Ketamine

If you've heard of ketamine, it's probably for its history of abuse as a club drug. But it could also be one of the biggest breakthroughs in treating severe depression in years. How can one drug hold such promise and peril? The answer lies in how it affects your brain. Ketamine works like a flash mob, temporarily taking over a certain chemical "receptor." In some cases and with expert medical care, that can be a good thing. But cross that line, and it's big trouble. Ketamine got its start as an anesthesia medicine in the 1960s. It was used on the battlefields of the Vietnam War. At lower doses, it can help ease pain. When misused, ketamine can change your sense of sight and sound. You can have hallucinations and feel out of touch with your surroundings - and even from yourself. It can make it hard to speak or move, and it's been abused as a date-rape drug. "Outside of the clinic, ketamine can cause tragedies, but in the right hands, it is a miracle," says John Abenstein, MD, president of the American Society of Anesthesiologists. When used recreationally at high doses, people can feel like they're in what's called a "K-hole." This happens when they are on the verge of becoming unconscious. It's possible to get addicted or need higher doses to feel the effects. (This is less likely to happen when you get ketamine for medical reasons.) An overdose can be deadly.

"Every drug that causes any change in the senses has been and will be abused," Abenstein says.

Webmd Ketamine page:
https://www.webmd.com/depression/features/what-does-ketamine-do-your-brain

Ketamine is an anesthetic that is abused for its hallucinogenic properties. Its predominant legitimate use is as a veterinary anesthetic; however, it has been approved for use with both animals and humans. Abuse of the drug gained popularity when users discovered that it produced effects similar to those associated with PCP. Because of its anesthetic properties, ketamine also reportedly has been used by sexual predators to incapacitate their intended victims.

DOJ National Drug Intelligence Center Ketamine Fast Facts (PDF 2 pages):
https://www.justice.gov/archive/ndic/pubs4/4769/4769p.pdf

Ketamine is a dissociative anesthetic used in human anesthesia and veterinary medicine. Dissociative drugs are hallucinogens that cause a person to feel detached from reality. Much of the ketamine sold on the street has been diverted from veterinarians' offices. Ketamine's chemical structure and mechanism of action are similar to those of PCP. Although it is manufactured as an injectable liquid, in illicit use ketamine is generally evaporated to form a powder. Ketamine is snorted or swallowed. It is odorless and tasteless, so it can be added to beverages without being detected, and it induces amnesia. Because it has been used to commit sexual assaults due to its ability to sedate and incapacitate unsuspecting victims, ketamine is also considered to be a "date rape" drug. Ketamine can cause dream-like states and hallucinations. People who use the drug report sensations ranging from a pleasant feeling of floating to being separated from their bodies. Some ketamine experiences involve a terrifying feeling of almost complete sensory detachment that is likened to a near-death experience. These experiences, similar to a "bad trip" on LSD, are called the "K-hole."

Flashbacks have been reported several weeks after ketamine is used.

Ketamine slang terms:
Cat Tranquilizer, Cat Valium, Jet K, Kit Kat, Purple, Special K, Special La Coke, Super Acid, Super K, and Vitamin K

Facts about ketamine:
https://drugfree.org/drug/ketamine/

Ketamine Factsheet:

Ketamine:
https://www.drugwise.org.uk/ketamine/

Ketamine is a medication that is used to induce loss of consciousness, or anesthesia. Controversy has arisen about using ketamine "off-label" to treat depression. Off-label uses of drugs are uses that are not approved by the the United States, (U.S.) Food and Drug Administration (FDA). Ketamine is safe to use in controlled, medical practice, but it has abuse potential. Used outside the approved limits, its adverse mental and physical health effects can be hazardous. Prolonged use can lead to tolerance and psychological addiction.

Ketamine is the most widely used anesthetic in veterinary medicine and is used for some surgical procedures in humans.

For medical purposes, ketamine is either injected into a muscle or given through an intravenous (IV) line. It is considered safe as an anesthetic, because it does not reduce blood pressure or lower the breathing rate. When used as an anesthetic in humans, doctors combine it with another drug to prevent hallucinations. The fact that it does not need an electricity supply, oxygen, or highly trained staff makes it a suitable option in less wealthy countries and in disaster zones.

As a drug of abuse ketamine is most often used in the dance club setting as a party drug. It produces an abrupt high that lasts for about an hour. Users report euphoria, along with feelings of floating and other "out of body" sensations. Hallucinations, similar to those experienced with LSD, are common. Ketamine toxicity alone is unlikely to lead to death, according to the WHO. However, combining it with other substances, such as alcohol, can increase the sedative effects, possibly leading to a fatal overdose.

Uses of Ketamine:
https://www.medicalnewstoday.com/articles/302663.php

Ketamine is a dissociative anesthetic that has some hallucinogenic effects. It distorts perceptions of sight and sound and makes the user feel disconnected and not in control. It is an injectable, short-acting anesthetic for use in humans and animals. It is referred to as a "dissociative anesthetic" because it makes patients feel detached from their pain and environment.

Ketamine can induce a state of sedation (feeling calm and relaxed), immobility, relief from pain, and amnesia (no memory of events while under the influence of the drug). It is abused for its ability to produce dissociative sensations and hallucinations.

Ketamine has also been used to facilitate sexual assault. There are also several drugs such as GHB, Rohypnol, and other depressants that are misused for their amnesiac or sedative properties to facilitate sexual assault.

Ketamine is produced commercially in a number of countries, including the United States. Since the 1970s, ketamine has been marketed in the United States as an injectable, short-acting anesthetic for use in humans and animals. Most of the ketamine illegally distributed in the United States is diverted or stolen from legitimate sources, particularly veterinary clinics, or smuggled into the United States from Mexico. Distribution of ketamine typically occurs among friends and acquaintances, most often at raves, nightclubs, and at private parties; street sales of ketamine are rare.

Ketamine comes in a clear liquid and a white or off-white powder. Powdered ketamine is typically is packaged in small glass vials, small plastic bags, and capsules as well as paper, glassine, or aluminum foil folds.

Ketamine, along with the other "club drugs," has become popular among teens and young adults at dance clubs and "raves." Ketamine is manufactured commercially as a powder or liquid. Powdered ketamine is also formed from pharmaceutical ketamine by evaporating the liquid using hot plates, warming trays, or microwave ovens, a process that results in the formation of crystals, which are then ground into powder. Powdered ketamine is cut into lines known as bumps and snorted, or it is smoked, typically in marijuana or tobacco cigarettes. Liquid ketamine is injected or mixed into drinks. Ketamine is found by itself or often in combination with MDMA, amphetamine, methamphetamine, or cocaine.

The onset of effects is rapid and often occurs within a few minutes of taking the drug, though taking it orally results in a slightly slower onset of effects. Flashbacks have been reported several weeks after ketamine is used. Ketamine may also cause agitation, depression, cognitive difficulties, unconsciousness, and amnesia.

A "Special K" trip is touted as better than that of LSD or PCP because its hallucinatory effects are relatively short in duration, lasting approximately 30 to 60 minutes as opposed to several hours.

A couple of minutes after taking the drug, the user may experience an increase in heart rate and blood pressure that gradually decreases over the next 10 to 20 minutes. Ketamine can make users unresponsive to stimuli. When in this state, users experience involuntarily rapid eye movement, dilated pupils, salivation, tear secretions, and stiffening of the muscles. An overdose can cause unconsciousness and dangerously slowed breathing.

DEA resource guide (PDF 1 page 68 of 94):
https://www.dea.gov/sites/default/files/sites/getsmartaboutdrugs.com/files/publications/DoA_2017Ed_Updated_6.16.17.pdf#page=68

History
Ketamine, developed in 1962, was initially promoted as a fast acting general anesthetic. A few years later, in 1970, the federal government approved ketamine for human use, and as a result it soon became popular as a battlefield anesthetic. The first evidence of illicit abuse of the drug was on the West Coast. Later, during the late 1970s and early 1980s abuse began to increase across the country. Around the same time, new forms of the drug were being introduced into the illegal drug markets including capsules, powder, crystals, tablets, and solutions, in addition to other injectable forms. Starting in the mid-1980s another increase in the social-recreational use of ketamine was beginning to be linked to various dance cultures, initially as an adulterant - an added ingredient that can alter the effects of the drug - of MDMA (ecstasy). In fact there are reports that party/club goers in the United Kingdom first used ketamine when they ingested a pill they thought to be ecstasy. Today, there are still valid medicinal uses of ketamine for anesthetic reasons, though use is uncommon and tightly restricted. It has been used in radiation and burn therapy, treatment of battlefield injuries, and for children who have adverse reactions to other anesthetics. Ketamine is generally preferred in many of these instances because it does not have as deep a sedative effect as other medications. Illicit use today is also of great concern to many. Despite difficulty in determining its prevalence, use is higher today than it was when first introduced.

University of Maryland Center for Substance Abuse Research Ketamine Profile:
http://www.cesar.umd.edu/cesar/drugs/ketamine.asp

Abuse:
Abuse of large doses can also lead to powerful visual hallucinations that are intensified by environmental stimuli. Coma and deep unconsciousness can occur. When higher doses of ketamine are abused, or during emergence, it is reported to produce and vivid dreams and an "out-of-body", "K-hole" or "near-death" hallucinogenic experience, often reported as terrifying (similar to bad LSD trip). Central nervous system side effects such as agitation are less intense than those seen with PCP abuse.

For those who abuse ketamine via snorting adverse reactions may be less serious, but still present. Fast heart rate, high blood pressure, hallucinations, and impaired consciousness upon presentation to the emergency department may be most common effects with "snorting".

Tolerance can build to the effects over time, requiring greater doses of the drug to reach the same level of effect. Reports suggest that the dissociative effect may also disappear over time. Withdrawal may occur after chronic, extended use of ketamine. Withdrawal symptoms may include chills, sweats, excitation, hallucinations, teary eyes, and drug cravings.

There is no antidote for this drug.

Overdose situations are treated with symptomatic and supportive care in the hospital setting. In the emergency department, adverse effects typically resolve in 1 to 3 hours.

Ketamine Abuse:
https://www.drugs.com/illicit/ketamine.html

Urban Dictionary Ketamine:

• Ketamine originally comes in liquid form, when used recreationally and medically this can be injected. Although when using recreationally it is most commonly snorted. Firstly you have to cook the k up, this can be done in a few ways, dried naturally, on the cooker, in the oven, in the microwave. Whichever way its done the liquid needs to evaporate, leaving a crystal like substance. When the k had cooled down this substance is then ground down into a powder. This powder is then racked up into lines and snorted. When you snort a line of k you have what we call a grace period, It is the time before the k takes over your body, the time that you know its coming and its gonna fuck u up, a bit like waiting to come up on a pill but more intense. This length of this grace period depends, it can be anywhere between 10 seconds and 10 minutes. It depends on the person taking it, their tolerance to k, the size of the line they snorted, the quality of the k. Once the grace period is over and the k kicks in the forst felling you get is that something had been missing but now your whole again its like the k has come home, where it should be, and then you enter the k worlds. You can pretty much keep a level of control on k unless you slip into a hole. A k hole is the most intense trip, you travel to different worlds, different planes, you don't just experience this universe, you experience 20 others. However you don't do it as a human because you don't realize your human, probably because you don't think to question it, any type of reality goes out the window. A k hole is an amazing place and the presence of k is something that nobody should be denied.

• The most common dosage is 3-4 bumps, which brings a "loose and flowy" feeling to the users limbs, and extreme euphoria. You can easily recognize people on ketamine because the way they walk is similar to someone that is extremely drunk. The peak lasts for 30-40 mins, and the comedown is another 60 mins. Some say that ketamine feels similar to MDMA, others claim that it can be as harsh as PCP. If the user takes too much, they can easily get stuck in a "k-hole", which can send you into another level of being. Ketamine has a bad reputation because it has been used as a horse tranquilizer in the past, although ketamines effects aren't as harsh as most say.

• makes everything feel distorted, messes with your perspectives. Small amounts make you feel light and boucy, larger amounts can temporarily paralyse you...

Urban Dictionary Ketamine:
https://www.urbandictionary.com/define.php?term=ketamine

One way to think about this is that the k hole is a state between intoxication and a coma. While the consciousness of the real world diminishes in a k hole, a fantasy world of delusions and hallucinations can take over.

K-Hole and the Awful Effects of Ketamine :
https://www.verywellmind.com/what-is-a-k-hole-21861

Be Careful:

• Because of prohibition, ketamine is difficult to obtain, and people often sell counterfeit drugs as ketamine. Sometimes these are other dissociative drugs such as methoxetamine, deschloroketamine or 3-MeO-PCP, which can have quite different effects, onset times and duration. Sometimes they aren't dissociatives at all. A white powder could be anything.
• Ketamine is extremely dangerous to combine with central nervous system (CNS) depressants like alcohol, benzos or GHB.
• Do not try to walk on high doses of ketamine. You may not be seeing what is actually in front of you. Many people have fallen and injured themselves.
• Never use ketamine alone. Always have a "sitter" when taking high doses (someone sober whose job it is to watch over you during the experience). People have died after taking high doses of ketamine when their breathing passage became obstructed.

Dancesafe.org Ketamine:
https://dancesafe.org/ketamine/

Ketamine (brand name Ketalar) is a cyclohexanone derivative used for induction of anesthesia. Ketalar is indicated as the sole anesthetic agent for diagnostic and surgical procedures that do not require skeletal muscle relaxation; also, it is indicated for the induction of anesthesia prior to the administration of other general anesthetic agents. Ketamine blocks NMDA receptors through an interaction with sites thought to be located within the ion channel pore region. However, the complete pharmacology of ketamine is more complex, and it is known to directly interact with a variety of other sites to varying degrees. Recently, it was shown that inclusion of the NR3B subunit does not alter the ketamine sensitivity of recombinant NR1/NR2 receptors expressed in oocytes. Likewise, 100 uM ketamine produced only weak inhibition of the glycine-induced current of NR1/NR3A/NR3B receptors. The side effects of ketamine noted in clinical studies include psychedelic symptoms (hallucinations, memory defects, panic attacks), nausea/vomiting, somnolence, cardiovascular stimulation and, in a minority of patients, hepatoxicity. The recreational use of ketamine is increasing and comes with a variety of additional risks ranging from bladder and renal complications to persistent psychotypical behaviour and memory defects. Ketamine was first synthesized in 1962 by Calvin Stevens at Parke-Davis Co (now Pfizer) as an alternative anesthetic to phencyclidine. It was first used in humans in 1965 by Corssen and Domino and was introduced into clinical practice by 1970.

Ketamine:
https://drugs.ncats.io/drug/690G0D6V8H

A 2008 analysis found that burn victims who were given ketamine were less likely to develop symptoms of post-traumatic stress disorder, even if their injuries were more severe. Those findings have been replicated, such as a 2014 clinical trial of 41 patients, who saw their PTSD symptoms diminish within 24 hours, an effect that lasted for two weeks.

"When somebody gets one of their limbs dramatically blown off or is shot in the face, it's a very traumatic event," O'Carroll says. In such a situation, giving ketamine not only provides instant pain relief, it could prevent long-lasting trauma.

But ketamine's side effects are less common and easier to manage than PCP. In fact, ketamine is one of the safest drugs used in medicine today and can even be given to young children. For example, ketamine was used to sedate the boys' soccer team trapped in a cave in Thailand last year. Putting the kids in a tranquilized state made it easier to rescue them, and ketamine is safer than the opioids or benzodiazepines that are also commonly used as sedatives. But it wasn't until the 1990s that what could turn out to be ketamine's most important function was discovered. A team from Yale University School of Medicine was examining the role of glutamate, a common neurotransmitter, in depression, and discovered something remarkable: ketamine could rapidly relieve depression symptoms.

"To our surprise, the patients started saying, they were better in a few hours," Dennis Charney, one of the researchers, told Bloomberg. This rapid relief was unheard of in psychiatry.

Glutamate is associated with neural plasticity, our brain's ability to adapt and change at the level of the neuron. Ketamine blocks certain glutamate receptors, but not others, and the end effect could be to promote the growth of new neurons while protecting old ones. This could explain how ketamine can help reset the brain, though the theory hasn't yet been definitively proven.

From Popular Anesthetic to Antidepressant, Ketamine Isn't the Drug You Think It Is:
http://blogs.discovermagazine.com/crux/2019/03/22/ketamine-depression-anesthetic-painkiller/

The most commonly used antidepressants are largely variations on a theme; they increase the supply within synapses of a class of neurotransmitters believed to play a role in depression. While these drugs relieve depression for some, there is a weeks-long delay before they take effect, and some people with "treatment-resistant" depression do not respond at all. The discovery of rapidly acting antidepressants has transformed our expectations - we now look for treatments that will work in 6 hours rather than 6 weeks. But ketamine has some disadvantages; it has to be administered intravenously, the effects are transient, and it has side effects that require careful monitoring.

Within 40 minutes after a single infusion of ketamine, treatment-resistant depressed bipolar disorder patients experienced a reversal of a key symptom - loss of interest in pleasurable activities - which lasted up to 14 days.

Ketamine: A New (and Faster) Path to Treating Depression:
https://www.nimh.nih.gov/about/strategic-planning-reports/highlights/highlight-ketamine-a-new-and-faster-path-to-treating-depression.shtml

March 5, 2019 the Food and Drug Administration (FDA) approved the first truly new medication for major depression in decades. The drug is a nasal spray called esketamine, derived from ketamine - an anesthetic that has made waves for its surprising antidepressant effect. Because treatment with esketamine might be so helpful to patients with treatment-resistant depression (meaning standard treatments had not helped them), the FDA expedited the approval process to make it more quickly available. "This is a game changer," says John Krystal, MD, chief psychiatrist at Yale Medicine and one of the pioneers of ketamine research in the country. The drug works differently than those used previously, he notes, calling ketamine "the anti-medication" medication. "With most medications, like valium, the anti-anxiety effect you get only lasts when it is in your system. When the valium goes away, you can get rebound anxiety. When you take ketamine, it triggers reactions in your cortex that enable brain connections to regrow. It's the reaction to ketamine, not the presence of ketamine in the body that constitutes its effects," he says.

Interestingly, studies from Yale research labs showed that the drug ketamine, which was widely used as anesthesia during surgeries, triggers glutamate production, which, in a complex, cascading series of events, prompts the brain to form new neural connections. This makes the brain more adaptable and able to create new pathways, and gives patients the opportunity to develop more positive thoughts and behaviors. This was an effect that had not been seen before, even with traditional antidepressants. The FDA-approved drug esketamine is one version of the ketamine molecule, and makes up half of what is found in the commonly used anesthetic form of the drug. It works similarly, but its chemical makeup allows it to bind more tightly to the NMDA glutamate receptors, making it two to five times more potent. This means that patients need a lower dose of esketamine than they do ketamine. The nasal spray allows the drug to be taken more easily in an outpatient treatment setting, making it more accessible for patients than the IV treatments currently required to deliver ketamine.

Esketamine is only part of the treatment for a person with depression. To date, it has only been shown to be effective when taken in combination with an oral antidepressant.

How New Ketamine Drug Helps with Depression:
https://www.yalemedicine.org/stories/ketamine-depression/

Ketamine was once used mainly as an anesthetic on battlefields and in operating rooms. Now this medication is gaining ground as a promising treatment for some cases of major depression. Because of its rapid action, ketamine could have a role to play in helping to prevent suicide. If a person responds to ketamine, it can rapidly reduce suicidality (life-threatening thoughts and acts) and relieve other serious symptoms of depression. Other treatments for suicidal thoughts and depression often take weeks or even months to take effect, and some people need to try several medications or approaches to gain relief. This is true for talk therapies, antidepressant medicines, transcranial magnetic stimulation (TMS), and electroconvulsive therapy (ECT), which is currently the most effective treatment for major depression that fails to respond to other therapies.

All drugs have side effects. When someone is suicidal or severely depressed, possible benefits may outweigh possible risks.

Ketamine for major depression: New tool, new questions:
https://www.health.harvard.edu/blog/ketamine-for-major-depression-new-tool-new-questions-2019052216673

A new study suggests that ketamine activates the brain's opioid receptors, complicating its use to treat clinical depression
Pioneering neuroscientist John Lilly, who famously attempted to facilitate communication between humans and dolphins, used the drug in the late 1970s during experiments in sensory deprivation tanks. By the 1990s, the drug had made its way to the dance floor as "special K." More recently, ketamine has taken on a third, wholly unexpected role. Since the early 2000s, the drug has been studied as a uniquely powerful medication for treating severe depression and obsessive-compulsive disorder (OCD). When given as an intravenous infusion, ketamine can lift symptoms of depression and OCD from patients who fail to respond to common antidepressants like Prozac and even resist treatments like electroconvulsive therapy (ECT). Exactly how ketamine produces antidepressant effects remains unclear, however. "The prevailing hypothesis for ketamine's antidepressant effect is that it blocks a receptor (or docking port) for glutamate," According to a recent study in the American Journal of Psychiatry by Rodriguez and her Stanford colleagues, ketamine might also activate a third system in the brain: opioid receptors. The study linking ketamine to opioid activity means an extra dose of caution is required. While ketamine acts quickly, the anti-depressive effects of the drug only last for a few days to a week, meaning repeat doses would be needed in practice. Researchers and clinicians should consider the risk of addiction in long-term use, Schatzberg says. "You're going to eventually get into some form of tolerance I think, and that's not good."

Ketamine Works as a Fast-Acting Antidepressant, But the Full Effects Are Still Unknown:
https://www.smithsonianmag.com/science-nature/ketamine-works-fast-acting-antidepressant-full-effects-are-still-unknown-180970265/

Ketamine is a tiny, chiral molecule that easily passes through the blood-brain barrier. It primarily is a glutamate modulator that acts on the NMDA receptors in the glutamate pathway. There are many different ways to get ketamine into the human body, and each route has a different amount of bioavailability (the amount of medicine that effectively reaches the brain).

Paradigms of Ketamine Treatment:
https://maps.org/news/bulletin/articles/436-maps-bulletin-spring-2019-vol-29,-no-1/7718-paradigms-of-ketamine-treatment-spring-2019

Ketalar (ketamine hydrochloride)

Maximum Dosage:
Prescribers Digital Reference
Ketalar - Drug Summary: https://www.pdr.net/drug-summary/Ketalar-ketamine-hydrochloride-1999
Adults:	Specific maximum dosage information is not available. Dosage must be individualized.
Geriatric:	Specific maximum dosage information is not available. Dosage must be individualized.
Adolescents:	16 to 17 years: Specific maximum dosage information is not available. Dosage must be individualized.
Adolescents:	13 to 15 years: Safety and efficacy have not been established. Specific maximum dosage information is not available. Dosage must be individualized.
Children:	Safety and efficacy have not been established. Specific maximum dosage information is not available. Dosage must be individualized.
Infants:	Safety and efficacy have not been established. Specific maximum dosage information is not available. Dosage must be individualized.
Neonates:	Safety and efficacy have not been established; some experts do not recommend the use of ketamine in this age group. Specific maximum dosage information is not available. Dosage must be individualized.

Ketamine

Duration: A short acting dissociative anaesthetic and hallucinogen commonly used in emergency medicine. It is the prototypical dissociative, and is widely used at sub-anesthetic doses recreationally. Small doses are comparable with alcohol, while larger doses are immobilising and lead to psychedelic experiences: the "K-Hole."
Route	Onset	Duration	After Effects
Tripsit Factsheets
Ketamine Basic Information: http://drugs.tripsit.me/ketamine
Intravenous:	0-2 minutes	1-2 hours	1-2 hours
Intramuscular:	2-7.5 minutes	1-2 hours	1-2 hours
Oral:	10-75 minutes	1-2 hours	1-2 hours
Insufflated:	7.5-20 minutes	1-2 hours	1-2 hours
Avoid: Driving. Moving and walking if possible. Mixing with other depressants like alcohol, benzos and opiates.
Effects: A feeling of drunkenness and well being at low doses. As dose increases the user may begin to feel a disconnection from their body. At 'khole' doses the user may become completely disconnected from both body and mind.

Ketalar (ketamine hydrochloride injection)

Side Effects:
Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.
RxList
Ketamine Information: https://www.rxlist.com/consumer_ketamine/drugs-condition.htm
Tell your caregivers at once if you have any of these serious side effects within 24 hours after you receive ketamine: severe confusion, hallucinations, unusual thoughts, or extreme fear.
Call your doctor at once if you have: painful or difficult urination, increased urination, loss of bladder control, blood in your urine a light-headed feeling, like you might pass out slow heart rate, weak or shallow breathing jerky muscle movements that may look like convulsions
Common side effects may include: dream-like feeling blurred vision, double vision dizziness, drowsiness nausea, vomiting, loss of appetite sleep problems (insomnia)
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Pediatric:
Appropriate studies have not been performed on the relationship of age to the effects of ketamine injection in children younger than 16 years of age.

Safety and efficacy have not been established.

Geriatric:
Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of ketamine injection in the elderly. However, elderly patients are more likely to have age-related kidney, liver, or heart problems, which may require caution and an adjustment in the dose for patients receiving ketamine injection.

Other Interactions:

• Ethanol

Other Medical Problems:
Make sure you tell your doctor if you have any other medical problems, especially:

• Alcohol, excessive use
• Brain or nerve disease
• Drug abuse or dependence, history of
• Heart disease
• Liver disease
• Lung or breathing problems - Use with caution. May make these conditions worse

• Hypertension (high blood pressure), severe - Should not be used in patients with this condition

Ketamine (Injection Route) (Ketalar):
https://www.mayoclinic.org/drugs-supplements/ketamine-injection-route/description/drg-20075559

Breastfeeding:

Summary of Use During Lactation:
Breastmilk levels of ketamine have not been measured after administration to humans.

Minimal data indicated that ketamine use in nursing mothers may not affect the breastfed infant or lactation.

Until more data are available, ketamine should only be used with careful monitoring during breastfeeding. Alternate agents are preferred.

Alternate Drugs to Consider:

• Dexmedetomidine
• Etomidate
• Methohexital
• Propofol
• Thiopental

Ketamine Drug Levels and Effects:
https://www.ncbi.nlm.nih.gov/books/NBK500566/

Liver:
Long term ketamine use can cause inflammation and irritation to the urinary bladder and urethra, and similar changes have recently been described in the biliary tract, resulting in an acute or chronic cholestatic liver injury that can resemble sclerosing cholangitis.

Ketamine Hepatotoxicity:
Short term use of ketamine for anesthesia has been associated with rare instances of serum enzyme elevations, but not with clinically apparent liver injury. With chronic or intermittent use, however, unusual biliary and hepatic complications have been described. In a manner similar to its effects on the urinary tract, ketamine can also cause abnormalities in the biliary system with dilation and irregularity of the intra- and extra-hepatic bile ducts. Patients typically developed right upper quadrant pain and tenderness associated with elevations in serum alkaline phosphatase and aminotransferase levels, with minimal or no increase in bilirubin (Case 1). Biliary imaging may reveal dilation and irregularity of the intra- and extra-hepatic bile ducts with fusiform dilation of the common bile duct suggestive of choledochal cysts. Liver biopsy demonstrates changes suggestive of chronic liver obstruction or sclerosing cholangitis. Discontinuation of ketamine is usually followed by slow improvement and the abnormalities found on biliary imaging may no longer be demonstrable several months later.

B Likelihood score: B (highly likely cause of clinically apparent biliary and hepatic injury).

Ketamine Overview:
https://www.ncbi.nlm.nih.gov/books/NBK548337/

Psychonautwiki Ketamine:
https://psychonautwiki.org/wiki/Ketamine

"Ketamine is a cat or horse tranquilizer and not suitable for human consumption" - A common misrepresentation by the media

This myth gives the impression that ketamine use in humans is somehow deviant. But despite its wider use in veterinary medicine, ketamine was originally devised for and tested on humans.

The Essential Guide to Ketamine:
https://thethirdwave.co/psychedelics/ketamine/

Student Doctor Network Ketamine:

• Can Ketamine be used for general anesthesia? Yes. It was a frequent anesthetic in Haiti after the earthquake... but that was from a lack of other anesthetic modalities (think pediatric extremity amputations under ketamine). Ketamine is a safe drug for the most part but not a go to for general anesthesia here in the US. Great adjunct for a multimodal approach.
  • You know what is interesting about the history of ketamine? It replaced PCP otherwise known as Sernyl which was used to help induce general anesthsia in the 1950's. That's right... part of the old school anesthesia actually used PCP as their GA cocktail.... until ketamine was discovered.
    • Ketamine is used for pain in the PACU, ICU, and Stepdown floors. We also use it in the ER for pain and moderate sedation. Works well in some, causes others to freak out and then they attempt to kill their nurse.
      • Ketamine is NOT a great sedative. It is "A" sedative, but a terrible one at that compared to what is available to us. It is one of my favorite drugs out there... but you need to understand it. It absolutely creates a dissociative state that is not optimal for the person who is not in the right presence of mind.

Student Doctor Network Ketamine:
https://forums.studentdoctor.net/threads/ketamine-infusions.1246231/

World Health Organization 2006:
Ketamine can produce a state of dependence as shown in various animal models. This is supported by some human data as reported by the WHO. Although one should keep in mind that monitoring of adverse effects in patients is quite different from monitoring effects in recreational users. Due to its pharmacological effects it produces a depression of the central nervous system, resulting in hallucinations, disturbances in thinking and perception and also in motor function.

There is evidence that ketamine is abused, but looking at the figures one can hardly consider this to constitute a public health and social problem. Especially when comparing ketamine to the other cyclidines.

The substance is difficult to synthesize, so illegal production is unlikely. Preparations are mainly used in hospitals and veterinary clinics, so it is not expected that diversion will take place on a large scale. Summarizing all the available information international control is not really necessary, but keeping the drug under surveillance could be considered.

World Health Organization Critical review of Ketamine (PDF 30 pages):
https://www.who.int/medicines/areas/quality_safety/4.3KetamineCritReview.pdf

World Health Organization 2014:
This NMDA-receptor-antagonist is used as an an aesthetic in both human and veterinary medicine for short diagnostic and surgical procedures that do not require skeletal muscle relaxation. Ketamine is marketed under many trade names. It can produce a depression of the central nervous system, resulting in hallucinations, disturbances in thinking, perceptions and also in motor function. However, adverse events in patients are quite different from those found in recreational users.

Ketamine has been misused as a hallucinogen for almost 30 years. The effects are similar to those of phencyclidine, but with a much shorter duration.

35th WHO Meeting Recommendation:
Although we acknowledge the concerns raised by some countries and UN organizations, ketamine abuse currently does not appear to pose a significant global public-health risk. On the other hand if ketamine were placed under international control, this would adversely impact its availability and accessibility. This in turn would limit access to essential and emergency surgery, which would constitute a public-health crisis in countries where no affordable alternative an aesthetic is available. On this basis, we, the Expert Committee, decided that bringing ketamine under international control is not appropriate.

World Health Organization Ketamine Update Review Report (PDF 45 pages):
https://www.who.int/medicines/areas/quality_safety/6_2_Update.pdf

Erowid Experience Vault:
https://erowid.org/experiences/subs/exp_Ketamine.shtml

ketamineadvocacynetwork.org Forums:
https://www.ketamineadvocacynetwork.org/discussion-forums/

Ketamine (1000 Threads):
https://drugs-forum.com/forums/ketamine.92/

r/Ketamine:
https://www.reddit.com/r/ketamine/

DEA Ketamine (PDF 1 page):
https://www.deadiversion.usdoj.gov/drug_chem_info/ketamine.pdf

FDA KETALAR (ketamine hydrochloride) injection (PDF 10 pages):
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/016812s043lbl.pdf

New Zealand Ketalar Data Sheet (PDF 12 pages):
https://www.medsafe.govt.nz/Profs/Datasheet/k/ketalar100mginj.pdf

Ketamine 50 mg/ml Injection Package Leaflet (PDF 2 pages):
https://www.medicines.org.uk/emc/files/pil.6935.pdf

European Monitoring Centre for Drugs and Drug Addiction - Risk Assessment of Ketamine (PDF 120 pages):
http://www.emcdda.europa.eu/system/files/publications/173/Risk3_62941.pdf

Austrailia Alcohol and Drug Foundation Ketamine:
https://adf.org.au/drug-facts/ketamine/

Nortwestern University Woman's Health Research Institute
A cystitis caused by abuse of the club drug ketamine looks very much like interstitial cystitis according to a new study done in Taiwan. This drug is especially popular among young people in Asia, where the study urologists practice .

Be aware that this is why your doctor may ask you about your recreational drug use, especially if you are young. The article describes the issue and reports specifically on the type of bladder damage ketamine causes.

Ketamine Cause Cystitis Symptoms:
https://www.womenshealth.northwestern.edu/blog/ketamine-club-drug-cause-cystitis-symptoms

Ketamine Monograph (PDF 19 pages):
http://www.swgdrug.org/Monographs/KETAMINE.pdf

Ketamine Safety Data Sheet (PDF 5 pages):
https://www.caymanchem.com/msdss/11630m.pdf

Ketamine:

The distinguishing features of ketamine anesthesia are preserved breathing and airway reflexes, stimulated heart function with increased blood pressure, and moderate bronchodilation.

• A medication primarily used for starting and maintaining anesthesia
• It induces dissociative anesthesia, a trance-like state providing pain relief, sedation, and amnesia.
• Psychiatric side effects are frequent as well as raised blood pressure and nausea.
• Discovered in 1956
• Approved for use in the United States in 1970
• Ketamine is on the World Health Organization's List of Essential Medicines
• It is available as a generic medication
• Veterinarians often use ketamine with sedative drugs to produce balanced anaesthesia and analgesia, and as a constant-rate infusion to help prevent pain wind-up.
• Ketamine is also used as a recreational drug for its hallucinogenic and dissociative effects.
• At sufficiently high doses, users may experience what is called the "K-hole", a state of dissociation with visual and auditory hallucinations.
• Because of its ability to cause confusion and amnesia, ketamine has been used for date rape.

It was extensively used for surgical anesthesia in the Vietnam War due to its safety

Liver and urinary toxicity are common among regular users of high doses of ketamine for recreational purposes.

Recreational ketamine use has been implicated in deaths globally, with more than 90 deaths in England and Wales in the years of 2005 - 2013. They include accidental poisonings, drownings, traffic accidents, and suicides.

The discovery of antidepressive action of ketamine in 2000 has been described as the single most important advance in the treatment of depression in over 50 years. It has sparked interest in NMDA receptor antagonists for depression, and has shifted the direction of antidepressant research and development.