Psychedelics and schizophrenia

Trends Neurosci. 2009 Apr;32(4):225-32. doi: 10.1016/j.tins.2008.12.005. Epub 2009 Mar 5.


Research on psychedelics such as lysergic acid diethylamide (LSD) and dissociative drugs such as phencyclidine (PCP) and the symptoms, neurochemical abnormalities and treatment of schizophrenia have converged. The effects of hallucinogenic drugs resemble some of the core symptoms of schizophrenia. Some atypical antipsychotic drugs were identified by their high affinity for serotonin 5-HT(2A) receptors, which is also the target of LSD-like drugs. Several effects of PCP-like drugs are strongly affected by both 5-HT(2A) and metabotropic glutamate 2/3 receptor modulation. A serotonin-glutamate receptor complex in cortical pyramidal neurons has been identified that might be the target both of psychedelics and the atypical and glutamate classes of antipsychotic drugs. Recent results on the receptor, signalling and circuit mechanisms underlying the response to psychedelic and antipsychotic drugs might lead to unification of the serotonin and glutamate neurochemical hypotheses of schizophrenia.

Publication types

  • Review

MeSH terms

  • Animals
  • Glutamic Acid / metabolism
  • Hallucinogens / adverse effects
  • Hallucinogens / antagonists & inhibitors
  • Hallucinogens / therapeutic use*
  • Humans
  • Models, Neurological
  • Receptor, Serotonin, 5-HT2A / genetics
  • Receptor, Serotonin, 5-HT2A / metabolism
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors
  • Receptors, Metabotropic Glutamate / metabolism
  • Schizophrenia / drug therapy*
  • Schizophrenia / genetics
  • Schizophrenia / physiopathology
  • Serotonin / metabolism
  • Serotonin 5-HT2 Receptor Agonists


  • Hallucinogens
  • Receptor, Serotonin, 5-HT2A
  • Receptors, Metabotropic Glutamate
  • Serotonin 5-HT2 Receptor Agonists
  • metabotropic glutamate receptor 2
  • Serotonin
  • Glutamic Acid