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Since the 1990s, there has been a renewal of scientific research into the potential medical and psychological therapeutic benefits of psilocybin for treating conditions including obsessive-compulsive disorder, cluster headaches, and anxiety related to terminal cancer.
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Psilocybin is rapidly dephosphorylated in the body to psilocin, which is a partial agonist for several serotonergic receptors. Psilocin has a high affinity for the 5-HT2A serotonin receptor in the brain, where it mimics the effects of serotonin (5-hydroxytryptamine, or 5-HT). Psilocin binds less tightly to other serotonergic receptors 5-HT1A, 5-HT1D, and 5-HT2C.[1] Serotonin receptors are located in numerous parts of the brain, including the cerebral cortex, and are involved in a wide range of functions, including regulation of mood and motivation.[81] The psychotomimetic (psychosis-mimicking) effects of psilocin can be blocked in a dose-dependent fashion by the 5-HT2A antagonist drugs ketanserin and risperidone.[82]
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For example, psilocin indirectly increases the concentration of the neurotransmitter dopamine in the basal ganglia, and some psychotomimetic symptoms of psilocin are reduced by haloperidol, a non-selective dopamine receptor antagonist. Taken together, these suggest that there may be an indirect dopaminergic contribution to psilocin's psychotomimetic effects.[85] In contrast to LSD, which binds to dopamine receptor D2, psilocybin and psilocin have no affinity for the dopamine D2 receptors.[1]
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About half of the study participants—described as healthy, "spiritually active", and many possessing postgraduate degrees—showed an increase in the personality dimension of openness (assessed using the Revised NEO Personality Inventory), and this positive effect was apparent more than a year after the psilocybin session. According to the study authors, the finding is significant because "no study has prospectively demonstrated personality change in healthy adults after an experimentally manipulated discrete event."[110]
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studied the effects of psilocybin on patients with obsessive–compulsive disorder (OCD). The pilot study found that, when administered by trained professionals in a medical setting, the use of psilocybin was associated with substantial reductions in OCD symptoms in several of the patients.[149][150] This effect is caused largely by psilocybin's ability to reduce the levels of the 5-HT2A receptor, resulting in decreased responsiveness to serotonin.[83] Psilocybin has additionally shown promise to ease the pain caused by cluster headaches,[151
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The psychotomimetic effects of psilocin can be blocked in a dose-dependent fashion by the 5-HT2A antagonist drugs ketanserin and risperidone.
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