Evidence That Cannabis Exposure, Abuse, and Dependence Are Related to Glutamate Metabolism and Glial Function in the Anterior Cingulate Cortex: A 1H-Magnetic Resonance Spectroscopy Study
Jeremy J. Watts, Ranjini Garani Ramesh, Tânia Maria Sarmento Silva, Nittha Lalang, Sofia Chavez, Romina Mizrahi
Frontiers in Psychiatry August 20, 2020 DOI: 10.3389/fpsyt.2020.00764 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 73 |
| Population | Long-term cannabis users and non-cannabis using healthy controls |
| Topics | Cannabis Addiction |
| Keywords | Glutamate receptor Glutamine Anterior cingulate cortex Endocrinology Biochemistry Cognition Amino acid |
| Citations | 21 |
| Key findings | Lower myo-inositol was linked to greater problematic drug use and cannabis dependence severity; past-year cannabis exposure was associated with higher glutamate metabolites in male but not female users. |
Abstract
There is evidence that long-term cannabis use is associated with alterations to glutamate neurotransmission and glial function. In this study, twenty-six long-term cannabis users (males=65.4%) and 47 non-cannabis using healthy controls (males=44.6%) underwent proton magnetic resonance spectroscopy (1H-MRS) of the anterior cingulate cortex (ACC) in order to characterize neurometabolite alterations in cannabis users and to examine associations between neurometabolites, cannabis exposure, and cannabis use behaviours. Myo-inositol, a marker of glial function, and glutamate metabolites did not differ between healthy controls and cannabis users or cannabis users who met criteria for DSM5 cannabis use disorder (n=17). Lower myo-inositol, a putative marker of glial function, was related to greater problematic drug use (F1,22=11.95,p=0.002; Cohen’s f=0.59, large effect; Drug Abuse Screening Test) and severity of cannabis dependence (F1,22=6.61, p=0.017; Cohen’s f=0.44, large effect). Further, past-year cannabis exposure exerted different effects on glutamate and glutamate+glutamine in males and females (glutamate: F1,21=6.31, p=.02; glutamate+glutamine: F1,21=7.20, p=.014), such that greater past-year cannabis exposure was related to higher concentrations of glutamate metabolites in male cannabis users (glutamate:F1,14=25.94, p=0.00016; Cohen’s f=1.32, large effect; Glutamate+glutamine:F1,14=23.24, p=0.00027, Cohen’s f=1.24, large effect) but not in female cannabis users (glutamate: F1,6=1.37, p=0.78; glutamate+glutamine: F1,6=0.001, p=0.97). The present results extend existing evidence of altered glial function and glutamate metabolism with cannabis use, by providing evidence linking problematic drug use behaviours with glial function as measured with myo-inositol and recent chronic cannabis exposure to alterations in glutamate metabolism. This provides novel directions for the interrogation of the impact of cannabis use on brain neurochemistry.
Comparable studies
Other observational and cohort studies on cannabis for addiction, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Ayahuasca-Assisted Therapy for Addiction: Results from a Preliminary Observational Study in Canada Rural aboriginal population | 2013 | Observational study | |
| Assessment of addiction severity among ritual users of ayahuasca Regular ayahuasca users (jungle-based and urban-based) and matched controls | 2010 | Observational cohort | n = 127 |
| Subcortical Local Functional Hyperconnectivity in Cannabis Dependence Young adults from the Human Connectome Project, including 30 subjects with cannabis... | 2017 | Case-control study | n = 441 |
| Who Turns to Amazonian Medicine for Treatment of Substance Use Disorder? Patient Characteristics at the Takiwasi Addiction Treatment Center Patients with substance use disorders seeking treatment | 2020 | Observational study | |
| Long-Term Mental Health and Wellbeing Outcomes Associated with Naturalistic Ayahuasca Consumption. Adults with no prior exposure to ayahuasca participating in neo-shamanic ayahuasca... | 2025 | Prospective cohort study | n = 66 |
Citations in the library
Cited by 3
- Impact of cannabis use on brain metabolism using 31P and 1H magnetic resonance spectroscopy Neuroradiology September 22, 2023
- What Do Thirty Years of Neuroimaging Research Tell Us About Recreational Cannabis Use and Brain Integrity? A Narrative Review of the Multimodal Neuroimaging Evidence to Date. Substance Abuse and Rehabilitation 2026
- Examination of gamma-aminobutyric acid and glutamate-glutamine levels in association with impulsive behavior in adolescent marijuana users. Drug and Alcohol Dependence April 1, 2022
Cites 5
- The neuropsychopharmacology of cannabis: A review of human imaging studies Pharmacology & Therapeutics October 20, 2018
- Sex Differences in Cannabis Use and Effects: A Cross-Sectional Survey of Cannabis Users. Cannabis and Cannabinoid Research 2016
- Adolescent exposure to THC in female rats disrupts developmental changes in the prefrontal cortex. Neurobiology of Disease 2015
- Neurochemical alterations in adolescent chronic marijuana smokers: a proton MRS study. Neuroimage July 1, 2011
- Dorsolateral prefrontal cortex N-acetylaspartate/total creatine (NAA/tCr) loss in male recreational cannabis users. Biological Psychiatry June 1, 2007