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What Are the Risks of Mixing Valium With Other Substances?

Mixing Valium with other substances has the potential to cause a dangerous reaction. Two major concerns are enhancing its ability to cause respiratory depression or enhancing its ability to cause drowsiness.

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A good rule is to always talk to a doctor before taking Valium in combination with any drug or other substance. 

How Does Valium Work?

The biomechanics of how Valium works, at a technical level, are fairly complex. In essence, Valium is a benzodiazepine, which is a class of drug that acts on benzodiazepine receptors in the central nervous system. This interaction helps to slow abnormal activity in the brain. 

This is how Valium (which is a brand name for the drug diazepam) can help to relieve anxiety, reduce agitation in people going through alcohol withdrawal, and treat various types of muscle spasms and spasticity issues. 

What Substances Should Not Be Mixed With Valium?

Valium is a powerful medication, and it can interact with both prescription and over-the-counter drugs. Sometimes, these reactions can lead to life-threatening problems. In general, you shouldn’t take anything with Valium without checking with your doctor first. However, the following substances are known to interact with Valium.

Other Benzodiazepines

Valium and other benzodiazepines are central nervous system depressants. Combining them can overwhelm your system, leading to significant respiratory depression. 

Without prompt treatment, a benzodiazepine overdose can cause brain cell damage or even death. Never add another benzo to your Valium dose without asking your doctor first.


Barbiturates like phenobarbital and pentobarbital are similar to Valium, in that they’re central nervous system depressants. Combining these medications with Valium can lead to life-threatening episodes of slow or shallow breathing. Sometimes, this combination causes deadly reactions.


Alcohol isn’t technically a drug, but it’s a sedative that’s capable of slowing brain activity and breathing rates. Using alcohol while taking Valium can lead to intense sedation and life-threatening coma-like states. Never drink alcohol while using Valium.


Painkillers like Vicodin and OxyContin are sedating drugs that can interact with Valium and cause life-threatening overdose episodes. In 2021, about 14% of opioid overdoses also involved benzodiazepines like Valium, so this problem is relatively widespread. Always ask your doctor before taking painkillers with Valium.

Muscle Relaxants

Valium and other benzodiazepines are sometimes used as muscle relaxants. However, there are other non-benzo muscle relaxers that can interact with Valium. 

Often, people take benzos, muscle relaxers, and painkillers all at once. Researchers say this triple-threat combination often lands people in the hospital. Never combine muscle relaxers with your Valium without asking your doctor first.

CYP3A4 Inhibitors

CPY34A is responsible for metabolizing drugs like Valium. Taking drugs that inhibit the production of this cytochrome can allow Valium to build up inside your body, and that can cause a variety of unpleasant side effects, including an increased risk of overdose.

Common substances in the CYP3A4 class include the following:

  • Itraconazole, an antifungal medication  
  • Ketoconazole, an antifungal medication
  • Clarithromycin, an antibiotic
  • Nefazodone, an antidepressant
  • Ritonavir, a protease inhibitor
  • Grapefruit juice


Antihistamines like diphenhydramine can interact with Valium and cause side effects like dizziness, confusion, and lack of coordination. Before using any kind of allergy or cold medication with Valium, ask your doctor first. A different solution for congestion might be smart.

Why Is Drug Mixing So Potentially Dangerous?

One major concern when mixing any substance with Valium is that you may enhance its ability to depress respiration. In other words, Valium can weaken the muscles necessary to breathe. Used as prescribed, this isn’t usually dangerous. 

However, if abused or if mixed with the wrong substances, one can cause significant enough respiration that the body may struggle to get enough oxygen to the brain. This has the potential to cause a person to experience a variety of issues, including feeling extremely confused or losing consciousness. In severe cases, it can cause permanent brain damage or death. 

Valium is also a sedative and can cause drowsiness. If taken with another substance that can also cause drowsiness or otherwise enhances Valium’s sedative qualities, it may make this effect too powerful. This has the potential to cause a person to be unable to stay awake (for reasons separate than those related to how respiratory depression can cause a similar phenomenon), even if losing consciousness would be dangerous, such as while driving. 

On a more basic level, mixing Valium (or any other drug) with substances that change how a prescribing doctor expects your medication to work means that you are essentially modifying your treatment. This could make your treatment less effective or cause an unexpected reaction between the substances that is difficult to predict. 

Updated March 21, 2024
  1. Benzodiazepines. (November 2022). StatPearls.
  2. Diazepam. (May 2021). National Library of Medicine.
  3. Benzodiazepine and Unhealthy Alcohol Use Among Adult Outpatients. (December 2019). American Journal of Managed Care.
  4. Benzodiazepines and Opioids. (November 2022). National Institute on Drug Abuse.
  5. Hospitalization and Combined Use of Opioids, Benzodiazepines, and Muscle Relaxants in the United States. (October 2020). Hospital Pharmacy.
  6. The Importance of Cytochrome P4503A4. (March 2014). MedSafe.
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