Cocaine addiction leads to accumulation of iron in the brain

The finding offers hope for new treatment options.

In a new Translational Psychiatry study, Karen Ersche of the University of Cambridge and colleagues demonstrate for the first time that chronic cocaine use is associated with iron build-up in the brain and lower iron concentration in the blood. Future studies will use these results to look at whether this could be a biological sign of addition, and whether it could be a treatment target for cocaine addiction.

We spoke with Ersche about the work.

ResearchGate: What motivated this study?

Karen Ersche: The impetus of the study was to understand the cause of a particular brain abnormality that we see regularly in people with cocaine addiction, namely the abnormal enlargement of a large nucleus of the forebrain, the putamen. Given that chronic cocaine use impairs innate immunity and renders chronic cocaine users vulnerable to infection and inflammation, we hypothesized that they may have disrupted iron homeostasis and as a result accumulate more iron in iron-rich areas of the brain.

RG: What were you results?

Ersche: For the first time, we demonstrate in humans that chronic cocaine use is associated with excessive iron accumulation in the brain. This increases the longer people have been using cocaine. Interestingly, we observed this excess iron accumulation not in the putamen, as we initially predicted, but in a neighbouring and closely connected region called the globus pallidus. This region plays a critical role in the inhibition of behaviour and in learning how to avoid negative consequences – both functions people with cocaine addiction struggle with. We also found that these individuals had low levels of iron in the body, further supporting the notion of disruptions in the regulation of iron in people with cocaine addiction.

RG: How did you discover this?

Ersche: With advances in MRI technology in humans, it is now possible to measure brain iron concentration non-invasively. The images are sensitive to iron’s ferromagnetic properties and in combination with innovative post-processing approaches such as quantitative susceptibility mapping, iron concentration in deep grey matter can be estimated quite precisely. We used this specific brain scan to determine iron concentration in the brain, and we drew blood to measure iron levels in the rest of the body.

RG: Why does the iron build-up occur? And what effect does it have on the brain?

Ersche: Iron is an essential micronutrient, which we cannot produce ourselves but must obtain from the diet. We cannot get rid of it either, except through bleeding. Iron homeostasis is therefore tightly regulated, and at present we think that when this is disrupted in cocaine addiction, it leads to the build-up of iron in the brain. We do not know the exact effect of this on the brain at the moment. We do know that iron accumulation in the brain is seen in various neurodegenerative diseases, and understanding the consequences of excess brain iron in cocaine addiction is something we’ll focus on now.

RG: What are the significance of your results for our understanding of addiction?

Ersche: Although neuroscientific research has greatly advanced our understanding of addiction, we still know surprisingly little about the neurobiological mechanisms by which stimulant drugs interact with the brain. Our findings of iron dysregulation in cocaine addiction raise several important questions, including how this abnormality develops over time, whether iron deficiency increases the vulnerability to developing cocaine addiction, whether it contributes to the persistence of addiction, and whether it may accelerate brain ageing.

RG: Can this help us treat addiction?

Ersche: One critical question to be addressed in future studies is whether impaired iron regulation might be a biomarker of the progression of addiction. Another is whether iron may be a therapeutic target for cocaine addiction, either through addressing peripheral iron deficiency to modify the course of addiction, or by slowing or reversing the central accumulation of iron. Given that cocaine addiction remains a significant public health problem with few pharmacological treatments and only modestly successful psychosocial treatments, elucidating this mechanism may offer the possibility of developing some much needed new interventions.