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

Abstract

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 delta9-tetrahydrocannabinol (delta9-THC) tests, each subject group was further divided into two subgroups: 'low-frequency' and 'high-frequency' cannabis users (lifetime use < or = 5 times and > 20 times, respectively). Serum delta9-THC was investigated to determine acute use and three patients were excluded from the analysis due to detectable delta9-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.

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  • Publisher Full Text
  • Authors

    Leweke FM, Giuffrida A, Koethe D, Schreiber D, Nolden BM, Kranaster L, Neatby MA, Schneider M, Gerth CW, Hellmich M, Klosterkötter J, Piomelli D

    Source

    Schizophrenia research 94:1-3 2007 Aug pg 29-36

    MeSH

    Acute Disease
    Adult
    Arachidonic Acids
    Cannabinoids
    Chromatography, Liquid
    Endocannabinoids
    Female
    Gas Chromatography-Mass Spectrometry
    Humans
    Male
    Marijuana Abuse
    Polyunsaturated Alkamides
    Prevalence
    Psychotic Disorders
    Schizophrenia
    Time Factors

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    17566707