Contrave: a new kid on the weight loss medication block?

What’s new on the weight-loss medication market?

My last blog and video on Ozempic and its use in weight-loss was a big hit! I certainly appreciate all the wonderful comments letting me know that I did a great job explaining how the drug works! My mommy will be proud to know that my decade of University and pharmacist training was totally worth the three pieces of paper I have hanging in my office and the mortgage-sized debt. Maybe the University of Alberta will name a classroom or a bench after me someday? I think that would be kinda cool.

I digress. Ozempic isn’t the only weight-loss medication on the block. Today, I want to talk about Contrave! The new but old kid on the block. What do I mean by that? Well, the medication known as Contrave is newish to the market, especially the Canadian market, but it is made up of two older medications that have both been around for some time! The first component is Bupropion, or some of you may know it as Wellbutrin for depression and Zyban as a quit smoking aid. The other component is naltrexone or Revia. A few geniuses in our world realized that bupropion and naltrexone on their own lead to some weight-loss, and they thought, “Well, if one is good. More is better?” They were right! When the two were combined, a greater amount of weight-loss was observed than either agent alone. Hopefully, someone got a promotion or at least a raise! 

What is Bupropion?

Bupropion is a norepinephrine (NE) and dopamine (DA) reuptake inhibitor. NE and DA are neurotransmitters (substances that send signals between neurons) found in the brain, and they help us regulate our mood, concentration, energy levels, etc. So, bupropion is like a plug and prevents NE and DA from being removed from the space between neurons, increasing their concentration and, accordingly, their activity!

NE helps with attention, focus, concentration, and energy levels. DA, on the other hand, is often referred to as our reward hormone. It gets released when your parents give you an “atta boy” for not flunking out of college, when you crave good food, when you have sex, or when you do anything that makes you feel good. Part of its role is to signal to our brain, “HEY! DO THAT AGAIN! THAT FELT GOOD!” Thus the behaviour is likely to be repeated. Think Pavlov’s dog. And, before you ask, yes, humans are as simple and reward-driven as animals. DA also helps with attention, memory, motivation and can even help with movement.

You can probably see the role that bupropion plays in managing our mood and maybe our food-seeking and eating behaviours. It can help decrease our wanting and drive for food, but also it may help with attention to and motivation for changing our patterns and behaviours! Bupropion does come in different formulations: IR (immediate-release), XL (extended-release)–this is Wellbutrin, and SR (sustained-release)–this is Zyban. SR is the formulation found in Contrave. Each formulation differs in how long it lasts in the body, with XL being the longest lasting.

What is Naltrexone?

Maybe you have heard about the opioid crisis? And, how paramedics, firefighters, and police officers use Naloxone to resuscitate individuals that have overdosed on opioids? Naltrexone is a sister drug to Naloxone. It is an opioid antagonist. Kind of like how Darth Vadar was an antagonist for Luke Skywalker?! Naltrexone blocks or opposes opioids at the opioid receptor in our bodies, except in a less father-son, lightsabering your head off kind of way. I have been waiting for the opportunity to insert a Star Wars analogy into one of my blog posts, so this is an exciting day! Anyways, what do opioids and Darth Vader have to do with weight loss and Obesity?

Well, our bodies naturally produce endogenous opioids or endorphins. Those crazy people addicted to running and the runner’s high are just getting hopped up on their own personally created opioids! When it comes to food and eating – our opioid receptors are involved in our liking of food. When you finally get to eat that glorious pizza, your opioid receptors play a role in how much you like that said pizza.

Fun fact: our endocannabinoid receptors also play a role in our food liking, so our bodies also produce endogenous cannabinoids. Anyone that has hung out with Mary Jane, experienced the munchies, and ended up crushing an entire box of Chips Ahoy cookies and no-name gummies from your friend’s pantry while they were sleeping might know what I’m talking about. No? Ya, me neither…

When Naltrexone comes along and blocks your opioid receptors, it will decrease our liking of food. Then when you have that pizza, it might not be as glorious as you remembered. Therefore, you might not crave or want that said pizza as much next time around.

I should mention that Naltrexone is also used to manage the cravings from Alcohol Use Disorder too!

What about Naltrexone and Bupropion together?

As I mentioned, there is some evidence to show that Naltrexone and Bupropion used separately can lead to weight-loss of ~1.2% and ~2.7%, respectively. However, when we combine the two, there seems to be a synergistic effect. Meaning, we see an even greater weight-loss (~5.4% from baseline) when the two are used together compared to either agent alone! Neat, right? Now all the intricacies as to how the two help us manage our weight are not entirely clear. We know what I described above plays a role. However, there may be another mechanism at play with action in our hypothalamus (appetite regulatory center) and our mesolimbic dopamine circuit (reward center).

Specifically, Bupropion seems to activate the Pro-opiomelanocortin (POMC) neurons in the hypothalamus of the brain, and Naltrexone seems to reinforce Bupropion’s activity of these neurons. When these neurons are activated, it leads to a reduction in appetite and an increase in energy output. In practice, my clients have noted a reduction in appetite and the ability to be more mindful. I believe this reduction in appetite is allowing for an increase in executive functioning. Or the part of your brain that helps you to choose the apple or the apple pie!

A number of studies have been done in a few different populations demonstrating the weight-loss benefit of Contrave. In a study by Wadden and friends, they used Contrave in conjunction with an intensive diet, exercise, and behaviour therapy program – which, in some respects, is similar to what our team at Healthcare Evolution provides. Wadden et al. found an 11.5% vs. 7.3% reduction in weight from baseline with Contrave and Placebo, respectively. This data was from all the individuals that completed their entire 56-week study! So, not only is intensive behaviour modification important and effective, when we add Contrave we get even better results. Now, it is not as wonderful as what was seen with Ozempic, but it is still impressive nonetheless!

Final Points

I know, I know this is a longer blog. So congrats if you are still with me at this point. I like writing, and sometimes I get a little carried away! As per some learnings from my last blog and Youtube video on Ozempic, I do want to mention a few final points.

First, side effects! Nausea is the main one. However, some people did note constipation, dry mouth, sweating, diarrhea, and headache. Most of these are short-lived and resolve once your body gets used to the medication, and that is also the reason we take it nice and slow in getting you up to the target dose of 4 tablets daily – 2 tablets twice a day (360/32mg total Bupropion/Naltrexone).

Other important mentions: if you are taking opioids or have a history of seizures, this medication is “No Bueno.” Other than that, it is an effective medication in Obesity management, even more so if you have a concurrent mood disorder such as depression. I have had some patients who had great success on it and have even added it to their regimen with Ozempic or Saxenda. There are lots of possibilities, and the future of this Obesity medicine has an exciting outlook! As always, if you think this medication might be a good fit for you, chat with your care team! 

Before I leave you, I wanted to ask: do you like blogs where I talk about drugs? Are there other topics you want to hear? Let me know via email at! Until then, stay awesome, my friends!


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