What medications interfere with nitrous oxide?

October 11, 2025 •

4 min read

According to research, over sixty medications have been identified to interact with nitrous oxide, with many interactions classified as moderate to severe. This makes it critically important for healthcare providers and patients alike to understand what medications interfere with nitrous oxide prior to any procedure.

Quick Summary

A variety of medications can interact with nitrous oxide, potentiating sedative effects, altering blood pressure, or causing nutritional deficiencies. Patients must inform their healthcare providers about all substances they use, from prescription drugs to supplements, to ensure safe administration.

Key Points

CNS Depressants: Combining nitrous oxide with other CNS depressants like opioids, benzodiazepines, or alcohol significantly increases the risk of excessive sedation and respiratory depression.
Blood Pressure Medications: Nitrous oxide can lower blood pressure, and when combined with antihypertensives, it can cause dangerously low blood pressure (hypotension).
Stimulants: Mixing nitrous oxide with stimulant drugs, such as amphetamines, can cause an increase in blood pressure and heart rate.
Vitamin B12 Depletion: Nitrous oxide can interfere with vitamin B12 metabolism, posing risks for individuals with pre-existing deficiencies, such as vegans or the elderly.
Psychiatric Medication Effects: While risks are generally minimal with professional consultation, some psychotropic medications can interact with nitrous oxide and warrant caution.
Recreational Drug Use: Concurrent use of recreational substances, particularly alcohol, is highly dangerous and increases the risk of overdose and other severe side effects.
Full Disclosure is Key: Providing a complete and accurate medical history, including all substances used, is the most crucial step for patient safety during nitrous oxide administration.

Understanding the Mechanisms of Interaction

Nitrous oxide is a central nervous system (CNS) depressant used for its analgesic and anxiolytic properties, commonly known as 'laughing gas'. It works by modulating neurotransmitter activity in the brain. When combined with other medications that affect the CNS or other bodily systems, the cumulative effects can be unpredictable and dangerous. Interactions can range from enhancing sedation to affecting blood pressure or causing nutritional deficiencies.

Medications that Enhance Central Nervous System (CNS) Depression

Perhaps the most significant and dangerous drug interaction with nitrous oxide involves other CNS depressants. These medications can synergistically increase sedation and respiratory depression, which can lead to serious complications, including respiratory arrest.

Opioid Pain Relievers: Drugs like hydrocodone (Norco) and codeine can potentiate the sedative and respiratory effects of nitrous oxide. Combining them requires careful monitoring and often a lower dose of nitrous oxide.
Benzodiazepines: Medications such as lorazepam (Ativan), diazepam (Valium), and alprazolam (Xanax) are commonly prescribed for anxiety and can significantly increase the risk of CNS and respiratory depression when combined with nitrous oxide.
Barbiturates and Hypnotics: Sleep aids like zolpidem (Ambien) and other sedative drugs can cause excessive sedation and impaired recovery when mixed with nitrous oxide.
Alcohol: Ethanol is a powerful CNS depressant. Using nitrous oxide with alcohol, especially in excess, can severely impair judgment and increase the risk of over-sedation, unconsciousness, and suffocation.

Medications Affecting Blood Pressure and Heart Function

Several drug classes can interfere with the cardiovascular effects of nitrous oxide, potentially causing dangerous fluctuations in blood pressure and heart rate.

Antihypertensives: Nitrous oxide can cause a decrease in blood pressure. Combined with blood pressure-lowering medications like ACE inhibitors (e.g., lisinopril) or beta-blockers, the risk of hypotension (dangerously low blood pressure) and hypoperfusion of vital organs increases.
Stimulants: In contrast, drugs like amphetamines (e.g., Adderall, Vyvanse) and other stimulants can increase blood pressure and heart rate. Combining these with nitrous oxide can lead to hypertensive events or arrhythmias.
Alpha-2 Adrenergic Agonists: Medications like clonidine, used for hypertension and sedation, can increase the risk of sedation when combined with nitrous oxide.

Interactions Related to Vitamin B12 and Other Nutrients

Nitrous oxide can interfere with the body's metabolism of vitamin B12 by oxidizing the cobalt ion in the vitamin, which inactivates it. This interference can have serious hematologic and neurologic consequences, particularly for individuals with pre-existing deficiencies.

Methotrexate: This chemotherapy and immunosuppressant drug affects folate metabolism. Since nitrous oxide affects B12, which is intertwined with folate metabolism, combining these can exacerbate the risk of hematologic issues.
Vitamin B12 Deficiency: People with a known or suspected vitamin B12 deficiency, such as vegans, the elderly, or those with pernicious anemia, are at high risk. Frequent or prolonged exposure to nitrous oxide can worsen their condition.

Psychiatric Medications and Other Drug Classes

Antidepressants and Anxiolytics: Certain psychotropic medications, including SSRIs (like sertraline/Zoloft) and SNRIs (like duloxetine/Cymbalta), can cause adverse effects when combined with nitrous oxide. While typically considered safe under medical supervision, they warrant caution, especially in patients with severe psychiatric conditions.
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): Some NSAIDs, like ibuprofen (Advil), may interfere with aspects of anesthesia and can affect nitric oxide (NO) rather than nitrous oxide (N2O) in some contexts. However, the direct interaction with N2O is usually minor but should be disclosed.
Herbal Supplements: Substances like St. John's Wort or Ginkgo Biloba can interact with anesthesia drugs by affecting enzymes or having anticoagulant properties. Patients must disclose all supplements.

The Importance of Full Disclosure

Given the wide range of potential interactions, it is crucial that patients provide a complete and accurate medical history to their healthcare provider. This includes all prescription drugs, over-the-counter medications, herbal remedies, and any recreational drug or alcohol use. The dose and duration of nitrous oxide administration can be adjusted based on the patient's medication profile to ensure safety. For a more technical breakdown of interaction mechanisms, a resource like DrugBank can be informative.

Comparison of Major Drug Interactions with Nitrous Oxide


Drug Class	Potential Interaction with Nitrous Oxide	Risk Level	Patient Considerations
Opioids	Increased sedation, respiratory depression, potential for overdose.	High	Close monitoring, potential for reduced nitrous oxide dose.
Benzodiazepines	Enhanced CNS depression, increased sedation, reduced respiratory rate.	High	Extreme caution, avoid concurrent use or significantly reduce dosages.
Antihypertensives	Exacerbated hypotension (low blood pressure).	Moderate to High	Pre-procedure medication adjustment may be necessary.
Stimulants (e.g., Amphetamines)	Increased blood pressure, risk of arrhythmia.	Moderate	Disclosure is essential for adjusting dosage and monitoring vital signs.
Methotrexate	Exacerbated B12/folate deficiency risk, potential hematologic issues.	Moderate	Assess B12 status; B12/folate supplementation may be needed.
Psychotropic Drugs	Exacerbation of underlying conditions, unpredictable CNS effects.	Low to Moderate	Consultation with a specialist and careful monitoring are advised.
Alcohol	Enhanced CNS depression, impaired judgment, overdose risk.	High	Advise patients to abstain before and after the procedure.

Conclusion

Nitrous oxide is a safe and effective agent for sedation and pain relief when administered by a trained professional. However, its safety is highly dependent on a patient's overall medication profile. A wide array of substances, including other CNS depressants, certain blood pressure medications, and recreational drugs, can interact with nitrous oxide, increasing the risk of adverse effects. Prior to any procedure involving nitrous oxide, patients should provide a complete and honest medical history to their provider. This transparent communication is the most critical step in preventing complications and ensuring a safe and successful medical or dental procedure. Understanding what medications interfere with nitrous oxide empowers patients to participate actively in their own healthcare and supports providers in delivering the safest possible treatment.

DrugBank - Nitrous oxide Drug Interactions

Frequently Asked Questions

While the interaction is generally considered minor, you should inform your doctor or dentist about all medications, including over-the-counter pain relievers like ibuprofen (Advil). This is crucial for a complete medical history, and any medication use prior to anesthesia should be discussed with a professional.

Combining nitrous oxide with alcohol is extremely dangerous. Alcohol and nitrous oxide are both CNS depressants, and their combined effect can lead to severe over-sedation, reduced breathing rate, unconsciousness, and an increased risk of suffocation.

Nitrous oxide can interfere with the body's metabolism of vitamin B12, particularly with repeated or prolonged exposure. It can lead to vitamin B12 deficiency, which can cause neurological and hematological issues. This is a concern for people with pre-existing low B12, like vegans.

Caution should be exercised if you take medication for anxiety, such as benzodiazepines. These drugs are CNS depressants, and the combination can lead to excessive sedation and respiratory issues. A consultation with your healthcare provider is necessary to assess the risk and adjust dosages if needed.

Interactions between nitrous oxide and psychiatric medications like antidepressants are possible, with some psychotropic drugs known to cause adverse effects. While not always severe, it is vital to inform your provider about your psychiatric medication regimen for a full risk assessment.

If you forget to mention a medication, you should inform your healthcare provider immediately, even if the procedure has already started. This allows them to monitor you for potential adverse reactions and take corrective action if necessary.

You should never stop or adjust your blood pressure medication without consulting your healthcare provider. Some blood pressure medications can increase the risk of hypotension when combined with nitrous oxide. Your provider may recommend a pre-procedure adjustment, but this must be done under their supervision.