Methadone and Buprenorphine Side Effects in Opioid Use Disorder Treatment

When someone is trying to recover from opioid addiction, medication can be a lifeline. Methadone and buprenorphine are two of the most trusted tools in this fight. They don’t just reduce cravings-they help people get back to work, reconnect with family, and stay alive. But they’re not without their downsides. The side effects can be heavy, confusing, and sometimes scary. Knowing what to expect isn’t about scaring people off-it’s about making sure they stay in treatment.

What Methadone Does to Your Body

Methadone is a full opioid agonist. That means it fully activates the same brain receptors as heroin or fentanyl, but without the high. It’s long-lasting, often working for 24 to 36 hours. That’s why people on methadone usually only need one dose a day. But that strength comes with risks.

Constipation is one of the most common complaints. Around 25 to 40% of people on methadone say they need laxatives just to go to the bathroom. It’s not just uncomfortable-it can lead to serious bowel issues if ignored. Nausea and vomiting affect up to one in three people, especially in the first few weeks. Sleepiness hits hard, too. Many users describe feeling "like a zombie," unable to focus at work or drive safely. One Reddit user wrote: "I stopped methadone because I couldn’t stay awake during my shift. I lost my job."

The biggest danger with methadone is its effect on the heart. It can stretch the QT interval on an EKG, which increases the risk of dangerous heart rhythms. At doses over 100mg a day, this happens in up to 35% of users. That’s why doctors recommend a baseline heart test before starting and regular checkups after. People with existing heart conditions or those taking other meds like antidepressants or antibiotics are at higher risk.

Sexual side effects are often left out of the conversation. About 30% of long-term methadone users report trouble getting or keeping an erection. Libido drops. For some, it’s a quiet, isolating burden that keeps them from talking to their doctor. And then there’s the risk of overdose-especially in the first weeks. Methadone builds up slowly in the body, so if someone takes too much too fast, they can stop breathing. That’s why methadone is only given in clinics at first, with daily supervision.

What Buprenorphine Does to Your Body

Buprenorphine is different. It’s a partial agonist. Think of it like turning a faucet halfway on instead of all the way. It reduces cravings and withdrawal, but it doesn’t produce the same intense high-or the same level of danger. That’s why it’s safer for home use and why it’s become the most prescribed medication for opioid addiction in the U.S.

The most common side effect? Mouth problems. Because it’s taken as a tablet or film that dissolves under the tongue, many people get numbness, tingling, or soreness in their mouth. Up to 35% report this. If you swallow it instead of letting it dissolve, you lose most of the dose. Some users say it tastes awful, like metal or plastic, and that makes sticking with it harder.

Headaches are another big one. Around 30 to 40% of buprenorphine users get them, sometimes daily. They’re usually mild, but they can be persistent enough to make people quit. Nausea still happens, but less than with methadone-closer to 20%. Constipation is also less common, affecting about 25% of users.

But here’s the catch: buprenorphine has a ceiling. After a certain dose-usually around 16 to 24mg-it stops working better. For someone with high opioid tolerance, especially after years of fentanyl use, that ceiling can feel like a wall. They might still feel cravings, still feel the urge to use. One user on Healthgrades wrote: "Suboxone helped me stop shooting up, but I still felt like I needed more. I ended up using on the side."

There’s also the risk of withdrawal if you take it too soon after using other opioids. If you’re still under the influence of heroin or oxycodone when you take buprenorphine, it can kick out those drugs from the receptors and trigger sudden, severe withdrawal. That’s called precipitated withdrawal. It happens in 15 to 25% of first-time users and can be so intense that people leave treatment before they even get started.

Which One Is Safer?

Safety isn’t just about overdose risk-it’s about what happens over time.

Methadone has a higher risk of fatal overdose, especially in the first month. Studies show it’s 2.5 times more likely than buprenorphine. But here’s the twist: people who stick with methadone are more likely to stay in treatment. One 2024 study found that 81.5% of methadone users were still in care after two years. For buprenorphine? Only about 11% stayed that long. That’s not because buprenorphine doesn’t work-it’s because many people feel it doesn’t work enough.

Buprenorphine is safer for the heart. It doesn’t stretch the QT interval the way methadone does. It’s also less likely to cause respiratory depression. That’s why it’s often recommended for people who live alone, have other health issues, or use alcohol or benzodiazepines. But if you’re someone who’s been using high doses of opioids for years, buprenorphine might not be strong enough.

And then there’s the mental side. Both meds can make it harder to focus. But studies show methadone users have worse memory and attention problems-especially when it comes to driving. One 2007 study found methadone users performed 25 to 30% worse on visual memory tests than buprenorphine users. That’s not just inconvenient-it’s dangerous.

What the Experts Say

There’s no one-size-fits-all answer. Dr. Nora Volkow from NIDA says methadone is more effective, but only if you can manage the risks. Dr. Keith Ahmad from Canada says buprenorphine should be first-line for most people because it’s safer and more accessible. Dr. John Renner from Boston says methadone is still the gold standard for people with severe, long-term addiction-especially those who’ve used fentanyl.

And the data backs them up. People with fentanyl use disorder are more likely to be put on methadone because it handles high tolerance better. Meanwhile, buprenorphine is more common for newer users, people with jobs, or those who need flexibility.

But access matters. Since 2023, any doctor can prescribe buprenorphine-no special waiver needed. That’s good. But a 2024 study found that 43% of primary care doctors don’t know how to start someone on it safely. That means people might get the wrong dose, or be put on it too soon, triggering withdrawal. Meanwhile, methadone clinics are still limited, especially in rural areas. You might need to drive hours for your daily dose.

What You Can Do About the Side Effects

Side effects don’t have to be permanent. Many fade after a few weeks as your body adjusts. But there are things you can do to make them easier.

• For constipation: Drink more water, eat fiber, move your body. If that doesn’t work, ask for a stool softener or laxative. Don’t suffer in silence.
• For drowsiness: Don’t drive or operate heavy machinery until you know how the med affects you. Most people find their energy returns after 4 to 6 weeks.
• For mouth issues (buprenorphine): Let the film or tablet dissolve completely. Don’t chew it. Don’t eat or drink for 15 minutes after. Rinse your mouth with water afterward.
• For headaches: Try over-the-counter pain relievers like acetaminophen. Avoid ibuprofen if you’re on methadone-it can affect liver enzymes.
• For heart concerns: If you’re on methadone and your dose is over 100mg, ask for an EKG. If you feel your heart racing, dizzy, or faint, get checked immediately.
• For sexual side effects: Talk to your provider. There are treatments. You’re not alone.

And never mix these meds with alcohol, benzodiazepines, sleep aids, or other opioids. That’s when overdoses happen. Even if you’ve been on one of these meds for months, adding another depressant can shut down your breathing.

What Comes Next?

New forms of buprenorphine are coming. There’s a monthly injection (Sublocade) and a six-month implant (Probuphine). They avoid mouth issues and daily dosing-but they can cause pain or swelling at the injection or implant site. About half of users report discomfort there.

Methadone is also being improved. New versions in clinical trials aim to reduce heart risks without losing effectiveness. And doctors are starting to use genetic tests to see how fast your body processes methadone. Some people break it down fast and need higher doses. Others break it down slow and get side effects even on low doses.

But the bottom line hasn’t changed: both methadone and buprenorphine save lives. The side effects are real-but so is the relief they bring. People on these meds are more likely to stay alive, hold a job, and rebuild relationships. The goal isn’t to be perfect. It’s to be stable.

If you’re struggling with side effects, talk to your provider. Don’t quit because it’s hard. Adjustments can be made. Doses can be changed. Support is there. You don’t have to suffer alone.

If you’re considering treatment, don’t let fear of side effects stop you. The goal isn’t to feel perfect-it’s to feel stable. And for millions of people, that’s exactly what these medications deliver.