Connection Between Serotonin and LSD

LSD and Serotonin are structually similar. It is for this reason that the effect of LSD on Serotonin receptors was first examined. It is believed that the drug interferes with Serotonin's normal action on the brain receptor sites. It has been found that the stimulis properties of LSD can be blocked by central acting serotonin agonists, but not by peripheral serotonin agonists. Therefore serotonin receptors in the Central Nervous System must somehow be involved in the subjective effects of LSD. Additionally, this was implicated in studies where rats were trained to give a response when electrically stimulated in the Raphe nucleus. The Raphe Nucleus is a serotonin containing area of the brain stem which aids in the regulation of sleep. The same trained response was observed in rats that had been given LSD. Therefore, the LSD must act on this nucleus as a serotonin antagonist.

Another theory stipulates that LSD acts as a partial agonist by binding to the 5HT receptors. Since serotonin has an inhibiting action at the 5HT receptors, LSD, being a partial agonist will cause disinhibition to take place. The reason LSD is called a "partial" agonist is because it will cause firing to take place but will do so at a fairly slow rate, thereby explaining why LSD has been thought to be an antagonist before. Fiorella et al. (1995) found that serotonin antagonists inhibit the hallucinogenic effects of LSD and postulate that LSD is an agonist.

Although it is not certain how, serotonergic neurons are involved in the control of dreaming (see page on Serotonin.) It has been hypothesized that LSD produces hallucinations by interfering with activity of seretonergic synapses in the Raphe Nucleus. In other words, LSD has the effect that it does by producing a dreamlike state in a waking being.