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Sex Differences in Polysubstance Use Symptoms: A Network Analysis

January 2025
International Journal of Mental Health and Addiction

Authors:

U.S. Department of Veterans Affairs

Many individuals with a substance use disorder (SUD) also experience polysubstance use (PSU), yet research often focuses on single substance use. Further, investigating sex differences is vital, as males and females may exhibit distinct substance use patterns, impacting treatment outcomes. This study employs a network analytic approach to examine sex differences in symptom patterns and interrelationships in PSU, analyzing data from 792 participants using two or more substances. The study evaluates symptoms of alcohol use disorder (AUD), cannabis use disorder (CUD), and drug use disorder (DUD). Results reveal distinct network structures for males and females. Network comparison tests indicate significant differences in specific connections between symptoms for males and females. In this sample, females’ polysubstance use was more strongly associated with more severe SUD symptoms. Conclusions emphasize the need for interventions that address sex-specific vulnerabilities, enhancing the effectiveness of prevention and treatment strategies in managing PSU. Understanding these differences is crucial for developing tailored approaches to support individuals facing SUD.

Centrality indices of female and male networks. S1: using more than planned; S2: difficulties cutting down; S3: significant time spent using/recovering from use; S4: cravings/urges to use; S5: neglecting responsibilities due to use; S6: relationships problems due to use; S7: giving up other important activities due to use; S8: using despite risk/risky behavior; S9: continued use despite negative consequences; S10: tolerance; S11: withdrawal; Alc: endorsed using alcohol; MJ: endorsed using marijuana; Coc: endorsed using cocaine; Sed: endorsed using sedatives; Op: endorsed using opioids; Stim: endorsed using stimulants. Nodes with underscore separating two classes of substances (e.g., MJ18_ALC) indicate item is co-use of those substances (e.g., co-use of marijuana and alcohol)

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Male and female networks. S1: using more than planned; S2: difficulties cutting down; S3: significant time spent using/recovering from use; S4: cravings/urges to use; S5: neglecting responsibilities due to use; S6: relationships problems due to use; S7: giving up other important activities due to use; S8: using despite risk/risky behavior; S9: continued use despite negative consequences; S10: tolerance; S11: withdrawal; Alc: endorsed using alcohol; MJ: endorsed using marijuana; Coc: endorsed using cocaine; Sed: endorsed using sedatives; Op: endorsed using opioids; Stim: endorsed using stimulants. Nodes with underscore separating two classes of substances (e.g., MJ18_ALC) indicate item is co-use of those substances (e.g., co-use of marijuana and alcohol)

…

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Vol.:(0123456789)

International Journal of Mental Health and Addiction

https://doi.org/10.1007/s11469-025-01449-7

ORIGINAL ARTICLE

Sex Diﬀerences inPolysubstance Use Symptoms: ANetwork

Analysis

EliFarmer1 · PollyIngram1· PeterFinn1

Accepted: 13 January 2025

Abstract

Many individuals with a substance use disorder (SUD) also experience polysubstance use

(PSU), yet research often focuses on single substance use. Further, investigating sex diﬀer-

ences is vital, as males and females may exhibit distinct substance use patterns, impacting

treatment outcomes. This study employs a network analytic approach to examine sex diﬀer-

ences in symptom patterns and interrelationships in PSU, analyzing data from 792 partici-

pants using two or more substances. The study evaluates symptoms of alcohol use disorder

(AUD), cannabis use disorder (CUD), and drug use disorder (DUD). Results reveal dis-

tinct network structures for males and females. Network comparison tests indicate signiﬁ-

cant diﬀerences in speciﬁc connections between symptoms for males and females. In this

sample, females’ polysubstance use was more strongly associated with more severe SUD

symptoms. Conclusions emphasize the need for interventions that address sex-speciﬁc vul-

nerabilities, enhancing the eﬀectiveness of prevention and treatment strategies in managing

PSU. Understanding these diﬀerences is crucial for developing tailored approaches to sup-

port individuals facing SUD.

Keywords Polysubstance use· Sex diﬀerences· Substance use· Network analysis

Substance use disorders (SUDs) pose a signiﬁcant public health challenge, impacting indi-

viduals’ physical (Crowe etal., 2000; Keaney etal., 2011; Lo et al., 2020; Struening &

Padgett, 1990) and mental health (Cuﬀel, 1996; Jones & McCance-Katz, 2019; Kingston

etal., 2017; Merikangas & McClair, 2012). Traditionally, research in the ﬁeld of SUDs has

predominantly focused on single substance use and neglects to account for the high preva-

lence and impact of polysubstance use (PSU) (Bailey etal., 2019; Ingram et al., 2022).

For instance, the Epidemiologic Survey on Alcohol and Related Conditions (NESARC)

found that the majority of individuals with an SUD had at least one other co-occurring

SUD and that these individuals had worse prognosis than those with single SUD (McCabe

etal., 2017). PSU, characterized by the concurrent consumption of multiple psychoactive

substances, presents a complex and multifaceted challenge in the ﬁeld of substance abuse

* Peter Finn

ﬁnnp@indiana.edu

1 Department ofPsychological andBrain Sciences, Indiana University, 1101 E. 10th Street,

Bloomington, IN47405-7007, USA

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Gender Differences in Cannabis Use Disorder Symptoms: A Network Analysis

Article

Full-text available

Dec 2022
DRUG ALCOHOL DEPEN

Background While cannabis use in women is increasing worldwide, research into gender differences in cannabis use disorder (CUD) symptomology is lacking. In response to limited effectiveness of addiction treatment, research focus has been shifting from clinical diagnoses towards interactions between symptoms, as patterns of symptoms and their interactions could be crucial in understanding etiological mechanisms in addiction. The aim of this study was to evaluate the CUD symptom network and assess whether there are gender differences therein. Methods A total of 1257 Dutch individuals reporting weekly cannabis use, including 745 men and 512 women, completed online questionnaires assessing DSM-5 CUD symptoms and additional items on plans to quit or reduce use, cigarette use, and the presence of psychological diagnoses. Gender differences were assessed for all variables and an Ising model estimation method was used to estimate CUD symptom networks in men and women using network comparison tests to assess differences. Results There were gender differences in the prevalence of 6 of the 11 symptoms, but symptom networks did not differ between men and women. Cigarette use appeared to only be connected to the network through withdrawal, indicating a potential role of cigarette smoking in enhancing cannabis withdrawal symptoms. Furthermore, there were gender differences in the network associations of mood and anxiety disorders with CUD symptoms. Conclusion The association between smoking and withdrawal as well as gender differences in the role of comorbidities in the CUD network highlight the value of using network models to understand CUD and how symptom interactions might affect treatment.

Sex Differences in Substance Use Disorders: A Neurobiological Perspective

Article

Full-text available

Dec 2021

Clinical studies provide fundamental knowledge of substance use behaviors (substance of abuse, patterns of use, relapse rates). The combination of neuroimaging approaches reveal correlation between substance use disorder (SUD) and changes in neural structure, function, and neurotransmission. Here, we review these advances, placing special emphasis on sex specific findings from structural neuroimaging studies of those dependent on alcohol, nicotine, cannabis, psychostimulants, or opioids. Recent clinical studies in SUD analyzing sex differences reveal neurobiological changes that are differentially impacted in common reward processing regions such as the striatum, hippocampus, amygdala, insula, and corpus collosum. We reflect on the contribution of sex hormones, period of drug use and abstinence, and the potential impact of these factors on the interpretation of the reported findings. With the overall recognition that SUD impacts the brains of females and males differentially, it is of fundamental importance that future research is designed with sex as a variable of study in this field. Improved understanding of neurobiological changes in males and females in SUD will advance knowledge underlying sex-specific susceptibility and the neurobiological impact in these disorders. Together these findings will inform future treatments that are tailor designed for improved efficacy in females and males with SUD.

A Gender Perspective of Addictive Disorders

Article

Full-text available

Feb 2021

Purpose of Review Substance use disorders (SUD) affect differentially women and men. Although the prevalence has been reported higher in men, those women with addictive disorders present a more vulnerable profile and are less likely to enter treatment than men. The aim of this paper is to present an overview of how sex and gender may influence epidemiology, clinical manifestations, social impact, and the neurobiological basis of these differences of women with SUD, based on human research. Recent Findings The differences in prevalence rates between genders are getting narrower; also, women tend to increase the amount of consumption more rapidly than men, showing an accelerated onset of the SUD (telescoping effect). In respect to clinical features, the most important differences are related to the risk of experience psychiatric comorbidity, the exposure to intimate partner violence, and the associated high risks in sexual and reproductive health; and those who are mothers and addicted to substances are at risk of losing the custody of children accumulating more adverse life events. Some of these differences can be based on neurobiological differences: pharmacokinetic response to substances, sensitivity to gonadal hormones, differences in neurobiological systems as glutamate, endocannabinoids, and genetic differences. Summary Specific research in women who use drugs is very scarce and treatments are not gender-sensitive oriented. For these reasons, it is important to guarantee access to the appropriate treatment of women who use drugs and a need for a gender perspective in the treatment and research of substance use disorders.

Substance Abuse and Public Health: A Multilevel Perspective and Multiple Responses

Article

Full-text available

Apr 2020
Int J Environ Res Publ Health

Substance abuse has been a thorny public health concern throughout human history. Manifestly, prevention and treatment are the two main strategies commonly adopted to tackle the problem of substance abuse. They are in fact cross-disciplinary, and they relate to the various domains of heredity, biology, psychology, cognitive science, family, social development and cultural structures. This special issue, “Substance Abuse, Environment and Public Health,” has published empirical studies from different regions and countries globally to enhance the international exchange of latest views and findings on the etiology, processes and influences of substance abuse across different domains, through which a multilevel perspective is considered more helpful for analyzing its complex nature, courses and consequences. This in turn suggests the possible need to employ multiple responses dynamically and integratively in the prevention and treatment of substance abuse.

Applying network analysis to investigate substance use symptoms associated with drug overdose

Article

Mar 2022
DRUG ALCOHOL DEPEN

Background Drug overdose deaths have been increasing over the last several decades. While single substance classes, such as opioids, have been implicated in this rise, less is known about the contributions of polysubstance use (PSU) and other combinations of specific substances and symptoms that may be a risk factor for drug overdose. Methods Symptoms of alcohol, cannabis, and other drug use disorders, as well as co-substance use indicators, were assessed and then examined via network analysis in a sample of young adults (N=1540). Features of the estimated symptom network were investigated, including topology and node centrality, as well as bridge centrality, which further examines node centrality while accounting for the nodes belonging to discrete communities. Results Individual symptoms were more strongly associated with other symptoms within the same substance class than across substance classes. Tolerance and withdrawal symptoms were the most central items in the network. However, when accounting for symptoms belonging to discrete substance classes, drug overdose emerged as a strong bridge symptom, among others. Conclusions As a strong bridge symptom, drug overdose had many connections with a variety of substances and symptoms, which might suggest that risk for drug overdose may be a function of overall substance use severity. Altogether, examining alcohol and substance use symptoms using a network analytic framework provided novel insights into the role PSU might play in conferring risk for drug overdose.

A Scoping Review of Gender, Sex and Sexuality Differences in Polysubstance Use in Adolescents and Adults

Article

Mar 2022
ALCOHOL ALCOHOLISM

Background: Polysubstance use is a common, problematic behavior that increases risk of harm to self and others. Research suggests that rates may vary based on gender, sex and sexuality. Understanding the current state of this literature may inform prevention and treatment of polysubstance use, leading to reduced public health burden. Objectives: This review aimed to synthesize research on gender, sex and sexuality differences in polysubstance use in adults and adolescents. Methods: A scoping review was conducted using all EBSCO databases, PubMed and Google Scholar to identify articles examining the effects of gender, sex and sexuality on polysubstance use. Polysubstance use was defined broadly as the use of any combination of substances over any time period and included licit (alcohol, tobacco) and illicit substances, concurrent and simultaneous use, from lifetime to daily use and use at any frequency. Studies were considered if they were published in peer-reviewed journals between January 1990 and October 2020 and were written in English. Publicly available data sources were also utilized to fully capture prevalence data that has not been published elsewhere. Results: Findings were mostly inconsistent and often conflicting. Only two findings were generally consistent: adult men were overall more likely to report polysubstance use than adult women, and sexual and gender minorities report more frequent polysubstance use than non-minorities. Conclusions: Research has been unable to clearly elucidate differences in polysubstance use prevalence and patterns according to gender, sex and sexuality. Several recommendations are offered to advance future research and address limitations of current research.

Patterns of polysubstance use and simultaneous co-use in high risk young adults

Article

Oct 2019
DRUG ALCOHOL DEPEN

Background: Polysubstance use (PSU) is associated with worse prognosis and poorer physical and mental health compared to single substance use. The current study provides information about PSU patterns by examining a diverse range of alcohol/substance use behaviors ranging from low-level experimentation to indicators of severe abuse. In addition, the current study, for the first time, examines how simultaneous co-use of multiple substances cluster with other more commonly studied PSU behaviors. Methods: Latent Class Analysis was used to identify patterns of substance use, in a sample of young-adults (n = 2098), using 25 items from the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA-II) including: items assessing severity of problems with alcohol, cannabis, stimulants, opiates, and sedatives; items assessing # of lifetime uses; items assessing simultaneous co-use of all combinations of substances. Then the association of class membership and age, antisocial and impulsive personality, experience seeking, anxiety, and neuroticism was examined using Multinomial Regression. Results: Fit indices (i.e. AIC, SSABIC, and entropy) and interpretability of classes supported a five-class solution: "Low Problems" (32% of sample), "Alcohol Primary" (11%), "Alcohol and Cannabis" (25%), "Moderate PSU" (23%), and "Severe PSU" (9%). Simultaneous co-use behaviors discriminated between lower and higher severity groups. Externalizing personality constructs robustly predicted membership in the "Moderate" and "Severe" PSU classes compared to the "Alcohol Primary" class. Conclusions: PSU patterns followed an additive pattern of use with lower severity classes using alcohol/cannabis and more severe classes using other illicit substances in addition. Co-use items provided valuable information about PSU severity.

Research on Women with Substance Use Disorders: Reviewing Progress and Developing a Research and Implementation Roadmap

Article

Feb 2019
DRUG ALCOHOL DEPEN

Background: Research on women with substance use disorders has expanded, yet knowledge and implementation gaps remain. Methods: Drawing from topics discussed at the 2017 meeting of InWomen's in Montreal, Canada, this article reviews key progress in research on substance use among women, adolescents, and families to delineate priorities for the next generation of research. Results: The field has seen significant accomplishments in multiple domains, including the management of pregnant women with substance use and comorbid psychiatric disorders, caring for neonates in opioid withdrawal, greater inclusion of and treatment options for LGBTQ + communities, gendered instrumentation, and gender-focused HIV interventions for adolescent girls and women. Women who use alcohol and other drugs often experience other comorbid medical conditions (chronic Hepatitis C and HIV), contextual confounders (intimate partner violence exposure, homelessness, trauma), and social expectations (e.g., as caretakers) that must be addressed as part of integrated care to effectively treat women's substance use issues. Although significant advances have been made in the field to date, gender-based issues for women remain a neglected area in much of substance abuse research. Few dedicated and gender-focused funding opportunities exist and research has been siloed, limiting the potential for collaborations or interdisciplinary cross-talk. Conclusion: Given renewed attention to substance use in the context of the burgeoning opioid epidemic and shifts in global politics that affect women's substance use, the field requires a strategic rethink to invigorate a pipeline of future research and researchers.

Co-Occurring substance use and mental disorders among adults with opioid use disorder

Article

Feb 2019
DRUG ALCOHOL DEPEN

Background Co-occurring substance use and mental disorders among people with opioid use disorder (OUD) increase risk for morbidity and mortality. Addressing these co-occurring conditions is critical for improving treatment and health outcomes. There is limited recent research on the prevalence of co-occurring disorders, demographic characteristics associated with co-occurring disorders, and receipt of mental health and substance use treatment services among those with OUD. This limits the development of targeted and resourced policies and clinical interventions. Methods Using 2015–2017 National Survey on Drug Use and Health data, prevalence of co-occurring substance use and mental disorders and receipt of mental health and substance use treatment services was estimated for adults aged 18–64 with OUD. Multivariable logistic regression assessed demographic and substance use characteristics associated with past-year mental illness (AMI) and serious mental illness (SMI) among adults with OUD as well as treatment receipt. Results Among adults with OUD, prevalence of specific co-occurring substance use disorders ranged from 26.4% (95% CI:23.6%–29.4%) for alcohol to 10.6% (95% CI:8.6%–13.0%) for methamphetamine. Prevalence of AMI was 64.3% (95% CI:60.4%–67.9%) and SMI was 26.9% (95% CI:24.2%–29.8%). Receiving both mental health and substance use treatment services in the past year was reported by 24.5% (95% CI:21.5%–29.9%) of adults with OUD and AMI and 29.6% (95% CI:23.3%–36.7%) of adults with OUD and SMI. Conclusions Co-occurring substance use and mental disorders are common among adults with OUD. Expanding access to comprehensive service delivery models that address the substance use and mental health co-morbidities of this population is urgently needed.

Borderline Personality Disorder Symptom Comorbidity Within a High Externalizing Sample: Relationship to the Internalizing-Externalizing Dimensional Structure of Psychopathology

Article

Feb 2019
J PERS DISORD

Borderline personality disorder (BPD) is highly comorbid with internalizing and externalizing psychopathology. The current study replicates findings indicating that BPD symptomatology is influenced by the distress subfactor of both the internalizing and the externalizing dimension of psychopathology. Confirmatory factor analysis of the covariance of continuous measures of externalizing pathology, internalizing pathology, and BPD symptoms was assessed in 837 young adults. The sample contained a range of externalizing severity from none to high severity, leading to an overrepresentation of externalizing problems. BPD symptoms were associated with both the externalizing dimension and the distress subfactor of the internalizing dimension. Interestingly, BPD had a stronger association with the externalizing dimension than observed in previous studies. Results replicated earlier findings using different and more dimensional measures. Findings indicated that BPD is more heavily influenced by the externalizing dimension of psychopathology within a high externalizing sample, such as those presenting for treatment of alcohol or substance use disorders.

Sex Differences in Polysubstance Use Symptoms: A Network Analysis

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