Andrew Huberman interviews Dr Abud Bakri on the science, uses, and safety of peptides
Andrew Huberman speaks with internal medicine physician Dr Abud Bakri about peptides.
Summary
Dr. Abud Bakri, an internal medicine physician with deep expertise in peptide science, joins Andrew Huberman to cover the biology, clinical use, regulation, and safety of peptides. He explains that peptides fall into two broad categories: those with known receptors (such as the GLP-1 agonists like semaglutide and retatrutide) and those without clearly identified receptors (such as BPC-157, TB-500, and the Russian bioregulator peptides), and argues that this distinction is fundamental to understanding their effects and risks. The episode traces the history of BPC-157 from Pavlov's gastric juice experiments through Croatian research in the 1990s, and explains that while animal data is extensive and largely positive, human clinical trial data is almost entirely absent — a situation described as both scientifically troubling and practically urgent given that millions of people are already self-administering these compounds through gray-market sources. A significant portion of the conversation explores BPC-157's neuropsychiatric and gut-brain axis effects, including its apparent blunting of alcohol intoxication, prevention of withdrawal symptoms, interaction with dopaminergic signaling (including blunting of Adderall effects), anhedonia reports, and a proposed homeostatic mechanism. The conversation also covers the thymus gland and its dramatic involution with age, the Russian bioregulator peptides including pinealon (EDR) and epitalon, GHK-copper for collagen and skin, growth hormone secretagogues, and the GLP-1 drugs — including the emerging "trinity stack" of GLP-1, growth hormone secretagogue, and androgen modulation used by many high-profile figures for rapid body recomposition.
Key Takeaways
FULL TRANSCRIPT
Introduction and the Two Categories of Peptides
Andrew Huberman: Dr Abud Bakri, welcome. Good to be here. Peptides — huge topic and huge category of biology and medicine. We should start off by breaking this into categories so that people can wrap their minds around it, because that word "peptides" has come to mean stuff people buy and take and maybe should or shouldn't buy and take. But there's a lot of important and quite simple biology to understand before anyone should even be thinking about any of that. So if I just push the word "peptides" towards you, how do you carve that up in terms of thinking about it as an MD, as a clinician, and maybe also put yourself into the mind of a peptide-curious person out there?
Dr Abud Bakri: Scientifically, I would say it's one of the languages of the human body. The body uses these different languages to communicate between cells — going from DNA to RNA to proteins, which can be broken down as polypeptides and peptides. Peptides are one of these languages. Steroid hormones are another language. Peptides can be broken down further into subcategories: whether or not they have receptors, or they have no receptor. That kind of changes the clinical effects we'll see — like the GLP-1s, which have a very strong clinical effect, compared to these more obscure peptides like BPC-157, TB-500, TB-4, that don't have a clear target. They have receptors, but they just have many of them, or they don't even have receptors. We don't have a receptor identified for BPC-157 or TB-4.
Huberman: Just stopping you right there. That's a very interesting distinction. I don't think anyone else has described peptides this way. Let's take BPC-157 for the moment — we're going to talk a lot about it today. If it doesn't have a receptor, what are some ways that it could impact cells and organs? Or is it that there are receptors, we just don't know what they are?
Dr. Bakri: It could be the latter — maybe the receptor is still elusive. Or it could be that it's modifying certain proteins that already exist, or linking different proteins together in a more favorable fashion for gene transcription. The Russian peptides are all epigenetic modifiers that bind to the groove of the DNA in certain spots that either open up or close the chromatin to certain areas of genetic expression. They've modeled this out — like a steroid hormone. Steroid hormones bind to a receptor — like the androgen receptor binds DHT or testosterone, goes into the nucleus, turns on all the androgenic genes.
Huberman: Puberty is a good example of that.
Dr. Bakri: Exactly. So pinealon, for example, shuttles heat shock proteins with androgen receptors.
Huberman: So if I just pause us for a second — we should think about this word "peptides" in two major categories at least. One is: has known receptors, plural, like the GLP-1s. The other category would be: does not have known receptors, might have receptors, but can definitely impact biology in interesting ways — or so say the animal data.
Dr. Bakri: A lot of animal data.
The History and Biology of BPC-157
Huberman: All right. I know a lot of people are interested in GLP-1s and I want to go there. But because most people are probably listening to this foremost because they want to hear about the other stuff, let's start with BPC-157. What is it? What do we know about it? We'll explore safety, and what is your stance on it from the perspective of a consumer and a clinician?
Dr. Bakri: The best way to look at it is that, as humans, we've been looking for medicines in plants for thousands of years. And in the last 150 years or so, we've been looking for medicines in cells. So animal-derived versus plant-derived medicines is the way to think about it. You think about aspirin, metformin, the statins — those were all discovered in plant tissues. Statins more so in fungi, but you get the point. Now we've been looking into animal tissues to find cures, medicines, treatments. A group in Croatia in the '90s looked for this peptide called BPC — and eventually named it BPC. It's a 40,000-dalton giant peptide called BPC. BPC-157 is 15 amino acids from that giant peptide. We don't naturally make BPC-157 — that's what you'll commonly hear online. We make BPC, the big protein.
Huberman: Did this group go looking for body protection compound? For those that aren't familiar, in the laboratory you can take a tissue, grind it up, and do what's called fractionation — separating cells and tissues and liquids according to the size of different proteins, like different filters that let sand through or pebbles through or boulders through. Then you figure out what the sequences are, throw them on cells or put them into animals, and try to figure out what they do. Why were they motivated to look for what eventually became BPC?
Dr. Bakri: Pavlov — the famous scientist who did the dog experiments with the bell, making the dogs salivate — the other work he did was on gastric juices of dogs. What he'd do is put a hole in the dogs' stomachs, feed them food, get the gastric juices, and sell that as a medicine. That was part of his business. He got a Nobel Prize. So this is before BPC-157 exists. There are probably other peptides and compounds in there, but they found that gastric juices had positive effects on healing in people who had GERD and these kinds of conditions.
Huberman: Wait — so people were taking BPC in the time of Pavlov?
Dr. Bakri: They didn't know what BPC was. They were taking gastric juices from dogs for GI distress, GI discomfort. Some people were trying it for wound healing. There was a big push in this era for finding animal tissues and putting them into humans. That science fizzled out. At the same time, there's a scientist, Selye, who's coming up with the stress adaptation theory. He notices that when animals are stressed out, three things happen: their adrenals get really big so they make more cortisol, their gastric lining gets destroyed, and then their thymus gland and lymphatics shrink down. He has this published paper where you can see the clear adrenal from a stressed animal versus a non-stressed animal, a thymus from a stressed animal versus not. So this group is looking and thinking: Pavlov had this gastric juice, Selye said there was damage during stress — there must be some kind of cytoprotective or organoprotective compound in the gut. The stomach is a very rich endocrine tissue. It makes ghrelin and all these other hormones. So they're thinking there must be something else in the gut juice that protects the gut lining from further damage.
Huberman: Were people drinking the gastric juices of dogs? Were they injecting them?
Dr. Bakri: Drinking was mostly what they did. It was supposed to be a medical elixir. It had many things in it, many peptides. Dyspepsia and upset stomach and this kind of stuff is what people were thinking. And then this other group in Croatia — their first paper was in 1991. They talked about how there must be some kind of compound. They identified the big 40-dalton protein BPC. And then they were like, what's causing the actual biological effects? They identified BPC-157, the 15 amino acid peptide that's causing all these effects. There are actually more peptides in gastric juices that some other scientists may or may not have already identified. This field of peptides is going to be very interesting because almost every organ has a signature of peptides. If you think back, Dr. Vladimir Cavinson in the 1850s to 1880s finds carnosine and carnitine in muscle of cattle. So you can think that the first peptides found are carnosine and then carnitine — the amino acid that has positive effects on strength training and performance. But that was the whole idea: gut peptides might have gut effects, muscle peptides might have muscle effects.
BPC-157 Animal Studies and Mechanisms
Huberman: So this Croatian group isolates this 15 amino acid kind of mini-segment of BPC. They and others start injecting it into mice, inducing injuries to nerve, to tendon. Maybe describe a few of those effects.
Dr. Bakri: They did all kinds of horrible things to these mice. They would sever tendons and then give them BPC through oral or intraperitoneal administration and they'd have faster healing times. They would sever the ACL of the mice. They would do burn wounds. When a patient has a burn wound in the ICU, they end up having crazy gastric ulcers — but if they were able to put BPC on topically for the mouse, they would have no gastric ulcers. They name it as this anti-stress compound. Now, when they do that Achilles paper on the mice, that's what explodes the bodybuilder interest and leads us to today where we are — oh, MSK injuries, must be BPC, tendons and muscle injuries. But the original idea of BPC was to use it as a gastric treatment, not as a musculoskeletal one.
Huberman: Let me pause here. People are probably saying, should I take it or shouldn't I? Just hang in there, folks, because this is really important. What is so striking to me about BPC — and by the way, that's not an endorsement for BPC — is that my lab worked for a long time on optic nerve repair and neural regeneration. Nerves don't like to regenerate in the central nervous system. In the peripheral nervous system they do it slowly, but not in the central nervous system. Ask anyone who's had a stroke or an optic nerve injury. There are data that I've seen with my own eyes showing that you can accelerate healing of tendon, of ligament, of nerve pathways — in animals. Thank you. And that it just generally promotes repair. That's kind of weird, right? Because I could spend the next ten hours telling you about all the ways that people have tried to get nerves to regenerate and couldn't. And as you point out, this thing doesn't really have one specific known receptor. So the data on the gut make a lot of sense — this is after all a gut peptide. But what is it doing mechanistically to support regeneration of all these different tissue types? Because a neuron is a very different cell type than a fibroblast or one of the bits of collagen that make up connective tissues.
Dr. Bakri: It's modulating a lot of these growth and healing pathways. In models of damaging the endothelial layer or the epithelial layer of different tissues, you'll get more VEGF signaling — that's the vascular endothelial growth factor — so you get more blood vessels and angiogenesis being formed, which creates a lot of the controversy around BPC safety. You'll get cell migration, especially when coupled with TB-500 and TB-4. You'll get more access of the healing factors to the area through androgenic pathways. On top of that, you'll get an anti-stress effect. The other big thing they did was give corticosteroids with BPC-157 to these mice. Usually when you have a wound and you give corticosteroids, the corticosteroids will slow or even stop wound healing. When BPC was administered, the healing was either the same or even better.
Huberman: Is BPC considered anti-inflammatory? Because based on what you just said, it almost seems like it helps maintain some of the pro-inflammatory response. Some people might be thinking, why would you want inflammation? What Dr. Bakri just said is: if you block inflammation with corticosteroids, you aren't going to call in the signals to repair tissues. So lowering inflammation is a dicey thing. Is it thought that BPC is lowering inflammation, or is it somehow hitting the gas pedal on all these regenerative and restorative biological processes?
Dr. Bakri: It's more putting the gas pedal on these processes to bring in the immune system and the healing factors. For example, in one tendon model, they noticed that it increased the amount of growth hormone receptors on the tendon. So theoretically, this would allow more growth hormone to dock in and cause the outgrowth and regrowth of the tendon. Downstream, it'll modulate nitric oxide synthesis — that's a big thing when it comes to wound healing because you need to dilate the blood vessels and call in different cells. So it's really changing the way cells behave at that level, but that's only for the tendon side of it. They also did interesting things on the neurological side — they would make these mice drunk, and then give them BPC, and they'd get less drunk when going through mazes.
Huberman: We did not just recommend you take BPC with alcohol. I want to be very clear. But very interesting.
Dr. Bakri: And then also, they would get the mice drunk and then have them withdraw from alcohol. Withdrawal is deadly — if we have a patient in the hospital who withdraws, they could die during that withdrawal if they're not given benzodiazepines. They got BPC and they didn't have the withdrawal symptoms. This is a very interesting compound. I think it gets all the hype for the MSK stuff, but I think the neurological, neuropsychiatric, and gastric effects are way more interesting, because it's modulating the gut-brain axis in an interesting way. We'll have people come to us and they're like, "My Adderall is not working since I've been taking oral BPC."
Huberman: Are they happy with that effect?
Dr. Bakri: No, they're very mad because it seems like it's blunting their Adderall. So it's doing something with dopaminergic signaling on both sides — both withdrawal when it comes to the GABAergic side, but also the peak of signaling. If you peruse Reddit — which you should never do — you'll find all these anhedonia discussions about BPC, people feeling depressed and low energy.
BPC-157 Safety, Adverse Events, and Legal Status
Huberman: Let's do something that normally I would do in a few minutes. I'm going to ask you some very direct questions. Are there any known adverse events from people taking BPC — known and documented, unrelated to contamination?
Dr. Bakri: In the literature, when it comes to the animal data, they've injected animals with a thousand times the dose of BPC with no real adverse effects. We don't even know the LD50 of BPC, which makes it hard for it to become FDA approved.
Huberman: Maybe define LD50.
Dr. Bakri: LD50 is the dose at which 50% of the animals would die if it was administered to them. We don't even know what that is. And that's actually an important number — as barbaric as it sounds — to determine for any drug. Every drug you take, on or off the counter, prescription or non-prescription, has gone through LD50 testing in animals. To be a clinician and prescribe this, we need to know what that is, which limits us. Now, there were two very small phase one and phase two trials on rectal BPC enemas in the early 2000s from that same Croatian group. That's the big concern with BPC — all the data comes from one group. People can be skeptical. There are a couple of Chinese groups that have also replicated some of their work. But those groups wanted to try to treat ulcerative colitis. They used enemas of BPC up to about 80 milligrams, which is much more than people would typically take.
Huberman: Most people are injecting micrograms — 100 or 200 micrograms per day or something. Maybe more, but you're talking about 80 milligrams.
Dr. Bakri: Yes, rectal enemas. They did a phase one and phase two trial over a few weeks, placebo controlled. The data is not available — only the abstracts are available, which also gives us some pause. The phase one trial showed no adverse effects. And they didn't even find BPC in the systemic system. That's a key point — orally administered or rectally administered BPC doesn't seem to go systemic.
Huberman: If you take aspirin and then measure blood aspirin levels, you'll notice the levels go up. When they measured BPC-157 levels in these individuals, they didn't find it in the blood. So either it was broken down very quickly or it stayed locally to the lining of the gastric tissues. That raises a question. Let's say somebody doesn't take any BPC-157 by enema or otherwise. If I were to draw your blood right now, is there BPC-157 in there?
Dr. Bakri: There's the bigger BPC protein. We don't have that data.
Huberman: Well, that's incredible, right? Because we're talking about these effects all over the body, and we don't even know if it leaves the gut.
Dr. Bakri: The injectable is going to go systemic. And most people, if they decide to do this, are going to take an oral or an injectable — either injected locally to the injury or intraperitoneally. There's actually a paper from 2024 that looked at this and could figure out if somebody had BPC administered for doping reasons, because it's on the WADA list now.
Huberman: And we don't know the results in terms of what those 80-milligram enemas of BPC did for the colitis?
Dr. Bakri: In the phase one trial, it was just a safety trial — no adverse effects. In the phase two trial, which was very small, about 40 patients, there was at least a positive signal on the ulcerative colitis.
Huberman: This was done in Croatia. To be quite direct: on one hand you have groups saying 80 milligrams of BPC by way of enema did not cause any adverse events. On the opposite side, many people — especially in the United States and Northern Europe — would say, well, those studies were in Croatia. I have many Croatian friends, that's not a knock on Croatia. But why would clinical trials in Croatia hold less weight?
Dr. Bakri: The groups seem to be very robust and they do really good randomized control, double-blind, placebo-controlled trials. I think we're very US-centric. We view ourselves as the premier science, and we are the premier science. So people kind of trust that more. There may also be perverse incentives when it comes to different government bodies — like Soviet-era research that might be pro-fabrication when it comes to certain compounds. There's a lot of Soviet-era compounds that sound fantastic, but when they get tested, maybe they're not as potent as the Soviet data would suggest.
Huberman: I always thought the Russian stuff was like the really potent stuff they didn't want anyone else to know about. That kind of goes the other way, right?
Dr. Bakri: It could go both ways. But they were more interested in performance — they wanted better astronauts, better Olympians, better soldiers. We care more about a profit drug model that gets people on a monthly subscription, unfortunately.
Huberman: So nowadays, is BPC-157 legal in the United States? If I wanted to go online and buy BPC-157, I can do it, right?
Dr. Bakri: Legally, for research purposes only. BPC-157 never got FDA approved. It gets into these compounding pharmacy lists. There's a category one, two, and three. Category one means the FDA thinks: this is not an approved drug, but we're okay with you compounding this. Category two means: do not compound. In late 2024, BPC-157 and about 20 other peptides got moved to this category two list. Since about 2017 to 2024, people had been prescribing BPC in alternative medicine and anti-aging practices. Once it gets removed from that list, compounding pharmacies rebrand it as PDA — pentadecapeptide arginate — but it's the same thing.
Huberman: Really?
Dr. Bakri: Yes. One will be an acetate, one will be an arginate, but the PDA is BPC-157. Just in April of this year it got removed from the category two list and it's not yet on the category one list, which would allow physicians to prescribe it through compounding pharmacies. But they can prescribe the PDA version. Now, state medical boards view that very differently. I got a letter from one of the states I'm licensed in — they reached out and said you cannot prescribe non-FDA approved peptides no matter what. So it's state by state.
Huberman: What about with telehealth? So somebody's on the East Coast in a state that allows them to write a script for what's effectively BPC. Can they send that to California or Wisconsin if the patient is there?
Dr. Bakri: The telehealth laws go into effect where the patient is. So if in California it's not allowed to have BPC according to the state board of pharmacy, even if you're a New York doctor licensed in California, that would be against the California Medical Board. Are boards cracking down on this? Not really. There are a couple of states that are cracking down, and people know to avoid those states. But it's going to be very dicey over the next few years.
Gray Market Peptides, Sourcing, and Quality
Huberman: The route that many people have gone for about a decade now, but primarily in the last three to five years, was to go to these "for research purposes only" gray market sources. Let's just name names because they're out of business now anyway — Peptide Sciences. Until a few years ago, you could go on there and buy pretty much any peptide. It would say "for research purposes only, not for animal or human use." And you'd have to Venmo them — they'd ask that you not send it to a Peptide Sciences account. It was like some random name and the names kept changing. So everyone knew they were in on something. By the way, I want to be very clear — I ended up getting these things. I was too frightened to take them later. I have taken BPC. I've tried it. I don't take it currently, but I've tried it through a compounding pharmacy. So I just want to be very clear about that.
Dr. Bakri: Eventually they actually got payment processors — this market evolved with the desire. I'd say there's maybe $5 to $10 billion on gray market peptides being spent in the United States in 2025, and that's going to grow this year.
Huberman: Standard pharma we know goes through the most stringent process. The stuff that you get from Novo Nordisk or Eli Lilly — you can be certain it's as clean as it gets, as pure as it gets. Compounding pharmacies are a mix. Do we know that gray market peptides had problems? Because there are people out there — certainly not physicians — like Robert Breedlove, who's best known for his work in crypto but is also very open about the fact that he's taken all these peptides and anabolics. I heard him online saying he's tested the gray market "for research purposes only" peptides and compared them to the compounding pharmacy versions and they're identical. As a physician, what is your stance on this?
Dr. Bakri: The API — the active pharmaceutical ingredient — for all these peptides comes from China. There are no such thing as American-made peptides. Everything comes from China. The synthesized semiglutide gets made in China. It would be very expensive to make it here. There are people starting to look at that because that's the next thing in the arms race — to make American peptides. The compounding pharmacies vary in grading. Some of them are really good. They do all the testing, sterility, very good quality control. So you get a good product, but they usually have to compound it with something else to get by the regulations — like they'll add in a B12 or a B6 to say the patient had nausea from the traditional semiglutide. The research stuff is all over the place. Some of it could be better than compounded stuff. It could be the wrong substance. There's a guy who went viral on Twitter a few weeks ago — he got retatrutide and started getting darker. He's like, "I don't think I'm injecting retatrutide."
Huberman: He was injecting melanotan 2.
Dr. Bakri: Yes. So all of the raw materials are coming from the same source, then getting filtered into different stringency bins. Standard pharma being the most stringent. Compounding pharmacies have varying levels of stringency — some are excellent, some are good, some are lousy. The gray market peptides presumably also come in anywhere from excellent to dreadful. We don't know which are which, and batch to batch — that's the big problem.
Huberman: So it is risky to get research-purposes-only peptides. That's the majority of the way people are consuming peptides. The move in 2024 to get these from the category one to the category two list and make them banned opened up this gray market zone. The gray market existed for the last 15 to 20 years. Bodybuilders would have anecdotes about BPC-157 and inject it post-squats for different injuries. Nobody really cared about it. It was with the GLP-1s and then the banning of the peptides, plus this anti-medicine kick that's been happening over the last five years since the pandemic, that people are like, you know what, I want to inject this because it gives them a sense of autonomy or their bro recommended it. The best job in 2025 was to be a peptide affiliate — people made a yearly salary in a month selling peptides illegally on TikTok.
Dr. Bakri: And I will say — more than half of the peptide market is female. Especially when we start getting into things like GHK-copper and talking about things for collagen and skin rejuvenation. I actually think in the long run it's going to exceed the peptide market in men financially.
Huberman: I think it already has, because soccer moms have become affiliates — like Amway and Herbalife was the big thing 20 years ago. Now soccer moms just do peptide affiliation.
Dr. Bakri: Black market is if you bought it directly from China — a vial of BPC costs five bucks to make. Someone will sell it to you for $1.99 depending on where. Black market is either your friend in China on WhatsApp sent you a vial of BPC — do not do this — or someone claims they synthesized it in their bathtub. Just like the underground gear, all the steroids from the '90s and 2000s. Who knows what that is.
Compounding Pharmacies, Pricing, and the GLP-1 Shortage
Huberman: With steroids, it went from the bodybuilding community to eventually hormone replacement — TRT, HRT. Peptides are different because the big explosion came through the GLP-1s. And I would argue that why so many people are now peptide curious is because people are now also very comfortable injecting themselves. Like five years ago, if you said you're going to inject yourself, people would be horrified. Then they realize it's this little tiny pin that hurts less than a mosquito bite. People are doing it on their skin and somebody's girlfriend or wife is doing it as if it's nothing.
Dr. Bakri: That changed everything. That destigmatized it.
Huberman: I want to touch on the question about adverse events. The concern I've always had was the angiogenesis — the growth of vasculature. If somebody happens to have a little tumor sitting on their liver or in their gut or in their pancreas, in theory it could vascularize that tumor and cause it to grow more quickly. Is there any evidence that that's actually happened?
Dr. Bakri: No. For example, most compounds that are carcinogenic will show that signature in animals — like cardarine GW, which was very promising because it had diabetic implications for metabolism. It had a signal of cancer in animal data, so that whole thing was scrapped. There's no signal from the animal literature on BPC-157 for cancers. Now, all that literature comes from one group, so we have to be very careful. There's a couple of Chinese studies on BPC-157, and now there's starting to be more interest here — I think there's a phase two trial on hamstrings happening in the United States.
Huberman: Really? Humans?
Dr. Bakri: Yes, phase two. We talked to an orthopedic group somewhere on the East Coast. They wanted to do a BPC trial, so we consulted with them. Especially if it moves to the category one list and people can be prescribed it, at least we can get a phase four trial where it's being prescribed and we can see what's happening to the people as they're getting it. We can aggregate all this anecdata into one place and report on it.
Huberman: Is that something you're personally working on — aggregating all this data together into one place?
Dr. Bakri: Yes. For example, on Reddit you'll find signals of hematomas getting worse, which makes sense with the VEGF pathway.
Huberman: I've heard this. A friend and physician who is peptide curious and positive told me that when he takes BPC-157 for a shoulder or knee injury, angiomas on his face — the sort of spiderweb angiomas — get worse. That's his personal observation. It makes sense if it's promoting angiogenesis.
Dr. Bakri: BPC-157 is not a uniform angiogenesis upregulator. In some models it decreases VEGF — in a melanoma cell line, for example. So it might be potentially anti-cancer, but we need to test it. We don't know, which is what's really unfortunate about this compound. It's very promising. It has all this cool literature in animals and we just don't know when it comes to humans. I could see a million use cases in the ICU — like if we knew it would work, I would love to give an infusion of BPC-157 to ICU patients who are getting gastric ulcers during critical illness. But we need data.
BPC-157 Patent, Clinical Trials, and Anecdotal Reports
Huberman: When is there going to be a formal randomized control trial on BPC, and who holds the patent?
Dr. Bakri: There are multiple patents on BPC-157 depending on which salt form it's in. The patent has been passed around a couple of times. Unfortunately, the company that had the patent under the peptide got acquired by Teva. Teva is this generic pharmaceutical company — they make Adderall and tons of other things. They don't really care about BPC-157. The other patent expires in about 10 years. I think Dr. Sikiric still has it — he's the guy behind BPC-157 in Croatia. The problem is I don't see the purpose of even having the patent because you can add one amino acid to the chain. This is the problem with peptides — you can modify one thing and suddenly it's a different compound.
Huberman: This is true for other pharmaceuticals. Like I'm familiar with some of the ketamine and ibogaine trials, and there's a company that took ibogaine and basically added a magnesium component to it and made it a completely new drug. So this game of protecting patents is rough. Plus, millions of people have already used BPC-157 through research-use-only websites. The cat's out of the bag. So there's no financial incentive to run the giant study unless we crowdfund it as peptide-curious people.
Dr. Bakri: Within the category of interesting anecdotal data — and in your role as a physician — what do you think are the most interesting potentially valid claims? If we were going to fund a clinical trial, we need to pick endpoints. Is it going to be recovery from injury? The gastric stuff? Mood and interaction with dopamine receptors? If we had a chunk of money and were going to design a study, what are the top three to five outcomes that you've heard where you have a good feeling there's something there?
I would say: complete the phase one and phase two on ulcerative colitis, do that phase three trial proving it has benefits for ulcerative colitis. I don't think we need to use enemas — we could probably have an encapsulated version that releases deeper into the intestines. In conjunction with that, you could do a trial on GERD — a simple condition, a lot of people have it — randomized to BPC-157 oral capsules versus pantoprazole.
Huberman: And you're basing this on the fact that you've seen and heard that people who have GERD get better when they take it?
Dr. Bakri: Anecdotally, when I travel, I have a bottle of BPC orally. I don't get travelers' diarrhea or get sick when I eat exotic foods in random places. My friends all get sick and I happen not to. Anecdote, right? But that's interesting. There seems to be some kind of gut protective effect. And that's what they noticed in the mice literature — they would have an offending agent in the gut and notice protection deeper down in the gastric tract from that offending agent. If you think about it, the gut is the most vulnerable part of the body — it's open to the outside world, it's a tube that runs through you. You have to have mechanisms — the prostaglandins, all these different hormones that are made. Potentially BPC-157 is part of this robust armory that the gut has to protect itself from further injuries.
Huberman: What are some things outside the gut that are also compelling?
Dr. Bakri: I would love to see some neuropsychiatric BPC studies when it comes to addictions. There's enough anecdote about people talking about addictions and like, "Hey, I don't need to crave insert drug here." Not recommending that anyone tries that out, but for alcohol or whatever it may be. Do you think that's likely due to interference with the reinforcing properties — like earlier you said people are getting less drunk, so people are getting less high, it becomes less reinforcing — or is it somehow touching the craving mechanisms themselves?
It's probably touching the craving mechanism through the gut-brain axis, because I don't think it's going systemic. I think it's locally in the gut shutting down the neurons. If BPC is what they claim it is — and that's a big if — if you have a noxious agent going into your gut, your body has to have a mechanism to lock down and protect your vital organs. Is BPC part of this giant transduction pathway to protect your vital organs — your brain, your heart, your kidneys — from further damage? We had Dr. Diego Bohórquez, who's out at Duke, who's really the world expert on these neuropod cells in the gut that signal through the nodose ganglion up the vagus to either promote or suppress release of dopamine to make you either approach or avoid certain foods. Very, very interesting.
Huberman: What are some other categories of interesting effects that deserve careful study?
Dr. Bakri: We need to see what BPC does on the musculoskeletal system — that's what the hype is, that's where everybody's focus is. As I look through what model I would look for, you want something that's not very vascularized but could be improved if blood flow was good, like a tendon injury. Perhaps a bicep or tricep tendon type of post-surgical outcome. Like: you get your bicep tendon torn, you get a repair, you get BPC either intraoperatively or postoperatively, and you see if that person heals faster. The idea is not that BPC is going to magically reattach an ACL that's torn. But can it further accelerate the healing from an ACL surgery so you come back in six months rather than twelve months? That's the big question, and that's what a lot of athletes are using BPC-157 for.
Huberman: Has anyone ever done the one-limb versus opposite-limb control experiment?
Dr. Bakri: I know. I've used BPC for one injury and had results on a different injury. Positive results. I'm like, "Oh, interesting — my shoulder feels better even though I was doing it for my elbow."
Huberman: This would be a good time to bracket what we're about to say by noting this is purely anecdotal. What's your favorite personal BPC story involving you and your body?
Dr. Bakri: I tore my tricep a few months ago. Tore it lifting with people I should not have been lifting with — they're much stronger than I was. Purple from here to here. I'm like, I'm going to have to have surgery. I don't have time for surgery because you're in a brace for three months. I put BPC in locally — don't try this at home, not medical advice — locally in the tissue spot with a couple of other peptides. Within three weeks, my PT is like, "What the hell are you doing? This is healing so fast." Would I have healed that fast anyway? I don't know. But that's typically a grade two tricep tear with a purple arm from top to bottom — usually a three-month recovery. To be back in three to four weeks was fantastic for me, which is why I'm so excited.
Huberman: What dosage were you injecting?
Dr. Bakri: A larger dose than people would typically use. Not micrograms — up in the milligrams. I think personally, and in some of our patients, we've used bigger dosages. I think that's the problem — the low dosages, even though they translate well from the mice data, for humans I think the dose is way higher. But people just go based on the dosage that would fit in the vial through a peptide sciences website rather than what we actually know the human dose to be. We don't know what the human dose is for BPC-157. When we spoke to the orthopedic group, they said, "Yeah, we're going to start with 250 micrograms." I'm like, I don't know if you're going to see an effect at that low a dose. But tricep was back to normal.
Huberman: I can't match your story. I can just say that I had a bad trap-neck pull where I couldn't turn my head. I had some BPC — only about 200 micrograms — and just injected it right into the upper trap area. Two days later, completely gone. Of course I don't know what would have happened had I just waited, but it seemed eerily fast. And that was obtained through a doctor's prescription from a compounding pharmacy, labeled BPC-157, not PDA.
Those are anecdotes. I've also read on X people saying they didn't feel well and stopped taking it — could be due to what it was dissolved in, could be due to their own unique response, could be due to bad sourcing or contamination. Not everyone has a great result, and some people have no result. But many many people report what can only be described as pretty astonishing positive results that cannot be directly ascribed to the BPC because of the placebo effect.
Dr. Bakri: There are two possibilities. Either BPC is as amazing as we think it is, and it's unfortunate that millions of people don't have access to it. Or BPC is actually either ineffective or harmful to people, and millions of people are injecting it right now by buying it through online sources. Both cases are very bad endpoints. That's why we need this data. If in 20 years we find out BPC is as good as the science suggests, then people are pissed off about all the joint replacements and injuries that didn't heal and athletes who maybe could have had a longer career. But if it's the opposite, and every 18-year-old kid in the gym is injecting BPC — that would be very unfortunate too.
The Thymus, Immunity, and Aging
Huberman: Let's talk about the thymus. Super interesting organ. We all have one when we're born. By the time we're what age is it mostly gone?
Dr. Bakri: The thymus grows under the influence of a lot of these youthful hormones — melatonin, growth hormone, DHEA — and then shrinks at the moment you hit puberty. From the day of birth until puberty, you grow this massive thymus. It sits right above your heart, right behind the collarbone. In a baby, it could be quite large — maybe the size of a baseball. Right now in our bodies, it's going to be a bunch of fat with a couple of different globules of thymic residue. Very tiny. In fact, most surgeons will just remove it when they do surgery nowadays for open heart. But there's good data from the New England Journal of Medicine that removing the thymus tissue leads to a mortality signal within the first five years after those surgeries.
Huberman: So people have died because of thymus removal?
Dr. Bakri: They'll have higher rates of cancers or higher rates of autoimmune diseases if their thymuses are removed. Now there are thymomas where people have to have their thymus removed, but we're talking about people where the surgeon is going in to do a coronary artery bypass surgery.
Huberman: Is the thymus neurally innervated?
Dr. Bakri: Yes. Vagus nerve. So it's getting signals from the brain — sympathetic and parasympathetic innervations for the thymus, which dictates its hormonal output. The thymus is a gland that both secretes hormones and develops the T-cells. Your lymphatic cells are found in your bone marrow — that's where they're made. The T-cells will travel up to the thymus and get trained so they don't kill you, don't attack your own tissue, but attack a foreign invader or a cancer. That process is very good in youth, and as you age you get more autoimmunity, more cancers, because the immune system is not as robust — both because the thymus makes less of the hormones that train the immune cells, and makes less of these immune cells themselves. When you're 15, you're making 10 to the eighth magnitude of these cells every single day — they're called naive T-cells, which will eventually become your CD4 and CD8 T-cells. As you age, this number dramatically decreases. Those cells will live somewhere between 10 and 15 years. When your thymus reaches a minimum level of output, you get a lot of these disorders — cancers, heart disease, autoimmunity. There's a Nature paper from 2026 that just came out that looked at cardiovascular disease and cancer mortality, and people who had higher thymic scores had less mortality across every single one of these conditions.
Huberman: You said that by the time you're in your 30s or 50s, you've got just a bit of residual tissue there.
Dr. Bakri: The rate of decrease varies dramatically from person to person. We call this thymic involution. From the moment puberty starts until you die, your thymus is slowly shrinking — the majority of that happening in your 20s and 30s, under the pressure of androgens, estrogens, progestins, and corticosteroids. Those are driving a lot of the shrinkage.
Huberman: So the hormones that everyone seems to want to increase the rest of their life, and that become very active during puberty, actually cause thymic involution.
Dr. Bakri: Yes. Castration will undo some of the thymic involution. Pregnancy is a great time to involute your thymus, which makes sense because you don't want to be having an immune attack against the baby. The thymus will involute and then regrow during the breastfeeding period under the influences of growth hormone and prolactin. Hibernating animals will have a dramatic shrinkage of the thymus during hibernation and then a regrowth during the feeding window.
Huberman: Is there any benefit to doing or taking something to either maintain or regenerate thymic size?
Dr. Bakri: There's an interesting study — the TRIIM trial from Dr. Greg Fahy. He did a study where he gave a cocktail of growth hormone, metformin, and DHEA for 12 months and had the thymic size increase on imaging. The amount of CD4 and CD8 T-cells increased and the ratio improved. Some of the markers that would show immune cell exhaustion like PD-1 also improved. So they're trying to use growth hormone to regrow the thymus.
Thymosin Alpha-1, TB-500, and Thymulin
Huberman: Getting us directly to peptides — many people who are peptide curious start asking about thymosin alpha-1. Is thymosin alpha-1 a peptide that comes from the thymus?
Dr. Bakri: Thymosin alpha-1 is part of this thymic family of hormones that gets secreted. It's at least 21 amino acids. It increases T-cell development in the thymus, increases T-cell proliferation outside the thymus, and makes the T-cells more likely to properly attack a pathogen. It's like jet fuel for the T-cells. It was FDA approved as Zadaxin for kids that were born without a thymus or a malfunctioning thymus — like DiGeorge syndrome — to help develop the T-cells that they had that weren't properly developed. In other countries it's approved as an adjuvant therapy for hepatitis B, hepatitis C, and in different cancers. The sepsis literature and the infectious literature is not that promising. It might be that if you take antibiotics with thymosin alpha-1 you might have a quicker bounce back. What I would be interested to see is: if you went to nursing homes, injected everybody with thymosin alpha-1 in November and December, would you have less flu in January and February?
Huberman: Have you taken thymosin alpha-1?
Dr. Bakri: I've used thymosin alpha-1 when I travel to avoid the cesspool of planes and hotels. This year on the wards was the first time I don't get flu, cold, whatever kind of infection. I did one course throughout and I didn't get sick a single time. Twice a week, time agnostic. We're talking about 2.5 milligrams as a prophylactic.
Huberman: When we hear about thymosin alpha-1, we usually hear about TB-500 also. What's TB-500 and how are the two related?
Dr. Bakri: While Cavinson is finding thymulin and injecting that into people, the Goldstein lab finds thymosin fraction 5, which is this giant protein that has many different peptides in it — thymosin alpha-1 being one of them and thymosin beta-4 being the other. Thymosin alpha-1 and thymosin beta-4 were discovered in the thymus but they're not exclusive to the thymus gland — they're also made in other tissues. Thymosin beta-4 seems to be this 43 amino acid peptide that helps in the actin cytoskeleton of cells. Immune cells have to move a lot, so they have to reorganize their actin cytoskeleton quite quickly. It seems to upregulate that movement, which the horse racing community has found a niche for — thymosin beta-4 is a very common doping agent for horses.
Huberman: There's been so much interest in NAD, NMN, and NR to upregulate NAD. When I hear about thymosin alpha-1, TB-500, BPC, it occupies this kind of middle ground for people who want to go beyond supplements but don't want to go all the way to blood cleansing and other extreme things. I think a lot of people are starting to think about these for their pets too.
Dr. Bakri: The pet peptide industry is going to be enormous — it already is. And because BPC — is it going to be treated as a supplement when it comes to oral capsules, or is it going to be treated as a medication? We haven't got that answer from the FDA. RFK himself has kind of said these are supplements, they're not medications. So the FDA said they're not going to regulate them as meds, which I don't know if the agency themselves is going to be too happy with.
Huberman: Is BPC going to be taken seriously as a drug, or is it more creatine-ish?
Dr. Bakri: For example, I could give you a B12 supplement you could buy on Amazon, or I could prescribe that to you. But if I was to give you an injectable B12 shot, you would need a prescription for that. Is that distinction going to apply to peptides? That's the big question that no one's answered. Pinealon is a supplement you can find over the counter in Kazakhstan, Russia, Ukraine, and various other countries.
Pinealon (EDR), Epitalon, and the Russian Bioregulators
Huberman: Let's talk about pinealon. I'll just go on record saying I've tried it a few times. I don't take it regularly, but I tried it before sleep. If I take it at the beginning of the night, it reduces my deep slow-wave sleep and gives me far more REM across the night — not a great situation. But if I go to sleep, get my usual ration of deep sleep, and then happen to wake up in the middle of the night to use the restroom, if I do a very small injection of pinealon at that point, the one and a half hours of REM that I would get in the final hours of my sleep — now I'm getting three hours in the same amount of sleep. It's just a higher fraction of REM. Sometimes I wake up feeling a little groggy, but it is a whole other life to get that much REM. I don't do it regularly — maybe three times a month. And here's the interesting thing: it improves my percentage of REM on all the other nights in between those three injections. You're interested in pinealon for a whole other set of reasons. But first of all, what is pinealon and where does it act? Does it have a known receptor?
Dr. Bakri: No known receptor. Pinealon is a tripeptide — EDR — discovered by Dr. Vladimir Cavinson. He's a Soviet researcher who comes out of this Soviet-era research to make soldiers, astronauts, and pilots better. There was concern that the US might be using lasers to shoot at soldiers. So the Soviet Union tasked him with identifying peptides to defend soldiers' eyes and then their aging, because what would happen is they'd be in a submarine for a few months — a nuclear sub — and they'd come back to shore looking 10 to 20 years older. The same thing happens to astronauts. Vladimir Cavinson is looking at this and thinking there's got to be a solution. There's been literature about using extracts of other tissues — notably the pineal gland and the thymus — from the late 1800s through to this 1970s point. He starts grinding up these extracts and injecting them into these people and undoing a lot of these aging effects through pineal extracts and thymus extracts. These soldiers had very bad circadian rhythmicity — they couldn't sleep properly, they had terrible immunity, they'd get sick often, they'd have autoimmune problems. They were able to undo this using these organ extracts. Vladimir Cavinson takes it a step further. He looks at what's causing this effect in these tissues. He finds peptides in these extracts and thinks: I wonder if these effects are from the peptides, not from the gland itself. So he sequences from the pineal gland epitalon, and from the thymus gland a couple of different peptides — thymulin, thyogen, crystagen — that on their own do a lot of the effects that the whole extract would do.
Huberman: Now you're talking about epitalon, but pinealon is not from the pineal gland.
Dr. Bakri: Correct. Even though everyone assumes it is. Epitalon does that — it has effects on pinealocytes. Pinealon comes from a ground-up brain extract called cortexin — from the cortex specifically, not the subcortical regions. So Cavinson identifies — he makes a drug in Russia called Epithalamine, which is the pineal gland extract, and it had great effects on circadian rhythmicity. It's rich with melatonin, basically giving people melatonin, but also upregulating the enzyme that creates melatonin from serotonin to acetyl serotonin to melatonin. When he gave it to young monkeys, the monkeys had no effect, but when he gave it to aged monkeys that have decreased melatonin — from puberty onwards your melatonin levels dramatically decrease — he was able to restore melatonin production in these aged animals and eventually replicated it in humans.
Huberman: So pinealon comes from the cortex, not the pineal. That's annoying. Maybe we just rename it today. We'll call it EDR — that's the three amino acid sequence. What are some of the known effects? Or am I just imagining this REM increase? Because I can't change what's happening to me during sleep. That would be an amazing placebo effect. For me it was just striking. So why would EDR — a tripeptide with no receptor — have this effect on REM sleep?
Dr. Bakri: I actually searched through all of the literature from Cavinson. He never mentions REM sleep once in his studies. He studied pinealon quite extensively on different neuronal tissue extracts, animal studies, even in athletes, and never mentions REM sleep. They didn't have Whoop in the 1970s in the Soviet Union. They didn't have sleep trackers. So there were no reports on that. But what seems to be happening with EDR — it's a tripeptide that meets the groove of the DNA of different key regions and helps the promoter region be exposed, so that DNA transcription can happen. It's turning on genetic programs. It's acting almost like a transcription factor, or maybe assisting transcription factors in accessing the DNA in the right places. In one sentence, pinealon is leading to better brain metabolism through modulating all these different pathways — for example GDF11, SOD1, SOD2, irisin, PPAR-alpha, PPAR-gamma. He made pinealon as an anti-stress cognitive performance compound. If you take a high enough dose there is sedation from it, but if you take it in the morning or pre-workout you get quite an interesting effect. He studied this compound on athletes — he would have them do their training session, go to exhaustion, and then do a test afterwards. The pinealon group could keep their performance up despite being maximally exhausted from their training.
Huberman: I feel like such a dummy. Here I am having elaborate dreams I don't really remember or care about when I could be actually thinking better during the daytime.
Dr. Bakri: A lot of people report less brain fog, better thinking. A friend who has a nine-figure company has all of his employees on pinealon. They're taking it in the morning. Orally, people will take anywhere between half a milligram up to three milligrams. The Cavinson ones that come from Russia are like 200 micrograms. Some people are injecting it — it goes systemic. It's orally available through these dipeptide transporters. It most likely crosses the blood-brain barrier — it's a tripeptide, small enough.
Huberman: Have you tried it?
Dr. Bakri: I took some last night. I will take larger dosages if I want to get good sleep. Some people it will cause a little bit of awakening at first — that may be why your deep sleep was going away. If I take half of what was recommended, I'm great. But I'm very sensitive to everything. If I take what was recommended, I fall very deeply asleep, I have elaborate dreams, and I wake up. Are there any known risks of EDR?
So far, nothing in the Russian literature — big caveat, it's Russian literature, not gold standard American research. Nothing has come up as a clear signal. The big theory of Cavinson is that when you're younger, you make a lot of these peptides naturally — these di-, tri-, and tetrapeptides — and as you age they go down in function and quantity. By replenishing these peptides you're restoring some aspect of youthfulness. Something similar happens in America with GHK-copper, which is another tripeptide — the collagen regulator, while EDR is the brain regulator. The side effects we've noticed: some people will have a little drop in blood sugar because it activates PPAR-alpha and PPAR-gamma, so it'll have positive metabolic effects. Some people have even had their A1C's drop. So hypoglycemics and people with blood sugar issues should take extra caution. And then very vivid dreams for some people — that could be disheartening if they have nightmares. But very vivid dreams as a result of pinealon, especially the color and quality of the dreams, is very different than you'd normally expect. What seems to be happening is just like psychedelics change the redox state of the brain, pinealon is doing something similar — you're getting more alertness during the day, less brain fog, better performance during high-intensity interval training, and then more REM sleep at night, because the neurons are in a better oxidative state thanks to the PPAR-alpha, PPAR-gamma, irisin, and all these different pathways it's modulating — with no clear single receptor that it's doing it through.
Epitalon, the Pineal Gland, and Longevity
Huberman: What about epitalon, which turns out comes from the pineal? I'd love your thoughts on this. I've heard — and I thought it was complete nonsense when I first heard it — that the pineal becomes calcified as people age. I used to co-teach neuroanatomy when I was at UCSD before moving my lab to Stanford with a guy named Harvey Karten. Unfortunately, he passed away. He was in his late 80s and had this incredible career as one of the greatest neuroanatomists of the last hundred years. I asked him about this calcification thing because he had looked at the brains of so many different species including humans. He was also an MD, and he said, "Yeah, I don't know whether or not this calcification thing is real," and kind of brushed it aside. I thought, well, Harvey doesn't take it seriously so I'm not going to take it seriously. But when I go to the literature now, it's a little bit tough because the cadavers you looked at in medical school are not all processed on the same timeline. Does our pineal calcify, and even if it does, does that somehow inhibit its ability to communicate with our other tissues?
Dr. Bakri: It's a big debatable thing in pineal research. If you look at the pineal gland Wikipedia page, it's very underdeveloped because it's kind of woo-woo. When you think of the pineal gland, you think of someone who's going to sell you crystals or something. It's not a very sexy area. But I think it's a key aspect of aging and longevity. From Cavinson's work, the decrease in pineal gland function with aging is more of a physiologic than an anatomic problem. I will see some calcification on MRIs when we have a patient come in for a stroke or TBI. But the question is what is actually leading to the deterioration of melatonin synthesis, because it decreases quite dramatically. Some people even think that might start puberty — if you have a pineal cyst you can have precocious puberty at eight or nine years old. The rhythmicity in melatonin — a very young baby's melatonin secretion is not very rhythmic, but they're in REM a lot. With time it becomes more rhythmic. And of course in today's day and age with all the artificial lighting and the lack of sunlight exposure, people are making themselves somewhat arrhythmic or phase-shifted.
Huberman: Epitalon is somehow restoring pinealocytes, somehow enhancing the general functioning of the pineal and other tissues.
Dr. Bakri: In Cavinson's work, he found that it will increase the expression of the different clock genes. In lymphocytes that he'll measure in peripheral tissues, he'll notice that the clock genes actually change to a more rhythmic pattern. He'll notice that morning cortisol is higher — which, by the way, you want your morning cortisol super high. You want your evening and nighttime cortisol low. The idea is it's restoring a more circadian-appropriate hormonal profile. Unlike a GLP-1 drug that you take today and have the effect for the next week, the idea from the Cavinson model is that you take these and then you accrue benefits when you're off of them. You notice with pinealon — you took it for a day or two or three days a month and had effects until you took the next dose. The idea is: can you accrue benefits from these compounds as they upregulate or downregulate certain genetic pathways in a more favorable state, and then keep those effects later on?
In Cavinson's seminal work, there was a 15-year longevity study. He got people in nursing homes — two groups. One got epitalon in the form of Epithalamine, which is the whole pineal gland extract, and then a thymus peptide called thymulin. Not thyulin — there are two different peptides, and a lot of people confuse them. He injected them for 15 years — a 10 or 20 day course per year, just at the beginning of the year and middle of the year. They had a significantly lower mortality when it came to cardiovascular disease, infectious risk, and cancers. Russian study, caveat, but that would be the most interesting longevity study I've seen done if accurate — because he was able to take nursing home patients, give them peptides for a very small amount of the year, and yet they accrued benefits the rest of the year.
Huberman: One of the things that really got me excited about epitalon is some interesting papers — and I can really gauge the data even though they're in mice — showing that you can use epitalon to combat some of the neurodegeneration in things like retinitis pigmentosa and downstream neurodegeneration in RP, which is a very common blinding disease, or even in glaucoma. I was intrigued. There's this molecule that's somehow involved in DNA repair, and it's either maintaining or restoring some of the machinery that would otherwise definitely be lost in one of these optic nerve damage conditions that model things like glaucoma, retinitis pigmentosa, stroke, traumatic head injury. So the reason it's so interesting to me is that it's getting to DNA repair as opposed to working on any number of vague receptor-ish, maybe no-receptor things. Do you think of epitalon as kind of a gene therapy of sorts, or do you think about it more as support for genetic machinery that has lots of downstream targets?
Dr. Bakri: I think it supports this genetic machinery. When it comes to the eyes, it seems to be repairing some of the photoreceptors that might get damaged in retinitis pigmentosa. Melanopsin wasn't discovered when Cavinson was working on this. But my theory is that epitalon is working on melanopsin — that it may be upregulating melanopsin levels and then making that morning sunlight more effective. The big problem is a lot of people will tell me, "Doc, I did morning sunlight and I didn't feel the effects." I'm like, have you had enough darkness to regenerate melanopsin levels? Because we know that in animal studies, five days of pure darkness dramatically increases the amount of melanopsin in the retina.
Huberman: I certainly have a lot of close friends who are in a position to do these studies. The podcast has a premium channel that funds research — we've given a lot of money away to excellent laboratories where they're free to explore these things. I'd love to see some of the studies we're talking about today supported. And that's done in collaboration with donors who do a match. The scientists we both know — the right ones — would try and disprove the hypothesis that any of this stuff was real. If some makes it through that filter, then they would conclude it's real. As a clinician, one of the key things for people to remember is that we've screwed up a lot of times as clinicians through different grotesque abuses of our trust. For example, in the 1910s to 1940s, we irradiated the thymuses of young kids to prevent SIDS. This was considered gold standard medicine.
Dr. Bakri: They thought that the thymus was too big and was sitting on the heart and that might be the cause. So tons of these kids — I think at least 10,000 — died from cancers. We have to be very cognizant of that history and know where we've been. There's a lot of grotesque abuses of medical power. We have to be very careful in which interventions we give people, and the first thing is: do no harm. While we are excited about these therapies, we have to be careful in where we're taking people.
Thymulin, Zinc, and Immune Function
Huberman: The French came up with the actual main thymus hormone — thymulin, not thymulin. Thymulin is the Russian polypeptide mix. Thymulin is a nine amino acid peptide that is the marker of thymus function. It also has very interesting neurological effects. It modulates what we're calling the thymus-pituitary-adrenal axis and the thymus-pituitary-gonadal axis. Thymulin is this peptide secreted by the thymus that dramatically decreases with age and is zinc-dependent. It's a nine amino acid peptide with zinc inside it to do its effects. It will develop NK cells and T-cells, stimulate the immune response. But also in the animal models — not replicated in humans yet — when they take out the pituitary and then inject hCG, the amount of thymulin sensitizes the end organ to production of the targeted hormone. For example, if you were just to give hCG alone to the animal, they would get more testosterone produced when they got hCG with thymulin versus hCG alone.
Huberman: So what you're saying is that thymulin specifically can augment the effects of endogenous and perhaps also exogenous hormones.
Dr. Bakri: Yes. And it makes sense — if you're not robust when it comes to immune status, you have no business investing in reproduction. You have no business creating a lot of corticosteroids. But if you're making a lot of corticosteroids, you're shrinking your thymus. So it creates a negative feedback loop to prevent you from overrunning your system. A lot of young guys will be like, "Oh, my immune system sucks and my testosterone is low." Is there a thymus link? That is the question.
Huberman: Is taking thymulin something that generally could be a good idea under certain circumstances?
Dr. Bakri: Thymulin itself has a very short half-life. The goal would be to increase endogenous production of thymulin itself. Sufficient zinc status is necessary to make thymulin. The first sign of zinc depletion — before RBC zinc or serum zinc decrease — is your thymulin levels tank.
Lymphocyte-to-Monocyte Ratio and Thymic Assessment
Huberman: Can I get some sense of my thymic size and output from a blood draw, or do I have to do whole-body imaging?
Dr. Bakri: On blood tests, we've been trying to work with a couple of different labs to figure out a thymic score. The most commercially available is going to be a lymphocyte count — looking at CD4 to CD8. There's an ideal CD4 to CD8 ratio that's more youthful. You don't want to have more CD8 cells than CD4 cells. But the most simple thing that almost every single person has gotten done but no one's looked at is their lymphocyte-to-monocyte ratio on their CBC. Almost everybody's had a CBC with diff — it's a $3 lab test. If you type in any disorder — cardiovascular disease, cancer, diabetes — and put lymphocyte-to-monocyte ratio, there's a study that will talk about how a low lymphocyte-to-monocyte ratio is associated with poor outcomes when it comes to that disease state. It gives you a general gestalt of what's going on with immunity. You want a high absolute lymphocyte count — not too high, because that's associated with lymphomas — but somewhere around 1,000 total lymphocytes is where the hazard of different cancer sites starts to increase. A young healthy person will be between 1,500 and 3,000 total lymphocytes. You want the ratio to the monocytes to be high. Monocytes are more inflammatory immune cells. If you have a robust amount of lymphocytes with a low amount of monocytes, that suggests you have a more ready and robust immune state.
Huberman: So a $3 lab test that everybody gets — almost every lab testing company now checks it — and no one really reports on it. But you can stratify people into disease risk based on that score. Out of a hundred randomly pulled physicians who received their license in the United States, how many of them probably know what you just described?
Dr. Bakri: Zero.
Huberman: Why not?
Dr. Bakri: It's a rabbit hole you kind of go down and find out. I've been lobbying everyone in the hospital to look at this. I started to care about the thymus post-pandemic because I noticed people's lymphocyte counts were lower. I could notice anecdotally that people who had lower lymphocyte counts had worse disease — like people who had cancers in their late 30s, early 40s all had lower lymphocyte counts. So I started digging into the literature and I'm lobbying a lot of the hematologists and infectious disease doctors in my hospital to start looking at this. Unfortunately, they're textbook — it's not part of the guidelines. It's not clear that if I check your lymphocyte-to-monocyte count right now it's going to change my management of you in the hospital today. It's more of a long-term look. That's where direct-to-consumer companies have an opportunity to modulate the way medicine is practiced. We've had people go from a 4:1 lymph-to-monocyte ratio to an 8:1 ratio using certain peptides. Now, is that significant? It seems to be significant. But no one's really discussing it unfortunately.
Growth Hormone Secretagogues and Somatopause
Huberman: There's a category of peptides such as growth hormone secretagogues — tesmorelin, MK-677 — that we could do a deep dive on. These are, to my understanding, FDA approved for certain indications. The framework I'm teeing up is that these molecules have been explored for their known biological function in animals. It's established that these molecules lead to an increase in growth hormone above what would normally be secreted. They do it indirectly — they're sort of the gas pedal on that system. Growth hormone secretagogues cause more growth hormone to be secreted, not actual growth hormone. They vary in terms of how much they stimulate hunger. Most people who are taking these things are doing so because they want to lose fat, gain muscle, recover from exercise more quickly, and look more youthful. Can we assume that those effects are real given that they were FDA approved for other things?
Dr. Bakri: When it comes to parsing out the effects and the different types of compounds in this category — there's the ghrelin side, the ghrelin agonists like MK-677, which is not FDA approved, an orally available pill that makes you bleed out growth hormone. You make so much growth hormone in response to that, in a non-pulsatile fashion. Growth hormone is a very circadian hormone that gets released in the first 90 minutes of slow-wave sleep. If you miss that big pulse, you're going to get small pulses throughout the day. The secretagogues will address the broader category of something called somatopause. You've heard of menopause, you've heard of andropause. Somatopause is this event that happens somewhere in the 30s where growth hormone production dramatically decreases. Your pineal gland is aging before puberty, your thymus right after puberty in your 20s, and in your 30s you're having somatopause — your growth hormone production is decreasing. You're having adrenopause where your adrenals stop making as much DHEA. And then you're having menopause, andropause, and all the other chronic conditions. So it's like your first 50 years of life, that's what you have to expect.
The question has been — and it's a big debate in the medical community — is replacing growth hormone and addressing somatopause useful? Because you can measure: if we had your IGF-1 when you're 18 and your IGF-1 when you're 30 and 50, it's going to be a dramatic decrease. Should we replenish this IGF-1? The proponents will say IGF-1 is important for skin, good quality sleep, muscle recovery, joints — and those are true. We know growth hormone has all these beneficial effects. We also know growth hormone is thymus-regenerative because it stimulates the regrowth of an aged, involuted thymus gland. Based on Dr. Fahy's work. The question is: is there an oncogenic signal when it comes to growth hormone?
Huberman: Does it cause cancer?
Dr. Bakri: Can it promote more rapid growth of existing cancer? I don't think anyone thinks it causes cancer. This is the big debate when people say BPC causes cancer — there's no mutagenic effect from BPC, like smoking a cigarette. Smoking a cigarette, you get carcinogenic damage to the lung tissue that causes cancer later on. There's no direct mechanism that would link any of these peptides to a carcinogenic effect. But is it a growth factor that could grow a cancer potentially? There isn't good data showing that. The debate may be: by boosting thymic function from growth hormone, are you increasing immunity and immune surveillance of different tumors, and therefore decreasing cancer risk? There's a big debate about whether growth hormone is even beneficial when it comes to aging, because growth hormone does grow certain tissues. There are models where people are growth hormone deficient and they live a lot longer. And growth hormone is not positive when it comes to a cardiometabolic perspective.
Huberman: In species like dogs, there's tremendous variation in the amount of IGF-1 made between a chihuahua and a Great Dane. The breed that makes more IGF-1 lives a lot shorter life than smaller versions of the same species. So you want a dog around for a long time, get a chihuahua. Then you get into antagonistic pleiotropy — is this something that's good in youth but detrimental for longevity? That's the big debate in the longevity field.
Dr. Bakri: Growth hormone has become very difficult to acquire through clinical prescriptions after the whole anabolic steroids act. So people have now shifted to using secretagogues in lieu of growth hormone. Also, growth hormone is very expensive — Pfizer's pens are in the thousands of dollars. So if you want it and you're rich you can afford it, but otherwise a secretagogue costs less than $100.
Huberman: I'm told that growth hormone doesn't shut down one's own production. I'm also told that when people take it, they feel awesome — which is scary to say on a podcast because you don't want everyone running out. But that combination of looking younger, feeling great, cognitively feeling great — I have some friends who've taken like an IU a night or even two IUs a night, five nights a week for years. And you go, "Hey, are you worried about some of the tumor effects?" And they're like, you just function at a whole other level.
Dr. Bakri: We don't have a data set that would show that. Like, where's the body count from growth hormone? The bodybuilder body counts are from other compounds, not growth hormone. When you go into a gym, you can tell who's doing growth hormone versus not based on their skin shining — you see a 45-year-old dude who's through somatopause but has perfect young skin. Growth hormone favors the conversion of T4 to T3, so it changes the thyroid dynamics. It can have pro-testicular effects as well from the IGF-1 perspective. The question is: is it a good idea to replace it? Traditionally the medical field is kind of anti using these secretagogues to augment somatopause. But I think there's going to be a role for it, perhaps cyclically. What if you did a cyclical course of tesmorelin for a certain amount of time, got your IGF-1 to a certain level under clinician guidance, measured your thymus on an MRI before and after, and saw that the thymus grew and you had higher CD4/CD8 count? That would be pretty interesting.
Huberman: A few years back I tried sermorelin. It dramatically increased my deep sleep and like nuked my REM sleep — the opposite of pinealon. The other thing it did — the reason I halted it almost right away — was that it spiked my PSA, my prostate-specific antigen. It had always been in range and relatively low. Boom. Spiked it. Off it. It reverted to a low level. So obviously I'm hyper-responsive in my prostate to sermorelin.
Dr. Bakri: As you age, your prostate gets bigger. The bane of every man is going to be BPH — that's going to be the reason you hate your life when you're in your 60s and 70s, because you have to wake up at night to pee. There are some prostate peptides we're looking at. The prostate is growing with age under the control of DHT, estrogen, and probably growth hormone. So the question is: do you want to be messing with that and increasing the size of that? There are concerns about cardiac growth, liver growth. Growth hormone and the secretagogues also have a negative effect on insulin sensitivity.
Huberman: Right.
Dr. Bakri: People's A1C's will usually jump. The joke in the bodybuilding community is you have to get lean enough and healthy enough to be able to take growth hormone. Tesmorelin especially, when combined with ipamorelin — tesmorelin is FDA approved, ipamorelin is not — those two together can create a giant growth hormone response where your IGF-1 is in the 380s, 390s. That's quite high — puberty levels of IGF-1. And you're hungry all the time with MK-677. Tesmorelin has more fidelity, less ghrelin effects, especially because you can have ghrelin effects, prolactin effects, and cortisol effects from whenever you're mucking around with the pituitary. MK-677 bleeds out the worst when it comes to having those other effects. MK is not a peptide — it's a non-peptide GHRP.
The Trinity Stack: GLP-1, Growth Hormone, and Androgen Modulation
Huberman: What's happened now is people are stacking their GLP-1 as their insulin sensitivity tool, their growth hormone or their GHRP, and their androgen modulation therapies as this trinity stack to get very fit, very healthy quickly. So a lot of these transformations you see in CEOs and celebrities is using a combination of those three things — your TRT plus maybe anavar with zepatide or retatrutide, and then using growth hormone modulation, whether you can afford growth hormone or that's more ipamorelin. And you're seeing people lose a lot of fat and gain a lot of muscle in short amounts of time. Is that healthy?
Dr. Bakri: We'll find out. But that is like the celebrity protocol.
GLP-1 Drugs: History, Mechanism, and Concerns
Huberman: Let's talk about GLP-1s. I've never taken one of these. We're hearing that some people — I think Sam Altman actually talked about this publicly — overdosed, and it was apparently a compounding pharmacy issue. He talked about the kind of lack of motivation, which many people have described anecdotally — lowered their food drive, but lowered their drive period. Do you think that's a real effect? Is that something people need to be concerned about?
Dr. Bakri: You have your semiglutide, which is Ozempic, and Wegovy is the FDA approved version for weight loss. For tirzepatide you have Zepbound and Mounjaro. These medications are genuinely transforming medicine, especially where I practice. If we zoom out, our medical system — if we didn't have these interventions — was going to collapse on itself thanks to the obesity, pre-diabetes, and diabetes epidemics. We don't have enough clinicians or finances to take care of all these people. Now these GLP-1s are coming in and kind of transforming that phase of medicine. We needed something to happen. Ideally, everybody would get morning sunlight, eat only healthy unprocessed foods, have low stress, and sleep great at night, and maybe no one would develop obesity. But the reality is people become overweight and obese. They get stuck in that hole. And if you just try to step out of the hole the way you came in, sometimes that doesn't work. You need a different path out of that problem. That's been the diet and exercise literature for the last 40 years. Millions of books have been sold on how to get people leaner. We now have interventions medically that can dramatically change people's weights for the first time. With the GLP-1s we're getting 10, 20, even 30% of body weight being shaved off of people, especially with the new retatrutide data. Is there a free lunch? That's the big question. So far the data is very promising when it comes to GLP-1s and reversing this rate of chronic disease. I'm cautiously optimistic. I've been prescribing them since I was a resident. In my VA clinic, I was putting all these vets that are 300 pounds on GLP-1s and they were losing 50, 100 pounds — before it was FDA approved for weight loss. We knew that if you put diabetics on this drug, they would lose weight, thanks to a lot of the bodybuilders who kind of pioneered that.
Huberman: When did the bodybuilders first start using GLP-1s?
Dr. Bakri: Late 2010s. And then the signal — I don't think Novo Nordisk or Lilly wanted to make these for obesity. They were focused on making diabetes drugs. This is another animal-derived compound, right? It's found in the saliva of the Gila monster. GLP-1 was discovered. It's too short-acting to have worked on its own. Then pharmaceutical companies — and this is where you've got to give pharma their credit — developed these drugs into more functioning versions that had longer half-lives and could stick around in the serum for longer to have the clinical effect. So then we started noticing that diabetics were losing weight and more energetic. It gets translated into obese people and overweight patients. The question is: what is the long-term effect of this? Do you have to stay on this drug forever? Can you taper it off? The pharmaceutical companies have not given us good guidelines on that. They've shown us what happens if you stop the drug — people tend to sometimes gain the weight back. Some people don't, but some people will regain back to baseline. Because the better way to think about weight loss is it's a calculation your brain does every single day with all the different hormones and peptides made from the gut — GIP, GLP, glucagon, insulin, testosterone, estrogen — all these things modulate whether you should eat or not eat. The GLP-1 is a giant signal to the brain of "don't eat." What happens to all these young kids that are 18, 19 years old on 5 milligrams of retatrutide that have lost 30, 40 pounds? Are they going to have to be on that for life now to maintain that weight?
Huberman: When people say perhaps you have to be on a drug for the rest of your life, I think: what's the availability, what's the cost, what's the real-world cost of taking six months off because you can't access it? I kind of feel like eventually there'll be some slow-release polymer that will just give you a micro dose of it. But what about these brain effects? I do worry about a brain that's developing in the context of a thousandfold or more increase in these GLP-1s. When we had Zach Knight on the podcast — he's a scientist at UCSF, Howard Hughes investigator — he described that the diabetic drugs would increase GLP-1 by like double or quadruple, but the weight loss effects weren't really there. But the drugs you rattled off — Mounjaro, Ozempic, and certainly retatrutide — we're talking about thousandfold increases in GLP-1. We don't know what the long-term effects of those are on neuroplasticity and learning.
Dr. Bakri: Could be positive. We shouldn't always assume those effects are bad. Like the effects for a 60-year-old pre-diabetic on Alzheimer's disease seems to be potentially positive. The question is: what about these cognitive effects? Is the effect happening from the drug itself? Is it from misuse of the drug — too high a dose, not getting enough electrolytes, not getting enough micronutrients, macronutrients, blood sugar is low? A lot of these patients — the way we approach it is a training wheel effect when it comes to GLP-1s. You come to us, you're a patient, you want to use GLP-1s, we'll give you the lowest dose possible that has an effect for you, in conjunction with lifestyle modification, dietary advice, exercise programs, and then hopefully peel away those training wheels or keep them on if you need them. When people do it that way, I don't hear a lot of these effects anecdotally from our patients that we hear about online where people are like, "Oh, I'm depressed, I hate my life from these drugs." The question is: are they just having low blood pressure because they're not consuming enough electrolytes or enough food? Some people will take a mega dose and end up not eating — a day goes by, they've eaten one meal. That's not conducive to feeling good. Eating is such a pleasurable and social experience for humans. If you're not eating with people at the same table, are you having less of that socialization aspect? I'm very curious when it comes to the cognitive effects — is it from the drug directly interacting with receptors in the brain, or is it because of the social aspects of the drug changing the way you behave and therefore leading to negative outcomes?
We know the literature shows that people are having less alcohol cravings from this. It might be changing the way dopaminergic signaling is happening in the brain, which is concerning. Because a lot of people will be stacking this with ADHD medications. What happens is people go to these websites, they buy one more peptide and they got a great result, and they'll be like, let me add three more peptides on top.
Huberman: Yes, it's an increasing average order value problem from these research sites.
Dr. Bakri: The reality is it's here. There is no pre-GLP-1 world for us as clinicians, as health enthusiasts. We're in a post-GLP world and everything kind of dictates downstream from that.
Retatrutide, Patent Strategy, and the Future of Peptide Medicine
Huberman: I put out a post on X. I thought — and I do still think — that retatrutide is going to be a trillion-dollar industry. Not because so many people are necessarily going to use it for weight loss, but because many people will use it for weight loss, and many people will use it for other things. You can be sure that Lilly is going to find other ways to market it. And you can protect a patent by finding additional uses for things.
Dr. Bakri: The big thing they're trying to do now is classify it as a biologic. Retatrutide has 39 amino acids. To be a biologic you have to be above 40 amino acids. And once you get to above 40 amino acids, if you are a biologic, then the patent lasts way longer — like 15 years. If it's 40 or below amino acids, it's something like five to seven years. So we're talking hundreds of millions, maybe billions of dollars. And more importantly, no one can compound it if it's a biologic. Something similar happened with hCG, where it was taken out of the compounders recently. This is a very important thing because if Lilly gets retatrutide classified as a biologic, the compounders are out of luck. They all have the formula for retatrutide, they're ready to make it — they can get the API from China and start compounding it as soon as it's available. It will make them all billions of dollars. But if Lilly is able to do this, they'll be able to protect themselves. The Trump administration is now trying to get Lilly and Novo Nordisk to drop their prices to make it more available, which has happened — now I think you can get a $300 monthly dose of tirzepatide available through these websites. And there's the oral semaglutide pill — you can pay $150 a month for that, which is not a peptide but still a GLP-1 agonist. Which kind of gets to the point: it doesn't matter if it's a peptide or not. What matters is where it touches, what receptor it touches. Because oral semaglutide is more similar to injectable semiglutide than BPC-157 is to semiglutide. So everyone online talking about peptides are good or peptides are bad — there's no actual scientific category of peptides that gives you a functional definition that's discussable between two people. Because what do you mean by peptide? Do you mean carnosine or do you mean retatrutide?
Huberman: Excellent point — speaks to a lot of the confusion. I'm going to put in a vote publicly right here and now: I think you should be in charge of a nomenclature committee. In the world of genetics, people would just name genes Sonic Hedgehog or whatever, and it was a mess. Eventually you have a meeting, you come up with a nomenclature committee, and you say this is ephrin 1, 2, 3, 4, 5, 6 — these are the sequences. The general public are diving right into this. They are the experiment. So what I think would be very useful would be a clear and accessible nomenclature to divide up what we've talked about today — BPC-157, peptides with and without known receptors, the regenerative peptides like thymosin alpha-1 and TB-500, which are immunogenic peptides. The word "peptides" is just too general.
Dr. Bakri: Right. We're not taking the stance these are good or bad, but just for sake of clarity, given that there are so many people who are peptide curious.
GHK-Copper and Collagen
Huberman: GHK-copper. Most of the questions I get about it are from women. I sent out a little informal poll to the women in my life including siblings, and almost all of them said, "What about GHK-copper? I hear it can be good for my skin. Should I use it topically, take it orally, or inject it?" A lot of interest in this. What is it? Why has it made it into this aesthetic category?
Dr. Bakri: GHK-copper is a tripeptide with a copper ion in the middle. It's glycine, histidine, and lysine. It's actually found in type one collagen fibers — all over your skin, hair, and connective tissue. Just like Vladimir Cavinson discovers these 40 different peptides from different organs, there's an American researcher, Dr. Loren Pickart — who has passed now — who discovers GHK-copper in the collagen tissue. He's like, hey, this might be the factor that controls collagen synthesis and also collagen breakdown. He does a bunch of studies — his work is all about this. So almost all the literature comes from this one lab, a common theme in peptides unfortunately. He discovers it in maybe the mid-70s. It's found to be very high in youth in serum levels — up to about 200 nanograms per whatever the unit was — and then gets down to the levels of the 60s by the age of 65. So it dramatically decreases with age. It's thought to be maybe what leads to the youthful appearance of young skin, and with age you lose that effect. He did a bunch of trials both topically for skin and for hair. There's now injectable work being done. Similar to BPC, they would cut rats open, inject GHK-copper in a different site, and they'd get faster wound repair of the skin tissue. It's become synonymous with BPC-157 and TB-500 — the "Wolverine stack," which someone online just made up.
Huberman: What's the Wolverine stack?
Dr. Bakri: TB-500 and BPC-157. Now people will add on GHK-copper and call it the glow stack.
Huberman: Oh, interesting. Someone has made it up in a research chemical context.
Dr. Bakri: There's a big debate about whether mixing those together causes denaturing of different peptides. But the point is GHK-copper both upregulates the synthesis side of collagen and the breakdown side of collagen. Because when you're remodeling tissue, if you're just rebuilding it, you're going to get very pathogenic structures. And if you're just breaking down, you're getting bad structures. So you're doing both. The Pickarts compared it to retinol and vitamin C creams with positive effects, and people anecdotally talk about their crow's feet going away topically. There was a study on hair that didn't seem too promising — it's not going to be better than minoxidil. Maybe it could be an adjunct. And now there's a Chinese group studying it for lung regeneration because there's a lot of connective tissue in the lungs between the different alveoli. Long COVID lung damage might be an interesting place for it to remain peptide curious.
Huberman: And thymic atrophy is a big part of post-COVID, I suspect.
Dr. Bakri: Yes, because any infection leads to thymic atrophy — the thymus kind of shrinks down and then the idea is that you recover, you convalesce, and then you regenerate your thymus in the state of health. I think the problem in modern day is people are stressed out, they're at work, they get sick, and they keep getting sick. So they never get this chance for thymus rejuvenation. Then they're constantly getting hit down and ending up with these diseases of aging that could have maybe been ameliorated had their thymus function been better in youth.
Huberman: If you look back at the literature on convalescing, how long were people recommended to take some time off after a cold or a flu? Do you think people are getting back to work too quickly?
Dr. Bakri: Nothing that they do once they come back is additive to healing. Their circadian rhythms are thrown off. They're under malilluminative lights all day. They're not getting sunlight. Their vitamin D levels are atrocious. Their blue light exposure at night is high. Their stress levels are very high. Their guts are inflamed from eating processed, hyper-palatable foods. They have obesity or they're pre-diabetic. So all these things lead to this inflammatory state, and they just got sick and their thymus didn't bounce back. Post-pandemic, a lot of my colleagues were like, "Dude, I get sick three or four times a winter now. Before, I'd get sick once a winter." So this is where the interest in thymic peptides is very relevant. We have to figure out if the synthetic thymic peptides or the purified thymic extracts are the more interesting ones. Vladimir Cavinson came up with the thymulin injectable and oral versions, and he had positive immune markers — CD4 cells come up, CD8 cells improve, all his immune markers become a more youthful state. But unfortunately, we don't have thyomologists — we don't have a branch of medicine dedicated to this aspect of immunity. Post-pandemic, a lot of people started to ask how they can have better immunity for themselves. And now finally people are starting to talk about the thymus. Unfortunately it's been too little too late. That would have been great during the pandemic — we could have used thymic-focused interventions, whether zinc or thymic peptides or purified thymic extracts, to augment immunity of the population as a whole.
Audience Questions: Endometriosis, CNS Effects, and TBI
Huberman: Before we wrap, I solicited X and Instagram for questions about peptides. One thing that came up several times is the question about women who have endometriosis or fibroids or other things related to reproductive health. Can things like BPC-157 help and or hurt those circumstances given their potential role in angiogenesis?
Dr. Bakri: No literature exists on either animal or human data that relates to those peptides in those conditions. I'd say those are more hormonal and metabolic issues that a good OB-GYN should take care of. They're very difficult to treat conditions. Those are more on the hormonal side. I think the hormonal lever is way stronger than a peptide lever like BPC or any of those. And as far as I'm concerned, there are no case reports or studies that would suggest positive or negative effects.
Huberman: CNS effects — central nervous system — of BPC-157 or other peptides that don't fall under the typical umbrella. You talked about some of the stuff related to alcohol and perhaps Adderall, but anything known about people feeling better or worse on different peptides psychologically or neurologically? And TBI — I know many people who reach out to me about that. Could it be beneficial in those cases?
Dr. Bakri: There were studies in Russia on TBI when it comes to cortexin and cerebrolysin, which would probably never be available in the United States. There's no good data on BPC and TBI. They theoretically could be useful from an anti-stress perspective. BPC's neurological effects are very homeostatic in nature. They don't let you get too high in the mice data at least — the mice can't get too drunk and they can't withdraw from alcohol. They can't get too high on methamphetamines and they don't withdraw either. So there's a homeostatic mechanism that might explain some of these anhedonia side effects that people are reporting, where BPC modulates the gut-brain axis in a way we do not understand — it's kind of woo-woo — that makes it so that your brain can't go too far in one direction. Maybe, if we think of a just-so story, it's putting you into a rest-and-digest state to heal whatever problem you have. If that's why BPC exists as a big parent compound, that might be part of the fact that if you secrete BPC, your body goes into a convalescent mode — it will take away stimulants, it will take away sedatives. There seems to be a homeostatic mechanism in BPC that needs to be explored further with good data.
How to Safely Obtain Peptides
Huberman: The major question was: what should people do if they are actually interested in obtaining peptides — let's set the GLP-1s aside — and they want to explore their use and be as safe as possible? Where shouldn't they look? And where should they look? Who should they talk to? At what point can they be confident that what they're taking is what the bottle claims and is free of contaminants?
Dr. Bakri: It's the most difficult question to answer because the majority of people are getting their peptides from research-only websites. Unfortunately, those are not reliable. We don't know what's in them. They could be good, could be bad, could be as good as a compounding pharmacy, could be much worse, could be the wrong peptide in the vial. What should happen over the next 6 to 24 months is there will be a lot of physician-led options for patients to get peptides. Number one, you should encourage your physician — if you don't have one, get one, and get a good relationship with one, because having a good relationship with your physician is a key aspect of driving good health. To my doctor friends: all of you are now living in a peptide era. You have no choice but to get educated. There will be a lot of telehealth options opening up soon through various companies that will offer these peptides, and it will be good for the consumer because it'll be a race down in price. You should get them from clinicians. The question that's going to happen is there's going to be a lot of these orally available peptides all over supplement websites — you'll find them with your magnesium and your creatine and then your pinealon or your BPC-157. We'd like our FDA overlords to give us some guidance on what can and cannot be sold and bought. But it should be physician-led. You should be doing this under the guidance of a physician who's monitoring you. You shouldn't be taking tesmorelin without checking IGF-1 levels. A GLP-1 even should be monitored by physicians who can counsel you on too much weight loss. Unless someone has the basics in place — morning sunlight, sleep, darkness at night, good diet, minimally processed food — there's no point in putting all these peptides in. The next phase of peptide-curious and peptide-driven discussions is going to be: how do you incorporate it into a giant health system? There's going to be protocols that develop. But I think within six months there'll be very good physician options for everybody.
Huberman: Abud, amazing. Thank you so much for coming here today and shedding so much light on what all of these things are. You have a clearly virtuoso-level understanding and ability to communicate about the history of these things, what they are, what they aren't, what we know, what we still don't know, the potential upsides, the potential hazards, the regulation, and on and on. There are 50 other topics that you and I must talk about at some point — your knowledge of hormones in men and women, pregnancy and women's hormones affecting the fetus, how progesterone impacts DHT and male offspring. Absolutely want to have you back to have that discussion. And I just want to say thank you for doing what you do. And if you don't mind me sharing — you're 33 years old. I love that you're a clinician and you're practicing medicine, but please keep up your efforts as a public educator. Come back and talk to us again. You're a gift to us all.
Dr. Bakri: Thank you. It's a pleasure to be here, and thank you for the kind words.