A novel compound similar in structure to the psychedelic drug ibogaine, but which has no hallucinogenic effects, has been found to rapidly reverse the effects of stress in mice.
Studies have shown that Ibogaine could hold promise for treating addiction, but it causes dangerous heart arrhythmias and is a powerful hallucinogen.
A study, published in Molecular Psychiatry, has shown that a single dose of tabernanthalog (TBG) can correct stress-induced behavioural deficits, including anxiety and cognitive inflexibility.
TBG was developed in the lab of study co-author David Olson at UC Davis. Zuo’s lab worked with Olson on the initial studies of TBG, reported in Nature in 2020. The new study focused on the deleterious effects of stress using a protocol in which mice are subjected to mild, unpredictable stressors over a period of several days.
Initial studies of TBG found that it had antidepressant effects and reduced addictive behaviours in rodents.
In this study, as well as its impact on anxiety and cognition, the researchers also found that TBG promotes the regrowth of neuronal connections and restores neural circuits in the brain that are disrupted by stress.
Yi Zuo, professor of molecular, cell, and developmental biology at UC Santa Cruz, commented: “It was very surprising that a single treatment with a low dose had such dramatic effects within a day. I had a hard time believing it even when I saw the initial data.”
On the behavioural level, stress causes increased anxiety, deficits in sensory processing, and reduced flexibility in decision-making. In the brain, stress disrupts the connections between neurons and alters the neuronal circuitry, resulting in an imbalance between excitation and inhibition.
“Amazingly, TBG reversed all of the effects of stress,” Zuo said. “This study provides significant insights into neural mechanisms underlying the therapeutic effects of psychedelic analogs on mental illnesses and paves the way for future investigations to understand their cellular and circuit mechanisms.”
The researchers conducted a range of tests to evaluate behavioural responses to stress and the effects of treatment with TBG. They also performed imaging studies to assess changes in the brains of the mice at the neuronal level.
TBG has not yet been tested in humans, but it lacks ibogaine’s toxicity in animal tests, and it doesn’t induce the head-twitch behaviour in mice caused by known hallucinogens.
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