The rate of overdose deaths due to fentanyl rose by 279% from 2016 to 2021 in the U.S., according to a new report by the Centers for Disease Control and Prevention (CDC).

Researchers found the rate of fentanyl-related overdose deaths increased from 5.7 per 100,000 to 21.6 per 100,000 during that period, ABC News reports.

Overdose deaths linked to several other substances, while lower, also rose, the CDC found. The rate of deaths linked to methamphetamine more than quadrupled, from 2.1 to 9.6 per 100,000, while the rate of deaths due to cocaine more than doubled, from 3.5 to 7.9 per 100,000.

Deaths due to heroin and oxycodone declined during the same five-year period. Rates of heroin overdose deaths dropped from 4.9 to 2.9 per 100,000, while oxycodone overdose death rates declined from 1.9 to 1.5 per 100,000.

“When it comes to overdose, really the biggest driver is folks who are really struggling with addiction primarily on street drugs, which fentanyl is primarily found in terms of the street drug supply rather than a prescription medication,” said Dr. Allison Lin, an addiction psychiatrist at University of Michigan Medical School, who was not involved in the report. “And it’s primarily folks who are struggling with addiction to multiple substances, so oftentimes, folks who are using not only fentanyl, but fentanyl plus cocaine or fentanyl plus methamphetamine.”