Scientists in Denmark believe the psychedelic substance psilocybin might produce rapid and lasting antidepressant effects in part because it enhances neuroplasticity in the brain. Their new research, published in the International Journal of Molecular Sciences, has found evidence that psilocybin increases the number of neuronal connections in the prefrontal cortex and hippocampus of pig brains.
Psilocybin — the active component in so-called “magic” mushrooms — has been shown to have profound and long-lasting effects on personality and mood. But the mechanisms behind these effects remain unclear. Researchers at Copenhagen University were interested in whether changes in neuroplasticity in brain regions associated with emotional processing could help explain psilocybin’s antidepressant effects.
“Both post-mortem human brain and in vivo studies in depressed individuals have shown a loss of synapses through the down-regulation of synaptic proteins and genes,” the authors of the study wrote. “Hence, upregulation of presynaptic proteins and an increase in synaptic density may be associated with the potential antidepressive effects of psychedelics.”
The researchers had previously conducted tests to establish the proper dose of psilocybin needed to produce psychoactive effects in pigs, who were examined because their brains are anatomically similar to the brains of humans.
A group of 12 pigs received a psychoactive dose of psilocybin, 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 examination of brain tissue from the hippocampus and prefrontal cortex revealed increases in the protein SV2A in pigs who had received psilocybin. SV2A, or synaptic vesicle glycoprotein 2A, is commonly used as a marker of the density of synaptic nerve endings in the brain. SV2A is typically reduced in patients with major depressive disorder.
“We find that a single dose of psilocybin increases the presynaptic marker SV2A already after one day and that it remains higher seven days after,” the researchers said, adding that the “increased levels of SV2A after intervention with a psychedelic drug adds to the scientific evidence that psychedelics enhance neuroplasticity, which may explain the mechanism of action of its antidepressant properties.”
The study, “A Single Dose of Psilocybin Increases Synaptic Density and Decreases 5-HT2A Receptor Density in the Pig Brain“, was authored by by Nakul Ravi Raval, Annette Johansen, Lene Lundgaard Donovan, Nídia Fernandez Ros, Brice Ozenne, Hanne Demant Hansen, and Gitte Moos Knudse.