Acamprosate: Definition, Mechanism of Action, Uses, Dosage, Side Effects, Alternatives

Acamprosate is a medication used to support alcohol abstinence. It functions by stabilizing neurotransmitter activity to reduce cravings and prevent relapse. According to Witkiewitz, K.’s 2012 study, ‘Acamprosate for treatment of alcohol dependence: mechanisms, efficacy, and clinical utility, ’ acamprosate reduced the risk of returning to any drinking by 86% and increased abstinence duration by 11% compared to placebo during treatment.

After treatment ended (3-12 months follow-up), acamprosate patients had a 9% lower risk of returning to drinking and 9% higher continuous abstinence duration than placebo recipients. In recent combination therapy studies, acamprosate with behavioral therapy showed success rates of 47.6% at treatment completion and 35% at 6-month follow-up. Acamprosate showed no significant advantage over placebo in preventing return to heavy drinking. The average time until first drinking day ranged from 66 to 81.5 days for patients taking acamprosate.

The mechanism of action of Acamprosate involves modulation of neurotransmitter activity in the central nervous system, primarily affecting glutamate and GABA systems. It acts as an antagonist of the NMDA receptor, reducing glutamatergic hyperexcitability during alcohol withdrawal. Acamprosate also enhances GABAergic inhibitory activity, helping to normalize neurotransmission, decrease withdrawal symptoms, and reduce cravings.

Acamprosate is primarily used for the maintenance treatment of alcohol use disorder (AUD) in patients who have already achieved abstinence. It helps prevent relapse by reducing alcohol cravings and withdrawal symptoms in people who have stopped drinking.

The recommended dose of Acamprosate is 666 mg daily, taken as two 333 mg tablets three times daily with meals; for kidney impairment (CrCl 30–50 mL/min), the dose is reduced to 333 mg three times daily, and it is not recommended for severe renal impairment.

The side effects of Acamprosate include common symptoms such as discouragement, sadness, irritability, loss of appetite, nervousness, insomnia, tiredness, and difficulty concentrating, along with serious effects like injury, bloating, burning, tingling, dizziness, dry mouth, excess gas, itching, pain, and increased sweating; monitoring symptoms and consulting a healthcare provider is necessary.

The main alternatives to Acamprosate for treating alcohol use disorder are Naltrexone, Disulfiram, and Nalmefene; Naltrexone blocks opioid receptors to reduce alcohol’s rewarding effects, Disulfiram causes unpleasant reactions when alcohol is consumed, and Nalmefene modulates opioid receptors to decrease alcohol intake.

What Is Acamprosate?

Acamprosate is a prescription medication approved in the United States under the brand name Campral. It is used specifically for the treatment of alcohol use disorder (AUD). The U.S. Food and Drug Administration (FDA) approved acamprosate in 2004 for use alongside psychosocial support to help maintain abstinence in patients who are already abstinent at the start of treatment. Clinical trials demonstrated that acamprosate significantly increases the rate of complete abstinence and prolongs the time to first drink compared to placebo, confirming its efficacy in supporting recovery from alcohol dependence.

What Is The Chemical Composition Of Acamprosate?

The chemical composition of Acamprosate includes its active ingredient, acamprosate calcium, which is the calcium salt of N-acetylhomotaurinate. This active component is responsible for its therapeutic effects in treating alcohol use disorder. The medication also contains inactive ingredients that vary depending on the formulation but typically include substances such as microcrystalline cellulose, sodium bicarbonate, and colloidal silicon dioxide, which serve as fillers, stabilizers, or agents to aid in the tablet’s manufacturing and absorption process. These components together ensure the stability, efficacy, and bioavailability of the drug.

What Is the Mechanism of Action of Acamprosate?

The mechanism of action of Acamprosate involves modulation of neurotransmitter activity in the central nervous system, particularly affecting glutamate and gamma-aminobutyric acid (GABA) systems. Acamprosate acts as a functional antagonist of the ionotropic glutamate N-methyl-D-aspartate (NMDA) receptor, which is involved in excitatory neurotransmission. It reduces the hyperexcitability of the glutamatergic system that occurs during alcohol withdrawal, thereby helping to normalize neurotransmission. Additionally, Acamprosate enhances GABAergic inhibitory activity, which contributes to reducing withdrawal symptoms and craving by restoring the balance between excitatory and inhibitory neurotransmitters. Neurochemical studies indicate that Acamprosate modulates NMDA receptor function, possibly through regulatory polyamine sites, and also influences metabotropic glutamate receptors, which further supports its role in stabilizing neurotransmitter activity disrupted by chronic alcohol use.

How Long Does It Take for Acamprosate to Work?

It takes for Acamprosate about several days to begin showing effects, with full therapeutic benefits typically occurring after 4 to 6 weeks of continuous use. Patients usually notice a gradual reduction in craving and withdrawal symptoms as the medication stabilizes neurotransmitter activity disrupted by alcohol dependence. Continuous use of Acamprosate is essential to maintain its efficacy in supporting abstinence and preventing relapse, as stopping the medication prematurely reduces its protective effects. The medication works best when combined with psychosocial support and adherence to the prescribed regimen.

What Are the Uses of Acamprosate?

The uses of acamprosate are primarily for the maintenance treatment of alcohol use disorder (AUD) in patients who have already achieved abstinence. The uses of acamprosate include preventing relapse by reducing alcohol cravings and withdrawal symptoms in people who have stopped drinking. FDA-approved Acamprosate works by restoring the brain’s chemical balance disrupted by chronic alcohol consumption, helping patients maintain long-term sobriety. This medication serves as an essential component of comprehensive AUD treatment programs, typically combined with counseling and psychosocial support to enhance recovery outcomes. Acamprosate’s main purpose is to support continued abstinence rather than helping patients through the initial detoxification process.

Are There Any Off-Label Uses of Acamprosate?

Yes, Acamprosate has off-label uses beyond its FDA-approved indication for alcohol use disorder (AUD). Potential benefits in other neuropsychiatric conditions due to its modulatory effects on neurotransmitters such as glutamate and GABA. 

According to Erickson, C. A.’s 2014 study,‘Impact of acamprosate on plasma amyloid-β precursor protein in youth: a pilot analysis in fragile X syndrome-associated and idiopathic autism spectrum disorder suggests a pharmacodynamic protein marker’, acamprosate has shown promise in several off-label applications beyond alcohol dependence treatment. Studies indicate potential benefits in autism spectrum disorder (both idiopathic and fragile X syndrome-associated) and other neurological conditions. As a glutamate and GABA modulator, it addresses neurotransmitter imbalances implicated in these disorders. While specific off-label prescription rates are not well documented, approximately 15-20% of patients experience mild side effects when used for these alternative indications.

Who Should Use Acamprosate?

Acamprosate should be used by patients diagnosed with alcohol use disorder (AUD) who have achieved abstinence and seek to maintain it, especially those with severe AUD or a history of multiple relapses. It benefits individuals aiming to prevent relapse by reducing cravings and withdrawal symptoms, supporting long-term sobriety as part of a comprehensive treatment plan. 

According to Mar, Y.’s 2023 study, ‘Treatment of alcohol use disorder, ’ acamprosate serves as an appropriate option for patients with AUD who experience significant hepatic dysfunction, as it bypasses liver metabolism. Clinicians need to measure CrCl before initiating treatment. Patients with CrCl between 30 and 50 mL/min or eGFR between 30 and 59 mL/min require dose reduction. For optimal effectiveness, clinicians initiate acamprosate within 7 days after alcohol abstention, particularly in highly motivated patients.

Who Should Not Use Acamprosate?

Patients with severe kidney disease or renal impairment should avoid taking Acamprosate, as the drug is primarily excreted through the kidneys, and accumulation leads to toxicity. Pregnant women should also avoid Acamprosate due to insufficient safety data during pregnancy. Additionally, individuals with known hypersensitivity to Acamprosate or any of its components should not use this medication.

What Is the Recommended Dosage of Acamprosate?

The standard recommended dose of Acamprosate is 666 mg per day, administered as two 333 mg tablets taken three times daily with meals. For adults with kidney impairment (creatinine clearance [CrCl] of 30–50 mL/min), the FDA-recommended initial dose is reduced to 333 mg (one tablet) three times daily. Acamprosate is not recommended for patients with severe renal impairment due to the risk of accumulation and toxicity. The FDA guidelines emphasize adherence to these dosing recommendations to ensure safety and efficacy in the treatment of alcohol use disorder. Acamprosate should be taken with meals to minimize gastrointestinal side effects and is initiated during a period of alcohol abstinence.

How Long Should You Take Acamprosate?

Individuals should take Acamprosate for six months to one year, with some patients continuing treatment beyond this timeframe. According to National Institute for Health and Care Excellence (NICE) guidelines (2011), Acamprosate “usually be prescribed for up to 6 months, or longer for those benefiting from the drug who want to continue with it.” Treatment duration depends on specific factors, including patient response to the medication, persistence of drinking behavior (treatment should be stopped if drinking persists 4-6 weeks after starting), liver function recovery, and patient motivation to maintain abstinence. 

According to the National Center for Biotechnology Information, 2025 publication, ‘PubChem Compound Summary for CID 71158, Acamprosate, ’ acamprosate has been evaluated in clinical trials for up to one year, with year-long studies showing a 2.4% rate of suicidal events compared to 0.8% in placebo groups. The medication appears to be generally well-tolerated during extended use, with no evidence of developing tolerance or dependence, and no withdrawal symptoms reported at therapeutic doses. Hypercalcemia has not been reported in acute overdose cases but should be considered as a risk in chronic overdosage, and long-term use has not been associated with liver enzyme elevations or clinically apparent liver injury.

What Should You Do If You Miss a Dose of Acamprosate?

Do take the missed dose as soon as you remember if you miss a dose of Acamprosate. Skip the missed dose and continue with the regular schedule if it is almost time for the next dose to avoid overdose risk. Taking double or extra doses is not advised.

What Are the Side Effects of Acamprosate?

The side effects of acamprosate are feelings of discouragement, sadness, irritability, diminished appetite, weakness, decreased interest in activities, anxiety, insomnia, fatigue, and concentration difficulties.

Here are both the common and serious side effects of acamprosate:

Common Side Effects of Acamprosate?

Common side effects of acamprosate include:

• Discouragement: A persistent feeling of hopelessness or lack of motivation occurs when using acamprosate.
• Feeling sad: Experiencing emotions of sorrow or unhappiness arises without an obvious cause during treatment.
• Irritability: A heightened state of frustration or annoyance develops in response to minor issues while on the medication.
• Lack of appetite: Reduced desire to eat leads to decreased food intake as a side effect of acamprosate.
• Lack or loss of strength: Feeling physically weak or drained of energy happens due to the medication’s impact.
• Loss of interest or pleasure: Diminished enjoyment or engagement in previously enjoyable activities manifests as a reaction to the drug.
• Nervousness: Experiencing restlessness or unease occurs due to anxiety or stress triggered by acamprosate.
• Sleeplessness: Difficulty falling asleep or staying asleep throughout the night results from the medication’s influence.
• Tiredness: Persistent fatigue or exhaustion that does not improve with rest develops as a side effect.
• Trouble concentrating: Inability to focus or maintain attention on tasks or activities arises during treatment.
• Trouble sleeping: Challenges in achieving restful or uninterrupted sleep occur as a result of using acamprosate.

Serious Side Effects of Acamprosate

Serious side effects of acamprosate include:

• Accidental injury: An increased likelihood of experiencing harm or injury arises due to impaired coordination, dizziness, or reduced awareness while on the medication.
• Bloated or full feeling: A sensation of abdominal swelling or discomfort develops as a result of trapped gas or slowed digestion caused by the drug’s impact on the gastrointestinal system.
• Burning, crawling, itching, numbness, prickling, “pins and needles”, or tingling feelings: Unusual nerve-related sensations occur, often felt on the skin or in the extremities, indicating potential effects on the nervous system.
• Dizziness: A feeling of lightheadedness or unsteadiness occurs, which leads to difficulty maintaining balance or performing tasks requiring focus.
• Dry mouth: Reduced saliva production leads to an uncomfortable dry sensation in the mouth, potentially causing difficulties with speaking, eating, or oral health.
• Excess air or gas in the stomach or intestines: Trapped gas accumulates in the digestive tract, causing bloating, pressure, or cramping as the body adjusts to the medication.
• Itching skin: Persistent or intense skin irritation occurs, leading to discomfort or the urge to scratch, often without an obvious external cause.
• Pain: Physical discomfort or aching arises, ranging from mild to severe, and affects various parts of the body during treatment.
• Passing gas: Frequent expulsion of gas from the digestive tract happens as the body attempts to relieve excess air buildup caused by gastrointestinal changes.
• Sweating: Excessive perspiration occurs, unrelated to physical activity or environmental heat, often resulting in discomfort or clamminess.

What Are The alternatives to Acamprosate?

The main alternatives to Acamprosate for treating alcohol use disorder include Naltrexone, Disulfiram, and Nalmefene. Naltrexone is a widely used alternative that works by blocking opioid receptors to diminish the rewarding effects of alcohol, showing effectiveness in relapse prevention and increasing abstinence rates. Disulfiram acts by causing unpleasant reactions when alcohol is consumed, thereby deterring drinking behavior. Nalmefene, similar to naltrexone, modulates opioid receptors and is used to reduce alcohol consumption in patients with AUD. These alternatives offer varied options depending on patient needs, treatment goals, and clinical considerations.

Alternatives to Acamprosate:

• Naltrexone
• Disulfiram
• Nalmefene

Naltrexone

Naltrexone is an opioid receptor antagonist approved for the treatment of alcohol use disorder (AUD). It helps reduce alcohol cravings and the rewarding effects of drinking by blocking opioid receptors in the brain, which decreases the desire to consume alcohol and supports relapse prevention.

According to McPheeter ’s 2023 study, ‘Pharmacotherapy for Alcohol Use Disorder: A Systematic Review and Meta-Analysis’, Naltrexone shows measurable effectiveness for alcohol use disorder treatment. Oral Naltrexone (50 mg daily) prevents 1 in 18 people from returning to any drinking and stops 1 in 11 people from returning to heavy drinking. Injectable Naltrexone reduces drinking by approximately 5 days over a 30-day treatment period. Side effects include increased risk of nausea (73% higher) and vomiting (53% higher) compared to placebo. The research confirms Naltrexone as a recommended first-line medication for alcohol use disorder when combined with counseling or behavioral therapy.

Disulfiram

Disulfiram is a medication used to support abstinence in alcohol use disorder by causing an adverse reaction when alcohol is consumed. It inhibits the enzyme acetaldehyde dehydrogenase, leading to the accumulation of acetaldehyde after alcohol intake, which produces unpleasant symptoms such as flushing, nausea, and palpitations. This reaction deters patients from drinking, thereby helping maintain sobriety.

According to Schallenberg, M.’s 2025 study, ‘Effectiveness of Disulfiram as Adjunct to Addiction-Focused Treatment for Persons With Severe Alcohol Use Disorder’, disulfiram demonstrated clear benefits for patients with severe alcohol use disorder. 50% of participants remained abstinent for at least 1 year. The medication prevents alcohol relapse through its aversive mechanism, causing unpleasant physical symptoms when alcohol is consumed. This helps patients resist cravings and avoid impulsive drinking. These results are significant considering alcohol typically recurs in 90% of cases without effective treatment.

Nalmefene

Nalmefene is an opioid receptor modulator approved in Europe for reducing alcohol consumption in patients with alcohol use disorder. It works by modulating the opioid system, similar to naltrexone, decreasing the reinforcing effects of alcohol and reducing the urge to drink. Nalmefene is used to reduce heavy drinking episodes and support controlled drinking or abstinence in patients with alcohol use disorder.

According to Miyata, H.’s 2019 study, ‘Nalmefene in alcohol‐dependent patients with a high drinking risk: Randomized controlled trial’, nalmefene significantly reduced heavy drinking days in alcohol-dependent patients. The 20 mg dose decreased drinking by 4.34 days per month and the 10 mg dose by 4.18 days per month compared to placebo. Both doses also reduced total alcohol consumption. Side effects were mostly mild to moderate, occurring in 87.9% (20 mg), 84.8% (10 mg), and 79.2% (placebo) of patients.

Can Acamprosate Cure Alcoholism?

No, acamprosate cannot cure alcoholism. According to Maisel, N. C.’s 2013 study, ‘Meta-analysis of naltrexone and acamprosate for treating alcohol use disorders: When are these medications most helpful?’, acamprosate is a medication that helps treat alcohol use disorders by modulating the glutamate system and “resetting” the balance between GABA and glutamate systems disrupted by alcohol, showing better efficacy for maintaining abstinence (especially when patients have been detoxified before treatment begins), but it is most effective as one component of treatment rather than a standalone cure for alcohol use disorders.

Can Acamprosate Help Prevent Alcohol Relapse?

Yes, Acamprosate helps prevent alcohol relapse by supporting abstinence and reducing cravings in individuals with alcohol use disorder. According to Venturella, F.’s 2014 study, ‘The control of abstinence in the treatment of alcohol dependence: the use of acamprosate in relapse prevention’., acamprosate reduces alcohol craving from medium-high levels in 68% of patients to low or none in 89% of patients after 3-4 months of treatment. The study examined 36 patients (25 men, 11 women) at two addiction centers. Biological markers improved significantly after 3-4 months. Acamprosate works alongside psychotherapy without causing addiction or interfering with other medications.

How Effective Is Acamprosate In Treating Alcohol Addiction?

Acamprosate is highly effective in treating alcohol addiction. According to Mann, K.’s 2004 study, ‘The efficacy of acamprosate in the maintenance of abstinence in alcohol-dependent individuals: results of a meta-analysis, ’ acamprosate improves abstinence rates in alcohol-dependent individuals. At 6 months, 36.1% of acamprosate patients maintain abstinence, compared to 23.4% of placebo patients. Acamprosate increases the likelihood of staying alcohol-free by 47%. The effectiveness of alcohol addiction treatment grows over time, with the advantage rising from 33% at 3 months to 95% at 12 months. The absolute success rate difference reaches 13.3% at one year.

Is Acamprosate A Controlled Substance?

No, Acamprosate is not a controlled substance. It is an FDA-approved prescription medication used to treat alcohol use disorder by helping maintain abstinence and reduce relapse risk, but it does not have abuse potential or dependence liability that would classify it as a controlled substance. 

According to FDA information, Acamprosate calcium (brand name CAMPRAL) is a prescription medication (Rx Only) used in the maintenance of alcohol abstinence. It is a synthetic compound with a chemical structure similar to the endogenous amino acid homotaurine and functions as a structural analogue of γ-aminobutyric acid and taurine. The drug contains acamprosate calcium 333 mg (equivalent to 300 mg of acamprosate) per tablet. While it requires a doctor’s prescription, Acamprosate does not carry the additional restrictions and regulatory controls that are imposed on controlled substances, which are categorized into different schedules under the Controlled Substances Act based on their potential for abuse and dependence.

Can You Take Acamprosate Without A Prescription?

No, you cannot take Acamprosate without a prescription. Acamprosate (also known by the brand name Campral) is a prescription medication approved by the FDA specifically for the treatment of alcohol dependence. It requires proper medical supervision due to potential side effects and the need for appropriate dosing.

How Does Acamprosate Differ From Other Alcohol Addiction Medications?

Acamprosate differs from other alcohol addiction medications in several key ways. Unlike naltrexone and nalmefene, which block opioid receptors to reduce alcohol’s rewarding effects, Acamprosate works by restoring balance to glutamate and GABA neurotransmission disrupted by chronic alcohol use. This unique mechanism helps reduce withdrawal symptoms and cravings. Acamprosate excels at maintaining abstinence after detoxification, while medications like naltrexone are better for preventing relapse during active drinking. With minimal liver metabolism, Acamprosate is safer for patients with liver impairment compared to alternatives.