At our integrative psychiatry and neurologic health clinic, Neuregen, located in Scottsdale, Arizona, we frequently utilize ketamine to treat a range of mental health and brain conditions, including depression, PTSD, chronic pain, and brain injury.
Below, we answer 30 of the most common questions about ketamine therapy, drawing on current scientific evidence and our experience gained from clinical practice, using ketamine near daily as a therapeutic agent. In each response below, we have attempted to provide medically, accurate, and evidence-based information in simple terms. We hope this is helpful!
1. What is ketamine therapy?
Ketamine therapy involves the medical use of ketamine, an anesthetic originally developed in the 1960s, to treat conditions like depression, anxiety, and chronic pain. It is administered in sub-anesthetic doses, often via intravenous (IV) infusions, to promote rapid symptom relief (Zorumski et al., 2019). However, the term ‘ketamine therapy’ can mean different things as ketamine has been used in different ways. For example, it can mean ‘ketamine infusions’, ‘ketamine used in conjunction with psychotherapy (ketamine-assisted psychotherapy), and even ‘ketamine used as a nasal spray’. The point is that ketamine is used in different ways to treat different conditions and thus ‘ketamine therapy’ can look different in different settings.
2. How many ketamine treatments are needed for depression?
Other than for anesthesia, ketamine has likely been explored for depression more than any other condition. As an illustration, a search on PubMed using the terms "ketamine" and "depression" yields over 1,000 results, indicating a substantial body of research on this topic. As such, various studies utilize different protocols. That said, as a “rule of thumb”, most protocols recommend an initial series of six infusions over two to three weeks, followed by maintenance treatments as needed. Studies suggest this schedule provides the most consistent antidepressant effects (McIntyre et al., 2021). The point is that multiple applications of ketamine should be expected when treating a chronic condition like depression or chronic pain.
3. When was ketamine first used for depression?
While anesthesiologists were likely observing the antidepressant effects of ketamine “by accident” for years, Ketamine’s antidepressant effects were formally reported in 2000 in a landmark study by Berman et al., demonstrating rapid symptom relief in treatment-resistant depression (Berman et al., 2000).
4. How many ketamine infusions are needed for chronic pain?
Chronic pain protocols often require a longer series of infusions, typically ranging from 6 to 10 treatments, depending on the condition's severity and the patient’s response (Cohen et al., 2018).
5. How many ketamine infusions for CRPS?
Patients with Complex Regional Pain Syndrome (CRPS) may require up to 10 infusions over a few weeks. Some studies suggest this helps reset pain pathways in the brain (Schwartzman et al., 2011).
6. Can ketamine help with anxiety?
Yes, ketamine has shown promise in treating anxiety disorders, including generalized anxiety disorder (GAD) and social anxiety. It works by modulating glutamate pathways, leading to rapid anxiolytic effects (Glue et al., 2018).
7. When did ketamine become popular?
Ketamine became popular in mental health treatment following groundbreaking research in the early 2000s, which highlighted its rapid antidepressant effects in treatment-resistant depression. Specifically, ketamine's ability to relieve depressive symptoms within hours, was highlighted as a significant contrast to traditional antidepressants that often take weeks to work (Berman et al., 2000).
Its popularity surged further in 2019 when the FDA approved esketamine (Spravato), a nasal spray derived from ketamine, for treatment-resistant depression (Zarate et al., 2017; FDA, 2019). This approval brought ketamine-based treatments into the mainstream and catalyzed interest in its broader mental health applications, including anxiety, PTSD, and addiction therapy.
Ketamine gained popularity as a mental health treatment after the FDA approved a derivative, esketamine (Spravato), in 2019 for treatment-resistant depression (Zarate et al., 2017).Of course, social interest was also spurred by a recent, ‘psychedelic renaissance’, which has seen a broad push for regulatory approval for mainstream medical applications of “psychedelic” agents like ketamine.
8. Can ketamine help with addiction?
Preliminary studies suggest ketamine may help reduce cravings and promote abstinence in substance use disorders, possibly by enhancing neuroplasticity and emotional processing (Dakwar et al., 2019).
9. Can ketamine improve memory?
While ketamine’s effects on memory are complex, low doses may enhance cognitive flexibility and emotional memory processing. However, it has also been suggested that higher doses can impair short-term memory (Morrison et al., 2019).
10. Ketamine: Where does it come from?
Ketamine was synthesized in 1962 by Dr. Calvin Stevens and approved for medical use in the U.S. in 1970. It is derived from phencyclidine (PCP), with a safer pharmacological profile (Domino, 2010).
11. What does ketamine feel like?
Patients often report a sense of detachment, euphoria, or dream-like states during infusions. These effects, known as dissociation, are temporary and managed in clinical settings (Luckenbaugh et al., 2014). However, the experience of ketamine can vary dramatically when doses are adjusted. For example, a higher dose infusion is far more likely to produce “psychedelic” type experiences, than a lower dose sublingual (oral) application for example, which may only produce a sense of being “enhanced” or “buzzed”.
12. Are ketamine treatments safe?
When administered under medical supervision, ketamine is generally safe. Common side effects include nausea, dizziness, and mild dissociation, which resolve quickly (Short et al., 2018). As an anesthetic ketamine is viewed favorably, largely because it does not exhibit cardio- or respiratory-depressive effects at therapeutic doses (i.e., it doesn’t slow the heart or breathing, like many other anesthetic agents) (Zacny et al., 1994).
13. How does ketamine work in the brain?
Ketamine blocks NMDA receptors, leading to increased glutamate activity. This enhances neuroplasticity and promotes the formation of new neural connections, crucial for mood regulation (Zorumski et al., 2019).
14. How does ketamine therapy work?
Ketamine therapy involves administering sub-anesthetic doses, often through IV, intranasal, intramuscular, or oral routes. It targets treatment-resistant symptoms by rapidly altering brain chemistry (McIntyre et al., 2021). In simple terms, it raises brain activity and promotes new connections in the brain, which generally makes people feel better.
15. How does ketamine help depression?
Ketamine’s rapid antidepressant effects stem from its ability to enhance neuroplasticity and regulate overactive glutamate systems, providing relief within hours (Zarate et al., 2006). Neuroplasticity might be thought of as “ramping up brain function” and “promoting new connections in the brain”, especially in areas of the brain that are thought to be “low functioning” in many cases of depression.
16. Can ketamine make depression worse?
While rare, some patients may experience transient mood disturbances or dissociation. Close monitoring and tailored dosing minimize these risks (McIntyre et al., 2021). The possibility that ketamine might make mental health symptoms worse is why we are very much in favor of ketamine being administered and overseen by psychiatry-trained professionals. In our view, if it is being used for mental health benefits and if it holds even a slightly chance of making mental health symptoms worse, patients undergoing ketamine therapy should be monitored by professionals trained in the medical management of psychiatric concerns.
17. Can ketamine cause anxiety?
Ketamine’s dissociative effects can occasionally trigger anxiety, but this is typically short-lived and manageable in a clinical setting (Luckenbaugh et al., 2014).
18. What does ketamine do to the brain?
Ketamine enhances synaptic connectivity and neuroplasticity, counteracting the effects of chronic stress and depression on the brain (Zorumski et al., 2019). While ketamine is in the system, the brain is excited in certain areas and is more likely to form new connections. This elevated level of activity and the formation of new connections can be very helpful in a range of brain conditions and mental health challenges.
19. Where did ketamine come from?
Ketamine was developed as an anesthetic alternative to PCP, offering a safer profile for medical use (Domino, 2010).
20. Can ketamine cause seizures?
Ketamine is not typically associated with seizures and may even have anticonvulsant properties. However, caution and careful observation is advised in patients with epilepsy (Löscher et al., 2021).
21. What is ketamine used for?
Ketamine is used for anesthesia, depression, anxiety, chronic pain, PTSD, and off-label for other conditions like OCD (Zarate et al., 2017).
22. Can ketamine cause panic attacks?
Though rare, dissociative effects might provoke panic in predisposed individuals. Proper patient screening and monitoring reduce this risk (Short et al., 2018).
23. Will ketamine show up on a drug test?
Standard drug tests do not typically screen for ketamine. Specialized tests can detect it, but this is uncommon (Chhabra et al., 2018).
24. Will ketamine make you sleepy?
Ketamine can cause mild sedation, but it is not a primary sedative. Patients may feel relaxed or slightly tired after treatment (Luckenbaugh et al., 2014).
25. How long does ketamine stay in the system?
Ketamine is metabolized quickly, with effects lasting a few hours. Traces can be detected in urine for up to 72 hours (Chhabra et al., 2018).
26. How long does ketamine last?
The antidepressant effects of ketamine can last from days to weeks after a single infusion, depending on individual response (Zarate et al., 2006).
27. Can ketamine cause constipation?
Constipation is not a common side effect of ketamine. Patients should report any unusual gastrointestinal symptoms to their provider (Short et al., 2018).
28. Why is ketamine contraindicated in hypertensive patients?
Ketamine can transiently raise blood pressure, posing risks for hypertensive patients. Careful monitoring and pre-treatment assessment mitigate this risk (Cohen et al., 2018). In the medical setting, you should always expect to have your blood pressure and pulse monitored during ketamine therapy.
29. Is ketamine therapy legal?
Yes, ketamine therapy is legal in the U.S. when administered by licensed providers for approved medical indications (McIntyre et al., 2021). The administration of ketamine falls within the scope of anesthesiologists (because it is an anesthetic) and psychiatry-trained professionals (because it affects psychiatric conditions).
30. Are ketamine infusions covered by insurance?
Coverage varies for ketamine. IV, intramuscular, and oral (sublingual) ketamine, applied in the context of ketamine therapy and ketamine-assisted-psychotherapy (KAP) is typically out-of-pocket (private pay) (Zorumski et al., 2019).
About the author: Dr. David George of Neuregen Integrative Psychiatry & Neurologic Health Clinic in Scottsdale, Arizona, is a clinician, clinical researcher, and early adopter of Ketamine as a therapeutic agent. Neuregen attends to a wide range of clients, ranging from those suffering from persistent symptoms of brain injury (e.g., concussion), dysautonomia (e.g., POTS), chronic pain (e.g., post-surgical, and complex regional pain), and mental health issues (e.g., PTSD, depression, and anxiety disorders).
References
Berman, R. M., Cappiello, A., Anand, A., et al. (2000). Antidepressant effects of ketamine in depressed patients. Biological Psychiatry, 47(4), 351-354.
Cohen, S. P., Bhatia, A., & Buvanendran, A. (2018). Ketamine infusions for chronic pain and depression: Innovations and recommendations. Journal of Clinical Pain, 34(7), 620-631.
Dakwar, E., Hart, C. L., Levin, F. R., et al. (2019). Therapeutic infusions of ketamine: Dose-response model for substance use disorders. American Journal of Psychiatry, 176(2), 111-122.
Domino, E. F. (2010). Taming the ketamine tiger. Anesthesiology, 113(3), 678-684.
Glue, P., Neehoff, S., & Medlicott, N. J. (2018). Ketamine's role in anxiety disorders: A rapid review. CNS Drugs, 32(4), 329-342.
McIntyre, R. S., Rodrigues, N. B., Lee, Y., & Lipsitz, O. (2021). The efficacy of ketamine in depression: A systematic review. The American Journal of Psychiatry, 178(9), 840-851.
Schwartzman, R. J., Alexander, G. M., & Grothusen, J. R. (2011). Ketamine in CRPS: An exploratory analysis. Pain Medicine, 12(6), 927-936.
Zarate, C. A., Singh, J. B., Carlson, P. J., et al. (2006). A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Archives of General Psychiatry, 63(8), 856-864.
Zorumski, C. F., Gross, C., & Paul, E. (2019). NMDA receptor modulators and the treatment of depression. Neuropsychopharmacology, 44(4), 211-218.
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