5/03/2019 Staff Writer

Biological Sex, Estrous Cycle and Drug Addiction

A growing body of research indicates that biological sex plays a role in drug abuse susceptibility, and recent studies in both humans and animals suggest that female hormones can enhance drug use and the feeling of euphoria associated with drug-taking. 

New research from Franklin & Marshall College shows that estrogen levels impact the intake of both cocaine and opioids. This finding is important to the investigation and treatment of drug addiction because it indicates that substance use disorders are potentially distinct processes between men and women. The results of the study suggest that a universal approach to substance use disorders treatment may not be the most successful strategy, particularly as it relates to males and females. Furthermore, the majority of animal research conducted in this field has focused primarily on males and this study aimed to help close that knowledge gap.

F&M’s Assistant Professor of Psychology Ryan Lacy, alumna Bridget Austin ’17, and postdoctoral fellow Justin Strickland of Johns Hopkins University applied behavioral economic demand theory in their research to characterize and assess drug abuse liability in rats. The use of behavioral economics is a newer method of analysis that allows the researchers to evaluate drug “prices” by changing the dose of the drug available for the animal to take. For example, animals that are willing to continue “paying” higher prices by continuing to take a drug even as the amount of the drug decreases are considered more likely to become addicted.

Lacy’s animal laboratory study, which used male and female Long-Evans rats, found that demand for cocaine and remifentanil (a powerful opioid drug) was higher in female rats during the cycle when their estrogen levels are higher. 

According to the study: “[F]emale subjects showed greater unconstrained demand for cocaine during estrus compared with metaestrus and diestrus. Similarly, unconstrained remifentanil demand was highest during estrus compared with other phases.” The estrus phase is the period in which female sex hormones are elevated and suggests that these hormones enhance the effect of drugs. 

Therefore, sex hormones represent “a biological mechanism that could increase drug use vulnerability and be targeted in future clinical applications,” Lacy said. 

Interestingly, according to the researchers, “The study also found that prior opioid exposure increased later demand for cocaine, which provides a possible explanation for recently documented increases in stimulant use observed across the United States in the wake of the opioid crisis.” 

According to the researchers, the assessment of economic demand for drugs of abuse represents an important factor underlying the risk for substance abuse disorders.

The study is one of the first systematic preclinical evaluations of the effect of sex and estrous cycle on cocaine and opioid demand.

This study was published in Addiction Biology and can be accessed here.

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