Drugs of abuse have profound effects on the endocrine system, influencing hormonal regulation and disrupting the hypothalamic-pituitary-endocrine (HPE) axis. The impact of these substances varies depending on the drug class with emerging evidence also suggesting that sex differences exist in drug-induced endocrine disruption. Opioids, stimulants, benzodiazepines, cannabis, and alcohol have all been implicated in altering hormone levels, but the mechanisms and consequences remain poorly understood.

Recent studies show that fentanyl can disrupt the HPE axis, leading to alterations in the release and regulation of steroid hormones. Additionally, stimulant use—particularly amphetamines and cocaine—has been shown to increase cortisol and alter the balance of reproductive hormones, which may have long-term effects on fertility and behavior. Alcohol and cannabis, while widely studied, continue to present conflicting findings regarding their effects on the endocrine system, with some studies showing hormonal changes, while others suggest minimal disruption.

Modeling these effects has been critical to understanding the pathways through which commonly misused drugs alter endocrine function. Animal models, including rodents and non-human primates, have provided valuable insights into these disruptions. However, limitations in these models, such as the inability to fully replicate human physiological responses, present challenges in generalizing findings. Understanding the endocrine cascades triggered by drug use, especially in the context of the progression of the addiction disease state, is vital for developing targeted therapeutic strategies and improving public health outcomes.

In this Research Topic, we are looking to address key aspects of endocrine dysfunction in response to drugs of abuse to promote discussion around this topic and to increase our understanding of the etiology of substance use disorders.

We particularly welcome submission of Original Research, Reviews, Methods, and Perspective articles on the following sub-topics:

• Sex and gender differences in substance use disorders
• Endocrine disruption by commonly misused substances
• Endocrine and behavioral modeling of sex differences in substance use disorders
• Impact of drugs of abuse on motivated behaviors (e.g., sexual behavior)
• Influence of hormonal modifications (e.g., hormonal contraceptives, menopause, hormonal treatments in oncology) on drug consumption
• Effect of drugs of abuse on hypothalamic-pituitary-adrenal (HPA), -thyroid (HPT), -gonadal (HPG), and -somatotropic (HPS) axes
• Neurosteroids, substance use disorder, and psychiatric comorbidity: from mechanisms to potential pharmacotherapy.

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Drugs of abuse and their endocrine effects