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

doi:10.1016/j.schres.2007.04.025

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

Department of Pharmacology

Research output: Contribution to journal › Article › peer-review

210 Scopus citations

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 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 language	English (US)
Pages (from-to)	29-36
Number of pages	8
Journal	Schizophrenia research
Volume	94
Issue number	1-3
DOIs	https://doi.org/10.1016/j.schres.2007.04.025
State	Published - Aug 2007

Keywords

Anandamide
Cannabis
Endocannabinoids
First episode
Schizophrenia

ASJC Scopus subject areas

Psychiatry and Mental health
Biological Psychiatry

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10.1016/j.schres.2007.04.025

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Leweke, F. M., Giuffrida, A., Koethe, D., Schreiber, D., Nolden, B. M., Kranaster, L., Neatby, M. A., Schneider, M., Gerth, C. W., Hellmich, M., Klosterkötter, J., & Piomelli, D. (2007). Anandamide levels in cerebrospinal fluid of first-episode schizophrenic patients: Impact of cannabis use. Schizophrenia research, 94(1-3), 29-36. https://doi.org/10.1016/j.schres.2007.04.025

Leweke, FM, Giuffrida, A, Koethe, D, Schreiber, D, Nolden, BM, Kranaster, L, Neatby, MA, Schneider, M, Gerth, CW, Hellmich, M, Klosterkötter, J & Piomelli, D 2007, 'Anandamide levels in cerebrospinal fluid of first-episode schizophrenic patients: Impact of cannabis use', Schizophrenia research, vol. 94, no. 1-3, pp. 29-36. https://doi.org/10.1016/j.schres.2007.04.025

@article{f8467000ddd14468baba497aac30938b,

title = "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-na{\"i}ve 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.",

keywords = "Anandamide, Cannabis, Endocannabinoids, First episode, Schizophrenia",

author = "Leweke, {F. Markus} and Andrea Giuffrida and Dagmar Koethe and Daniela Schreiber and Nolden, {Brit M.} and Laura Kranaster and Neatby, {Miriam A.} and Miriam Schneider and Gerth, {Christoph W.} and Martin Hellmich and Joachim Klosterk{\"o}tter and Daniele Piomelli",

note = "Funding Information: Funding for this study was provided by the Stanley Medical Research Institute (SMRI grants 01-315 and 03-NV-003 to FML), the Koeln Fortune Program (108-2000 to FML), NARSAD (to DP), and the National Institute on Drug Abuse (DA12413 and DA12653 to DP); all funding sources had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. No review or approval of the manuscript was required. ",

year = "2007",

month = aug,

doi = "10.1016/j.schres.2007.04.025",

language = "English (US)",

volume = "94",

pages = "29--36",

journal = "Schizophrenia research",

issn = "0920-9964",

publisher = "Elsevier B.V.",

number = "1-3",

}

TY - JOUR

T1 - Anandamide levels in cerebrospinal fluid of first-episode schizophrenic patients

T2 - Impact of cannabis use

AU - Leweke, F. Markus

AU - Giuffrida, Andrea

AU - Koethe, Dagmar

AU - Schreiber, Daniela

AU - Nolden, Brit M.

AU - Kranaster, Laura

AU - Neatby, Miriam A.

AU - Schneider, Miriam

AU - Gerth, Christoph W.

AU - Hellmich, Martin

AU - Klosterkötter, Joachim

AU - Piomelli, Daniele

N1 - Funding Information: Funding for this study was provided by the Stanley Medical Research Institute (SMRI grants 01-315 and 03-NV-003 to FML), the Koeln Fortune Program (108-2000 to FML), NARSAD (to DP), and the National Institute on Drug Abuse (DA12413 and DA12653 to DP); all funding sources had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. No review or approval of the manuscript was required.

PY - 2007/8

Y1 - 2007/8

N2 - 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.

AB - 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.

KW - Anandamide

KW - Cannabis

KW - Endocannabinoids

KW - First episode

KW - Schizophrenia

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

Abstract

Keywords

ASJC Scopus subject areas

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