Ketamine: What’s the Most Effective Form of Administration?

Ketamine has been an established anesthetic since its discovery in 1956. However, interest in its hallucinogenic qualities, as well as other potential medical benefits, has meant its popularity has soared.

Not only are people curious about its effects but also what the most effective form of administration is.

First, let’s take a look at what ketamine is and what it’s used for.

What Is Ketamine?

Calvin L. Stevens, an American chemist, first synthesized ketamine in 1962. The compound demonstrated beneficial anesthetic effects, low behavioral toxicity, and was extremely fast-acting.

After the FDA approved its medical use in 1970, it became an important drug for emergency surgery during the Vietnam war.

In more modern times, research into ketamine’s other uses has begun, including how it might impact depression.

The drug is also widely used in veterinary medicine to sedate and even manage pain in larger animals. Cats, dogs, mice, rabbits, and horses are just a few examples. This is no doubt, where it gets its reputation as a ‘horse tranquilizer’.

Ketamine is also a well-known hallucinogenic. Taken in subanesthetic doses, the drug causes a sedentary state, which many describe as a ‘trance’. It also produces several dissociative effects that may include, but are not limited to:

  • Visual distortions, including the perception of color
  • Auditory hallucinations
  • Dizziness
  • A sense of euphoria
  • Limited or irregular speech function

This has led ketamine to be regarded as both a recreational and medically beneficial drug.

An Overview of Ketamine Administration

When it comes to administering, ketamine is a highly versatile drug, as it is both water and lipid-soluble. Oral, intravenous, epidural, and transnasal are just a few ways ketamine is known to be used.


Because of this, ketamine comes in many forms; this includes:

  • Pills or tablets
  • White crystalline powder
  • Clear liquid
  • Nasal and oral sprays

Like most drugs, efficacy is determined by several factors, which may include; prior drug use, individual physiology, desired outcome, as well as dose size. Therefore, labeling one method of administration as more effective than another is often complicated.

Nonetheless, knowing the differences can be important.

Let’s take a look at both popular medical and recreational methods of consuming ketamine.

Administration of Liquid Ketamine

Ketamine is most predominantly used as an anesthetic. In these instances, ketamine administration is typically intravenous, in other words, injected into a vein.

Once ketamine has reached the bloodstream, it circulates through the body and binds to NMDA receptors. Many theorize this may encourage its hallucinogenic and analgesic qualities. However, the mechanism is not fully understood.


The main benefit of this method is that it bypasses the digestive system, which slows down drug onset. This delay may be due to:

  • First-pass effect: A process where the liver or gut partially metabolizes the drug. This results in a smaller concentration of the drug reaching systemic circulation.
  • Incomplete gastric-intestinal absorption: This happens when the drug consumed is only partially absorbed through the intestinal wall.

When consumed orally, ketamine can take up to 30 minutes before effects are felt. In comparison, when injected in liquid form, the effects of ketamine can be felt within a few minutes. This is why it’s so useful as an emergency sedative.

Aside from being fast-acting, research suggests injecting liquid ketamine also promotes bioavailability to 90%. This may be much less in oral administration.

In fact, as an injected medicine, ketamine is included in the World Health Organization’s List of Essential Medicines, proving its global importance.

Problems for Ketamine as an Anesthetic

One problem with using ketamine as an anesthetic is that doses need to be high.

At high doses, ketamine can display psychoactive side effects such as confusion, hallucinations, and sometimes memory loss. All of which can interfere with the drug’s intended purpose.

This is why ketamine is often used as a secondary rather than primary anesthetic.

However, ketamine has also shown analgesic effects. When used as a treatment for pain management, the psychotropic side effects are much more manageable, as doses tend to be lower.

Research into appropriate administration for pain relief is still on-going.

Ketamine Nasal and Oral Spray

In March 2019, the FDA approved an esketamine nasal spray for treatment-resistant depression.

Ketamine is a chiral compound; it has two enantiomers; esketamine (S-ketamine) and arketamine (R-Ketamine). While many medications contain both compounds, esketamine is thought to impact the NMDA receptors to a greater extent.

As a nasal spray, esketamine is administered intranasally or up the nose. Once the drug coats the soft nasal walls, it is then absorbed into the bloodstream, where it can travel to the NMDA receptors.

While snorting esketamine does not produce effects as quickly as injecting, many believe it has a longer duration.

In one study, researchers investigated esketaine efficacy on depression. Participants administered the drug intranasally twice weekly for the first 2 weeks, before dropping to only one dose every 3 weeks. When compared to the placebo group, researchers found that participants experienced improved depressive symptoms, even when doses were less frequent.

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However, much more testing is needed before we have conclusive evidence on effective dosing and administration for depression.

Non-Medicinal Administration of Ketamine

Recreational ketamine-use typically takes the form of a white crystalline powder, and less commonly a tablet or injection.

Typically, the ketamine power is consumed by snorting. Like we have previously mentioned, this often leads to a longer duration of effects. In this form, users typically experience subanesthetic effects, such as relaxation and dream-like states.

However, as ketamine is a sedative, determining an appropriate dose can be difficult. Users may be vulnerable to side effects, which can include:

  • Increased heart rate and blood pressure
  • Agitation and delirium
  • Paralysis
  • Abdominal pain
  • Liver damage
  • Damage to the urinary tract

Not to mention that in the US, as well as many other places in the world, recreational ketamine use is illegal.

Final Thoughts on Effective Ketamine Administration

It’s clear that the efficacy of ketamine is determined by its purpose. For instance, as an anesthetic medicine, injecting ketamine is certainly the most effective form. In comparison, the intranasal administration of esketamine may be more useful for depression.

In essence, it’s impossible to generalize one form as superior to another. This is especially true considering long-term research is still very limited on ketamine’s uses.

Recreational ketamine use is highly illegal in most places around the world. In light of that, this information is intended for informational purposes only.

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