These combinations are not usually physically harmful, but may produce undesirable effects. Use caution.
Note: Both substances potentiate the ataxia and sedation caused by the other, and may increase the risk of loss of consciousness at higher dosages. While unconscious, vomit aspiration is a risk if not placed in the recovery position. The combination may increase inhibition and risk of injury. Additionally, abuse of nitrous while under the influence of pregabalin may increase the risk of seizures. Medical dosages are unlikely to be a concern.
Substances in these categories
Nitrous
Pregabalin
Sources
- Glutamatergic Mechanisms Associated with Seizures and Epilepsy. Cold Spring Harbor Perspectives in Medicine, 5(8), a022863. — Barker-Haliski, M., & White, H. S. (2015)
- Pregabalin Pharmacology and Its Relevance to Clinical Practice. Epilepsia, 45(s6), 13–18. — Ben‐Menachem, E. (2004)
- Pregabalin. In StatPearls. StatPearls Publishing. — Cross, A. L., Viswanath, O., & Sherman, A. L. (2025)
- Recreational use of nitrous oxide causes seizure, pneumothorax, pneumomediastinum, and pneumopericardium: nitrous oxide and its harm, a case report. Upsala Journal of Medical Sciences, 128, 10.48101/ujms.v128.10281. — Davidson, L. T. (2023)
- Pregabalin monotherapy in patients with partial-onset seizures: A historical-controlled trial. Neurology, 82(7), 590–597. — French, J., Kwan, P., Fakhoury, T., Pitman, V., DuBrava, S., Knapp, L., & Yurkewicz, L. (2014)
- Aggravation of epilepsy by anti‐epileptic drugs. Developmental Medicine & Child Neurology, 48(5), 394–398. — Gayatri, N., & Livingston, J. (2006)
- Drugs that lower the seizure threshold. Adverse Drug Reaction Bulletin, 298(1), 1151–1154. — Hitchings, A. W. (2016)
- Pregabalin poisoning and rising recreational use: a retrospective observational series. British Journal of Clinical Pharmacology, 86(12), 2435–2440. — Isoardi, K. Z., Polkinghorne, G., Harris, K., & Isbister, G. K. (2020)
- Nitrous Oxide. In StatPearls. StatPearls Publishing. — Knuf, K., & Maani, C. V. (2025)
- Evidence that pregabalin reduces neuropathic pain by inhibiting the spinal release of glutamate. Journal of Neurochemistry, 113(2), 552–561. — Kumar, N., Laferriere, A., Yu, J. S. C., Leavitt, A., & Coderre, T. J. (2010)
- Pregabalin and paradoxical reaction of seizures in a large overdose. Toxicology Communications, 2(1), 19–20. — Slocum, G. W., Schult, R. F., Gorodetsky, R. M., Wiegand, T. J., Kamali, M., & Acquisto, N. M. (2018)
- Asphyxial Deaths from the Recreational Use of Nitrous Oxide. Journal of Forensic Sciences, 37(4), 1008–1015. — Wagner, S., Clark, M., Wesche, D., Doedens, D., & Lloyd, A. (1992)
Interaction Matrix
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These drugs work together to cause an effect greater than the sum of its parts. They aren't likely to cause an adverse or undesirable reaction when used carefully.
Effects are additive. The combination is unlikely to cause any adverse or undesirable reaction beyond those that might ordinarily be expected from these drugs.
One substance may reduce or counteract some of the effects of the other.
These combinations are not usually physically harmful, but may produce undesirable effects. Use caution.
There is considerable risk of physical harm when combining these substances. Use extreme caution.
These combinations are considered dangerous and should be avoided.
The interactions between these substances are not well documented.