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Serotonin and hallucinogens.

G K Aghajanian1, G J Marek

  • 1Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA.

Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology
|August 5, 1999
PubMed
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Psychedelic hallucinogens like LSD act as partial agonists at serotonin 5-HT2A receptors. These drugs enhance glutamatergic transmission in the brain, potentially causing cognitive and perceptual changes.

Area of Science:

  • Neuroscience
  • Psychopharmacology

Background:

  • The serotonin (5-HT) hypothesis explains hallucinogenic drug action.
  • Psychedelics, including indoleamines (e.g., LSD) and phenethylamines (e.g., mescaline), have been studied for decades.

Purpose of the Study:

  • To review the serotonin hypothesis of hallucinogenic drug action.
  • To investigate the neurobiological mechanisms underlying psychedelic effects.

Main Methods:

  • Biochemical studies
  • Electrophysiological recordings
  • Behavioral analyses

Main Results:

  • Converging evidence supports a common action site for major psychedelic classes at serotonin 5-HT2A receptors.
  • Hallucinogens affect regions like the locus coeruleus and cerebral cortex via 5-HT2A receptors.

Related Experiment Videos

  • A novel finding is the 5-HT2A receptor-mediated enhancement of glutamatergic excitatory postsynaptic potentials in cortical pyramidal cells.

    • Conclusions:

    • Hallucinogens act as partial agonists at central nervous system 5-HT2A receptors.
    • Enhanced glutamatergic transmission in the cortex may underlie the cognitive, perceptual, and affective distortions caused by these drugs.