Jeff Winograd didn’t know an adult life without depression. Since he was 20 years old, he had tried virtually every antidepressant on the market. But he says, “The depression was just a constant.”

By the time he was 45 years old, by then a father of two small children and a struggling-at-the-time film and video producer in Portland, OR, Winograd had hit rock bottom. The depression was so severe that he felt paralyzed by it.

“I sat on the couch all day, unable to move, I couldn’t move my feet,” he says. “And I was suicidal. I would sit and try to figure out how I was going to do it without hurting my kids.”

It was around that time that a doctor friend told him about ketamine for treatment-resistant depression.

What Is Ketamine?

Ketamine got its start in Belgium in the 1960s as an anesthesia medicine for animals. The FDA approved it as an anesthetic for people in 1970. It was used in treating injured soldiers on the battlefields in the Vietnam War. Unlike other anesthetics, ketamine doesn’t slow breathing or heart rate, so patients don’t need to be on a ventilator to receive it.

“When enough stories like that started to pile up, doctors said, ‘Maybe there’s something here,’” says Stewart, an emergency physician and founder of Insight Ketamine in Santa Fe, NM. Like the drug itself, Stewart got his start in combat medicine during the Vietnam War. Some doctors also use ketamine to treat suicidal thoughts.

Ketamine causes what doctors call a “dissociative experience” and what most anyone else would call a “trip.” That’s how it became a club drug, called K, Special K, Super K, and Vitamin K among others. Partiers inject it, put it in drinks, snort it, or add it to joints or cigarettes.

But the drug’s potential as a treatment for depression and antidote to suicidal thoughts has drawn researchers’ attention. They’ve studied and administered it in controlled, clinical settings to help with treatment-resistant depression and other conditions.

To be clear: Casual use is not a treatment for depression. But doctors have developed a protocol for medically supervised use that may help people who don’t get relief from other medications.

“We’re reaching out in a new way to patients who have not responded to other kinds of treatments and providing, for some of them, the first time that they’ve gotten better from their depression,” Krystal says.

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Ketamine comes in several forms. The only one that the FDA has approved as a medication for depression is a nasal spray called esketamine (Spravato). It’s for adults who either haven’t been helped by antidepressant pills, have major depressive disorder, or are suicidal. They continue on their antidepressant and receive esketamine at a doctor’s office or in a clinic, where a health care provider watches over them for 2 hours after the dose.

For treatment-resistant depression, patients usually get the nasal spray twice a week for 1 to 4 weeks; then once a week for weeks 5 to 9; and then once every week or 2 after that.

Most research stops the initial treatment at 6 weeks. There’s no research to suggest that more than 6 weeks in a row brings more benefits, though people do go back for boosters if symptoms return.

The IV infusion lasts about 40 minutes. The dissociative experience starts quickly and takes about 15 to 20 minutes to wear off after the drip ends. A doctor is always on site during the whole process. The doctor isn’t necessarily in the room with the person being treated but is available if they need anything or become anxious or confused.

Winograd describes it similarly. He talks about feeling like he was floating in a color. “It was the first time I understood the expression ‘happy place.’ It was this space where everything that had to do with my real life disappeared, and I didn’t have any of that weight that I carry with me everywhere I go.”

The antidepressant effects of ketamine wear off in hours, days, or a couple weeks in people who only get a single infusion. The series of infusions has longer-lasting effects.

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At Stewart’s clinic, after the mind-altering part of the ketamine experience is over, a health provider sits and talks with the patient in a process called integration. Other clinics may recommend that patients continue their talk therapy elsewhere.

“It’s my sense that this is important,” Stewart says. “When people come out of this really profound experience, they have a lot to say, and these are people who have a lot of baggage and a lot of experiential pain. A lot of times, ketamine leads to an unpacking of that baggage.”

Krystal, who provides IV and intranasal ketamine for treatment-resistant mood disorders at the VA Connecticut Health System and Yale-New Haven Hospital, encourages patients to continue with their psychotherapy after ketamine treatment.

Doctors who administer IV ketamine tend to recommend patients continue with their regular antidepressant regimen, too. As for the nasal spray, it’s only approved for use along with an oral antidepressant.

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For both Winograd and Coulter-Scott, and an estimated 70% of people who try medically supervised ketamine for a mental health condition, the benefits of ketamine continue after the trip is over. Researchers are studying why that may be.

Here’s what they know so far: A few depressed people won’t have the drug trip that ketamine typically causes, yet they still report relief from depression, starting a few days after a dose.

“We think that the number of synapses goes down because depression is so stressful that you actually prune or lose some of the synaptic connections in the brain,” Krystal says.

But research shows that within 24 hours of the first dose of medically supervised ketamine, those lost connections start to regrow. The more synapses they grow, the better the antidepressant effects of ketamine are for them.

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Ketamine may work in other ways in the brain, too.

Some nerve cells (neurons) in the brain involved in mood use a chemical (neurotransmitter) called glutamate to communicate with each other. The nerve cells need glutamate receptors — think of them like catcher’s mitts for glutamate — in order to join in this communication.

In the brains of some people with depression, those nerve cells don’t get so excited by glutamate anymore. It’s as if the glutamate receptors — the catcher’s mitts — are deactivated or weakened.

But after people with this particular problem receive ketamine, those nerve cell connections get restocked with new glutamate receptors. It’s as if ketamine helps make new catcher’s mitts for the glutamate, so that the nerve cells can respond to it again.

Research suggests that though ketamine’s main action is in glutamate receptors, it needs opioid receptors to have its antidepressant effects, too. For psychiatrist Alan Shatzberg, MD, who did some of the research that uncovered this, that’s concerning.

“I think it’s probably less addictive than opioids, but it’s not without its risks,” says Shatzberg, who is the director of Stanford University’s Mood Disorders Center. Indeed, case studies have described people who showed signs of addiction or abused the drug.

Because it’s an off-label treatment, it may be too soon to tell whether the risk of addiction or tolerance outweighs the possible benefits. It’s important to note though that some recommendations suggest it may not be safe for people who have a history of substance abuse. Many clinical trials have barred people with substance use problems.

It also may not be safe for people who have schizophrenia. “At the antidepressant dose, ketamine transiently worsens their symptoms of psychosis,” Krystal says.

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As for the drug’s action on glutamate receptors: Regrowing and reactivating synapses helps the brain’s ability to change, which may help it shift out of depression. That may also explain why antidepressants or psychotherapy that didn’t help before ketamine may help afterward.

Before ketamine, Winograd says he only went to therapy because his family begged him to go. “After I started to feel better,” Winograd says, “my therapist started to make more sense.”

As for Coulter-Scott, she’s only four infusions into her six-dose treatment, and already she says she sleeps better at night. Trouble sleeping is a common symptom of depression. Raising her 4-year-old granddaughter on her own, she says, she still feels stress, but it doesn’t come along with the darkness and anxiety that she had lived with until now.

Costs and Insurance – Buy ketamine hcl powder

Typically, the only ketamine treatment for depression that insurance will cover is the FDA-approved nasal spray called esketamine (Spravato).

Because the FDA has not approved IV ketamine for depression, most insurance doesn’t cover it. Without insurance coverage, an infusion costs about $450. That comes to about $3,000 to $4,000 for the research-based six infusions over 3 weeks. That doesn’t include boosters for whenever symptoms reappear.

Insurance disputes have prevented Winograd from getting a booster, even with the nasal spray, though he and his health care providers feel that he would benefit from it. Still, he says, the big changes that the first series of treatments brought about have lasted.

“That wasn’t a temporary change,” he says. “It was a shift in who I am, how I approach the world, and my feelings towards my own emotions.”