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Understanding Contrave: How It Works as a Weight Loss Medication

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Science & Humans

Medically approved by

Maria Jacob

Last updated

Tuesday, February 6, 2024

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A variety of dietary mixes and medications, along with lifestyle adjustments, have been introduced in efforts to address weight loss. Studies have investigated the efficacy of Contrave for weight loss, revealing its potential as a pharmacological intervention in managing obesity. Exploring Contrave benefits under medical guidance can offer a comprehensive approach to weight loss, addressing both physical and behavioral aspects. Here, we present an update on Contrave uses and its prescribing information. 

What is Contrave?

Contrave for weight loss is a novel fixed-dose combination product composed of naltrexone and bupropion. Naltrexone is an opioid receptor antagonist used for treating alcohol and opioid addictions (Lobmaier et al., 2011). Bupropion is a dopamine and norepinephrine reuptake inhibitor mainly used for treating depression and helping with smoking cessation (Rueda-Clausen et al., 2013). 

Naltrexone exerts an influence on the opioid receptors within the brain, potentially mitigating food cravings. Meanwhile, bupropion modulates neurotransmitters implicated in appetite regulation and metabolic processes, resulting in reduced appetite and a possible elevation in calorie expenditure. This dual action contributes to Contrave for weight loss by influencing both food consumption and the energy balance (Kosmalski et al., 2023).

Contrave comes in the form of a sustained-release tri-layer tablet (Mercer 2011). Patients with a BMI of 30 kg/m2 or higher, or 27 kg/m2 with at least one accompanying condition like arterial hypertension, type-2 diabetes mellitus, or dyslipidemia, are advised for Contrave prescription (Ahmad et al., 2021). The initial dosage of Contrave is one tablet by mouth (orally) daily (8 mg naltrexone/90 mg bupropion), titrated over 4 weeks to 2 tablets orally twice daily (Mercer 2011).

Is Contrave Used for Weight Loss?

Contrave medication seems like an interesting drug to reduce appetite and therefore induce weight loss. Contrave weight loss medication can be effective when combined with a diet and exercise program. Table 1 below presents an overview of some important clinical trials assessing the efficacy and safety of Contrave for weight loss. Studies discussed in the table below show that combination therapy of naltrexone and bupropion (Contrave weight loss medication) has demonstrated effectiveness in both healthy patients and individuals with additional conditions like arterial hypertension, type-2 diabetes mellitus, or dyslipidemia.

Major clinical trials evaluating naltrexone plus bupropion (Contrave) for weight loss


Study Population Outcomes Reference
A Phase II, 24-week randomized, blinded, placebo-controlled trial. 238 male and female subjects at least 18–60 years of age with a BMI of 30–40 kg/m2. Sustained weight loss through 24 weeks of treatment. Also, well tolerated. No serious AE was attributed to the study drug. The common AE was nausea. Greenway et al., 2009
(COR-I): A Phase III, 56-week randomized, double-blind, placebo-controlled trial. (Patients were on Contrave plus a mild hypocaloric diet and exercise)

1742 patients ages 18–65 years with an uncomplicated BMI of 30–45 kg/m2

or BMI of 27–45 kg/m2 plus

dyslipidemia or hypertension.

A body mass reduction of 6.1% was noted in the 360 mg/32 mg dose group, and 5.0% was noted in the 360 mg/16 mg dose group. No SAEs are attributed to the study drug. The common AEs were nausea, headache, and constipation. Greenway et al., 2010
(COR-BMOD trial): A Phase III, 56-week, randomized, placebo-controlled trial. (Patients were on Contrave plus an energy-reduced diet)

793 participants (BMI = 36.5 ± 4.2 kg/m2).

A body mass reduction of 9.3% was noted in the 360 mg/32 mg +BMOD dose group. Two SAEs (cholecystitis) were considered possibly related to the study drug. The common AEs reported were nausea, constipation, dizziness, dry mouth, tremor, abdominal pain, and tinnitus. Wadden et al., 2011
(COR-II): A Phase III, 56-week, double-blind, placebo-controlled trial. (Patients were on Contrave plus a hypocaloric diet and exercise) 1,496 obese (BMI 30-45 kg/m2) or overweight (27-45 kg/m2) with dyslipidemia and/or hypertension. A body mass reduction of 6.5% was noted in the 360 mg/32 mg dose group. Two SAEs were reported (myocardial infarction and seizure). The common AEs were nausea, headache, and constipation.

Apovian et al., 2013

A Phase III, 56-week, double-blind, placebo-controlled trial. (Patients were on Contrave plus behavioral modification and increased physical activity) 505 overweight/obese individuals with type 2 diabetes aged 18–70 years, with a BMI of ≥27 and ≤45 kg/m2, HbA1c between 7% and 10%, and FPG < 270 mg/dL A body mass reduction of 5.0% was noted in the 360 mg/32 mg dose group. Generally, it was well tolerated and had a safety profile similar to that of patients without diabetes. The common AEs were nausea, constipation, vomiting, and diarrhea.

Hollander et al., 2013


Side Effects of Contrave

Common side effects

According to the clinical trial published, common Contrave side effects include (FDA 2014):

  • Nausea,
  • Constipation,
  • Headache
  • Vomiting,
  • Diarrhea
  • Dizziness
  • Dry mouth

Serious side effects

Contrave weight loss pills can have serious but rare side effects (FDA 2014). Serious Contrave side effects are listed below:

  • High blood pressure (hypertension)
  • Increased heart rate (tachycardia)
  • Seizure
  • Suicidal behavior and ideation
  • Allergic reactions

Pros and Cons of Taking Contrave for Weight Loss

Pros of taking Contrave

  • Contrave weight loss medication because of its unique combination of two active ingredients, bupropion and naltrexone, which work on two different mechanisms. Contrave weight loss pills help with weight loss by curbing appetite and cravings while potentially increasing metabolism. If a patient experiences substantial cravings or engages in emotional eating, Contrave might be recommended to assist in diminishing these cravings.
  • Patients with excess weight or obesity face heightened risks of cardiovascular disease (CVD) and mortality related to cardiovascular issues (Whitlock et al., 2009). There has been discussion about Contrave and its long-term safety in terms of the cardiovascular system. A recent systematic review result does not suggest a higher likelihood of CVD or major adverse cardiac events (MACE) after using naltrexone/bupropion ER (Contrave pills), naltrexone, or bupropion individually or in combination (Dahlberg et al., 2022).
  • Contrave also has a positive effect on the lipid profile (low-density lipoprotein, high-density lipoprotein, and triglycerides) and on insulin resistance (Caixàs et al., 2014).
  • Contrave weight loss pills have also been studied for weight loss in overweight or obese patients with major depressive disorder (although not FDA-approved for this use). This pilot study showed a significant improvement in both depression and body weight loss in patients taking Contrave pills and receiving dietary and behavioral counseling (McElroy et al., 2013). 

Cons of taking Contrave

  • There are concerns raised due to the treatment being linked with an average rise in both systolic and diastolic blood pressure. Individuals with a history of hypersensitive reactions to naltrexone or any ingredient within the preparation should not use this medication due to contraindications (Theriot et al., 2023).
  • When contemplating the administration of Contrave medication to a specific patient, it is important to recall that it is not suitable for individuals with a history of seizures, eating disorders, or those currently consuming alcohol (Kosmalski et al., 2023).

Cost of Contrave

Contrave medication comes in tablet form, containing 8 mg of naltrexone hydrochloride and 90 mg of bupropion hydrochloride. The suggested dosage of Contrave for weight loss is two tablets taken twice a day. Contrave is not covered by the Pharmaceutical Schedule, so there is an associated cost. The Contrave cost can depend on the treatment plan, pharmacy, and residing area. One should always check if their health insurance covers the treatment plan involving Contrave for weight loss. One tablet of Contrave can cost $2.21, which is $8.84 per day (CADTH 2020). The treatment may have some indirect costs, like doctor, prescription, and pharmacy fees, along with the cost of Contrave pills. You can get a Contrave online prescription through authorized healthcare platforms.

Drug Interactions and Warnings with Contrave

Some of the significant drug interactions include (FDA 2014):

  • Monoamine Oxidase Inhibitors (MAOIs): Concomitant use of bupropion and MAOIs (a class of anti-depressants that includes medicines like phenelzine and tranylcypromine) is contraindicated as these can increase the risk for hypertensive reactions.
  • Opioid Analgesics: Naltrexone blocks the effects of opioids, thereby reducing their effectiveness. 
  • Blood Pressure Medications: Concomitant use of blood pressure medicine and Contrave may lead to an increase in blood pressure and a resting heart rate.
  • Seizure Medications: Bupropion, a component of the Contrave pill, can cause seizures. Combining it with other seizure medicines can lower the seizure threshold. 
  • Parkinson’s Medications: Bupropion, if coadministered with levodopa or amantadine, can cause CNS toxicity due to an increase level of dopamine.
  • Antidepressants and Psychiatric Medications: Co-administration should be done with caution and should be initiated within the low dose range of the concomitant medication.

Warnings for Contrave include (FDA 2014):

  • Suicidal Behavior and Ideation: Contrave should be discontinued if symptoms are noted.
  • Angle-closure glaucoma: bupropion, a component of Contrave, may trigger an angle-closure attack in a patient with an anatomically narrow angle. 
  • Contrave should not be prescribed to an individual with a known allergy to any of its two constituents.
  • Contrave is contraindicated for pregnant women, nursing mothers, pediatrics, the older population (≥65 years-old), and for those with renal and hepatic impairment.

Alternatives to Contrave for Weight Loss

Here are a few alternatives to Contrave for weight loss (Kosmalski et al., 2023):

  • Orlistat
  • Liraglutide (Saxenda)
  • Semaglutide (Wegovy)
  • Phentermine-Topiramate (Qsymia)
  • Lorcaserin
  • There are other drugs that are approved for other diseases but demonstrate weight loss. These include exenatide, dulaglutide, and tirzepatide.


Contrave benefits include its potential to curb cravings and reduce appetite, aiding in weight management for certain individuals. Obtaining a Contrave prescription online requires consultation with a licensed healthcare provider through authorized platforms. The Contrave cost may vary based on dosage, location, and insurance coverage. You can visit https://www.scienceandhumans.com/ to consult a healthcare practitioner or to get more information on weight loss and Contrave.



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  • CADTH Canadian Drug Expert Committee Recommendation: Naltrexone Hydrochloride and Bupropion Hydrochloride (Contrave — Bausch Health, Canada Inc.): Indication: An adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial body mass index of 30 kg/m2 or greater (obese) or 27 kg/m2 or greater (overweight) in the presence of at least one weight-related comorbidity (e.g., controlled hypertension, type 2 diabetes mellitus, or dyslipidemia) [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2020 Jun. Available from: https://www.ncbi.nlm.nih.gov/books/NBK565294/ 

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