Affiliations: McGill University, Canada
Journal reference: https://doi.org/10.1002/hbm.25141
Summary: Although cocaine use is harmful to everyone, women may have a greater predisposition to its negative effects. In this article we explore how cocaine use is associated with specific detrimental effects in the brains of women. Findings could lead to gender-specialized interventions for problematic cocaine use.
Cocaine and the brain
Gray matter volume reductions
Cocaine dependence is characterized by a persistent use of cocaine despite negative or even catastrophic consequences. Studies have consistently reported that chronic cocaine use is harmful to the brain. It is associated with lower gray matter volume as shown by measuring brain cell density in several particular brain regions that support every day processes such as muscle control, sensory perception, and cognitive abilities.
Two brain regions are affected: frontal cortical regions and limbic regions
Interestingly, cocaine-associated gray matter volume reductions are not widespread across the brain, but tend to appear predominantly in two types of brain regions: frontal cortical regions and limbic regions. Frontal cortical regions of the brain are implicated in higher cognitive functions such as planning abilities and decision-making while the limbic regions of the brain (which include the amygdala, hippocampus, thalamus, hypothalamus, and basal ganglia) are primarily responsible for emotional responses, associative memory, and reinforcing behaviors. Importantly, decreased gray matter volume in these regions may be associated with a compromise in the related functions.
Gender differences in cocaine dependence
Women seem to be at a greater risk of developing cocaine dependence
While rates of cocaine dependence are twice as high in men compared to women, women are at a greater risk of developing cocaine dependence, have greater difficulty quitting, and have worse treatment outcomes. Research in both humans and animals suggests that women may be more vulnerable to the euphoric effects of cocaine and estrogen may be one factor contributing to this increased sensitivity.
Gender-based brain differences in healthy subjects in the absence of cocaine
Structural differences between the brains of men and women are well established. With respect to frontal and limbic regions, men have greater gray matter volume in the amygdala and hippocampus, while women have greater gray matter volume in the insula as well as in many frontal regions. These gender differences in gray matter volume may, in part, contribute to the varying clinical outcomes and neural reactivity observed between men and women with cocaine dependence.
Gender-based differences in brain responses to cocaine images
Studies employing functional magnetic resonance imaging have further investigated gender differences in cocaine dependence. These studies examined brain responses (measured as blood flow) to known triggers of cocaine use such as pictures of cocaine, cocaine paraphernalia (i.e. cocaine equipment such as a straw or a rolled bill), and stress-related imagery. Interestingly, results revealed that men exhibited greater blood flow abnormalities in response to drug cues, while women exhibited greater blood flow abnormalities in response to stress cues, particularly in the frontal and limbic regions of the brain.
Rationale: The goal of this study was to examine interaction effects between gender and cocaine dependence on gray matter volume. More specifically, we sought to identify brain regions where gender had a stronger effect on differences in gray matter volume in individuals with cocaine dependence compared with healthy individuals. While previous studies have investigated this relationship, they have been limited by small sample sizes, especially among the group of women with cocaine dependence (N<30). To overcome this limitation, the current study used data collected from multiple laboratories worldwide that are part of the ENIGMA Addiction Consortium, an initiative to aggregate and leverage neuroimaging data to better understand addiction disorders.
Method: In the current study, seven ENIGMA sites contributed data to yield a total sample of 420 participants: 140 cocaine-dependent men and 70 cocaine-dependent women who were compared with a matched control sample (individuals with no psychiatric disorders) of 140 men and 70 women. Statistical analyses were conducted to determine interaction effects between gender and cocaine dependence on gray matter volume as well as to explore gender-specific relationships between duration of cocaine use and gray matter volume. In addition, in our analyses we controlled for gender-based structural differences to ensure that these differences did not contribute to our results.
Results: Results indicated that compared to healthy women controls, cocaine-dependent women had lower gray matter volume in the insula, while no group differences were found in men. However, cocaine-dependent men demonstrated a significant relationship between increasing duration of cocaine use and lower gray matter volume in the hippocampus, an association that was not observed in women. These findings provide further support for gender differences in cocaine dependence, particularly in the limbic structures of the brain. Given the importance of the insula to interoception (the perception of sensations from inside the body) and subjective craving and the hippocampus to learning contextual associations, our results may point to gender-specific processes implicated in cocaine dependence.
Therefore, gender-specialized interventions may offer help for treating these individuals. For example, treatment for women may emphasize targeting interoceptive processes, such as self-awareness and greater attention to body sensations including craving. In contrast, men may benefit from interventions that focus on extinguishing drug-related memories. These types of neuroimaging studies help pinpoint which mechanisms might be targeted in future interventions, and highlight interesting areas for further investigation.