is known for two things: its reputation in some circles as a panacea for addiction and the visceral hallucinations it induces. Positive anecdotes abound from people who have sought out the illegal drug at underground clinics. Just one dose, they say, brings near-instant relief from cravings and withdrawal symptoms, a veritable miracle for seemingly intractable addictions. But the side effects of this plant-derived substance can be dangerous or even deadly. Now, with encouraging evidence from animal studies, drugs are being developed to replicate ibogaine's impact on addiction without the side effects. A drug that is chemically related to ibogaine but lacks its hallucinogenic properties is set to begin phase II clinical trials in California early this year. If the results continue to be promising, addiction treatment as we know it could change radically.
For decades research on ibogaine has been stymied by its classification as a Schedule I drug, the most tightly regulated category. Yet the results of animal studies have been intriguing. In May 2016 a meta-analysis examining 32 such studies, mostly in mice and rats, found that ibogaine reduced self-administration of cocaine, opioids and alcohol. An earlier study from 2015 found that noribogaine, the substance that ibogaine breaks down to when ingested, reduced self-administration of nicotine in addicted rats by 64 percent.
Now Savant HWP, a pharmaceutical company in California, has developed a drug called 18-MC, a compound chemically related to ibogaine, which it hopes will produce the antiaddictive properties without triggering hallucinations. They are betting that the “trip” is not a necessary component of the therapy—an idea shared by some academics. In 2014 the company completed phase I trials in Brazil with 14 healthy volunteers to determine whether the drug is safe, which they do not plan to publish (as long as the data are provided to the FDA, no publication is required). Savant HWP CEO Stephen Hurst reports that overall the drug was “well tolerated” and there were “no serious adverse effects,” although it was “much more potent than we were expecting.” Phase II trials of the drug's efficacy are set to begin in the U.S. in early 2017.
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Some hold out hope that ibogaine in its natural form could also become a standard treatment for addicts, but other experts urge caution. They warn that not enough is known about the risks of taking the drug, which has a long history of use in West Central African shamanistic rituals. Reported adverse effects include heart attack and seizures, and several people have died while seeking addiction relief with ibogaine.
Also mysterious is how ibogaine works to disrupt the cycle of addiction. People who have tried it have likened the intense hallucinogenic trip to going through years' worth of therapy in 24 hours, with flashbacks to childhood and pivotal experiences. “It was so vivid. It was like watching a movie with your eyes closed,” says Kevin (whose name has been changed to protect his identity), who tried ibogaine for multiple addictions during a stay at a clinic in Mexico. “I had visions of me being 16 years old when I used to drink cough syrup, and my mom caught me one night and she was crying.”
But experiences with ibogaine vary from person to person—not everyone, for instance, experiences the drug's trippy effects—and its neurochemistry and biophysics are perplexing. Research indicates that ibogaine acts on dopamine, serotonin and other neurotransmitter pathways strongly linked to addiction and reward, similar to other psychedelics currently being explored for addiction and mental illness treatment. Yet preliminary studies suggest that ibogaine attaches to other molecules in a unique way. “The mechanism of action at the molecular level is peculiar,” wholly unlike that of “traditional” drugs, says Emeline Maillet, a co-author of the 2015 study on rats and nicotine, who was then at DemeRx in Miami. Most active compounds work by binding to a receptor on the outside of a cell membrane. But ibogaine seems to do the opposite, binding to the inside of the membrane—something no other naturally occurring molecule is known to do, says Maillet, who observed this effect in another 2015 study examining ibogaine's effect on opioid receptors.
Gary Rudnick, a professor of pharmacology at Yale University, observed a similar phenomenon in a 2016 study on ibogaine and serotonin, finding that ibogaine blocked cocaine molecules by binding to “inward-facing,” “mutually exclusive” locations on serotonin transporters. “All inhibitors except for ibogaine bind in an outward-facing configuration. So ibogaine is unique,” Rudnick says. But we are still far from knowing the truth about how the drug works, he adds: “Ibogaine has a lot of effects on many different proteins. It's not a very clean drug. We're not sure which targets are responsible” for its addiction-interrupting ability versus its other effects.
Experts emphasize that ibogaine treatment, which can cost up to $10,000 on the black market, is not a cure. Relapse is likely in people who use ibogaine as their sole means of therapy without changing their other harmful patterns. Until we learn more about the drug's mysterious effects and until safer versions become available, the best advice for people struggling with addiction is to follow proved methods, including cognitive-behavioral therapy, support groups and approved antiaddiction medication.