Ketamine Basics
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Ketamine Basics

If you’re just starting out, the world of ketamine can be confusing.
Welcome to your ketamine primer - we’ve put together key pieces of information to get you started.

Keep scrolling to start learning, or choose from a topic below:
What is Ketamine?Is Ketamine Safe?The Different Types
of KetamineKetamine and Therapy
Table of Contents
What is Ketamine?Is Ketamine Safe?The Different Types
of KetamineKetamine and Therapy

science stuff

NMDA receptors play a crucial role in the communication between nerve cells, or neurons. These receptors are involved in a process called synaptic plasticity or neuroplasticity, which is the brain's ability to adapt and change in response to experiences, learning, and memory.

NMDA receptors are activated by a neurotransmitter called glutamate. Glutamate helps neurons send signals to each other. In cases of depression and anxiety, there can be imbalances in the levels of glutamate or in how NMDA receptors respond to glutamate. These imbalances can result in altered neural connectivity and reduced synaptic plasticity, which contributes to the cognitive and emotional symptoms experienced by individuals with depression and anxiety, such as disturbances in mood regulation and memory formation.

Ketamine is an NMDA receptor antagonist, meaning it temporarily blocks or reduces the activity of these receptors. This leads to increased levels of a protein called brain-derived neurotrophic factor (BDNF), which enhances neuroplasticity by promoting the growth and survival of neurons and the formation of new connections between brain cells.

By blocking NMDA receptors and boosting BDNF levels, ketamine resets the communication between neurons, helping to correct the imbalances and disruptions seen in depression and anxiety
Ketamine is a medication originally known for its anesthetic and pain-relieving properties. It is increasingly being used for psychiatric purposes treat depression, anxiety, suicidal ideation, PTSD, and other mood conditions. At certain dosage levels, ketamine produces a therapeutic dissociative state that allows users to experience a new perspective of their usual reality.
‍
That might be a bit confusing, so here's a bit of a simplification:

Think of a brain as a complex conversation...

Inside, all of the brain cells are constantly talking with one another.

To facilitate these conversations, the cells talk to each other using special "doors" called receptors.

NMDA (N-methyl-D-aspartate) receptors are important doors that play a role in learning, memory, and mood.
When someone is depressed or anxious, these NMDA receptors can get a bit "stuck" and not work as well.

Ketamine steps in and unjams those doors. It's like a special oil that makes the doors work again.

When someone with depression or anxiety takes ketamine, it opens up those NMDA receptors.

This can improve communication in the brain and relieve those heavy feelings.

Think of a brain as a complex conversation...

Inside, all of the brain cells are constantly talking with one another.

To help facilitate these conversations, the cells talk to each other using special "doors" called receptors.
‍
NMDA (N-methyl-D-aspartate) receptors are important doors that play a role in learning, memory, and mood.

When someone is depressed or anxious, these NMDA receptors can get a bit "stuck" or not work as well.

It's like the doors are a bit jammed, and this affects the brain's communication.

This can lead to feelings of sadness, worry, and even difficulty concentrating.

This is where ketamine can help

Ketamine steps in and helps unjam those doors. It's like a special oil that makes the doors work better again.

When someone with depression or anxiety takes Ketamine, it helps open up those NMDA receptors.

This can improve communication in the brain and might bring relief from those heavy feelings.

the gist

Ketamine is a medicine used for pain relief and anesthesia. It's also used to treat conditions like depression and anxiety. In the brain, there are receptors that help cells communicate. Ketamine unblocks these receptors, which can get stuck in conditions like depression. This can improve brain communication to ease negative feelings.

science stuff

Wanna get a little nerdier? We're with you, we love being nerdy. Here's a little more info to whet your appetite.
Learn More
Ketamine was first synthesized in 1962 at the Parke-Davis Research Laboratories in Ann Arbor, Michigan. It was designed as a less hallucinogenic and shorter acting anesthesia alternative to phencyclidine, more commonly known by the shorthand PCP.
It wasn't until 1970 that the Food and Drug Administration (FDA) approved Ketamine for medical use as a general anesthetic. To this day, ketamine is commonly used as an anesthetic during surgeries mainly because it does not have a substantial effect on the patient's breathing during surgery as well as possible post-surgery pain reduction.
However, during the 1980s and 90s, ketamine gained a reputation as a party drug due to its dissociative and hallucinogenic effects.

In 1999, the US Government made ketamine a federally controlled substance. While this was mainly meant to curb illicit use, it created a stigma around ketamine about its potential dangers. When repeatedly abused, there is a possibility of creating a psychological dependence on ketamine. However, many studies have shown that, when ketamine is administered by a licensed medical professional, there is little risk of dependency.

Despite the increased stigma, researchers continued performing trials on ketamine to understand more about its potential benefits as an antidepressant. During this time, the Yale School of Medicine published the first randomized controlled trial that demonstrated ketamine's rapid antidepressant effects.
By 2010, after several additional clinical trials, the medical community at large adopted ketamine off-label into their clinical practices to treat depression and other mental disorders. These results were extremely promising, but due to the off-label nature of it's administration for mental disorders, generic ketamine has struggled to become widely known and accepted for its treatment potential.
In 2019, the FDA approved Esketamine, the first ketamine-based antidepressant to treat treatment-resistant depression (TRD), which is generally understood as a form of major depressive disorder that occurs when a patient doesn't respond adequately to multiple courses of different antidepressant treatments.
Esketamine is more widely known under the brand name Spravato™️ and is available as a nasal spray. The approval of Esketamine has helped to reduce the stigma around ketamine as a psychiatric treatment.
The recent increase in the use of ketamine to treat psychiatric disorders has also led to a growing number of providers and companies offering ketamine treatments. In 2023, the FDA published a warning to patients seeking these treatments to exercise caution in use. While ketamine is generally considered a safe treatment option for depression and anxiety, when administered in a clinical setting, under the supervision of a licensed medical professional, it’s not without risk. Companies offering at-home ketamine treatments have seen successful clinical outcomes, but it’s also important to consider the power of these therapies and the safest settings to undergo these treatments.
Ketamine was first synthesized in 1962 as a less hallucinogenic and shorter acting anesthesia alternative to phencyclidine, more commonly known by the shorthand PCP. It wasn't until 1970 that the Food and Drug Administration (FDA) approved Ketamine for medical use as a general anesthetic. To this day, ketamine is commonly used as an anesthetic during surgeries mainly because it does not have a substantial effect on the patient's breathing during surgery as well as possible post-surgery pain reduction.
Parke-Davis Research Laboratories in Ann Arbor, Michigan
Ketamine was first synthesized here in 1962
However, during the 1980s, ketamine gained a reputation as a party drug due to its dissociative and hallucinogenic effects. In 1999, the US Government made ketamine a federally controlled substance. While this was mainly meant to curb illicit use, it created a stigma around ketamine about its potential dangers. When repeatedly abused, there is a possibility of creating a psychological dependence on ketamine. However, many studies have shown that, when ketamine is administered by a licensed medical professional, there is little risk of dependency.
In 2000, researchers began noticing the benefits of ketamine's antidepressant properties
During this time, the Yale School of Medicine published the first randomized controlled trial that demonstrated ketamine's antidepressant effects. By 2010, after several additional clinical trials, the medical community at large adopted ketamine off-label into their clinical practices to treat depression and other mental disorders. These results were extremely promising, but due to the off-label nature of it's administration for mental disorders, generic ketamine has struggled to become widely known and accepted for it's treatment potential.
Johnson & Johnson developed Spravato, which became the first ketamine derivative to be FDA approved as an anti-depressant.
In 2019, the FDA approved Esketamine, the first ketamine-based antidepressant to treat treatment-resistant depression (TRD), which is generally understood as a form of major depressive disorder that occurs when a patient doesn't respond adequately to multiple courses of different antidepressant treatments. Esketamine is more widely known under the brand name Spravato™️ and is available as a nasal spray. With the approval of Esketamine, many proponents of ketamine-assisted psychotherapies are hopeful that the stigma will begin to diminish and become more accepted as a form of treatment for mental disorders.

off label drug use

You might be wondering a bit about what off-label drug use means. No worries, we got you. Off-label drug use involves using a medication in a way not initially approved by regulatory agencies. It doesn't mean just throwing anything at the wall and seeing what sticks, but rather comes when there is a considerable amount of research performed by doctors and researchers as to the effectiveness of the drug for this alternate use. The three big considerations with off label drug use are: ‍
a) Doctors have experience with it
b) Ongoing research supports its use
c) The benefits outweigh the risks.
In general, safety depends on the specific drug, condition, and patient. Patients and doctors must make informed decisions, monitor effects, and consider the evidence. It's also crucial to follow legal and ethical guidelines. But at the end of the day, off label drug use is extremely common and predominantly as safe as on label usage.

podcasts

Interested in learning a bit more about the world of ketamine, it's safety, and overall practicality? Awesome! Here are a couple of podcast episodes that we enjoy that talk a bit more about ketamine in depth:
Tim Ferriss Interview With Dr. John KrystalHuberman lab episode on ketamine

off label drug use

Off-label drug use involves using a medication in a way not initially approved by regulatory agencies. Doctors prescribe medication in this way when there is a considerable amount of research performed by doctors and researchers as to the effectiveness of the drug for this alternate use. The three big considerations with off label drug use are:
a) Doctors have experience with it
b) Ongoing research supports its use
c) The benefits outweigh the risks.
In general, safety depends on the specific drug, condition, and patient. Patients and doctors must make informed decisions, monitor effects, and consider the evidence. It's also crucial to follow legal and ethical guidelines. For more information, you can read the FDA’s article explaining Off Label drug use.

podcasts

Want to learn more about the world of ketamine, its safety, and overall practicality? Here are a couple of podcasts that we enjoy!
Tim Ferriss Interview With Dr. John KrystalHuberman lab episode on ketamine

the legal stuff

The information and statistics provided below are generalized for the purpose of approachability. Each patient, their experience, and the medical professional they work with may have different experiences or recommendations. Please speak with a licensed medical provider to understand how ketamine therapy might work for you. We are not suggesting or recommending any course of care for readers. We are providing this information for educational purposes only.

Intravenous

Intramuscular

Sublingual/Oral

Esketamine

Setting

where the patient will receive their dose of ketamine

Clinical Setting

Clinical Setting

Clinical or Home Setting

Clinical Setting

Bioavailability

proportion of a drug substance which enters circulation

High

High

Low

Medium

Onset

the average length of time it takes for the ketamine to take effect

Within Seconds

2 - 4 Minutes

5 - 10 Minutes

~ 10 Minutes

Duration

the average length of time the patient feels the effect of ketamine

1 - 2 Hours

1 - 2 Hours

2 - 4 Hours

2 - 4 Hours

Frequency

how often the patient does a session for an average treatment.

6 infusions
over 2 - 3 weeks

6 injections
over 2 - 3 weeks

6 treatments
over 4 - 6 weeks

12 treatments
over 8 weeks

Cost

average out of pocket cost for the patient

$400 - $1,000
per infusion

$250 - $750
per injection

$150 - $200
per treatment

Cost determined by insurance

Ketamine Types
‍a little bit about each type of ketamine and what how they are administered

Intravenous

A needle or catheter with a solution of ketamine is injected into the patient’s veins

Intramuscular

The ketamine solution is injected into the muscles of either the patient's leg or arm

Oral/Sublingual

A lozenge or oral solution is held in the mouth for approximately 10 to 15 minutes as it is slowly absorbed into the bloodstream.

Esketamine

Also known under the brand name Spravato™️, the ketamine derivative nasal spray is delivered as one spray in each nostril, at 15 minute intervals, either twice or three times, depending on the dose recommended by the provider.

Nearly all forms of ketamine will require the patient to receive their dose in either a clinical or healthcare setting under the direct supervision of a licensed clinician. However, some ketamine lozenges can be taken at home without direct supervision or guidance. Of course, if lozenges are the preferred method for a patient, they may also be taken under direct supervision at a clinic instead. As for Esketamine, it must be administered in a healthcare setting that is certified in the Spravato™️ program under direct observation by a healthcare provider for at least 2 hours after the administration.

Setting  where the patient will receive their dose of ketamine

Intravenous

Clinical Setting

Intramuscular

Clinical Setting

Oral/Sublingual

Clinical or Home Setting

Esketamine

Clinical Setting

Nearly all forms of ketamine will require the patient to receive their dose in either a clinical or healthcare setting under the direct supervision of a licensed clinician. However, some ketamine lozenges can be taken at home without direct supervision or guidance. Of course, if lozenges are the preferred method for a patient, they may also be taken under direct supervision at a clinic instead. As for Esketamine, it must be administered in a healthcare setting that is certified in the Spravato™️ program under direct observation by a healthcare provider for at least 2 hours after the administration.

Bioavailability  the proportion of a drug or other substance which enters the circulation when introduced into the body and so is able to have an active effect

Intravenous

High

Intramuscular

High

Oral/Sublingual

Low

Esketamine

Medium

In general, bioavailability is determined by a patient's body weight and may vary slightly from patient to patient. Further, the bioavailability does not necessarily indicate the effectiveness of the ketamine on the patient. Like with all medications, consult with your physician or clinician to find out more information.

Onset  the average length of time it takes for the ketamine to take effect

Intravenous

Within Seconds

Intramuscular

2 - 4 Minutes

Oral/Sublingual

5 - 10 Minutes

Esketamine

~ 10 Minutes

Duration  the average length of time the patient feels the effect of ketamine

Intravenous

1 - 2 Hours

Intramuscular

1 - 2 Hours

Oral/Sublingual

2 - 4 Hours

Esketamine

2 - 4 Hours

Frequency  how often the patient does a session for an average treatment

Intravenous

6 infusions
over 2 - 3 weeks

Intramuscular

6 injections
over 2 - 3 weeks

Oral/Sublingual

6 treatments
over 4 - 6 weeks

Esketamine

12 treatments
over 8 weeks

Frequency can be a bit of a tricky one to nail down, as the number and frequency of sessions depend on the purpose of treatment, the effectiveness of the first few sessions, the side effects experienced, and other factors. As is stated above, an average patient will receive 6 treatments over several weeks as well as any additional injections that their provider recommends. Esketamine, however, has a more unique dosage structure that is spread out over a longer period of time and frequently involves treatments every one to two weeks after the initial phase. As always, speak with your provider to create a plan that is catered towards your needs.

Cost  average out-of-pocket cost for patients

Intravenous

$400 - $1,000
per infusion

Intramuscular

$250 - $750
per injection

Oral/Sublingual

$150 - $200
per treatment

Esketamine

$590 - $895
per treatment

The data reported above are average ranges observed in the United States in a range of clinical settings. They are not considerate of insurance coverage or reimbursement.

Ketamine Types a little bit about each type of ketamine and what how they are administered

Intravenous

Intramuscular

Oral/Sublingual

Esketamine

A needle or catheter with a solution of ketamine is injected into the patient’s veins

The ketamine solution is injected into the muscles of either the patient's leg or arm

A lozenge or oral solution is held in the mouth for approximately 10 to 15 minutes as it is slowly absorbed into the bloodstream.

Also known by the brand name Spravato™️, the ketamine derivative nasal spray is delivered as one spray in each nostril, at 15 minute intervals, either twice or three times, depending on the  recommended dose.

Some providers offer only one form of ketamine, while others offer either ketamine or Spravato in their practice. If you're averse to needles, oral ketamine or Spravato could be a good option for you. As with all medical decisions, it's up to you and your provider to determine the best course of action for you.

Setting  where the patient will receive their dose of ketamine

Intravenous

Intramuscular

Oral/Sublingual

Esketamine

Clinical Setting

Clinical Setting

Clinical or Home Setting

Clinical Setting

Nearly all forms of ketamine will require the patient to receive their dose in either a clinical or healthcare setting under the direct supervision of a licensed clinician. However, some ketamine lozenges can be taken at home without direct supervision or guidance. Of course, if lozenges are the preferred method for a patient, they may also be taken under direct supervision at a clinic instead. As for Esketamine, it must be administered in a healthcare setting that is certified in the Spravato™️ program under direct observation by a healthcare provider for at least 2 hours after the administration.

Bioavailability  the proportion of a drug or other substance which enters the circulation when introduced into the body and so is able to have an active effect

Intravenous

Intramuscular

Oral/Sublingual

Esketamine

High

High

Low

Medium

In general, bioavailability is determined by a patient's body weight and may vary slightly from patient to patient. Further, the bioavailability does not necessarily indicate the effectiveness of the ketamine on the patient. Like with all medications, consult with your physician or clinician to find out more information.

Onset  the average length of time it takes for the ketamine to take effect

Intravenous

Intramuscular

Oral/Sublingual

Esketamine

Within Seconds

2 - 4 Minutes

5 - 10 Minutes

~ 10 Minutes

Duration  the average length of time the patient feels the effect of ketamine

Intravenous

Intramuscular

Oral/Sublingual

Esketamine

1 - 2 Hours

1 - 2 Hours

2 - 4 Hours

2 - 4 Hours

Frequency  how often the patient does a session for an average treatment

Intravenous

Intramuscular

Oral/Sublingual

Esketamine

6 infusions
over 2 - 3 weeks

6 injections
over 2 - 3 weeks

6 treatments
over 4 - 6 weeks

12 treatments
over 8 weeks*

Frequency can be a bit of a tricky one to nail down, as the number and frequency of sessions depend on the purpose of treatment, the effectiveness of the first few sessions, the side effects experienced, and other factors. As is stated above, an average patient will receive 6 treatments over several weeks as well as any additional injections that their provider recommends.

*Esketamine, however, has a more unique dosage structure that is spread out over a longer period of time and frequently involves treatments every one to two weeks after the initial phase. As always, speak with your provider to create a plan that is catered towards your needs.

Cost  average out-of-pocket cost for patients

Intravenous

Intramuscular

Oral/Sublingual

Esketamine

$400 - $1,000
per infusion

$250 - $750
per injection

$150 - $200
per treatment

Cost determined by insurance

The data reported above are average ranges observed in the United States in a range of clinical settings. They are not considerate of insurance coverage or reimbursement.

Ketamine Treatment

Ketamine treatments focus on the neurobiologic benefits of ketamine. It is typically offered in hospitals, interventional psychiatry clinics, or multi-service behavioral health practices. Under this modality, ketamine, or esketamine, is administered and you remain in the clinic for ~2 hours under clinical observation. During this time you might wear an eye mask, listen to music, or sit quietly.

Research has found that the antidepressant effects of a single ketamine treatment under the medicalized approach can be felt within 2-24 hours and last for up to 1-2 weeks. Many providers suggest a course of multiple treatments over a fixed period of time (typically 6-8 treatments over 3-6 weeks), called an induction period, to achieve maximum impact and increase the duration of the antidepressant effects of ketamine.

Ketamine-Assisted Psychotherapy

Ketamine-Assisted Psychotherapy (KAP), combines talk therapy with a ketamine treatment. While KAP providers may take different approaches, most care models involve a talk therapy session before (called preparation) and after (called integration) a ketamine treatment, and sometimes involve an active conversation during the ketamine treatment.

When talk therapy occurs during the treatment, patients report experiencing a sense of liberation from defensiveness and self-consciousness, leading to the emergence of fresh ways of perceiving and addressing problems. The therapy session following your ketamine session, often occurs within 24 hours of your treatment, is aimed at “integrating”, or cementing, the learnings derived from your ketamine session.

some terms

check our work

We at Moss are a bunch of nerds and we love to cite our work. Here's a link to check out where we learned some of this information.
Learn More

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Outside Sources

Ketamine-Assisted Psychotherapy vs. Ketamine Infusion Therapy - Psychedelic Research and Training Institute

‍How Long Does Ketamine Last? Maintenance and Integration in Ketamine Therapy - Maya Health
‍
‍Ketamine Assisted Psychotherapy: A Systematic Narrative Review of the Literature - Journal of Pain Research

‍Cognitive behavior therapy may sustain antidepressant effects of intravenous ketamine in treatment-resistant depression - Psychotherapy and Psychosomatics

‍A Proof-of-Concept Study of Subanesthetic Intravenous Ketamine Combined With Prolonged Exposure Therapy Among Veterans With Posttraumatic Stress Disorder - The Journal of Clinical Psychology

Comparison of the efficacy of ketamine– propofol versus sodium thiopental–fentanyl in sedation: a randomised clinical trial - Emergency Medicine Journal

Continuous thoracic spinal anesthesia with local anesthetic plus midazolam and ketamine is superior to local anesthetic plus fentanyl in major abdominal surgery - Surgery Open Science

Parke-Davis Research Laboratories, Ann Arbor, Michigan -- 1960s aerial postcard - Wystan on Flickr - Used under CC BY-SA 2.0 license