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

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.

In the evidence

This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.

• State of the evidence: Cannabis for addiction ↕Mixed

  Lower myo-inositol was related to greater problematic drug use and cannabis dependence severity, and past-year cannabis exposure was associated with higher glutamate metabolites in male but not female users.

  Synthesized September 21, 2026

Comparable studies

Other observational and cohort studies on cannabis for addiction, most cited first.