Pharmacology Information

The active compounds found in Psilocybin mushrooms are known as Psilocybin and Psilocin. When ingested Psilocybin is rapidly dephosphorylated by the liver into Psilocin. Psilocin has a molecular structure very similar to the endogenous neurotransmitter serotonin, this allows it to bind to the 5-HT2A serotonin receptor, producing the positive effects on mood, anxiety, focus, creativity, and memory that are currently being researched. 

Stimulating the 5-HT2A receptor leads to two  important results:

  • The production of “Brain Derived Neurotrophic Factor” (BDNF) which is “like Miracle-Gro for your brain. It stimulates growth, connections, and activity.”
  • The increased transmission of “Glutamate,”  the neurotransmitter most responsible for brain functions like cognition, learning, and memory.
neural connections on psilocybin
Glutamate and BDNF work congruently in ways scientists are only beginning to understanding, however it is clear that higher levels of each are responsible for many of the benefits associated with both Micro and Macro dosing.
In addition to the secretion of Glutamate and BDNF Psilocybin also connects regions of the brain that in the "sober" state of consciousness do not communicate. These unique connections are formed via the dampening of activity in an often over-used part of our brain called the “Default Mode Network” (DMN).

The DMN is responsible for a variety of cognitive functions including day-dreaming, self-reflection, and the ability to perceive the past, present, and future. Some studies suggest that depression is linked to an overactive DMN. The theory behind this is the possibility that a highly active DMN causes us to extensively ruminate, over-analyze, and become removed from the present moment to question the past and the future.

DMN suppression may help explain why psychedelic substances could be used to combat depression and anxiety, and also lead to insights and creative perspectives that remain inaccessible to the "sober" state of consciousness.
summary of psilocybins neuropharmalogical effects
Serotonin, the moleis a key neuromodulator known to be involved in brain development, perception, cognition, and mood. The vast majority of antidepressants (Selective Serotonin Reuptake Inhibitors, or SSRIs) act on the serotonergic system. Psilocybin engages the same system, however in multiple importantly different ways.
Psilocybin molecules are close enough in molecular structure to bind with serotonin receptors, mimicking serotonin, whereas SSRI's inhibit reuptake into the presynaptic cell, increasing the level of serotonin in the synaptic cleft available to bind to the postsynaptic receptor. Higher levels of serotonin are not always beneficial for two reasons, first because, similar to numerous other hormones, when an excess is detected by the body endogenous production is limited, and secondly because increased serotonin levels have been postulated to "dull" or "dampen" emotion, resulting in suppression of emotions rather than causal exploration.
Another key difference between Psilocybin and SSRI's is the antagonization of the Dopaminergic system. SSRI's often trigger a dopamine response, giving them serious addictive potential, while Psilocybin minimally affects dopamine secretion

 *Life cycle of a serotonin molecule



In conclusion, Psilocybin acts as a serotonergic antagonist, binding to the 5HT2 receptor and stimulating the production of Glutamate and BDNF. It drastically changes neural informational paths, attenuates the DMN allowing the brain to make unique connections between areas that don’t usually communicate, while interacting minimally and only indirectly with dopaminergic system. These properties are all congruent with the ability to re-wire fear condition responses, alleviate anxiety, deepen emotion, increase focus, and stimulate creativity.