Lsd And Serotonin

LSD is known to affect many places in the brain where the body's neurotransmitter serotonin naturally has actions and effects, and the biochemical effects of LSD in the brain are mostly linked to those sites related to serotonin. LSD acts as a kind of impostor at receptors that recognize serotonin. LSD is like serotonin but different. Thus with LSD, the receptor signals other parts of the brain that there is too much serotonin, and these parts of the brain respond by tuning down cells that make serotonin. Yet, in fact, the chief effect of LSD is to cause less serotonin to be released in the neighborhood of the receptor—rather than too much, there is too little. This is one example of how LSD miscues the systems governing the flow of information between various brain neurons. In fact, overloading the brain with serotonin can reduce the LSD effect, and diminishing brain supplies of serotonin will increase LSD effects. Yet serotonin itself does not cause the scrambled perceptions that LSD does. How this miscue by LSD leads to the vivid effects is still unknown.

LSD, other indole-type psychedelics, and many hallucinogens related to mescaline (but surprisingly not mescaline itself) are known to act especially at a subtype of the serotonin receptor called the 5HT2 receptor. In laboratory animals, daily doses of LSD or psilocybin lead to fewer of these receptors, an effect that would be expected to produce tolerance; however, with 3 or 4 days off the drug, the number of 5HT2 receptors returns to normal. Both LSD and mescaline act at certain brain neurons, such as the locus coeruleus, and make it more responsive to inputs from the environment—such as a pinch. Researchers speak of such effects as lowering the gates to sensory input. We know the ways by which LSD affects certain brain systems but still far less than we need to know to explain the full panoply of effects.

Although many of the psychedelic drugs are known to interact with serotonergic 5HT2 receptors, and this interaction appears to be of critical importance in producing their hallucinogenic effects, the hallucinogenic drugs can bind to a subtype of serotonin receptors that is located on serotonin nerve-cell bodies and on their terminals (which release serotonin that goes to the adjacent nerves with 5HT2 receptors). Interactions with these various receptors can lead to changes in the firing rate of such cells. The designer drugs MDMA and MDA cause the release of both dopamine and serotonin, effects that might contribute to their psychostimulant properties. The differential interactions of the various hallucinogens with multiple sites and systems may underlie the qualitative differences in the experience they produce.

(SEE ALSO: Cults and Drug Use; Hallucinogenic Plants; High School Senior Survey; Plants, Drugs from; Yippies)


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