Anon-hallucinogenic version of the psychedelic drug ibogaine, with potential
for treating addiction, depression and other psychiatric disorders, has been
developed by researchers at the University of California, Davis. A paper
describing the work is published Dec. 9 in Nature.
“Psychedelics are some of the most powerful drugs we know of that affect the
brain,” said David Olson, assistant professor of chemistry at UC Davis and
senior author on the paper. “It’s unbelievable how little we know about
them.”
Ibogaine is extracted from the plant Tabernanthe iboga. There are anecdotal
reports that it can have powerful anti-addiction effects such as reducing
drug cravings and preventing relapse. But there are also serious
side-effects, including hallucinations and cardiac toxicity, and the drug is
a Schedule 1 controlled substance under U.S. law.
Olson’s laboratory at UC Davis is one of a few in the U.S. licensed to work
with Schedule 1 substances. They set out to create a synthetic analog of
ibogaine which retained therapeutic properties without the undesired effects
of the psychedelic compound. Olson’s team worked through a series of similar
compounds by swapping out parts of the ibogaine molecule. They engineered a
new, synthetic molecule which they named tabernanthalog or TBG.
Models of anxiety, depression and addiction
Unlike ibogaine, the new molecule is water-soluble and can be synthesized in
a single step. Experiments with cell cultures and zebrafish show that it is
less toxic than ibogaine, which can cause heart attacks and has been
responsible for several deaths.
TBG increased formation of new dendrites (branches) in rat nerve cells, and
of new spines on those dendrites. That’s similar to the effect of drugs like
ketamine, LSD, MDMA and DMT (the active component in the plant extract
ayahuasca) on connections between nerve cells.
TBG did not, however, cause a head twitch response in mice, which is known
to correlate with hallucinations in humans.
A series of experiments in rodent models of depression and addiction show
that the new drug has promising positive effects. These animal models –
conducted in accordance with NIH regulations and reviewed and approved by
Institutional Animal Care and Use Committees – remain vital to investigating
complex psychiatric disorders.
Mice trained to drink alcohol cut back their consumption after a single dose
of TBG. Rats were trained to associate a light and tone with pressing a
lever to get a dose of heroin. When the opiate is taken away, the rats
develop signs of withdrawal and press the lever again when given the light
and sound cues. Treating the rats with TBG had a long-lasting effect on
opiate relapse.
Olson thinks that TBG works by changing the structure of neurons in key
brain circuits involved in depression, anxiety, post-traumatic stress
disorder and addiction.
“We’ve been focused on treating one psychiatric disease at a time, but we
know that these illnesses overlap,” Olson said. “It might be possible to
treat multiple diseases with the same drug.”
Indeed, psychedelic therapies have been attracting new interest in recent
years. But taking patients on individual ‘trips’ is time consuming and
costly, requiring hours of close medical supervision apart from the possible
negative effects.
“We need a drug that people can keep in their medicine cabinet and this is a
significant step in that direction,” Olson said.
Reference:
Lindsay P. Cameron, Robert J. Tombari, Ju Lu, Alexander J. Pell, Zefan Q.
Hurley, Yann Ehinger, Maxemiliano V. Vargas, Matthew N. McCarroll, Jack C.
Taylor, Douglas Myers-Turnbull, Taohui Liu, Bianca Yaghoobi, Lauren J.
Laskowski, Emilie I. Anderson, Guoliang Zhang, Jayashri Viswanathan, Brandon
M. Brown, Michelle Tjia, Lee E. Dunlap, Zachary T. Rabow, Oliver Fiehn,
Heike Wulff, John D. McCorvy, Pamela J. Lein, David Kokel, Dorit Ron, Jamie
Peters, Yi Zuo, David E. Olson. A non-hallucinogenic psychedelic analogue
with therapeutic potential. Nature, 2020; DOI:
10.1038/s41586-020-3008-z