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In this episode, we take a deep dive into Tesofensine, a research compound that has gained attention for its potential effects on appetite regulation, weight loss, and metabolic health. We'll explore how Tesofensine works through dopamine, serotonin, and norepinephrine pathways, what the research shows, and why it was never brought to market despite promising clinical results.

We'll also discuss how Tesofensine differs from GLP-1 medications, why some GLP-1 users experience low motivation or anhedonia, and the potential role Tesofensine may play in supporting appetite control, energy, and reward signaling. As always, we'll review the science, discuss potential risks and considerations, and separate fact from hype so you can make more informed decisions about your health and wellness journey.

Topics covered:

• What Tesofensine is and how it works

• Research on weight loss and appetite suppression

• Dopamine, serotonin, and norepinephrine explained

• Why Tesofensine never reached commercialization

• Tesofensine vs. GLP-1 medications

• Anhedonia, motivation, and reward signaling

• Potential benefits, risks, and safety considerations

• Who may and may not be an appropriate candidate

This content is for educational and research purposes only. Not medical advice. Not intended to diagnose, treat, cure, or prevent any disease.

All right, welcome back, everyone.

I'm so sorry I did not get an episode out last week.

Things have been a little hectic at the West House.

Both of my children, I have a daughter and a son, they have both decided they're going to get married.

And so I was like, couldn't y' all just spread it out just a little bit?

They're a little over two years apart, and I don't know, when they were little, it never dawned on me that they would get married at the same time.

But here we are, and so we are super excited.

We love their fiance.

We cannot wait to have them officially as part of our families.

They already feel part of our.

And so we.

We just could not be more thrilled.

So we have a lot of west weddings coming up in the near future.

But because of that and the busyness with the peptique and everything else, I just ran out of time.

That's the only excuse I have is I ran out of time last week.

And I'm gonna try to get another episode out before the 4th of July.

We'll see if that actually happens, but fingers crossed that it does.

And so just bear with me.

I had a lot of people reach out to me and say I didn't get an episode this week.

What's going on?

Well, just the busyness of life.

That's what's going on.

Okay, so let's talk about today's topic.

And I've been getting a lot of questions lately about Tazofine and specifically how Tazofenzine can come alongside a glp.

And there's a lot of different ways that it can help support a glp.

And so we're going to talk about that, because when I get a lot of questions about something, that's what prompts me to really think, okay, probably need to stop and do an episode on this, because I'm getting a lot of questions on it.

So we're going to talk about how it can come alongside a GLP and compliment it, how you can use it outside of the GLP on its own, and all the good things.

So, as I always say, let's dive in.

First of all, what is Tazofenzine?

Well, it's what's known as a triple monomine, reuptake inhibitors, meaning it affects three major neurotransmitters in the brain.

Dopamine and serotonin.

And it slows the reuptake of these neurotransmitters.

So it allows them to stay active longer within the nervous system.

Okay, so let's start with dopamine and how this is impacted.

Most people think of dopamine as the brain's feel good chemical.

Okay.

And that's actually a little bit of an oversimplification because dopamine is really more of a motivation and reward transmitter neurotransmitter.

So it's involved in things like desire, anticipation, cravings, reward seeking behavior, motivation, habit formation, things like that.

So in simple terms, dipping is often what makes you want something or makes you want to do something.

So for some people, that's food.

For others, that's shopping.

For me, it's working.

I know I'm one of those weird people that love to work, but I love what I do.

So I get very motivated by work or any other rewarding behavior.

Dopamine helps drive the pursuit of that reward.

And when we talk about obesity, researchers have realized that it's not always a problem of just being physically hungry.

For many people, it's a problem of constantly thinking about food.

The planning of the next meal, the cravings of the snacks, the not knowing when to put that cheeseburger down, which, if y' all know me, you know, I love a good cheeseburger.

If I'm going to have a cheap food, that's probably going to be it.

Things like wanting dessert even when they're already full.

Like, we're all guilty of that.

But this is more of, like, people that struggle with the chronic issue of these sorts of things.

In other words, the brain's reward system can.

Can become heavily involved in the eating behavior.

So what tazofitzine does is it doesn't force your brain to make huge amounts of dopamine.

Instead, it slows down the dopamine reuptake.

So normally when dopamine is released, it sends its message, and then it's quickly pulled back into the nerve cell that released it.

So tazofenzine slows that process up.

And as a result, the dopamine, the dopamine that's already been released, stays active a little longer before it's removed.

So tazofenzine doesn't make the dopamine signal louder, it makes the signal last longer.

So I think there's some confusion surrounding this because I get questions a lot that if you are seeking that reward behavior and you have dopamine hanging around longer, wouldn't that just make you want to keep wanting more food?

And the truth is, it's the opposite, right?

Because the dopamine's Released once you are being actively involved in that reward seeking behavior.

So I eating a pint of ice cream, the dopamine's released.

And so keeping it in your system longer and allowing it to remain longer actually reduces the desire and the need to want more.

And so you're not stuck in constantly chasing that reward.

Hopefully that makes sense.

Okay, so let's talk about the next one, which is serotonin.

So how does tazofensine impact serotonin?

Well, most people have heard of serotonin in relation to mood.

And while that's certainly one of its roles, serotonin does much more than simply influence happiness.

Serotonin is involved in satiety, or the feeling of being satisfied after eating.

Mood and emotional well being, impulse control, decision making, cravings, eating behavior.

In simple terms, serotonin helps signal the brain, I've had enough, enough food, enough reward, enough stimulation.

So it's one of the systems that helps create a sense of satisfaction and contentment.

So now think about how often people continue eating after they're physically full.

Maybe it's because the food tastes really good, maybe it's stress eating, maybe it's boredom, maybe it's emotional eating.

In many cases, the issue isn't hunger.

The issue is that the brain never quite gets the message that it's satisfied.

And this is where serotonin becomes important.

Just like dopamine, serotonin is released by the nerve cells and then normally gets pulled back into those cells through a process called reuptake, like we already talked about.

But tazofenzine, like with the dopamine, it slows that reuptake process down to.

So serotonin is staying in your system longer, and that signal of satisfaction sticks around.

And over time, this can help reduce the urge to continue eating when your body's needs have already been met.

So this is one of the reasons researchers believe serotonin plays such an important role in appetite regulation and weight management.

So when, when serotonin signaling is functioning well, people often feel more satisfied and are less driven by cravings or impulse eating behaviors.

So while the dopamine can help explain the reduction in food seeking behavior and food obsession, serotonin can help explain the increase in sense of satisfaction and satiety that many people experience.

They do totally different things, but there's some crossover here as well.

Okay, so together these effects create this powerful shift in how somebody relates to food.

And so much of our struggle with food is our relationship with it, right?

How we view it, how the chemistry in our brain reacts to it all the things.

So this can really help switch this to a more healthy thought pattern.

Okay, so let's move on to norepinephrine.

So norepinephrine is sometimes called the brain's alertness and an action neurotransmitter.

It's involved in things like focus, attention, energy, motivation, alertness, reaction time, appetite regulation.

So if dopamine is involved in wanting something and serotonin is involved in feeling satisfied, norepinephrine is often involved in helping you stay awake, engaged, and mentally focused.

So think about how you feel after a great night's sleep.

You're alert, you're focused, you're productive.

You have energy to get things done.

Norepinephrine is one of the neurotransmitters helping create that state.

So just like dopamine and serotonin, norepinephrine is released and then quickly pulled back into their nerve cells through this reuptake.

And just like the others, the tezofensine slows that reuptake process down.

So this can be important because when people are dieting, one of the biggest challenges is not it's often not just hunger.

It's low energy, low motivation, mental fatigue.

Many people feel sluggish when they have reduction in calories.

Their energy drops, their focus suffers, and eventually it's harder to stay consistent.

So norepinephrine may help counter some of that.

And researchers believe increased norepinephrine signaling can contribute to appetite suppression while also helping maintain alertness and mental energy.

And this is one reason some people describe Tazofenzine very differently than GLP1s.

We're going to go into the GLP1s in more detail in a little bit.

You do have to be careful with this because this component of it can cause side effects.

People mention insomnia, feeling wired, a little bit of an increased heart rate, feeling jittery, anxiety, and sensitive individuals.

So you do definitely want to be careful in the dosing.

So you have to think about it, that a little more epinephrine signaling may help reduce appetite and improve focus, but too much may leave someone feeling overstimulated.

So when we're looking at the big picture with these three, dopamine, again, can help reduce the constant pursuit of faith, serotonin can help increase the feelings of satisfaction and satiety, and the norepinephrine can help reduce appetite while supporting energy alertness and focus.

And it's the combination of all three working together that makes Teslanzine so unique.

Rather than targeting a single pathway.

Okay, so it appears to really influence several of these major brain systems involved in the hunger, cravings and reward motivation, which is heavily tied into our eating behaviors.

Okay, so, so that's all great.

We kind of understand now its mechanisms of action, what it does, that sort of thing.

But let's talk about the what the research actually shows.

And the results were pretty impressive.

Participants taking 0.25mg for 250mcgs lost an additional 4.5% of body weight compared to the placebo.

And participants taking 0.5mg or 500mcgs lost an additional 9.2% of body weight compared to the placebo.

And participants taking 1 milligram lost an additional 10.6% of body weight compared to the placebo.

So researchers concluded that spice that 0.5 milligram or 500 mct dose had the potential to produce approximately twice the weight loss of the obesity medications available at that time.

And the research just didn't see weight loss.

They also saw meaningful reductions in appetite and follow up analysis found that tazofensine significantly improved satiety scores, meaning that participants felt fuller and more satisfied and less hungry.

And these improvements had a direct correlation with the amount of weight that people lost.

Researchers also found that tazofensine appears to work primarily by reducing food intake rather than dramatically increasing metabolism.

Although there is some increase in the energy expenditure with the norepinephrine.

So longer term extension data showed that weight loss was sustained.

Participants who continued treatment for up to 48 weeks achieved an average of total weight loss of approximately 29 to 31 pounds.

And the most common side effects it reported were dry mouth, nausea, constipation, insomnia and diarrhea.

Researchers also observed dose dependent increases in heart rate and the commonly studied 0.5 milligram dose.

The heart rate was increased by approximately 7 beats per minute.

So despite that they they did note that blood pressure generally remained unchanged of that dose.

So when we look at the totality of the evidence, the research suggests that tazofenzine is one of the most effective oral weight loss compounds study and producing roughly 9 to 11% weight loss in just 24 weeks while simultaneously reducing hunger, increasing satiety and decreasing food intake.

So here's the question, right?

If kesofensine works so well.

Why isn't it FDA approved?

The answer isn't that it didn't work.

Okay, the facts that we just went over proves that it actually did work.

The challenge was really due to a combination of safety concerns, regulatory hurdles and timing.

Because tazofensine works on dopamine, serotonin and norepinephrine regulators, it was viewed differently than medications like the glp.

So historically, several weight loss drugs that had acted on the brain neurotransmitters have been associated with these cardiovascular and psychiatric safety concerns, which made regulators extremely cautious.

In the tazofenzine trials, researchers observed modest increases, which we just mentioned, in heart rate, particularly at higher doses.

Not so much the the 0.5 milligram dose.

They weren't noted as necessarily dangerous, but they were enough to warrant additional long term safety evaluation.

And this is something that we're actually seeing with retatrue Tide.

At least that's kind of the rumor that I'm hearing that it hasn't been released yet because for those of y' all who are familiar with retatrue Tide, that is one of the common side effects is an increased heart rate.

And so I think they're kind of putting on hold until they can get some more data research to confirm that that's not a safety issue.

And that's kind of what happened here.

And at this same time, by the time tazofensine got to this point, the, the obesity treatment landscape was changing rapidly and pharmaceutical companies were shifting their focus toward these GLP1 therapies.

So it kind of just kind of fell off the radar, so to speak.

So as investment shifted toward GLPs, the interest in developing Tazofenzine just fizzled out and declined.

It wasn't abandoned because it was failed.

I think it was more of a victim of timing and some of these other things that we just went over in this research compound peptide space.

This is why it continued to generate interest nearly two decades after the original studies were published, because of how effective it can actually be.

So here begs the question, is tezofensine safe to use?

And the honest answer is we don't have a simple yes or no.

What we can say is that in the human clinical trials, tazofensine was generally well tolerated and researchers did not identify any major safety signals that stopped development.

Many participants remained on the medications for months while achieving significant weight loss without side effects.

That said, it's important to remember, just like everything else, that it is just that a research compound.

And because it influences things like dopamine, serotonin or epinephrine, it means that it not only has effects on appetite, but also on the nervous system.

So just something to keep in mind, and I mentioned this before, but I'll go over it again.

The most common side effects are dry mouth, insomnia, constipation, and headache.

I will go over my own experience with tazofensine here in a bit and I will let you know what I observed while I was taking it.

And you have to consider this increased heart rate.

Okay.

For most helping individuals, this wasn't considered dangerous, but it was enough to raise questions about long term cardiovascular risk safety, and ultimately did contribute to some of the additional regulatory hurdles surrounding this particular compound.

So when people ask whether tezofensine is safe, I think the better question is safe for whom?

And a healthy individual with no history of cardiovascular disease, uncontrolled hypertension, arrhythmias, severe anxiety, severe depression, or stimulant sensitivity, may have a very different risk profile than with someone who does have those underlying conditions.

Okay.

And so we're gonna go into a little bit more of that in just a minute.

My personal view on this is that the available research suggests that tazofensine can be a very effective tool for appetite control and weight loss, but it should also be respected.

Okay.

It's not a supplement.

It's a potent neuroactive compound that deserves the same level of consideration and caution as any medication that affects the brain and the nervous system.

So I think if you don't have any of this underlying issues, I think you know, this, this might be something that you could potentially try and be okay with.

I also think that you've heard me talk a lot about my own issues with getting my nervous system under control because I stay in a fight or flight state.

So if you're someone that's really, really struggling with that at this current point in time, I would say it may not be the best thing for you to use.

And if you struggle with insomnia, definitely say it's not the best thing to use.

And again, I'm going to go over my own experience with this, but these are some things you really, really want to consider before you start taking it.

One of the questions I often get too is can you take tazofensine when you're on an antidepressant or anti anxiety medication?

This is an area where caution is warranted because tezofensine affects dopamine, serotonin and norepinephrine so there's a potential for interactions with medications that affect those same neurotransmitters.

One important limitation is that tazofenz obesity trials, the ones we talked about, generally excluded patients taking any psychiatric medications.

So we don't really have a lot of robust human data on this to compare it to.

And so I just think it's something that you want to be very, very careful with if you are all on those medications.

And I think you have to consider what dose, if you're on super high doses of those, what that looks like as well.

As far as anti anxiety medications, I think there's a little bit less of concern.

But some people may find, like I said, that tazofenzine stimulating effects counteract that calming effect of these medications and can kind of worsen underlying anxiety.

So I wouldn't say it's a hard no, but I would definitely say do your own research.

I'm just delivering information.

I'm not a doctor.

I don't know your medical history.

I don't know what medications you're on.

I don't know how they would all interact.

I'm definitely not telling you to go out there and try this.

Definitely speak with your healthcare provider that knows your history before you would do anything like that.

I certainly wouldn't consider it just like cold turkey in lieu of any of those things either.

So you don't want to play around with that.

So I just have to get that little disclaimer.

I'm providing educational information and then you need to do your own due diligence.

I'm not suggesting you just go out and take this.

Okay, so enough for the disclaimers.

Okay, so let's move on from that.

Why would you want to take Tazofenzine, especially in the world of GLPs.

And I think there's a place for it.

I think for people who maybe don't want to go up on their dose of GLP but still want to reach their goal weight or maybe need to limit some of that speed noise, this could be a great thing to add in.

I also think for people who are taking a break on the GLP but would still like some appetite suppression, this could be a great thing to take as a substitute while you are taking a break from the glp.

I know that sometimes I like to take it situationally, so it's not something that has to build in your system.

You normally feel the impact of it right away and says oftentimes, I'll take this with me when I'm traveling or during the holidays where I'm not as active and I have more temptation around me in regards to food.

I've used this before, and it works very, very well in those situations.

But one of the main reasons I see for Tesla becoming increasingly popular is to help with glps related anhedonia.

And so this is one of the major drivers for me wanting to do this episode, to break down what tezofensine does.

So you're not just grabbing for something.

You have a basic understanding of what it actually does.

And in this world of GLPs that so many people are using, how this might come in and really help certain people that are struggling with this related side effect.

So let's dive into that a little bit.

What is anhedonia?

Anhedonia is the reduced ability to experience pleasure, excitement, motivation, or reward from things that would normally bring enjoyment.

Not everyone experiences this on a glp, but for some individuals, they report feeling emotionally flat, less motivated, or simply less interested in things they used to enjoy.

So why does this happen?

The GLPs don't appear to lower dopamine levels directly.

Instead, they seem to reduce the dopamine response to rewarding stimuli, particularly things like food.

So they make food less rewarding, and that actually is one of the reasons they work so well.

The cravings decrease, the food noise quiets down.

The constant drive towards food becomes easier to control.

So for most people, this is a tremendous benefit.

But for some individuals, the reduction in reward signaling may feel broader than just fear.

They start to feel less excitement, less anticipation.

What I hear is a lack of motivation.

And this is where tazofenzine becomes really interesting in the discussion, because unlike GLPs, tazofenzine directly affects dopamine, and dopamine is involved again in the motivation and reward.

So tezofencine may help restore some of that motivation, engagement, and reward signaling that certain individuals feel they've lost while using a glp.

And we don't have clinical data showing this, but I can tell you, with all the people that I have worked with and even myself, having experienced a little bit of this, it.

It really can help.

Okay.

And when you look at how the two compounds work, the theory really does make sense.

So GLPs appear to reduce the reward value of food.

Tazofenzine enhances some of the neurotransmitter systems involved in reward, motivation, and drive.

And so this is why a lot of people report feeling that Tazofenzine helps bring back a sense of energy, motivation, and enjoyment while still supporting appetite.

Control.

So hopefully that makes sense.

I think that this is a really important discussion, and I will talk about my own personal experience with this.

I recently started a cycle of retatrutide, and I have not taken it in a while.

I kind of rotate through.

I've did some.

I did terzepatide for a little while, and then I'm switching.

I switched over to ret, a true Tide.

And for whatever reason, it kind of hit me a little different this time.

And I don't take really high doses of a glp.

I try to stay on the lower doses.

But this time I did experience some of that.

The things that I usually.

That usually motivate me and those things, the biggest things, like I mentioned earlier, work.

I love to get up and look forward to my day and what I have on the docket and what needs to get done and how we can push things forward, and how can I talk to each and to all of you and what information I can put out there and things like going to the gym.

You know, I love going to the gym, working out, getting that sense of satisfaction that's accomplished and how it makes you feel afterwards and all the things.

And that just started to decline.

And I noticed that I just wasn't as excited anymore about those.

About those things.

And it took me a little bit to kind of figure out, like, okay, what's going on?

Like, wasn't getting out of bed as easy.

I wasn't just, you know, I wasn't pushing to start my day like I normally do.

And it hit me like, oh, my gosh, this is what people talk about when they start experiencing this.

And so I was reminded of Tazofenzine.

And look, the first time I tried Tazofenzine, I didn't like it.

It actually made me super nauseous.

And so I was like, okay, I'm not gonna do this, but you've heard me say this multiple times.

Just because you start something one time and you didn't like the impact, don't completely write it off.

Try it again.

And it may have been at that particular time that I took it.

I didn't meet it necessarily.

And I think this time I actually did, which is why I didn't experience any of that.

And so what I did experience was my motivation coming back and my desire to do the things that I love to do coming back.

And also, I think it really helps with energy.

I have definitely felt like it's helped me with my energy level, and it definitely helps with the appetite.

Again, I don't stay on a really high dose of a glp.

So I have a little bit of appetite suppression.

This kind of just obliterates the appetite.

You heard me say earlier how I've used it situationally during holidays and stuff.

And.

And so it.

It's helped in both of those scenarios.

You have to really be careful with it because you don't want too much appetite depression.

You want to make sure you're getting your nutritional intake in, you're eating enough protein and all the things, so you want to be careful with that.

But definitely crushes the appetite.

So overall, it.

I would say it's just been a really positive experience for me this time.

Side effects that I've experienced.

The first couple of nights I took it, I probably took it a little too late in the morning.

I would say this is one of those things you want to get up, and the second your feet hit the ground, you want to take it because you want it to get in your system and out of your system by the end of the day.

And so I definitely struggled with some insomnia, which y' all also know I struggle with sleep, so that was not a good thing.

I get up pretty early.

I found that if I take it right when I wake up in the morning, then I'm not struggling with sleep at night.

I have not experienced any anxiety with it.

I have definitely experienced dry mouth.

I think that's probably the biggest side effect, and I think maybe a headache here or there a couple of times.

I find that if I drink enough water and keep my hydration packets going at least once day daily, that I don't really struggle with the headaches.

It's when I skip those things that I realize I have a headache, um, and see what else.

I think that's it.

In the way of side effects dosing, a lot of people like to start with 250mcgs, which is great.

I did not have that option because at the Peptique, we only carry the 500 mcgs, and that is the recommended dose for most people.

Clinically, the data supports that.

And again, like I said, the first time I took it, I felt nauseous.

But that.

That's only happened to me one time.

And the 500 mcg dose, or half a milligram, 0.5 milligrams is very effective.

And so that's the dose that I've been on.

That's the dose that works for me.

That's the dose that I recommend.

I would not recommend going higher than that.

I guess for some people, there may be a reason for that.

But even in the research, there wasn't a huge gain between the 5, the 500mcgs and the 1mg dose.

So to me, it's like you want to stay in the lowest dose possible and still get the benefit.

And to me, it seems kind of pointless to go up that high.

I've never tried to go that high, but I don't know that I would like the way that it made me feel if I did.

So just stick with that half a milligram, 500mcg dose in regards to that.

All right.

So I think that kind of wraps this episode up, I hope.

If you are someone that's on a GLP and you're struggling with that lack of motivation, something like, you know, drive, whatever.

Even if you're not on a GLP and you're struggling with lack of motivation and drive and just feeling frustrated with that, or you don't want to do a GLP for whatever reason and you want some help with some of that food noise, this may be something that you try.

I think it's a great compound.

It's like everything else.

I think you cycle it.

I don't think that you take it, you know, forever.

I think you cycle things.

And I think this would be a good one to try it just because of the nature of it.

I would say approach it with a lot of research in your back pocket so you really fully understand it and consider your own medical history and what you may be dealing with before you just go out there and buy this and try it.

Because the key here is to be safe and careful and make sure that it's something that you're going to tolerate well.

Okay, that wraps it up.

As far as everything else, some housekeeping.

I always say this.

If you are a woman and you are interested in peptides or you wanting to learn more about peptides, you can join my free group.

It's for women only.

It's Women's Peptide Collective.

And the link is in the show notes.

I saw a comment the other day somewhere that the free pep guide I offer is hard to find you.

I say this on every episode, so I don't.

I don't think it's hard to find.

You just have to email me.

My email's in the show notes.

If for some reason I don't respond to you, it's just because I get a million emails a day.

It may got missed, it may have been in my spam, but I try to respond to those within 24 hours unless it's over the weekend, and so it shouldn't be that hard to find.

So my point is, if you want a free peptide guide, email me.

I will send it to you.

And let's see what else.

I think that might be it.

So hopefully I'll get another episode out before the 4th if I don't have a wonderful, safe 4th of July.

So, like I always say, until next time, everyone, have a blessed day.