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The Dangers of Mixing Opioids With Other Substances

Opioids are powerful depressants and shouldn’t be mixed with other types of drugs without first talking to a doctor. There is a real risk that the effects of the drugs you mix might stack and cause a dangerous overdose or other complications.[1]

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Mixing opioids with other substances like alcohol or benzodiazepines increases the likelihood of opioid overdose, which can be fatal.

The Basics of Polydrug Use

Polydrug use is any kind of drug use in which a person is taking multiple drugs at once. It is often used in the context of drug misuse and abuse, but many patients also engage in legitimate polydrug use if their doctor has prescribed them multiple medications. It can therefore be considered a neutral term, neither inherently negative nor positive, but it is something a person should generally avoid if unnecessary. 

Mixing drugs can cause them to interact or otherwise affect the body in ways that aren’t always easy to predict. Especially when done recreationally, polydrug use has the potential to be dangerous, accelerating the potential for overdose.

In the case of opioids, polydrug use should only be done if the other drugs one is taking have been approved by a doctor. Opioids have legitimate medical uses, but they also carry many dangers. They can be addictive, and their misuse has the potential to cause an overdose that might result in permanent brain damage or death. 

These dangers can be enhanced if one is also mixing opioids with the wrong substances, especially if you’re doing so in an attempt to enhance or alter their effects in a way not prescribed by a doctor. Combining opioids with any other substances can be harmful, including benzodiazepines, alcohol, other opioids, or stimulants.[1]

Substances Commonly Mixed With Opioids

Some of the most common drugs taken with opioids include the following:[2]


One of the more dangerous drugs that is commonly mixed with opioids is alcohol. As is true of many items on this list, alcohol is a depressant. 

The major concern when taking a depressant with an opioid is that opioids are also depressants. Depressants slow down important signals in the body, and they can slow the heart and weaken breathing.[3] This can lead to death.

Other Opioids

Mixing opioids will stack their effects, as will taking more of the same opioid.[4] For many of the same reasons that it is dangerous to drink alcohol with opioids, taking opioids on top of each other has the potential to be life-threatening. 

As is true of any prescription drug but especially opioids, you should only take a given opioid as prescribed by a doctor, and never mix them with other drugs unless you’ve first confirmed with your doctor that it’s safe to do so. Taking excessive amounts of opioids not only increases your risk of overdose, but it can also significantly increase your chance of developing an opioid use disorder (OUD).


While there are some legitimate medical reasons for a person to be prescribed benzodiazepines with opioids, this combination is typically avoided by medical experts. It has been shown to increase a person’s risk of overdose death as much as 10-fold if both opioids and benzodiazepines are prescribed together.[5] 

Keep in mind that this is the risk when the drugs are prescribed. The risk of an overdose if one is intentionally abusing one or both drugs is likely even higher. 

The reason this combination is dangerous is again due to the stacking of effects. Benzodiazepines cause sedation and suppress breathing, as do opioids.[5] 


Some people mix methamphetamine use with opioids.[6] Meth is a stimulant, and stimulants can mask the unwanted effects of depressants like opioids, which some people may view as counteracting their downsides. 

This type of effect stacking is always imperfect; eventually, one drug or the other will begin to wear off. This can result in the body suddenly getting a fuller effect from the other drug, which can potentially lead to an overdose. If using one drug to mask the effects of another drug causes a person to take a higher dose than they normally would, their risk of an overdose will increase significantly.

Is Mixing Other Drugs With Opioid Use Always Dangerous?

There are reasons someone might mix opioid use with other types of drug use, but only if that drug use is doctor-prescribed. For example, a person might have severe pain but also need to take other medications for other health reasons. 

Even then, having legitimate reasons to take multiple medications doesn’t mean any relevant dangers don’t exist. Some people may need to take benzodiazepines with opioids due to an unfortunate combination of conditions. This is still something that needs to be done with extreme care and only when a doctor is sure it’s necessary. A patient also needs to be informed about the dangers associated with these combinations. 

It’s also worth noting not all drug mixing is equally dangerous. While it’s a good habit to always talk to a doctor before taking any drug with a prescription medication, especially opioids, the real danger is in how any two drugs will interact. Some drugs won’t meaningfully interact with opioids, while others can be quite dangerous. 

Get Help for Polysubstance Abuse

If you have been intentionally mixing opioids with other substances to experience a greater high, it’s a clear sign that help is needed. Polysubstance abuse is likely to result in overdose eventually, but with addiction treatment, you can stop all opioid misuse for good.[7] 

Reach out for help today.

Updated May 6, 2024
  1. Drug interactions of clinical importance among the opioids, methadone and buprenorphine, and other frequently prescribed medications: A review. McCance-Katz EF, Sullivan LE, Nallani S. American Journal on Addictions. 2010;19(1):4-16.
  2. Opioid overdose crisis compounded by polysubstance use. The Pew Charitable Trusts. Published October 8, 2020. Accessed November 25, 2023.
  3. Alcohol and opioid use, co-use, and chronic pain in the context of the opioid epidemic: A critical review. Witkiewitz K, Vowles KE. Alcoholism: Clinical and Experimental Research. 2018;42(3):478-488.
  4. Patient safety events involving opioid dose stacking. Agency for Healthcare Research and Quality. Published April 17, 2022. Accessed November 25, 2023.
  5. Benzodiazepines and opioids. National Institute on Drug Abuse. Published April 21, 2022. Accessed November 25, 2023.
  6. Association of methamphetamine and opioid use with nonfatal overdose in rural communities. Korthuis PT, Cook RR, Foot CA, et al. JAMA Network Open. 2022;5(8):e2226544-e2226544.
  7. Polysubstance use facts. Centers for Disease Control and Prevention. Published August 18, 2021. Accessed November 25, 2023.
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