Researchers Are Closer to Understanding How Psilocybin Impacts the Brain

A recent study may have brought us closer to understanding how psilocybin impacts the brain. Researchers in Denmark examined the brains of pigs after psilocybin administration and discovered that a single dose of the psychedelic substance increased neuroplasticity, and had marked and long-lasting antidepressant effects.

Several studies have proven that psilocybin has a positive impact on mood and decreases depressive symptoms, but the mechanism of action was never determined. 

“The fact that there are therapeutic properties in psilocybin is not a doubt anymore,” said study author Nakul Ravi Raval of the University of Denmark in Copenhagen. “Though, the understanding behind its neurobiology remains unclear. There are many hypotheses and models that some people have defined, but they are still not proven. This is a small step at understanding the effects that can be seen directly in the brain.”

Researchers administered psilocybin to 12 pigs and a saline placebo to 12 pigs, and then examined the brains of the subjects. Six of the pigs were euthanized and examined one day after administration of psilocybin, and six were euthanized and examined 7 days after administration.

The brains of the pigs that had been given psilocybin had markedly increased amounts of SV2, synaptic vesicle glycoprotein 2A, a protein associated with the density of synaptic nerve endings. The seven-day samples also showed an increase in SV2A indicating that the changes associated with psilocybin are longer-lasting than previously thought. 

It may be worth noting that SV2A is found in decreased quantities in patients diagnosed with major depressive disorder. 

While it might seem strange to use pigs in a psychedelics study, they are the only large mammal with similar brain structure to that found in the human brain. 

“Believe it or not, they are much closer to humans than other laboratory animals. For instance, they have a gyrated brain like humans. Physiological too, they are more similar to humans,” says Raval. “They are also very genetically different from one another, just like us humans. Though, genetic variability is a double-edged sword. On the other hand, they are great as a tool for neuroimaging. Our lab has tested and optimized many positron emission tomography tracers in pigs before human trials. Pigs also have giant brains compared to rodents. The size of the brain allows for multiple studies from a single batch of an experiment.” He adds that the steep price of housing pigs often prevents such studies from being frequently conducted.”. 

Raval explains that depression and related disorders are correlated with neural atrophy, meaning there are “lesser connections” of functional neurons. In vitro studies, or “test-tube experiments,” show that “when neurons (in cell cultures) are treated with psychedelics, there is an increase in structural and functional plasticity,” he says.

“What this means is that there is an apparent increase of connections in the neuronal cell. We believe the immediate and prolonged antidepressive effect of psilocybin is due to this increase in connections and function.”

Because the animals used in the study were all healthy and not depressed, the researchers had to make the connection between psilocybin’s neurological effects, and its antidepressant qualities. “Just like the in vitro studies, we can only add one to one,” says Raval. “However, this is the first time that such an effect is seen in a large animal study. Unfortunately, with the lack of good large animal models for depression, this study has to be performed on healthy animals.”

Raval says this research has paved the way for multiple studies in their laboratory, and others. 

“We are trying to translate these findings into humans. Research never stops; one question is always followed by another. [But] it will surely help in the understanding of the neurobiology of psychedelics.”