Ketamine at a new frontier of research: treating addiction
Researchers found that a one-off dose of the drug could help heavy drinkers refuse alcohol
It is perhaps better known as an illegal hallucinogenic party drug but in recent years ketamine has acquired an unexpected reputation: as a medicinal substance at the front line of scientific research.
Introduced about 50 years ago as an anaesthetic and commonly used as a horse tranquilliser, ketamine is now touted as a remedy against depression, post-traumatic stress disorder (PTSD) and migraines. To that list we can add addiction, after a team of psychopharmacologists from University College London revealed that a one-off dose of the drug could help heavy drinkers refuse alcohol.
The research, led by Dr Ravi Das, centred on retraining the participants’ brains. On day one, the researchers placed a beer in front of each participant, which they were allowed to drink after they had viewed pictures of beer and drinkers. The next day, the same routine took place, yet this time before they could reach for the glass, the beer was removed and instead a dose of ketamine was administered intravenously.
By unexpectedly removing the anticipated reward (beer), the researchers were disrupting learnt associations (see beer, like beer, drink beer). Normally, the brain would reset in the minutes following that disruption, but that is where the ketamine came in: the researchers believe that it blocks a receptor that binds these memories together. So by withdrawing the beer and administering the drug, they were resetting the drinkers’ reward centres.
If that all sounds complicated, then the results were straightforward and eyecatching: in the nine months after the one-off dose, the average alcohol consumption among the subjects, who were all heavy drinkers to begin with, halved. It was as though their brains had forgotten that they were addicted to alcohol.
“We found that heavy drinkers experienced a longterm improvement after a quick and simple experimental treatment,” said Das. “For a single treatment that’s really good. A lot of people don’t actually complete the course on most current treatments [for alcohol addiction]. Most people relapse within a year.”
Trials are still in their early stages, but it’s not yet clear whether any potential ketamine treatment would be a one off, taken every nine months, or over a different time period.
“This is all stuff that needs to be figured out,” says Das.
“We’ve shown that it works in principle, now it’s about what’s the optimal dose, the optimal treatment.”
It is important to note that the medical-grade dose used is different from recreational ketamine, which is often snorted, leading to a quick and dangerous spike though the side effects are the same: hallucinations, drowsiness, dissociation from the body, nausea and more.
But Das is excited by its potential effect. “We chose alcohol because it’ sa particularly difficult addiction,” he says. “People are exposed to alcohol adverts on a daily basis, and there’s lots of social stuff around drinking that makes it harder.”
And its benefits go beyond alcohol addiction. Das says that in theory, ketamine could be used to treat “any psychiatric problem where problematic memories are known to play an important role”. An article in the journal earlier this year said ketamine “may prove to be a viable tool in treating PTSD for those who fail more conventional treatments”.
The University College London experiment involved only 90 people. A clinical trial and passing rigorous guidelines would be required before ketamine is commonly used to treat addiction. Das believes “if everything works out well, it could be within a decade”.
Ketamine is already used on the National Health Service in Britain to treat pain “that is difficult to control”.
In March, however, the drug was licensed in the US for another problem: depression. Sufferers who have already attempted two other medications unsuccessfully can apply to use it in the form of a nasal spray. It became the first new depression drug in more than three decades.
According to Brett Melanson, a PhD student writing in The Conversation earlier in 2019, ketamine works “within hours and its effects are maintained for at least one week. Most strikingly, ketamine is effective in those patients who are resistant to ordinary antidepressants,” which he said makes up 30%-50% of depression sufferers.
This is because the drug’s antidepressant effect is unique. Mostly, antidepressants control levels of neurotransmitters in the brain such as serotonin. Ketamine, however, targets glutamate, the brain’s principal excitatory neurotransmitter.
“One of the fascinating findings about ketamine is that it can rapidly reduce depressive symptoms in patients who do not respond to typical monoamine antidepressants,” writes Melanson.
“This suggests the role of glutamate in depression.”
The European Medicines Agency is considering the same approach as the US’s Food and Drug Administration, which could open the door to its use for depression in the UK.
There is also evidence ketamine can help migraine sufferers, which would be (quiet) music to the ears of the 6-million people affected in the UK, according to the National Institute for Health and Care Excellence.
A US study from 2017 found three-quarters of migraine sufferers who were given ketamine reported an improvement. “Our study focused on short-term relief,” said Dr Eric Schwenk, “but it is encouraging that this treatment might have the potential to help patients long term.”
Das puts ketamine’s versatility down to its “broad pharmacological action in the brain. It works on two or three systems. The first one is opioid receptors that is how you get the pain relief. It also binds the NMDA receptors, which is the reason we use it, we know that’s the one that’s key in destabilising memories.”
Prof Celia Morgan, a psychopharmacologist at the University of Exeter, said: “Ketamine is an addictive substance and associated with harms to bladder and a risk of accidents, so we have to be cautious when using it in groups who are prone to addictive behaviour. But this is important work trying to drive the science of ketamine and memory forwards.”
From pain to PTSD, bipolar disorder to migraines, and depression to addiction, ketamine has the potential to cure a wide range of issues.
“I’m sure people are going to start looking at it for a lot of things now,” says Das. /©
WE’VE SHOWN THAT IT WORKS IN PRINCIPLE, NOW IT’S ABOUT WHAT’S THE OPTIMAL DOSE, THE OPTIMAL TREATMENT