They discover why women are less addicted to fentanyl than men

BarcelonaFemale sex hormones are responsible for protecting women against drug and opioid abuse in cases of chronic pain, according to a study conducted in mice at Washington University School of Medicine in St. Louis. The study found that male rats self-administer larger amounts of opioids, specifically fentanyl, than female rats in cases of chronic pain, a finding that opens the door to new pain treatments using estrogen.

The opioid epidemic has caused more than half a million deaths in the United States since 1999, and three-quarters of these deaths have been men, according to official health system data. Although disproportionate rates of opioid use and overdose deaths in men are well documented, the reason for these gender differences has not yet been answered.

This new study suggests, therefore, that one of the underlying causes could be biological. Researchers believe it is proven that differences in self-administration of pain-relieving drugs are directly influenced by sex hormones: when male rats were treated with the hormone estrogen, these animals – like female rats – maintained stable doses of fentanyl.

The report, which has been published in the journal Neuron, shows that a better understanding of sex hormones and how they interact with chronic pain could open new avenues for addressing an opioid epidemic. “These data suggest that men may be inherently predisposed to opioid abuse in the context of pain due to the balance of their sex hormones,” says Jessica Higginbotham, Ph.D., senior author of the study and a postdoctoral researcher. “We focused on estrogen in this study, but I doubt that the observed effect is due to this hormone alone. It is more likely that it is the balance of all the sex hormones in the body that influences risk. Men and women have the same sex hormones, but in different amounts, and our data suggest that women have a balance. of opioids could also change,” she says.

The influence between pain and opioid use

Most people who abuse opioids do so for pain relief, but men are more likely to overdose than women, even though they suffer less chronic pain, survey data show. Scientists think something other than chronic pain must be putting men at higher risk for opioid problems.

When a person — or rat — takes an opioid such as fentanyl, it acts on the brain in two ways. The drug blocks the transmission of pain signals, thereby relieving pain, triggering the release of dopamine from the brain’s reward center, which creates a feeling of euphoria.

Researchers studied rats with chronic paw pain and found no difference between males and females in the amount of pain they experienced, as measured by how quickly they withdrew their paw when touched. They also found no difference between the sexes in the amount of pain that a dose of fentanyl relieved. However, males continued to increase their fentanyl use over the three weeks of the study, while females did not.

The study did reveal a significant difference between males and females in the amount of dopamine released after a dose of fentanyl. Females produced the same amount of dopamine throughout the experiment, regardless of whether they were in pain or not. Males who were pain-free responded like females. In contrast, males with chronic pain experienced greater opioid-induced pleasure, a reaction not seen in females.

"We thought it might be that males developed tolerance to fentanyl, requiring larger amounts for pain, but that wasn't the case," the study's authors note. "Males took more and more fentanyl to feel an increasingly intense euphoric effect," they conclude. Further experiments revealed that sex hormones were responsible for the different dopamine responses in male and female rats.

The researchers found that female rats with their ovaries removed responded to fentanyl like males, with increased dopamine production and opioid seeking. In contrast, males given estrogen showed a response in terms of dopamine generation and opioid-seeking behavior similar to females.