Invited reviewMultiple receptors contribute to the behavioral effects of indoleamine hallucinogens

Serotonergic hallucinogens produce profound changes in perception, mood, and cognition. These drugs include phenylalkylamines such as mescaline and 2,5-dimethoxy-4-methylamphetamine (DOM), and indoleamines such as (+)-lysergic acid diethylamide (LSD) and psilocybin. Despite their differences in chemical structure, the two classes of hallucinogens produce remarkably similar subjective effects in humans, and induce cross-tolerance. The phenylalkylamine hallucinogens are selective 5-HT2 receptor agonists, whereas the indoleamines are relatively non-selective for serotonin (5-HT) receptors. There is extensive evidence, from both animal and human studies, that the characteristic effects of hallucinogens are mediated by interactions with the 5-HT2A receptor. Nevertheless, there is also evidence that interactions with other receptor sites contribute to the psychopharmacological and behavioral effects of the indoleamine hallucinogens. This article reviews the evidence demonstrating that the effects of indoleamine hallucinogens in a variety of animal behavioral paradigms are mediated by both 5-HT2 and non-5-HT2 receptors.

► Serotonergic hallucinogens are classified as phenylalkylamines and indoleamines. ► The two classes of hallucinogens produce similar subjective effects in humans. ► Differences exist in the serotonin receptor selectivity of these two compound classes. ► Phenylalkylamine effects are primarily mediated by the serotonin 5-HT2A receptor. ► The effects of the indoleamines are mediated by both 5-HT2 and non-5-HT2 receptors.