What should you not mix with diazepam? A Guide to Dangerous Drug Interactions

October 10, 2025 •

4 min read

According to the U.S. Food and Drug Administration (FDA), combining benzodiazepines like diazepam with opioids can result in profound sedation, respiratory depression, and death. This stark fact underscores why understanding what you should not mix with diazepam is critically important for anyone taking this medication.

Quick Summary

Combining diazepam with other substances, particularly central nervous system depressants like alcohol and opioids, can cause dangerously enhanced sedation, respiratory depression, and increase the risk of fatal overdose. Consult a healthcare provider before mixing any medications, supplements, or alcohol with diazepam.

Key Points

Avoid Alcohol Completely: Consuming alcohol with diazepam significantly amplifies sedative and respiratory depressant effects, dramatically increasing the risk of overdose.
Never Mix with Opioids: The FDA has issued a black box warning against combining diazepam with opioids due to the high risk of fatal respiratory depression.
Be Wary of Other CNS Depressants: Avoid mixing diazepam with other sedating drugs, including sleep aids, muscle relaxants, and certain antidepressants, which can cause excessive drowsiness and slowed breathing.
Steer Clear of Grapefruit: Grapefruit and its juice can interfere with the metabolism of diazepam, leading to elevated drug levels and an increased risk of side effects.
Inform Your Doctor of All Substances: Always tell your healthcare provider about all prescription drugs, over-the-counter medications, herbal supplements, and recreational drugs you use.

Diazepam, also known by the brand name Valium, is a benzodiazepine that acts as a central nervous system (CNS) depressant. It works by enhancing the effects of gamma-aminobutyric acid (GABA), a neurotransmitter that calms nerve activity in the brain. While effective for treating conditions like anxiety, seizures, and muscle spasms when used as prescribed, mixing it with certain other substances can lead to severe and potentially fatal consequences. The amplified depressant effects can overwhelm the body's vital functions, particularly breathing.

Dangerous Substance Combinations to Avoid

Alcohol

Mixing diazepam with alcohol is one of the most hazardous combinations. Both substances are powerful CNS depressants and intensify each other's effects dramatically. This interaction significantly increases the risk of severe side effects, including extreme drowsiness, impaired coordination, confusion, and a dangerously slowed heart rate and breathing (respiratory depression). There is no safe amount of alcohol to consume while taking diazepam, as even a small amount can lead to unpredictable and severe outcomes. Overdose potential is significantly higher when these two substances are combined.

Opioids and Other Narcotic Pain Medications

The combined use of diazepam and opioids carries a black box warning from the FDA, indicating a serious risk of profound sedation, respiratory depression, coma, and death. This risk is elevated even when taking the medications for a short time. Both opioids (e.g., hydrocodone, oxycodone, morphine, methadone) and diazepam suppress the CNS, and their combined effect can be deadly. The risk of fatal overdose is significantly higher than with either substance alone. Healthcare providers are advised to limit co-prescription and monitor patients closely.

Other Central Nervous System Depressants

Mixing diazepam with other substances that also slow down brain activity is extremely dangerous. This includes other benzodiazepines, sleep aids, and muscle relaxants.

Other Benzodiazepines: Taking diazepam with another benzodiazepine, such as alprazolam (Xanax) or lorazepam (Ativan), can lead to an additive effect, causing excessive sedation and increasing the risk of overdose.
Sleep Medications: Sedatives and hypnotics like zolpidem (Ambien), zaleplon (Sonata), or eszopiclone (Lunesta) combined with diazepam can cause excessive sleepiness and slowed breathing.
Muscle Relaxants: Medications such as cyclobenzaprine or baclofen also cause drowsiness and amplify this effect when taken with diazepam, increasing the risk of respiratory issues and overdose.
Certain Antidepressants and Antipsychotics: Some psychiatric medications, including certain antidepressants (like fluoxetine and fluvoxamine) and antipsychotics (like quetiapine), can also increase drowsiness and, in some cases, alter diazepam levels in the body.

Over-the-Counter Medications and Supplements

Many non-prescription products can interact dangerously with diazepam. Sedating antihistamines found in many cold and allergy medicines (e.g., diphenhydramine) and herbal supplements like valerian root, kava, and melatonin can intensify diazepam's sedative effects. Always inform your doctor and pharmacist about all over-the-counter and natural supplements you are taking.

Grapefruit and Grapefruit Juice

Grapefruit and its juice contain compounds that inhibit CYP3A4, an enzyme in the liver responsible for breaking down diazepam. By blocking this enzyme, grapefruit can cause higher concentrations of diazepam to build up in the bloodstream. This leads to an increased risk of side effects like excessive drowsiness, dizziness, and impaired coordination. It is best to avoid grapefruit and grapefruit juice entirely while on diazepam.

Comparison of Safe vs. Unsafe Combinations with Diazepam


Combination	Safety Level	Potential Risk / Effect	Notes
Alcohol	Extremely Dangerous	Severe sedation, respiratory depression, coma, and death.	No safe amount to consume.
Opioids	Extremely Dangerous	Profound sedation, respiratory depression, coma, and death.	FDA black box warning for this combination.
Other Benzodiazepines	High Risk	Excessive sedation, overdose, and heightened CNS depression.	Leads to additive and unpredictable effects.
Sleep Aids (e.g., Ambien)	High Risk	Excessive sleepiness, slowed breathing.	Can suppress respiratory function.
Muscle Relaxants	High Risk	Increased drowsiness, risk of respiratory depression and overdose.	Additive CNS depressant effects.
Sedating Antihistamines	Moderate to High Risk	Excessive drowsiness and impaired concentration.	Common in OTC cold and allergy meds.
Grapefruit Juice	Moderate Risk	Increased diazepam levels in the blood, heightened side effects.	Inhibits the enzyme that metabolizes diazepam.
Herbal Sleep Aids (e.g., Valerian)	Moderate Risk	Enhanced sedative effects and drowsiness.	Can have unpredictable interactions.
Stimulants (e.g., Adderall)	High Risk	Increased strain on the heart, heart attack, and overdose.	The conflicting effects on the CNS are dangerous.
Tylenol or Ibuprofen	Generally Safe	Minimal to no interaction is expected.	Always consult a doctor first, especially if you have other health conditions.

Conclusion: Prioritize Safety and Professional Guidance

Given the wide array of potential drug interactions, it is essential for anyone taking diazepam to be vigilant about what they consume. The most severe risks involve combining diazepam with other CNS depressants, particularly alcohol and opioids, which have a well-documented and high potential for fatal outcomes. The central takeaway is to never mix any substance with diazepam without explicit approval from a healthcare professional.

To ensure your safety, always provide your doctor and pharmacist with a complete list of all medications, supplements, and illicit substances you use. Healthcare professionals can identify potentially dangerous interactions and adjust your treatment plan accordingly. For those struggling with substance misuse involving diazepam, seeking addiction treatment is a critical step towards recovery. The National Alliance on Mental Illness (NAMI) offers resources and support for individuals with mental health conditions and substance use disorders. Ultimately, a proactive and transparent approach with your healthcare team is the best way to prevent dangerous and potentially life-threatening drug interactions.

Frequently Asked Questions

No, there is no safe amount of alcohol to drink while taking diazepam. The combination of these two CNS depressants can lead to unpredictable and severe side effects, including dangerously slowed breathing, even with a single drink.

If you accidentally take diazepam with an opioid and experience symptoms like unusual dizziness, extreme sleepiness, or slowed breathing, seek emergency medical care immediately. This combination can be fatal due to amplified respiratory depression.

No, you should not take over-the-counter sleep aids, such as those containing diphenhydramine or doxylamine, with diazepam. Both are CNS depressants, and mixing them can cause excessive sedation and a higher risk of overdose.

Grapefruit and grapefruit juice contain compounds that block a liver enzyme (CYP3A4) responsible for metabolizing diazepam. This can cause higher blood levels of the medication, increasing the risk and severity of its side effects.

Herbal remedies for anxiety or insomnia, such as valerian or kava, can increase the sedative effects of diazepam and should be avoided. There is limited testing on how herbal supplements interact with prescription drugs, making them potentially unsafe.

Signs of a diazepam overdose, which are amplified when mixed with other substances, include severe drowsiness, confusion, slowed or difficult breathing, loss of consciousness, and a very slow heartbeat. Call emergency services immediately if you suspect an overdose.

To prevent dangerous interactions, provide your doctor and pharmacist with a complete list of all medications and supplements you take. They can screen for potential issues and advise you on safe options. Do not start any new medication, over-the-counter or prescribed, without consulting your healthcare provider.