Taking opioids in combination with other central nervous system depressants—like benzodiazepines, alcohol, or xylazine—increases the risk of life-threatening overdose. Learn more about the effects of taking more than one type of drug (polysubstance use) from the U.S. Centers for Disease Control and Prevention (CDC).

Image

In 2021, nearly 14% of overdose deaths involving opioids also involved benzodiazepines, a type of prescription sedative commonly prescribed for anxiety or to help with insomnia. Benzodiazepines (sometimes called “benzos”) work to calm or sedate a person, by raising the level of the inhibitory neurotransmitter GABA in the brain. Common benzodiazepines include diazepam (Valium), alprazolam (Xanax), and clonazepam (Klonopin), among others.

Researchers have also found benzodiazepines in the illicit opioid supply in some areas, which may mean that people are taking benzodiazepines in combination with illicit opioids knowingly or unknowingly.

Co-Prescribing Opioids and Benzodiazepines

Every day, approximately 220 Americans die after overdosing on opioids. Combining opioids and benzodiazepines can increase risk of overdose because both types of drugs can cause sedation and suppress breathing—the cause of overdose fatality—in addition to impairing cognitive functions. Research shows that people who use opioids and benzodiazepines concurrently are at higher risk of visiting the emergency department, being admitted to a hospital for a drug-related emergency, and dying of drug overdose.

For example, a cohort study in North Carolina found that the overdose death rate among patients receiving both types of medications was 10 times higher than among those only receiving opioids. A study among U.S. veterans with an opioid prescription found that receiving a benzodiazepine prescription was associated with increased risk of drug overdose death in a dose-dependent manner.

The Centers for Disease Control and Prevention (CDC) Clinical Practice Guideline for Prescribing Opioids for Pain recommends that clinicians use particular caution when prescribing benzodiazepines concurrently with opioids and consider whether benefits outweigh risks.  Both prescription opioids and benzodiazepines now carry U.S. Food and Drug Administration boxed warnings on their labels highlighting the potential dangers of using these drugs together.

People being prescribed any medication should disclose all other substances and medications they use and consult with their health care teams about avoiding or managing the risks of using certain medications and substances in combination.