One 10 ml vial of 1000 mg ketamine. Credit: Psychonaught/Wikipedia

Ashley Blanco, 27, has grappled with anxiety, depression and obsessive-compulsive disorder for the better part of a decade. Antidepressants and therapy didn't help. After she graduated college, the COVID-19 pandemic hit. It sent her mental health to an all-time low.

"I couldn't function. I wouldn't leave my room," she said. "I completely lost who I was."

The Miami resident was desperate to return to her old self. Her dad saw the intensity of her crisis in January 2021 and decided to recommend something new he had heard about from a friend: ketamine infusions. Blanco was hesitant at first, but gave it a try.

"He basically saved my life," Blanco said. "It's the best decision I could have ever made."

Ketamine is perhaps most well-known as a party drug that causes disassociation and hallucinations, dubbed "Special K." When used frequently and recreationally, especially at high doses, ketamine can actually cause depression or agitation, lead to dependence, or cause life-threatening effects, the Drug Enforcement Administration warns.

In medicine, however, ketamine has long been used as a general anesthetic: it received Food and Drug Administration approval for this purpose in 1970.

In more recent years, doctors have begun prescribing it off-label to treat depression, anxiety, drug addiction and other issues.

A review of 83 studies published in Cambridge University Press found support for its effect on depression, while evidence for other associations was less robust.

The treatment, once rare, has found virtual and in-person footholds throughout Central Florida. In Kissimmee, there's Revitalizing Infusion Therapies. Altamonte Springs hosts one of five Florida locations of the chain that treated Blanco, Ketamine Health Centers. The clinic is currently seeing about 30 to 40 patients, estimated Dr. Raul Cruz, the chain's medical director for anesthesiology.

A growing body of evidence suggests ketamine provides many people at least temporary relief as a fast-acting antidepressant. It is particularly helpful for the estimated one in three people with who can't find relief after trying at least two traditional antidepressants, potentially because it targets different parts of the brain, though more is needed to determine its long-term effects and safety, a 2017 report by an American Psychiatric Association task force noted.

"It is like night and day," said Robert Fay, a licensed mental health counselor with Thriveworks in Maitland who has seen over a dozen clients try infusions. "Now they have a meaning, a purpose, a value, a path. It's incredible."

How ketamine works

Depression is one of the leading causes of disability worldwide, according to the World Health Organization. Despite this, neither the disorder nor its treatments are completely understood.

Ketamine is theorized to reduce depression by affecting a chemical that helps to rewire the brain and create more positive thought patterns, said Ketamine Health Centers Director for Psychiatry Dr. Juan D. Oms.

"That's why you see a lot of these patients that will tell you, 'Well, I have a new perspective,' or, 'I see things in a different light,'" Oms said.

Blanco started with an approximately 80-minute IV infusion of ketamine to address her mental issues as well as some chronic pain. She sat down in an exam chair, covered her eyes, and listened to soothing music as the dose entered her bloodstream.

She felt detached and experienced mild hallucinations. With her eyes closed, she saw a kaleidoscope of colors, animals, and greenery. At one point, she felt her grandfather—who had passed away a year earlier—holding her hand.

She didn't have any negative side effects, though others sometimes report dissociation, anxiety, intoxication, sedation, high blood pressure, headache, nausea and vomiting, according to a blog post from Dr. Peter Grinspoon via Harvard Health Publishing.

That first session didn't get her back to normal, but after several more, she felt reinvigorated. She goes back regularly for boosters, currently works at a health care startup and is considering going back to get her masters in the health care field.

Objections, regulation issues remain

The practice has its drawbacks, however.

The Food and Drug Administration has not reviewed or approved ketamine infusions as a treatment for depression.

A 2017 report by an American Psychiatric Association task force noted there's extremely limited data on long-term ketamine use.

Oms said he thinks because ketamine leaves a person's system after a few hours, it's unlikely to cause long-term side effects.

Fay, who is not affiliated with the ketamine industry, cautions against trying it without first testing out traditional methods such as antidepressants, or even medical marijuana, from which he's seen patients get great results—"like [their] soul drank a cup of coffee."

"It's not my frontline yet because I'm a scientist and I want more research. I want to see more peer-reviewed about it and to be honest with you, I'm looking for buy-in on their part," Fay said.

In addition, there are no set guidelines enforced for using ketamine as a treatment for depression.

Cruz said Ketamine Health Centers follows best practices as recommended by the American Society of Ketamine Physicians, Psychotherapists, as do many reputable clinics—but this is optional.

"You could have somebody open one of these clinics that's maybe not well versed in psychiatry, anesthesiology... some entrepreneur that was like, 'Okay, well, how can we make more money?'" Cruz said. "We obviously would like to get rid of those clinics and the bad actors that might be out there."

Treatments range from spaced-out infusions done in a under close supervision at Ketamine Health Centers to mail-order lozenges prescribed after a telehealth consultation at various online companies.

At-home administration has received sharp criticism from others in the mental health sphere.

"We strongly advise against the prescription of at-home self-administration of ketamine; it remains prudent to have all doses administered with medical supervision until more safety information obtained under controlled situations can be collected," the APA task force's 2017 report read.

Many of these telehealth ketamine companies are based in Florida, which has had some of the laxest telemedicine laws since even before the pandemic.

In April, Gov. Ron DeSantis made it easier for doctors to virtually prescribe ketamine by signing into law legislation that removes prior restrictions on telemedicine prescribing of controlled substances.

Another potential issue is the price. The cost of an infusion typically starts at around $400, not covered by insurance, and patients typically get multiple infusions, plus boosters.

Ketamine Health Centers charges $4,000 for six infusion sessions according to its website. This also includes two 30-minute therapy sessions, one ketamine-assisted psychotherapy session, a medical assessment, physical and a psychiatry consult.

After initial treatment, it costs $350 per infusion for seven boosters over three months.

Cruz said patients who cannot afford the treatment are offered discounts and payment plans.

Progress is being made

The only version of ketamine approved to treat depression is a derivative, esketamine, which is manufactured by Janssen Pharmaceuticals and sold as a patented nasal spray called Spravato—but it comes with its own drawbacks.

Unlike ketamine, it is only available through a restricted distribution system with strict guidelines, such as monitoring a patient for two hours after treatment, a news release announcing the approval states.

Patients have to prove they have treatment-resistant depression, a process that involves trying out multiple different antidepressants.

It also comes with a boxed warning of the potential for sedation, abuse and misuse, difficulty with attention, judgment and thinking, and suicidal thoughts and behaviors.

In addition, even Spravato has been met with criticism that the research supporting it was rushed and could be stronger, Kaiser Health News reported shortly after its approval.

Further, not all insurances cover it.

Ketamine Health Centers is certified to administer Spravato and was at one point their largest network in Florida, but now only administers it to patients who were previously approved and is not accepting new Spravato patients. This could change in the future.

"It is very cumbersome to get the insurances to cover it. It's a lot of work," Oms said.

Still, it may be worth it to take Spravato instead of ketamine, said Sasha Griffin, a researcher for a Spravato clinical trial at APG Healthcare in Orlando. The center is one of several in Florida that is certified to administer the drug.

She said while ketamine very well might be helpful, effective, and safe, there are not enough studies to prove that.

"There's not enough evidence-based practice done there with research to be able to have a confirmed opinion," Sasha said. "Esketamine is the only one that has clinical-based evidence research behind it to stand behind it that it's actually beneficial and safe to use."

Oms, though, is convinced that as becomes more mainstream, it will gain widespread acceptance.

"You've got to be open-minded," Oms said. "It's part of the future of psychiatry."