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 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 the lab developed in 2015, the author and 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.
The project hinged on the genomic analysis. The 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 the 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, the author 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,” the author said.
But looking at molecular changes in animal models, such as the brains of mice, allows scientists to peer into what the author calls the black box of neuroscience to understand the biological processes at work. While the brains of mice are very different from human brains, The author said there are enough similarities to make valid comparisons between the two.
The 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. The 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, the author said. The findings were published in Cell Reports.
Single exposure to psychedelic alters epigenetics and synaptic plasticity
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