CDC Study Finds 15% of Overdose Deaths Linked to Benadryl, Other Antihistamines

Benadryl and other antihistamines can interfere with drugs used to prevent overdose deaths, researchers warn.

Opioids and many street drugs are commonly cut with antihistamines, such as Benadryl, which make fatal overdoses more likely, according to the findings of a new federal study.

Researchers from the U.S. Centers for Disease Control and Prevention (CDC) warn that approximately about one of seven overdose deaths involve the use of antihistamines together with opioids and other illicit street drugs. Antihistamines have a sedating effect, which can make overdose more likely and rescue medications less effective.

A study published last week in the CDC’s Morbidity and Mortality Weekly Report highlights the increasing use of antihistamines, like over-the-counter Benadryl, as an additive to street drugs, especially opioids. The study tracked data collected from 43 states on fatal drug overdoses from 2019-2020. The data included 92,000 drug overdose deaths recorded during the study period.

Of those, 13,500 were antihistamine-positive and another 3,345 fatal overdoses listed an antihistamine as partial cause of the victim’s death. An overdose was considered antihistamine-positive if any antihistamine was detected on drug toxicology or was listed as a cause of death.

The findings indicate antihistamines were involved in 15% of opioid overdoses from 2019 to 2020. Most of the overdoses involving antihistamines involved the drug diphenhydramine, the active ingredient in Benadryl, which is a common over-the-counter medication for allergies.

Antihistamine Abuse

Antihistamines are commonly used to treat allergy symptoms. Antihistamines are also often used by those who misuse and abuse opioids because opioids can cause itchy skin. Benadryl is commonly mixed into street formulas to reduce the symptoms of itchiness, but it has a sedative effect.

Misuse of antihistamines is primarily documented in teens and young adults, but this latest study highlighted the involvement of antihistamines in the fatal overdoses across the country.

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Another problem complicating the involvement of antihistamines in street drugs is that diphenhydramine can make naloxone less effective on overdose victims.

Naloxone is known as the overdose reversal drug and is now commonly carried by first responders, schools, and other facilities to combat drug overdoses. Antihistamines do not respond to naloxone, making opioid overdose reversal difficult, thus increasing the risk of overdose deaths.

Overdoses involving opioids and antihistamines may need naloxone plus another type of medication or medical response to prevent death after overdose. If that additional medication or medical treatment is not given, the overdose may become fatal.

“(T)hese data highlight the importance of continued surveillance to understand the drugs and drug combinations contributing to overdose deaths and to guide awareness efforts about the potential dangers of the unpredictable illicit drug supply and the intentional or unintentional co-use of substances, including antihistamines and opioids,” CDC researchers concluded.


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