Lower distress intolerance is associated with higher glutathione levels in adolescent cannabis users

Cannabis (CB) use and psychological stressors increase oxidative stress in the brain. Glutathione (GSH), the most abundant antioxidant in the brain, protects against oxidative stress. Furthermore, distress intolerance, the inability to tolerate psychological or physiological stress is a risk factor for CB use. The relationship between CB use, brain GSH levels and distress intolerance remains unknown. Therefore, we examined GSH levels in the anterior cingulate cortex (ACC), as a measure of oxidative stress, and its relationship with distress intolerance in adolescent CB users and healthy controls (HC). Sixteen HC and 17 CB-using adolescents were included in the analysis. GSH levels were measured in the ACC using a metabolite-edited proton magnetic resonance spectroscopy sequence on a 3T scanner. Distress intolerance was assessed using the Distress Intolerance Index (DII) and CB use was evaluated using a structured clinical interview. In the CB group, lower CSF-corrected GSH levels in the ACC were correlated with higher DII scores. However, no significant between group differences were observed for ACC CSF-corrected GSH levels or on DII scores. No significant correlations were observed in the HC group between GSH levels and DII. Our findings suggests that the association between lower GSH levels and greater distress intolerance in CB users might reflect alterations in the balance between protective and oxidative stress conditions linked to the ability to tolerate distress. Further examination into this relationship can provide important insights into neurobiological correlates and risk factors associated with CB use to help inform preventive and treatment targets in the future.