The Naltrexone Comeback: Less Alcohol Drinking, Less Pain?

For decades, naltrexone was an obscure prescription medicine. Doctors prescribed it to help people overcome opioid dependence or reduce alcohol cravings. Most Americans had never heard of it. That is changing. The naltrexone comeback could have benefits for people suffering from chronic pain, long COVID, substance abuse and other compulsive behaviors.

A Short History of Naltrexone

The FDA first approved naltrexone in 1984 under the brand name Trexan. This drug was originally designed to help people better cope with a dependence on opioid drugs such as heroin. It works by blocking the effects of narcotics.

A decade later, the FDA approved naltrexone (ReVia) for treating alcohol dependence. In this case, the compound works to limit alcohol cravings because it interferes with opioid receptors in the brain. These provide a critical link between alcohol consumption and the buzz brought on by booze. By interrupting the opioid-related reward pathway in the brain, naltrexone disrupts the system that reinforces drinking.

My Interest in Drug Dependency

More than four decades since naltrexone was approved, scientists are beginning to get a handle on the roots of cravings. When I was a graduate student in pharmacology at the University of Michigan Medical School, there was a huge research program on drug dependency.

The Chairman of the Department was Dr. Maurice Seevers. He was a pioneer in the field of drug addiction. In the basement of our building was a colony of rhesus monkeys. I always felt bad for these primates because our program had enabled them to self-administer a number of highly addictive substances, from morphine and cocaine to alcohol and pentobarbital.

Attempts to Defeat Drug Dependency Have Been Disappointing

For a very long time, “experts” in drug dependency believed that they could help people overcome their cravings through “aversive conditioning.” That’s a fancy way of saying punishment and pain. As a grad student at U of M, I remember being taught about disulfiram (Antabuse).

When someone drinks alcohol (ethanol), the body converts it to acetaldehyde. It’s a very nasty chemical that causes flushing, nausea, vomiting, headaches, dizziness and cardiovascular complications. Normally, the body converts ethanol to acetic acid (vinegar) very quickly through an enzymatic pathway involving aldehyde dehydrogenase (ALDH).

OK, that’s enough pharmacology for one article. The point is that the drug disulfiram blocks the ALDH enzyme from eliminating acetaldehyde. The end result is that if someone has a drink or three of alcohol while disulfiram is on board, they get VERY sick VERY fast.

The trouble is that the drug never really helped that many people with an alcohol problem kick their cravings, even though they got super sick. I am not saying that Antabuse never worked. It’s just that the cravings continued, even if people became sick every time they snuck some alcohol.

Other approaches to opioid abuse involved providing the abused substance in a controlled manner. That led to drugs such as methadone and buprenorphine (Suboxone). Providing an opioid to control opioid use disorder has helped many people, but it certainly has not ended the “opioid epidemic.”

The Dynamic Duo That Creates Cravings

Naltrexone works differently. It is an opioid antagonist. It blocks opioid receptors in the brain. My favorite analogy is bubble gum stuffed into a lock.

Imagine for a moment thousands of tiny chemical locks in your brain and throughout your body (opioid receptors). There are opioid receptors in the digestive tract, on the skin, in muscles and joints, on white blood cells, in the spinal cord and brainstem as well as in the brain. When opioid “keys” (like heroin or oxycodone) get into the body, they fit into those opioid receptors. So do the body’s natural “keys” called endorphins.

The dynamic duo (think Batman and Robin) is endorphins and dopamine together. Endorphins fit into opioid receptors, block pain, provide pleasure and generally make people feel very good. When that happens, dopamine is released in the brain and says MORE!

The behavioral loop is completed. Whether it is drinking alcohol, injecting heroin or gambling, the endorphin/dopamine dynamic duo reinforces the behavior that leads to cravings and urges that in turn lead to repeated behaviors. It can turn into an endless negative loop.

The Naltrexone Comeback: Diminishing the Cravings

Now imagine tiny bits of bubble gum fitting into all those chemical receptors. Naltrexone is like bubble gum. It fits into opioid receptors and blocks the dynamic duo of the endorphin high and the dopamine reinforcement of MORE, PLEASE.

Dr. John Sinclair was a brilliant researcher. He discovered that a drink of alcohol strengthens certain synapses in the brain because of endorphin release. Naltrexone weakens those synapses. His claim to fame with regard to his under appreciated naltrexone protocol had to do with reducing the cravings!

A key study was published in the Journal of Clinical Psychopharmacology, June 2001. The research was conducted in Finland. Dr. Sinclair and his colleagues did not require people to stop drinking. In fact, their research was “the first controlled study to use naltrexone with patients addicted to alcohol who were currently drinking.” The bottom line seems to be that naltrexone, when taken an hour before drinking, may reduce cravings and help control alcohol abuse.

What about “casual drinkers”? Could Dr. Sinclair’s concept apply to other cravings as well?

Why Is Alcohol Suddenly Under Scrutiny?

For years, many Americans believed that moderate alcohol consumption might be good for the heart. A glass of red wine with dinner was often portrayed as a healthy habit.

A new analysis published in the Journal of Studies on Alcohol and Drugs (June 8, 2026) challenges that assumption. Researchers found no overall health benefit from alcohol consumption, even at relatively low levels.

The investigators estimated that men and women consuming more than about seven drinks a week face a lifetime risk of alcohol-attributable death greater than 1 in 1,000. At just over eight drinks weekly, the risk increased to more than 1 in 100.

Perhaps most surprising, the researchers calculated that men consuming 14 drinks a week—the upper limit in previous U.S. Dietary Guidelines—face roughly a 1-in-25 risk of an alcohol-related death over a lifetime.

The authors concluded that current drinking guidelines should be tightened and that both men and women should limit alcohol consumption to no more than one drink a day. That recommendation may be easier said than done.

Could the Naltrexone Comeback Help People Drink Less?

Remember that naltrexone “gums up” opioid receptors in the brain. That appears to diminish the dopamine reward impact of drinking alcohol. Such a pharmacological effect could reduce alcohol cravings and make drinking less appealing.

This possible mechanism could well encourage current drinkers to cut back. That is exactly where naltrexone comes in. People who find it hard to drink less may discover that taking naltrexone could help.

One reader described her experience with naltrexone:

“A year and a half ago I was drinking a bottle of wine a night (sometimes more). I could stop drinking for long periods of time, but I always wanted to drink. Eventually I would go back and start drinking the same amount as before.

“‘This Naked Mind’ by Annie Grace is a wonderful book and helped me a lot. However, I was still struggling. I heard about the Sinclair Method from Annie Grace and her YouTube channel, where she interviewed Claudia Christian. I then watched Claudia’s TED talk about naltrexone.

“I started taking naltrexone using the Sinclair Method. When I started tracking my drinks on an app, I was at 60 drinks a week. With the first pill, my drinking immediately dropped to 30 drinks per week and never got any higher.

“I followed the Sinclair Method completely for over a year and my drinking plummeted to less than 8 to 10 drinks per week. Now I have two glasses of wine a week when I go out to dinner. I don’t drink at home at all.

“The best part about this: in the past, I could stop drinking, but I hoped to stop wanting to drink. That is what naltrexone did for me. No craving, no obsessive thoughts, I don’t even think about alcohol anymore. I feel completely in control and I’m so thankful for this pill and the Sinclair Method.”

What Is the Sinclair Method?

The Sinclair Method (TSM) takes a different approach from traditional abstinence-based programs. Instead of taking naltrexone every day, patients take a dose about an hour before drinking alcohol.

The medication blocks much of alcohol’s rewarding effect. Over time, many people report that cravings diminish and drinking becomes easier for them to control.

Not everyone benefits. Naltrexone can cause side effects such as nausea, digestive upset, insomnia, drowsiness and, in rare cases, liver problems. Medical supervision is essential, but it will require a healthcare professional who is familiar with the Sinclair Method. TSM is far more popular and accepted in Europe than in the U.S.

Still, studies suggest that oral naltrexone can help many people reduce alcohol consumption, especially when combined with counseling or behavioral support.

Carl shares his naltrexone story:

“I am a 62-year-old male emergency room nurse with a history of drinking 6 to 8 alcoholic drinks a day for the past 30 years or so. My drinking is confined to the hours between 5 and 10 PM. My motivation for drinking is I like the “buzz.” I honestly don’t believe my alcohol use is a coping mechanism, as both my personal and professional life is very satisfying and successful.

“I do however have an addictive personality. (I was a 2 to 3 pack a day smoker until 20 years ago when I stopped cold turkey). I have no desire to stop drinking, but I realize that if I continue my present rate of consumption I will sooner or later suffer health problems. I just want to reduce my consumption to a reasonable level.

“I heard an interview with Dr. Eskapa on NPR and bought and read his book (The Cure for Alcoholism: Drink Your Way Sober Without Willpower, Abstinence or Discomfort). I started on naltrexone on January 5th.

“I could become the poster child for this drug. In the 3 weeks I have been taking it, I’ve had 1 to 3 drinks a day (usually 2), and have suffered absolutely no side effects. Indeed, the subtitle to the book (Without Willpower, Abstinence or Discomfort) has proved 100% true.

“I realize I am still very early in the game, but I am absolutely convinced that this is a life changer for me. I have spoken to a number of my friends and coworkers about naltrexone and am amazed at the interest they have shown, either for themselves or their loved ones.

“If the drug continues to be as successful as it appears to be over the next 3 to 4 months, I intend to very actively and publicly promote its use. I would very much like to learn of other people’s experience with naltrexone.”

Not everyone will solve an alcohol problem with naltrexone. Nevertheless, some people do discover that their cravings are diminished. We share Carl’s interest in hearing from others who have had experience with naltrexone, either positive or negative. Share your story in the comment section below.

The Naltrexone Comeback: Not Just for Opioids & Alcohol Anymore

What makes this story especially intriguing is that naltrexone’s resurgence is not limited to alcohol use disorder. Researchers are looking into the ability of naltrexone to help control dopamine surges that can create compulsive behaviors. Could this drug assist in managing trichotillomania (the urge to pull out hair), kleptomania, binge eating, pornography overuse, compulsive buying and uncontrollable gambling urges?

Much more research is necessary before we can say with any certainty that naltrexone would be helpful. Remember, the drug is available generically at a low cost. No pharmaceutical manufacturer is likely to spend the big bucks necessary to demonstrate efficacy.

What About Low-Dose Naltrexone (LDN) for Pain?

Researchers and patients have become increasingly interested in low-dose naltrexone, commonly called LDN.

Standard doses for treating alcohol use disorder are typically 50 milligrams. Low-dose naltrexone generally ranges from 1 to 4.5 milligrams—often less than one-tenth of the conventional dose.

At these tiny doses, scientists believe naltrexone may work very differently.

Rather than simply blocking opioid receptors, LDN appears to influence inflammation, immune signaling and the body’s production of natural endorphins. Although researchers are still debating exactly how it works, the growing interest has been remarkable.

Could Low-Dose Naltrexone Ease Chronic Pain?

People living with chronic pain often feel trapped. Opioids remain controversial. NSAIDs such as diclofenac, ibuprofen, meloxicam and naproxen can increase the risk of stomach bleeding, elevated blood pressure and cardiovascular complications. Drugs such as gabapentin and pregabalin can cause dizziness, fatigue and cognitive problems.

That helps explain why some patients are eager to try alternatives.

One reader with spinal stenosis and osteoarthritis told us:

“My first clue that low-dose naltrexone was helping came when I slept through the night for the first time in months. I thought my bladder was waking me up. It turned out that pain was the culprit.

“I used to limit yard work to two hours. Now I can work for five. I used to hesitate before bending over to pick something up. Now it’s routine.”

Another reader who cannot take anti-inflammatory drugs because of blood-thinner therapy reported:

“I didn’t realize how much low-dose naltrexone was helping until I forgot it on vacation. I couldn’t wait to get home and start taking it again.”

Why Aren’t More Doctors Prescribing LDN?

Many physicians never learned about low-dose naltrexone in medical school or residency training.

The FDA has not approved LDN for chronic pain, fibromyalgia, arthritis, long COVID or autoimmune disorders. Most studies have been relatively small.

There is another big challenge. Because naltrexone is an old generic medicine, no pharmaceutical company is likely to spend hundreds of millions of dollars conducting the large clinical trials needed for additional FDA approvals.

As a result, doctors face a difficult dilemma. Patients report meaningful benefits, but the evidence has not yet reached the level many clinicians would like to see.

Could Low-Dose Naltrexone Help Long COVID?

One reason for the growing interest in LDN is the lack of effective treatments for long COVID. Several small studies suggest that low-dose naltrexone may improve fatigue, pain and overall well-being in some people suffering from persistent symptoms after COVID infection.

Researchers emphasize that larger randomized clinical trials are needed. Nonetheless, patients and practitioners continue to explore whether this inexpensive medication might offer relief when other approaches have failed.

Why the Naltrexone Comeback Matters

Naltrexone has been available for over 40 years. It was originally developed to combat opioid dependence. Later, it received FDA-approved treatment for alcohol use disorder. Today, researchers are exploring whether tiny doses may help people with chronic pain, fibromyalgia, autoimmune disorders and long COVID.

Will naltrexone combat compulsive behaviors such as gambling or shopping? We don’t yet know. This drug won’t work for everyone. Some visitors to this website tell us it makes a difference for pain control. Others say it was not helpful. Until there is far more research into naltrexone, we won’t know the true benefits and risks of this drug to to treat compulsive behaviors or pain.

What we do know is that this old drug is attracting more attention today than it has in decades.

Have you tried naltrexone or low-dose naltrexone? We’d love to hear about your experience in the comment section below. We would also be grateful if you would share this overview with acquaintances. Do you know anyone with an alcohol problem? If so, they might appreciate this article. People with chronic pain may also benefit. Thank you for supporting our work.