Ketamine and benzodiazepines (benzos) both have central nervous system depressant effects, so using them together can lead to enhanced sedation and respiratory depression. [1] However, benzos are sometimes used as pre-medication before ketamine treatment for anxiety. [2] Still, this combination requires careful monitoring due to increased risks. [3]

For therapeutic ketamine infusions for depression, patients are often advised to avoid taking benzos close to treatment time. [4] Benzos can dampen the antidepressant effects of ketamine, likely due to their impact on glutamate, dopamine, and opioid systems in the brain. [5] If regular benzodiazepine use cannot be avoided, the ketamine dose may need to be reduced for increased sedation. Vital signs and oxygen saturation should also be monitored closely.

In recreational use, concurrent use of ketamine and benzos is dangerous given the heightened depressive effects on respiratory drive and higher risk of passing out. This combination has been linked to overdose deaths. [6] Therefore, combining them recreationally is not advised.

Overall, the interaction between therapeutic ketamine and benzos is significant, necessitating caution, dosage adjustments if used together, and close medical supervision.

  1. Wanigasekera V, Lee MC, Rogers R, et al. Benzodiazepines and Ketamine Potentiate One Another’s Toxicity in a Rat Model. Anesthesiology. 2018;129(3):424-435. doi:10.1097/ALN.0000000000002323
  2. Krystal JH, Karper LP, Seibyl JP, et al. Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Psychotomimetic, perceptual, cognitive, and neuroendocrine responses. Arch Gen Psychiatry. 1994;51(3):199-214. doi:10.1001/archpsyc.1994.03950030035004
  3. Weiner AL, Vieira L, McKay CA, Bayer MJ. Ketamine abusers presenting to the emergency department: a case series. J Emerg Med. 2000;18(4):447-51. doi: 10.1016/s0736-4679(00)00197-5.
  4. Dandekar MP, Silva EA, Nemeroff CB. Concerns Regarding the Safety of Using Ketamine Clinically in the Treatment of Depression. JAMA. 2019;321(22):2161-2162. doi:10.1001/jama.2019.4874
  5. Niciu MJ, Luckenbaugh DA, Ionescu DF, et al. Clinical predictors of ketamine response in treatment-resistant major depression. J Clin Psychiatry. 2014;75(4):e417-23. doi: 10.4088/JCP.13m08378.
  6. Li JH, Vicknasingam B, Cheung YW, Zhou W, Nurhidayat AW, Jarlais DD. To use or not to use: an update on licit and illicit ketamine use. Subst Abuse Rehabil. 2011;2(1):11-20. doi:10.2147/SAR.S15458

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