Normal glutathione levels in autopsied brain of chronic users of heroin and of cocaine

Abstract

Background: Animal studies suggest that exposure to either of the two widely used drugs of abuse, heroin or cocaine, causes depletion of the antioxidant, reduced glutathione, a hallmark of oxidative stress, in the brain. However, the relevance of the animal findings to the human is uncertain and clinical trials with the antioxidant GSH precursor n-acetylcysteine have produced mixed results in cocaine dependence.

Methods: Our major objective was to compare glutathione levels, determined by an HPLC-coulometric procedure, in autopsied brain of chronic heroin (n = 11) and cocaine users (n = 9), who were positive for the drugs in the brain, to those of matched controls (n = 16). Six brain regions were examined, including caudate, hippocampus, thalamus and frontal, temporal and insular cortices.

Results: In contrast to experimental animal findings, we found no statistically significant difference between mean levels of reduced or oxidized glutathione in the drug user vs. control groups. Moreover, no correlation was found between levels of drugs in the brain and those of glutathione.

Conclusions: Acknowledging the many generic limitations of an autopsied human brain study and the preliminary nature of the findings, our data nevertheless suggest that any oxidative stress caused by heroin or cocaine in chronic users of the drugs might not be sufficient to cause substantial loss of stores of glutathione in the human brain, at least during early withdrawal. These findings, requiring replication, might also have some relevance to future clinical trials employing glutathione supplement therapy as an anti-oxidative strategy in chronic users of the two abused drugs.

Keywords: Cocaine; Glutathione; Heroin; Human brain; Oxidative stress; Postmortem.

Figure 1.

Scatter plots of levels of reduced glutathione (GSH) in brain of users of heroin and cocaine and control subjects. Circled up-triangles identify two heroin users with high blood levels of propoxyphene and metabolite norpropoxyphene; circled down-triangles identify three cocaine users with high levels of cocaine and metabolites in brain.