Last November, on her 29th birthday, Amanda Fulkerson went to a dark room in Los Angeles to get high. She lay back in a chair, the drug entered her bloodstream and music pounded in her ears. She started to hallucinate, imagining she was seeing wild animals. But this wasn’t a club or house party: Fulkerson was in a plush doctor’s office, taking ketamine for depression.
Fulkerson is one of a growing number of Americans who are receiving ketamine intravenously to treat depression, with clinics springing up across the US. The restaurant manager has struggled with depression since she was nine. "I was at the end of my wit," she tells me. "I was like, I’m done, I don’t want to live anymore." Then a friend told her about the LA clinic. She’d never tried hallucinogens before, but her antidepressants weren’t helping anymore and she was desperate. She made an appointment.
"You’re in a comfy chair, they give you music and blankets. They hook you up to an IV and administer [ketamine] for 50 minutes. The first time I was nervous as hell. It’s like you’re getting on a ride at Disneyland and you have no idea what the hell's gonna happen. It’s definitely like you’re on a hallucinogenic, like acid or LSD. You feel high as a kite."
Fulkerson had six treatments, and felt better almost instantly. "For somebody who’s suffered from depression for so long, it’s a feeling I never knew [was] possible. My energy and willingness to do things is 100% different."
It’s estimated that 3 million people in the UK have depression, but scientific research suggests up to 20% of sufferers don’t respond to standard treatments. It’s thought that this 'treatment-resistant' group could especially benefit from ketamine. Many know the hallucinogen as a club drug. 'Ket' or 'special k' makes you feel dreamy and detached. But it’s also one of the world’s most common general anaesthetics, used by doctors and surgeons for decades.
Ketamine is a Schedule III drug in America, meaning it has a low to moderate potential for dependence (testosterone and codeine also fall into this category). It’s illegal to use recreationally, but can be used medically by a licensed professional. In the UK ketamine is Class B: illegal to possess but licensed as an anaesthetic. Doctors in both countries use it 'off-label', for something other than what it was originally approved for (a widespread, legal practice).
Scientists have been researching ketamine and depression since the ‘90s. What they’re finding is that ketamine has powerful antidepressant effects - and works much faster than traditional medication. In March the US' Food and Drug Administration approved a nasal spray derived from ketamine (esketamine). It’s been called a game-changer, the biggest advance in depression treatment for decades.
"Most people find [the IV treatments] to be really life-changing," says Sam Mandel, the COO of Ketamine Clinics of Los Angeles, one of the first in the US. He co-founded the service five years ago with his father, anaesthesiologist Dr. Steven L Mandel. "We’ve had patients going three months on average without return of their symptoms. People actually feel happy. They don’t feel numbed out, where the lows aren’t as low but the highs aren’t there - and I mean the highs of life."
Patients are usually given between 0.5mg and 0.6mg of ketamine per kilogram of bodyweight, over the course of almost an hour. This is the big difference between the medical treatments and ketamine taken recreationally. People snorting the drug in powder form usually take much more (100-250mg is a heavy dose) in a much shorter space of time.
Therapist Katherine Hartley, 35, has had depression since high school. "I’ve tried every medication under the sun," she says. "Nothing was helping. I was always functioning, but my depression got a lot worse about two years ago. It got so debilitating that even going to see friends or family was impossible. I felt like I was constantly having to pretend I was happy but on the inside everything just felt completely grey."
Hartley decided to try ketamine. "I was pretty scared initially. I’ve smoked a little pot, but never mind-altering drugs. My first treatment was so unbelievably… beautiful, is the only word I can use. I felt this intense sense of peace and calm."
Did she hallucinate? "Yes. I lost my mother to cancer in 2010, and my grandmother a year later. They were with me and all three of us were holding hands. My grandmother said, 'you’re going to be ok'. [It was] like a beautiful dream state. I had tears streaming down my face. It was such a comforting feeling."
Hartley says the ketamine worked for her in a way nothing else has. "What I noticed within about the first three treatments was that things started to feel brighter. I noticed a sense of hope. I felt more motivated to do things, socialise with friends, go out to dinner. My sleep got much better. I felt a lot less flat. I was smiling and making jokes again."
How exactly does ketamine help? Most antidepressants increase our serotonin levels, basically, the happy chemical. Ketamine works in a totally different way. It increases production of a neurotransmitter called glutamate, which prompts the brain to make new connections. Researchers think this makes our minds more adaptable, potentially allowing patients to develop more positive thoughts.
"Nobody knows exactly how ketamine is producing the rapid antidepressant effects," says Dr. Gerard Sanacora, a professor of psychiatry at the Yale School of Medicine, which is one of the research pioneers in this area. "But we believe it involves the drug’s action on the glutamate chemical messenger system that alters the physical connections between brain cells, and ultimately allows for different brain circuits to be strengthened or weakened."
Sanacora stresses that ketamine should be one part of a patient’s overall treatment, including more standard antidepressants and therapies like cognitive behavioural therapy, which encourages you to reframe negative thought patterns as positive ones. "If the drug is increasing the brain’s ability to form new connections, it may provide an opportune time to teach patients CBT skills to enhance resiliency and prevent future depression episodes."
So what’s the situation in the UK, could we follow the same path as the US?
Psychiatrist Dr. Rupert McShane runs a private ketamine clinic in Oxford, which has treated 170 patients so far. And in October 2018, Janssen, the company that makes the esketamine nasal spray in the US, applied to market the product in Europe. McShane believes "it’s very likely" to get the license, but points out that the restrictions here could be different, and it must also be approved by the UK regulator.
Of course, ketamine isn’t without downsides. One is the price: at Ketamine Clinics of Los Angeles, the total cost for their recommended course of six infusions is $3,900 (just under £3,000), and most health insurance doesn’t cover it.
There are physical side-effects too. Sanacora says it can affect blood pressure, heart rate and ability to think clearly. "There is also some evidence that longer-term, frequent use can be toxic to the brain and bladder."
Hartley had bad nausea and headaches after her infusions, but tells me she didn’t care - she was already feeling awful from depression. "The ketamine I believe in my heart turned things around for me."
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