Ketamine: The History, Science, and Facts About This Emerging Psychedelic

Maybe you’ve heard about ketamine and its potential to help treat mood disorders such as depression, anxiety, and more. There’s a fair chance you’ve heard of it as a party drug, but it has so much more potential than that. Ketamine is an emerging power player in the world of psychedelic medicine, and as we learn more about it from ongoing research and clinical trials, we also learn about its potential to become a significant part of a therapeutic toolkit.

Compared to traditional psychedelics like peyote and Ayahuasca, ketamine is relatively new. It was invented in 1962, and thanks to its anesthetic properties, the substance was added to the World Health Organization’s Model List of Essential Medicines in 1984. But what about its role in managing symptoms of depression, anxiety, and more? Can ketamine’s psychedelic experiences help with mental illness and support better mental health?

We’re breaking down the facts about ketamine, how it works, and how it’s used. Whether you’re new to psychedelics or you’ve tried ketamine before, here’s what you should know. Let’s dive in.

What Is Ketamine?

Ketamine is a dissociative anesthetic, which means that it makes people feel detached from their body and environment. It’s a surgical anesthetic and analgesic (pain relief) medication in adults, children, and animals. It’s fast-acting and, unlike other anesthetics, it doesn’t have a substantial impact on breathing or heart function in clinical settings. 1

Ketamine is also part of the emerging field of psychedelic therapy. Depending on factors like dose, setting, and a person’s biology, ketamine can cause a variety of experiences, ranging from sedation and diminished sensations to euphoria and hallucination. As an off-label use, ketamine may help treat drug-resistant mental health conditions like depression, anxiety, and post-traumatic stress disorder (PTSD).

Unfortunately, due to its ability to cause confusion, sedation, and amnesia, ketamine has a history of use for sexual assault. It is grouped with GHB (gamma-hydroxybutyric acid) and Rohypnol as a common “date-rape” drug.

Street names for ketamine

Ketamine is also known by the following names: 2

Special K
Cat Valium
Kit Kat
K
Super Acid
Super K
Purple
Special La Coke
Jet
Vitamin K

A brief history of ketamine

Ketamine was created in 1962 by a researcher named Calvin Stevens, who was looking for a shorter-acting and less toxic alternative to phencyclidine (PCP).3 In 1970, the FDA approved ketamine as an anesthetic, and the U.S. military used the drug during the Vietnam War.

It’s still used in clinical settings today for sedation, relaxing spasming airways, and helping military medics intubate patients while in helicopter flights, among other applications. 4

Shortly after it was invented, ketamine was used non-medically by two groups: recreational users and professionals who used it to explore psychedelic states of consciousness at high doses.5

Ketamine has a complicated reputation with the general public today. In the 1960s, it was associated with prominent psychonauts (a person who explores altered states of consciousness through meditation or substances). Ketamine also played a role in American underground dance culture through the 1990s.

In 1999, ketamine became a Schedule III non-narcotic substance under the Controlled Substances Act, which means that it has moderate to low potential for physical and psychological dependence. It’s in the same category as Vicodin® and Tylenol® with codeine.

In 2000, researchers began using ketamine to treat depressive symptoms due to its effects on certain receptors in the brain.6 (More on that below.) In 2019, the FDA approved a form of ketamine called esketamine which is administered as a nasal spray for treatment-resistant depression.

Today, ketamine maintains multiple identities: It’s still a widely used anesthetic and still used recreationally, although it’s not as common as other psychedelics.7 Ketamine is also an emerging form of therapy for treatment-resistant mental health disorders, including depression, anxiety, and PTSD.

What Does Ketamine Do?

Ketamine is unique for two reasons:

It acts quickly. People can rapidly feel the effects of ketamine, depending on how it’s administered. On an empty stomach, an oral dose can cause effects within 10 to 30 minutes.5 In comparison, a tab of LSD can start to take effect within 20 to 90 minutes.8
It acts on particular areas of the brain. Spoiler: We don’t 100% know how ketamine works, but researchers do know that ketamine is what pharmacologists informally call a “dirty drug.” That means it acts on different parts of the brain at once. Ketamine’s psychedelic and therapeutic qualities may come from its effects on the parts of the brain that play a role in learning and memory.

Let’s take a closer look at what ketamine does and why that matters.

How does ketamine work?

Ketamine may activate different pathways in the brain. Your brain is constantly sending messages. Chemical messengers called neurotransmitters help nerve cells talk to each other. Neurotransmitters have a lot of jobs, ranging from signaling that you’re hungry to managing your sleep-wake cycle. Ketamine has unique effects on the neurotransmitter glutamate, which is a major messenger throughout your central nervous system.

Normally, glutamate crosses the threshold between cells and binds to specific landing pads called NMDA receptors.5 Ketamine temporarily blocks NMDA receptors because it’s an antagonist (receptor blocker) of glutamate. That means glutamate can’t grab onto enough receptors to activate anything. It’s locked out. This blockage contributes to the dissociative feeling associated with psychedelic doses of ketamine.9

The thing is, when you let glutamate hang around, it triggers different signals. Higher levels of glutamate may activate two important pathways: brain-derived neurotrophic factor (BDNF) and mechanistic target of rapamycin (mTOR). BDNF is a molecule that contributes to learning and memory, and mTOR regulates healthy cell growth. Activating BDNF and mTOR is associated with synaptic plasticity and strength, also known as strong, healthy brain cells.10

This activity might be one of the reasons that ketamine is an emerging therapeutic medicine with a potential antidepressant effect. A growing body of research suggests that glutamate may be involved in the processes that contribute to depression, and some researchers suggest that glutamate could be dysregulated in major depressive disorder.11 12

It’s important to note that this research is focused on animal studies, and rodents aren’t humans. However, these findings signal opportunities for future clinical research.

How Ketamine Is Used

We’ve touched on what ketamine does in the brain, but the science behind it is just part of the picture. Ketamine is used medically as an anesthetic, therapeutically for mood disorders, and non-medically for recreation. Here’s an overview of the ways ketamine is generally used.

Ketamine in medical anesthesia

Ketamine is an FDA-approved anesthetic in surgical procedures. It has been found to reduce pain medicine use, pain level, nausea, and vomiting after surgery. 13

Ketamine for pain management

Among patients who have a high tolerance for opioids or experience treatment-resistant chronic pain, ketamine for pain management is particularly helpful.14 But clinical research is limited in this area.

Currently, there isn’t a specific treatment regimen for ketamine in palliative care or chronic noncancer pain (CNCP). CNCP refers to moderate or severe pain that lasts for six or more months and is attributed to conditions such as neuropathic pain, arthritis, lower back pain, and fibromyalgia.15

Treatment-resistant mood disorders

Ketamine is a powerful tool for treating (and understanding) depression, particularly in cases that are resistant to standard forms of treatment.

SSRIs are a widely used type of antidepressant. They work by increasing levels of serotonin, a neurotransmitter that helps to regulate your mood. Ketamine works differently because of the way it impacts glutamate and NMDA receptors.

Here’s one example: In 2000, a placebo-controlled, double-blind trial (the gold standard of human research) assessed the treatment effects of ketamine as an NMDA receptor antagonist in patients with depression.6

The participants reported significant improvements in their symptoms within 72 hours after taking ketamine for depression. The sample size was small, with just seven subjects. But studies such as these can help uncover how ketamine interacts with glutamate and what that means for mood disorders.

The benefits of ketamine treatment for depression might also be related to the medication’s dissociative qualities. In 2014, researchers found that ketamine’s dissociative side effects predicted a more robust and sustained antidepressant response among 108 participants. The study’s authors suggest that dissociation, or out-of-body feeling, may be related to ketamine’s effects on glutamate release.16

Other drug-resistant mood disorders have benefited from ketamine, including bipolar disorder, obsessive-compulsive disorder, and social anxiety disorder. However, these are early trials with small sample sizes, and more research is needed to examine ketamine’s long-term effectiveness in mental health.17 18 19

Ketamine is prescribed as an anesthetic, so using it for mental health treatment is considered off-label use. That doesn’t mean it’s illegal. In fact, ketamine is one of the only psychedelics that has never been illegal in the United States. Off-label means medicine is being used for a condition that it isn’t officially approved to treat.

There is one exception: In 2019,the FDA approved a ketamine nasal spray called esketamine for the treatment of drug-resistant depression and suicidal ideation. Esketamine was approved after a series of large, randomized, placebo-controlled trials, and its approval involved the creation of strict guidelines to inform health practitioners how to use the product. This is one path that other forms of ketamine would need to follow to be considered on-label for mental health treatment.

Recreational use of ketamine

Soon after it was invented in the 1960s, ketamine entered the underground psychedelic world. In the 1970s, early trailblazers Marcia Moore, Howard Alltounian, and psychiatrist John Lilly used ketamine to explore altered states of consciousness, to very different ends. Ketamine overdose is rare, but the work of these early ketamine pioneers illustrated both the psychedelic potential of ketamine and the effects of ketamine abuse.

From the mid-1980s onward, ketamine grew in popularity as a club drug in the United States, Europe, Australia, and Asia. In some regions, ketamine is popular as a “post clubbing” experience due to its sedative, dissociative effects.20

Ketamine’s effects are dose-dependent, which means that you get different effects at different doses. Psychedelic doses are about 10% to 25% of anesthetic doses, and the effects can vary depending on the dose, route, set, and setting.5

Ketamine and near-death experiences

Some people experience effects like out-of-body experiences, transcendence of time, the dissolution of identity, and vivid dreams. At higher doses, people can experience a phenomenon called the “K-hole,” a state of dissociation that researchers liken to a near-death experience.21

These experiences can be profound, transformative tools, which is why ketamine’s dissociative effects are considered such a major part of its therapeutic potential. This is another big reason why ketamine shouldn’t be used without appropriate supervision.

Ketamine Modes of Administration

Ketamine is commonly administered as an intravenous (IV) injection, intramuscular (IM) injection, sublingual (under the tongue) liquid, and oral dose in pill form. Nonmedically, it’s also found as a white powder that can be taken intranasally, or “snorted.”

Nobody loves needles, but IV injections have been shown to have the most rapid effects on mood disorders.22 Nasal sprays and pills are convenient but potentially less effective than using an IV because they’re less bioavailable. “Bioavailability” means your body can absorb and use the intended dose of any medicine.

IM injections are 93% bioavailable, sublingual doses are 30% bioavailable, oral doses are 16% to 20% bioavailable, and nasal sprays are 25% to 50% bioavailable.23 In comparison, IV injections are 100% bioavailable by definition.

How Does Ketamine Feel?

Ketamine can make people feel relaxed, detached, and calm. As a dissociative anesthetic, ketamine reduces sensations in the body. Some people might feel confused or agitated, particularly if they go into a ketamine experience with a negative mindset.

At higher doses, people can have an intense dissociative experience called the “K-hole.” In this state, a person might have an out-of-body experience and the sensation of being detached from reality.

Coming down from ketamine

Ketamine comedowns can vary, depending on what a person has taken and how it was administered. People might experience:

Confusion
Depression
Disorientation
Fatigue
Headaches

Ketamine Dosages

For anesthesia in adults, the initial IV dose of ketamine ranges from 1 to 4.5 mg/kg (0.5 to 2 mg/lb) administered over 60 seconds. A dose of 2 mg/kg (1 mg/lb) is the average amount required to produce 5 to 10 minutes of dissociative anesthesia.24

Psychedelic doses are about 10% to 25% of anesthetic doses. Generally, a club “bump” for intranasal use is around 200 mg, an IM injection is 50-150 mg, and oral doses are 350-500 mg.5 That’s a pretty wide range, which is why it’s important to work with a qualified professional to determine the right dosage and to take ketamine with appropriate supervision.

How to Prepare for Your Ketamine Session

You might have heard the phrase, “Perfect planning prevents poor performance.” Ketamine isn’t a magic bullet, and getting the most out of its effects involves the right preparation. Most importantly, that means working with an experienced professional.

A growing number of clinicians and clinics offer ketamine therapy. Before your first session, you’ll speak with a healthcare practitioner who will evaluate your health and medical history to make sure that ketamine therapy is right for you. They’ll also give you specific tips to properly prepare for your first session. Generally, here’s what you might expect:

Fast. Ketamine can cause nausea or vomiting in some people, so your therapist might request that you don’t eat or drink anything before your session. You should be prepared to fast for about six to eight hours before your appointment. Follow your therapist’s guidance here.
Get a good night’s sleep. You’ll want to relax into your treatment, and it’s a lot easier to unwind and de-stress when your mind and body are well-rested.
Wear comfortable clothing. Sessions can last up to three hours from start to finish, so wear something cozy. Sweats? Pajamas? Your therapist won’t judge.
Be mindful. Ketamine alters your mental state, so it’s important to enter the experience with a clean slate. Avoid substances (including alcohol), activities, and interactions that make you feel anxious, stressed, or uncomfortable in the time leading up to your session. Now is the time to focus on yourself and what brings you joy.
Set an intention. Think of your intention as the goal that anchors you to your experience. What do you want to accomplish with your treatment? Find a short phrase (like “I want to feel peaceful” or “I want to let go”) and keep that intention in mind before, during, and after your treatment.
Plan ahead. Arrange for a friend or family member to bring you home after your session, and plan on taking it easy for the rest of the day. Now is not the time for a big hike or major presentation.

How Long Does Ketamine Last?

People can feel the effects of ketamine relatively quickly, depending on how it’s administered. On an empty stomach, an oral dose can cause effects within 10 to 30 minutes and last for about four hours.5 In comparison, people can start to feel the effects of taking a tab of LSD within 20 to 90 minutes, and the experience can last as long as 12 hours.8

Generally, ketamine treatments last about an hour, and the psychedelic effects subside within three hours.

Suggested Ketamine Protocols

Work with a medical professional to determine your ketamine dosage and frequency. Some people feel better after just one infusion, but the effects depend on your biology, mental state, and successful integration after your sessions.

Generally, ketamine infusion therapy involves a series of six infusions spaced out over two to three weeks.25 26

Ketamine Contraindications

During your initial consultation with a healthcare professional, you’ll discuss potential contraindications. This term refers to conditions that might prevent you from getting ketamine treatments because they increase your risk of health complications.

Here are a few underlying conditions that make ketamine inadvisable:24

Heart conditions, such as aortic dissection, uncontrolled hypertension, or myocardial infarctions
Prior hypersensitivity to ketamine
Pregnant or breastfeeding, because researchers don’t know if ketamine crosses the placenta or passes into breast milk
Alcohol intoxication (don’t show up to your session inebriated)
Schizophrenia

Always share your complete medical history with your therapist so that they can determine whether or not you are a candidate for ketamine therapy.

Ketamine Side Effects and Risks

When properly administered by a qualified professional, ketamine is generally considered safe to use. But even in the safest conditions, there’s a level of risk with any psychedelic, such as:24

Allergic reactions, such as breathing difficulties and hives
Elevated blood pressure
Changes to your heart rate
Nausea
Vomiting
Muscle stiffness
Confusion
Seizures
Amnesia
Anxiety
Changes in mood
Insomnia
Double vision
Involuntary eye movement
Slow breathing
Addiction when used recreationally
Bladder and kidney problems (with prolonged ketamine abuse)

In 2019, National Institutes of Health researchers found that a single, low-dose ketamine infusion had minimal side effects among patients with treatment-resistant depression.27 The most common reaction was feeling strange or loopy (beyond the dissociative experience), which resolved within two hours.

Ketamine can cause cardiovascular stimulation, which means it can increase heart rate and blood pressure.28 29 For this reason, your vitals should be monitored during a ketamine session.

The recreational use of ketamine (that is, outside of a clinical setting) comes with additional risks because all the controls that keep you safe go out the window, like assessing appropriate dosages and having a healthcare professional available to monitor your vitals. We’re going to sound like a broken record here, but this is all the more reason to work with a professional in a clinical setting when you’re getting ketamine treatments.

Risks can range from bladder and kidney complications to changes in memory and mood, particularly among people who abuse ketamine (like over two years, at least three times a week). 30 31

Is ketamine addictive?

The downside of ketamine also stems from its dissociative effects and potential for addiction. Dissociation can be massively transformative, but ketamine’s hallucinogenic effects can also take you in the opposite direction. It’s possible to have a “bad trip” on ketamine, particularly if you enter the experience in a negative headspace. This is one of the reasons you shouldn’t take ketamine without any supervision.

Ketamine addiction is rare, but it can happen. The substance can be addictive when it is taken frequently over an extended period. In one case study, a woman became addicted to ketamine after self-injecting 50 mg of ketamine once a week to cope with her major depression, gradually increasing to 2 g daily in the following six months.32 That dose is far higher and far more frequent than what you would get in a clinical setting, which is why the risk of ketamine addiction is low when it’s administered under medical supervision.

If you or someone you know are struggling with substance use or addiction, reach out to the Substance Abuse and Mental Health Services Administration (SAMHSA) National Helpline at 1-800-662-4357 for information about support and treatment facilities in your area.

Personal Stories About ketamine

We’ve covered what ketamine does and how it works, but what does ketamine do in the real world? Here are a few real stories from people who have benefited from ketamine therapy.

Steven Gerritse, “The Experimental Ketamine Cure for Depression” – Vice

Based in New Jersey, Steven is a ketamine infusion patient who lives with depression. His sessions at the Ketamine Treatment Centers of Princeton have helped him manage his symptoms, allowing him to feel relief that he didn’t get from conventional antidepressants. “I’m not incapacitated anymore,” he said after his session.

Jacky and Beverly, “Like Minds” – BBC Stories

Jacky was 14 years old when she first attempted suicide. Regular medication wasn’t helping until she found medically-supervised, low-dose ketamine treatments. Beverly is a mother who lives with bipolar disorder, and she takes ketamine during depressive episodes. “For me, there’s no other option,” she said about her ketamine treatments. “I want to be a mom. I want to have a life again.”

Lauren is a Chicago preschool teacher who has struggled with depression and previously attempted suicide. But she found a new treatment path with ketamine for anxiety and depression, and the mood boost can last for weeks. “It’s kind of like a reboot for your life. It’s like a restart button,” she said.

—Lauren Pestikas – Associated Press

How to Safely Source Ketamine

The safest way to source ketamine is to work directly with a healthcare professional, such as a doctor at a ketamine clinic. You can find providers by using directories like:

We do not recommend that you use ketamine without medical supervision, as there are serious dangers involved.

If you are going to use ketamine recreationally, seriously consider purchasing a drug testing kit. When you get ketamine outside of a clinical setting, you run the risk of taking a product that is laced with other substances that can cause harm.

Drug testing kits take just a few minutes, and they allow you to easily test for different substances before you take any psychedelics. Here are a few places to start:

DanceSafe: Specifically tests for ketamine and can detect the presence of other substances, like DCK and cocaine.
NarcoCheck: Identifies ketamine and other substances in the same family, and it also indicates the presence of PCP.
Elevation Chemicals: Provides a range of testing kits for different substances, including LSD, ketamine, and MDMA. Contact the company directly to determine the right kit for your needs.

Ketamine Frequently Asked Questions

Is ketamine legal?

Ketamine is FDA-approved as an anesthetic. Ketamine is used off-label to treat depression, but it’s not illegal for a doctor to administer it. However, it’s illegal to abuse ketamine because it’s a Schedule III controlled substance.

How long does ketamine stay in your system?

Ketamine’s half-life, which is the amount of time it takes for the amount of a drug in your body to be reduced by 50%, is approximately 45 minutes.24

In a small study that examined four adult volunteers, ketamine was detected in scalp samples up to 48 hours later.33 Factors like your age, weight, metabolism, dose, and route of administration can all affect how long it takes for ketamine to be fully eliminated from your system.

What is the difference between ketamine and esketamine?

Ketamine is injected, while esketamine is a nasal spray. Esketamine is sold under the name Spravato, and it’s prescribed for people with treatment-resistant depression. Esketamine is more potent than ketamine, so it can be prescribed at lower doses. Both ketamine and esketamine are used for treatment-resistant depression.34

Do I need a referral to get ketamine treatments?

It depends on your provider. The process usually begins with a psychiatric evaluation, and some clinics require a referral from a psychiatrist or other physician. Plan on speaking with your healthcare provider to understand your treatment options and whether ketamine is right for you.

How much does ketamine therapy cost?

Cost varies depending on factors like the condition being treated, frequency, and insurance coverage. Health insurance generally doesn’t cover ketamine infusions, but some clinics have financing plans available.

What does ketamine smell and taste like?

Ketamine is odorless, but not tasteless. The taste is described as extremely bitter and unpleasant.

Can I mix ketamine with alcohol or other drugs?

Ketamine should not be combined with alcohol or other drugs. Combining ketamine and other substances can increase your risk of adverse side effects, overdose, and even death.

Can I microdose ketamine?

It’s possible to take microdoses of ketamine. A microdose is usually one-tenth of an active dose. However, although anecdotal reports describe the beneficial effects of microdosing for mood and cognition, minimal research exists that studies the benefits of microdosing ketamine in humans.35

Can I overdose with ketamine?

It’s rare, but it’s possible to overdose on ketamine. This is especially true if you combine ketamine with other substances. Overdosing on ketamine can increase your risk of respiratory failure, coma, and death. Symptoms of overdose include slow heart rate, slow breathing, and unconsciousness.

Final Thoughts

Ketamine was first approved by the FDA in 1970 as a surgical anesthetic. Today, ketamine is an emerging drug in the world of psychedelic-assisted psychotherapy. At psychedelic doses, ketamine may help with treatment-resistant mood disorders like depression and anxiety. However, how ketamine compares to other psychedelic therapies remains to be seen.