Ketamine: What Is It And How Does It Work?

Also used as a recreational drug, ketamine is a dissociative anesthetic used medically as anesthesia. Compared to drugs with similar effects which are irritating, flammable, or even explosive, ketamine is simple to administer and highly tolerable.

Preserved airway reflexes and breathing, stimulated heart function with blood pressure increased, and moderate bronchodilation are the distinguishing features of ketamine anesthesia. At lower doses, ketamine is a promising agent for pain and treatment-resistant depression. However, the antidepressant action of a single administration of ketamine wanes over time. The long-term effects of repeated use are mostly unknown, and remain under investigation.

Derived from PCP, ketamine is a novel compound, created in pursuit of a safer anesthetic. At anesthetic doses, ketamine induces a trance-like state of “dissociative anesthesia”, offering sedation, acute pain management, and amnesia.

Regular, recreational users of high doses exhibit liver and urinary toxicity. Ketamine is an NMDA receptor pore blocker, which accounts for most of its actions. The mechanism of ketamine’s antidepressant effects remains a matter of research.

Read more information about ketamine as an anesthetic here :

In this post, we’ll cover:

  • The history and therapeutic uses of ketamine
  • What to expect from ketamine and how to take it
  • Substances that are similar to ketamine
  • Pharmacokinetics and effects of ketamine
  • Legality of ketamine

Read on to learn all about ketamine and its uses.

Overview of Ketamine

Emergency responders rescuing patients from suicide attempts were the first to observe the potential use of ketamine in treating depression.

Ketamine produces a dissociative experience or trip—this was the basis for its original popularity on the club drug scene, where it is called by street names such as K, vitamin K, kit kat, special K, super K, and others. Recreational users have been known to consume this psychedelic drug by smoking, snorting, or injecting it in various ways.

But more recently, doctors have developed a protocol for ketamine use that, while technically off-label, is still medically supervised and safe. This offers more avenues for accessing the potential of ketamine for treatment-resistant depression and other conditions.

How Do You Take Ketamine?

There are several ways people use kratom to dissociate, or for doctors to use this to anesthetize patients.

The only FDA approved form used in psychiatry to treat depression is the nasal spray called esketamine or brand name Spravato. This is obviously an intranasal prescription medication comes in the form of a nasal spray and is intended for people who have taken antidepressant pills, but have major depressive disorder, or are suicidal and not been helped by their medication.

The patient keeps taking their antidepressant—that is important—and they receive esketamine at a clinic or doctor’s office where a clinician or other healthcare provider supervises them for at least 2 hours after they receive their dose. The research indicates that patients who take esketamine show a significant, rapid improvement in symptoms of depression compared with placebo.

Typically for the first 1 to 4 weeks, patients with treatment-resistant depression will receive the nasal spray twice weekly. After that, they receive the spray once a week for 5 to 9 weeks. Next, they will receive the spray either once every week or every other week.

Other forms of ketamine are not FDA-approved for treating mental health conditions but are still being used that way. These include IV infusion, IM injections, and lozenges. Most current research focuses on IV ketamine infusions for patients with treatment-resistant depression.

For patients taking these infusions, they start with two infusions a week, each one lasting about 40 minutes. After that they go down to one infusion a week, and eventually most people end up at one infusion every 2 to 4 weeks until they stop coming—though of course they can return if symptoms do.

During each 40 minute infusion the patient has a dissociative experience that starts quickly and lasts until 15 to 20 minutes after the drip ends. They are supervised throughout the process. They usually appear to be asleep throughout this period. Most clinics talk through the experience with patients afterwards in an integration process. Ongoing therapy and antidepressant treatment is always recommended.

Is It Really Ketamine?

An overdose of ketamine can cause dangerously slowed breathing and unconsciousness. Benzodiazepines such as valium can cause similar effects.

Other hallucinogenic drugs such as PCP, LSD, and mescaline can cause hallucinations. Several other drugs such as Rohypnol, GHB, and other depressants are misused in a similar way to ketamine for their sedative/amnesiac qualities to facilitate sexual assault.

History and Use of Ketamine

ketamine molecule

Ketamine was first used as a veterinary anesthetic or tranquilizer in 1960s Belgium. The US Food and Drug Administration (FDA) approved it as an anesthetic for humans in 1970, and soon thereafter it was used during the Vietnam War to treat injured soldiers, to relieve them of paine.

The use of ketamine as an anesthetic is ideal for short-term procedures which do not require muscle relaxation. Ketamine suppresses the respiratory system less and stimulates the circulatory system more than other anesthetics.

This preserves protective airway reflexes and the use of ketamine is safe even among severely injured people. These bronchodilating properties allow ketamine to be used in patients with chronic obstructive airway disease, asthma, and active bronchospasm and other forms of severe reactive airway disease.

Ketamine is also an option in children, as an induction agent or the sole anesthetic for minor procedures. Children with neuromuscular disorders and cyanotic heart disease in particular are good candidates for ketamine anesthesia.

Veterinary use of ketamine is also common. Ketamine is often used as an anesthetic and analgesic on dogs, cats, rats, rabbits, horses, and other animals.

Therapeutic Uses of Ketamine

Acute and Chronic Pain Treatment

During the perioperative period and in emergency departments, ketamine infusions are used in individuals with acute, refractory, and chronic pain. These lower, sub-anesthetic doses of ketamine given adjunctive to morphine or alone reduce pain level, morphine use, and vomiting and nausea after surgery.

Ketamine is most likely to benefit opioid-tolerant patients and surgical patients where severe postoperative pain is predicted. Ketamine is about as effective as opioids in a hospital emergency department and may also prevent postanesthetic shivering and opioid-induced hyperalgesia.

Ketamine is also an effective intravenous analgesic for chronic pain, especially neuropathic pain and other neurological issues, because in multiple clinical trials it also counteracts wind-up phenomena or spinal sensitization, which is commonly experienced with chronic pain.

Ketamine for Depression

As mentioned above, esketamine, the nasal spray version of ketamine which is commercially sold as Spravato, is now FDA-approved as an antidepressant and sold for treatment-resistant depression in the US and elsewhere.

Pharmacodynamics and Mechanism of Action

Ketamine produces analgesic, anesthetic, and psychotomimetic effects by pore blocking the NMDA receptor and acting as an ionotropic glutamate receptor. This in turn interferes with pain transmission in the spinal cord and prevents central sensitization in dorsal horn neurons. It is not clear whether the NMDA receptor acts alone or whether it interacts with other receptors such as the AMPA receptors, which in turn might help mediate antidepressant effects.

Ketamine itself is a blend of equal amounts of two enantiomers: arketamine and esketamine. Because NMDA receptor antagonism is thought to be the foundation of the antidepressant properties of ketamine, researchers developed esketamine as an antidepressant, thinking it was the more potent dissociative hallucinogen and NMDA receptor pore blocker than arketamine.

Short-Term and Long-Term Effects of Ketamine

Smaller and typically-sized sub-anesthetic doses of ketamine can create distorted and unreal sensations, hallucinations and flashbacks, an “off” sense of one’s body, temporarily unusual thoughts and beliefs, a dissociative state, and a buzz or euphoria. The ketamine trip usually lasts about two hours.

Side effects of ketamine at higher doses can include lowered heart rate, high blood pressure, unconsciousness, sedation, psychosis, and dangerously slow breathing. High doses of the drug, especially repeatedly, can cause long-term problems, such as kidney problems and ulcers.

Because ketamine can cause symptoms of psychosis, it is not indicated for patients with schizophrenia.

At high enough doses, some users experience the k-hole, a near-death state of dissociation with visual and auditory hallucinations. This psychonautic experience with ketamine is sometimes sought after, but not for beginners.

Urinary and Liver Toxicity

Urinary toxicity is most common among routine users of large amounts of ketamine. Complaints may include urinary urgency, dysuria, cystitis, blood in urine, frequent or painful urination, hydronephrosis, cystitis, or kidney failure. Similarly, liver toxicity related to ketamine use involves repeated use of higher doses.


Main contraindications for ketamine include:

  • Age less than 3 months
  • Pregnancy
  • Active substance use disorder
  • Poorly controlled psychosis/schizophrenia
  • Severe cardiovascular disease such as unstable angina or poorly controlled hypertension
  • Severe liver disease such as cirrhosis

Legality of Ketamine

The legal status of ketamine changes from place to place. Although it is a medical compound in some places, in many countries it is a controlled substance, but it is also widely recognized as having medical value, at least as an anesthetic. Here are a few examples:

Final Thoughts on Ketamine

Ketamine is certainly not the first-line treatment for everyone. But for people who have struggled for years with depression and felt like nothing else has worked, ketamine may offer new hope for success.