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Nitrous oxide (drug interactions)

Nitrous oxide, commonly known as laughing gas, is a widely used anesthetic and analgesic agent, particularly in dental and medical settings. However, it has notable drug interactions that can lead to significant health implications, particularly concerning vitamin B12 deficiency. This deficiency can be exacerbated in individuals who already have low levels of B12, such as vegetarians or healthcare professionals frequently exposed to nitrous oxide. The deficiency can also affect folate levels, making supplementation of both vitamins important to prevent complications.

Over sixty medications have been identified to interact with nitrous oxide, with interactions ranging from moderate to severe. Certain substances, including alcohol, sedatives, antihistamines, and psychotropic medications, are known to pose particularly serious risks. Additionally, certain populations, such as individuals with severe cardiac disorders, pregnant women in their first trimester, or those with specific medical conditions like pulmonary hypertension, should avoid nitrous oxide altogether. Discussing all medications and health conditions with a healthcare provider prior to using nitrous oxide is crucial for safe administration.

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DEFINITION: Gas used as a local anesthetic in dentistry and in certain phases of cardiac bypass surgery.

  • INTERACTIONS: Folate, vitamin B12, alcohol, sedatives, antihistamines, psychotropic medications

Folate and Vitamin B12

Effect: Supplementation Possibly Helpful

Nitrous oxide can occasionally cause significant vitamin B12 deficiency, especially in people who are already borderline deficient in the vitamin (vegetarians, for example) or in such persons as dentists and anesthesiologists, who are frequently exposed to the gas. The effect on B12 impacts folate, too.

Taking folate and B12 supplements at the US Dietary Reference Intake (formerly known as the Recommended Dietary Allowance) levels should prevent any problems from developing.

Nitrous oxide is known to interact with many other medications, and many of these interactions are considered moderate to severe. Patients should discuss all medications with their doctors and dentists before receiving nitrous oxide. Alcohol, sedatives, antihistamines, and psychotropic medications are known to cause especially severe interactions with nitrous oxide. Further, patients with severe cardiac disorders, women in the first trimester of pregnancy, and people suffering from conditions such as pulmonary hypertension or small bowel obstruction should not be administered nitrous oxide.


Bibliography

Alai, Ally N. “Nitrous Oxide Administration: Overview, Indications, Contraindications.” Medscape Reference, 29 Oct. 2022, emedicine.medscape.com/article/1413427-overview?form=fpf. Accessed 12 Dec. 2025.

Ermens, A. A., et al. "Monitoring Cobalamin Inactivation During Nitrous Oxide Anesthesia by Determination of Homocysteine and Folate Plasma and Urine." Clinical Pharmacology and Therapeutics, vol. 49, 1991, pp. 385-93.

Flippo, T. S., and W. D. Holder Jr. "Neurologic Degeneration Associated with Nitrous Oxide Anesthesia in Patients with Vitamin B12 Deficiency." Archives of Surgery, vol. 128, 1993, pp. 1391-95.

Knuf, Kayla, and Christopher V. Maani. "Nitrous Oxide - StatPearls." NCBI, 28 Aug. 2023, www.ncbi.nlm.nih.gov/books/NBK532922. Accessed 12 Dec. 2025.

“Nitrous Oxide Drug Interactions.” Drugs.com, www.drugs.com/drug-interactions/nitrous-oxide-index.html. Accessed 12 Dec. 2025.

“Nitrous Oxide (Laughing Gas).” Cleveland Clinic, 20 Nov. 2023, my.clevelandclinic.org/health/treatments/nitrous-oxide-laughing-gas. Accessed 12 Dec. 2025.

Full Article

DEFINITION: Gas used as a local anesthetic in dentistry and in certain phases of cardiac bypass surgery.

  • INTERACTIONS: Folate, vitamin B12, alcohol, sedatives, antihistamines, psychotropic medications

Folate and Vitamin B12

Effect: Supplementation Possibly Helpful

Nitrous oxide can occasionally cause significant vitamin B12 deficiency, especially in people who are already borderline deficient in the vitamin (vegetarians, for example) or in such persons as dentists and anesthesiologists, who are frequently exposed to the gas. The effect on B12 impacts folate, too.

Taking folate and B12 supplements at the US Dietary Reference Intake (formerly known as the Recommended Dietary Allowance) levels should prevent any problems from developing.

Nitrous oxide is known to interact with many other medications, and many of these interactions are considered moderate to severe. Patients should discuss all medications with their doctors and dentists before receiving nitrous oxide. Alcohol, sedatives, antihistamines, and psychotropic medications are known to cause especially severe interactions with nitrous oxide. Further, patients with severe cardiac disorders, women in the first trimester of pregnancy, and people suffering from conditions such as pulmonary hypertension or small bowel obstruction should not be administered nitrous oxide.


Bibliography

Alai, Ally N. “Nitrous Oxide Administration: Overview, Indications, Contraindications.” Medscape Reference, 29 Oct. 2022, emedicine.medscape.com/article/1413427-overview?form=fpf. Accessed 12 Dec. 2025.

Ermens, A. A., et al. "Monitoring Cobalamin Inactivation During Nitrous Oxide Anesthesia by Determination of Homocysteine and Folate Plasma and Urine." Clinical Pharmacology and Therapeutics, vol. 49, 1991, pp. 385-93.

Flippo, T. S., and W. D. Holder Jr. "Neurologic Degeneration Associated with Nitrous Oxide Anesthesia in Patients with Vitamin B12 Deficiency." Archives of Surgery, vol. 128, 1993, pp. 1391-95.

Knuf, Kayla, and Christopher V. Maani. "Nitrous Oxide - StatPearls." NCBI, 28 Aug. 2023, www.ncbi.nlm.nih.gov/books/NBK532922. Accessed 12 Dec. 2025.

“Nitrous Oxide Drug Interactions.” Drugs.com, www.drugs.com/drug-interactions/nitrous-oxide-index.html. Accessed 12 Dec. 2025.

“Nitrous Oxide (Laughing Gas).” Cleveland Clinic, 20 Nov. 2023, my.clevelandclinic.org/health/treatments/nitrous-oxide-laughing-gas. Accessed 12 Dec. 2025.

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