Scientists from Copenhagen University Hospital tested whether a single dose of psilocybin increases synapse density - the contacts between nerve cells through which they exchange signals. The work was published in Translational Psychiatry.
The study involved 15 healthy adults, median age 32.5 years, of whom 5 were women. Each received a single oral dose of psilocybin calculated to produce an intense psychedelic experience. The first five people took the substance lying in an MRI scanner and performed tasks, while the other ten did so in a separate room with music. In both cases, two facilitators were present, providing psychological support.
Before intake and a week after it, participants underwent positron emission tomography (PET) - an imaging method that allows tracking the distribution of radioactive substances in the body. It was used to measure the level of the SV2A protein, which is located in synapses and serves as an indirect marker of their density. Previously, in experiments on pigs, the same researchers found an increase in SV2A a week after a dose of psilocybin.
In the whole group, no statistically significant increase in SV2A was found. Average changes were small, about 2-3%, and the study was stopped early after a planned interim analysis: reaching the target result seemed unlikely. The main result does not confirm that psilocybin increased the measured synapse marker.
In additional analyses, participants in the room reported more intense mystical experiences and more pronounced positive long-term effects at three months than those who took the substance in the scanner. The groups did not differ in negative long-term effects.
The dynamics of SV2A also differed. In the room group, the average increase was about 5-6% in the frontal cortex and hippocampus, whereas in the scanner group there was no increase. The difference between the groups was statistically significant in the frontal cortex but not in the hippocampus, and the within-group increase in the room group itself did not reach statistical significance. More vivid mystical experiences were associated with a greater increase in SV2A, but this association was also not statistically significant. A correlation is a statistical relationship that by itself does not prove causation.
The authors conclude: "these results indicate that the neuroplastic effects of psilocybin are modulated by the surrounding environment, which has important implications for psychedelic therapy." However, in the same paper they call the differences between conditions "preliminary and hypothesis-generating rather than conclusive" because of the small sample. The researchers suggest that a supportive environment may promote positive emotions and a sense of safety, facilitating changes in brain connections, whereas a stressful or distracting setting, such as an MRI scanner, may limit them.
The work has serious limitations. There was no placebo group, and participants were not randomly assigned to conditions: the five in the scanner were simply the first five recruited. The scanner group is very small, and the settings differed in many parameters at once - the noise and confinement of the scanner, the tasks, the music. In addition, the participants were healthy people, not patients receiving psilocybin as treatment; the authors note that effects may be stronger in people with depression, since they usually have lower SV2A levels. Previous work has shown that on repeat scanning SV2A measures tend to decrease, so the study may have underestimated a possible increase. One of the authors received a salary with support from COMPASS Pathways - a company developing psilocybin-based therapy - and two others are affiliated with companies creating psychedelic drugs.