Tag Archive for: addiction

Behind the Science: Breaking the Mold: Gender, Cannabis, and Substance Use Disorders

Interviewee: Dr. Justin Matheson,  | Authors/Editors: Romina Garcia de leon, Janielle Richards (Blog Co-coordinators)

Published: September 6th, 2024

Can you briefly explain your research?

My research focuses on understanding how sex and gender shape substance use health, which encompasses the continuum from initial drug use experiences to substance use disorders. Specifically, in my current research, I am concentrating on two main areas. The first is examining differences in acute responses to cannabis using a human behavioral pharmacology paradigm. In this paradigm, participants smoke cannabis in the lab, and we observe categorical differences in their responses, such as how high they feel and their cognitive and sometimes driving performance. The second focus is on how gender influences trajectories and experiences in cannabis use disorder treatment, including the type and severity of symptoms experienced by individuals undergoing treatment to reduce or stop cannabis use. The aim is to better understand these trajectories, particularly in cisgender women and gender minorities, and to improve prevention and treatment strategies for substance use disorders, especially cannabis use disorders.

How did you get into this research?

I kind of stumbled into this field when, as a PhD student, my supervisor suggested that we explore differences in our initial cannabis lab study for a conference presentation. As I reviewed the literature, I became increasingly aware of how much harm in science has been caused by andronormativity, the focus on men and male bodies. Substance use has often been framed as a “men’s issue,” and addiction in women is less understood, with limited research on addiction in gender minorities. As a gender-fluid person, I felt it was important to work towards gendered health equity in the addiction field within a restorative social justice framework, addressing gaps in understanding how substance use affects cisgender women and gender minorities.

How do you define sex and gender in your work?

Initially, my approach was to use a classic categorical difference model—males versus females. However, I am now shifting towards exploring the underlying factors driving these categorical differences. For example, I am interested in the relationship between gonadal hormone levels and acute responses to drugs, and how these relationships vary with the menstrual cycle or menopause. There is a significant lack of empirical evidence on how menopause might impact addiction risk. While my research is still grounded in binary categories, I aim to move beyond this binary to examine associated factors that affect all bodies differently based on gender. I think of gender as a way of making meaning of bodies and how societal understandings of gender influence how individuals are treated. Historically, substance use has been more stigmatized for women, contributing to underreporting and less focus in research. Women with cannabis use disorders often face more interpersonal conflicts, while men may experience more neurobiological or pharmacological harm. My research seeks to understand how gender and biology interact and how these interactions influence substance use and addiction.

Are there any findings you could share with us?

In our human laboratory work, we’ve encountered challenges. For example, in my initial PhD research, female participants smoked less cannabis than males and had lower THC levels in their blood than expected. Despite reporting similar subjective and cognitive effects as males, the difference in blood THC levels was significant. However, subsequent attempts to replicate this finding have been inconclusive. We are exploring how contextual factors (e.g., mood, expectations, prior cannabis use history) might moderate the relationship between THC exposure and intoxication states. We are also investigating the impact of menstrual cycle phase, estrogens, and androgens on cannabis use. In our gender-related research, which is primarily qualitative, we’ve identified notable gender narratives. For instance, men often seek treatment after struggling to cut back on cannabis, while women frequently cite external pressures and shame related to their cannabis use. These preliminary findings suggest a need for further exploration of how gender influences treatment-seeking behaviors and barriers to accessing care.

Where do you hope to see this work in 10 years?

In the next decade, I hope to secure more funding for research on specific factors related to substance use. There is a significant gap in understanding how menstrual cycle phases impact cannabis use, with only one published study in this area. I aim to fill this gap and explore neuroendocrinological approaches, including hormone modeling and genetic factors. Additionally, I hope to integrate gender more systematically into laboratory studies, moving beyond qualitative research to develop quantitative measures of gender. For example, understanding how individuals who identify as more feminine may experience cannabis intoxication differently could be crucial. Ultimately, I aim to merge research on gender and cannabis use disorder with studies on individual differences in drug responses, to improve prevention and treatment strategies for cannabis use disorders and other substance use disorders.

Where can you learn more about Dr. Justin Matheson’s work?

Website: https://www.justinrmatheson.com/ 

Twitter/X: https://x.com/justinrmatheson 

Understanding Sex Difference in Addiction: The Road to Tailored Treatments

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