Research conducted at West Virginia University suggests consuming alcohol with fentanyl and other drugs may explain, in part, why more men than women die from unintentional overdoses.

Zheng Dai, assistant director of health analytics at the WVU Health Affairs Institute, led the study.

“Nationally and in West Virginia, the proportion of men and women actually using illicit substances is about equal, yet far more men are dying from overdoses,” Dai said. “We know men are more likely to drink a greater amount of alcohol than women, and in our overdose analysis, we saw men are more likely to drink alcohol while using a substance.”

Dai explained that since alcohol and opioid intoxication each cause respiratory depression, combining the two produces enhanced toxicity, increasing susceptibility to fatal overdose.

“Oftentimes, because alcohol and opioids are two different substances, people don’t realize they can have the same harmful effect on the body,” he said.

The research was published in the Journal of Studies on Alcohol and Drugs, and draws on forensic research data the investigators developed in collaboration with the West Virginia Office of the Chief Medical Examiner to determine how sex differences play a role in the deaths. Marie Abate, professor of clinical pharmacy in the WVU School of Pharmacy, and Gordon Smith, Stuart M. and Joyce N. Robbins Distinguished Professor in the WVU School of Public Health, developed a system to filter that data to identify not only unintentional overdose deaths, but also all drugs involved and their concentrations in the blood.

West Virginia ranks highest in the U.S. for overdose deaths per capita, despite a recent decline. Between 2005 and early 2023, the study identified 2,057 unintentional overdose deaths in the state involving alcohol and at least one other substance. Of those, 1,578 were males and 479 were females.

Dai said men exhibiting more risky behavior than women could also influence those statistics.

“If people use a substance without a bystander or without naloxone as an antidote, that can put them in a very dangerous situation. Males are more likely to engage in this kind of risky drug use behavior,” he said.

The study showed opioids represented 85% of the nonalcoholic substances present in the toxicology data, followed by stimulants and benzodiazepines. Fentanyl was the most common opioid involved in overdose deaths.

Dosage matters, Dai emphasized.

“Even though we couldn’t identify the dosage ingested before the death, we can analyze the concentration of each substance present in the blood,” he said. “We were able to identify the ‘parent’ drug and metabolized concentrations. This could provide some deeper understanding into why males in West Virginia and in other parts of the U.S. account for two to three times more drug-related deaths than females.”

He added that physiological or dosing differences between males and females might cause men to have higher concentrations of some substances.

However, the study also showed alcohol use and involvement in unintentional overdose deaths among women increased during the pandemic, a factor Dai said raises the possibility that female death rates could rise in the future.

“Alcohol increases the risk of drug overdose mortality for anyone,” Dai said. “Alcohol involvement should not be underestimated. It should be stressed in prevention effort strategies. People think alcohol use is safe when combined with opioids and other substances, but it’s not.”