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Medical Uses of Ketamine + New Research (incl. Depression)

Written by Puya Yazdi, MD | Last updated:
Jonathan Ritter
Matt Carland
Medically reviewed by
Jonathan Ritter, PharmD, PhD (Pharmacology), Matt Carland, PhD (Neuroscience) | Written by Puya Yazdi, MD | Last updated:

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Ketamine is a medication used primarily as an anesthetic. Some early evidence also suggests that it may have the potential for treating a variety of other health conditions, although these uses have not been fully approved yet. Read on to learn more about the medical uses of and new research about this drug.

Disclaimer: This post is not an endorsement or recommendation for the use of ketamine under any circumstances, except when prescribed and used under supervision by a qualified medical professional. We have written this post for informational purposes only, and our goal is solely to educate people about the potential medical uses of ketamine, as well as the science behind its effects and mechanisms.

What is Ketamine?

Ketamine – sometimes also known as Ketalar or Ketaject – is a drug that initiates and maintains anesthesia [1].

The original compound was first discovered in the early 1960s and was approved for use in the United States in 1970. Now it is considered by the World Health Organization (WHO) as one of the safest and most essential drugs in the healthcare system [2].

Ketamine is considered a Schedule III controlled substance by the FDA, which means that it requires a written, oral, or electronic prescription to legally buy or possess the drug [3].

Ketamine is also classified as a “dissociative” drug, which means that it alters the senses, leading to hallucinations and feelings of detachment from the environment and oneself [1].

Unfortunately, these dissociative effects are why some people abuse ketamine for recreational purposes – even in spite of the many risks and dangers that are associated with ketamine abuse. For this reason, ketamine has a significant and well-documented potential for abuse and addiction [4, 5].

Ketamine is an anesthetic drug that was discovered in the 1960s. It is a schedule III controlled substance, meaning that it requires a doctor’s prescription to legally buy or possess it.

Dangers of Ketamine

Like any drug, ketamine has a number of potential adverse side-effects that are important to be aware of. To learn about the side effects, drug interactions, and other potential dangers of ketamine, check out this post.

Official Medical Uses of Ketamine

Ketamine has a number of accepted medical uses for treating certain specific medical conditions and situations. Although this means that the evidence for its efficacy in these conditions is relatively solid, always keep in mind that this is a federally-controlled prescription medication that must only be used under the direction and supervision of a qualified medical professional.

Additionally, none of these medical uses should be interpreted as general “benefits” for health! For all of the cases described below, any reported medical benefits only apply to contexts in which ketamine is being administered by qualified medical professionals in a controlled setting. There is no reason to expect any beneficial or therapeutic effects if ketamine is abused recreationally or taken outside of a conventional medical setting.

In medical settings, ketamine is most commonly used as an anesthetic (i.e. to make people unconscious during medical procedures). It is officially approved for this purpose by the FDA and is widely used both by itself and in combination with other anesthetic drugs [3].

Ketamine is also sometimes used – usually at lower doses – as a fast-acting sedative [3].

For example, when ketamine was administered intravenously in 30 children, all patients experienced sedation within 2 minutes [6].

In another study of 431 children, ketamine was administered through the muscles. In this study, 98% of patients experienced rapid sedation [7].

In a medical setting, ketamine is most often used as an anesthetic. It may also be used as a fast-acting sedative.

Off-Label Medical Uses of Ketamine

Occasionally, doctors will prescribe medications to help treat conditions that fall outside of the official uses approved by the FDA – also known as “off-label” drug use [8]. Usually, this is done because there is actually decent evidence that the drug may help, although this evidence might not be quite strong enough to get full FDA approval (which generally has very strict requirements).

As always, however, always remember that the decision to use medications in this way can only be made by a licensed medical professional.

Ketamine and Pain Relief

In addition to its official use as an anesthetic, ketamine also has a number of effects that can significantly reduce the perception of pain (i.e. an analgesic effect). Because of this, it is frequently used by doctors – albeit “unofficially” – to help control and manage pain. In this context, ketamine can be used either by itself or in combination with other pain-killing drugs [3].

For example, when administered by doctors, ketamine may potentially aid in reducing chronic pain. In a study of 12 male volunteers, low doses of ketamine were reported to activate portions of the brain that are believed to be involved in the inhibition of pain (such as the prefrontal cortex and certain areas of the brainstem) [9].

In one 11-week double-blind randomized controlled trial of 60 female patients with complex regional pain syndrome (CRPS), a steady 100-hour intravenous infusion of ketamine was reported to significantly relieve pain. This effect was even reported to last up to 3 months following treatment [10].

Additionally, a study of 12 cancer patients with severe cancer pain reported that patients required 50% less morphine to reduce their pain after prolonged use of ketamine [11].

Ketamine also reportedly enhanced the effectiveness of spinal cord (“intrathecal”) injections of morphine treatment in a double-blind randomized control trial in 20 cancer pain patients [12].

Some preliminary evidence suggests that ketamine may also be especially effective at reducing pain when combined with certain other medications. For example, a combination of ketamine and a local anesthetic (bupivacaine) reduced post-operative pain in a double-blind randomized placebo-controlled trial of 53 amputee patients [13].

When used as a local anesthetic with diazepam (a benzodiazepine), meperidine (also known as Demerol – a narcotic pain-killer medication), and nitrous oxide, ketamine was reported to reduce pain, discomfort, and anxiety in a study of 40 healthy adults undergoing oral surgery [14].

Ketamine has an off-label use as a painkiller, but it should never be used for this purpose without the direct supervision of a medical professional.

Potential New Medical Uses of Ketamine

In addition to some of the relatively well-accepted (but still technically unofficial) “off-label” uses, ketamine has also been studied for its potential to treat a variety of other health conditions.

However, keep in mind that the evidence supporting these potential applications is still very preliminary, and a lot more additional research would still be needed before any of these applications are ever officially approved for medical use. Therefore, it is important to take all of the information below with a healthy grain of salt, and never use ketamine without the prescription and supervision of a medical professional.

1) Ketamine and Depression

One of the most promising potential medical applications of ketamine is for treating depression – especially forms of depression that have not responded to many of the more common, “conventional” forms of treatment, such as SSRIs [3].

For example, in a double-blind randomized controlled trial of 7 patients with major depression, ketamine was reported to reduce depression symptoms after just 72 hours [15].

Some early evidence also suggests that ketamine may also be effective in alleviating symptoms in patients with treatment-resistant depression (TRD). For example, in one review, it was reported that a single dose of ketamine (administered intravenously) produced a strong and rapid antidepressant effect, and which lasted up to 1 week in patients with TRD [16].

Additionally, it was reported that depressive symptoms improved just 40 minutes after ketamine use in one 14-day double-blind randomized controlled trial of 18 treatment-resistant bipolar depression patients [17].

In a randomized control study of 73 patients over 24 hours, patients who used ketamine were reported to show a greater improvement in their scores on the Montgomery-Åsberg Depression Rating Scale (MADRS), one of the tests that psychiatrists use to measure the relative severity of individual cases of depression. According to the authors of this study, ketamine’s effects on depression symptoms were significantly stronger than midazolam (a benzodiazepine) [18].

However, while some of these early results might seem promising, there is one major catch: we really don’t know much about the long-term effects of ketamine, or how safe it would be to use on a regular basis.

Furthermore, the little data that currently exists on using ketamine more than just once paints a very complex and inconclusive picture.

For example, one study of 24 TRD patients over 83 days reported that many patients experienced over 2 weeks of sustained improvement of their symptoms after 6 repeated doses of ketamine [19].

Another study reported that ketamine, when used in combination with the electroconvulsive therapy (commonly used to treat depression), was more effective in improving depression symptoms than another anesthetic, propofol, in a year-long study of 31 inpatients [20].

In a 4-week double-blind randomized controlled trial, 42 depression patients were given an initial dose of ketamine followed by a dose of riluzole (a drug that increases glutamate). About a fourth of the patients did not experience a depression relapse by the end of the trial. However, riluzole did not potentiate the antidepressant effects of ketamine [21].

Similar to ketamine, esketamine (the name given to just the “S(+) enantiomer” form of ketamine) has been reported to be a rapid-acting antidepressant. However, in a review comparing the individual effects of ketamine isomers, it was found that arketamine (the R(-) enantiomer form) was a safer and more effective antidepressant than esketamine [22, 23, 24].

While these early studies might seem encouraging, other, larger-scale studies have come to opposing conclusions.

For example, according to a larger-scale review, the authors concluded that ketamine probably only has relatively short-term effects on alleviating depression symptoms [25].

Similarly, another large-scale review concluded that while ketamine may act as an effective antidepressant (likely by blocking NMDA receptors), it may have significant dissociative side-effects (disconnecting from one’s sense of identity) if used long-term [26].

All in all, a lot more research will be needed before we can know just how safe or effective ketamine might be when it comes to treating depression.

Also, its high potential for abuse – combined with the potentially serious side-effects associated with it – also makes it quite unlikely that the FDA will ever approve ketamine for widespread use.

Ultimately, even if ketamine does turn out to be effective for depression, the most realistic scenario is that it will be reserved only for a minority of the most severe cases of depression, and would only be used once all other treatment options have already been tried. In other words, it’s not likely that we’ll see widespread use of ketamine anytime soon!

Some researchers are currently investigating whether ketamine, in any form or at any dose, could help alleviate the symptoms of depression. It may help in the short term but have detrimental effects in the long term.

2) Ketamine and Seizure Control

Some preliminary evidence suggests that ketamine may be useful in reducing the duration or severity of seizures.

For example, ketamine was reported to decrease the duration of seizures in 10 patients undergoing electroconvulsive therapy [27].

While much more human studies will be needed to confirm this finding, there are a few animal studies that tentatively back this up.

For example, in rats, ketamine effectively controlled seizures in all animals 1 hour after seizure stimulation [28].

Another study in rats found that ketamine stopped seizure activity in 3 rats 30 minutes after administration [29].

Because of its potential to reduce the severity and length of seizures, some evidence suggests that ketamine may also be useful in partially protecting the brain from damage during seizures.

For example, ketamine was reported to reduce damage from increased intracranial pressure (pressure inside the skull) in traumatic brain injury patients during propofol sedation in a study of 8 male patients [30].

Similarly, ketamine was reported to significant protect 22 out of 24 regions of the rat brain after artificially-induced seizures [29].

Systematic dosing of ketamine also prevented the loss of neurons caused by persistent seizures in rats [31].

According to several cell studies, ketamine may help preserve the function and structure of brain cells during hypoxia (lack of oxygen) [32].

Nonetheless, given that most of these findings have only been reported in cell- or animal studies, a lot more research will be needed to know whether ketamine might be effective for controlling and managing seizures in actual human patients.

Ketamine is under investigation for potential use controlling seizures, but much of the research so far has been done in animals and cells.

3) Ketamine and PTSD

Some early evidence suggests that ketamine might be potentially useful in treating PTSD – but the science behind this is still very young, and it’s still far too early to draw any solid conclusions yet.

According to one study, ketamine quickly and effectively reduced the symptoms of PTSD compared to midazolam (a benzodiazepine) 24 hours after administration in a double-blind randomized controlled trial of 41 patients with chronic PTSD [33].

In a study of 603 burn victims, patients who received ketamine after being operated on were reported to show lower rates of later developing PTSD, compared to burn patients who received other post-operative drugs [34]. Although this finding could be taken to suggest that ketamine had a “protective” effect, it’s more likely that PTSD rates were lower in the ketamine group simply because it was just more effective at controlling and reducing pain in general.

In very limited clinical trials, ketamine is under investigation as a potential PTSD drug. However, the research is early and the evidence is sparse.

4) Ketamine and Asthma

According to one study, ketamine improved the breathing of 11 patients with severe asthma 2 hours after administration, when other therapies, as well as assisted breathing, failed [35].

While the authors of this study concluded that ketamine was potentially “a useful and safe drug” for treating certain cases of asthma, they also noted that it should only be considered when other, more conventional treatments have failed – in other words, it’s quite unlikely that ketamine will become a common treatment for asthma anytime soon!

5) Ketamine and Obsessive-Compulsive Disorder (OCD)

There’s some very early evidence suggesting that ketamine may target some of the symptoms associated with OCD – however, this evidence is still extremely preliminary, and should be taken with some skepticism.

According to a 1-week double-blind randomized controlled trial of 15 drug-free OCD adults, ketamine significantly improved obsessive symptoms in comparison to treatment with a placebo [36].

In another study of 10 treatment-resistant OCD patients, 35% of patients reported improvement in their symptoms after 3 days of ketamine treatment [37].

While these studies might sound promising, one major limitation is their relatively small sample sizes – just 15 and 10 patients each – which means that a lot more research would be needed to justify the use of ketamine in treating OCD.

In a handful of patients, ketamine reduced symptoms of OCD. However, the available studies have been very small and limited; a great deal more research is required.

Takeaway

Ketamine is an anesthetic drug that was discovered in the 1960s. It is a schedule III controlled substance, meaning that it requires a doctor’s prescription to legally buy or possess it. In medical settings, it is used as an anesthetic or occasionally as an off-label painkiller.

New research is ongoing into other potential uses of ketamine, including for depression, seizure control, PTSD, asthma, and OCD. However, there is currently nowhere near enough evidence to recommend the use of ketamine for these purposes. Ketamine should only ever be taken or administered under the careful, direct supervision of a medical professional.

Further Reading

About the Author

Puya Yazdi

Puya Yazdi

MD
Dr. Puya Yazdi is a physician-scientist with 14+ years of experience in clinical medicine, life sciences, biotechnology, and nutraceuticals.
As a physician-scientist with expertise in genomics, biotechnology, and nutraceuticals, he has made it his mission to bring precision medicine to the bedside and help transform healthcare in the 21st century.He received his undergraduate education at the University of California at Irvine, a Medical Doctorate from the University of Southern California, and was a Resident Physician at Stanford University. He then proceeded to serve as a Clinical Fellow of The California Institute of Regenerative Medicine at The University of California at Irvine, where he conducted research of stem cells, epigenetics, and genomics. He was also a Medical Director for Cyvex Nutrition before serving as president of Systomic Health, a biotechnology consulting agency, where he served as an expert on genomics and other high-throughput technologies. His previous clients include Allergan, Caladrius Biosciences, and Omega Protein. He has a history of peer-reviewed publications, intellectual property discoveries (patents, etc.), clinical trial design, and a thorough knowledge of the regulatory landscape in biotechnology.He is leading our entire scientific and medical team in order to ensure accuracy and scientific validity of our content and products.

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