Medication to Stop Drinking: Naltrexone & Acamprosate

Three medications have strong clinical evidence behind them for stopping alcohol use: naltrexone, acamprosate, and disulfiram. None of them are a standalone cure, and none of them manage withdrawal, that is a separate medical problem requiring its own treatment. What they do is change the brain chemistry that keeps you drinking after you have stopped, making it significantly easier to stay stopped. Most patients who benefit from these medications were never told they existed.

Most people who walk into our clinic have spent years trying to quit through willpower alone. When I tell them there are medications that reduce cravings and block the reward signal of alcohol, the most common response is: “Why did nobody tell me this sooner?” The evidence for naltrexone and acamprosate is solid, not perfect, but solid, and the fact that they are underused is one of the more frustrating realities of addiction treatment.

How These Medications Actually Work

Alcohol affects your brain through two main systems. The first is the opioid reward pathway: when you drink, your brain releases endorphins, which bind to mu-opioid receptors and produce feelings of pleasure and relief. Over time, your brain recalibrates around this. The second is the glutamate and GABA system: alcohol suppresses glutamate (an excitatory chemical) and amplifies GABA (an inhibitory chemical), which is why it relaxes you. When alcohol-dependent people stop drinking, glutamate rebounds aggressively, causing anxiety, agitation, and, in serious cases, seizures.

Naltrexone targets the first system. Acamprosate targets the second. Disulfiram works differently again: it does not change cravings at all, it just makes drinking physically unpleasant enough that most people choose not to.

Understanding which system is driving your drinking matters for choosing the right medication. That is a clinical decision, not a self-diagnosis.

Naltrexone: What It Does and Who It Helps

Naltrexone is a mu-opioid receptor antagonist. It blocks the receptors that alcohol-triggered endorphins bind to. Drink on naltrexone and the reward signal is blunted. The alcohol still hits your bloodstream, but the brain does not get the flood of “that felt good, do it again” feedback it normally gets.

The clinical result: many patients report that alcohol becomes less interesting. Not disgusting, not aversive, just flatter. Less worth the effort.

The COMBINE Trial and What It Showed

The COMBINE trial, the largest randomised controlled trial of alcohol pharmacotherapy, showed naltrexone significantly increased abstinence rates and reduced heavy drinking days compared to placebo. Patients who received naltrexone plus medical management did as well as those who received specialist behavioural therapy without medication. The combination of both was not dramatically better than either alone, which surprised a lot of people in the field, but it confirmed that medication alone, done properly, is a legitimate treatment.

Naltrexone Dosing and Timing

Standard oral naltrexone is 50mg once daily. It reaches therapeutic levels within hours and maintains them reliably if taken every day. An injectable extended-release form, Vivitrol, is given monthly and removes the compliance problem entirely: useful for patients who know they will stop taking tablets when cravings get bad.

Do not start naltrexone until you have been opioid-free for at least 7 to 10 days. If opioids are still in your system, naltrexone will trigger immediate, severe withdrawal. This is not a mild side effect: it is genuinely dangerous.

Naltrexone and the OPRM1 Gene

There is a genetic variant worth knowing about: the OPRM1 A118G polymorphism. People who carry the G allele (roughly 20-30% of the population) have a stronger opioid reward response to alcohol, and they also respond better to naltrexone. The PREDICT trial specifically examined this and found clinically meaningful differences in treatment response by genotype. Pharmacogenomic testing for this is not standard practice everywhere, but it is available and can help when a patient has not responded as expected.

Never take naltrexone if you are using opioid medications (opioid painkillers, methadone, buprenorphine) or have used heroin, fentanyl, or codeine within the past 7-10 days. Doing so can cause sudden, severe opioid withdrawal: extreme pain, vomiting, and dangerously elevated heart rate. Tell your prescribing doctor about every substance you use, including medications prescribed by other doctors.

Acamprosate: What It Does and Who It Helps

Photo by Austrian National Library on Unsplash

Acamprosate works on a completely different target. After prolonged heavy drinking, your brain’s glutamate system becomes chronically overactive. This is part of why early abstinence feels so uncomfortable: anxiety, restlessness, difficulty sleeping, an almost physical sense of unease. Acamprosate modulates NMDA glutamate receptors and GABA-A receptors to dampen this hyperexcitability.

The practical effect: it reduces the physical discomfort of early abstinence. Patients describe it as taking the edge off, making the first weeks of sobriety feel less like white-knuckling through a storm.

Who Responds Best to Acamprosate

The evidence suggests acamprosate works best in patients who are already abstinent and want to stay that way, particularly those whose drinking was driven by anxiety, restlessness, or the physical craving to feel normal rather than the pleasure of intoxication. A 2014 Cochrane review of 27 trials confirmed acamprosate significantly reduced the risk of any drinking compared to placebo, with a number needed to treat of around nine, which is clinically meaningful in this field.

Patients with severe liver disease handle acamprosate better than naltrexone because acamprosate is renally excreted rather than hepatically metabolised. The reverse is true for patients with significant kidney disease.

Acamprosate Dosing and Timing

The standard dose is 666mg three times daily with meals, giving a total daily dose of 1,998mg. Start it after withdrawal is complete, typically 5 to 7 days after your last drink. Taking it before withdrawal is resolved adds no benefit and misses the mechanism entirely.

The most common side effect is diarrhoea, usually in the first week. It settles for most patients. If it does not, dose timing adjustments can help.

Acamprosate takes 5 to 8 days to reach steady plasma levels. Do not judge whether it is working in the first few days. Most patients who stop it early do so before the medication has had a chance to do anything.

Naltrexone vs Acamprosate: Choosing the Right Medication

The two medications can be combined. COMBINE trial data did not show dramatically additive benefit in the general population, but clinically, patients with both reward-craving and abstinence-anxiety components sometimes do better on both.

Disulfiram (Antabuse): The Aversion Medication

Disulfiram works by blocking aldehyde dehydrogenase (ALDH2), the enzyme your liver uses to break down acetaldehyde, the toxic byproduct produced when alcohol is metabolised. Normally, ALDH2 clears acetaldehyde quickly. If you drink on disulfiram, acetaldehyde accumulates. Within 10 to 30 minutes you will experience flushing, nausea, vomiting, palpitations, and a pounding headache. Severe reactions can cause hypotension and, rarely, cardiovascular events.

The mechanism is the same reaction seen in people with the ALDH22 genetic variant, common in East and Southeast Asian populations, the so-called “Asian flush.” Disulfiram essentially imposes that reaction pharmacologically on anyone who drinks.

Does Disulfiram Actually Work?

Supervised disulfiram has a reasonable evidence base. Unsupervised disulfiram is much less effective because patients simply stop taking it when they want to drink. The MATCH study and several European trials showed benefit primarily when a third party, typically a spouse or clinical worker, observed daily dosing. If compliance can be ensured, disulfiram is useful. If it cannot, naltrexone or acamprosate are more practical choices.

Disulfiram reactions are not just unpleasant: they can be dangerous in patients with cardiac conditions, severe hypertension, or diabetes. Do not take disulfiram without a full medical assessment. Some foods, mouthwashes, and medications contain small amounts of alcohol that can trigger a reaction. Your prescribing doctor needs to review everything you use.

What About Medications for Alcohol Withdrawal Specifically?

This is the most important distinction to get right: naltrexone, acamprosate, and disulfiram do not treat withdrawal. They are not interchangeable with the medications used to manage acute withdrawal.

Alcohol withdrawal can be life-threatening. If you are physically dependent on alcohol and stop abruptly, your GABA-A receptors, previously suppressed by chronic alcohol exposure, become suddenly underactivated. Glutamate rebounds. The result can be severe anxiety, seizures, and delirium tremens (DT), which carries a mortality rate of up to 15% if untreated.

Withdrawal is managed with benzodiazepines (typically diazepam or chlordiazepoxide) titrated using the CIWA-Ar scale, or in some settings with phenobarbital or gabapentin. You can read more about how Librium (chlordiazepoxide) is used in medically supervised alcohol withdrawal, and about the real risks of untreated severe withdrawal, in our separate clinical guides.

The sequence is: manage withdrawal first, then start relapse-prevention medication once withdrawal has resolved.

If you are drinking daily and cannot get through more than 12-16 hours without shaking, sweating, or feeling seriously unwell, you may be physically dependent and need medically supervised withdrawal before any relapse-prevention medication is appropriate. This is not optional. Unsupported withdrawal from alcohol carries genuine medical risk.

Off-Label Medications With Evidence

Gabapentin

Gabapentin (brand name Neurontin) is not approved specifically for alcohol use disorder in most countries, but it has meaningful evidence. A 2014 randomised controlled trial by Mason et al. published in JAMA Internal Medicine showed gabapentin significantly improved abstinence rates and reduced heavy drinking compared to placebo, with a dose-response relationship. It also helps with the sleep disruption and anxiety of early abstinence, which are significant relapse triggers. The main risks are sedation and, importantly, its own potential for dependence and misuse, which must be factored into patient selection.

Topiramate

Topiramate modulates GABA and glutamate transmission and has shown efficacy in several trials for reducing heavy drinking days. It is not FDA-approved for alcohol use disorder but is sometimes prescribed off-label. Side effects including cognitive blunting and word-finding difficulties limit tolerability for some patients.

Baclofen

Baclofen, a GABA-B receptor agonist, has been used in France and has a dedicated patient base in some European countries following Ameisen’s publications. The evidence is mixed. Some trials show benefit, particularly in patients with liver disease where other options are limited, but the data is not as clean as naltrexone or acamprosate. Overdose risk is real. This is a medication where honest uncertainty is the right clinical posture.

Medication Alone Is Not the Full Answer

Every major trial of pharmacotherapy for alcohol use disorder shows better outcomes when medication is combined with some form of psychosocial support. This does not have to mean years of intensive therapy. The COMBINE trial showed even brief, structured medical management sessions, provided by a primary care physician, not a specialist, significantly improved outcomes over medication alone.

The mechanism makes sense. Medication changes the neurochemical environment. Therapy and support help you rebuild the behavioural patterns and coping strategies that were displaced by alcohol. Both matter. Neither replaces the other.

Knowing the stages of alcohol dependence you are dealing with also changes the treatment approach: what works for someone in early problematic drinking differs from what works for someone with years of severe physical dependence.

If alcohol is something you think about most days, if you have tried to stop and found you could not, or if cutting back feels impossible rather than just difficult, that fits the clinical picture of alcohol use disorder as defined by DSM-5. It is a medical condition, not a character failure. The diagnostic criteria include things like tolerance, withdrawal, persistent desire to cut back, and continued use despite knowing the harm it causes. Three or more of eleven criteria in a 12-month period meets the threshold for diagnosis. That context matters because it means medication is not a crutch, it is an evidence-based treatment for a recognised medical condition.

At Phuket Island Rehab, we assess each patient’s neurobiology and drinking history before recommending a pharmacotherapy approach. Some patients do well on naltrexone alone with structured check-ins. Others need inpatient medical detox first, followed by a combined pharmacological and therapeutic programme. The approach is built around you, not around a fixed protocol.

Naltrexone and acamprosate are the two most evidence-supported medications for stopping alcohol use. They work through different mechanisms and suit different patient profiles, but they are not mutually exclusive, and neither replaces withdrawal management or psychological support. Disulfiram remains useful under supervised conditions. Off-label options including gabapentin and topiramate have genuine evidence behind them and are appropriate in specific clinical contexts. The key clinical principle is sequencing: withdrawal first, relapse prevention second, and psychosocial support running alongside both.

From a practical standpoint, if you are physically dependent on alcohol, the first conversation to have with a doctor is about safe withdrawal, not about which relapse-prevention tablet to start. Once you are through withdrawal and medically stable, naltrexone is a reasonable first choice for most patients unless there is an opioid use history or significant liver disease, in which case acamprosate becomes the more appropriate option. Neither medication requires you to believe in them. They work at a pharmacological level regardless of motivation, though motivation absolutely affects whether you take them consistently.

As John A. Smith of Phuket Island Rehab puts it: “Patients ask me whether these medications mean they are not really doing the work themselves. My answer is always the same: a diabetic who manages their condition with insulin is doing the work. Medication that corrects a neurochemical imbalance is not cheating. It is treatment.”

What is the best medication to stop drinking alcohol?

Naltrexone has the strongest evidence base for reducing heavy drinking days and preventing relapse to heavy use, while acamprosate has the strongest evidence for maintaining complete abstinence. The best choice depends on your specific situation: your liver function, whether you use opioids, and whether your main struggle is the reward craving or the physical discomfort of not drinking. A prescribing doctor who understands alcohol use disorder can make this call properly; there is no universal best option.

Can I get medication to stop drinking without going to rehab?

Yes. Naltrexone and acamprosate are prescribed by general practitioners and addiction medicine doctors in outpatient settings, and in many countries they are government-subsidised or covered by insurance. You do not need to be admitted to a residential programme to access them. That said, if you are physically dependent on alcohol and at risk of severe withdrawal, inpatient or medically supervised detox may be necessary as a first step before any relapse-prevention medication can begin.

Does naltrexone make you stop wanting to drink?

Naltrexone does not eliminate the desire to drink, but it blunts the reward signal that makes alcohol feel reinforcing. Most patients describe alcohol as becoming less interesting rather than suddenly aversive. Over time, this reduced reward response makes it easier to choose not to drink, and the habitual pattern weakens. Some patients experience a notable reduction in cravings; others experience a more subtle shift. It is not the same as having no interest in alcohol whatsoever.

How long do you need to take medication for alcohol use disorder?

Most clinical guidelines suggest a minimum of three to six months, with twelve months being a common treatment duration for both naltrexone and acamprosate. There is no fixed upper limit. Some patients do well coming off medication after a year with strong support systems in place; others find longer-term treatment keeps them stable. This should be a joint decision with your prescribing doctor based on how you are doing, not a predetermined endpoint.

Is it safe to drink alcohol while taking naltrexone or acamprosate?

Neither naltrexone nor acamprosate will make you seriously ill if you drink, unlike disulfiram. Naltrexone will blunt the reward you get from alcohol; acamprosate will not interact with alcohol in a pharmacologically dangerous way. That said, drinking on either medication typically means the medication is not achieving its goal, and a relapse during treatment should prompt a clinical review rather than just resuming the tablets and hoping for the best.

Can medication help with alcohol withdrawal symptoms?

Naltrexone, acamprosate, and disulfiram do not treat withdrawal. Withdrawal from alcohol is managed with a different class of medications, primarily benzodiazepines like diazepam or chlordiazepoxide, titrated carefully against withdrawal severity using a clinical scale called the CIWA-Ar. Untreated severe alcohol withdrawal carries real medical risk, including seizures and delirium tremens. Relapse-prevention medications are only started after withdrawal has been safely managed.

What happens if you drink on disulfiram?

Drinking alcohol while taking disulfiram causes an acetaldehyde reaction: flushing, nausea, vomiting, palpitations, and severe headache beginning within 10 to 30 minutes of alcohol exposure. This happens because disulfiram blocks the enzyme ALDH2, preventing your liver from clearing acetaldehyde, a toxic metabolic byproduct of alcohol. In patients with underlying cardiac or cardiovascular conditions, these reactions can be medically serious. Even small amounts of alcohol found in mouthwash, certain sauces, or medications can trigger a reaction.

John A. Smith is a Medical Professional and Addiction Counselor at Phuket Island Rehab with over 15 years of clinical experience in alcohol and substance use disorder treatment. He has worked with patients across the full spectrum of alcohol dependence, from early intervention to complex cases requiring medically supervised detox and long-term pharmacotherapy. His clinical approach integrates evidence-based medication protocols with individualised psychosocial support.

This article is for informational purposes only and does not constitute medical advice, diagnosis, or treatment. Medications for alcohol use disorder should only be prescribed and monitored by a qualified healthcare provider following a full clinical assessment. If you are experiencing alcohol withdrawal symptoms, seek emergency medical care immediately. If you are in crisis, contact a local emergency service or crisis line.