The first patients are being screened to see if they are eligible to take part in the £2.4 million phase III trial led by the University of Exeter. The trial will initially be delivered at eight NHS sites across the UK including Oxford Health.

The study, called Multicentre Investigation of Ketamine for Reduction of Alcohol Relapse (MORE-KARE), is co-funded by a partnership between the National Institute for Health and Care Research (NIHR), the Medical Research Council (MRC), and biotech company Awakn Life Sciences. It is managed by the Exeter Clinical Trials Unit. 

The latest trial builds on positive initial findings of an earlier phase II trial, which showed combined ketamine and therapy treatment was safe and tolerable for people with severe alcohol use disorder. The previous trial found that participants who had ketamine combined with therapy went from drinking every day to remaining sober 86 per cent of the time over a six-month period

Now, the new trial, called MORE-KARE, will further test this finding, with the aim of rolling it out into the NHS if the combined treatment proves effective.

Trial lead Professor Celia Morgan, from the University of Exeter, said:

“More than half a million UK adults have serious alcohol problems that require help, yet only one in five of those get treatment. Current treatments have low success rates – we know that three out of four people who quit alcohol will be back drinking heavily after a year. This new trial is helping to fill the gap in the urgent search for new treatments. We’re excited that the NIHR and Awakn Life Sciences have funded this study, which is the largest study of ketamine combined with psychological therapy to take place anywhere in the world.”

Early research conducted in the 1980s found promising reductions in alcohol relapse rates following ketamine treatment. More recent studies have also shown that ketamine has a fast-acting anti-depressant effect and may improve learning of new information – both of which may help prevent relapse in alcohol use disorder.

In a recent paper, the KARE team shed new light on why ketamine may be effective. A pilot study involved 28 people being given ketamine, or a placebo, combined with mindfulness therapy. They found that ketamine may improve treatment outcomes by making people more receptive to mindfulness therapy, increasing engagement with the therapy.

Prof Rupert McShane

Associate Professor Rupert McShane, Consultant Psychiatrist at the University of Oxford who leads the Oxfordshire ECT and ketamine services at Oxford Health NHS Foundation Trust  and collaborator on the trial, said:

“Alcohol problems affect not only the individual but families, friends and communities, and related deaths have increased still further since the pandemic. Alcohol-related harm is estimated to cost the NHS around £3.5 billion each year, and wider UK society around £40 billion. We urgently need new treatments.  If this trial establishes that combined ketamine and therapy works, this will be a step closer towards seeing it used in the NHS, to help people turn their lives around.”

Participants will be randomly allocated to receive a different dose of ketamine infusion, via a drip.  They will also receive psychological support sessions with a trial therapist.  The ketamine dose and type of psychological support received by each participant will be randomly assigned by a computer. Neither the participant nor the site research team will be told which dose/support they are given. To measure how effective the treatment is, alcohol use will be monitored via drink diaries and daily self-breathalysing. Participants will be followed up in person at three and six months. Recruitment is currently open in Exeter and Oxford, with more locations expected to open soon.

To find out more, visit the website: Home > MORE-KARE (exeter.ac.uk)

Ketamine trial helped Alex kick 20 years of daily drinking 

As a freelancer sports photographer with a busy social life, Alex could always find some reason to drink daily. For years, he didn’t see it as a problem – but when he tried to kick the habit, he just couldn’t – until he finally found success when he took part in the Ketamine for Reduction of Alcohol Relapse (KARE trial).

Alex, 45, took part in an earlier (phase II) trial led by the University of Exeter more than six years ago, and has not drunk alcohol since. He said:

“It worked incredibly well for me. My relationship with alcohol is now non-existent. That’s a massive turnaround from where I was.”

Rewind six years, and Alex would take up every opportunity to drink socially, and then continue at home in the evening.

The father-of-two from South London said: “I’d say I was on the moderate end of having a drinking problem, which I suspect is quite relatable to a lot of people. I wasn’t missing any work deadlines, and I was coping in my everyday life, but I wanted to stop drinking every day and I just couldn’t do it. I kept making excuses to allow myself to drink, to nip to the supermarket late at night because we were out of milk, pick up a few more beers, and drink them on the couch. I’d been trying to stop for a year, but I’d never managed it.”

Alex had just embarked on a Psychology degree when he heard about the KARE trial. He said:

“I thought it could help me break my habit, and I was interested in contributing to research in this area. I went into it with some apprehension. I gave up alcohol two weeks before the trial to fulfil the criteria for abstinence, and it was the longest time in two decades I’d gone without booze. I’d never tried ketamine before, and it was odd not knowing what arm of the trial I was going to get. Taking part in the trial was one of the more intense experiences of my life. Everything was completely internalised – no body, no outside world. I felt sucked into an internal void.”

Some initial anxiety gave way to a strong sense of internal monologue, and a feeling of dissociation. Alex said:

“At times it felt like I no longer existed, like I was in some kind of afterlife, but I was accepting of that. I’d say acceptance was a big theme of my experience throughout. It was interesting, but it left me quite confused, and it took me a while to make any sense of it.”

Alex was sceptical about the psychotherapy that followed each of three ketamine sessions, but diligently threw himself into the tasks set, such as keeping a diary and listing high-risk situations in which he would be prone to drink. He said:

“It’s impossible for me to know which aspect is responsible for the benefits I experienced, whether it’s the ketamine, the therapy or the combination. All I know for sure is that I haven’t had a drink since that first treatment more than six years ago, and before that I drank virtually every day for 20 years.”

Now, working as a psychologist, Alex never regrets his decision to quit booze. He said:

“It’s not like the trial flicked a switch. For the first year I struggled. It was a daily battle, and I was irritable and short-tempered. My wife and family really supported me. But now I can go into a pub where my friends are drinking, and it doesn’t even cross my mind to order alcohol. The trial changed my life – there was absolutely no chance I’d have got to this point on my own.”

Alex’s psychology experience led him to support some initial work in the MORE-KARE trial, helping to identify suitable participants, before moving on to take up clinical psychology training.