RESEARCH in animals suggests that the new compound is neither toxic nor hallucinogenic and that it may help treat a range of psychiatric disorders, including depression and addiction, and possibly anxiety and post-traumatic stress disorder (PTSD).
While there have been no placebo-controlled clinical trials of ibogaine, anecdotal reports and small open-label studies suggest that it can reduce drug cravings and prevent relapse.
However, ibogaine is a hallucinogen classed as a Schedule I controlled substance in the United States. It is also toxic and can cause cardiac arrhythmia.
Researchers have linked the use of ibogaine to several deaths.
David Olson, an assistant professor of biochemistry and molecular medicine at the University of California, Davis, and colleagues set out to create a safer version of ibogaine that retains its anti-addictive properties but is neither toxic nor hallucinogenic.
Olson’s lab, one of only a few in the United States licensed to work with Schedule I substances, investigates psychoplastogens — molecules such as the psychedelics ibogaine and DMT that promote neural plasticity, or the capacity of the brain to rewire and regain some of its former flexibility.
“Psychedelics are some of the most powerful drugs we know of that affect the brain,” says Olson, the senior author of the study paper. “It’s unbelievable how little we know about them.”
First, Olson and colleagues identified the parts of the ibogaine molecule that may be responsible for its therapeutic effects. They then engineered these features into a new molecule: tabernanthalog (TBG).
They derived the name from the Latin name for this group of plants, Tabernanthe iboga, meaning “tavern flower.”
Unlike ibogaine, TBG is water-soluble, which may make it less toxic and less likely to adversely affect the heart. It can also be synthesized in a lab in a single step.
When the researchers tested TBG on zebrafish, they found it to be less toxic than ibogaine.
In cultures of rat nerve cells, TBG increased the formation of new nerve branches, or dendrites. It also promoted the growth of new dendritic spines, the tiny protuberances that receive signals from other nerves. Other drugs that increase neural plasticity, such as ketamine and DMT, have similar effects on nerve cells.
Next, the researchers tested their new compound in several animal models of addiction and depression.
In a standard test designed to model binge drinking in humans, mice trained to crave alcohol consumed less after a single dose of TBG.
