Taking Contrave and St. John’s Wort Together: Is it Unsafe?

The rising popularity of prescription weight loss medication like Contrave, combined with the widespread use of herbal remedies such as St. John’s Wort, raises a critical question for patients trying to lose weight safely: Can you take Contrave and St. John’s Wort together, or is it unsafe?

Contrave is a prescription drug that contains two active ingredients—bupropion and naltrexone—designed to help regulate appetite and influence the brain’s reward pathways. St. John’s Wort, on the other hand, is a widely available herbal supplement often used to treat depression and mood disorders by increasing serotonin levels. While both substances affect the central nervous system, using them together may pose serious health risks, especially in people with preexisting medical conditions like bipolar disorder, seizure disorders, or high blood pressure.

“Many patients are unaware that mixing prescription weight loss drugs with certain dietary supplements can result in potentially life-threatening interactions,” says Dr. Matthew Olesiak, Chief Medical Director of SANE MD. “This is especially true with compounds that affect serotonin levels, like St. John’s Wort.”

Understanding how these two drugs interact—alongside the potential consequences—is crucial for anyone considering taking Contrave and St. John’s Wort together.

Key Takeaways

• Taking Contrave and St. John’s Wort together may significantly increase the risk of serotonin syndrome, a potentially life-threatening condition caused by excessive serotonin in the brain.
• Patients with underlying medical conditions such as seizure disorders, high blood pressure, or liver disease are at an even higher risk of serious drug interactions.
• Always consult your healthcare provider before combining prescription medications with over-the-counter supplements or other drugs.

Understanding Contrave

Contrave combines sustained-release bupropion and extended-release naltrexone—two drugs that target appetite regulation and the brain’s reward pathways to support weight loss for certain individuals. Bupropion is also used in smoking cessation and as an antidepressant, while naltrexone is typically used to manage alcohol and opioid dependence.

The way bupropion affects dopamine and norepinephrine makes it a unique prescription weight loss medication. However, it also lowers the seizure threshold, which can increase the risk of seizures—especially when combined with other drugs or supplements that affect serotonin or the central nervous system.

People with a history of seizure disorders, eating disorders, or those who drink alcohol excessively may face an increased risk when using Contrave. The medication guide also warns against abrupt discontinuation, as it may cause mood destabilization and other withdrawal symptoms. Weight gain may also occur.

What Is St. John’s Wort?

St. John’s Wort (Hypericum perforatum) is an herbal supplement commonly used to treat depression, mood swings, and mild anxiety. It influences neurotransmitters like serotonin, dopamine, and norepinephrine, similar to selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs).

Because of its wide-ranging effects on the brain, St. John’s Wort is known to interact with many other medications. These drug interactions may affect everything from the liver’s ability to metabolize drugs to serotonin levels in the brain.

Despite being classified as a dietary supplement, St. John’s Wort is a potent compound and should never be considered harmless—especially when used with other medications.

Why Taking Contrave and St. John’s Wort Together Is Risky

Combining two drugs that influence serotonin—like Contrave and St. John’s Wort—can increase the risk of serotonin syndrome, a rare but potentially fatal condition marked by confusion, agitation, tremors, sweating, high blood pressure, and trouble breathing.

This is especially concerning for compatible patients taking Contrave for weight loss, as many may not realize that bupropion can amplify serotonin activity indirectly. When paired with another serotonergic agent, the effects may be compounded.

“Most healthcare providers warn against combining serotonergic medications with herbal supplements like St. John’s Wort because of the increased risk of serotonin syndrome,” says Dr. Olesiak. “It’s essential to inform your doctor about all the medications and supplements you take—even those you consider harmless.”

St. John’s Wort can also accelerate the metabolism of bupropion and naltrexone in the liver, reducing their effectiveness and altering the drug’s intended balance. This not only reduces the drug’s weight loss benefits but may also contribute to unusual symptoms like irritability, sleep disturbances, or dry mouth.

Additionally, combining these two drugs may:

• Increase the risk of hypertensive crisis, especially in those with high blood pressure or on monoamine oxidase inhibitors (MAOIs).
• Trigger mood destabilization in individuals with bipolar disorder or other mood disorders.
• Elevate seizure risk in people with existing seizure disorders or those prone to abrupt discontinuation of medications.

Drug Interactions: What You Need to Know

When it comes to weight loss drugs, drug interactions are a critical factor in patient safety. Contrave, because it combines two active agents—sustained release bupropion and extended release naltrexone—has a particularly high potential for drug interactions with both prescription medications and over-the-counter medications.

The way these components work—affecting dopamine, norepinephrine, and the brain’s reward pathways—makes it essential to screen for other compounds that might amplify, diminish, or dangerously alter their effects.

One such compound is St. John’s Wort. While often perceived as a natural remedy for mood disorders or to treat depression, it’s far from benign when taken with prescription medications. St. John’s Wort has a well-documented history of interfering with liver enzymes (particularly CYP3A4), which break down many medicines in the body. This can lead to increased risk of drug toxicity or decreased drug efficacy.

St. John’s Wort is known to interfere with many other drugs, including:

• Antidepressants such as tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), and serotonin norepinephrine reuptake inhibitors (SNRIs) – potentially leading to serotonin syndrome, especially when combined with bupropion in Contrave.
• Birth control pills – reducing their effectiveness and increasing the risk of unintended pregnancy. (Contrave may also reduce the effectiveness of hormonal birth control._
• Blood thinners like warfarin – which can lead to either excessive bleeding or clotting.
• Immunosuppressants such as cyclosporine – lowering blood levels and potentially causing organ rejection.
• Antiepileptics – which may become less effective, raising the risk of seizures in those with seizure disorders.

Additionally, Contrave itself interacts with a broad range of certain medications. These include:

• Monoamine oxidase inhibitors (MAOIs) – the combination can result in a hypertensive crisis or other potentially life-threatening conditions.
• Mood stabilizers – which may be affected by the dopaminergic and noradrenergic activity of bupropion.
• Medications that affect the central nervous system, including sedatives, stimulants, and antipsychotics, including Haldol.

When patients take other medications alongside Contrave or St. John’s Wort, the potential drug interactions multiply. These combinations don’t just alter effectiveness—they can drastically increase the risk of adverse events like high blood pressure, skin rash, unusual symptoms, or mood swings.

The central nervous system is especially sensitive to overlapping influences from multiple drugs. Combining two drugs like Contrave and St. John’s Wort, both of which have psychoactive properties, places extra strain on neurotransmitter balance and regulatory systems in the body. These risks are amplified in patients with underlying medical conditions such as bipolar disorder, liver disease, or those who drink alcohol regularly.

Many people also mistakenly believe that if a supplement is “natural,” it can be used freely. But dietary supplements like St. John’s Wort can pose just as many risks as synthetic drugs when it comes to interactions—especially with a prescription weight loss medication.

Combining bupropion with herbal supplements like St. John’s Wort can lead to significant drug interactions. According to the FDA, St. John’s Wort is known to interact with various cytochrome P450 enzymes and transporter systems, which can alter the metabolism of many drugs, including bupropion . Additionally, a study published in the British Journal of Clinical Psychopharmacology reported a case where the concurrent use of bupropion and St. John’s Wort resulted in prolonged oro-facial dystonia, highlighting the potential for serious neurological side effects .

Therefore, it is crucial to consult with a healthcare provider before combining bupropion with any herbal supplements to avoid adverse effects.​

In practice, this means that healthcare providers must conduct a thorough medication review before prescribing Contrave—and patients must be honest and proactive in disclosing all the medications and supplements they’re taking, including herbal remedies like St. John’s Wort.

Even a single unreported supplement can result in an increased risk of life-threatening conditions or reduce the effectiveness of medications meant to help you lose weight and improve your health.

Health Conditions That Increase the Risk

Individuals with certain medical conditions should be especially cautious—or avoid entirely—taking Contrave and St. John’s Wort together. While each substance has legitimate therapeutic uses, combining them can pose a serious health risk, particularly in vulnerable populations.

Below are the key conditions that raise the increased risk of dangerous drug interactions and complications:

• Seizure disorders: Contrave contains bupropion, which is known to lower the seizure threshold. When combined with other substances that stimulate the central nervous system, such as St. John’s Wort, the chance of a seizure increases dramatically. This makes the drug combination unsuitable for individuals with a current or past history of epilepsy or other seizure disorders.
• Bipolar disorder: Both bupropion and St. John’s Wort can influence mood and neurotransmitter balance. While bupropion is sometimes used to treat depression, it may trigger mood destabilization or manic episodes in people with bipolar disorder. St. John’s Wort, due to its serotonergic properties, may also disrupt mood regulation, especially when combined with other antidepressants or central nervous system stimulants.
• Liver disease or kidney disease: Both Contrave and St. John’s Wort are metabolized through hepatic (liver) and renal (kidney) pathways. People with liver disease or kidney disease may experience slower drug clearance, leading to an increased risk of accumulation and toxicity. The altered metabolism can intensify side effects or reduce the expected therapeutic effect of either drug.
• Heart disease or high blood pressure: Naltrexone and bupropion can increase blood pressure, and when paired with a substance like St. John’s Wort—which may alter drug metabolism and central neurotransmission—this effect may become exaggerated. The combination raises the risk of hypertensive crisis, especially in individuals already diagnosed with high blood pressure or any form of heart disease.
• Eating disorders: Individuals with a history of eating disorders (especially bulimia or anorexia nervosa) are at heightened risk when using bupropion, as this population is more prone to seizure disorders and mood disturbances. Adding St. John’s Wort—often perceived as a natural mood booster—can further destabilize mood or contribute to dangerous behavior if not closely monitored.

For patients with an initial body mass index (BMI) of 30 or higher—or 27 with associated comorbidities such as high blood pressure—Contrave may be recommended as part of a supervised treatment plan to lose weight. However, the increased risk posed by certain underlying health conditions must be weighed carefully against the potential benefits of weight loss.

Even among healthy volunteers, clinical trials have demonstrated that bupropion, when used alongside other serotonergic agents, can produce symptoms of serotonin syndrome and central nervous system overstimulation—ranging from mild (anxiety, agitation) to severe (confusion, muscle rigidity, or fever).

In these cases, the presence of any preexisting medical condition can amplify the potentially life-threatening conditions associated with polypharmacy. This is why healthcare providers emphasize the importance of medical history screening before initiating prescription weight loss medication, particularly one like Contrave that carries a range of neurological and cardiovascular precautions.

By openly discussing all current health issues and medications—including dietary supplements like St. John’s Wort—patients can reduce their increased risk of adverse outcomes and receive more personalized, safer care.

What About Over-the-Counter Medications?

Many people assume that over-the-counter medications and herbal supplements are inherently safe, especially when compared to prescription drugs. But this assumption can be dangerous—particularly when these products are taken alongside prescription weight loss medication like Contrave.

One of the most well-known examples is St. John’s Wort, which is commonly used to treat depression, relieve anxiety, and support mood balance. Despite being marketed as a natural remedy, St. John’s Wort is far from harmless when combined with other medications.

In fact, St. John’s Wort is associated with a wide range of potential drug interactions, many of which are serious. It significantly affects the activity of liver enzymes, particularly CYP3A4, which are responsible for metabolizing many commonly used drugs—including antidepressants, anticonvulsants, birth control pills, and weight loss drugs.

This enzyme-inducing effect can lead to reduced efficacy of medications, rendering them less effective or entirely ineffective. In other cases, it may enhance drug activity to dangerous levels, contributing to increased risk of side effects or toxicity.

For instance, the NIH reports that St. John’s Wort can:

• Decrease the effectiveness of oral contraceptives, leading to unintended pregnancy. (Contrave may also decrease the effectiveness of hormonal birth control.)
• Weaken the effects of immunosuppressants like cyclosporine, potentially leading to organ rejection
• Interfere with HIV medications, making viral suppression less effective
• Contribute to serotonin syndrome when taken with serotonergic medications such as SSRIs, SNRIs, or bupropion therapy
• Trigger unusual symptoms like skin rash, sun sensitivity (photosensitivity), dizziness, or confusion—especially when combined with other central nervous system stimulants

Because of these effects, even a seemingly innocent supplement can interact dangerously with Contrave, especially considering its influence on dopamine, appetite regulation, and brain function. Patients who drink alcohol, have bipolar disorder, or are managing multiple medical conditions face a particularly higher risk when mixing unverified supplements with prescription treatments.

The takeaway is simple but critical: just because a product is available without a prescription does not mean it’s free from health risks or compatible with your current medications.

Before starting any dietary supplement, herbal remedy, or over-the-counter medication, patients using Contrave should speak with a qualified healthcare provider to avoid dangerous drug interactions and protect their progress toward weight loss and overall health.

Lifestyle Considerations While Taking Contrave

When using Contrave as part of a treatment plan for weight loss, it’s important to understand that the medication is not a quick fix. Its effectiveness hinges on several critical lifestyle elements, including a reduced-calorie diet, consistent physical activity, and medical supervision. These foundational strategies help support long-term behavior change and maximize the benefit of prescription weight loss medication.

Adding unregulated dietary supplements like St. John’s Wort into this mix, however, may not only diminish the benefits of Contrave but also increase the likelihood of adverse effects and serious drug interactions. Herbal compounds can alter how Contrave is absorbed, metabolized, and excreted—ultimately throwing off the drug’s delicate balance within the central nervous system.

Here are some key considerations to ensure you’re using Contrave safely and effectively:

• Avoid high-fat meals when taking Contrave. A high-fat meal can significantly increase the plasma concentration of sustained-release bupropion, raising the likelihood of side effects such as high blood pressure, nausea, or even triggering a seizure in at-risk individuals. Stick with balanced meals that are nutrient-dense and aligned with your reduced-calorie diet goals.
• Do not abruptly discontinue Contrave. Stopping the medication suddenly—especially without the guidance of a healthcare provider—can lead to mood destabilization, irritability, or withdrawal symptoms. If side effects arise or the medication no longer seems effective, work with your provider to taper off safely.
• Be cautious about missed doses. It may be tempting to take an extra pill to “make up” for a missed dose, but this approach increases the risk of seizure disorders, elevated blood pressure, and other complications. Follow the instructions in your medication guide or speak to your healthcare provider about the safest course of action.
• Report any unusual symptoms immediately. This includes persistent dry mouth, dizziness, confusion, agitation, sleep problems, or sudden mood swings. These symptoms may indicate a drug interaction, especially if you’re also using St. John’s Wort or other over-the-counter medications.
• Limit alcohol consumption. Patients using Contrave should not drink alcohol excessively. Alcohol can increase the risk of seizures and central nervous system side effects, particularly in individuals with a history of bipolar disorder, depression, or those prone to abrupt discontinuation of mood-altering medications. For some, complete abstinence may be recommended during bupropion therapy.
• Watch for interaction with physical exertion. Because Contrave affects neurotransmitters involved in energy, reward, and impulse control, combining the drug with intense physical activity may amplify sensations like racing heart or dizziness—especially in warmer environments. Stay hydrated, monitor your blood pressure, and pace workouts according to your tolerance level.
• Keep your provider informed about all the medications and supplements you’re taking. Even a well-intentioned supplement like St. John’s Wort can undermine your weight loss efforts by causing potential drug interactions that interfere with how Contrave works—or worse, lead to a potentially life-threatening condition like serotonin syndrome or hypertensive crisis.

While many people are motivated to lose weight quickly, using multiple substances that act on the brain and body simultaneously should never be done without guidance. Combining two drugs—particularly those with serotonergic, dopaminergic, or stimulant-like properties—can tax the brain involved in mood regulation, appetite control, and impulse moderation.

It’s also worth noting that patients with a history of eating disorders, seizure disorders, or mood disorders are more susceptible to complications, including unusual symptoms and serious medical conditions. That’s why lifestyle choices and honest communication with your healthcare provider are critical throughout the course of treatment.

Making well-informed choices, staying consistent with your reduced-calorie diet and physical activity, and avoiding unapproved supplements can help maximize Contrave’s benefits and reduce your increased risk of complications.

When to Seek Immediate Medical Attention

Call your healthcare provider immediately or seek emergency care if you notice signs of:

• Serotonin syndrome: confusion, rapid heartbeat, sweating, tremors
• Hypertensive crisis: severe headache, chest pain, blurred vision. Check out our guide to discover if Contrave can increase blood pressure — and why.
• Allergic reaction: hives, swelling, or trouble breathing
• Mood swings or signs of manic behavior in bipolar individuals

These symptoms may indicate that your medications—or dietary supplements—are interacting in dangerous ways.

Can You Ever Safely Take Contrave and St. John’s Wort?

There may be cases where low-dose, short-term use of St. John’s Wort is considered, but this should only be done under the direction of a healthcare provider familiar with all the medications you’re taking.

In most cases, patients seeking mood support should explore safer alternatives, especially since Contrave itself is contraindicated in patients currently being treated with monoamine oxidase inhibitors, tricyclic antidepressants, or serotonergic agents.

Frequently Asked Questions (FAQ)

When it comes to combining prescription weight loss medication like Contrave with dietary supplements or antidepressants, it’s natural to have concerns.

The following FAQs address some of the most common questions about drug interactions and safety when using Contrave, bupropion, St. John’s Wort, and other medications that affect the central nervous system.

1. Can I take St. John’s Wort with bupropion?

It is generally not recommended to take St. John’s Wort with bupropion due to the increased risk of serious drug interactions. Both substances influence brain neurotransmitters and may lead to serotonin syndrome, a potentially life-threatening condition. St. John’s Wort can also induce liver enzymes that alter how bupropion is metabolized, reducing its effectiveness or increasing side effects.

Patients treated with bupropion should consult their healthcare provider before using any herbal supplements, including St. John’s Wort.

2. What medications should not be taken with Contrave?

Contrave should not be taken with monoamine oxidase inhibitors (MAOIs) like Nardil, other bupropion-containing medications, opioids like hydromorphone, or drugs like Wellbutrin that lower the seizure threshold.

Combining Contrave with other medications that affect serotonin—such as SSRIs, SNRIs, or St. John’s Wort—can increase the risk of serotonin syndrome. Individuals with seizure disorders, eating disorders, or those who drink alcohol heavily are especially vulnerable to complications.

Always review your current prescriptions, supplements, and over-the-counter medications with your healthcare provider before starting Contrave.

3. What drugs should not be taken with St. John’s Wort?

St. John’s Wort can interfere with a wide range of medications, including antidepressants (SSRIs, SNRIs, tricyclic antidepressants), birth control pills, blood thinners, and immunosuppressants. It may reduce drug effectiveness by speeding up liver metabolism and increase the chance of adverse effects by amplifying serotonin activity. When taken with serotonergic drugs, it may lead to serotonin syndrome.

People taking prescription weight loss drugs, mood stabilizers, or treatments for heart disease, bipolar disorder, or seizure disorders should avoid using St. John’s Wort without medical supervision.

4. Can you take Contrave with an SSRI?

Using Contrave with a selective serotonin reuptake inhibitor (SSRI), such as Prozac and Zoloft, can be risky due to the potential for drug interactions affecting serotonin levels. Since Contrave includes bupropion, which can indirectly influence serotonin, adding an SSRI may increase the risk of serotonin syndrome.

This risk is higher in patients with bipolar disorder, those who have high blood pressure, or who are already taking other serotonergic drugs or supplements like St. John’s Wort.

Your healthcare provider may recommend an alternative treatment plan or close monitoring if both are prescribed.

Summary: The Risks Outweigh the Benefits

Using Contrave and St. John’s Wort together can increase the risk of serious drug interactions, including serotonin syndrome, seizure, mood instability, and reduced medication effectiveness. For patients trying to lose weight with Contrave, the risks of combining it with herbal antidepressants far outweigh any potential benefits.

Your best bet is to work closely with your healthcare provider to develop a comprehensive, safe treatment plan that includes a reduced-calorie diet, physical activity, and the right medications for your needs.

References

FDA

British Journal of Clinical Pharmacology

NIH