Contrave Guide

How Contrave Works

Bupropion stimulates hypothalamic pro-opiomelanocortin (POMC) neurons, which release alpha-MSH to reduce appetite, but POMC neurons also release beta-endorphin, which feeds back onto mu-opioid receptors on the POMC neurons themselves and shuts them off — limiting the appetite-suppressing effect. Naltrexone, by blocking those mu-opioid receptors, disables that auto-inhibitory feedback loop and allows bupropion's POMC activation to persist longer and more strongly. The two agents together also modulate the mesolimbic dopamine reward circuit (ventral tegmental area to nucleus accumbens), which is thought to reduce food cravings and the hedonic drive to eat palatable foods.^[2]

Dosing Schedule

Contrave uses a gradual dose escalation to minimize side effects. Always follow your prescriber's guidance and the current FDA label^[1].

Side Effects

Clinical Trial Results

“

Contrave's FDA approval was supported by four pivotal 56-week phase 3 trials in the Contrave Obesity Research (COR) program. COR-I (Greenway FL et al., Lancet 2010, PMID 20673995; N=1,742 adults at BMI 30-45, or BMI 27-45 alongside dyslipidemia or hypertension) put mean weight loss at 6.1% on the naltrexone SR 32 mg with bupropion SR 360 mg combination, against 1.3% on placebo, and 48% of patients on the maintenance dose lost ≥5% body weight vs 16% on placebo. COR-II (Apovian CM et al., Obesity 2013, PMID 23408728; N=1,496) confirmed the COR-I efficacy in a second randomized trial of the 32/360 mg dose, with mean weight loss of 6.4% versus 1.2% placebo and 50.5% achieving ≥5% loss versus 17.1%. COR-Diabetes (Hollander P et al., Diabetes Care 2013, PMID 24144653; N=505 adults with type 2 diabetes) showed 5.0% weight loss vs 1.8% placebo plus a 0.6 percentage-point greater HbA1c reduction at 56 weeks. COR-BMOD (Wadden TA et al., Obesity 2011, PMID 20559296; N=793) tested Contrave layered onto an intensive behavior-modification program and produced 9.3% weight loss vs 5.1% with placebo plus behavior modification — the largest absolute weight-loss effect in the COR program, attributable to the added behavioral arm. Across all four trials, placebo-subtracted weight loss was approximately 4-5% body weight, substantially below the 11-15% placebo-subtracted weight loss seen in modern GLP-1 trials (STEP-1, SURMOUNT-1).^[2]

Where to Get Contrave

Sellers in our register that will dispense naltrexone hydrochloride / bupropion hydrochloride, or a compounded version of it, after an online consultation — shipped to your door.

What each seller in the register charges to start on a compounded GLP-1, cheapest at the top. Compounded naltrexone hydrochloride / bupropion hydrochloride from licensed 503A and 503B pharmacies is legal under federal compounding law^[3], and the rules have historically loosened further for any molecule sitting on the FDA Drug Shortage List^[4]. An FSA or HSA will generally cover either kind of prescription, compounded or branded, under IRS Publication 502^[5]. What you actually pay moves with your dose and with whatever promotion happens to be running.

Contrave Head-to-Head Comparisons

Short verdict pages setting Contrave against the other GLP-1 options, working from the trial results, the dose ladders on each label, and what the manufacturers charge today.

See all drug-vs-drug verdicts.

Frequently Asked Questions