You might have heard of ketamine therapy as an emerging form of mental health therapy. It’s often framed as a cure-all, capable of producing life-changing effects in people who haven’t seen success with other forms of treatment.
Clinical trials show that ketamine is helpful for people with treatment-resistant mood disorders, such as depression and bipolar disorder. “Treatment-resistant” means that other forms of therapy, like conventional antidepressants and talk therapy, haven’t improved a person’s symptoms.
But what is ketamine therapy, and is it worth the hype?
What is Ketamine?
Ketamine is a dissociative drug, which means that it makes people feel detached from reality.
At higher doses, ketamine quickly induces sedation and amnesia. The FDA approved ketamine as a medical anesthetic in 1970. The drug has been used in operating rooms for over 50 years. Ketamine is used for surgical procedures and pain management in adults, children, and animals. 1 2
Ketamine is also used in psychedelic-assisted psychotherapy. Studies have shown that ketamine improves symptoms of mood disorders like depression and bipolar disorder, although researchers are still investigating why. (One hypothesis is that ketamine changes levels of the neurotransmitter glutamate. 3) It’s legal for licensed clinicians to prescribe and administer ketamine for off-label use, which is why you’ll find ketamine clinics throughout the United States.
There’s also a complicated side to ketamine: Ketamine is a popular club drug. It has a history of use for sexual assault due to its ability to induce amnesia and sedation. Regular recreational use can increase a person’s tolerance and risk of psychological dependence. And ketamine abuse is associated with health risks like organ damage, particularly in the bladder and kidneys.
It’s essential to understand this drug’s full context as ketamine clinics become more popular. (In 2021, the New Yorker published an article titled: “Ketamine Therapy Is Going Mainstream. Are We Ready?”) Ketamine’s psychedelic effects are promising, but this drug is more of a tool in a therapeutic toolkit than a panacea for better health.
Below, we’ll look at ketamine therapy and how it works.
What is Ketamine Therapy?
Ketamine therapy uses low doses of ketamine, administered via an intravenous (IV) drip to produce a dissociative experience. Ketamine’s effects vary depending on the dose, set, and setting. Broadly, ketamine therapy can make a person experience the following:
- A sense of calm
- Visual and auditory hallucinations
That ’s a pretty extensive range. As with other psychedelic drugs, there’s no way to know how a person will react to ketamine. That’s one reason why ketamine shouldn’t be taken without medical supervision.
Although ketamine is also available in pill form, most research about its therapeutic benefits has focused on ketamine IV infusions. The FDA approved a ketamine nasal spray called Spravato (esketamine) for treatment-resistant depression in 2019. 4 There’s less research on esketamine’s effectiveness in treating depression compared to ketamine IV infusions.
How it works
It’s not entirely clear how ketamine works in the body. However, some researchers believe that ketamine’s antidepressant effects have to do with how it binds to receptors in the brain.
Your brain uses chemical messengers called neurotransmitters to send signals throughout your body. Normally, those neurotransmitters bind to specific receptors to do their jobs. However, ketamine temporarily blocks NMDA receptors, which increases the amount of the neurotransmitter glutamate in the brain. 5 3
When glutamate builds up, it triggers different signals in the brain and allows neurons to communicate with each other along new pathways. That process might affect cognition, mood, and thought patterns.
Ketamine is a “dirty drug,” which means it simultaneously acts on many different brain areas. Unfortunately, that multiplicity also means that we can’t say with absolute certainty how ketamine works because, well, science hasn’t gotten there yet.
Ketamine Therapy and Mental Issues
Even if we don’t know exactly how ketamine works, there’s strong evidence that this drug is a powerful tool for treatment-resistant mood disorders.
Depression and anxiety
Treatment-resistant depression is one of the most studied applications of non-surgical uses for ketamine.
In a double-blind, randomized, placebo-controlled study of ketamine infusion therapy in depressed patients, researchers found that ketamine therapy significantly improved depressive symptoms than those receiving a placebo after two weeks. 6 A 2020 study found that the optimal dose for ketamine’s antidepressant effects is 0.5?mg/kg and 1.0?mg/kg, far lower than anesthetic doses. 7
Ketamine’s therapeutic benefits might be related to its dissociative qualities. In 2014, a National Institute of Mental Health (NIMH) report found that dissociation predicted more robust and sustained antidepressant effects. 8
These findings are promising, considering that conventional antidepressant medication such as selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) have not been shown to improve a person’s long-term quality of life, according to a 2022 article published in PLOS One. 9
More recent research explores whether ketamine is a viable treatment option for post-traumatic stress disorder (PTSD). In a review article published in 2020, the authors noted that most of these studies focus on animal models, and more human studies are needed. 10
In a small proof-of-concept trial, a single dose of ketamine improved chronic PTSD symptoms 24 hours after infusion compared to the placebo group. Some participants noted improvements as long as two weeks after ketamine therapy. 11
A randomized controlled trial echoed these findings in 2021. Thirty people with chronic PTSD received six infusions of ketamine or a placebo. At the end of two weeks, the ketamine group showed more significant improvements in PTSD symptoms, including intrusive thoughts, avoidance, and negative mood. 12
Multiple meta-analyses conclude that ketamine also has antidepressant benefits for people with bipolar disorder. However, one study suggests the antidepressant effects are greater for people with major depressive disorder (also known as unipolar depression). 13 14
Preliminary research shows that ketamine infusions decrease suicidal ideation. 1516 That’s a significant finding because suicidality accounts for 15–20% of deaths in people with bipolar disorder. 17
That said, ketamine for bipolar disorder is understudied. More clinical trials are needed to understand ketamine’s benefits for bipolar disorder.
What Makes Ketamine Therapy Better than Other Medications?
For some people, ketamine’s rapid effects and dissociative qualities may make it more effective than other forms of treatment. However, ketamine therapy isn’t inherently better or worse than other medications.
Researchers have found that a single dose of ketamine improved depressive symptoms within 24 to 72 hours. 18 (Those improvements dissipate within two weeks if ketamine isn’t retaken.) In comparison, SSRIs can take up to six weeks to produce noticeable changes.
Ketamine doesn’t work for everyone. However, people who have been diagnosed with mood disorders may benefit from ketamine therapy if their symptoms haven’t improved with other forms of treatment. Talk to your doctor before making any decisions.
What to Expect from Ketamine Therapy
We’ve talked about how ketamine therapy works, but what happens during treatment? Generally, here’s what to expect from a ketamine clinic:
Before treatment: You’ll have an initial consult with a doctor to assess whether you’re eligible for ketamine therapy. Then, on the day of treatment, it’s common for clinics to monitor your vitals, like blood pressure and heart rate.
During treatment: Treatment usually occurs in a private space. Guided meditations, dim lights, and nonverbal music help a person let go and relax into the experience (an important part of set and setting). Ketamine is administered via an intramuscular (IM) shot or IV infusion, and most people start with a moderate dose.
During the infusion, you might experience various effects, like numbness, relaxation, hallucinations, and out-of-body experiences (at higher doses). It’s also possible to experience adverse effects, like agitation, amnesia, and nausea.
After treatment: Ketamine treatments last about one to two hours, and most people are back to baseline within three hours. Don’t plan on driving yourself home after receiving ketamine: It’s common to feel too groggy and tired to drive.
Depending on the ketamine clinic, you may have access to integration counseling. Integration is an essential part of psychedelic-assisted therapy because it allows you to reflect on and retain any insights from the experience.
Ketamine Therapy FAQs
Am I eligible for ketamine therapy?
You need a prescription for ketamine. If you have a diagnosed mood disorder, have already tried other treatment options, and don’t have any contraindications, you may be eligible for ketamine therapy.
Doctors tend not to accept patients who exhibit drug-seeking behavior or have a history of psychosis, drug abuse, or cardiovascular conditions.
What does ketamine therapy feel like?
Ketamine causes people to enter a dissociative state, which can feel different for everyone. Generally, ketamine therapy induces feelings of euphoria, sedation, and relaxation, coupled with visual and auditory hallucinations.
How much does ketamine therapy cost?
Cost varies widely. Health insurance generally doesn’t cover ketamine therapy because it’s considered off-label use. As a result, infusions can cost anywhere from $400 to thousands of dollars, depending on factors like dose, frequency, and location.
Is Ketamine Therapy Worth Trying?
Ketamine therapy is promising for people who have treatment-resistant mood disorders, such as depression and bipolar disorder. This drug’s antidepressant effects work quickly and take effect sooner than conventional antidepressant medications.
However, ketamine therapy isn’t right for everyone. Psychedelics aren’t recommended for people who have a history of psychotic disorders, substance abuse issues, or heart conditions, among other contraindications.
Talk to your doctor to see if ketamine therapy is right for you.
Things to Know
Ketamine therapy is effective for certain mood disorders
According to clinical trials, people with treatment-resistant depression may benefit from ketamine therapy. Preliminary research suggests ketamine therapy is also helpful for people who suffer from suicidality and bipolar disorder.
A licensed clinician must prescribe ketamine
- Ketamine is a Schedule III controlled substance in the United States, which means it can only be prescribed and administered by a licensed medical professional
- This drug is FDA-approved as a medical anesthetic
- Clinicians can prescribe ketamine off-label to help treat certain mood disorders
- A person isn’t eligible for ketamine therapy if they have a history of substance abuse issues or psychotic disorders
- Ketamine can increase a person’s heart rate and blood pressure, so it isn’t recommended for people with heart problems
- Usually, ketamine therapy isn’t covered by health insurance
Ketamine therapy is a little different for everyone
- Ketamine clinics might administer the drug with an IM shot or IV infusion
- Most clinics give patients private spaces for their session
- Soft lights, instrumental music, and guided meditations are common ways to ease into a session
- Ketamine therapy tends to last about an hour
- People return to baseline within three hours
- Integration is an important part of retaining any insights from the psychedelic experience
Ketamine therapy isn’t a magical cure-all
Ketamine acts on different parts of the brain than conventional antidepressants. However, ketamine doesn’t work for everyone. Nevertheless, it’s a promising tool in a person’s mental health toolkit and is best combined with other forms of therapy.
1. Gao M, Rejaei D, Liu H. Ketamine use in current clinical practice. Acta Pharmacol Sin. 2016;37(7):865-872. doi:10.1038/aps.2016.5
2. Brinck EC, Tiippana E, Heesen M, et al. Perioperative intravenous ketamine for acute postoperative pain in adults. Cochrane Database Syst Rev. 2018;12:CD012033. doi:10.1002/14651858.CD012033.pub4
3. Ingram R, Kang H, Lightman S, et al. Some distorted thoughts about ketamine as a psychedelic and a novel hypothesis based on NMDA receptor-mediated synaptic plasticity. Neuropharmacology. 2018;142:30-40. doi:10.1016/j.neuropharm.2018.06.008
4. FDA approves new nasal spray medication for treatment-resistant depression; available only at a certified doctor’s office or clinic | FDA. Accessed April 22, 2022. https://www.fda.gov/news-events/press-announcements/fda-approves-new-nasal-spray-medication-treatment-resistant-depression-available-only-certified
5. Jansen KL. A review of the nonmedical use of ketamine: use, users and consequences. J Psychoactive Drugs. 2000;32(4):419-433. doi:10.1080/02791072.2000.10400244
6. Singh JB, Fedgchin M, Daly EJ, et al. A Double-Blind, Randomized, Placebo-Controlled, Dose-Frequency Study of Intravenous Ketamine in Patients With Treatment-Resistant Depression. Am J Psychiatry. 2016;173(8):816-826. doi:10.1176/appi.ajp.2016.16010037
7. Fava M, Freeman MP, Flynn M, et al. Double-blind, placebo-controlled, dose-ranging trial of intravenous ketamine as adjunctive therapy in treatment-resistant depression (TRD). Mol Psychiatry. 2020;25(7):1592-1603. doi:10.1038/s41380-018-0256-5
8. Luckenbaugh DA, Niciu MJ, Ionescu DF, et al. Do the dissociative side effects of ketamine mediate its antidepressant effects? J Affect Disord. 2014;159:56-61. doi:10.1016/j.jad.2014.02.017
9. Almohammed OA, Alsalem AA, Almangour AA, Alotaibi LH, Al Yami MS, Lai L. Antidepressants and health-related quality of life (HRQoL) for patients with depression: Analysis of the medical expenditure panel survey from the United States. PLoS ONE. 2022;17(4):e0265928. doi:10.1371/journal.pone.0265928
10. Feder A, Rutter SB, Schiller D, Charney DS. The emergence of ketamine as a novel treatment for posttraumatic stress disorder. Adv Pharmacol. 2020;89:261-286. doi:10.1016/bs.apha.2020.05.004
11. Feder A, Parides MK, Murrough JW, et al. Efficacy of intravenous ketamine for treatment of chronic posttraumatic stress disorder: a randomized clinical trial. JAMA Psychiatry. 2014;71(6):681-688. doi:10.1001/jamapsychiatry.2014.62
12. Feder A, Costi S, Rutter SB, et al. A randomized controlled trial of repeated ketamine administration for chronic posttraumatic stress disorder. Am J Psychiatry. 2021;178(2):193-202. doi:10.1176/appi.ajp.2020.20050596
13. Matveychuk D, Thomas RK, Swainson J, et al. Ketamine as an antidepressant: overview of its mechanisms of action and potential predictive biomarkers. Ther Adv Psychopharmacol. 2020;10:2045125320916657. doi:10.1177/2045125320916657
14. McGirr A, Berlim MT, Bond DJ, Fleck MP, Yatham LN, Lam RW. A systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials of ketamine in the rapid treatment of major depressive episodes. Psychol Med. 2015;45(4):693-704. doi:10.1017/S0033291714001603
15. Bartoli F, Riboldi I, Crocamo C, Di Brita C, Clerici M, Carrà G. Ketamine as a rapid-acting agent for suicidal ideation: A meta-analysis. Neurosci Biobehav Rev. 2017;77:232-236. doi:10.1016/j.neubiorev.2017.03.010
16. Ballard ED, Ionescu DF, Vande Voort JL, et al. Improvement in suicidal ideation after ketamine infusion: relationship to reductions in depression and anxiety. J Psychiatr Res. 2014;58:161-166. doi:10.1016/j.jpsychires.2014.07.027
17. Wilkowska A, Sza?ach ?, Cuba?a WJ. Ketamine in bipolar disorder: A review. Neuropsychiatr Dis Treat. 2020;16:2707-2717. doi:10.2147/NDT.S282208
18. Krystal JH, Abdallah CG, Sanacora G, Charney DS, Duman RS. Ketamine: A paradigm shift for depression research and treatment. Neuron. 2019;101(5):774-778. doi:10.1016/j.neuron.2019.02.005