By now, you’ve probably heard of ketamine. It’s often described as a “miracle drug” for people living with major depressive disorder (MDD), particularly treatment-resistant depression (TRD) and post-traumatic stress disorder (PTSD). [1, 2]
But you may not yet know about ketamine’s potentially significant effects on sleep. This article will explore everything you need to know about ketamine and sleep.
What is ketamine?
Ketamine is an anesthetic (tranquilizer) and mental health medication that blocks N-methyl-D-aspartate (NMDA) receptors in the brain. [1] Ketamine therapy, meanwhile, is a form of mental health treatment that combines the use of ketamine with therapy sessions, under doctor supervision.
Because of its effects on NMDA, ketamine “can make one experience dissociation and sedation, which can be therapeutic,” says Niloufar Esmaeilpour, founder and clinical director of Lotus Therapy & Counseling Centre in British Columbia, Canada.
How does ketamine work?
NMDA is responsible for allowing neurons in the synapses within your brain to communicate and work in concert with the perception of pain and making memories. [3]
By blocking NMDA, ketamine has both sedative and stimulatory effects. This means it can have significant effects on your sleep. [4]
Ketamine historically has been administered intravenously (IV). [5]
“However, many doctors now prefer intramuscular injection as it is easier to dose and administer and causes fewer adverse effects,” says Jared L. Ross, DO, president and founder of the medical education and consulting firm EMSEC, LLC, in Sedalia, Mo.
Ross explains that ketamine also can be administered via lozenges that are dissolved under the tongue, or via rectal suppositories.
Ketamine should be taken only under the guidance of a medical professional.
“Careful medical assessment and a review of medical history with the attending health provider have to be done before treatment with ketamine,” says Esmaeilpour.
Ketamine and sleep: What’s the connection?
“Ketamine has been shown to have significant negative short-term effects on sleep,” says Ross, “including increased time to fall asleep, decreased total sleep, decreased REM sleep, decreased slow-wave sleep, and decreased sleep quality.” [6]
For this reason, he recommends that people with sleep disturbances avoid ketamine after 12 pm.
Ketamine and depression
Ketamine has rapid-acting antidepressant activity, Esmaeilpour says.
According to a review of the research on ketamine reported in the journal Progress in Neurobiology, “The discovery of ketamine’s rapid antidepressant effects is arguably one of the most substantial advances in modern psychiatry.” [7]
The review notes that, in contrast to conventional antidepressant drugs that may require months of daily use before seeing results, a single infusion of ketamine “often relieves symptoms in mere hours” and its antidepressant effects typically last for up to a week. [7]
Ketamine and sleep disorders
Because depression tends to alter a person’s sleeping pattern, leading to problems like insomnia or hypersomnia (excessive sleep), Esmaeilpour adds that ketamine’s sedative characteristics “might be sleep-promoting for some patients.”
She cautions, however, that “its effects on sleep architecture, such as the distribution of sleep stages across the night, vary widely among individuals.”
When depression is the primary reason for poor sleep, a 2023 literature review states ketamine can improve sleep. [8] But for those with such sleep disorders as narcolepsy or sleep apnea, Ross says ketamine is “unlikely to help.”
Esmaeilpour says ketamine is “generally not a good idea” with regard to sleep disorders.
“Sleep apnea relates to respiratory functions,” she says, “whereas narcolepsy is all about neurological functions, and the primary effects of ketamine do not deal with the underlying causes of these two sleep disorders.” [9]
Ketamine and insomnia
“Ketamine may worsen insomnia in most patients by decreasing slow-wave and REM sleep, and decreasing sleep quality,” Ross says. [6] “However, in patients with insomnia due to major depressive disorder (MDD), specifically treatment-resistant depression (TRD) and post-traumatic stress disorder (PTSD), ketamine can be very helpful.” [2]
Esmaeilpour adds that ketamine may give some temporary relief to insomnia due to its sedative effect—but its long-term effects on sleep patterns are unpredictable, making it a double-edged sword. [8, 10]
She adds that some people may get “rebound insomnia” when the drug effects wear off. [11]
Ketamine and REM sleep
Ross says ketamine decreases REM sleep and slow-wave sleep, the deepest level of non-REM sleep. [6]
“The effects of ketamine on REM sleep are important,” Esmaeilpour says, “because this stage is essential to emotional and cognitive health. It has been noted that ketamine depresses the REM stage of sleep during the initial hours after administration.”
This could serve to interrupt the normal sleep cycle and affect the restorative properties of sleep, notes Esmaeilpour, “though the clinical significance of these effects does vary.”
Risks of ketamine
It’s important to emphasize that ketamine is a powerful drug and should only be used under medical supervision. It can have severe adverse effects.
“Ketamine can cause significant nausea and vomiting,” Ross says, especially when administered by IV or in lozenges under the tongue. [12] “Some patients experience an emergence reaction where they get confused and agitated as the ketamine is wearing off.” [13]
He adds that other adverse effects such as increased saliva production and decreased breathing “are very rare.”
Some people should avoid ketamine altogether.
“Ketamine can trigger psychosis in patients who are at increased risk,” Ross says. “People with a strong family history of psychosis (such as schizophrenia) or serious mood disorders (such as bipolar disorder) might want to avoid ketamine.” [13]
He adds that people with well-controlled schizophrenia or bipolar disorder should avoid ketamine as well. He notes, though, that “ketamine is frequently used to treat acute exacerbations of schizophrenia and bipolar disorder.” [13]
Esmaeilpour says people considering ketamine also need to be informed about side effects. Common ones include dissociation, dizziness, nausea, and an increase in blood pressure. [12]
She adds that “the probability of psychological effects, such as hallucinations or altered perception” is just as high as the other side effects.
“Depending on the dose and response of the individual, the side effects may be intense but very short-lived,” says Esmaeilpour. Those with a history of substance abuse, as well as severe psychiatric disorders, may be predisposed to serious adverse events.
She adds that “individuals with uncontrolled hypertension or at risk of glaucoma may need to avoid ketamine because of its potential to worsen these conditions.” [14, 15]
People who have any issues with their bladder or severe addiction issues should avoid ketamine, says Abigail Lev, PsyD, a San Francisco-based clinical psychologist who provides ketamine-assisted therapy with the Bay Area CBT Center. [11, 16]
She stresses that the drug should be taken in moderation and with a physician’s assistance, “and be very careful because it can become addictive and should not be abused.”
If you believe ketamine therapy may be right for you, then begin your search for a qualified medical provider here.
FAQs
What’s the link between ketamine and sleep enhancements?
”Using ketamine together with zolpidem may increase side effects such as dizziness, drowsiness, confusion, difficulty concentrating, excessive sedation, and respiratory depression,” according to drugs.com. [17] “Some people, especially the elderly, may also experience impairment in thinking, judgment, and motor coordination.”
The Cleveland Clinic also warns not to combine ketamine with other medications that can make you drowsy such as sleep medications, anti-anxiety medications, narcotic pain medications, or alcohol. [18]
Can ketamine be used to treat sleep disorders?
Ketamine isn’t typically used to treat sleep disorders, such as narcolepsy or sleep apnea. It’s used, however, to treat mental health disorders that commonly interfere with your ability to get a good night’s sleep.
Are there any side effects of using ketamine for sleep?
It’s important to understand that ketamine isn’t a sleep aid, per se, but rather a drug used to treat depression and PTSD that can interfere with sleep.
What’s the best way to sleep with anxiety? Check out our guide to anxiety and sleep for expert advice.
References
- Matveychuk, D., Thomas, R. K., Swainson, J., Khullar, A., MacKay, A., Baker, G. B., & Dursun, S. M. (2020). Ketamine as an antidepressant: Overview of its mechanisms of action and potential predictive biomarkers. Therapeutic Advances in Psychopharmacology, 10, 2045125320916657. https://doi.org/10.1177/2045125320916657
- Almeida, T. M., Pires, J. P., Borges, I. N., Muniz Martins, C. R., Cordeiro, Q., & Uchida, R. R. (2024). Effectiveness of Ketamine for the Treatment of Post-Traumatic Stress Disorder – A Systematic Review and Meta-Analysis. Clinical Neuropsychiatry, 21(1), 22. https://doi.org/10.36131/cnfioritieditore20240102
- Dupuis, J. P., Nicole, O., & Groc, L. (2023). NMDA receptor functions in health and disease: Old actor, new dimensions. Neuron, 111(15), 2312-2328. https://doi.org/10.1016/j.neuron.2023.05.002
- Li, L., & Vlisides, P. E. (2016). Ketamine: 50 Years of Modulating the Mind. Frontiers in Human Neuroscience, 10, 226940. https://doi.org/10.3389/fnhum.2016.00612
- Mion, Georges. History of anaesthesia: The ketamine story – past, present and future. European Journal of Anaesthesiology 34(9):p 571-575, September 2017. | DOI: 10.1097/EJA.0000000000000638
- Wang, Y., Melgers, M., Meijer, J. H., & Deboer, T. (2023). Comparison of sleep deprivation and a low dose of ketamine on sleep and the electroencephalogram in Brown Norway rats. Journal of Sleep Research, 32(5), e13863. https://doi.org/10.1111/jsr.13863
- Alitalo, O., Saarreharju, R., Henter, I. D., Kohtala, S., & Rantamäki, T. (2021). A wake-up call: Sleep physiology and related translational discrepancies in studies of rapid-acting antidepressants. Progress in Neurobiology, 206, 102140. https://doi.org/10.1016/j.pneurobio.2021.102140
- Kwaśny, A., Włodarczyk, A., Ogonowski, D., & Cubała, W. J. (2023). Effect of Ketamine on Sleep in Treatment-Resistant Depression: A Systematic Review. Pharmaceuticals, 16(4), 568. https://doi.org/10.3390/ph16040568
- Titone, M. K., Hunt, C., Bismark, A., Nokes, B., Lee, E., Ramanathan, D., Park, J., & Colvonen, P. (2023). The effect of obstructive sleep apnea severity on PTSD symptoms during the course of esketamine treatment: a retrospective clinical study. Journal of Clinical Sleep Medicine, 19(12), 2043–2051. https://doi.org/10.5664/jcsm.10746
- United States Drug Enforcement Administration. Ketamine. https://www.dea.gov/factsheets/ketamine
- American Addiction Centers. Ketamine Withdrawal Symptoms, Timeline, and Detox Treatment. https://americanaddictioncenters.org/withdrawal-timelines-treatments/ketamine
- Andrade C. (2019). Oral Ketamine for Depression, 2: Practical Considerations. The Journal of clinical psychiatry, 80(2), 19f12838. https://doi.org/10.4088/JCP.19f12838
- Aroke, E. N., Crawford, S. L., & Dungan, J. R. (2017). Pharmacogenetics of Ketamine-Induced Emergence Phenomena: A Pilot Study. Nursing Research, 66(2), 105. https://doi.org/10.1097/NNR.0000000000000197
- Ansari, M., Pittman, B., Tylee, D. S., Ostroff, R., Wilkinson, S. T., & Nikayin, S. (2024). Blood pressure changes during ketamine infusion for the treatment of depression. General hospital psychiatry, 90, 62–67. https://doi.org/10.1016/j.genhosppsych.2024.07.001
- EyeWiki. Sedation for ER ophthalmic evaluation. https://eyewiki.org/Sedation_for_ER_Ophthalmic_Evaluation
- Lamers, G., Van Dyck, J., Schapmans, S., De Coster, K., Mortier, D., & Zabegalina, N. (2022). Ketamine-induced uropathy: A diagnostic pitfall in an increasing healthcare issue in youngsters. Urology Case Reports, 42, 102019. https://doi.org/10.1016/j.eucr.2022.102019
- Drugs.com. Drug Interactions between Ambien and ketamine. https://www.drugs.com/drug-interactions/ambien-with-ketamine-2333-1544-1411-0.html
- Cleveland Clinic. Ketamine injection. https://my.clevelandclinic.org/health/drugs/18102-ketamine-injection
