A non-hallucinogenic psychedelic analogue reverses the effects of stress in the mouse study

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A single dose of tabernanthalog (TBG) promotes the formation of dendritic spines in the cortical neurons of mice. Credit: Chelsea Kintz

A new compound similar in structure to the psychedelic drug ibogaine, but lacking toxic and hallucinogenic effects, has been found to rapidly reverse the effects of stress in mice.

The researchers found that a single dose of tabernanthalog (TBG) could be corrected -induced behavioral deficits, including anxiety and cognitive inflexibility, and also promotes the regrowth of neural connections and restores neural circuits in the brain that are altered by stress. The study was published on May 25 a Molecular psychiatry.

“It was very surprising that a single low-dose treatment had such dramatic effects in one day,” said corresponding author Yi Zuo, a professor of molecular, cellular and developmental biology at UC Santa Cruz. “I had a hard time believing it even when I saw the initial data.”

TBG was developed in the lab by co-author David Olson of UC Davis. Zuo’s lab worked with Olson in the initial TBG studies, reported in Nature in 2020. The new study focused on the harmful effects of stress through a protocol in which mice are subjected to mild and unpredictable stressors over a period of several days.

At the behavioral level, stress causes increased anxiety, deficits in sensory processing, and reduced flexibility in decision making. In the brain, stress alters connections between neurons and alters neural circuits, causing an imbalance between arousal and inhibition.

“Surprisingly, TBG reversed all the effects of stress,” Zuo said. “This study provides a meaningful insight into the neural mechanisms underlying the therapeutic effects of psychedelic analogues on mental illness and paves the way for future research to understand their cellular and circuit mechanisms.”

In recent years, there has been renewed interest in the use of psychedelic substances to treat diseases such as addiction, depression, anxiety and post-traumatic stress disorder. The hallucinogenic effects of these drugs remain a concern, but scientists do not know whether hallucinations are therapeutically important or just a side effect.

Ibogaine has been shown to be promising for treating addiction, but it causes dangerous heart arrhythmias, in addition to being a potent hallucinogen. TBG has not yet been tested in humans, but has no ibogaine toxicity , and does not induce head contraction behavior in mice caused by known hallucinogens.

Initial TBG studies found that it had antidepressant effects and reduced the addictive behavior of rodents. The new study was started by co – author Michelle Tjia, then in in Zuo’s lab studying the . After Tjia left for a postdoctoral fellowship, co-author Ju Lu, a project scientist in the lab, conducted additional studies. The researchers conducted a series of tests to evaluate behavioral responses to stress and the effects of TBG treatment. They also performed imaging studies to assess changes in the brains of mice at the neuronal level.

Studies using animal models (conducted in accordance with NIH regulations and reviewed and approved by the Institutional Committees for Animal Care and Use) continue to be vital for investigating complex psychiatric disorders.


A new compound related to psychedelic ibogaine could treat addiction, depression


More information:
Ju Lu et al, an analogue of psychedelics restores functional neural circuits interrupted by unpredictable stress, Molecular psychiatry (2021). DOI: 10.1038 / s41380-021-01159-1

Citation: Non-hallucinogenic psychedelic analogue reverses the effects of stress in the mouse study (2021, May 25) retrieved May 25, 2021 at https://medicalxpress.com/news/2021-05 -non-hallucinogenic-psychedelic-analog-reverse-effects. html

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