Psilocin finds its way to the brain in about 30 minutes. There it interacts with the brain by mostly influencing the serotoninergic system. In a way, it mimics the function of serotonin. Serotonin itself is a monoamine neurotransmitter. It has many complex (not perfectly understood) function in the brain linked with learning, memory, happiness, and more.
Serotonin (left) and psilocin (right)
The most receptors for serotonin are in the cerebral cortex (the outer part of the brain, about 40% of the brain’s mass). Psilocin binds to these and specifically 3 receptors called 5-HT2B, 5-HT2C, and 5-HT1A. The HT stands for hydroxytryptamine, which is another word for serotonin (i.e. it binds to the receptors that serotonin normally binds to). At this moment we’ve identified 7 main receptors of serotonin.
Notably, other drugs also bind to receptors for serotonin. LSD for instance also has a strong affinity for 5-HT2A. But let’s park the discussion of how different drugs work on the brain for another time.
Psilocybin has effects that are larger than only at the specific receptors for serotonin. When brains were looked at with a functional MRI (fMRI) scanner, two main things stand out. The first is that there was less blood flow (interpreted as fewer connections) between the medial prefrontal cortex (mPFC) and the posterior cingulate cortex (PCC). This effect was seen also in different ‘hub’ regions of the brain (like the thalamus and anterior cingulate cortex.
The hypothesis here is that the subjective effects of psilocybin are caused by decreased activity and connectivity in those hub regions. Thus enabling a state of unconstrained cognition.
The second finding is that psychedelics produce an ‘entropic’ brain state. Entropic here refers to being in more disorder, or being more ‘disintegrated’. This means that whilst there are fewer ‘hub’ regions being activated, the brain is overall more connected.
The changes in the brain are not only visible during the psychedelic experience (we will discuss the duration in a moment), but can also be seen on fMRI scans and subjective reports of mental health at 5 weeks. Those with the biggest changes in the brain were also those who had the best subjective outcomes.