Why This Antidepressant Cancer Discovery Might Be Dangerous

An antidepressant that kills cancer? Here's what the biology actually shows before you try it.

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Episode Description:

There’s a claim spreading fast:

An old, cheap antidepressant can "kill cancer".

It targets a real cancer protein.
There’s a real research paper behind it.
It’s already FDA approved. 

So… what’s the catch? 

Before you run out and start taking an off-label antidepressant, there’s one very simple question that changes everything. 

In our newest post and video, Dr. Chaplin follows the biology all the way through — not the Facebook version, not the meme version — the actual data. 

Because sometimes the most important part of a study is what can’t happen inside the human body. 

If you’ve seen this claim circulating, this one is worth your time.

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info@elevatingcancertreatment.com

https://elevatingcancertreatment.com

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Disclaimer:
The information provided in this podcast is for educational and informational purposes only, and does not constitute medical advice. It is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have heard or read in this podcast or on this channel.
Reliance on any information provided by Dr. Jay Chaplin or Elevating Cancer Treatment is solely at your own risk. Dr. Jay Chaplin is a scientist and drug developer, not a medical doctor providing patient care. The content presented here reflects general scientific understanding and research, and may not be applicable to your individual health circumstances. Individual medical conditions and treatments vary, and no two situations are exactly alike.
Always consult with your personal healthcare provider before making any decisions about your health or treatment plan.

Transcript

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If you have cancer, a claim like this one is really hard to ignore. An old, familiar, cheap, generic antidepressant supposedly targets cancer growth and kills tumors. Like that. This starts with a real cancer protein, a really good research paper, which you know I'm excited about, and it's FDA approved. Alright, great. The problem is what happens when you ask one very simple question. Does this actually work in the human body? Before you decide what to think, and before you run out and start taking off-label antidepressants, we need to follow the biology. Hello and welcome to Elevating Cancer Treatment, where we explain the science and debunk myths to help you navigate your health journey. My background is a little different. Beyond educating about cancer, I'm actually designing new drugs that are defining the future of oncology. This direct hands-on experience offers me a very different perspective of how these cancer treatments work on the body, interact with the cancer cells, and cause side effects. And these are insights that I'm excited to share with you. If that sounds interesting, make sure to like this video, subscribe to the channel, and hit that notification bell so you never miss an update. And please share it if you find it useful. I'm Dr. Jay Chaplin. An important reminder, I'm a PhD, not an MD. The information in this video is education and it's not medical advice. Every cancer is unique and no general information applies to everyone. Please remember that. Always consult with your healthcare provider for guidance on your specific situation. And two quick things. First, as a thank you for being here, I've created a free resource, 10 things to Elevate Your Chemo Journey, which you can download from the link below. And second, by signing up, you'll also get updates on that innovative cancer treatment I'm working on. I'm confident it represents a significant advancement in immunotherapy. So please take a moment, download your free guide, and join us in shaping the future of cancer treatment. So, this video is for you if you've seen posts claiming an old antidepressant suppresses or kills cancer. Two, you're curious about repurposed drugs but don't want to hurt yourself. Three, you've wondered if it really works, why isn't my oncologist using it? Or four, you just want the actual biology, not some detail-free Facebook summary with a big splashy, colorful meme. So let us know down in the comments which one of these best describes you. Now, as we go through this, I want you to be thinking about your specific cancer type, because that detail matters more often than most people realize. First part, where does this claim even come from? So there's a protein called NED4, NEDD4. In most cancers, NED4 is overexpressed, and its activity helps drive cancer growth and survival. This is not something that you'd likely see on a biomarker test, as it usually isn't mutated, it's just overexpressed. Something upstream of it will be mutated, it'll be always on, and that will drive the upregulation of NED4, coming from other growth factors. So, in theory, if we could suppress NED4 or turn it off, we could probably slow tumor progression, maybe kill it. That part is real, it's very solid biology. I put links down below. Now, here's where the internet takes a sharp left turn. There was a research paper and some follow-up work from a group in Spain showing that an old tricyclic antidepressant called colomopramine was useful as a research tool in suppressing NED4 activity. It squashed it down. That should be useful for cancer. Very exciting. And Facebook did what Facebook does best. It skipped about 12 steps in the middle and landed on this clickbait. Old antidepressant kills cancer. That's what I was seeing. Let's dig into the details because the details, as always, matter, and they matter a lot. Clomopramine, also known as anaphenil, is a tricyclic antidepressant. It's from before the Prozac era. It's old, known for having significant side effects. Some of them a big deal. Dry mouth, dizziness, drowsiness, constipation, nausea, tremors, weight gain, sexual dysfunction, seizures, heart rhythm issues, urinary retention, that can lead to BTIs, severe confusion and worsening mood, or suicidal ideation, wanting to kill yourself. And if that isn't enough, here's another critical detail that gets left out. Clomapramine itself doesn't inhibit NED-4. That's been shown. The compound that actually showed activity in that study was a breakdown product called norclomapramine. In other words, you're not even taking the active compound if you take that antidepressant. You're taking something that partially turns into it. You can't just measure the input. You can't just measure the size of a clomapramine pill and know that you're there. That would be too easy and probably inaccurate. That's like trying to measure the amount of clay needed in buckets or gallons to build a brick house. It's way easier to measure the bricks needed after you've converted them from clay to bricks. Already this should raise a few eyebrows because it's a little wonky. But get prepared because I'm gonna do the math with you. So, to generate measurable amounts of norclomapramine, I'm going to assume that people would be taking the drug clomapramine at the very top end of its therapeutic window. That's where it's most likely to have those serious side effects. Already not great. So we know from these studies that norclomapramine must be at 200 micromolar concentration in order to bind to NED4 and have any anti-cancer effect. So the question is, how much norclomopramine builds up in the bloodstream with long-term dosing? More than you'd think, more than I thought. I was actually surprised by this. It turns out that norclomapramine is more stable than the drug it comes from. And it builds up to about 300 nanograms per milliliter in the bloodstream. We're going to do that math, it's just unit conversion, but it's a lot of unit conversion. So, general chemistry type stuff. That 300 nanograms per milliliter is the same as 300 micrograms per liter, which is the same as 3 times 10 to the negative 4th grams per liter. Norclomopramine is about 300 grams per mole. That gives us 1 micromolar. That's 1 200th of what we need to see an anti-cancer effect. So when we look at real patient data, people taking the maximum doses of clomopramine, the serum concentration of norclomopramine, the maximum that they can get, is about one two-hundredth of what's required to meaningfully suppress cancer growth through that NED-4 pathway. Half a percent. So let me ask you something, very directly. Would you take a drug with real neurological and cardiac side effects for half a percent of the minimum dose needed to even start working? I don't think it's a good trade-off. I know many of you are looking for anything to give you a boost on your therapy, but does that sound like a good trade-off to you? Because that's the math here, and there's really no way around it. If you've watched this channel for any length of time, you know I love a good repurposed drug and loathe a bad one. This is not a good one. And this is exactly the kind of reason that we did a video on dosages and how to calculate them and how to think about them. Here's a link right here. But it worked in the study. Isn't that exciting? Yeah, it is. It worked in cell culture. And again, if you've been watching me for a while, you have also heard me say this many times before. You know what's coming. Everything works in cell culture. You can crank up concentrations beyond anything achievable in real life, even by IV. You can remove metabolism issues, there's no liver or kidneys, so there's no breakdown or elimination of the drugs. You can ignore toxicity issues with target tissues, no heart in the dish means no dead trial patients. You can create conditions that literally cannot exist in a human body. Cell culture tells us what might be worth exploring. It does not tell us what you should put into your body. And the researchers themselves, to their credit, understood this. Their takeaway wasn't people should take this drug. It was something very different. It was, now that we have a tool compound, how do we modify it to bind NED4 better? They actually did the smart thing. They figured out how norclomopramine binds to NED4 and blocks it. Then they tried making new molecules that are similar to norclomopramine that would bind better and tighter and be better drugs for this specific system. These are not antidepressants anymore, but anti-cancer drugs. They're redesigning the drugs to be better. Those modified compounds have not entered phase 1 clinical trials yet. They haven't been tested in humans at all, they haven't even been tested in animals, they're still in the screening and optimization phase. Best case scenario, they are decades away from clinical use. I hope they do, and we can't assume that. Because assuming that is assuming they work, they're safe, and the side effect profile is tolerable. That's a lot of assumptions stacked on top of each other. Most drugs fail. So please know that I want to see more drugs like this get pushed through. I want to see more options for people. I want to see more ingenuity in this space because it really needs it. I am invested in having better solutions. Now, here's another part that nobody's mentioned yet, and it's kind of important. Not every cancer overexpresses NED4. Most do. But some cancers, pancreatic cancer and neuroblastoma in particular, actually downregulate it. That's part of their growth pathway, because they have different factors that make them grow. So if you were to suppress NED4 in pancreatic cancer, you could potentially accelerate disease progression even further, not slow it down. This is why one size fits all cancer guidance is really dangerous. What helps one cancer can dramatically backfire in another. Understanding these subtle differences, but very important ones, is one way that we help our clients wade through all the misinformation out there and get the treatment plan that is specific to them and their biomarkers. Currently, there are other things that I would suggest to a client well before this. For example, apigenin, which we covered, or curcumin. You can follow those links. So let's pull all this back together again. Can you take enough clomapramine to generate enough norclomapramine in your body, sustain those adequate blood levels, and suppress cancer growth without having massive unacceptable side effects and without risking harm in certain cancer types? No, no, no, no, no, no. No, no, across the board, you can't. This is promising research and a promising way to develop a new drug. In and of itself, this is not a treatment. Facebook is great at building interest. It is less great at accuracy, and that's being generous. Now, this really isn't about cloma premine. It's about the assumption if something could work, it must work now in its current form. That's really not true. That's not the way the world works. Most drug development is taking old things that kind of work and modifying them. Dosage matters, metabolism matters, mutation status matters, details always matter, structure matters a lot, little tweaks can dramatically improve drugs. If you want to understand what does help in the right biological context, watch these next videos right here, where I walk through evidence based strategies like aspirin and apigenin and explain when repurposed drugs actually make sense and when they don't. If this video was helpful, please like the video, subscribe for more science first breakdowns like this, and share it with anyone who might have seen this claim online. Please let us know in the comments have you seen clomapramine recommended for cancer treatment?