When someone is fighting opioid use disorder, medications like methadone and buprenorphine can be life-changing. They don’t just reduce cravings-they help people rebuild their lives. But no medication comes without trade-offs. The side effects of methadone and buprenorphine are real, sometimes intense, and often misunderstood. If you’re considering treatment or already on one of these drugs, knowing what to expect isn’t just helpful-it’s critical for staying safe and sticking with treatment.
How Methadone and Buprenorphine Work Differently
Methadone and buprenorphine both target the same brain receptors as opioids like heroin or fentanyl, but they do it in opposite ways. Methadone is a full agonist. That means it fully activates the opioid receptors, giving strong, steady relief from withdrawal and cravings. It’s been used since the 1940s and works best for people with long-term, high-severity addiction, especially those using fentanyl.
Buprenorphine, on the other hand, is a partial agonist. It activates the receptors just enough to ease withdrawal and cravings but doesn’t produce the same intense high. It also has a built-in safety feature called a ceiling effect: after a certain dose (usually around 24 mg), increasing the amount doesn’t increase the effect-especially when it comes to breathing. This makes overdose much less likely compared to methadone.
Because of this, methadone is usually given in specialized clinics where you have to show up daily for supervised doses. Buprenorphine, especially in the form of Suboxone (which combines buprenorphine with naloxone), can be prescribed by doctors in regular offices. That makes it easier to access, but not always easier to manage.
Common Side Effects: What You’ll Likely Experience
Both medications cause similar side effects, especially in the first few weeks. Most of these fade as your body adjusts, but some stick around.
- Lightheadedness and dizziness: Happens in about 1 in 5 people. Standing up too fast can make it worse.
- Sleepiness or fatigue: Around 1 in 4 users feel unusually tired. This can affect driving, work, or school.
- Nausea and vomiting: Up to 1 in 3 people feel sick to their stomach, especially when starting treatment.
- Sweating: More than 1 in 10 people report excessive sweating, even when it’s not hot.
- Constipation: This is one of the most persistent problems. Nearly 3 in 10 people need laxatives or stool softeners daily.
These aren’t rare side effects-they’re normal. Many people stop treatment because they think these symptoms mean the drug isn’t working, when in fact, they’re just signs their body is adapting.
Methadone’s Unique Risks
Methadone’s strength is also its danger. Because it fully activates opioid receptors, it carries risks buprenorphine doesn’t.
- Heart rhythm problems: Methadone can prolong the QTc interval on an EKG, which increases the risk of dangerous heart arrhythmias. At doses over 100 mg per day, this affects up to 1 in 3 people. A baseline EKG is recommended before starting, and follow-ups are needed if the dose goes up.
- Respiratory depression: While rare at stable doses, methadone can slow breathing enough to be life-threatening-especially if mixed with alcohol, benzodiazepines, or sleep aids. The risk is highest during the first two weeks of treatment.
- Sexual dysfunction: About 3 in 10 long-term methadone users report reduced libido, erectile dysfunction, or menstrual irregularities. This isn’t talked about enough, but it’s common and can strain relationships.
- Seizures: Though rare (1-3% of users), methadone lowers the seizure threshold, especially in people with a history of head injury or epilepsy.
One Reddit user wrote: “I felt like a zombie. I could barely stay awake at work. My boss thought I was slacking, but I couldn’t even focus on my coffee.” That’s not weakness-it’s methadone’s effect on the central nervous system.
Buprenorphine’s Hidden Challenges
Buprenorphine is safer, but it’s not without its own problems.
- Headaches: Nearly 4 in 10 users get them. Sometimes they’re mild, sometimes they’re debilitating.
- Mouth issues: Suboxone dissolves under the tongue. If not placed correctly, it can cause numbness, burning, or pain in the mouth. Up to 1 in 3 people report this. Swallowing it instead of letting it dissolve cuts absorption by up to 60%.
- Inadequate symptom control: Because of the ceiling effect, people with very high opioid tolerance may not get enough relief from buprenorphine-even at the maximum dose. This can lead to breakthrough cravings and, in some cases, relapse.
- Precipitated withdrawal: If you take buprenorphine too soon after using another opioid, it can kick out the other drugs from the receptors and cause sudden, severe withdrawal. That’s why you need to wait 12-24 hours after your last opioid use before starting.
One patient on Healthgrades said: “Suboxone helped me stop using heroin, but I still had cravings. I’d sit in my car for 20 minutes trying to decide whether to use again.” That’s the ceiling effect in action.
Which One Has Better Outcomes?
It’s not just about side effects-it’s about what works long-term.
Studies show methadone keeps more people in treatment. One 2024 study found that 81.5% of methadone patients stayed in care after two years. For buprenorphine, nearly 9 out of 10 people left treatment within that time. Why? Because methadone’s longer half-life (8-59 hours) gives steadier relief. Buprenorphine wears off faster, which can lead to more cravings and more temptation to use.
But methadone is also more dangerous. In the first four weeks of treatment, the risk of fatal overdose is 2.5 times higher with methadone than with buprenorphine. That’s why clinics monitor doses so closely.
For people with severe addiction, especially those using fentanyl, methadone often works better. For people with less history of opioid use, or those who can’t visit a clinic daily, buprenorphine is the safer, more practical choice.
Real People, Real Experiences
Survey data from over 2,000 patients tells a clear story:
- On methadone: 55% said they felt too drowsy to work. 68% needed daily laxatives for constipation. 38% reported sexual problems.
- On buprenorphine: 73% said the dose didn’t fully control their cravings. 52% had mouth pain or numbness. Only 28% felt constantly tired.
There’s no perfect drug. Methadone gives you stability at the cost of energy and comfort. Buprenorphine gives you freedom and fewer sedating effects-but not always enough relief.
What You Can Do to Manage Side Effects
Side effects don’t have to be a reason to quit.
For constipation: Drink more water, eat fiber-rich foods (oats, beans, vegetables), and use stool softeners like docusate. Avoid stimulant laxatives long-term-they can damage your colon.
For drowsiness: Don’t drive or operate heavy machinery until you know how the drug affects you. Try taking your dose at night if your clinic allows it.
For mouth issues with buprenorphine: Place the tablet under your tongue and let it dissolve completely. Don’t chew, swallow, or talk while it’s dissolving. Rinse your mouth with water afterward to reduce irritation.
For heart risks with methadone: Get an EKG before starting and again if your dose increases past 100 mg/day. Tell your doctor if you feel palpitations, fainting, or shortness of breath.
For cravings: If buprenorphine isn’t working well enough, talk to your provider about switching to methadone-or adding counseling. Medication alone isn’t enough. Therapy, peer support, and structure make a huge difference.
What’s New in Treatment
There are new options that might change the game.
Sublocade is a monthly buprenorphine injection. It eliminates daily mouth issues and dosing errors. But 40-50% of users get pain or swelling at the injection site.
Probuphine is a six-month implant under the skin. It’s great for people who forget to take pills-but it’s harder to remove if side effects become too much.
Researchers are also testing new methadone formulas that don’t affect the heart as much. Early results are promising.
And in 2024, the government started pushing for naloxone to be given with every prescription for methadone or buprenorphine. That’s a big step. If someone accidentally overdoses, naloxone can reverse it.
Final Thoughts: It’s Not About Choosing the ‘Best’ Drug
There’s no single best medication for opioid use disorder. The right one depends on your history, your lifestyle, your tolerance, and your goals.
If you’re new to treatment and want to avoid daily clinic visits, buprenorphine might be your best start. If you’ve tried everything and still crave opioids, methadone might be the only thing that gives you real relief.
Side effects aren’t a sign you’re failing. They’re a sign your body is adjusting. Talk to your provider. Don’t quit because of nausea or a headache. But also don’t ignore chest pain or fainting. Know the warning signs. And remember: the goal isn’t to feel perfect. It’s to stay alive, stay in control, and get your life back.
Written by Connor Back
View all posts by: Connor Back