Contrave is an FDA-approved drug for adults with a body mass index (BMI) of 30 or higher who wants to lose weight. In some cases, doctors recommend this drug for patients with a BMI of 27 or higher who have one or more weight-related condition or illness, such as hypertension, high cholesterol, or type 2 diabetes.  The active ingredients in contrave are bupropion, an antidepressant, and naltrexone, a drug used to combat opioid addiction.
The exact neurochemical mechanism by which contrave exerts its weight loss effects is by affecting the function of the hypothalamus, the hunger center of your brain. This in turn promotes satiety, reduces food intake, and boosts energy expenditure. The combination of bupropion and naltrexone also work on the mesolimbic pathway, the brain network that provides rewarding feelings. By regulating this pathway, food-seeking behaviors will be significantly reduced.
Overall Health Benefits of Contrave
- Promotes weight loss [2-22]
- Wards off depression [23-36]
- Reduces blood sugar levels [2, 37-38]
- Improves sexual function [39-47]
- Improves cholesterol levels [48-50]
- Treats cigarette addiction [51-55]
Proven Health Benefits of Contrave
Promotes Weight Loss
The main benefit of this FDA-approved drug is to help overweight and obese people achieve healthier weight and lower their risk for weight-related medical conditions. An overwhelming body of clinical evidence supports this:
- In overweight/obese individuals with type 2 diabetes, administration of 32 mg naltrexone sustained-release (SR)/360 mg bupropion SR (NB) resulted in significantly greater weight reduction. 
- In non-diabetic patients, three phase 3 trials of naltrexone SR plus bupropion SR (NB) demonstrated significant weight loss without any adverse side effects. [3-5]
- When combined with lifestyle intervention and modest calorie reduction, the naltrexone–bupropion combination appears to achieve clinically significant weight loss (over 5% of total body weight) after 6 months to 1 year of treatment. 
- A study found that contrave treatment was associated with 3 to 7% weight loss and improvements in obesity-related comorbidities and cardiovascular risk factors. 
- Patients who received 1 year of naltrexone ER/bupropion ER combination therapy with greater than 5% weight lost are likely to maintain clinically significant results. 
- In overweight and obese patients, naltrexone/bupropion (NB) combination therapy was associated with significantly greater weight loss. 
- In patients with uncomplicated obesity, combined bupropion and naltrexone therapy caused gradual sustained weight loss over 48 weeks. 
- In middle-aged white females, contrave treatment significantly reduced weight. [11-13]
- In obese mice, contrave significantly reduced weight by increasing the activity of POMC cells, which are peptides that play an integral role in weight regulation. 
- Direct injection of bupropion and naltrexone in mice produced greater reduction in food intake. [15-16]
- In obese patients, contrave treatment reduced body fat and visceral adipose tissue. 
- A study found that contrave has a greater weight loss efficacy than other FDA-approved drugs for obesity, such as orlistat and lorcaserin. 
- Studies also found that contrave has favorable effects on obesity, medication-related weight gain, and binge eating behaviors. [19-22]
Wards Off Depression
There’s also a good deal of evidence supporting the mood-boosting properties of this FDA-approved weight loss drug:
- An analysis of several studies found that there is a strong correlation between obesity and depression, suggesting that weight loss treatment with contrave can have positive effects on mood. [23-31]
- In overweight/obese women with major depressive disorder, contrave therapy for 24 weeks was associated with improvement in depressive symptoms. 
- A large pooled analysis of 5 clinical trials found that contrave was associated with lesser depressive symptoms and psychiatric adverse events compared to placebo. [33-34]
- In patients with major depression, treatment with contrave reduced binge eating, a common symptom of depression. 
- Administration of low-dose naltrexone in combination with bupropion in patients with major depressive disorder significantly reduced the incidence of relapse and recurrence. 
Reduces Blood Sugar Levels
Not only does contrave improves body composition but it can also help bring down high levels of blood sugar. Evidence suggests that it can be beneficial for diabetic patients as well as those with chronic elevated blood sugar levels:
- In overweight and obese patients with type 2 diabetes, treatment with 32 mg naltrexone sustained-release (SR)/360 mg bupropion SR (NB) was associated with improvement in blood sugar control as evidenced by greater reduction in hemoglobin A1c (HbA1c). 
- In diabetic patients, naltrexone/bupropion therapy decreased HbA1c approximately 0.5% more than placebo. 
- In overweight and obese patients, contrave also decreased major cardiovascular risk factors such as high blood sugar. 
Improves Sexual Function
Evidence suggests that contrave has beneficial effects on sexual health of both men and women:
- Studies suggest that obesity is linked with greater impairment in sexual function, suggesting that losing weight through contrave supplementation can have a positive impact on sexual health. [39-42]
- Bupropion, the component of contrave, has been reported to have pro‐sexual effects. [43-46]
- In obese patients, administration of contrave significantly improved sexual function as well as quality of life. 
Improves Cholesterol Levels
Contrave-induced weight loss is known to play a role in reducing high cholesterol levels. Studies found that patients taking this drug had better lipid profile:
- In obese patients, naltrexone/bupropion combination significantly reduced the levels of low-density lipoprotein (bad cholesterol) and increased the levels of high-density lipoprotein (good cholesterol). 
- In overweight and obese patients, daily treatment with contrave increased high-density lipoprotein cholesterol and decreased triglycerides. 
- In obese adults undergoing weight management, contrave administration also increased high-density lipoprotein cholesterol. 
Treats Cigarette Addiction
High quality clinical trials show that contrave treatment can be considered as a safe and effective smoking cessation strategy:
- A preliminary investigation of the combination of naltrexone and bupropion as treatment for cigarette addiction showed lower smoking cessation rates. 
- Smokers who received contrave treatment for 7 weeks reported reduced nicotine withdrawal. 
- A study found that both naltrexone and bupropion can help improve adherence to smoking cessation interventions. 
- One clinical trial found that subjects treated with low-dose naltrexone combined with bupropion stopped cigarette smoking with lesser weight gain. 
- In overweight or obese smokers, combination therapy of naltrexone and bupropion was associated with decreased nicotine use, limited nicotine withdrawal symptoms, and no significant weight gain. 
- Contrave–a combination of bupropion and naltrexone for weight loss. Med Lett Drugs Ther. 2014;56(1455):112-4.
- Hollander P, Gupta AK, Plodkowski R, et al. Effects of naltrexone sustained-release/bupropion sustained-release combination therapy on body weight and glycemic parameters in overweight and obese patients with type 2 diabetes [published correction appears in Diabetes Care. 2014 Feb;37(2):587]. Diabetes Care. 2013;36(12):4022–4029. doi:10.2337/dc13-0234.
- Apovian CM, Aronne LJ, Rubino DM, et al. COR-II Study Group A randomized, phase 3 trial of naltrexone SR/bupropion SR on weight and obesity-related risk factors (COR-II). Obesity (Silver Spring) 2013;21:935–943.
- Greenway FL, Fujioka K, Plodkowski RA, et al. COR-I Study Group Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2010;376:595–605.
- Wadden TA, Foreyt JP, Foster GD, et al. Weight loss with naltrexone SR/bupropion SR combination therapy as an adjunct to behavior modification: the COR-BMOD trial. Obesity (Silver Spring) 2011;19:110–120.
- Tek C. Naltrexone HCI/bupropion HCI for chronic weight management in obese adults: patient selection and perspectives. Patient Prefer Adherence. 2016;10:751–759. Published 2016 May 4. doi:10.2147/PPA.S84778.
- Padwal R. Contrave, a bupropion and naltrexone combination therapy for the potential treatment of obesity. Curr Opin Investig Drugs. 2009;10(10):1117-25.
- Fujioka K, Plodkowski R, O’neil PM, Gilder K, Walsh B, Greenway FL. The relationship between early weight loss and weight loss at 1 year with naltrexone ER/bupropion ER combination therapy. Int J Obes (Lond). 2016;40(9):1369-75.
- Apovian CM, Aronne L, Rubino D, et al. A randomized, phase 3 trial of naltrexone SR/bupropion SR on weight and obesity-related risk factors (COR-II). Obesity (Silver Spring). 2013;21(5):935–943. doi:10.1002/oby.20309.
- Greenway FL, Dunayevich E, Tollefson G, et al. Comparison of combined bupropion and naltrexone therapy for obesity with monotherapy and placebo. J Clin Endocrinol Metab. 2009;94(12):4898-906.
- Li Z, Maglione M, Tu W, et al. Meta-analysis: pharmacologic treatment of obesity. Ann Intern Med. 2005;142:532–546.
- Rucker D, Padwal R, Li SK, Curioni C, Lau DC. Long term pharmacotherapy for obesity and overweight: updated meta-analysis. BMJ. 2007;335:1194–1199.
- Health I. Plymouth, PA: The National Disease and Therapeutic Index; pp. 1998–2003.
- Greenway FL, Whitehouse MJ, Guttadauria M, et al. Rational design of a combination medication for the treatment of obesity. Obesity (Silver Spring). 2009;17(1):30-9.
- Available from https://www.scienceopen.com/document?vid=675a2d4d-d825-45be-bf9c-716f23852839.
- Wright FL, Rodgers RJ. Acute behavioural effects of bupropion and naltrexone, alone and in combination, in non-deprived male rats presented with palatable mash. Psychopharmacology (Berl). 2013;228(2):291-307.
- Smith SR, Fujioka K, Gupta AK, et al. Combination therapy with naltrexone and bupropion for obesity reduces total and visceral adiposity. Diabetes Obes Metab. 2013;15(9):863-6.
- Verpeut JL, Bello NT. Drug safety evaluation of naltrexone/bupropion for the treatment of obesity. Expert Opin Drug Saf. 2014;13(6):831-41.
- Howland RH. Melatonin, Liraglutide, and Naltrexone/Bupropion for the Treatment of Obesity and Medication-Related Weight Gain. J Psychosoc Nurs Ment Health Serv. 2015;53(6):19-22.
- Padwal R. Contrave, a bupropion and naltrexone combination therapy for the potential treatment of obesity. Curr Opin Investig Drugs. 2009;10(10):1117-1125.
- Caixàs A, Albert L, Capel I, Rigla M. Naltrexone sustained-release/bupropion sustained-release for the management of obesity: review of the data to date. Drug Des Devel Ther. 2014;8:1419-1427. Published 2014 Sep 18. doi:10.2147/DDDT.S55587.
- Avaialble from https://www.researchgate.net/publication/341060191_An_open-label_trial_on_the_efficacy_and_tolerability_of_naltrexonebupropion_SR_for_treating_altered_eating_behaviours_and_weight_loss_in_binge_eating_disorder.
- de Wit L, Luppino F, van Straten A, et al. Depression and obesity: a meta-analysis of community-based studies. Psychiatry Res. 2010;178(2):230–235.
- Luppino FS, de Wit LM, Bouvy PF, et al. Overweight, obesity, and depression: a systematic review and meta-analysis of longitudinal studies. Arch Gen Psychiatry. 2010;67(3):220–229.
- Blaine B. Does depression cause obesity? a meta-analysis of longitudinal studies of depression and weight control. J Health Psychol. 2008;13(8):1190–1197.
- Khan A, Schwartz KA, Kolts RL, et al. BMI, sex, and antidepressant response. J Affect Disord. 2007;99(1–3):101–106.
- Kloiber S, Ising M, Reppermund S, et al. Overweight and obesity affect treatment response in major depression. Biol Psychiatry. 2007;62(4):321–326.
- Papakostas GI, Petersen T, Iosifescu DV, et al. Obesity among outpatients with major depressive disorder. Int J Neuropsychopharmacol. 2005;8(1):59–63.
- Uher R, Mors O, Hauser J, et al. Body weight as a predictor of antidepressant efficacy in the GENDEP project. J Affect Disord. 2009;118(1–3):147–154.
- Oskooilar N, Wilcox CS, Tong ML, et al. Body mass index and response to antidepressants in depressed research subjects. J Clin Psychiatry. 2009;70(11):1609–1610.
- Murphy JM, Horton NJ, Burke JD, Jr, et al. Obesity and weight gain in relation to depression: findings from the Stirling County Study. Int J Obes (Lond) 2009;33(3):335–341.
- Mcelroy SL, Guerdjikova AI, Kim DD, et al. Naltrexone/Bupropion combination therapy in overweight or obese patients with major depressive disorder: results of a pilot study. Prim Care Companion CNS Disord. 2013;15(3).
- Pi-sunyer X, Apovian CM, Mcelroy SL, Dunayevich E, Acevedo LM, Greenway FL. Psychiatric adverse events and effects on mood with prolonged-release naltrexone/bupropion combination therapy: a pooled analysis. Int J Obes (Lond). 2019.
- Available from https://www.nature.com/articles/s41366-018-0302-z.
- Guerdjikova AI, Walsh B, Shan K, Halseth AE, Dunayevich E, Mcelroy SL. Concurrent Improvement in Both Binge Eating and Depressive Symptoms with Naltrexone/Bupropion Therapy in Overweight or Obese Subjects with Major Depressive Disorder in an Open-Label, Uncontrolled Study. Adv Ther. 2017;34(10):2307-2315.
- Available from https://clinicaltrials.gov/ct2/show/NCT01874951.
- Makowski CT, Gwinn KM, Hurren KM. Naltrexone/bupropion: an investigational combination for weight loss and maintenance. Obes Facts. 2011;4(6):489-94.
- Nissen SE, Wolski KE, Prcela L, et al. Effect of Naltrexone-Bupropion on Major Adverse Cardiovascular Events in Overweight and Obese Patients With Cardiovascular Risk Factors: A Randomized Clinical Trial. JAMA. 2016;315(10):990-1004.
- Sarwer DB, Steffen KJ. Quality of life, body image and sexual functioning in bariatric surgery patients. Eur Eat Disord Rev 2015; 23: 504–508.
- Steffen KJ, King WC, White GE, et al. Sexual functioning of men and women with severe obesity before bariatric surgery. Surg Obes Relat Dis 2017; 13: 334–343.
- Sarwer DB, Spitzer JC, Wadden TA, et al. Changes in sexual functioning and sex hormone levels in women following bariatric surgery. JAMA Surg 2014; 149: 26–33.
- Sarwer DB, Lavery M, Spitzer JC. A review of the relationships between extreme obesity, quality of life, and sexual function. Obes Surg 2012; 22: 668–676.
- Patel K, Allen S, Haque MN, Angelescu I, Baumeister D, Tracy DK. Bupropion: a systematic review and meta‐analysis of effectiveness as an antidepressant. Ther Adv Psychopharmacol 2016; 6: 99–144.
- Gardner EA, Johnson JA. Bupropion: an antidepressant without sexual pathophysiological action. J Clin Psychopharmacol 1985; 5: 24–9.
- Walker PW, Cole JO, Gardner EA, et al. Improvement in fluoxetine-associated sexual dysfunction in patients switched to bupropion. J Clin Psychiatry 1993; 54: 459–65.
- Labbate LA, Pollack MH. Treatment of fluoxetine-induced sexual dysfunction with bupropion: a case report. Ann Clin Psychiatry 1994; 6: 13–5.
- Halseth A, Shan K, Gilder K, Malone M, Acevedo L, Fujioka K. Quality of life, binge eating and sexual function in participants treated for obesity with sustained release naltrexone/bupropion. Obes Sci Pract. 2018;4(2):141–152. Published 2018 Feb 23. doi:10.1002/osp4.156.
- Christou GA, Kiortsis DN. The efficacy and safety of the naltrexone/bupropion combination for the treatment of obesity: an update. Hormones (Athens). 2015;14(3):370-5.
- Yanovski SZ, Yanovski JA. Naltrexone extended-release plus bupropion extended-release for treatment of obesity. JAMA. 2015;313(12):1213–1214. doi:10.1001/jama.2015.1617.
- Sherman MM, Ungureanu S, Rey JA. Naltrexone/Bupropion ER (Contrave): Newly Approved Treatment Option for Chronic Weight Management in Obese Adults. P T. 2016;41(3):164–172.
- Toll, B. A., Leary, V., Wu, R., Salovey, P., Meandzija, B., & O’Malley, S. S. (2008). A preliminary investigation of naltrexone augmentation of bupropion to stop smoking with less weight gain. Addictive Behaviors, 33, 173-179. doi:10.1016/j.addbeh.2007.05.012.
- Mooney ME, Schmitz JM, Allen S, et al. Bupropion and naltrexone for smoking cessation: A double-blind randomized placebo-controlled clinical trial. Clin Pharmacol Ther. 2016;100(4):344-52.
- Pacek LR, Mcclernon FJ, Bosworth HB. Adherence to Pharmacological Smoking Cessation Interventions: A Literature Review and Synthesis of Correlates and Barriers. Nicotine Tob Res. 2018;20(10):1163-1172.
- Available from https://clinicaltrials.gov/ct2/show/results/NCT00129246?view=results.
- Wilcox CS, Oskooilar N, Erickson JS, Billes SK, Katz BB, Tollefson G, et al. An open‐label study of naltrexone and bupropion combination therapy for smoking cessation in overweight and obese subjects. Addictive Behaviors 2010;35(3):229‐34.