Side Effects of Naltrexone: Why Are They Too Much for Some People?

Medically reviewed by John Mendelson, M.D. on March 10, 2021

Table of Contents

Naltrexone is an FDA-approved medication that has been repeatedly shown to significantly reduce drinking, and subscribers to the Sinclair Method swear by its effectiveness. But does it work for everyone? And when can the side effects of naltrexone, which are normally very mild, get to be too much for some people?

Below, Katie Lain sits down with Ria Health’s Chief Medical Officer, Dr. John Mendelson, to discuss frequently asked questions about the side effects of naltrexone. Watch the conversation below, or read a transcript of it, which has been lightly edited for clarity.

Read more about Naltrexone for Alcohol Use Disorder

Dr. John Mendelson Explains the Side Effects of Naltrexone

Katie Lain: Hi everybody—it’s Katie with Ria Health, and today I’m here with Dr. Mendelson, researcher and physician here at Ria Health. Dr. Mendelson and I were just chatting about the online Sinclair Method communities, where some people are sharing that perhaps they’re not getting the results they hoped for on the medication naltrexone. And I wanted to talk to Dr. Mendelson today about his perspective on what the medication naltrexone is, why some people don’t get the results that others do, and what can be done about it. So thank you for being here, Dr. Mendelson. I look forward to hearing what you have to say.

Dr. John Mendelson: It’s a pleasure being able to talk to people. I want to say, I’ve been reading many of the comments coming through the Sinclair Method Warriors group Facebook page. This is not directed to any one person’s comments. I’m not trying to give medical advice here, so I’m going to keep this very general. But some people struggle with naltrexone. The drug can be difficult for some patients. At Ria, about 10 percent of our patients just don’t tolerate it at all, and that’s due to side effects of naltrexone. And they don’t tolerate it at any dose. Even when we reduce it down to 12.5mg a day, they have intolerable side effects.

While naltrexone works for many people, not everyone is going to get a good response, and it’s not just because they didn’t give it a good effort. It’s because their biology is different. And for those individuals, we do have medications that are effective and safe and can work well. You’ll need to work with your physicians on that—a good, knowledgeable physician.

Related Post: Naltrexone Uses and Side Effects: Is it Right for You?

help with alcohol addiction ria health
Need Help or Have Questions?

Schedule a private call with a Ria Health team member and we can help you get started.

What causes someone to experience side effects on naltrexone? And why are they different between people?

That’s a really interesting question, and it’s because naltrexone is a really complicated drug. In addition to having effects at what are called “mu opiate receptors,” which are the ones that seem to mediate pain and pleasure, naltrexone can also have effects at “kappa opiate receptors,” which are ones that cause discomfort or displeasure.

In some people, naltrexone appears to be a kappa agonist—that means it increases the effects of kappa, which means that it has unpleasant effects. Many patients report, when they take naltrexone, that they feel some kind of strange intoxication. They feel weird. And some people say things like, “I felt high all day, I couldn’t sleep, and I had weird dreams.” Many of us think that’s due to the kappa agonist effects of naltrexone, which, although minimal, are ones that your body doesn’t usually see. If you’re a person who responds that way—you have a strong kappa response to naltrexone—you may never be able to get rid of those adverse side effects of naltrexone, and it won’t be a medication you can use.

At Ria, about 10 percent of our patients just don’t tolerate [naltrexone] at all, and that’s due to side effects.

So my big point here is, while naltrexone works for many people, not everyone is going to get a good response, and it’s not just because they didn’t give it a good effort. It’s because their biology is different. And for those individuals, we do have medications that are effective and safe and can work well. You’ll need to work with your physicians on that—a good, knowledgeable physician.

Download Our Naltrexone Guide

Learn more about Naltrexone by downloading our guide. Just enter your email address and we will send you a PDF file right to your inbox to download. 

Naltrexone e-book

What are some of the common side effects?

One set of adverse effects is that weirdness, that feeling weird, high, intoxicated. Another are the G.I. ones—gastrointestinal—where people have nausea, they have diarrhea, they’re queasy all the time. That is probably due to some of the mu effects, as well as the kappa effects of the drug. And it’s probably more a dose-dependent phenomenon. So if you’re have a lot of G.I. stuff, you may be able to affect that by either increasing or decreasing the dose and waiting. It turns out the amount of opiate receptors in your gut exceed the amount of opiate receptors in your brain.

Katie: Interesting.

John: In fact, opiate receptors were initially isolated from guinea pigs’ ileum, which is part of the small intestine. Because that’s where most of them are. And drugs that constipate you, if you have diarrhea—like Lomotil—those are all opiates. And in opiate withdrawal, one of the principal symptoms is vomiting and diarrhea, as well as abdominal pain and cramping.

Some of us are willing to tolerate some medication side effects if we’re getting better as a result. If we take an antihistamine because we have allergies, and it’s sedating, it beats the heck out of sneezing continuously, right?

There are also some gastrointestinal side effects of naltrexone. Most of them aren’t bothersome enough for people to stop medication. Some of us are willing to tolerate some medication side effects if we’re getting better as a result. For example, if we take an antihistamine because we have allergies, and it’s sedating, it beats the heck out of sneezing continuously, right? But on the other hand, if we don’t have any symptoms, and it makes us sedated, the medication’s doing no benefit. It’s only giving us problems.

So many people find when they cut their drinking down, some of the adverse effects of naltrexone begin to emerge for them. And that’s because they’re better!

So many people find when they cut their drinking down, some of the adverse effects of naltrexone begin to emerge for them. And that’s because they’re better! So maybe it’s a subtle message that they’re actually better and they don’t need the medication as much. But at any rate, the point is that you can have good effects of naltrexone that later turn into neutral-to-negative effects, because maybe you’re better. It could also be that the G.I. system is responding different than the brain—we really don’t have a good science handle on that. Also, naltrexone has other effects on other receptor systems that can vary between people. Therefore, naltrexone may not work for everyone.

Do naltrexone side effects go away?

Katie: What is the amount of time someone should really give to see if this medication is going to work for them? Because I know some people get side effects early on, and then they go away. I also see people in online forums who spend months and they’re still having severe side effects and they’re not seeing a reduction in drinking. So, in general, what are your thoughts and recommendations there?

For most people, side effects of naltrexone do go away with time as your body adjusts to the medication. Side effects are most apparent within the first 30 days of taking naltrexone.

John: For most people, side effects of naltrexone do go away with time as your body adjusts to the medication. Side effects are most apparent within the first 30 days of taking naltrexone. I think if you’re not seeing an effect at one month, and you’re still having severe side effects, it’s time to look at something else. You should see some sort of an effect within the first month and the side effects should start to dissipate by this time. If you’re still having side effects then it may be that you will be a part of the people who do not tolerate this medication. And don’t be worried because there are different medication options. The question always is, “What constitutes better? What is better? And do the benefits outweigh the challenges?”

What about increasing the dose of naltrexone?

The final point I’ll make on naltrexone: I see a lot of people talking about increasing doses. And I don’t think that’s particularly bad, but there is a risk of liver problems from naltrexone. And it’s a good idea, if you’re going to increase the dose, that you have a physician following you. I wouldn’t do this at home alone. At this point, you need professional help. Someone should be monitoring blood tests, or at least symptoms, to make sure that you’re not getting into any risks with naltrexone.

Doses below 100 mg appear to be very safe, other than these side effects we just talked about—the weird intoxication and the G.I. stuff. It’s pretty hard to hurt someone with naltrexone unless they’re opiate-dependent and having those side effects. But if you escalate doses, risks do increase, and you want to have a professional working with you at that point.

It’s a good idea, if you’re going to increase the dose, that you have a physician following you. I wouldn’t do this at home alone.


Do you want to regain control of your drinking? Ria Health uses medication-assisted treatment and 24/7 support to help its members drink less. Learn more about our program, or
get started today.

Written By:
Katie Lain Goyatton
Leading video blogger and advocate for medication-based treatment for alcohol use disorder.
Reviewed By:
Evan O'Donnell
NYC-based content strategist with over 3 years editing and writing in the recovery space. Strong believer in accessible, empathic, and fact-based communication.
Is My Drinking Normal?

Take our short alcohol quiz to learn where you fall on the drinking spectrum and if you might benefit from quitting or cutting back on alcohol.