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
Schizophrenia Research August 2007 DOI: 10.1016/j.schres.2007.04.025 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cross-sectional study Peer reviewed |
|---|---|
| Sample size | 128 |
| Population | First-episode, antipsychotic-naïve schizophrenia patients and healthy volunteers, divided by lifetime cannabis use frequency |
| Topics | Cannabis |
| Key findings | Schizophrenia patients with low-frequency cannabis use had more than 10-fold higher CSF anandamide levels than schizophrenia patients with high-frequency use (p=0.008) and than healthy low- or high-frequency users (p<0.001 for both). No significant serum anandamide differences were found among the four subgroups. The authors suggest frequent cannabis exposure may down-regulate CNS anandamide signaling in schizophrenia patients but not healthy individuals. |
Abstract
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. 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. 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. 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.
Comparable studies
Other cross-sectional and survey studies on cannabis, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Cannabis use before age 15 and subsequent executive functioning 104 chronic cannabis users (49 early-onset before age 15, 55 late-onset after age 15)... | 2011 | Observational cross-sectional study | n = 148 |
| Patterns of simultaneous polysubstance use in drug using university students Drug-using university students | 2006 | Cross-sectional survey | n = 149 |
| Persisting Reductions in Cannabis, Opioid, and Stimulant Misuse After Naturalistic Psychedelic Use: An Online Survey Online survey respondents | 2020 | Cross-sectional survey | |
| User perceptions of the benefits and harms of hallucinogenic drug use: A web-based questionnaire study Users of hallucinogenic drugs who completed a web-based questionnaire | 2010 | Cross-sectional survey | n = 600 |
| Illicit Use of LSD or Psilocybin, but not MDMA or Nonpsychedelic Drugs, is Associated with Mystical Experiences in a Dose-Dependent Manner Adults recruited from the MAPS website and newsletter, most reporting use of various... | 2012 | Cross-sectional survey | n = 337 |
Citations in the library
Cited by 26
- Long-term consequences of adolescent cannabinoid exposure in adult psychopathology Frontiers in Neuroscience November 10, 2014
- Cannabinoids and Vanilloids in Schizophrenia: Neurophysiological Evidence and Directions for Basic Research Frontiers in Pharmacology June 21, 2017
- Effects of Cannabidiol and Delta-9-Tetrahydrocannabinol on Plasma Endocannabinoid Levels in Healthy Volunteers: A Randomized Double-Blind Four-Arm Crossover Study Cannabis and Cannabinoid Research December 9, 2022
- Cross cultural studies on adolescent cannabis use and psychosis 2011
- CB1 receptor-enriched functional connectivity analysis revealed target-specific modulation by cannabidiol in early psychosis. Journal of Psychopharmacology August 5, 2026
and 21 more in the library
Cites 7
- Causal association between cannabis and psychosis: examination of the evidence The British Journal of Psychiatry January 30, 2004
- Disturbances of visual information processing in early states of psychosis and experimental delta-9-tetrahydrocannabinol altered states of consciousness. Schizophrenia Research December 1, 2006
- Delta-9-tetrahydrocannabinol effects in schizophrenia: implications for cognition, psychosis, and addiction. Biological Psychiatry March 15, 2005
- The psychotomimetic effects of intravenous delta-9-tetrahydrocannabinol in healthy individuals: implications for psychosis. Neuropsychopharmacology August 2004
- Elevated endogenous cannabinoids in schizophrenia. Neuroreport June 3, 1999
and 2 more in the library