Harm Reduction Medications for Alcohol Use Disorder

This essay is specifically on harm-reduction medications and so does not cover traditional drugs that support abstinence, such as disulfiram (Antabuse). Those unfamiliar with harm reduction in alcohol use disorders might want to read the first essay in this series, available here.

In addition to kratom, covered in this essay, several prescription drugs and one herb may help gradually reduce and even extinguish problematic drinking: baclofen, naltrexone, nalmefene, and topiramate, all more widely prescribed in Europe and Australia than in the US. In addition, anecdotal evidence suggests that a newly-popular weight-loss drug, semaglutide, reduces alcohol consumption in some users, though more rigorous research has barely begun. With baclofen, patients take increasing oral doses until their craving for alcohol disappears. With naltrexone or nalmefene, patients take an oral dose before drinking to diminish alcohol’s positive reinforcement, reducing or eliminating the desire to drink over time. With topiramate, patients take a daily oral dose to reduce consumption, the number of drinking days, and the amount consumed. With semaglutide, patients take a weekly dose by injection, which reduces the appeal of alcohol in some yet-to-be-determined way. Finally, with the herb kudzu and a kudzu-derived medication (puerarin), patients take an oral dose before drinking to reduce the amount consumed on that occasion.

What follows is an admittedly dry summary of current research on these medications. I’m not a physician, nor have I ever played one on TV, so I urge readers to do their own research by following the many links provided. And, for those currently struggling with serious alcohol issues, please bear in mind the following facts about medication-assisted treatment:

First, because human brains are different, the effectiveness of any medication targeting the human brain varies a lot from person to person. A drug that may be life-changing for one person may leave the next person with nothing but a headache and growing doubt in the efficacy of any medication for alcohol use disorders.

For that reason, if you have such a disorder, you may have to try more than one medication before you find a good fit. Sure, some of the description that follows might help you start in a productive place, but please, please don’t give up if your starting-place doesn’t turn out to be the medication you were hoping for. The next one could be.

Finally, it’s my experience—and the experience of the more intelligent drunks I’ve talked with—that there’s no magic bullet for alcohol use disorders, no pill or herb or therapeutic method that will, on its own, transform us into non-drinkers or “moderate” drinkers. That said, there are pills, herbs, and therapeutic methods that can help us transform ourselves if we’re willing to put in the time and effort of finding the ones that work for us.

Baclofen

Baclofen is a muscle relaxant that may target GABA-B deficiency and diminish self-medication with alcohol. The drug can be used to extinguish drinking entirely or reduce it to manageable levels. Recent research indicates that baclofen is more useful with heavier drinkers and is relatively safe for patients with liver disease. That said, baclofen remains a controversial drug, not least because its efficacy varies widely, as do its side effects.

Baclofen received a lot of attention following a French physician’s self-administration of the drug for his alcohol use disorder. See Olivier Ameisen’s 2008 book Heal Thyself (alternate titles The Last Glass, The End of My Addiction). A brief explanation of Ameisen’s method may also be found in his initial report.

The method involves administering higher and higher dosages of baclofen until alcohol craving disappears. The dosage at which craving disappears varies but averages slightly less than 150 mg/day. For extreme, treatment-resistant alcohol use disorder, much higher doses (over 300 mg/day) have been used with some success. Baclofen is not dangerous at high doses, but a recent study claims high doses are not well-tolerated because of side-effects.

A 2016 article in The Guardian describes Ameisen’s story and its influence, summarizing some of the work cited in this segment. It’s a good introduction, though a bit dated, lacking in references, and occasionally sensationalist. It does, however, indicate why high doses of baclofen should be taken under a physician’s care.

The French medical establishment has been most receptive to using baclofen for alcohol use disorders, and L’association Baclofène has a web site with a lot of information on the drug, most of it in French. It includes an excellent archive of papers in English, including a 2017 prescription guide for physicians and patients.

Baclofen Treatment for Alcoholism is a comprehensive English-language resource sponsored by an Australian physician Amanda Stafford. See especially “If baclofen is so great why isn’t everyone using it already?” (video and text) in which Dr. Stafford reviews the controversy over prescribing baclofen for alcohol use disorders.

American researchers and physicians have been much more timid in their approach to baclofen, partly because, according to Professor James Garbutt, Americans are historically reluctant to treat alcohol use disorders with any medication and partly because of some inconsistency in research findings, which he attributes to the fact that different people respond differently to the same drug. Garbutt more recently (2021) completed a study demonstrating the effectiveness of baclofen if variables such as gender and the severity of an alcohol use disorder are taken into consideration when prescribing. He further proposed devoting more research to other medications targeting the GABA-B receptor, in hope of discovering some that work better with fewer side-effects.

Naltrexone and Nalmefene

Naltrexone and nalmefene are opiate antagonists that block some of the pleasurable effects of drinking. They are used in different ways in different parts of the world.

Naltrexone is prescribed in the US to prevent relapse in abstinent alcoholics, even though it doesn’t actually do that for most patients. What it will do, if it’s taken every day, is help prevent a lapse from becoming a binge or a full relapse. That said, there’s a price to pay for continuously blocking endogenous opiates in newly abstinent patients, who are already hypoopioidergic (meaning low in endogenous opiates). In other (plainer) words, quitting drinking has already reduced your feel-good brain chemicals, so blocking the few you still have may not be a very good idea.

In Europe, however, naltrexone (and nalmefene) are prescribed to reduce or extinguish drinking, which is harm reduction, and studies show a 78 to 80 percent success rate for the European method, sometimes called “The Sinclair Method” after its originator, Dr. David Sinclair. Sinclair or European Method patients take a dose of naltrexone or nalmefene about an hour before they plan to drink.

In an excellent 2015 article, an American reporter describes the Sinclair or European use of naltrexone (and tries it out on herself). The article is about more than the drug, however, so, if you’re in a hurry, you can skip to the section that begins, “For a glimpse of how treatment works elsewhere, I traveled to Finland.” When it comes to research, this classic study demonstrates that naltrexone does not support abstinence (American method) but does help reduce or attenuate drinking (Sinclair/European method).

If you prefer video, Amazon Prime is showing “One Little Pill,” a 2014 film about using naltrexone to extinguish problem drinking.

Those interested in trying the Sinclair Method can easily find a specialized provider (Google the term, as every link I’ve posted has expired within a few months). Alternatively, a personal physician who is current on addiction medicine (or willing to read a recent research paper) could simply prescribe naltrexone for you and monitor your health as you use it.

Nalmefene, a newer drug, binds to more receptors, which may make it a better choice for those with access to it. This study shows a decided advantage. At the same time, discussions in online forums suggest that nalmefene may have more dramatic side effects. And it may not be available in your part of the world. For a good overall picture of the drug’s efficacy, look here.

Topiramate

Originally developed to treat epilepsy and migraines, topiramate is an anticonvulsant that may reduce problem drinking in patients, especially those with the CC genotype of the GRIK1 polymorphism (about 40 percent of European-Americans). Most of the research on topiramate is a decade or more old, but this 2014 study found that a 200 mg daily dose reduced heavy drinking in people with AUDs, and  this 2015 review article found the medication to be safe and well-tolerated, as well as particularly effective in compulsive and obsessive drinkers.

Semaglutide

A medication that has been all over the news lately, semaglutide has been approved for the treatment of obesity and type-two diabetes but is increasingly prescribed off-label for people seeking to lose small amounts of weight. Driven by social media, semaglutide (and other GLP-1 agonists) have become wildly popular despite high prices when used off-label, and it’s this popularity that has revealed the drug’s effect on alcohol consumption, as some users report losing interest in drinking while taking the drug. Interestingly, the one existing clinical trial, which tested the drug exenatide, found that this loss of interest in alcohol was not universal but specific to one group of subjects: people with obesity (BMI >30), who showed significant reductions in heavy drinking days and in overall alcohol consumption. Such results, plus online reports from semaglutide-users susprised fo find themselves drinking less, have led some physicians to begin prescribing semaglutide and similar medications for alcohol use disorders.

Kudzu Extract (including puerarin, one of kudzu’s isoflavones)

Kudzu is used in Chinese traditional medicine for alcohol-related problems. New research finds that Kudzu Extract reduces alcohol consumption (though not cravings) among men and women who drink heavily. It may work by speeding up the entry of alcohol into the central nervous system and thus slowing down subsequent drinking. It also seems mildly protective of a heavy drinker’s liver.

Most of the academic research originates from one laboratory, but it’s a good one, and the lead researchers have prestigious academic appointments. They also have data from human subjects. In this preliminary study, subjects received 1200 mg of puerarin (the primary isoflavone in Kudzu) prior to an afternoon drinking session and consumed less than with placebo. A second, longer study gave male alcohol dependents kudzu extract every day and tracked them for four weeks, registering a weekly decrease in alcohol consumption of 34 to 57 percent. A third study found that a single dose of kudzu extract reduced consumption from an average of 3.4 beers in a 90-minute drinking session to 1.9 beers.

A fourth study is underway at the University of California, San Francisco and is seeking healthy hazardous drinkers between the ages of 18 and 70, specifically volunteers who have engaged in binge drinking followed by sexual activity. More information here for those interested.

Conclusion

In researching these drugs, you’ll encounter a lot of glowing testimonials from people the drugs have helped (along with scathing criticism from abstinence-only traditionalists). It’s important to remember that, while all the drugs and herbs I’ve mentioned help some people, none helps everybody. This variability can make prospects of medication-assisted recovery appear dim, when, in fact, they are brightening for those willing to do some research and try multiple approaches. Do not be discouraged by studies such as this meta-analysis, which found “no high grade evidence for pharmacological treatment to control drinking using nalmefene, naltrexone, . . . baclofen, or topiramate.” That conclusion sounds depressing, but what it actually means is that no single medication works well for a majority of people struggling with an alcohol use disorder. Some work for some people, and others work for other people, which means only that you may have to experiment a bit to find the one that helps you.