Could Ketamine Cure Addiction?

We spoke to the team behind some groundbreaking new research.

by Ben Bryant
Jun 30 2017, 6:44pm

En person snortar ketamin, vilket inte är metoden som bör tillämpas i medicinska sammanhang.

The tube was full of translucent solution. It coiled into Timmy's arm, shimmering in the fluorescent lights of the hospital. There was nothing to feel at first, except a lightheadedness—probably nerves, Timmy reasoned.

Five minutes passed. Ten. Then, faint nausea began pooling at the base of Timmy's throat. He was becoming lighter. Just 15 minutes ago, he'd felt tethered to his rigid frame. Now his body coalesced with the world around it. He was leaking through his papier-mache skin. Adrift from his body, he began floating up and over it, like water on mercury.

"It's this strange thing of feeling in your body, but not in your body at the same time," he said, as the researchers around him took notes.

Timmy had taken ketamine before at parties, where getting into the "K-hole"—a state of intense dissociation—was the point.

The difference this time was that Timmy was in a hospital, not at a party. And the ketamine in his veins was there to help him stop drinking—by weakening his memories of the pleasure he associates with alcohol. Timmy was one of 90 hazardous drinkers participating in the first-ever human study to see if it can help them cut down their drinking.

It's the subject of Eternal K-Hole of the Spotless Mind, VICE's new film, which you can watch above. The results of the study are not yet known—the University College London (UCL) team are currently analyzing the data they collected.

However, the experiment builds on years of research that shows that ketamine has a unique potential to weaken memories safely. And if researchers are successful, they will likely not only impact the way we treat addiction, PTSD, and phobias, but will also end a global search for a forgetting pill: A drug that can safely target unwanted memories, and weaken them forever.

This search started 17 years ago, when a team of Canadian researchers—led by Karim Nader—conducted a now famous experiment.

They conditioned rats to associate a tone with a shock. The rats froze whenever the tone was played because they remembered that it was associated with pain. A "fear memory" had been created.

Next, the researchers gave the rats a drug called anisomycin, which inhibits protein synthesis. When this was administered six hours after playing the tone, it had no effect on the rats. But when the researchers gave the drug soon after playing the tone, the rats seemed to forget the association. Playing the tone no longer scared them.

The research suggested that each time a memory is recalled, it enters a "labile" period—a fragile state where it can be altered or weakened. Protein synthesis is required so that memories can be packed away properly—or stabilized—but the anisomycin was preventing this.

Nader's research had huge implications. If this drug could weaken fear memories, then why not other memories? Researchers could foresee potential clinical applications in PTSD, phobias, and addiction. Except there was one problem: anisomycin is toxic in humans.

Around the same time, ketamine's effects on memory were being studied by a team of researchers at UCL, led by professor Helen Valerie Curran. They had published papers from April of 2000 onwards that showed that ketamine had a profound impact on short and long-term memory.

"It's a bit like opening up a Word document on your computer, making a lot of changes and then—instead of re-saving it—pulling the plug, so that you might potentially lose the file completely."

Dr. Ravi Das was part of a different team of researchers in UCL's psychopharmacology unit who wondered whether this effect could be used to target specific memories. "Memories are essentially networks of connections in your brain, and the strength between those connections are determined by [the NMDA] receptor," said Das.

The researchers theorized that blocking the NMDA receptor when a memory is recalled could block the cellular processes that are required for that memory to be re-stabilized. Ketamine happened to be very good at blocking that receptor.

"It's a bit like opening up a Word document on your computer, making a lot of changes and then—instead of re-saving it—pulling the plug, so that you might potentially lose the file completely. That's the kind of thing we're trying to do by giving ketamine straight after destabilizing people's drinking memories."

Memory is the driving force of addiction because it reminds us of the pleasure that we associate with a drug.

"Your brain's really well adapted to learning about rewards," said Dr. Das. "Addictive drugs like alcohol activate the reward centers in your brain, so when you have a drink, for instance, your brain's learning about all the things in the environment that are associated with that drink and that rewarding effect."

The clink of a glass, the sight of a beer, and all the associated sensory stimuli are memory associations that drive cravings—a powerful motivational response that can be hard to resist.

"What we're trying to do is break down those memory links between things in the environment that trigger cravings and that kind of automatic use of drugs. So we think that by destabilizing people's memories and giving them ketamine, we might be able to weaken them."

Loosening the grip that triggers have over users presents another interesting possibility: People with hazardous drinking patterns may be able to return to moderate levels of drinking, rather than abstaining completely.

In the film, Timmy returns to drinking after several weeks of abstinence, but he is drinking far less than before.

"I think whether people go for moderation or abstinence really depends on the individual," said Dr. Das. "Some people need to be completely abstinent. Other people will be able to handle moderation."

The experiment could provide "a helping hand by reducing those triggered urges so people can regain control, and for some that will be drinking less; for others that will be not drinking."

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