Sex and gender differences in substance use disorders
Open accessAbstract
The gender gap in substance use disorders (SUDs), characterized by greater prevalence in men, is narrowing, highlighting the importance of understanding sex and gender differences in SUD etiology and maintenance. In this critical review, we provide an overview of sex/gender differences in the biology, epidemiology and treatment of SUDs. Biological sex differences are evident across an array of systems, including brain structure and function, endocrine function, and metabolic function. Gender (i.e., environmentally and socioculturally defined roles for men and women) also contributes to the initiation and course of substance use and SUDs. Adverse medical, psychiatric, and functional consequences associated with SUDs are often more severe in women. However, men and women do not substantively differ with respect to SUD treatment outcomes. Although several trends are beginning to emerge in the literature, findings on sex and gender differences in SUDs are complicated by the interacting contributions of biological and environmental factors. Future research is needed to further elucidate sex and gender differences, especially focusing on hormonal factors in SUD course and treatment outcomes; research translating findings between animal and human models; and gender differences in understudied populations, such as those with co-occurring psychiatric disorders and gender-specific populations, such as pregnant women.
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Women have lower concentrations of gastric alcohol dehydrogenase and lower total body water, leading to higher blood alcohol levels and greater intoxication after consuming equivalent amounts of alcohol as men.
“For example, women have lower concentrations of gastric alcohol dehydrogenase, the primary en zyme for alcohol metabolism, and a lower total percentage of body water, leading to higher blood alcohol levels and greater levels of in toxication after consuming equivalent amounts of alcohol as men 334 .”
From Substance use disorders: a comprehensive update of classification, epidemiology, neurobiology, clinical aspects, treatment and prevention (2023) · cites this paper as [334]
The Biological Sex Differences in Substance Use section (page unavailable) says women have lower gastric alcohol dehydrogenase activity and lower total body water, resulting in higher blood alcohol concentrations and greater intoxication after equivalent alcohol consumption. It does not establish a lower concentration of the enzyme itself or call it the primary enzyme for alcohol metabolism. (LLM, conf=0.86)
Experimental — accuracy not yet measuredResearch suggests sex and gender differences in SUD are narrowing.
“research suggests sex and gender differences in SUD are narrowing and should continue to be monitored among the college student population (McHugh et al., 2018).”
From The substance use disorder treatment gap among US college students: Findings from the 2021 National Survey on Drug Use and Health (2024) · cites this paper as McHugh et al., 2018
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Similar discriminative-stimulus effects of d-amphetamine in women and men
Vansickel, A. R., Lile, J. A., Stoops, W. W., & Rush, C. R. (2007) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2007.05.003 · Cited by 24 · see citing works
Menstrual cycle and cue reactivity in women smokers
Gray, K. M., DeSantis, S. M., Carpenter, M. J., et al. (2009) · Nicotine & Tobacco Research · doi:10.1093/ntr/ntp179 · Cited by 24 · see citing works
Incentives for retention of pregnant substance users: A secondary analysis
Brigham, G. S., Winhusen, T. M., Lewis, D. F., et al. (2009) · Journal of Substance Abuse Treatment · doi:10.1016/j.jsat.2009.05.005 · Cited by 23 · see citing works
Flagged first, then by citations
Research works printed but not linked: 4
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- Najavits LM Weiss RD Shaw SR Muenz LR 1998 “Seeking safety”: outcome of a new cognitive-behavioral psychotherapy for women with posttraumatic stress disorder and substance dependence Journal of Traumatic Stress 11 3 437 456 10.1023/a:1024496427434 9690186 · DOI · Paper page
- Seedat S Scott KM Angermeyer MC Berglund P Bromet EJ Brugha TS Kessler RC 2009b Cross-national associations between gender and mental disorders in the World Health Organization World Mental Health Surveys Archives of General Psychiatry 66 7 785 795 10.1001/archgenpsychiatry.2009.36 19581570 PMC2810067 · DOI · Paper page
- Smith K Lipari R 2013 Women of Childbearing Age and Opioids The CBHSQ Report Rockville MD 28252898
Cited by
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Volkow, N. D., & Blanco, C. (2023) · World psychiatry · doi:10.1002/wps.21073 · Cited by 503 · see citing works
Attanasio, R. (2019) · Environmental Pollution · doi:10.1016/j.envpol.2019.113061 · Cited by 72 · see citing works
Davis, J. P., Dworkin, E. R., Helton, J., Prindle, J., Patel, S., Dumas, T. M., & Miller, S. (2019) · Child Abuse & Neglect · doi:10.1016/j.chiabu.2019.01.009 · Cited by 66 · see citing works
Comorbidity of opioid-related and anxiety-related symptoms and disorders
Langdon, K. J., Dove, K., & Ramsey, S. (2019) · Current Opinion in Psychology · doi:10.1016/j.copsyc.2018.12.020 · Cited by 53 · see citing works
El-Gabalawy, R., & Sommer, J. L. (2021) · The Canadian Journal of Psychiatry · doi:10.1177/0706743721989162 · Cited by 50 · see citing works
Johnstone, S., Dela Cruz, G. A., Kalb, N., Tyagi, S. V., Potenza, M. N., George, T. P., & Castle, D. J. (2023) · The American Journal of Drug and Alcohol Abuse · doi:10.1080/00952990.2022.2130348 · Cited by 47 · see citing works
Turhan Gürbüz, P., Çoban, Ö. G., Erdoğan, A., Kopuz, H. Y., Adanir, A. S., & Önder, A. (2021) · Substance Use & Misuse · doi:10.1080/10826084.2021.1958856 · Cited by 38 · see citing works
Andersson, H. W., Mosti, M. P., & Nordfjaern, T. (2023) · BMC Psychiatry · doi:10.1186/s12888-023-04632-z · Cited by 35 · see citing works
DNA Epigenetics in Addiction Susceptibility
Kaplan, G., Xu, H., Abreu, K., & Feng, J. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.806685 · Cited by 34 · see citing works
Amphetamine disrupts dopamine axon growth in adolescence by a sex-specific mechanism in mice
Reynolds, L. M., Hernandez, G., MacGowan, D., Popescu, C., Nouel, D., Cuesta, S., Burke, S., Savell, K. E., Zhao, J., Restrepo-Lozano, J. M., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-39665-1 · Cited by 30 · see citing works
Özgen, H., Spijkerman, R., Noack, M., Holtmann, M., Schellekens, A., Dalsgaard, S., van den Brink, W., & Hendriks, V. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10173908 · Cited by 27 · see citing works
Pasman, E., Blair, L., Solberg, M. A., McCabe, S. E., Schepis, T., & Resko, S. M. (2024) · Drug and Alcohol Dependence Reports · doi:10.1016/j.dadr.2024.100279 · Cited by 24 · see citing works
Mental health literacy in a sample of Canadian adults.
Gallagher, C. E., & Watt, M. C. (2019) · Canadian Journal of Behavioural Science / Revue canadienne des sciences du comportement · doi:10.1037/cbs0000129 · Cited by 9 · see citing works
Skrzynski, C. J., Karoly, H., Ellingson, J., Hangerty, S., Bryan, A. D., & Hutchison, K. E. (2023) · Journal of Studies on Alcohol and Drugs · doi:10.15288/jsad.21-00392 · Cited by 9 · see citing works
Bates, M. L. S., Arner, J. R., Curtis, A. L., Valentino, R., & Bhatnagar, S. (2023) · Neuropharmacology · doi:10.1016/j.neuropharm.2022.109317 · Cited by 7 · see citing works
Age and gender differences in motives for z-drug misuse: Findings from the 2015 to 2019 NSDUH survey
Ellis, R. A., Trapani, E., & McHugh, R. K. (2024) · The American Journal on Addictions · doi:10.1111/ajad.13639 · Cited by 4 · see citing works
Self-citation
- Authors
- McHugh, R. K., Votaw, V. R., Sugarman, D. E., & Greenfield, S. F.
- Affiliations
- Harvard University (US)
- McLean Hospital (US)
- Corresponding author
- McHugh, R. Kathryn
- Venue
- Clinical Psychology Review
- Publisher
- Elsevier BV
- Published
- 2018-12
- Volume
- 66
- Pages
- 12-23
- ISSN
- 0272-7358 (ISSN-L)
- PMC
- PMC5945349
- OpenAlex
- W2767393753
- Cited by
- 1,076
- References
- 211
- Citations by year
- 2026: 118 · 2025: 174 · 2024: 170 · 2023: 184 · 2022: 132 · 2021: 122 · 2020: 127 · 2019: 38 · 2018: 9
- FWCI
- 6.30
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Clinical Psychology Review (acceptedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIDA (UG1 DA015831, K23 DA035297)
- Topics
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Sex and Gender in Healthcare
- Social Sciences › Psychology › Clinical Psychology › Gambling Behavior and Treatments
- Keywords
- sex differences, gender differences, substance use disorders, women, men, brain structure and function, endocrine function, metabolic function, hormonal factors, gender roles, psychiatric comorbidity, pregnancy, animal-to-human translation
- MeSH terms
- Female, Humans, Male, Sex Characteristics, Sex Factors, Substance-Related Disorders
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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