Ketamine is an anesthetic used for pain management. It's also used as an animal tranquilizer. Ketamine was developed in the 1960’s as an alternative to PCP and its associated more serious hallucinations. It was widely used during the Vietnam War.

Ketamine works by altering the inhibiting brain neurotransmitters, known as NMDA receptors. This inhibits the brains neurotransmitters ability to interact with glutamate, serotonin and dopamine. Ketamine does not affect the same neurotransmitters that are targeted by more traditional antidepressants. Ketamine blocks glutamate receptors impacting communications between the brain and the body.

Blocking this communication is what makes it an effective anesthetic. Ketamine creates a feeling of detachment, because it impacts the recipient’s sense of sight and sound. Like PCP, this has lead to it being adopted by the recreational drug crowd and is found in clubs, bars and parties and is known as "Special K."

Two main types of ketamine are used to treat major depression that hasn’t responded to two or more medications (treatment-resistant depression).

Racemic ketamine, which is most often given as an infusion into the bloodstream. This is sometimes called intravenous, or IV, ketamine. It is a mixture of two mirror-image molecules: “R” and “S” ketamine. While it was approved decades ago as an anesthetic by the FDA, it is used off-label to treat depression.

Esketamine (Spravato), which the FDA approved in March, is given as a nasal spray. It uses only the "S" molecule. Thus far, most research has been on ketamine infusions.

The two forms of ketamine interact differently with receptors in the brain. The delivery of ketamine and the type given affect drug effectiveness and side effects. We don’t yet know which type is more effective or how much side effects may differ. Further research comparing effectiveness and side effects is needed.

The side effects of taking too much Ketamine include loss of memory, delusions, hallucinations, loss of motor control, aggression, grandiosity and increased heart rate. More serious overdoses can lead to users experiencing near-death sensations, or while not common, actual death. Google ketamine, or Special K overdoses and you will find some pretty ugly stories.

In 2000, researchers started studying ketamine as a treatment for depression. Over the years, they've discovered it improves mood much faster than traditional antidepressant drugs, and it works when some of these drugs have failed.

Ketamine is FDA-approved as an anesthetic for surgery and diagnostic procedures. It's also used off-label to treat depression, suicidal thoughts, post traumatic disorder (PTSD), other mood disorders, and nerve-related pain.

Ketamine can be injected in low doses and can provide relief for several weeks for Major Depressive Disorder (MDD) and Bipolar Disorder. It is still under study and not approved by the FDA, so its use is considered off-label.

Research into using Ketamine in combination with other drugs such as D-cycloserine and lurasidone has shown promising results and may extend the efficacy of Ketamine out to 8 weeks. There have been no, or little studies about the impact of long term use.