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Ketamine Could Be the New Depression Treatment of Choice

The strange journey of the party drug that may be the key to rewiring the brain

I’ve never read Watchmen nor seen the 2008 film, but suddenly I’m existing inside one of its stark posters. My consciousness unfolds into a quiet noir — a black-and-gray cityscape that melts and stretches like bands of saltwater taffy. My eyes are closed, tucked under a soft mask, but I’m just as abstracted from my face as I am from the electrodes stuck to my chest and the emergency call button resting in my palm. My inner monologue has dissipated, but it hasn’t completely vanished. I’m alone now, in an unnameable place, definitely not where I started.

There’s gravity to being intangible. This nothingness feels fresh. I feel like I’ve transcended into being the world, instead of being just a person in it. That said, it’s more reductive than expansive. If all of my thoughts were fractions, they’d suddenly become simplified by their common denominator. I’m empty and curious, gazing up at scaffolding and skyscrapers that disappear when I stare at them. There’s no logic or perceived sense of control. I simply receive what comes to me, like the fresh breaths that continue to arrive without being ordered to do so.

Eventually, one thought becomes clear: “Tierney Finster is a person who will die.”

I don’t try to make meaning out of that thought; I accept its obvious truth. No wheels turn. Nothing reels. There’s nothing for me to catalogue or critique about it. I’m just being, knowing eventually I won’t.

A long time passes before the smoky tones lift. Bright light emerges — radiance that floods my consciousness and interior field of vision. It’s warm and comforting. I’m warm and comforting. The sparkle of the sunset as it hits the ocean. I’m hot sand. A Rothko painting. I’m the dribble of honey dissolving into hot tea. A nameless molecule in Heaven’s heart chakra. I’m peace.

Or at least, I’m deeply at peace when the rockabilly nurse returns to the room to tell me the treatment is done. “Just stay right there until you come to,” she instructs.

I peek out from beneath the eye mask to watch my own hand strike my own thigh. How could these be mine? I recognize my physical body and am in awe of it, in awe that I was just completely disembodied, void of my physical parts as I floated through somewhere, only to be back now looking at the stock photo of the Caribbean stuck to the wall and wondering when this returned sense of corporeal ownership will reach my feet.

There’s a huge glass window to my left revealing a band of gorgeous clouds. An ambulance zips down the street below and reminds me to remove my earbuds, the ones connected to the clinic’s pre-loaded iPod full of meditation music. Celtic faerie music soundtracked my out-of-body experience, but now it’s New Age intonations are nauseating. I try to fix my gaze on the glossy, aquamarine art peace or the gorgeous sky, but everything makes me feel worse.

Dizzy. Hot. Clammy. Unwell.

I should never have worn fleece-lined leggings. They’re stifling. It feels like waking from surgery — and having undergone an unexpected operation just last year, I’m triggered by the familiarity of this heavy vulnerability. I’m more scared to come back to myself than I was to leave. I weep. I’m afraid I’ll collapse. I need help getting to the bathroom, where the additional medication I consented to prevents me from vomiting. I gag and gag. Afterward, the nurse helps me find my Uber downstairs.

The stop-start of rush-hour traffic is rough. I’m sickly. Miserable. I want to grab my boyfriend, my mom or my best friend — reminders of what my life is — and absorb their energy like a healing crystal. My stomach spins and my head is heavy as I crawl into bed. I feel dopesick like a junkie, like one of my friends who overdosed on opiates and died. Not to mention, I’ve just been reminded that one way or another, I will too.

But 36 hours later — or maybe it was 48 — I feel pretty fucking good.

Medicated, but good.

Relieved even.

I’d achieved a sort of tranquility you only get when you’re, well, tranquilized.

My treatment — “ketamine infusion therapy” — had been administered by Dr. Steven Mandel, who spends five days a week, morning till night, infusing ketamine into the bloodstreams of patients looking to treat pain and mood disorders. At his place of business, Ketamine Clinics Los Angeles, a ketamine infusion means having a digital pump steadily deposit ketamine through a tube into your vein over the course of 50 to 55 minutes — a longer period of time and a slightly higher dose of medicine than most other clinics doing the same thing. According to Mandel, this pump also distinguishes his clinic’s offerings from those of his competitors, who distribute their ketamine through a typical I.V. bag.

“The pumps allows us to monitor and adjust each individual’s dose throughout their infusion, as to achieve an optimum dose for each patient,” he tells me.

During the single session I described above, Mandel’s signature pump unloaded 101 milligrams of ketamine into my vein, a sub-anesthetic dose based on my weight, over the course of 50 minutes. Typically, patients purchase a package of six infusions (mood disorder patients are charged $1,500 for the first two infusions, then $600 for each subsequent infusion, most of which can’t be billed to insurance). Studies show mood improvement after single doses, but more sustainable effects after a series of infusions. A typical first-time patient at Ketamine Clinics Los Angeles will receive their six infusions over the course of two weeks, most of whom are seeking treatment for the following mood disorders:

  • Major depressive disorder
  • Bipolar depression
  • Suicidality
  • Post-traumatic stress disorder
  • Anxiety
  • Obsessive compulsive disorder
  • Postpartum depression

Of course, using ketamine in this way isn’t FDA-approved or a widely accepted mental health treatment, despite its increased popularity at clinics across the country.

Ketamine was first conceived in 1962 as a replacement for PCP, which had been used as an anesthetic until its side effects proved psychotic. It’s still one of the cheapest and most widely used anesthetics in the world. Although like PCP, it’s often associated with its recreational reputation more than its medicinal purpose. Part and parcel of raves, grime and sex-and-drug cocktails involving other substances like ecstasy and GHB, “Special K” is known to fuel music festivals and orgies more than it’s thought to reverse serious mood disorders.

Mandel, however, doesn’t expect this to be the case for much longer.

He began experimenting with ketamine’s uses beyond anesthesia earlier this decade, when studies suggested its usefulness in treating mood disorders. A career anesthesiologist who focused on psychiatry before shifting gears in med school, Mandel started hosting ketamine trials for depression out of outpatient clinics and freestanding ambulatory surgery centers, most of which were used for plastic surgery. He’s never been a psychiatrist or psychologist, but given his previous education — and longtime interest in studying approaches to treating depression and suicidality — he kept up with literature indicating ketamine’s emergent uses beyond putting people under (and partying).

He sourced a lot of his early patients from the internet. He was already acquainted with others. Most of them carried the diagnosis of a major depressive disorder or bipolar disorder, and many were suicidal. The results from his first infusions were so successful that four years ago, Mandel began doing the work full-time, starting his own company and appointing his son Sam, who promotes his IMDB entry on the clinic’s website, to chief operating officer. And while Mandel’s practice does treat a few patients who experience chronic pain, the crux of his business is caring for depressed, suicidal and mentally ill people.

He’s treated more than 600 patients to date, meaning he’s administered upwards of 4,000 ketamine infusions, and he boasts a reported 83 percent effectiveness rate — higher than the reported rate in the literature and research at large of around 70 percent. His youngest patients was 15, and his oldest so far was 88. On the day of my infusion, I’m surprised to see a dad in the waiting room greet his young teenage son following the latter’s treatment, groggy and slow, and I’m curious about where the teen’s mind went during his disassociation, a decidedly heavy experience.

Big Pharma, including Johnson & Johnson, is trying to create ketamine copycats that produce a similar effect without prompting such a trip, but Mandel contends that this disassociation is a vital part of the potential healing:

“Ketamine gives people some space from their internal judge and evaluator and taskmaster. Many of us, particularly the depressed amongst us, have an internal judge who’s constantly making harsh and negative evaluations of ourselves and others. Ketamine quiets that judge and creates distance from it. I think most of us think of that judge as just us, who we are, but what we get from the ketamine is the realization that the judge is just a part of us. It’s in all of us, but it can be a small part of us. Ketamine creates a space that’s safe and free, where you can consider things without worrying about those surface-level judgments and worry.”

Some people consider the dissociative out-of-body experience a “near-death experience.” I didn’t feel “near death,” as much as I felt “mortal,” but I get why that description is used. Mandel says it’s common. “Many people talk about about seeing a light or feeling like they’ve had some contact with a spiritual connection, but not in a frightening way,” he explains. “Many people talk about being in a place where they can balance life and death.”

When I tell him that was the most significant part of my experience, he’s pleased. “I’m glad you were able to have that taste.”

Aside from distancing our minds from our bodies, the second component to how ketamine treats depression is the effect it has on the brain. This promise — neuroplasticity — is what brought me to Mandel’s office in the first place. Research on lab animals shows that ketamine is able to generate increased levels of a protein known as BDNF (brain-derived neurotrophic factor), which stimulates growth in areas of the brain that have shrunken or knotted as a result of depression. Well aware of my own history of mania and depression, I contacted Mandel in hopes of repaving some of the roadways in my brain that depression and negative thinking — that insufferable inner judge — had worn down.

Neuroplasticity is still a relatively new concept, discovered in 1999. Before that, humans thought the condition and function of one’s brain was fixed at childhood. Now we know our brains can evolve and develop throughout the course of our lifetime, something doctors like Mandel and his colleagues see happening thanks to their infusions.

Although not as recent as the eve of the new millennium, chemical treatment for depression is also a relatively new concept, starting in the 1950s with a series of ineffective drugs and leading to the eventual creation of selective serotonin reuptake inhibitors like Prozac, which hit the market in 1987. While very popular, SSRIs are known to cause side effects in many patients (insomnia, erectile dysfunction and blurred vision, to name a few). For others, the ineffectiveness of the first SSRIs they try sends them down a path of trial and error, where experimenting with different formulations brings them to emotional lows worse than those they experienced before they began chemical treatment.

Worse yet, despite their ubiquity, the overall effectiveness of SSRIs isn’t great in general. For example: The most thorough, long-term study of depression treatments ever conducted found that over the course of trying four SSRIs within five years, 30 percent of the participants still weren’t symptom-free and that upon trying each new drug, it became harder to get better results (“the odds of beating the depression diminish with every additional treatment strategy needed”).

While most of his patients are still identified as having “treatment-resistant” depression, meaning their ketamine infusions are a last-ditch effort before other serious procedures like electroconvulsive therapy, Mandel believes sooner than later, ketamine will be a mainstream treatment for mood disorders, not just something reserved for the toughest cases of enduring depression.

“I’m sure that’s going to happen, as sure as I can be about the future,” he says.

“When this was considered experimental and nobody was confident it wouldn’t hurt anyone, it was put lower on the list of options than the more conventional treatments. But this works better than the more conventional treatments. And it works more quickly, and in a higher percentage of patients. It has a better risk and safety profile than they do, too, so there’s no reason that people should have to fail the trials of those in order to try this. On the contrary, they should try this first.”

Before discovering Mandel’s work, I only knew ketamine as the horse tranquilizer James St. James and other Club Kids from the 1990s did. I was offered my first bump of it a few years ago in a gold-lined bathroom at an art collector’s luxury flat in London. I declined. A year or so later, I snorted a tiny amount, curious, but not enough to get high. I sat in a hot tub and listened to Lana Del Rey. I felt unsurprisingly great, given that combination of my favorite things, but nothing discernible as a ketamine high.

Recreationally, ketamine is a different drug than what happens in the clinic, which creates a certain bias against ketamine therapy among those who view it as a party drug. The horse tranquilizer reputation is perhaps most popular, simply because in addition to humans, ketamine has long been used in veterinary medicine. But according to this ketamine advocate, “Calling ketamine a ‘horse tranquilizer’ is akin to calling a plastic bag a ‘human suffocator.’ It is intentionally misleading.

The K-hole is also closely associated with recreational ketamine use, referring to the delirious, incapacitating, hallucinogenic experience of ingesting too much. I asked Mandel if the infusions worked by sending patients into K-holes via sedation, and he told me no. The amount in each of his clinic’s infusions wasn’t enough to create such an experience. This raised an interesting question: If my dosage wasn’t enough to drop into a K-hole, how much were ravers snorting?

For Mandel, the safety and effectiveness of ketamine is all about context. “Nobody comes to my office to get high,” he says. “There’s a major distinction between people using ketamine to treat suicidality or mood disorder and people using ketamine for better dancing or sex.”

But some interested patients and their families need more convincing. “I met a mother from Houston and her suicidal daughter about three years ago,” Mandel says. “They’d flown up from Texas to consider treatment. The mom had found the girl on the ledge of their apartment, but was still not convinced ketamine was an appropriate treatment. She wanted to know if her daughter would become addicted. I said to her, ‘Do you want to risk her becoming addicted to ketamine? Or risk that she’ll step off the window ledge?’ She later understood that this wasn’t going to be something her daughter liked. She was only going to like the result.”

But there are still plenty of qualified critics of ketamine as a way to treat depression. Earlier this year, for instance, The Journal of the American Medical Association critiqued how quickly studies promoting the effectiveness of ketamine for mood disorders were being put into action by medical professionals, despite the “relatively small sample sizes, lack of longer-term data on efficacy and limited data on safety provided by these studies.”

This study, in fact, suggests that ketamine’s potential for neurotoxicity in the developing brain is just as great as its potential for neuroprotection.

“It’s weird being a human guinea pig, but medicine has already failed us in terms of most antidepressants, ” Pat, 45, tells me.

Pat has struggled with depression all his life, which eventually led to serious addiction issues. Prior to ketamine infusions, Pat tried a slew of drugs including Celexa, Seroquel, Trintellix, Lamictal and Prozac without lasting positive results. He finished his first round of six ketamine infusions with Mandel in July.

“Ketamine isn’t part of the mainstream medical establishment at this point,” Pat says. “I was almost thinking of doing electroconvulsive therapy over ketamine. I couldn’t figure out which was the worse option. But for me, [the infusions] prompted a change in my perception from inside to out. After my third treatment, I realized that I’d had a good weekend for the first time in months. I was no longer trapped in my depression, within my own depressed subjectivity. Through the disassociation, I came to see things more clearly.”

Not that it always sticks. “I was expecting longer term effects after the treatment,” says Don, 70, who has struggled with depression his entire life and has been on antidepressants since the mid-1970s. After unsuccessfully trying electroconvulsive therapy in summer 2016, Don went to Mandel for ketamine therapy for the first time in February. Although he says he did feel better during his infusions, at the end of them, he asserts that “the results were debatable.”

“It took about two and half months after the infusions before I started to relapse,” Don continues. “But I didn’t report that until July, because I wasn’t sure if it was really a relapse or not,” Don tells me. The clinic offered him “booster” infusions at a reduced rate upon hearing that his symptoms had returned. Additionally, Don purchased the clinic’s ketamine lozenges — the first of their kind in the U.S., according to Mandel. “They contain a lighter dose of ketamine that isn’t sufficient to get people out of a bad depression, but it’s super good at maintaining the benefit they already got from intravenous infusions,” Mandel says.

Yet, despite experiencing episodes of major depression after his treatment, Don still supports the widespread use of ketamine therapy: “I highly recommend these treatments be made available to more people, and I can’t say enough about Dr. Mandel and his staff. It’s almost like going to see your family, which is why I’m a little hesitant to be so honest about the fact that I’m not completely cured.”

I’ve spent my whole life trying not be depressed. I’ve blamed my depression on everyone but myself and have done my best to strategize my way around its heft — mostly by lying to myself or failing to admit how I really feel. As such, for most of my life, I’ve ignored the fear, distrust and guilt that still reign inside me, often allowing them to manifest as anger and rage that I take out on those closest to me, usually my parents. I blame my volatility on their mood disorders, refusing to be accountable for my dragging them through our family’s past over and over again.

But last year, I moved back in with my parents after breaking my leg, and for the first time in almost a decade, I had to face my relationship with myself and my family every minute of every day. More or less bedridden, I could no longer retreat from myself by prioritizing the external world — work, nightlife and other people’s drama. I could no longer channel my pain into productivity. I could no longer pretend I trusted myself or all the good people in my life. I could no longer feel okay about emotionally abusing my mother, attacking her character and vilifying her selfless parenting in big, vicious scenes, simply because I was very, very sad. I was almost 25. I could no longer pretend my depression and anxiety were merely teen angst.

I wrote a lot, finally admitting to myself that I needed to heal. I still find these diary entries in Google docs and scribbled onto pink Post-Its. One such entry:

“My new goal is to make the happiness of what I know my life to be match how I feel inside. I wish I was one of those people who didn’t feel such guilt and shame for just being me. My self-loathing is starting to seem like a selfish joke, but I don’t know how to stop.

I’ve programmed myself in an unsavory way, and if I don’t concentrate on the opposite of my triggers, I’m going to go to waste. So yeah, I’m coming to terms with how I sabotage myself and itemizing the ways I abuse people close to me by pretending I hate them instead of myself.”

I sought ketamine therapy in hopes of remodeling my brain, hoping to make it healthier than it had been before. I needed the opportunity to feel distance between myself and my internal antagonist. And I did notice positive results after a single infusion. I got more done and took better care of myself than usual — or at least, it was easier to get more done and take better care of myself than usual. Once the initial nausea and lethargy wore off, I felt focused, clear and happy. I had the same thought I had when I tried half a bar of Xanax from the comfort of my old apartment: Is this how normal people feel?

But given the quick succession of infusions, my second appointment crept up on me right as I began feeling the positive effects of the first. Although Mandel promised me the second infusion wouldn’t feel as heavy as the first, I wasn’t ready to repeat the cycle. I wasn’t suicidal. This was something that could help me, but it wasn’t something I needed. So I canceled my second infusion, and a few days later, the results of my first wore off. I felt a drop in my mood, but it was manageable. I may eventually go back for more treatments — I know firsthand how immediately transformational they can be — but I would only do so under dire circumstances.

I also know I’m not alone in wishing my own mental health were easier to manage or stabilize; depression is the leading cause of disability in the world, which is why using ketamine in this way is so potentially powerful. But the intensity of my infusion made me doubt it was the correct treatment for me right now. I was privileged to try such an expensive, experimental medication and even more privileged to recognize I can rewire those pathways in my brain eroded by a quarter-century of anxiety and depression without it.

To that end, I’m making great strides in getting a handle on myself. In the last year, my rage has subsided and my sense of self-worth has grown. I realize that I deserve love and trust that those closest to me actually love me for the first time in a long time, if ever. I feel like I can finally just be, without honoring the hateful voice inside my head, even when she still gets loud.