Will new trial prove ‘miracle’ weight loss drug Wegovy can curb a craving for alcohol?

It is the type 2 diabetes and weight-loss drug that has taken the world by storm. But studies now suggest semaglutide — better known by the brand names Ozempic and Wegovy — could also help people addicted to alcohol.

About 1.7 million adults are drinking at levels likely to negatively affect their health, according to The Health Survey for England 2021.

Anecdotal reports first surfaced last summer that the obesity ‘wonder’ drug — taken as a daily pill or injection — was also curbing the taste for alcohol among those prescribed it for weight loss.

Now the first clinical trials in humans are under way after those beneficial effects were confirmed in animal studies.

Researchers at Oklahoma State University in the U.S. have set up the Semaglutide Therapy for Alcohol Reduction (STAR) study — in which 80 people who are abusing alcohol, or who are alcohol dependent — will receive weekly semaglutide or placebo injections over 12 weeks.

The semaglutide group will start with a dose of 0.25 mg a week for four weeks, eventually rising to 1 mg a week — the same dosing schedule used when starting semaglutide for type 2 diabetes.

The study will measure changes in alcohol consumption, as well as changes in brain activity using scans such as functional magnetic resonance imaging (fMRI).

Kyle Simmons, a professor of pharmacology and physiology who is running the trial, told Good Health: ‘Semaglutide appears to modulate activity in the brain’s reward circuitry, making food and alcohol less rewarding.

‘In other words, with semaglutide on-board, that food or alcohol in front of you isn’t as ‘hot’ a stimulus to your brain as it would otherwise be.

‘We don’t know yet whether semaglutide is safe and effective for treating alcohol use disorder, but data from studies with rodents and monkeys suggest it will be and anecdotal evidence in humans suggests it might be.’

While the results of the trial may not be known until 2025 at the earliest, data from animal research has generated much interest in the drug’s potential.

A study conducted by scientists at Gothenburg University in Sweden, published in the journal eBioMedicine in June, found semaglutide reduced alcohol intake in rats by 60 per cent.

The researchers attached a fluorescent molecule to the semaglutide to track where it went in the rats’ bodies and found it bound itself to the nucleus accumbens, a region of the brain involved in the reward system — although how exactly it has an effect there is not clear, said study co-author Elisabet Jerlhag Holm, a professor of pharmacology.

‘Semaglutide blocks the rewarding experience of alcohol,’ she told Good Health.

‘In [the] nucleus accumbens we know that it binds, but we don’t know the mechanisms yet.’ One theory is that it enhances transmission of GABA (gamma-aminobutyric acid), a chemical messenger involved in reward.

Another study, by the University of Copenhagen in Denmark, presented at the Research Society on Alcoholism conference in June, looked at how much alcohol monkeys consumed when it was made available to them — along with water — for four hours a day.

Half the monkeys were then given semaglutide and half a placebo, before being allowed access to alcohol again.

This time, the semaglutide group consumed 40 per cent less alcohol than the placebo group.

‘That is a huge effect,’ notes Professor Simmons. Indeed, Professor Anders Fink-Jensen, a psychiatrist who led the University of Copenhagen study, said semaglutide was up to 20 per cent more effective at curbing alcohol consumption than other drugs in the same class they had previously tried.

The Health Survey for England 2021 found one in five adults (ten million people) drink above the recommended weekly limit of 14 units — and 1.7 million of them are drinking 35-50 units a week.

So could semaglutide help ‘social’ drinkers to cut down, as well as the alcohol dependent?

‘The answer depends a bit on what we find in the trials, but the potential is there for it to help both patients who want to quit drinking completely, as well as those who simply want to drink less,’ says Professor Simmons.

‘One potentially interesting scenario is that it could be used to help support sobriety during the first six months or year of overall treatment for alcohol-use disorder, when patients are at a greater risk of relapse, and while they are gaining skills through psychotherapy and making other life changes.’ But there may be pitfalls. Because semaglutide appears to work by altering the way the brain experiences reward, there is concern it could also affect people’s mood and cause depression in those susceptible to the condition.

In July, the Medicines and Healthcare products Regulatory Agency (MHRA) launched a review of the class of drugs to which semaglutide belongs after receiving five reports of ‘suicidal and self-injurious behaviour’ via its Yellow Card scheme for monitoring drug safety and possible side-effects.

This review is ongoing. The MHRA told Good Health: ‘We are considering all available evidence and will communicate any further advice to patients and healthcare professionals as appropriate.’

Professor Simmons adds: ‘If the medication is altering the activity of the brain’s reward circuitry, we need to make certain that it doesn’t promote anhedonia — a general loss of interest in pleasure.

‘It would not be ideal for patients to have to choose between reducing the harms associated with heavy drinking and losing some of their ability to enjoy life’s pleasures more generally, such as social interaction or sex, for instance.

‘Anhedonia is also a potential risk for patients who might have a history of depression but where the illness is currently in remission.

‘We want to be certain that the treatment for alcohol-use disorder doesn’t bring about an anhedonia that makes relapse into depression more likely.’

Matt Field, a professor of psychology at Sheffield University, adds: ‘Semaglutide may reduce the likelihood that you will drink to excess after consuming one or two drinks.

‘But there are many examples of addiction medications that seemed to work in animals but didn’t work at all in humans for one reason or another.’

Currently, drugs that are approved to treat alcohol dependence in the UK include acamprosate calcium (brand name Campral); disulfiram (Antabuse); and nalmefene.

Acamprosate works by affecting levels of GABA, which is thought to influence cravings.

The NHS says it is used to help prevent a relapse in people who have successfully stopped drinking, and is usually offered in combination with counselling.

Disulfiram, meanwhile, is prescribed to people trying to stop drinking but where there is a concern about them relapsing; it works as a deterrent by causing unpleasant physical reactions, such as nausea and vomiting, if the person drinks.

Nalmefene blocks opioid receptors in the brain to reduce cravings, to prevent a relapse or limit the amount a person drinks.

Another, more controversial, option is treating patients with the ‘party drug’ ketamine.

Last year, Exeter University researchers published results of a study involving 96 people that showed a combination of cognitive behavioural therapy — a talking therapy — and low doses of ketamine helped drinkers stay completely sober for 162 of 180 days in the six-month follow-up period, representing 87 per cent abstinence, reported the American Journal of Psychiatry.

Research leader Celia Morgan, a professor of psychopharmacology, told Good Health: ‘We think the ketamine facilitates the psychological therapy by both affecting neuroplasticity in the brain — which means it is able to learn more readily — and by giving people a new perspective on their problems through the unique subjective effects.’

Professor Morgan’s team has now been awarded £2.4 million by the Medical Research Council, the National Institute for Health and Care Research and a private company to carry out a larger trial across seven NHS sites.

Dr Emily Finch, chair of the Addictions Faculty at the Royal College of Psychiatrists, says new pharmacological treatments for alcohol addiction ‘will always be welcomed’, but need to undergo ‘extensive research and rigorous clinical trials’.