The influence of sex and gender factors on the modulation of vulnerability to addictions: a narrative review (2025)

This narrative review identifies the sex- and gender-related factors that influence individual vulnerability to developing addictive disorders. Addiction arises from the complex interaction between neurobiological and psychosocial factors. Sex-based brain dimorphisms, shaped by genetic, hormonal, and epigenetic influences, lead to differences in neural circuits involved in reward, emotional regulation, and executive functioning. Pharmacokinetic differences, such as higher blood alcohol levels, faster nicotine metabolism, and slower µ-opioid receptor internalization in women, contribute to earlier medical complications and faster addiction progression. Gender, understood as a system of socially constructed roles and expectations, further modulates these vulnerabilities. Traditional masculine norms are associated with higher substance use, while certain aspects of femininity may increase risk (e.g., emotional repression or partner dependence) or serve as protective factors through help-seeking behavior. Sexual and gender minorities experience the most significant disparities. Lesbian and bisexual women show the highest rates of substance use disorders; gay and bisexual men report greater illicit drug use; and bisexual individuals consistently display the highest overall risk. Transgender and non-binary populations exhibit increased prevalence of tobacco, stimulant, and chemsex-related substance use, often as a response to minority stress and exclusion from cisnormative care systems. Psychiatric comorbidity affects 50-80% of cases. Women show higher rates of anxiety, trauma histories, and adverse clinical outcomes. Many face "triple stigma" due to their gender, mental health condition, and substance use. Addressing these disparities requires an intersectional, gender-informed, and culturally competent approach to prevention, diagnosis, and treatment. [Author's abstract]