‘How Special is Special K?’: The Science Behind the Ketamine Hype

Ketamine –  the drug of the moment. It’s used as a horse tranquilliser, or, more commonly, the go-to party drug for those looking to feel a little lighter and a little loopier on the dance floor. 

In recent years we have also come to know Special K as having – depending on who you speak to – huge potential for the treatment of depression. In times where the benefits of medicinal cannabis, mushrooms and MDMA are being explored in the science community, ketamine’s early results in the treatment of depression, its potential as an alternative for antidepressants, and its proven ability to help assuage those at crisis points, has seen it touted as a modern fix to the deteriorating mental health crises dotting the globe.

The hype, originating in the US, has made its way down to Australia. Both countries are grappling with mental health crises, exacerbated by the pandemic. In the US, ketamine clinics have popped up around the country, since the nasally-administered version of ketamine was approved by the FDA in August 2020. In Australia, ketamine research is still ongoing.

This new vanguard of mental health treatment has signalled an exciting move away from the decades-long demonisation and mischaracterisation of recreational substances, offering an ostensibly hopeful alternative to our current system. But is it just hype? Does ketamine really pose a viable solution to the mental health crisis?

It was this quandary that Wendy Zukerman, Australian-American journalist and host of the Spotify Original Science VS podcast, was compelled to explore.

For the recently released episode, How Special is Special K?, Zukerman and the Science Vs team spoke with leading researchers in the field, including professor Colleen Loo of Sydney’s Black Dog Institute, and professor Gerard Sanacora, translational neurologist and director of the Yale Depression Research Program, to figure out exactly where the research stands across Australia and the US.

Is ket all it’s purported to be? VICE sat down with Zukerman to find out.

Wendy Zukerman: In America right now, ketamine is just exploding. There are ads for it all over social media in the US. It’s being promoted to help with depression, that’s the big thing, but then there’s a whole bunch of other conditions – autism, PTSD, OCD. 

It's been on my radar for a while. When I was in the States, I’d started seeing clinics opening up in New York where you could go and get a ketamine infusion. It’s sort of being advertised like a spa experience. And then, just recently, it really exploded – the interest, excitement, the amount of people getting it. So we thought: alright, it's time to really dive in and look at the science and find out what’s going on here. Can ketamine actually help with depression, and all these other conditions? What is it doing in people's brains? Because a lot of people, including me, just know it as a horse tranquilliser and a party drug – the idea that it could help with depression was definitely very intriguing, and a little “huh?”.

What were the key things you were trying to find out?

The big questions I had going in were, could it really help with depression? In the news there were all these stories of individuals who had had depression for a really long time and nothing else had worked, and ketamine was the thing that turned it around. And any time I hear a story like that, it always makes me wonder: sure, but how common is that experience? And is it gonna help your friend’s depression, your depression, your mom's depression, your granddad's depression…?

So, I was wanting to know the data there. And was it as good as the ads were claiming? That was a big question. And then from there, if it is helping, I wanted to know how. What is it doing in your brain?

And that’s where I wanted to start. Did you find out if it works? How does ketamine help with depression?

Yes, we did. We found out where the data is at the moment and it’s super, super interesting. In the 90s, early 2000s, researchers started testing whether ketamine infusions could help people with treatment-resistant depression, which is depression where other medication hadn't worked. And they were getting these super exciting results. 

We spoke to two researchers who had these patients come in who were suicidal, having suicidal thoughts, they’d give them ketamine and have them come to the lab the next day, then ask them these questionnaires. And they said as soon as [the patients] walked into the room they were like completely different people. One of the researchers we spoke to was astounded. And so all of this data started coming out showing that 24 hours after having ketamine, for people who are suicidal, having terrible depression, it can really turn things around. 

But then, as the research has come along, what they've realised is that the benefits on average don't last that long. It’s lasting, on average, one to two weeks. In the data, you can see what's called “super responders”. They'll have a benefit lasting months, one of the researchers we spoke to said they’d had patients where one dose of ketamine has benefitted them for five months – which is huge – for anyone who's experienced mental health issues, that is really amazing. But most people aren't like that. Most people can expect to start to relapse within one to two weeks. 

Now researchers are trying to work out how to make the benefits last longer. They’re doing things like increasing doses, just giving people more ketamine – the two weeks wraps up, you give it again, and you give it again, then you're one of the researchers we spoke to who was like, what's the end game? 

Y’know, it's like: are we going to be giving people ketamine treatments for the rest of their lives? Is it inherently a problem, if you look at antidepressants? But we don't know the long term effects yet. So it's not all as exciting as those early results were showing.

What are some of the potential issues for needing to have ketamine treatments for the rest of your life?

Most of the long term data is in recreational use, because we haven't been studying this in depression for that long. 

It’s interesting. You look at recreational users who use ketamine a lot as a clue to see what if we did put people on a lot of ketamine over the course of their life? and there are two big things that have crept up. Have you heard of bladder issues with ketamine?

Oh no. I’ve heard of liver issues with ket.

Yes, the liver is another one, because you're processing ketamine in the liver if you take a tonne of it. The ketamine gets broken down in your liver, and that gets sent to your bladder to get peed out. And what they’ve found is that those “breakdown products” of ketamine can irritate your bladder. It doesn’t happen to everyone, but for really heavy users they’ve found that it increases your chance of having an irritated bladder. It feels a bit like a UTI – you need to pee a lot, it’s painful to pee, it can feel like barbed wire when you pee. 

What the research is starting to show, though, is if you identify that you have this, and you stop taking ketamine immediately – you let your body repair itself, you flush ketamine out of your system by peeing it out – then it’s not a problem. 

A researcher we spoke to, she said when she does see the odd case – they’re looking out for the symptoms – from the moment they see it they just stop the ketamine, give the body a break, and then it’s not a problem. It’s only an issue if you keep taking ketamine after having those symptoms. Which you might do. Those early users kept doing it because they didn’t know it was associated with ketamine. If you’d had a UTI before, you’d just get antibiotics for it. I wouldn’t start blaming my weekend drug use on painful peeing, unless I knew it was a symptom. It is really important for anyone using ketamine to know this, whether it’s for depression or not.

It seems that, at this point, the ways people are accessing ketamine treatment, and the doses, are sort of scattered. You can have the racemic ketamine injections, or the nasal spray, and then there are these “ketamine clinics” in the US. Is there a push to standardise doses or are people just going for it?

In the US at the moment, there is an FDA approved nasal spray that is approved for treatment resistant depression. But in the States, you can just go to a fancy New York clinic for ketamine, because it's been approved as an anaesthetic. That's what doctors use it for, so it's already on the market. So they're using the off-label versions of it. Scientists want to get to the bottom of what is the best way to deliver it, but at the moment, they don't even know the right dose, they don't even know how often you should be getting it… These are huge, important questions. And it is a bit of a wild west at the moment. 

One of the researchers we spoke to said that he's on this big task force. Him and these other scientists sat down and were like, alright, let's write some basic guidelines, and started looking at the research. But there's just not enough data. 

Currently, doctors are just using their judgement. There are some doses that have sort of become accepted. And then they'll see: Is the patient getting better? They responded, that's awesome. Okay, they're starting to relapse, Should we try it again? Okay. Next. 

It’s case by case. Some researchers are a little worried about this wild west system. Because you really are relying on a good doctor – when you don't have real clear guidelines, you're really just going off a doctor being like, let's give it a go. 

Did you come across many common myths that you were able to bust about ketamine treatment for depression?

I think the big one was that it's not lasting. It was being talked about like the “hero’s dose” with magic mushrooms: people take this huge dose, they fall into a k-hole, and then they’re cured forever. And that doesn’t seem to be the story. Even giving someone such a huge dose that they get to a k-hole doesn’t seem to be right. They’re working out the dosage, but they’ve seen in studies on rats: if you give a big dose of ketamine, it’s an anaesthetic, so people just go under. And anywhere in between, that’s where they start feeling a bit woozy and euphoric. So they’re working out the point where you get those antidepressant effects.

The second was the bladder problems. I was really surprised, because it just sounded like a scare tactic to make you afraid of drugs, but it’s real.

Also, what’s going on in the brain is really interesting. If you imagine the way your neurons talk to each other in the brain are like roads, in the brain of someone who has had depression for a long time, there are less of those roads. Your ability to think different thoughts is thought to be related to why people might ruminate over and over, because there are less of these neural connections, and what ketamine might do is help build new roads. 

They’re seeing it in studies on rodents, and they’re seeing these neurons grow, and get healthier, and build new connections. But then the fact that people are relapsing is really disappointing. It could be that you start to get these roads, the way one researcher put it, but if you don’t drive them, maybe they just disappear again. So now there are these questions, like what if you did ketamine but you did therapy at the same time? Could that make the effects last longer?

Do you think that’s the biggest limitation of ketamine, that the effects don’t really stick around or last for that long?

I think so. Depending on your perspective it’s either like the new exciting frontier of research or it’s disappointing. The response rate for people who have depression, and get ketamine, and get relief in a 24 hour period, is only half. It doesn’t help everyone. And even people it does help, it often doesn’t last long.

Do they know what that’s dependent on? If people don’t respond?

No. One researcher we spoke to really wanted to get to the heart of this and she looked at case studies and research with hundreds of participants and looked at everything, race, gender, everything, and came up with nothing. 

After all of your research in producing this episode of the podcast, do you think ketamine could be a viable solution to the mental health crisis?

I don't think it's going to solve the mental health crisis. I do think it's going to help some people, and I think for those who nothing else has worked, I think it is worth trying it, as bullshit as that does sound to say when it can be hard to access [in Australia].

Even with the data we have now, we know that it is really effective when people are suicidal, like, at a crisis point. If they could come into a hospital and get ketamine, it can shake them out of that. 

In one dataset, for 8% of people who tried it who had depression, their symptoms got worse. So 50% are responding, roughly 1 in 10 people, it’s not working at all, so that’s something people need to be careful with.

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