Authors: Tanisse Epp, PhD Student, Carleton University, MSc Neuroscience, University of British Columbia | Editors: Romina Garcia de leon, Shayda Swann (Blog Coordinators)
Published: Dec 1, 2023
For a long time, society believed that alcohol and drug use was primarily a problem for men. As a result, research has mostly focused on studying addiction in men. But in recent years, there has been more attention to women and how they use drugs and alcohol. As the number of women using drugs and alcohol keeps increasing, closing the gap between men and women has become extremely important. Recently, there has been a promising rise in research looking at sex differences within addiction research. This research has highlighted significant differences in how addiction develops and progresses differently in men and women. These differences have important implications for treatment and relapse risk.
Consumption Patterns
Despite men having higher rates of substance use disorders than women, women are more vulnerable to many aspects of the disorder. For example, women have a shorter time period from initial drug use to meeting the criteria for substance use disorder and seeking treatment compared to men. This phenomenon is called the 'telescoping effect.' It means that women tend to develop problematic substance use issues in fewer years compared to men. This effect has been reported across multiple drug classes, including cocaine, methamphetamine, alcohol, opioids, tobacco, and cannabis, and non-pharmacological addictions, such as gambling.
Pre-clinical research has proposed a potential mechanism underlying this sex difference in the nucleus accumbens (the dopamine centre involved in addiction) and the dorsal striatum (the action-oriented center driving the physical action of taking substances). For instance, when exposed to drugs, female rats show a smaller response in the nucleus accumbens at first, but they have a quicker and stronger reaction in the dorsal striatum, driving an escalation in drug use. Additionally, gonadal hormones have been proposed to be involved. Research, both in clinical and pre-clinical settings, has demonstrated that estradiol, a female hormone, can lead to an increased 'high' from smoking cocaine and a stronger drive to obtain cocaine. This suggests that estradiol may play a role in the quicker progression from casual to chronic cocaine use in females compared to males.
Craving
While the telescoping effect plays a significant role in the early stages of addiction, craving becomes a crucial factor in sustaining addiction and raising the risk of relapse after quitting. Exploring potential sex differences in craving will contribute to a greater understanding of how we can support both men and women during abstinence to decrease the risk of relapse. Current research on the sex differences within craving is mixed. Some studies have found no significant differences in craving between men and women for cocaine or alcohol use disorder. In contrast, for opioid use disorder, women have greater craving scores than men. These mixed findings may be related to the involvement of sex hormones in the changes in spine density in neurons and how this impacts craving. Changes to neuronal spine density (how neurons connect in the brain) in the nucleus accumbens are thought to promote craving over time. Sex hormones impact spine density, where testosterone decreases and estradiol increases spine density. The interactions between sex hormones, types of substances used, and their impact on neuronal connections likely contribute to variations in craving.
Psychosocial Factors
Psychosocial factors are known to impact the onset of addiction, such as stressful life events and childhood trauma. One study found that greater severity of childhood emotional trauma, sexual trauma, and overall childhood trauma was associated with higher cocaine use and an increased risk of relapse in women with cocaine use disorder, and this association was not found in men. This association is not limited to childhood trauma, but previous research has shown that women have a greater daily use of cocaine following stress-induced relapse compared to men. Both stress and trauma-related findings are theorized to be related to hypoactivation observed in the ventromedial prefrontal cortex (vmPFC; a key brain region contributing to reward and decision-making) in women. The dysregulation of the vmPFC is suggested to increase relapse and drug-seeking behaviour in women as it creates a more significant obstacle in self-regulation and control over emotionally regulated behaviours.
Implications and Treatment
While acknowledging the neural and behavioural sex differences in addiction has gained research interest, sex has not been well-considered in the development of treatment options for addiction. While some specific targets, such as noradrenergic, cholinergic, antidepressants, and GABA, have been examined in addiction research, there is a lack of focus on how sex differences affect these areas. Only noradrenergic targets consistently show that women tend to have better outcomes with tobacco and cocaine addiction. However, other treatment strategies, like withdrawal treatment or reinforcement blocking, do not have apparent sex-specific effects. Sex considerations should influence addiction medication and treatment development, given that women often experience more stress-related vulnerability, quicker addiction onset, and severe withdrawal symptoms, making research into these areas essential for sex-informed treatments.
*This blog was posted in honour of Substance Use Awarenss Week