Serotonin and hallucinogenic activity

Serotonin and hallucinogenic activity
There is abundant experimental evidence to show that serotonin plays a
major role in the mechanism of action of hallucinogens, but it is presently
unclear whether the actions of hallucinogens can be explained by their
agonistic or antagonistic actions. LSD, for example, may behave either as an
agonist or antagonist depending on the particular tissue, concentration and
experimental condition, whereas the tryptamine type of hallucinogens usually act as agonists. Experimental evidence nevertheless suggests that
the behavioural effects of a number of indole alkylamine (e.g. LSD-like) and
phenylalkylamine (e.g. mescaline-like) hallucinogens can be attenuated by
5-HT2A antagonists and that the potency of these classes of hallucinogens at
5-HT2A (and possibly 5-HT2C) sites correlate with their hallucinogenic
potency in man. It seems unlikely however that all hallucinogens owe their
activity to their potency in stimulating 5-HT2A receptors; LSD and
5-methoxydimethyltryptamine for example interact with 5-HT2C sites, while
phenyclidine may owe its hallucinogenic potency to an action on N-methyl-
D-aspartate (NMDA) and a subclass of sigma receptors. Nevertheless, the
balance of evidence suggests that most ‘‘classical’’ hallucinogens such as
LSD, mescaline and psilocybin act as partial agonists on 5-HT2A receptors.