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PSYCHEDELICS SHOW PROMISE IN TREATING MENTAL ILLNESS: DEPRESSION, ANXIETY,
ADDICTION, AND PTSD

TOPICS:AddictionAnxiety DisordersMental HealthPopularPTSDVirginia Tech

By Virginia Tech November 27, 2021

One in five U.S. adults will experience a mental illness in their lifetime,
according to the National Alliance of Mental Health. But standard treatments can
be slow to work and cause side effects.

To find better solutions, a Virginia Tech researcher has joined a renaissance of
research on a long-banned class of drugs that could combat several forms of
mental illness and, in mice, have achieved long-lasting results from just one
dose.



Using a process his lab developed in 2015, Chang Lu, the Fred W. Bull Professor
of Chemical Engineering in the College of Engineering, is helping his Virginia
Commonwealth University collaborators study the epigenomic effects of
psychedelics. 

Their findings give insight into how psychedelic substances like psilocybin,
mescaline, LSD, and similar drugs may relieve symptoms of addiction, anxiety,
depression, and post-traumatic stress disorder. The drugs appear to work faster
and last longer than current medications — all with fewer side effects.

Doctoral student Bohan Zhu works in the lab of Chang Lu on projects that could
lead to new treatments for depression, anxiety, and substance use disorder.
Credit: Tonia Moxley for Virginia Tech

The project hinged on Lu’s genomic analysis. His process allows researchers to
use very small samples of tissue, down to hundreds to thousands of cells, and
draw meaningful conclusions from them. Older processes require much larger
sample sizes, so Lu’s approach enables the studies using just a small quantity
of material from a specific region of a mouse brain.

And looking at the effects of psychedelics on brain tissues is especially
important.

Researchers can do human clinical trials with the substances, taking blood and
urine samples and observing behaviors, Lu said. “But the thing is, the
behavioral data will tell you the result, but it doesn’t tell you why it works
in a certain way,” he said.

But looking at molecular changes in animal models, such as the brains of mice,
allows scientists to peer into what Lu calls the black box of neuroscience to
understand the biological processes at work. While the brains of mice are very
different from human brains, Lu said there are enough similarities to make valid
comparisons between the two.

Chang Lu, Fred W. Bull Professor of Chemical Engineering in the College of
Engineering recently collaborated with a Virginia Commonwealth University
pharmacology lab on research into the use of psychedelics to treat mental
illness. Doctoral student Bohan Zhu is a co-author on the paper. Credit: Tonia
Moxley for Virginia Tech

VCU pharmacologist Javier González-Maeso has made a career of studying
psychedelics, which had been banned after recreational use of the drugs was
popularized in the 1960s. But in recent years, regulators have begun allowing
research on the drugs to proceed.

In work by other researchers, primarily on psilocybin, a substance found in more
than 200 species of fungi, González-Maeso said psychedelics have shown promise
in alleviating major depression and anxiety disorders. “They induce profound
effects in perception,” he said. “But I was interested in how these drugs
actually induce behavioral effects in mice.”

To explore the genomic basis of those effects, he teamed up with Lu.

In the joint Virginia Tech – VCU study, González-Maeso’s team used
2,5-dimethoxy-4-iodoamphetamine, or DOI, a drug similar to LSD, administering it
to mice that had been trained to fear certain triggers. Lu’s lab then analyzed
brain samples for changes in the epigenome and the gene expression. They
discovered that the epigenomic variations were generally more long-lasting than
the changes in gene expression, thus more likely to link with the long-term
effects of a psychedelic.

After one dose of DOI, the mice that had reacted to fear triggers no longer
responded to them with anxious behaviors. Their brains also showed effects, even
after the substance was no longer detectable in the tissues, Lu said.
The findings were published in the October issue of Cell Reports. 

It’s a hopeful development for those who suffer from mental illness and the
people who love them. In fact, it wasn’t just the science that drew Lu to the
project. 

For him, it’s also personal.

“My older brother has had schizophrenia for the last 30 years, basically. So
I’ve always been intrigued by mental health,” Lu said. “And then once I found
that our approach can be applied to look at processes like that — that’s why I
decided to do research in the field of brain neuroscience.”

González-Maeso said research on psychedelics is still in its early stages, and
there’s much work to be done before treatments derived from them could be widely
available.

Reference: “Prolonged epigenomic and synaptic plasticity alterations following
single exposure to a psychedelic in mice” by Mario de la Fuente Revenga, Bohan
Zhu, Christopher A. Guevara, Lynette B. Naler, Justin M. Saunders, Zirui Zhou,
Rudy Toneatti, Salvador Sierra, Jennifer T. Wolstenholme, Patrick M. Beardsley,
George W. Huntley and Chang Lu, 19 October 2021, Cell Reports.
DOI: 10.1016/j.celrep.2021.109836


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 1. REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of
    Psychedelics
    R. L. Carhart-Harris et al., Pharmacol Rev, 2019
 2. Lysergic Acid Diethylamide (LSD)
    Kristine Anne Hwang et al., StatPearls, 2020
 3. Philanthropists Fund Johns Hopkins Center for Study of Psychedelics
    Rita Rubin et al., Journal of American Medical Association, 2019
 4. Two Models of Legalization of Psychedelic Substances: Reasons for Concern
    William R. Smith et al., Journal of American Medical Association
 5. Be Sure: Bimekizumab versus Adalimumab in Plaque Psoriasis
    Richard B. Warren et al., NEJM, 2021

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