Contrave and Morphine Drug Interactions: What to Know

Understanding the potential Contrave and morphine drug interactions is crucial for individuals managing weight loss while requiring pain management. Contrave is a prescription medication combining naltrexone and bupropion, approved for chronic weight management in certain adults with an initial body mass index (BMI) of 30 kg/m² or greater or 27 kg/m² with at least one weight-related comorbidity. Morphine is a potent opioid analgesic used to treat severe pain.

Combining these medications can lead to significant drug interactions, primarily due to naltrexone’s role as an opioid antagonist, which can precipitate opioid withdrawal and affect pain management efficacy.​

Dr. Matthew Olesiak, Chief Medical Director at SANE MD, emphasizes, “​Patients must inform their healthcare providers about all medications they are taking, including over-the-counter drugs and supplements, to prevent adverse interactions between Contrave and opioid medications like morphine.”​

Key Takeaways

• Naltrexone, a component of Contrave, can block the effects of opioids like morphine, potentially leading to opioid withdrawal symptoms.
• Both naltrexone and bupropion can influence blood pressure, necessitating careful monitoring when combined with other medications affecting cardiovascular health.

Comprehensive communication with a healthcare provider is essential to manage potential interactions and ensure safe medication use.

Medication Guide

Before starting Contrave treatment, patients should carefully review the medication guide provided by their healthcare provider or pharmacist. The medication guide contains important details about how to take Contrave, potential drug interactions, and possible adverse reactions.

It is essential to follow the guidelines outlined in the medication guide to avoid serious complications, such as opioid withdrawal, high blood pressure, or serotonin syndrome. If there are any concerns or questions about the medication guide, patients should consult their healthcare provider for clarification.

Contrave and Morphine Drug Interaction Table

Interaction	Effect	Recommendation
Opioid Withdrawal	Naltrexone in Contrave blocks opioid receptors, leading to withdrawal symptoms if opioids like morphine are used.	Avoid opioid use while taking Contrave. Detox from opioids for at least 7-10 days before starting Contrave.
Reduced Pain Management	Naltrexone blocks the pain-relieving effects of morphine, making it ineffective.	Use non-opioid alternatives such as acetaminophen or NSAIDs for pain relief.
Blood Pressure Variations	Bupropion in Contrave can increase blood pressure, while morphine may lower it, causing unpredictable fluctuations.	Monitor blood pressure regularly and consult a healthcare provider if fluctuations occur.
Increased Seizure Risk	Bupropion lowers seizure threshold, and opioid withdrawal may increase seizure risk.	Avoid alcohol, sudden discontinuation of Contrave, and other seizure-inducing medications.
Liver Health Concerns	Both Contrave and morphine are metabolized in the liver, potentially increasing toxicity risk in individuals with liver disease.	Regular liver function tests are recommended for patients with liver conditions. Avoid high-fat meals while on Contrave.
Medication Alternatives	Morphine is ineffective while taking Contrave due to naltrexone’s opioid blockade.	Consider non-opioid pain relief options such as NSAIDs, acetaminophen, or nerve pain medications like gabapentin.
Emergency Pain Management	Contrave blocks opioid efficacy, making emergency pain relief difficult.	Inform healthcare providers about Contrave use before surgeries or procedures requiring opioids. Temporary discontinuation of Contrave may be necessary.

What Is Contrave?

Contrave is a prescription medication approved for chronic weight management in adults with an initial body mass index (BMI) of 30 or higher, or 27 or higher with weight-related conditions such as high blood pressure or type 2 diabetes. It combines naltrexone and bupropion, two drugs that work together to help compatible patients lose weight when used alongside a reduced-calorie diet and physical activity.

• Naltrexone is an opioid antagonist primarily used to treat alcohol and opioid dependence. In Contrave, it plays a role in reducing food cravings.
• Bupropion is an antidepressant that helps regulate appetite and energy balance. It is also used to treat depression and aid in smoking cessation.

Taking Contrave requires medical supervision, especially for individuals with high blood pressure, mental illness, or a history of eating disorders such as anorexia nervosa.

The medication is available in the form of extended-release tablets. It is important to avoid using it if you have taken monoamine oxidase inhibitors (MAO inhibitors) within the last two weeks.

What Is Morphine?

Morphine is a powerful opioid medication prescribed to treat pain, particularly severe pain that does not respond to other pain relievers. It works by binding to opioid receptors in the brain and spinal cord, reducing the perception of pain.

Morphine is available in various forms, including extended-release and immediate-release tablets, as well as injectable and liquid formulations. While effective for pain management, morphine use carries risks, including dependence, tolerance, and opioid withdrawal symptoms if suddenly discontinued.

Patients with liver disease, renal impairment, or head injury should use morphine with caution. Additionally, combining morphine with other central nervous system depressants, including alcohol, can lead to trouble breathing and life-threatening complications. Individuals using morphine should follow their healthcare provider’s guidance to minimize the risk of serious injury or overdose.

How Contrave and Morphine Affect the Body

Contrave is used for chronic weight management in certain individuals with an initial body mass index (BMI) above a certain threshold. It combines naltrexone and bupropion, where naltrexone is an opioid antagonist, and bupropion is an antidepressant that may treat depression and help with weight loss. Morphine, on the other hand, is a severe pain reliever belonging to the opioid medications class.

When taking Contrave, patients should avoid opioids, including morphine, as naltrexone can block their effects, rendering them ineffective and leading to opioid withdrawal. Additionally, both medications can elevate blood pressure, increasing the increased risk of chest pain and cardiovascular morbidity.

Mechanism of Action: Contrave and Morphine

Contrave combines two active ingredients:

1. Naltrexone: An opioid antagonist that blocks opioid receptors, reducing the rewarding effects of alcohol and opioids.
2. Bupropion: An aminoketone antidepressant that inhibits the reuptake of norepinephrine and dopamine, neurotransmitters involved in regulating mood and appetite.

Together, these components target central nervous system pathways to aid in weight management.​

Morphine is an opioid analgesic that binds to opioid receptors in the brain and spinal cord to alleviate pain. However, when naltrexone is present, it can block these receptors, rendering morphine less effective or ineffective. This antagonistic action can precipitate opioid withdrawal symptoms in individuals dependent on opioids.​

Potential Risks of Combining Contrave and Morphine

1. Opioid Withdrawal

Administering naltrexone to individuals dependent on opioids like morphine can induce acute withdrawal symptoms, which may be severe and require immediate medical attention. Because naltrexone is an opioid antagonist, it rapidly displaces opioids from their receptors, leading to sudden and intense withdrawal effects.

Symptoms may include severe nausea, vomiting, sweating, tremors, rapid heartbeat, high blood pressure, agitation, confusion, and intense cravings. In extreme cases, withdrawal can lead to dehydration, cardiovascular instability, or seizures, requiring hospitalization.

Individuals who have been on long-term opioid therapy should not take Contrave unless they have fully detoxed from opioids for at least 7-10 days, as recommended by the FDA. Even in patients who are not opioid-dependent, taking Contrave after recent opioid use (such as post-surgical morphine administration) can trigger partial withdrawal symptoms, leading to discomfort and distress.

2. Altered Pain Management

Because naltrexone blocks opioid receptors, it can significantly reduce the analgesic effects of morphine and other opioid medications. This poses a serious challenge for individuals managing chronic pain, post-surgical recovery, or acute injuries requiring opioid analgesia. If a patient taking Contrave needs pain relief, alternative non-opioid pain management strategies, such as acetaminophen, NSAIDs (like ibuprofen or naproxen), or nerve pain medications (such as gabapentin), should be considered.

However, naltrexone’s effects on opioid receptors can last for up to 24 hours, meaning that even if opioid medications are later introduced, they may not work effectively until naltrexone has cleared the body. For individuals needing emergency or post-surgical opioid pain management, tell your doctor about taking Contrave in advance so proper pain relief strategies can be planned.

3. Blood Pressure Variations

Bupropion, one of the active ingredients in Contrave, is known to increase blood pressure and heart rate, potentially leading to high or severely high blood pressure in susceptible individuals (FDA).

Since morphine can sometimes cause low blood pressure, the combination of these two drugs may create unpredictable blood pressure fluctuations, putting additional strain on the cardiovascular system.

Patients with pre-existing hypertension, cardiovascular disease, or a history of stroke are at increased risk of complications. Tell your doctor before taking Contrave if you have high blood pressure or any other cardiovascular morbidity to ensure appropriate monitoring.

Blood pressure should be regularly checked while on Contrave treatment, and adjustments to medication or lifestyle factors (such as a reduced calorie diet and physical activity) may be required.

4. Seizure Risk

Bupropion is known to lower the seizure threshold, meaning that individuals taking Contrave are at an increased risk of seizures, particularly if they have predisposing conditions such as a history of seizures, head injury, or eating disorders like anorexia nervosa or bulimia nervosa. (NIH).

Additionally, opioid withdrawal itself can induce seizures, particularly if withdrawal symptoms are severe and include rapid changes in blood pressure, dehydration, or extreme agitation. If Contrave is taken by someone who is physically dependent on morphine, the risk of seizure activity may be even higher due to a combination of withdrawal effects and bupropion’s pro-seizure potential.

To minimize risk:

• Do not suddenly stop drinking alcohol while taking Contrave, as alcohol withdrawal can also increase seizure risk.
• Avoid other medications that lower the seizure threshold, such as certain antidepressants, tramadol, or high doses of stimulants.
• Tell your doctor if you have a history of head injury, seizure disorder, or eating disorders before taking Contrave.

5. Liver Health Considerations

Both naltrexone and bupropion undergo hepatic metabolism, meaning that liver disease can impact how these drugs are processed, potentially leading to systemic exposure and increased risk of toxicity. (NCBI).

Individuals with moderate to severe liver disease should avoid Contrave treatment, as impaired liver function may cause the medication to accumulate in the body, leading to higher-than-intended doses and increased side effects.

Additionally, morphine is metabolized primarily in the liver and kidneys, meaning that individuals with liver disease or renal impairment may experience longer drug half-life and stronger effects, including an increased risk of respiratory depression and serious injury due to prolonged sedation.

To ensure safety:

• Tell your doctor if you have liver disease before taking Contrave.
• Monitor liver enzymes regularly if prescribed Contrave treatment while having a history of liver conditions.
• Avoid high-fat meals, which may increase bupropion’s systemic exposure, leading to enhanced drug effects.
• Use alternative pain management methods if opioid medications are necessary.

Safety Recommendations

1. Comprehensive Medication Review

Before starting Contrave treatment, it is essential to provide a complete list of all medications—including prescription drugs, over-the-counter medications, herbal preparations, and dietary supplements—to your healthcare provider. This step ensures that potential drug interactions can be identified early, reducing the increased risk of complications such as opioid withdrawal, high blood pressure, and serious allergic reaction.

For example, individuals who are already taking opioid medications for severe pain may face serious issues if they start taking Contrave, as naltrexone will block opioid effects and could lead to withdrawal symptoms. Additionally, certain other medications, such as monoamine oxidase inhibitors (MAO inhibitors) used for depression or mental illness, can dangerously interact with naltrexone and bupropion, leading to conditions like serotonin syndrome or severely high blood pressure. (FDA)

To ensure safety, individuals should tell their doctor if they are taking:

• Opioid medications, including morphine, oxycodone, fentanyl, or tramadol
• Antidepressants like Lexapro, or mood stabilizers, particularly MAO inhibitors
• Medications like propranolol  for high blood pressure or cardiovascular conditions
• Other weight loss medications or stimulants
• Drugs for mental health conditions, including treatments for bipolar disorder
• Over-the-counter drugs such as NSAIDs, cough suppressants, and decongestants
• Herbal preparations that could interfere with liver metabolism

2. Avoidance of Opioid Use

Because Contrave contains naltrexone, an opioid antagonist, it completely blocks the effects of opioids. Patients undergoing Contrave treatment should avoid using opioid-containing medications to prevent opioid withdrawal and ensure that the weight loss regimen is effective.

Even if a person is not currently dependent on opioids, using morphine or other opioid pain relievers while taking Contrave may still lead to unexpected complications. In emergency situations where opioid pain relief is necessary (such as following dental surgery or a serious injury), the healthcare provider may need to adjust the treatment plan by either:

• Temporarily stopping Contrave before opioid administration
• Using non-opioid pain relief alternatives, such as acetaminophen or NSAIDs
• Monitoring patients closely for signs of opioid withdrawal or pain management failure

Patients considering Contrave treatment should ensure they have been opioid-free for at least 7–10 days before starting the medication. (NIH) If there is uncertainty about past opioid use, a urine drug test may be performed before prescribing Contrave.

3. Regular Monitoring

Due to the potential side effects of naltrexone and bupropion, regular monitoring by a healthcare provider is essential while taking Contrave.

Key aspects of monitoring include:

• Blood Pressure Checks – Bupropion can increase blood pressure, so individuals with high blood pressure or cardiovascular morbidity should have regular readings taken. In some cases, additional medication adjustments or lifestyle modifications may be needed to prevent complications.
• Mood and Mental Health Assessments – Taking Contrave can lead to suicidal thoughts, false beliefs, or worsening mental illness, particularly in individuals with bipolar disorder or depression. Any signs of hallucinations, agitation, or mood instability should be reported to a healthcare provider immediately.
• Metabolic and Liver Function Tests – Because Contrave treatment affects liver disease and metabolism, routine liver enzyme tests may be required, particularly in individuals with a history of hepatic impairment or those who drink alcohol regularly.
• Weight Loss Progress—Patients using Contrave for chronic weight management should track their weight changes, ensuring that the medication is effectively helping them lose weight in combination with a reduced-calorie diet and physical activity.

Dr. Matthew Olesiak states, “Ongoing monitoring while taking Contrave ensures that potential risks—such as changes in blood pressure, mental health, or liver function—are managed before they escalate into serious complications.”

4. Patient Education

Patients should be fully informed about the potential risks and side effects of Contrave treatment, including:

• Recognizing signs of opioid withdrawal – Symptoms such as trouble breathing, eye pain, chest pain, or severe nausea could indicate withdrawal triggered by naltrexone. (FDA)
• Understanding the risks of low blood sugar—Contrave can contribute to low blood sugar, particularly in individuals with diabetes or those using other weight loss medications. Symptoms such as dizziness, confusion, or unusual sweating should be reported immediately.
• Identifying early signs of serotonin syndrome – A potentially life-threatening condition that can occur when bupropion interacts with certain other drugs (such as antidepressants or migraine medications). Symptoms include rapid heart rate, agitation, muscle stiffness, and high fever.
• Monitoring for allergic reactions—Some individuals may experience a serious allergic reaction while taking Contrave, such as rash, swelling, difficulty breathing, or anaphylaxis. If this occurs, seek immediate medical attention.

Patients should also be advised never to suddenly stop drinking alcohol while taking Contrave, as alcohol withdrawal combined with bupropion could increase the risk of seizures or severe mood changes. (NIH)

By staying informed and communicating regularly with their healthcare provider, patients can ensure that their Contrave treatment remains safe and effective.

Frequently Asked Questions (FAQ) About Contrave and Morphine

Understanding the potential interactions between Contrave and morphine is crucial for those using these medications. Since Contrave contains naltrexone and bupropion, it can significantly impact the effects of opioid medications like morphine.

Below are answers to common questions regarding the safety, risks, and recommended alternatives when taking these drugs together.

1. What medications should not be taken with Contrave?

Several medications should not be taken with Contrave, as they can lead to serious interactions or health risks. Opioid medications (such as morphine, oxycodone, and fentanyl) should be avoided because naltrexone blocks opioid receptors, potentially triggering opioid withdrawal. Monoamine oxidase inhibitors (MAO inhibitors), used to treat depression and mental illness, should not be combined with Contrave, as this could cause severely high blood pressure or serotonin syndrome.

Additionally, medications that lower the seizure threshold, such as other antidepressants, tramadol, or stimulant drugs, should be used with caution due to the risk of seizures. Check out our guide to see how Contrave interacts with other drugs.

Always tell your doctor about all prescription drugs, over-the-counter medications, and supplements before taking Contrave to prevent dangerous interactions. (FDA)

2. Can you take morphine while taking naltrexone?

No, morphine should not be taken while using naltrexone, as naltrexone is an opioid antagonist that blocks opioid receptors. This means morphine will not work to relieve pain, making it ineffective for treating moderate to severe pain.

Additionally, if a person is dependent on opioids, naltrexone can trigger sudden and severe opioid withdrawal, leading to symptoms such as nausea, vomiting, sweating, tremors, rapid heart rate, high blood pressure, and intense cravings.

Patients requiring opioid medications for pain relief should wait at least 7-10 days after stopping opioids before beginning naltrexone-based treatments like Contrave. (NIH)

3. What painkillers can I take with Contrave?

Since Contrave contains naltrexone, which blocks opioids, opioid-based painkillers (e.g., morphine, oxycodone, hydrocodone, and codeine) should be avoided. However, non-opioid pain relievers such as acetaminophen (Tylenol), ibuprofen (Advil, Motrin), and naproxen (Aleve) are generally safe alternatives for pain management while taking Contrave.

Some prescription nerve pain medications, such as gabapentin or pregabalin, may also be options for patients needing chronic pain relief. Before taking any pain relievers, consult your healthcare provider to ensure there are no additional risks based on your medical history.

4. What drugs cannot be taken with morphine?

Morphine should not be combined with medications that depress the central nervous system (CNS) or affect opioid metabolism.

Drugs to avoid include:

• Other opioid medications (e.g., oxycodone, codeine, fentanyl) due to overdose risk.
• Benzodiazepines (e.g., Xanax, Valium) and muscle relaxants, as they increase the risk of trouble breathing and life-threatening respiratory depression.
• MAO inhibitors, which can cause severe high blood pressure and dangerous CNS interactions.
• Certain antidepressants, which can increase the risk of serotonin syndrome.
• Alcohol, as it enhances sedation and may cause serious injury or death due to respiratory depression.

Always tell your doctor about all other medications before using morphine, as drug interactions can have severe and life-threatening consequences. (FDA)

5. What happens if you take opioids with Contrave?

If a person taking Contrave (which contains naltrexone and bupropion) also takes opioids, the opioid effects will be blocked, making them ineffective for pain relief. In individuals who regularly use opioids, this interaction can lead to sudden opioid withdrawal, causing symptoms such as nausea, sweating, anxiety, tremors, and severe flu-like discomfort.

This withdrawal can be dangerous and may require hospitalization if severe. Additionally, if someone attempts to take higher opioid doses to override the naltrexone block, this significantly increases the risk of overdose once naltrexone wears off.

If pain management is necessary while on Contrave, tell your doctor to discuss alternative treatment options.

6. Can you take bupropion and morphine together?

Bupropion and morphine should be used together with caution, as bupropion can lower the seizure threshold, and opioids like morphine may increase sedation and respiratory depression. Additionally, bupropion affects dopamine and norepinephrine, which could interact with morphine’s central nervous system effects, leading to unpredictable mood or neurological changes.

Patients with a history of seizures, head injury, or substance use disorder should be particularly cautious. While these two drugs are not always contraindicated, combining them should only be done under the supervision of a healthcare provider who can monitor for potential adverse effects.

Conclusion

The combination of Contrave and morphine presents significant interaction risks due to naltrexone’s opioid antagonism and bupropion’s effects on blood pressure and seizure threshold. Thorough communication with a healthcare provider is essential to navigate these risks effectively.

To ensure safe and effective treatment outcomes, patients should adhere to prescribed guidelines, report all medications and supplements they are taking, and attend regular medical appointments.​

For more detailed information, consult the FDA’s prescribing information for Contrave and the NCBI’s LiverTox database on naltrexone and bupropion.