Serotonin and the psychedelics

Mitul A. Mehta, Mark D. Tricklebank

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review


Serotonergic hallucinogens produce alterations of perceptions, mood, and cognition, and have putative anxiolytic, antidepressant, and antiaddictive properties. There are many sources of compounds which act as serotonin agonist hallucinogens and psychedelics. Studies in experimental animals and ex vivo have provided strong evidence for the involvement of the 5-HT2A receptor subtype as the principal mediator of psychedelic effects, assessed preclinically as head twitches and “wet dog” shakes as well as through expression of specific proteins. The use of specific antagonists and drug discrimination paradigms in which the interoceptive stimulus induced by the drug serves to guide or cue the animal to press one of two levers to obtain a food reward have been important methods here. In humans, the blockade model is limited by available safe drugs, but ketanserin (a nonselective 5-HT2 antagonist) has been important in helping determine which cognitive and subjective effects are mediated via the 5-HT2 versus 5-HT1 receptor subclasses, again pointing strongly to 5-HT2. Neuroimaging studies in humans are beginning to unpick the network-level mechanisms. Many networks are altered by drugs such as psilocybin, lysergic acid diethylamide, and ayahuasca, but the important hubs of the default mode network are consistent in their involvement, although the precise role in specific symptoms is only beginning to be understood.

Original languageEnglish
Title of host publicationThe Serotonin System
Subtitle of host publicationHistory, Neuropharmacology, and Pathology
Number of pages10
ISBN (Electronic)9780128133231
ISBN (Print)9780128133248
Publication statusPublished - 1 Jan 2019


  • Hallucinogen
  • LSD
  • Psilocybin
  • Psychedelic


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