The Sleep Peptide Nobody Can Explain

[00:00:00]Quick question before we start. How did you sleep last night? And maybe more importantly, how do you know? Are you basing this on how you feel, how long you were physically in bed, or maybe the last time you remember looking at the clock before your alarm went off? And how do you know your brain did the deep, slow delta wave thing it's supposed to do down there in the dark, the part you have zero memory and zero control over?

[00:00:21]Drop your answer in the comments down below. Because honestly, we don't really know. We just guess every morning. But what if you could just reach down inside of that black box from the outside with one molecule mailed to your door and plug in that deep potentially missing piece? So today we're diving into DIP, aka delta sleepind inducing peptide. And it's the exact peptide making that promise. And just like inception, there are layers to this story. So today we're diving deep into the dream. But before we hook up our IVs and drift off, I've got a request for you guys. If you haven't done it yet, please take a quick moment to like this video and subscribe.

[00:00:59]It takes just a moment of your time. It cost you nothing. And when you do that, it tells YouTube that this video is worth showing to the next insomniac at 2 a.m. Okay, so what is DIP? Well, DIP is a peptide, specifically a noneptide, which means nine amino acids all strung in a line. We're talking tryptophan, alanine, glycine, glycine, aspartic acid, alanine, serarine, glycine, and glutamate. And if you want to sound smart at a longevity dinner, the official drug name, or at least the one the FDA uses, is Emma Deltide. And remember that word because it's going to matter whenever we get to the government part. It weighs about 849 dottons. And I know most normal people don't have a gut feel for dolins. So let's put it on the scale that we always use. A quick reminder over here, we've got simaglutide, aka ompic, and it's a giant at over 4,000 doltons. BPC-157, the one that everyone's injecting into their soft tissue for injuries, is about 1,419.

[00:01:53]Then DIP slots in down here at around 849, which is bigger than KPV at 342 and bigger than epitalon at 390 from our last video. But it's still a small, simple, and easy to make little molecule. But easy to synthesize does not mean easy to understand. It turns out that a molecule a sophomore OEM student can build is biologically a riddle that nobody has solved in 50 years. A smart sophomore that is. I barely made it out of organic chemistry alive. So, how did we end up with a sleep peptide who built this dream world we're about to walk into? Well, it all started with two guys from Basil, Switzerland back in the 1960s, Marcel Manet and Guido Shawnberger. And they were working on one of the oldest, weirdest ideas in sleep science, that sleep might be a chemical. And the experiment that they designed to prove it was wild. First, they took a rabbit.

[00:02:41]Then they put a tiny electrode deep in its brain in a sleepreated part of the phalamus and they stimulated it at a low frequency until the rabbit drifted off into a sleep-like state. Then they collected the blood that came out of that sleeping rabbit's brain, filtered it down, and then mainlined it into a second wide awake rabbit, and the second rabbit got sleepy. We're talking sleep in a syringe transferred from one animal to another. And over about a decade, they chased that activity down to a single peptide, sequenced it, synthesized it, and in 1977, they published it, and gave it a name straight out of an EEG readout, delta sleep inducing peptide. Now, delta waves are the big slow rollers your brain makes in the deepest stage of sleep. So, our boys Marcel and Guido decided to name the molecule after the dream that it was supposed to produce. Ronic, we need to develop goth girl sleep peptide.

[00:03:33]You got to name it after the dreams you want to have. If only you could see my IG real algo for him.

[00:03:39]>> It's a beautiful origin story. A lone obsessive idea chased for 10 years captured in a bottle. But when they went looking the next layer down, there wasn't anything there. Now in Inception, the deepest layer is called limbo, unstructured dream space. You go down far enough and there's nothing built, no architecture, just raw formless subconscious. And you can get lost down there for what feels like 50 years.

[00:04:03]Well, turns out that's also a great description of DIP's mechanism section.

[00:04:08]Welcome to limbo. Because here's the problem. For most hormones and signaling molecules in your body, we can tell you the full story. Here's the gene that codes for it. Here's the bigger protein that it gets cut out of. And here's the specific receptor it locks into, like a key and a lock. Cause effect. Done. Now, this isn't true for everything. For example, we still have no idea how BPC57 works, and we have no idea if it even has a receptor. But when it comes to DIP, even now, 50 years later, we still haven't even figured out the gene that makes it. We haven't nailed down the precursor protein it's supposed to come from, and we still haven't found a specific decent receptor. So, we built a sleep drug, named it after brain waves, ran it into human veins, and we can't even prove that your body makes it naturally. And again, to be fair, none of the drugs that we use for blood pressure, cholesterol, or heck, even chemical sleep aids like ambient are found naturally. But that's something you have to know when we're talking about decent. Is it a peptide?

[00:05:08]Absolutely. But is it natural? Uh, we don't know. Now, for those of you that are already starting to fall asleep and can't stand to hear another word about DIP's mechanistic mystery, go ahead and skip to our protocol section at the timestamp down below. But hit that like button before you go. And if you stick with me for 90 seconds, I'll give you the actual leads. Because although we don't know the mechanism, doesn't mean we don't know what's happening. We've basically got a pile of clues, but no confession. And here they are. Clue one is the pineal gland. Dip nudges an enzyme in the pineal gland, aka the gland in charge of your circadian rhythm, through an adinuric pathway, which is the same wiring your fight orflight system uses. So there's a real circadium clock adjacent fingerprint.

[00:05:54]demonstrated in rats. Clue two are your own opioids. Now, don't panic. DIP doesn't plug into opioid receptors itself, but in brain stem tissue, it triggers the release of MET and which is one of your body's homemade opioids. And some experiments showed that administering the anti-opioid medication nlloxxone actually blunted animals response to DIP. That's the thread that people pulled on for the withdrawal studies that we'll get to later. Include three are the excitatory and calming channels known as the NMDA and GABA systems which are basically the volume knobs for your nervous system. DIP seems to fiddle with both mostly in stroke and seizure models in rats. Always in rats.

[00:06:32]And then there's a fourth thing that's honestly the strangest and it breaks the whole more is better instinct that most of us have when thinking about these types of compounds. If we're looking at a graph and we're looking at drugs effect versus dose trend, it usually looks more like a straight line before eventually leveling out, which means more dose, more effect up to a point.

[00:06:52]But dip is super weird. A little does a lot, but more does less. You can easily overshoot it or inception terms, you can go too deep. And put a pin in that, too, because it makes the dosing section a minefield. Now, before we leave the biology section of this, we have to cover the single weirdest thing about how this molecule behaves once it's in you. In the bloodstream, DIP is actually gone in about 2 to 4 minutes. Your enzymes shred it almost instantly. But old human reports describe effects that take about an hour to kick in and then linger for up to 20 hours. 2 minutes in the blood, 20 hours of effect. That math does not math. It's like the slow motion van falling off the bridge in Inception.

[00:07:34]what only takes 5 seconds up top feels like an eternity down in the dream. Now, to be fair, we do see similar patterns with other proteins and peptides. For example, the circulating half-life of human growth hormone is only about 10 to 30 minutes because it exerts its effect by boosting IGF-1, which has a half-life of 15 hours. So, its effects are felt much longer than its own short half-life. Remember when I said that dip triggers the release of natural opioids like met and keylin? Now, moving on to our evidence ladder. Where on the ladder does the data supporting DIP actually stand? Just a quick reminder, at the top rung, we've got big randomized controlled human trials, aka the gold standard. Meanwhile, at the bottom rungs, we've got a dish on a bench, a mouse, and a guy on Reddit. Now, due to DIP's origin story in rabbits, its benchtop and animal data kind of get mushed together. After DIP was isolated, researchers started to simultaneously explore its effects in animals outside of just rabbits. while later working to unravel its origins using benchtop experiments. And the animal data is broad. Rabbits get more of those slow delta and spindle waves. Cats, and this is the fun part, cats didn't do the deep sleep thing cuz they never really do.

[00:08:45]They actually got more rim sleep, which is the dreaming stage. Same molecule, different species, different sleep. Rats showed more slowwave sleep and a bump in growth hormone. And a 2021 rat study dripped dip up the nose before inducing a stroke. And the stroke damage didn't meanly shrink by a statistically significant amount, but the rat's motor recovery on a little rotating treadmill did improve. That is really interesting.

[00:09:10]It is also, every word of it, in animals. Now for the part you actually came for, the data in humans. And here's the honest headline. The human data on DIP is small, old, and it's mixed. And most of it is from the 1980s before modern trial standards even existed.

[00:09:26]Now, some of the earliest human studies mostly came from the same Swiss group that discovered it. They ran dies into the veins of insomniacs and reported their sleep normalizing, sometimes after just a few sessions. Now, this is encouraging, but these studies were also open label and performed by the same people who discovered the molecule. And once better controlled studies showed up, the air started to leak out of the DIP bubble. A 1987 crossover study in chronic insomniacs concluded the improvement was of little clinical significance. And the most rigorous trial we have is a 1992 double blind study looking at 16 chronic insomniacs with a real placebo control. And it found yes technically sleep efficiency was a bit higher and people fell asleep a little faster on DIP, but the effect was weak. The trial was small and it might have been partly due to the placebo group drifting. People didn't even subjectively report that their sleep felt better. And the author's own conclusion was that short-term desip was quote not likely to be a major therapeutic benefit. That's the strongest human sleep study on this peptide. And its conclusion is basically a meh. And outside of sleep, things get even thinner. A couple of open uncontrolled series from the 80s and an open opioid detox trial in the '90s looked at DIP as a potential treatment to help with withdrawal from alcohol and opioids. But these had no real control group. There was a pilot study in seven people looking at its application of chronic pain and there is a single case report looking at its effects in a one patient with narcolepsy. So where does that leave us on our ladder here? Well, almost everything we just covered either lives in a dish in a mouse or in a handful of tiny old mostly uncontrolled human studies. The promise we read about in biohacking forums is somewhere up here in a Manhattan level high-rise. But the level of proof that we have is down here still living in its mom's basement.

[00:11:16]Quick break from the existential dread.

[00:11:17]If you too want to advertise your hobby of using your own body as a vehicle for unsanctioned experimentation, Lab Rat Legion merch is down in the description.

[00:11:26]Is it good? Surprisingly, yes. Can we handle a return if it doesn't fit?

[00:11:30]Absolutely not. We are a YouTube channel run by a urologist and a hostage.

[00:11:35]>> Silence. Back to DIP. If the human evidence shrugs, how did DIP end up as a vial in a bubble mailer on your porch?

[00:11:43]Well, it's the usual pipeline. A molecule with a great story and relatively thin data gets discovered by Reddit gets name dropped on a few podcasts and suddenly research use only suppliers are shipping it next to their gray market reatride. Now there is one real regulated product out there and it's worth knowing about. In Russia there is an approved drug called Deltaran which is DIIP. It's a nasal spray dosed at 0.3 milligrams an ampule and it's officially approved for alcohol withdrawal and stress states but not insomnia. Interestingly enough, the one place on Earth where DIP is an actual approved medicine, it's not approved for sleep. Meanwhile, the gray market has settled into its own insane routines.

[00:12:22]Which brings us to dosing.

[00:12:24]Disclaimer to the FBI field office. This is not a how-to. I am not telling you to buy this, reconstitute it, or stick it in your stomach before bed. I'm just telling you what the literature and the market actually describe. I am not your doctor. Well, I mean, I am a doctor, just not yours, probably. Now, there is a real mismatch here between what was studied and what's being done right now in the real world. Every controlled human study that matters used one route and one weight-based dosing paradigm.

[00:12:50]Deit was administered through an IV slowly at about 21 micrograms per kilo, aka about a milligram and a half for a 70 kilo adult with a slow push that the researchers said was essential. And now the gray market is doing a fraction of that under the skin or up the nose at home. We have a different route, a different dose, and different everything. All extrapolated from Russian deltaran dosing and IV studies that themselves barely cleared the bar.

[00:13:15]And remember that U-shaped curve from earlier? We know that more is not better when it comes to desip. It may actually be worse. So, the just double it and see if it works instinct just doesn't work here. And again, not that I'm endorsing any of this. I'm describing the forest, not telling you to go camping. Ronic, run the disclaimer.

[00:13:34]So, is decent dangerous? Well, the honest answer is we haven't seen evidence of that and we mostly don't know. But not knowing itself is kind of its own risk. Now, the good news, such as it is, is that the old IV studies reported that it was well tolerated with that slow injection. A few people had headaches, but no fireworks. Now, some regulators have raised the spectre of potential immune system reactions to compounded desip, but per my latest review of the literature, that concern seems to be purely theoretical. much like growth hormone and BBC57 and their cancer risk. But don't get me started on that. If you want that rant, the video's up here. Now, if we look at the one real label out there, the Russian one, it is worth noting that pregnancy, breastfeeding, and being younger than 18 are considered contraindications, and caution is advised to patients with a very slow heart rate. All right, now we get to get into the current regulatory mess that DIP finds itself in here in the United States. Now, DIP used to be eligible for compounding here in the US until it was ripped off the shelves by the Biden FDA in 2023 for apparently no reason, but now our current FDA has taken a batch of 12 peptides out of the regulatory penalty box, which is a list called category 2, and is considering putting them back in the game. DIP under its government name, Emadeltide, is on that list. Seven of those 12 peptides, including DIP, get a hearing on July 23rd and 24th later this year. DIP is on day two, July 24th, sharing the bill with two peptides we've also covered, CAX and Epalon. Same hearing, same docket. Links to both those videos are up here or down there somewhere. And if Ronic forgets to drop them down there, I give you permission to harass him in the comments. Now, the committee evaluating these compounds is called the PCAC, aka the pharmacy compounding advisory committee. But there are some things that you need to understand for this whole process to make sense. Number one, this committee is considered independent from the FDA itself and its advisory only. It considers the available data, votes regarding what their recommendation to the FDA should be, but the vote does not bind the FDA. Now, they usually go along with it, but usually is not always. Number two, although these compounds have already been pulled out of the category 2 penalty box, that is not the same as being widely legal to compound. In order for that to be the case, the PCAC would need to recommend that the FDA formally put it back into category one and then the FDA would have to follow that recommendation. Right now, DIP is still in regulatory limbo. It's out of the penalty box, but it's kind of stuck on the bench. It isn't in the field yet.

[00:15:59]And number three, it's worth knowing that the uses the FD is actually reviewing for DEIP are opioid withdrawal, chronic insomnia, and narcolepsy. the exact three buckets where the old foreign literature is the thickest but modern evidence is the thinnest. So if you've got a real documented experience or if you just suffer from insomnia and you want access to DIP or any of these other peptides, please share that. It makes a bigger difference than you think. But make sure to comment on our video first before you click over there. Okay, Dr. Hat all the way on. What do I actually think about DIP? First, I think we need to stop thinking about Dip like ambient. It's not a sedative. Nothing in the human record describes a molecule that drops you in 20 minutes. Dip seems to behave more like a slow nudge to your sleep system and your body clock than a hammer to your consciousness. A chronobiologic much like melatonin but not a knockout.

[00:16:47]Second is that I can't really do the Cax thing here. With CAX, I was able to give it credit with a real world track record of over 30 years of approved use in Russia that, you know, fair is fair beats a lot of internet peptides. Dip kind of has that, but not for the indication that most people are interested in using it for. And third is where we cash in on our top from the start of the video. You all know the end of Inception. Cobb finally makes it home. He spins his totem, the little top that he keeps with him to figure out whether or not he's in reality or still dreaming. If it topples, he's awake. But if it keeps spinning forever, he's in a dream. And then he walks away from it to go hug his kids. And then Nolan cuts to black. The top is still spinning and we never see it fall. And that uncertainty is kind of where we stand on DIP. The most rigorous study we have spun the top and we saw a wobble, but the camera cut away before we could see whether or not it falls. The effect was there, but it was weak. We honestly just need more data. So, here's my actual verdict. If you're an adult with a genuinely wrecked sleep system, gray market dip should not be the first thing you reach for.

[00:17:52]Rather, you need to focus on the basics.

[00:17:54]Stick with a consistent schedule for both falling asleep and waking up.

[00:17:58]Expose yourself to sunlight, but avoid screens at night. Sleep in a dark, cold room. lay off the alcohol and make sure you've ruled out sleep apnnea as a confounding factor. And then if you've done all of that and you're still interested in DIP, go make a comment on the upcoming hearing. Why? Because we'll never get the data we need to make a decision about DIP until we have widespread access to it. And that won't happen unless the PCAC gives it the green flag. So if you're interested, go make your voice heard. Now, if you found this video useful, maybe toss this video a like. Subscribe if you love science and databacked tools to improve your life. And check out our other peptide videos. We have now officially covered each of the seven peptides up for consideration this coming July. And until next time, guys, I'm Dr. Alex.

[00:18:42]Stay curious, stay skeptical, and as always, proceed accordingly.