Cocaine Research Report
How is cutting-edge science helping us better understand addiction?

Two cutting-edge areas of science, genetics and brain imaging, are significantly advancing our understanding of cocaine addiction.

Researchers estimate that genetics contributes 42 to 79 percent of the risk for cocaine use and dependence.63 Of course, with a complex disease such as addiction, many different genes are involved, and their expression can be influenced by the environment. There appears to be significant overlap in the genes that put people at risk for all addictive substances, perhaps indicating a common biological pathway for addiction regardless of the drug.63

In genome-wide association studies (GWAS), researchers examine whether certain gene variants are more frequently found in people with a substance use disorder, which eventually might help identify those at increased risk for drug addiction.64,65 Identifying genes linked to addiction is only the first step. Candidate-gene research examines the links between substance use and specific genes that encode proteins that appear to be related to addiction. For example, researchers have found connections between various aspects of cocaine addiction and the genes that encode for particular dopamine receptors and the enzymes that break down this neurotransmitter.63

Because environmental factors typically shape the impact of genes on disease risk, researchers must also identify how particular gene-by-environment interactions influence the course of addiction.63 Research in the field of epigenetics is uncovering how the environment induces long-term changes in gene expression—influencing the pattern of gene expression—without altering the DNA sequence.66

In animal research, scientists are determining how long-term cocaine exposure changes gene expression in the brain, particularly in the reward pathway. Studies have linked specific cocaine-induced epigenetic changes to neuroadaptations67 and behavioral hallmarks of addiction, such as sensitivity to cocaine’s rewarding effects.66,67 The epigenetic changes induced by cocaine can be passed to the next generation, even if the drug exposure does not occur prenatally.68 Although much more genetic and epigenetic research is needed, understanding addiction at the molecular level offers great promise for improving diagnosis, for example by discovering biomarkers for disease severity or treatment response.66

Although more research is needed, brain-imaging might be used to detect biomarkers for drug addiction vulnerability, as these technologies have yielded insights into the processes underlying craving and how medications may quell the brain’s response to cocaine cues.69 A relatively new neuroimaging technology called default-mode or resting-state functional magnetic resonance imaging (rs-fMRI) reveals brain activity when people are alert but not performing a particular task; researchers use this technique to compare functional brain networks of people who have used cocaine for a long time and those who have not. These studies suggest that there is reduced connectivity between various brain circuits70–72 and between the two hemispheres73 among people with cocaine dependence. Researchers have also correlated reduced connectivity between particular brain circuits with important addiction-related behaviors, including risk for relapse71 and impulsivity.72

Neuroimaging technologies are also documenting how the brains of cocaine users may recover after periods of abstinence. For example, these techniques indicate that years of cocaine use are associated with reduced grey matter in particular brain regions. However, people who maintained cocaine abstinence for approximately 9 months showed grey matter levels similar to or greater than those of people who had never used the drug.74 Further analysis indicated that the increased grey matter occurred in regions other than the ones altered by cocaine use, suggesting that the neurobiological changes involved in recovery are more complex than simply reversing the changes related to addiction.74 The researchers also found that increased grey matter volume in brain regions involved with behavioral control were associated with longer duration of abstinence.74

fMRI technologies have also revealed that abstinence from cocaine has important, restorative effects on the brain. Although current cocaine users demonstrated reduced brain activity in a brain circuit that mediates response inhibition during a motor control task, individuals who had attained abstinence for an average of 8 months showed similar patterns of activation and levels of performance to those who had never used the drug.75 The results suggest that abstinence helps restore the functioning of this brain circuit.

Researchers are engaged in several large-scale, collaborative projects to map the human connectome, which is the brain’s network of interconnected circuits. For example, the National Institutes of Health supports the Human Connectome Project to generate maps of the developing, adult, and aging brain. By having a map of the typical brain, scientists will further understand how neural functioning differs in behavioral disorders—knowledge that will drive improved diagnostics and treatments.