LSD affects a large number of the G protein coupled receptors, including all dopamine receptor subtypes, and all adrenoreceptor subtypes, as well as many others. LSD binds to most serotonin receptor subtypes except for 5-HT3 and 5-HT4. However, most of these receptors are affected at too low affinity to be sufficiently activated by the brain concentration of approximately 10–20 nM. In humans, recreational doses of LSD can affect 5-HT1A, 5-HT2A, 5-HT2C, 5-HT5A, and 5-HT6 receptors. 5-HT5B receptors, which are not present in humans, also have a high affinity for LSD. The psychedelic effects of LSD are attributed to its strong partial agonist effects at 5-HT2A receptors as specific 5-HT2A agonists are psychedelics and largely 5-HT2A specific antagonists block the psychedelic activity of LSD. Exactly how this produces the drug's effects is unknown, but it is thought that it works by increasing glutamate release in the cerebral cortex and therefore excitation in this area, specifically in layers IV and V. LSD, like many other drugs, has been shown to activate DARPP-32-related pathways.
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