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Curr Top Behav Neurosci. 2018;36:45-73. doi: 10.1007/7854_2017_478.

Hallucinogens and Serotonin 5-HT2A Receptor-Mediated Signaling Pathways.

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Instituto de Biomedicina y Biotecnología de Cantabria IBBTEC-CSIC, 39011, Santander, Cantabria, Spain.
Department of Physiology and Biophysics, School of Medicine, Virginia Commonwealth University, Richmond, VA, 23298, USA.


The neuropsychological effects of naturally occurring psychoactive chemicals have been recognized for millennia. Hallucinogens, which include naturally occurring chemicals such as mescaline and psilocybin, as well as synthetic compounds, such as lysergic acid diethylamide (LSD), induce profound alterations of human consciousness, emotion, and cognition. The discovery of the hallucinogenic effects of LSD and the observations that LSD and the endogenous ligand serotonin share chemical and pharmacological profiles led to the suggestion that biogenic amines like serotonin were involved in the psychosis of mental disorders such as schizophrenia. Although they bind other G protein-coupled receptor (GPCR) subtypes, studies indicate that several effects of hallucinogens involve agonist activity at the serotonin 5-HT2A receptor. In this chapter, we review recent advances in understanding hallucinogen drug action through characterization of structure, neuroanatomical location, and function of the 5-HT2A receptor.


5-HT2A receptor; Antipsychotics; G protein-coupled receptor (GPCR); Hallucinogen; Lysergic acid diethylamide (LSD); Mescaline; Psilocin; Psilocybin; Psychedelics; Psychosis; Schizophrenia; Serotonin

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