Ketamine: Effective against pain and depression

Ketamine is an  active ingredient that  plays a major role in emergency medicine as a fast-acting  pain reliever . But the drug is also used as an anesthetic and  antidepressant  . In this article, you will learn what other uses ketamine is used for, what effects it has on the body, and why it is precisely the undesirable side effects of ketamine that have prompted its abuse as a drug.

What is ketamine?

The active ingredient ketamine, originally developed as an anesthetic, has been known since 1963. Today it is also used to  treat depression  and pain. Ketamine is a prescription drug that is not available over the counter. The most common application is as an infusion solution. It can also be taken in through the nose (nasal) or mouth (oral).

Ketamine, Esketamine and S-Ketamine – What’s the Difference?

In terms of naming, the spellings esketamine or S-ketamine are also more common. This expression refers to the molecular composition of the substance, so it has a chemical background.

In chemistry, a distinction is made between molecules with the same structural formula, i.e. with the same blueprint, the so-called enantiomers. One can think of enantiomers as mirror images. If you look at a written word in a mirror, the writing looks “upside down” to us. The situation is similar with molecules.

Scientists distinguish between S-enantiomers and R-enantiomers. To stay with the analogy, S-enantiomers would be the mirror image and R-enantiomers would be the mirror image. Although the substances have the same structure in terms of their structural formula, they have different modes of action.

Another analogy to better understand this circumstance is the image of two identical gloves. Trying to put the right glove on the left hand will not produce the desired result. The situation is similar with the enantiomers. Although the S and R enantiomers are structurally identical, they cause different reactions in the body.

The active ingredient ketamine is a mixture of fifty percent S-ketamine and fifty percent R-ketamine.

How does ketamine work?

Ketamine acts on many different parts of the body. One of the most important receptors to which ketamine docks and on which it develops its effect bears the complicated name of N-methyl-D-aspartate (short: NMDA receptor). This is where ketamine is antagonistic, meaning it blocks these receptors, preventing the release of  glutamate . Glutamate is a neurotransmitter in our brain that activates neurons. So ketamine works by inhibiting glutamate, so fewer signals reach our brain.

The mode of action of ketamine is described in medicine with the term  “dissociative anaesthesia”  . Four effects are summarized under this expression:

  • Loss of consciousness: Those affected by ketamine lack psychological awareness of what is happening
  • Analgesia: The sensation of pain is blocked by ketamine
  • Amnesia: Those affected cannot remember
  • Preservation of the protective reflexes: This is particularly desirable in emergency medicine, since spontaneous breathing is not suppressed by ketamine, so those affected can continue to breathe independently despite the anesthetic

In addition to acting as a dissociative anesthetic, ketamine can affect other areas of the body:

  • Bronchi: Ketamine dilates the bronchi
  • Cardiovascular system: Ketamine increases blood pressure and heart rate
  • Brain: increase in intracranial pressure
  • Salivary glands: Ketamine promotes the production of  saliva

Ketamine in medicine – where is it used?

Ketamine’s profile of action makes it an ideal emergency drug, used by paramedics after accidents, for example. In contrast to similar active ingredients such as propofol, ketamine stabilizes the circulation and at the same time reduces the sensation of pain.

Because of its bronchodilator effect, ketamine can also be used as a remedy for status asthmaticus. Physicians understand status asthmaticus to be a life-threatening asthma attack in which those affected cannot breathe sufficiently despite taking medication. 

Ketamine is also used in anesthesia. Here mostly in the form of  Ketanest®  as a ketamine infusion. This is a pre-packaged solution of esketamine that has the dosage of the drug pre-determined.

If the anesthesiologist wants to induce  anesthesia  with ketamine, a  dosage  of 0.5 to 1 mg of esketamine per kilogram of the patient’s body weight is used. The duration of action of ketamine is quite short at ten to fifteen minutes, which is why ketamine can be added via the IV as needed during a procedure.

In addition, ketamine is also used in pain therapy, depression and as a drug.

Ketamine in pain therapy

If the dose of ketamine is reduced, the effects on consciousness disappear (in professional circles this is referred to as subnarcotic doses). Under these conditions, mainly the anti-pain effect is preserved. This is used, for example, when changing the dressing of large burns.

Another area of ​​application for ketamine is in the therapy of complex regional pain syndrome ( CRPS ). This phenomenon can occur after trauma, for example after a  broken bone . The exact cause of CRPS has not yet been conclusively researched, but the syndrome is associated with chronic pain and limited mobility in the affected area. If the usual therapies fail, one can try to combat the complex regional pain syndrome with a continuous infusion of ketamine over four days.

Opioids, such as morphine or  fentanyl  , can provide pain relief that is as good as ketamine therapy. However, these have an even higher potential for dependency and are associated with many side effects such as severe  constipation  .

Ketamine nasal spray – a new therapeutic approach for depression

The drug esketamine hydrochloride has been approved in the USA as a nasal drug for depression since 2019. Ketamine acts as an antidepressant in these cases and is sold in nasal spray form.

Initial clinical studies have described positive experiences with the new active ingredient, especially in patients with  bipolar  disorders and suicidal thoughts. The rapid onset of action, sometimes within two hours of application, was particularly noteworthy.

However, the molecular mechanisms behind this have not yet been clarified. It is controversial whether ketamine itself acts as an antidepressant or whether it only enhances other antidepressants.

Ketamine as a drug

Hallucinations are common with ketamine administration. While this is an undesirable side effect in medicine, it helped ketamine become popular on the drug scene. Ketamine belongs to the class of drugs  called hallucinogens , which also includes phencyclidine (PCP). Also known as “Angel Dust”, PCP was popular in the 1960’s and 1970’s, however the side effects were unpredictable and quite severe. 

Ketamine – also known by the names “Special-K”, “Kate”, “Keta” or “Vitamin K” – works within a very short time. If given intravenously within a minute, if taken orally as a tablet it may take ten to fifteen minutes.

In most cases, the substance comes from burglaries in pharmacies or practices. You can buy the drug in pharmacies or order it online, but since it requires a prescription, you need a prescription. In addition to the side effects of ketamine, the preparations purchased as a drug have the potential to be contaminated, making consumption even more dangerous than it already is.

The effects of a ketamine high are often described as colorful hallucinations. In addition, users report the following sensations during a trip: 

  • Having near-death experiences
  • Feeling of being detached from your own body
  • euphoric effect
  • Perception of space and time is distorted

Ketamine overdose

“Falling into the K-Hole” – this is how the condition of a ketamine overdose is described in the drug scene. The danger of a deadly ketamine intoxication is increased, especially in mixed consumption with alcohol. In too high doses, ketamine suppresses the reflexes in our respiratory center. In the worst case, respiratory arrest and death occur. 

Since some other substances besides ketamine, such as opioids, can cause such respiratory depression, the  detectability  of the drug is crucial in order to be able to decide on a possible treatment. However, ketamine is not easily detectable. It can only be detected in urine for two to four days and only if a special laboratory has been requested. For this reason, if an overdose is suspected, it is especially important to alert paramedics to the fact that the person has been taking ketamine.

In the worst case, ketamine can be life-threatening because there is no antidote to an overdose. To save sufferers from suffocation, they often have to be given artificial respiration to give the body time to rid itself of the drug.

Side Effects and Interactions

Like any drug, along with its beneficial effects, ketamine also has some undesirable side effects. These include: 

  • increase in intracranial pressure
  • nausea
  • hallucinations
  • Can lead to dependency
  • If the dose is too high: respiratory arrest

In medicine, ketamine is often combined with midazolam. Midazolam belongs to the drug class of tranquilizers (barbiturates) and prevents severe nightmares after ketamine administration.

Conclusion: Ketamine as a versatile active ingredient

Ketamine is a widely used drug that was originally developed for anesthesia. Today, however, it is only used there under certain circumstances, especially in emergency medicine, as some undesirable side effects have been observed. These side effects meant that the drug was also used in the drug scene as a party drug. 

In recent years, research has enabled the use of ketamine in new medical areas. The fast and strong effect on severe depression has awakened hope among scientists for new therapeutic approaches.


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