Single Use of Psilocybin Enhances Neuroplasticity Gene Activity
Scientific publications on the properties of psychedelics are being released almost daily, which is why our era is often called the renaissance of psychedelic therapy. Since the 1950s, when psychedelics first gained widespread attention, research was largely based on empirical experience. In the 1970s, all studies were halted as LSD and other substances in this group were classified as Schedule I drugs. Thirty years later, these substances returned to laboratories and therapists’ offices, now accompanied by entirely new scientific tools. Neuroimaging and genetics are gradually bringing us closer to understanding the mysteries of these molecules.
One such study, published in the Journal of Psychopharmacology, focuses on the activity of brain genes after a single use of psilocybin.
How Psychedelics Affect the Brain
Over the past 20 years, scientists have made significant progress in uncovering the pharmacological effects of psychoactive substances derived from mushrooms and plants. The main effect is linked to the rapid impact on a subgroup of serotonin 5HT receptors. This interaction is responsible for hallucinations during high doses of entheogens (plant-based psychoactive substances) and the so-called “unification” effect in the brain. This means that neural networks, which are usually isolated from each other in adulthood, “forget” their boundaries under the influence of psychedelics and start working from a “clean slate,” sometimes resulting in reversible synesthesia.
But what about the long-term neuroplasticity effects after taking these substances? This question has been partially answered. Since the 1990s, it has been known that psilocybin and LSD affect the so-called immediate early genes (IEGs) in the prefrontal and somatosensory cortex, hippocampus, and midbrain of rodents.
Immediate Early Genes and Brain Adaptation
Immediate early genes in neural tissue are genes that are easily “switched on” in response to external or internal stimuli and enhance synaptic transmission between neurons for an extended period. In other words, their activity determines how quickly the brain adapts to new environmental conditions.
New Research on Psilocybin and Neuroplasticity
A study led by Danish scientist Oskar Jefsen, published in the Journal of Psychopharmacology in 2020, further explores this topic. It demonstrates not only psilocybin’s influence on neuroplasticity in other brain regions but also the degree of its persistence.
The experiment involved 70 mice, each given a single dose of psilocybin in varying amounts, while 10 mice received a saline solution as a control group. Ninety minutes later, using genetic methods, researchers examined the activity of 54 brain genes previously studied in psychedelic research, as well as protein synthesis (translation) associated with their activity, which characterizes the long-term genetic effects.
The results showed that psilocybin dose-dependently activates genes related to synaptic plasticity, even after a single, brief administration. Moreover, the neuronal activity triggered by psilocybin was more pronounced in the prefrontal cortex (where there are more 5HT2 receptors) compared to the hippocampus (where 5HT1 receptors are more prevalent), and this activity was more persistent over time than previously thought.
Implications and Future Directions
Despite several limitations (such as differences in sensitivity to psychedelics between humans and rodents, and the challenge of capturing rapidly reversible gene changes), the authors suggest that both short-term and long-term molecular events triggered by psilocybin may, in the future, provide a better understanding of the positive effects of psychedelics on the brain.