I have heard anectdotal evidence that psilocybin (and to a lesser extent, LSD), can be used as a form of migraine therapy which can prevent future attacks, and are in fact being studied in the US by the Multidisciplinary Association for Psychedelic Studies as a new form of treatment for migraines/cluster headaches. Currently, many migraine drugs, such as Imitrex, Midrin, etc. are 5-HT1D agonists which are meant to abort migraine attacks already in progress. However, these drugs carry a host of nasty side effects, ranging from sedation to dysphoria to (in SWIM's experience) having the headache actually increase in intensity. Unlike the current migraine drugs, Psilocybin is a 5-HT2A receptor antagonist, and seemingly should not influence migraines, since conventional therapies target a different serotonin receptor subtype. I have read on erowid, and experienced firsthand, that even a small recreational dose can prevent future migraine attacks for months, even after the user is exposed to a stimuli which would normally trigger a migraine. There is some debate as to how, neurochemically, migraines occur, but they do seem to occur in the absence of normal levels of serotonin, which may explain why 5-HT agonists can serve to stop a migraine in progress. I am wondering if psilocybin's action at the 5-HT2A receptors somehow trigger a cascade of events that effect long term changes (lasting months) in the brain that make serotonin levels increased for a while? Or, perhaps, they change binding affinities of other receptor subtypes, or change the number of receptors on cells. Any of these effects could potentially prevent future migraines, and would make psilocybin a more useful tool, therapeutically, than Imitrex or other medications which only work after a person is already suffering. I would like to know if anyone has input on the pharmacology behind this; for example, if they can propose a way that this could work, or if anyone has any studies or evidence pertaining to this theory (SWIM searched but couldn't find any specific articles), or if anyone has experiences with treating migraines using mushrooms or another psychedelic, please share them!