Part of the Neuron Affected, Inhibitory or Excitatory Potential
Changes and Ion Channels Affected by Psilocybin
Psilocybin belongs to the classification of drugs called
hallucinogens. Hallucinogens typically act by stimulating
serotonin receptors at different times or for longer durations
than serotonin itself would (Kalat 2004). When psilocybin enters
the brain, the enzyme alkaline breaks down one of its phosphate
groups through hydrolysis. It then becomes psilocin, an even
stronger hallucinogen (Psilocybin 2003). It is particularly
potent due to the position of its hydroxyl group (Jacobs 1984).
Psilocin is a postsynaptic serotonin receptor agonist. In other
words, its similar structure allows it to mimic serotonin,
fitting into some types of serotonin receptors and producing the
same effect as endogenous serotonin (Merriam Webster 2003).
Specifically, psilocin activates the 5HT2A and 5HT1A receptors.
Stimulation of 5HT1 receptors is associated with an inhibitory
response while stimulation of the 5HT2 receptors is associated
with an excitatory response. Soma of the serotonergic neurons
are located in the midline raphe nuclei of the pons and in the
medulla oblongata. Axons extend to the basal ganglia,
hypothalamus, limbic forebrain, parts of the cerebral cortex,
and to the spinal cord (Kruk and Pycock 1979). Functions
believed to be moderated by serotonin include sleep, mood,
arousal, control of motor activity, hunger, thermoregulation,
and some neuroendocrine control mechanisms in the hypothalamus.
(Powell 2004, Kruk and Pycock 1979).
One theory states that effects caused by psilocin result from
stimulation of receptors in the raphe nuclei. According to this
theory, the raphe system has two main functions. One is related
to stimulation of motor neurons when a person is awake. The
other is to suppress sensory systems during the waking state
(Powell 2004). When psilocin binds to the 5HT2A receptors, it
inhibits the uptake of serotonin, thereby decreasing inhibitory
serotonin activity. This results in an increase of alertness and
arousal. Another theory asserts that the important activity of
psilocin takes place at the proximal dendrites of level V
pyramidal cells, as this is the area of the brain with the
highest concentration of 5HT2A receptors. In support of this
theory, this is the only area of the brain where directly
applies serotonin excites cells. The receptors do not activate
pyramidal cells directly but through action potential. This is
demonstrated by the fact that drugs that stop the action
potential prevent the 5HT2A induced excitation. While action
potential is required for such excitation, stimulation of the
5HT2A receptors does not result in increased action potential.
The excitation mechanism can also be blocked by presynaptic
inhibitors, showing that activity in the presynaptic 5HT2A
receptors that connect with pyramidal cells is...