, Volume 54, Issue 1, pp 9–16 | Cite as

Endogenous ligands of a putative LSD-serotonin receptor in the cerebrospinal fluid: Higher level of LSD-displacing factors (LDF) in unmedicated psychotic patients

  • E. Mehl
  • E. Rüther
  • J. Redemann
Original Investigations


In human cerebrospinal fluid substances were detected that are capable of reversibly displacing the hallucinogen d-lysergic acid diethylamide (LSD) from its high-affinity binding sites in neuronal membranes. The binding sites may represent a specific type of LSD-serotonin receptor protein. The LSD-displacing factors (LDF) occur physiologically in concentrations high enough to interact with the putative LSD-serotonin receptors. The LDF can be separated from proteins and inorganic salts. LDF was found to be clearly different from endogenous indoleamine ligands such as serotonin, being anionic at pH 7.4.

The LDF concentration was assayed in the cerebrospinal fluid of 49 nonpsychotic and of 19 acute psychotic patients before 30 days therapy with the antipsychotic drugs haloperidol or clozapine. LDF concentration was found to be significantly higher (P<0.001) in the group of unmedicated acute psychotic patients (5.55 U/ml) in comparison to the control group (3.56 U/ml). Within this group of acute psychotic patients, a high positive correlation was found between concentration of LDF and clinical improvement (r=0.650). Thus, a nosological subgroup was traced out, characterized by both a higher concentration of LDF and a higher responsiveness to antipsychotic drugs (P<0.01). Ratings of clinical improvement and determinations of the concentration of LDF before drug therapy were performed in a doubleblind study. Since antipsychotic drugs act on dopamine receptors and LDF acts on putative serotonin receptors, dopamine and serotonin receptors may both be affected in the psychotic state. A working hypothesis is offered that links the dopamine and the serotonin hypotheses.

Key words

LSD Serotonin Receptor Endogenous ligand Acute schizophrenia Antipsychotic drug 


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Copyright information

© Springer-Verlag 1977

Authors and Affiliations

  • E. Mehl
    • 1
  • E. Rüther
    • 2
  • J. Redemann
    • 1
  1. 1.Neurochemische AbteilungMax-Planck-Institut für PsychiatrieMünchen 40Federal Republic of Germany
  2. 2.Universitäts-NervenklinikMünchenFederal Republic of Germany

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