A substance known largely as a club drug is receiving an increasing amount of attention as a possible treatment for people with depression when other methods have failed.

Once viewed with intense skepticism, the anesthetic ketamine continues to gain traction for treating complicated depression that doesn’t respond to medications.

Treatment-resistant depression affects of all people with major depressive disorders.

People with treatment-resistant depression often go through a variety of different medications.

This can mean longer waits for medication to work, increased dosage, or an increase in unwanted side effects.

Dr. Theodore Henderson, Ph.D., medical director of Neuro-Luminance Ketamine Infusion Centers in Denver, says he’s treated about 345 patients with treatment-resistant depression with ketamine. About 80 percent of them responded well to the treatment. He says ketamine should be continually explored as a treatment option for people with depression.

“To not use ketamine when it is available, I think is ethically and morally repugnant because we’re saving lives,” he told Healthline.

Some organizations like the American Psychiatric Association (APA) have warned about addiction potential, but many groups are now opening up to the idea, although safety is still a major concern.

The APA Task Force on Novel Biomarkers and Treatments along with a sub-group are creating a treatment advisory for the current use of ketamine.

There is also a current clinical trial sponsored by the National Institute of Mental Health to test the safety and effectiveness of ketamine for major depression. The trial, which includes 324 people, is scheduled for completion in April 2017.

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Using Ketamine in a Clinical Setting

When used as a recreational drug or to begin anesthesia, ketamine puts users in a trance-like state where pain is reduced and a person feels sleepy and possibly hallucinates.

It’s been used in medical practice since 1970 and was added to the list of controlled substances in 1999.

Ketamine is sometimes referred to as “Special K” when used for nonmedical reasons. In those situations, users typically ingest a 1- to 40-mg dose. However, in clinical settings, like those Henderson oversees, doses are at 0.5 mg and diffused over 30 to 40 minutes.

Patients often report feeling the effect immediately, which is known as the “happy juice effect,” Henderson says.

“If the happy juice effect was all that occurred, I wouldn’t have opened a center,” he said.

But, the lasting changes in the brain, Henderson says, are due to ketamine’s ability to activate the growth of new neurons, causing the cells’ dendrites to branch like growing trees and create new synapses.

This is due to brain-derived neurotrophic factor (BDNF), a protein in the brain that can become depleted after repeated stress or chronic depression. Lowered levels of BDNF can lead to atrophy of the hippocampus, a pivotal part of the brain related to memory.

“Depression is a physical, physiological disease process,” Henderson said. “Neurons are dying. Synapses are being destroyed.”

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Effects Are Temporary

The secondary effects of ketamine therapy typically only last between four to 10 days.

As part of the treatment at Neuro-Luminance, patients are given an average of 4.3 infusions, administered in sessions at least a week apart, and under the care of a psychiatrist and anesthetist. A patient’s vital signs are closely monitored during the process.

“If I’m targeting the parts of the brain showing the damage depression does, it makes sense it will take time,” Henderson said.

In a paper published in Neural Regeneration Research, Henderson reports that of the 100 patients who were willing to be studied, 80 have shown clinically significant improvement.

To receive the treatment, patients must have tried at least five different antidepressant medications without success. Interestingly, after therapy with ketamine, most patients studied were taking medications that controlled their symptoms.

“Those treatments work better because the brain is healthier,” Henderson said.

He also noted that adverse effects are low. The most common side effect patients report is brief periods of dizziness during treatment, and a small amount experience raised blood pressure.

Some believe that in order to experience the full effects of ketamine therapy, patients must experience hallucinations.

“That’s absolutely untrue,” Henderson said, adding he’s only had one patient who briefly experienced hallucinations.