Psilocybin does not appear to severely impact gene expression, according to a new study published in European Neuropsychopharmacology. But the psychedelic substance — which is found in “magic” mushrooms — might produce lasting changes to the expression of a few immune-related genes in the brain.
“It is really intriguing that just a single psychedelic dose of psilocybin has such profound long-lasting effects on people’s personality and mood. We wanted to understand the mechanism behind this effect because it could be key to understanding the drug’s effects in general,” said study author Gitte Moos Knudsen, a professor at the University of Copenhagen and chair of the neurobiology research unit at Rigshospitalet.
In the study, which examined brain tissue from pigs, the researchers first conducted tests to establish the proper dose to produce psychoactive effects in the animals. Pigs were used because their brains are anatomically similar the brains of humans.
Knudsen and her colleagues then administered a psychoactive dose of psilocybin to 12 pigs, while a separate group of 12 pigs received inert saline injections. Half of the pigs were euthanized one day after the administration of psilocybin, while the rest were euthanized one week later.
An analysis of prefrontal cortex tissue revealed that 19 genes were differentially expressed one day after psilocybin administration. But only 3 genes were differentially expressed in the brain tissue one week later.
“This observation was unexpected, given the profound and lasting effects that have been observed after a single dose of psilocybin,” the researchers said.
Knudsen told PsyPost that there were “surprisingly few changes to be observed in the brain 24 hours and 7 days after a single dose of psilocybin.”
Immune-related genes constituted the largest group of genes impacted one week after psilocybin administration, suggesting that the long-lasting effects of the psychedelic substance might be related to neuroinflammation.
“Neuroinflammation is now recognised as key player in psychiatric diseases, such as depression, with positive outcomes of treatment with anti-inflammatory compounds,” the researchers wrote.
Scientists proposed in 2018 that psychedelic substances act as anti-inflammatory agents via the activation of the serotonin 2A receptor, which is known to play a key role in regulating immune function.
But there is currently very little research establishing a link between psychedelic drugs and neuroinflammation. Knudsen and her colleagues caution that “the ability of psilocybin to influence neuroinflammation remains to be further tested.”
In addition, “we only looked at two time points and cannot say anything about changes that occur outside these time points,” Knudsen said.
The study, “Effects of a single dose of psilocybin on behaviour, brain 5-HT 2A receptor occupancy and gene expression in the pig“, was authored by Lene Lundgaard Donovan, Jens Vilstrup Johansen, Nídia Fernandez Ros, Elham Jaberi, Kristian Linnet, Sys Stybe Johansen, Brice Ozenne, Shohreh Issazadeh-Navikas, Hanne Demant Hansen, and Gitte Moos Knudsen.