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Is It Safe to Mix Opioids and Benzodiazepines?

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Polysubstance use—the use of more than one drug at a time—is pretty common within the drug-using community. Liz Brico is here to break down if it is safe to mix opioids and benzodiazepines.

Among people who use opioids, benzodiazepines—sometimes shortened to “benzos”—are known to potentiate the euphoric effects of short-acting opioids like heroin or fentanyl, resulting in a stronger high. Even if you’re not sure what a “benzodiazepine” is, you’ve probably heard of them; Xanax, Klonopin, and Valum are three benzos commonly found on the street, and which many people who use opioids take in order to strengthen their high. Billie Eilish famously serenaded/warned against the drug in her song “Xanny,” employing a well-known nickname for Xanax in the title. The warning is merited: When benzodiazepines potentiate the euphoric effects of opioids, they also potentiate the depressive effects. This means that mixing the two drugs increases the likelihood that a user will experience breathing problems and other symptoms of central nervous system depression, including fatal overdose. In fact, a 2017 paper in the Journal of Addiction Medicine identified that over 30% of opioid-related deaths also involved benzodiazepines.

But What About Prescriptions?

We know that combining non-prescribed benzodiazepines and opioids is really unsafe (even if it feels good sometimes), but what about people who have prescriptions? Benzos are typically prescribed for anxiety or seizure disorders, and sometimes also for sleep problems like insomnia. People who have clinical anxiety or post-traumatic stress disorder (PTSD) may be prescribed fast-acting benzo like alprazolam (Xanax) or lorazepam (Ativan) to help as-needed with anxiety or panic attacks. In some cases, like extreme anxiety or seizure disorders, these drugs may be prescribed for daily use. 

Like opioids, benzos are dependency-forming, meaning that anybody who takes them on a daily basis for long enough will develop a physical dependence, even if they are not misusing the prescription. Unlike opioids (typically), the withdrawals can be fatal in otherwise healthy adults. Many treatment facilities, especially those with a detox component, will not admit patients who turn up positive for benzodiazepines due to the danger and liability associated with a benzo detox. 

Patients who are prescribed both benzodiazepines and opioids face an increased risk of serious complications like respiratory depression and death. It is not uncommon for methadone clinics to have blanket policies disallowing the use of benzos, and many clinics will drastically reduce a polysubstance using the patient’s dose until he no longer tests positive for benzos. 

These policies are problematic, especially for patients with legitimate prescriptions for benzodiazepines. It is possible for someone to be safely co-prescribed opioids and benzos, but their doses must be carefully monitored by the prescribing physician, and the patient must be careful to follow dosing instructions precisely. If a patient is prescribed these medications by separate providers, it is important that she let all of her prescribing physicians know about the medications (and any changes that take place), so that any dose adjustments take into account the other prescription(s). This is generally true about any medication, but especially important when it comes to receiving benzodiazepine and opioid prescriptions.

The Food and Drug Administration (FDA) recently expanded its warning regarding the concurrent use of benzodiazepines and three medications commonly used to treat opioid use disorder: methadone, buprenorphine, and buprenorphine/naloxone. The FDA warning includes informing patients about the risk of excessive sleepiness, respiratory depression, and death, and now also advises patients on how to minimize the use of both drugs. It is also noted that opioid-replacement therapies are often the best options for patients with opioid use disorders

As with any medical condition, a physician needs to individually assess each patient’s needs. Due to the risk of combining opioids and benzos, it is a good idea for physicians to work with patients on alternatives if at all possible. When the benefits of co-prescribing opioids and benzos outweigh the risks, physicians should carefully counsel patients on proper dosage and administration, and on the importance of following these instructions. They should also send the patient home with naloxone.

Safer Practices for Recreational Use

When it comes to recreational or non-prescribed use of opioids and benzos, the safest action is abstinence. But if someone chooses to mix these drugs, there are a few basic steps they can take to reduce potential harms. They should make sure not to use alone, and to inform whomever they are with about what drugs they are mixing and at what doses. This will make it easier for medical professionals to treat them should the need occur. Users should always make sure to have naloxone (Narcan) on hand and to make sure that others around them know where it is and how to administer it. If they are mixing street drugs, like heroin and Xanax, it is a good idea to test for fentanyl. Because fentanyl is typically stronger than heroin, combining it with benzos is even more dangerous—and a great contributor to the recent surge in overdose deaths. Pills bought on the street are turning up that look like pharmaceutical benzodiazepines, but end up being pressed pills containing any number of other ingredients alongside or instead of the benzo—including fentanyl. Testing a small piece of the pill before ingestion can prevent the accidental ingestion of fentanyl, and possibly save a life—maybe even your own.

Elizabeth Brico is a freelance writer with an MFA in Writing & Poetics from Naropa University. She is a journalism fellow with TalkPoverty and a recipient of the 2021/22 Unicorn Fund. She is also a regular contributing writer for HealthyPlace’s trauma blog. Her work has appeared on Vice, Vox, Stat News, The Fix, and others. When she isn’t working, she can usually be found reading, writing, or watching speculative fiction.

Any general advice posted on our blog, website, or app is for informational purposes only and is not intended to replace or substitute for any medical or other advice. Workit Health, Inc. and its affiliated professional entities make no representations or warranties and expressly disclaim any and all liability concerning any treatment, action by, or effect on any person following the general information offered or provided within or through the blog, website, or app. If you have specific concerns or a situation arises in which you require medical advice, you should consult with an appropriately trained and qualified medical services provider.

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