There is considerable risk of physical harm when combining these substances. Use extreme caution.
Note: Pregabalin and DXM may increase each other’s effects such as inhibition, dizziness, sedation. At higher doses this can lead to unexpected loss of consciousness. Both drugs have seizure concerns which is greatly increased in combination.
Substances in these categories
Dextromethorphan
Pregabalin
Sources
- Pregabalin (Lyrica) - Erowid Exp - “Heart Arrhythmia, Seizure : Not Recreational.” — Altair. (n.d.-a)
- 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 Suppl 6, 13–18. — Ben-Menachem, E. (2004)
- Pregabalin & Tramadol - Erowid Exp - “Grand Mal Seizures.” — Douke, R. (n.d.)
- Pregabalin monotherapy in patients with partial-onset seizures. 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 and Child Neurology, 48(5), 394–398. — Gayatri, N. A., & Livingston, J. H. (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)
- Dextromethorphan Toxicity. In StatPearls. StatPearls Publishing. — Journey, J. D., Agrawal, S., & Stern, E. (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)
- Dextromethorphan. In StatPearls. StatPearls Publishing. — Oh, S., Agrawal, S., Sabir, S., & Taylor, A. (2025)
- Pregabalin - Erowid Exp - “Stay Away.” — Sean. (n.d.-b)
- 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)
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.