Wellness: Ketamine

Is ketamine the next big thing in psychiatric therapy?
Illustration by Drew Bardana

A self-professed “advocate of psychedelics,” Ryan Duey has begun experimenting with ketamine to expand his mind. In February, Duey went to ShaMynds Healing Center in midtown for a dose of ketamine delivered intravenously and monitored by a doctor and a nurse. Coupled with psychotherapy sessions, ketamine has proven to be a valuable tool in treating drug-resistant depression and post-traumatic stress disorder, as well as providing some patients with greater insight, as Duey is seeking. “I have a healthy mind according to my doctors,” says Duey, a 36-yearold business owner from Auburn. “I’m not depressed; I don’t have PTSD. But I do have areas in my life that hold me back from being the best person I can be. These tools, such as ketamine, give me insight.”

Duey says when he entered ShaMynds, he was welcomed into a room with soft lights and gentle music playing, although he elected to use headphones during his session. His vitals were taken by a nurse and the ketamine dosage was administered. Ketamine is known to elevate heart rates and blood pressure. Duey says he didn’t have a hallucinogenic experience, but rather could “see” his intentions.

“I still had a profound experience and noticed areas of procrastination,” Duey says. “I didn’t have the imagery, but I saw it nonetheless in my mind’s eye.”

Duey was scheduled for one more session and wanted some additional clarity on a pressing issue in his life: whether or not to become a father. He says it’s easy to come up with reasons not to become one, all selfish. But his first two sessions helped him see a different perspective.

“I’ve found that clarity and peace to become a father,” he says. “I used to think of all the reasons why a child would subtract from my life. But for the first time, I feel freed up, and I now see how a child would add to my life.”

Duey says he has had experience with psychedelics such as LSD, “magic mushrooms” and ayahuasca, another plant-based psychedelic. He’s also taken ketamine in a recreational setting but got nauseated, he says. This was the first time he’d taken a psychedelic in a controlled, clinical environment.

“Ketamine treatment isn’t cheap. It’s an investment, but it’s worth it,” he says. “Your mind is still present compared to other drugs. I call ketamine a ‘graceful psychedelic.’”

The drug was first synthesized in 1962 and approved for use in the United States in 1970. It was used mostly in veterinary medicine in its early history, but also used extensively as a surgical anesthesia during the Vietnam War.

Ketamine in its powder or liquid form has been used as a recreational drug called “Special K” because of its hallucinogenic and dissociative effects.

Ketamine was approved by the Food and Drug Administration for treatment of psychiatric disorders in 2019, but only in a nasal spray called Spravato.

Tasnim Khan, M.D., is co-owner of ShaMynds. She’s been a family physician for 25 years and trained in ketamine-assisted therapy at the Integrative Psychiatry Institute. Only recently has she become aware of the power of psychedelics in the treatment of psychiatric ailments. She opened ShaMynds last November.

“The [COVID-19] pandemic made me realize that there’s a mental health pandemic,” Khan says. “There are so many gaps in how we diagnose and treat mental health issues. I saw the data. I went on my own personal journey, and it was magnificently transformative. Everything became clear. It was hard as a doctor to admit that I had experienced depression, and that there’s help in a nontraditional health path. Now it’s all about how do we increase access and deepen our toolbox to deal with chronic pain, opioid abuse, depression, OCD and PTSD?”

Khan says that ketamine is not a panacea, that patients must still do the work in psychotherapy. The insight that ketamine may provide means nothing if it isn’t applied to the real world. It is ketamine-assisted psychotherapy, after all, Khan says, noting that therapy often includes sound therapy, trauma yoga and diet and exercise advice, as well as neuropsychedelics.

“It’s all very holistic,” Khan says. “It’s whole-ism of the individual and how they can then function in a community.”

Kaiser Permanente was guarded in its response to whether its doctors use ketamine as a therapeutic but did respond with this statement: “Providing high-quality care that is safe and personalized to the individual needs of the patient is of the highest priority at Kaiser Permanente. We use a structured, robust evidence-based process in the evaluation of medications, and ketamine is used for treatment-resistant depression.”

Dignity Health and Sutter Health did not respond to inquiries, although Sutter Health does mention ketamine infusion therapy on its interventional psychiatry website. There are three ketamine clinics in Sacramento other than ShaMynds and one each in Elk Grove and Roseville. The UC Davis Health system is set to begin using ketamine therapy later this year, according to Jagdeep Kaur, M.D. Kaur is an addictive psychiatry doctor with UC Davis Health and had experience prescribing and administering ketamine therapy when she practiced in Pennsylvania two years ago.

She says she is trying to get clearances through UC Davis Health to administer ketamine in the form of Spravato. She predicts those clearances will be made by July.

“Not everyone has dissociative effects (with ketamine),” Kaur says. “But we do see the therapeutic effects within 24 hours of taking a dose.”

Kaur says that the protocol for using ketamine for pain management is 1 milligram per 1 kilogram of patient weight. That jumps to 150 milligrams per 1 kilogram for use as an anesthetic, she says, while the first dose in ketamine-assisted therapy is 56 milligrams regardless of the patient’s weight, and 84 milligrams is the maximum single dosage. The usual length of treatment is twice a week for four to six weeks, and the maintenance schedule is usually once every two weeks, she says.

“It can get expensive. Our prices in Pennsylvania were around $800 a dose,” Kaur says. “A lot will depend on the health plans, but we’re talking about treatment-resistant diseases.”

David Olson, M.D., has studied the effects of ketamine and sees the benefits. But he also sees ketamine’s limitations. Olson studied chemistry and neuroscience at Stanford University and the Stanley Center for Psychiatric Research at Broad Institute of MIT and Harvard. He came to UC Davis in 2015 as an associate professor and researcher, and his lab was recognized last year with the UC Davis Innovator of the Year award.

“The last innovation in psychiatric medicine was Prozac back in the late 1980s,” Olson says. “Ketamine is a new way to treat an old disorder, and it promotes regrowth through neuroplasticity. But it’s an imperfect drug. It will be replaced by a safer alternative.”

That’s where psychoplastogens come in.

Working in his lab at UC Davis, Olson discovered that psychedelics promote neuroplasticity in the prefrontal cortex, where cognitive control takes place. The prefrontal cortex influences mood, joy, fear and impulse inhibition.

Olson coined the term “psychoplastogen” to describe small molecules that produce rapid and long-lasting psychedelicand ketamine-like effects on neurons. His lab invented the first non-hallucinogenic, single-dose psychoplastogens that have produced long-lasting effects.

With many neuropsychiatric diseases such as severe depression, post traumatic stress disorder and addiction, neurons in the prefrontal cortex atrophy and the gaps between them—the synapses—widen and are lost. Psychoplastogens are molecules that heal the neural networks, leading to regrowth and the possibility of rewiring the mind.

Olson has compared the brain’s neurons to a tree, with the receiving part of the neuron—the dendrites—as the branches and the synapses as the leaves. In neuropsychiatric diseases, the leaves fall off and the branches are pruned. Olson carries the metaphor further, comparing the psychoplastogen molecules to Miracle-Gro. The psychoplastogens can heal the brain, not just treat the symptoms of neuropsychiatric diseases.

Olson says that first-generation psychoplastogens such as ketamine can be abused and have adverse cardiovascular effects and hallucinogenic properties that make in-clinic administration and patient monitoring imperative. That increases cost and decreases the ability to reach more patients, he says.

“(Ketamine) abuse potential and the dissociative effects dramatically reduce the scalability,” Olson says. “One in five will suffer some sort of psychiatric issue in their lifetime, but we can’t have 1 billion people using ketamine.”

Olson is a co-founder and chief innovation officer for Delix Therapeutics, a Boston-based startup looking to bring to the market psychedelic-like compounds that heal without hallucinations.

“We started to learn a lot around 2010, and by 2018 we showed demonstrable growth,” Olson says of his groundbreaking 2018 study in animals that showed psychedelics promoted synaptic growth. “We saw that LSD and psilocybins also promoted neuroplasticity. It works for substance abuse, PTSD and depression. But it’s not a panacea. They just target the prefrontal cortex.”

Delix Therapeutics was founded in 2019, and according to its website, the company has synthesized approximately 1,000 compounds within eight classes of psychedelics including LSD, tryptamines including “magic mushrooms” and amphetamines such as MDMA (ecstasy).

The company raised $70 million in financing last year, Olson says. He expects to have compounds in clinics within 10 years.

“Each new discovery is advancing the field,” Olson says. “I want Delix to impact humanity. I want to see it through and get (psychoplastogens) into the hands of patients. Much like the mRNA platform from Moderna, I’m hoping that Delix has the same impact in neuroscience.”

The stigma concerning psychedelics use is dissolving. With each medical advance, with new and compelling research described in peer-reviewed papers, and with each compound produced that moves toward full FDA approval and over-the-counter access, ketamine and other psychoplastogens are becoming more accepted and more mainstream.

Doctors Khan and Kaur are working in the now, while Olson is building for the future. Patients such as Duey stand to benefit.

“The stigma is absolutely changing,” Duey says. “Why is it changing? Because
these psychedelics work.”