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

- By SOPHIE FREEMAN

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’.

 ?? Picture: SHUTTERSTO­CK ??
Picture: SHUTTERSTO­CK

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