The results of this study suggest that many drug abusers may experience similar changes in the patterns of global gene expression in their brains, irrespective of their drug of choice. Whether longtime drug abusers favor cocaine, marijuana, or PCP, their autopsied brains showed a number of common gene changes consistent with diminished brain plasticity— i.e., the ability to learn from new experiences and adapt to new situations. Therefore, brain functions may be similarly impaired as the result of chronically abusing different drugs.

Background: Chronic drug abuse can change the structure and function of several brain regions. Recent advances in genomic technologies allow us to monitor the expression level of thousands of genes simultaneously in specific parts of the brain, including the anterior prefrontal cortex (aPFC), a region that plays an important role in decision making. A dysfunctional aPFC appears to be a characteristic feature of the brains of drug abusers. Researchers wanted to know if different drugs of abuse can compromise the normal patterns of gene expression that converge in common pathways, resulting in similar changes in the brains of drug abusers.

Study Design: NIDA scientists compiled clinical case histories and toxicology reports to establish the primary drug of abuse of 42 deceased drug abusers. The drugs examined included cocaine, marijuana, and PCP. The researchers then measured the level of expression of more than 9000 individual genes in small brain tissue samples obtained from the aPFC.

What They Found: Although many effects were specific to each drug, the scientists also found that nearly 80 percent of the drug abuse cases displayed similar alterations in genetic output compared to the controls. For example, genes involved in calcium signaling were turned down, while genes involved in lipid- and cholesterol-related pathways were turned up.

Comments from the Authors: The aPFC is characterized by a particularly dense and complex network of neural connections. Our results show that cocaine, marijuana, and PCP can alter the function of this critical brain area in similar ways, which could threaten the drug abuser’s ability to make sound decisions.

What’s Next: Many of the gene families identified here point to common downstream pathways that should be studied further in order to understand their specific contributions to the long-term effects of abused drugs on the human brain.

Source: The study, led by Dr. Elin Lehrmann of the Cellular Neurobiology Research Branch in NIDA’s Intramural Research Program in Baltimore, was published in the open access journal PLoS ONE on December 27, 2006 (PLoS ONE 1:e114).