Overcoming alcoholism is notoriously difficult, but researchers are hoping a new treatment combination might help: ketamine and psychological therapy. The use of psychedelics alongside therapy is a booming area of research, with ketamine, MDMA and psilocybin – the active ingredient of magic mushrooms – among the drugs that are being studied to tackle mental health problems ranging from depression to PTSD. Now researchers are set to launch a £2.4m phase 3 trial, the largest of its kind, to explore the use of ketamine in treating severe alcohol use disorder. Prof Celia Morgan of the University of Exeter, who is leading the new trial, said people with alcohol problems could find it difficult to engage with psychological interventions, but that ketamine could help. “Our model is really using the ketamine as a catalyst for the therapy,” she said. The team behind the study, known as Ketamine for Reduction of Alcohol Relapse (Kare), previously completed a proof of concept trial that suggested people with severe alcohol use disorder who were given ketamine alongside psychological therapy were more likely to remain completely abstinent six months later than those who were given a placebo. “This phase 3 trial seeks to find definitive evidence of this effect so that hopefully we might be able to roll out this treatment eventually to patients and the NHS,” said Morgan. While other scientists have also looked at tackling alcohol problems with a ketamine-based treatment, Morgan noted some of those studies had focused on social drinkers and used a one-off memory disruption intervention. By contrast the new trial will take place at seven NHS sites across the UK and is expected to involve 280 participants with severe alcohol use disorder – the group, Morgan noted, that is the most difficult to treat and the most likely to relapse. With previous work showing ketamine boosts the effect of psychological therapy, the participants will be split into two groups. Half the participants will be given three separate infusions of a very low dose of ketamine, 0.01mg/kg, over a period of one to two months, with educational sessions about relaxation and the harmful effects of alcohol given before and after each dosing, with a seventh educational session at the end of the intervention period. Morgan said the very low dose was not expected to have any therapeutic effects but would help to keep participants unaware of which of the two study groups they were in, helping the team control for placebo effects. The other group of participants will be given three infusions of a much larger dose of ketamine, 0.8mg/kg, together with seven psychological therapy sessions. That level of ketamine, said Morgan, was on a par with a large recreational dose. “In our proof of concept study, people were experiencing some quite unusual things like having out of body experiences, feeling like they were having these insights and epiphanies into their life,” she said. Morgan said such experiences could be useful in helping participants shift their perspective and view their alcohol problems in a different way, while ketamine also promoted the growth of new synapses in the brain – an effect thought to peak 24 hours after taking the drug. “We time one of our psychological therapies so that the brain is really primed for new learning,” she said. Both groups of participants will be followed up at three and six months, with their alcohol intake measured via a combination of self-report, smartphone-mounted breathalysers and wearable devices. “We are looking for significant differences in abstinence at six months,” said Morgan. Morgan stressed the drug alone was not thought to help people with alcohol problems, adding that the trial would be carried out in safe, carefully controlled conditions alongside therapy. Mitul Mehta, aprofessor of neuroimaging and psychopharmacology at King’s College London, who is not involved in the research, welcomed the trial. “The earlier trial warrants this larger investigation. We also need a push to better understand the mechanisms of the treatment effect so that patients most likely to respond can be selected and appropriately monitored,” he said. “By carefully examining the mechanisms we can also learn about the most effective ways to refine treatment in the future.”