Psilocybin rapidly increases the expression of several genes related to neuroplasticity in the rat brain, according to new research published in the Journal of Psychopharmacology. The new findings might help explain the underlying neurobiological mechanisms responsible for long-lasting changes associated with psychedelic drug use.

“Psilocybin induces remarkable subjective effects, but has been largely ignored, scientifically, for many years. Recent studies suggest that it might, in combination with psychotherapy, be effective for treating certain mental disorders. As an aspiring scientific researcher it is very exciting to be part of the re-opening of a scientific field that has been hibernating for decades,” said study author Oskar Hougaard Jefsen, a visiting researcher at the Translational Neuropsychiatry Unit at Aarhus University.

Psilocybin produces profound changes in perception and consciousness through stimulation of serotonin receptors in the brain. But the researchers were interested in learning why the substance has also been shown to produce long-term positive effects on several clinical symptoms.

In their study, 80 rats were injected with one of seven different doses of psilocybin or an inert saline solution. Ninety minutes later, the animals were euthanized so the researchers could extract RNA samples from key brain regions.

The researchers found that psilocybin increased the expression of several plasticity-related genes in the rodent’s prefrontal cortex and hippocampus, areas of the brain associated with executive functioning and memory.

“Psilocybin induces immediate changes in rat brains that resemble the changes we see when nerve cells are stimulated to form new connections. These changes may be part of the explanation why a psilocybin-trip sometimes induces lasting changes in the brain,” Jefsen told PsyPost.

The findings are in line with some previous research. For instance, a study published in Cell Reports found psychedelic drugs increased the number of neuronal branches (dendrites), the density of small protrusions on these branches (dendritic spines), and the number of connections between neurons (synapses) in rats and flies.

But Jefsen cautions that the research is still in its early stages.

“We still really don’t know 1) if human and rodent brains react similarly to psychedelic drugs and 2) which of the neurobiological effects that should be considered as important and which should be considered as irrelevant/by-products of the drug effects. It is very difficult to compare effects on rats with effects on humans because rats do not speak (or we don’t speak Rat),” he explained.

“Always be careful of hype and confirmation bias,” Jefsen added. “The evidence that psilocybin is effective for treating psychiatric disorders such as major depressive disorder is still rather weak because of small studies and methodological limitations.”

The study, “Transcriptional regulation in the rat prefrontal cortex and hippocampus after a single administration of psilocybin“, was published November 4, 2020.

(Photo credit: ZEISS Microscopy)