Of mice and zen: Psychedelic compounds can drastically reduce stress in mice, study finds
- A single dose of tabernanthalog (TBG) can lower anxiety and cognitive inflexibility in mice
- TBG is a non-hallucinogenic psychedelic similar to ibogaine
- Mice were given stressors such as reduced cage space, loud noises and the introduction of new mice
- The compound was engineered in 2020 by UC Davis researchers
- TBG has not yet been tested in humans, but it does not show toxicity in animals
This gives new meaning to the phrase, ‘take a chill pill.’
Researchers at UC Santa Cruz have found that a non-hallucinogenic psychedelic similar to the psychoactive substance ibogaine drastically lowers the levels of stress in mice.
A single dose of tabernanthalog (TBG) can lower anxiety and cognitive inflexibility in the rodents.
It also has the ability to promote the regrowth of neuronal connections and restoring neural circuits that are negatively impacted from stress.
‘It was very surprising that a single treatment with a low dose had such dramatic effects within a day,’ said one of the study’s co-authors Yi Zuo, professor of molecular, cell, and developmental biology at UC Santa Cruz, in a statement.
‘I had a hard time believing it even when I saw the initial data.’
The new findings, published in Molecular Psychiatry, had two-month old mice subjected to ‘mild, unpredictable stressors’ over a period of seven days.
The TBG compound was responsible for making it seem as if the stressors, which include a reduction in cage space, exposure to a new room, loud noises and new mice, were never there.
‘Amazingly, TBG reversed all of the effects of stress,’ Zuo added.
TBG was engineered in 2020 by researchers from UC Davis and published in the scientific journal Nature in the latter part of the year.
The researchers looked at the behavioral responses to the stressors and the subsequent effects of TBG.
They also looked at imaging studies of the brains of the mice to come up with their findings.
TBG has not yet been tested in humans, but it does not show toxicity in animals, nor does it induce actions such as head-twitching seen with other hallucinogens.
A single dose of tabernanthalog (TBG) can lower anxiety and cognitive inflexibility in mice
A single treatment with a low dose had ‘such dramatic effects within a day,’ one of the study’s co-authors Yi Zuo, said
TBG promotes spine formation after UMS-induced spine loss in the mouse cortex
TBG also slightly elevates the survival of mice and results in more spines on the neural network, following stress incidents
‘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,’ Zuo explained.
The researchers note that human clinical trials are needed to determine whether it is indeed non-hallucinogenic, but it may have benefits over classic psychedelics, such as LSD.
‘Our data show that TBG promotes rapid spine formation and slightly elevates their rate survival, leading to more newly formed spines being consolidated into the neuronal network,’ they wrote in the study.
‘The functional implication of such effects remains to be elucidated. With the possibility of being developed into take-home medicines to facilitate patient access, this novel class of neuroplasticity-promoting (i.e., psychoplastogenic) compounds possess significant advantages over classical psychedelics.’
A number of psychedelic substances have been introduced in recent years to treat conditions such as depression and post-traumatic stress disorder (PTSD).
However, there has been concern from researchers about the hallucinogenic effects of the drugs and whether they are important from a therapeutic perspective or just a side effect.
Ibogaine might be useful for treating addiction, but it can also cause dangerous heart arrhythmias.
In April, scientists identified the AAZ-A-154 molecule, a ‘previously unstudied’ molecule, which also does not cause hallucinations.
THE PSYCHEDELIC DRUGS BEING STUDIED FOR MENTAL HEALTH BENEFITS
In recent years, scientists have increasingly looked to psychedelic drugs as promising therapies for treatment-resistant mental illness.
Currently, such mind-altering drugs are largely illegal in the US.
But ongoing clinical trials suggest that drugs once beloved by hippies and club kids might have medical benefits, too.
Scientists are investigating:
KETAMINE
The club drug and tranquilizer has been in tests for treating depression for several years.
In March 2019, the US Food and Drug Administration approved the first nasal spray version of the drug.
Ketamine works much more quickly than traditional antidepressants, and scientists believe it encourages new neural connections that can help overwrite unhealthy, depressive thought patterns.
PSILOCYBIN
The active ingredient in ‘magic mushrooms,’ psilocybin is a powerful hallucinogen.
It, too, acts far more quickly than traditional drugs and is being analyzed for use in patients with both depression and PTSD.
Psyilocybin helps encourage neurplasticity and is thought to quiet down the ‘default mode network’ in the brain, and activate the ‘salience network’ that is involved in medication.
In August, the FDA cleared the largest clinical trial for psilocybin to-date.
MDMA
The club drug MDMA – sometimes called ‘Molly’ – is currently in trials to treat PTSD.
MDMA appears to quiet activity in the amygdala and hippocampus, regions of the brain involved in emotional processing and fear responses, which are over-active in those with PTSD.
Patients participating in MDMA trials take a dose of the drug, and remain in an eight-hour session with two therapists who guide their experience.
LSD
The psychedelic compound LSD has a similar structure to the brain chemical, serotonin.
LSD’s discovery played a role in our discovery of how serotonin works in the brain and why imbalances of the neurochemical are involved in depression and anxiety.
Trials using LSD-assisted therapy to treat anxiety are ongoing and have shown early promise.
DMT
London-based firm Small Pharma is giving volunteers with depression DMT, a hallucinogenic tryptamine with similar psychedelic effects to LSD and magic mushrooms.
One of the active ingredients of DMT is ‘ayahuasca’ which is a traditional Amazonian plant medicine used ritually by some tribes to bring ‘spiritual enlightenment’.
The developers hope the drug will help a ‘significant number’ of people who don’t currently respond to conventional treatments or medication for depression.
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