Anandamide levels in cerebrospinal fluid of first-episode schizophrenic patients: impact of cannabis use.
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.
Leweke
F Markus
FM
Department of Psychiatry and Psychotherapy, University of Cologne, Kerpener Str. 62, 50924 Cologne, Germany. leweke@ecnp.net
Giuffrida
Andrea
A
Koethe
Dagmar
D
Schreiber
Daniela
D
Nolden
Brit M
BM
Kranaster
Laura
L
Neatby
Miriam A
MA
Schneider
Miriam
M
Gerth
Christoph W
CW
Hellmich
Martin
M
Klosterkötter
Joachim
J
Piomelli
Daniele
D
D000208:Acute Disease; D000328:Adult; D001095:Arachidonic Acids / Q000134:cerebrospinal fluid*; D002186:Cannabinoids / Q000134:cerebrospinal fluid; D002853:Chromatography, Liquid; D063388:Endocannabinoids; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008297:Male; D002189:Marijuana Abuse / Q000453:epidemiology*; D053284:Polyunsaturated Alkamides / Q000134:cerebrospinal fluid*; D015995:Prevalence; D011618:Psychotic Disorders / Q000134:cerebrospinal fluid / Q000453:epidemiology; D012559:Schizophrenia / Q000134:cerebrospinal fluid* / Q000453:epidemiology*; D013997:Time Factors
D001095:Arachidonic Acids; D002186:Cannabinoids; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; C078814:anandamide