Evidence for 5-HT2 involvement in the mechanism of action of hallucinogenic agents

Life Sci. 1984 Dec 17;35(25):2505-11. doi: 10.1016/0024-3205(84)90436-3.


The affinities (Ki values) of twenty two psycho-active agents, including LSD, 5-OMe DMT and a series of phenalkylamine derivatives, for cortical 5-HT1 and 5-HT2 binding sites were compared with two measures of behavioral activity. It was found that a significant correlation (r = 0.938) exists between the 5-HT2 binding affinities of these agents and their ED50 values as determined in tests of stimulus generalization using 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) as the training drug. Furthermore, for fifteen of these agents where human data were available, a significant correlation (r = 0.924) also exists between 5-HT2 binding affinities and their human hallucinogenic potencies. The results of this study suggest that the mechanism of action of these agents involves 5-HT2-related events.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 2,5-Dimethoxy-4-Methylamphetamine / metabolism
  • 2,5-Dimethoxy-4-Methylamphetamine / pharmacology
  • Animals
  • Hallucinogens / pharmacology*
  • Humans
  • Lysergic Acid Diethylamide / metabolism
  • Lysergic Acid Diethylamide / pharmacology
  • Male
  • Methoxydimethyltryptamines / metabolism
  • Methoxydimethyltryptamines / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Receptors, Serotonin / metabolism
  • Receptors, Serotonin / physiology
  • Serotonin / physiology*


  • Hallucinogens
  • Methoxydimethyltryptamines
  • Receptors, Serotonin
  • 2,5-Dimethoxy-4-Methylamphetamine
  • Serotonin
  • Lysergic Acid Diethylamide