Can Cocaine Addiction Lead to Faster Brain Aging?

Cells in a specific area of the brain thought to be important for inhibitory control appear biologically older in individuals with cocaine use disorder (CUD), suggesting that the cells may age faster when exposed to cocaine, researchers report.  

In a novel study of postmortem brain tissue, "we detected a trend towards stronger biological aging of the brain in individuals with cocaine use disorder compared to individuals without cocaine use disorder," lead investigator Stephanie Witt, PhD, Central Institute of Mental Health, Mannheim, Germany, said in a news release.

"This could be caused by cocaine-related disease processes in the brain, such as inflammation or cell death," Witt added.

The findings were published online February 14 in Frontiers in Psychiatry.

Novel Study

CUD is characterized by a loss of control over cocaine use and is associated with structural, functional, and molecular alterations in the human brain.

Most evidence of cocaine-associated epigenetic changes derives from rodent studies, while only a few studies have been performed using human tissue.

Witt and colleagues assessed epigenome-wide DNA methylation signatures of CUD in human postmortem brain tissue of Brodmann area 9 (BA9) in 42 deceased males. Of these, 21 had a CUD diagnosis and 21 did not.

After correcting for differences in age, time since death, brain pH, and other conditions such as depressive disorder and alcohol use disorder, the researchers observed that cells in BA9 appeared biologically older in the men who had CUD.

Using patterns of DNA methylation as a measure of the biological age of cells, a total of 20 differentially methylated regions were significantly associated with CUD status after multiple testing correction.

Seventeen (85%) of these genomic regions were hypermethylated and three (15%) were hypomethylated.

More Research Needed

"As DNA methylation is an important regulatory mechanism for gene expression, the identified DNA methylation alterations might contribute to functional changes in the human brain and thereby to the associated behavioral aspects of addiction," first author Eric Poisel, a PhD student at the Central Institute of Mental Health in Mannheim, said in the release.

Changes in DNA methylation were especially prominent in genes that regulate the activity of neurons and the connectivity between them.

"Interestingly, differential DNA methylation was related to several transcription factors and proteins with DNA binding domains, which implies direct effects of these DNA methylation changes on gene expression. This needs to be followed up in further studies," Poisel noted.

Witt said it was also "fascinating that among those genes that showed the strongest changes in DNA methylation levels in our study, two genes were previously reported to regulate behavioral aspects of cocaine intake in rodent experiments."

However, she cautioned that because biological age estimation is "a very recent concept in addiction research and is influenced by many factors, further studies are required to investigate this phenomenon, with larger sample sizes than were possible here."

Funding for the study was provided in part by the German Federal Ministry of Education and Research, the Hetzler Foundation for Addiction Research, and the German Research Foundation. The authors report no relevant financial relationships.

Front Psych. Published online February 14, 2023. Full article.

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Cite this: Can Cocaine Addiction Lead to Faster Brain Aging? - Medscape - Feb 17, 2023.