Anandamide levels in cerebrospinal fluid of first-episode schizophrenic patients: Impact of cannabis use

F. Markus Leweke, Andrea Giuffrida, Dagmar Koethe, Daniela Schreiber, Brit M. Nolden, Laura Kranaster, Miriam A. Neatby, Miriam Schneider, Christoph W. Gerth, Martin Hellmich, Joachim Klosterkötter, Daniele Piomelli

Research output: Contribution to journalArticlepeer-review

166 Scopus citations


Background: Previous studies have shown that cerebrospinal fluid (CSF) from schizophrenic patients contains significantly higher levels of the endogenous cannabinoid anandamide than does CSF from healthy volunteers. Moreover, CSF anandamide levels correlated inversely with psychotic symptoms, suggesting that anandamide release in the central nervous system (CNS) may serve as an adaptive mechanism countering neurotransmitter abnormalities in acute psychoses. In the present study we examined whether cannabis use may alter such a mechanism. Methods: We used liquid chromatography/mass spectrometry (LC/MS) to measure anandamide levels in serum and CSF from first-episode, antipsychotic-naïve schizophrenics (n = 47) and healthy volunteers (n = 81). Based on reported patterns of cannabis use and urine Δ9-tetrahydrocannabinol (Δ9-THC) tests, each subject group was further divided into two subgroups: 'low-frequency' and 'high-frequency' cannabis users (lifetime use ≤ 5 times and > 20 times, respectively). Serum Δ9-THC was investigated to determine acute use and three patients were excluded from the analysis due to detectable Δ9-THC levels in serum. Results: Schizophrenic low-frequency cannabis users (n = 25) exhibited > 10-fold higher CSF anandamide levels than did schizophrenic high-frequency users (n = 19, p = 0.008), healthy low-frequency (n = 55, p < 0.001) or high-frequency users (n = 26, p < 0.001). In contrast, no significant differences in serum anandamide levels were found among the four subgroups. CSF anandamide levels and disease symptoms were negatively correlated in both user groups. Conclusions: The results indicate that frequent cannabis exposure may down-regulate anandamide signaling in the CNS of schizophrenic patients, but not of healthy individuals. Thus, our findings suggest that alterations in endocannabinoid signaling might be an important component of the mechanism through which cannabis impacts mental health.

Original languageEnglish (US)
Pages (from-to)29-36
Number of pages8
JournalSchizophrenia research
Issue number1-3
StatePublished - Aug 2007


  • Anandamide
  • Cannabis
  • Endocannabinoids
  • First episode
  • Schizophrenia

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry


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