Hemorphin (Hemorphins)
A family of 'atypical' opioid peptides released from hemoglobin — they bind opioid receptors and act on the blood-pressure system. Research molecules, not drugs
Hemorphins are opioid peptides hidden inside hemoglobin, the oxygen-carrying protein of red blood cells. When the hemoglobin beta-chain is broken down, it releases short peptides built around the core sequence Tyr-Pro-Trp-Thr — hemorphin-4 — which can be extended into hemorphin-7 (YPWTQRF), LVV-hemorphin-7 (LVVYPWTQRF), VV-hemorphin-7, and valorphin (VV-hemorphin-5), among others. They are called 'atypical' opioid peptides because, beyond binding opioid receptors, they do something most opioids don't: they act on the renin-angiotensin system that controls blood pressure, inhibiting angiotensin-converting enzyme (ACE) and modulating the angiotensin II type-1 receptor. That dual personality — pain and blood pressure — has made them a long-running research subject, alongside roles in memory and as biomarkers that rise in conditions from sepsis to tumours. Chemists have built many analogs to sharpen their analgesic or anticonvulsant effects. Hemorphins are studied as endogenous regulators and leads; they are not approved medicines and have not been given to people as a treatment.
No established human dose Details ↓
Recommended Dosing
No established human dose
Hemorphins are peptides the body makes when hemoglobin is broken down; none has been given to people as a treatment. The work is in cells and animals (often with synthetic analogs) at experimental amounts that do not carry over to people, and the human studies only measure natural hemorphin levels.
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What is it?
Hemoglobin is best known for carrying oxygen, but when its beta-chain is digested it yields bioactive peptides. In 1986, Brantl and colleagues described a set of opioid peptides derived from hemoglobin and named them hemorphins. They are built around a short core, Tyr-Pro-Trp-Thr (hemorphin-4), which is extended to give hemorphin-7 (YPWTQRF), LVV-hemorphin-7 (LVVYPWTQRF), VV-hemorphin-7 (VVYPWTQRF), valorphin (VV-hemorphin-5, VVYPWTQ) and related forms. The spinal peptide spinorphin (LVVYPWT) is a close relative from the same region of hemoglobin.
Hemorphins are described as 'atypical' opioid peptides: they bind opioid receptors and can also release other endogenous opioids, giving them analgesic activity. What sets them apart from classic opioid peptides is a second target — the renin-angiotensin system that governs blood pressure. Hemorphins inhibit angiotensin-converting enzyme (ACE), and LVV-hemorphin-7 was shown to act as a positive allosteric modulator of the angiotensin II type-1 receptor (AT1R): in cell and molecular-dynamics studies it bound an intracellular region of the receptor and enhanced angiotensin II binding, consistent with its reported role in blood-pressure control.
Their analgesic side has been explored mostly through analogs. Valorphin (VV-hemorphin-5) analogs carrying aminophosphonate groups produced significant pain relief in the mouse formalin test, with the design (which residues, how many) shaping potency in the acute versus inflammatory phases. Other work built a light-switchable (azobenzene) valorphin analog whose 'Z' form had anticonvulsant activity in mouse seizure tests — illustrating how hemorphin scaffolds are engineered to probe and tune central effects.
Hemorphins have also emerged as biomarkers, because they appear when hemoglobin is broken down. In a prospective ICU cohort, LVV-hemorphin-7 levels were associated with sepsis and with shock in critically ill patients, alongside the lysosomal enzymes (cathepsins) that help generate it — an observational association, not a treatment. Hemorphins have likewise been studied as markers in other conditions and proposed as part of the mechanism behind cupping analgesia, where hemoglobin breakdown under the skin could release them locally.
Across all of this, hemorphins are endogenous peptides and research subjects. No published study has given a hemorphin to people as a treatment, none is approved anywhere, and material sold online under these names is an unregulated research chemical. Nothing here is a dose or a therapy; this page records what the published science says.
Mechanism of Action
Hemorphins are hemoglobin-beta-derived 'atypical' opioid peptides. They bind opioid receptors (analgesia) and also act on the renin-angiotensin system — inhibiting ACE and positively modulating the angiotensin II type-1 receptor — linking them to blood-pressure control. They appear when hemoglobin is broken down, giving them biomarker roles.
Hemoglobin breakdown
Released by proteolysis of the hemoglobin beta-chain (core Tyr-Pro-Trp-Thr, extended to hemorphin-7, LVV-/VV-hemorphin forms, valorphin) (PMID 3743640).
Opioid-receptor action
Bind opioid receptors and can release other endogenous opioids, giving analgesia in animal models (PMIDs 32798365, 37273272).
Renin-angiotensin / blood pressure
Inhibit ACE and positively modulate the angiotensin II type-1 receptor (AT1R), linking hemorphins to vascular and renal physiology (PMID 33379211).
Published Research
These are studies of hemorphins read from their PubMed records on November 7, 2026: the 1986 discovery paper describing opioid peptides from hemoglobin; a study of LVV-hemorphin-7's positive modulation of the angiotensin II type-1 receptor; animal studies of valorphin (VV-hemorphin-5) analogs for pain and seizures; a human ICU cohort linking LVV-hemorphin-7 to sepsis and shock; and a review proposing hemorphin-based analgesia in cupping. The human data are observational biomarker work; hemorphins have not been given to people as a treatment.
Discovery: opioid peptides derived from hemoglobin (hemorphins)
Brantl and colleagues identified a set of opioid peptides derived from hemoglobin and named them hemorphins, characterising their opioid activity in smooth-muscle (opioid) bioassays — the founding description of the hemorphin family of hemoglobin-derived opioid peptides (a discovery study).
LVV-hemorphin-7 positively modulates the angiotensin II type-1 receptor
In HEK293 cells and molecular-dynamics simulations, LVV-hemorphin-7 bound an intracellular region of the angiotensin II type-1 receptor (AT1R) and acted as a positive allosteric modulator, enhancing angiotensin II binding — supporting the pharmacological targeting of AT1R by hemorphins, with implications for vascular and renal physiology (a mechanistic study).
Valorphin (VV-hemorphin-5) analogs relieve pain in mice
Valorphin (VV-hemorphin-5) and aminophosphonate-modified analogs produced significant antinociceptive effects in both the acute and inflammatory phases of the mouse formalin pain test; modified heptapeptide analogs matched or exceeded the parent peptide, clarifying how valine residues and peptide length shape hemorphin analgesia (a preclinical result).
A light-switchable valorphin analog with anticonvulsant activity (mice)
An azobenzene-containing VV-hemorphin-5 analog was synthesised as a photoswitch; its light-induced 'Z' isomer showed higher anticonvulsant potency than the 'E' isomer in mouse 6-Hz psychomotor and pentylenetetrazol seizure tests and altered model lipid-membrane electrical properties — demonstrating a tunable hemorphin scaffold (a preclinical result).
LVV-hemorphin-7 is associated with sepsis and shock (human ICU cohort)
In a prospective cohort of critically ill ICU patients, blood LVV-hemorphin-7 differed between septic and non-septic patients and was a significant predictor of both sepsis and shock, alongside the lysosomal enzymes cathepsin D and G that help generate it from cell-free hemoglobin — an observational biomarker association, not a trial of giving hemorphin.
Hemorphin-based analgesia as a mechanism of cupping (review/hypothesis)
A review proposing that the local analgesia of cupping may involve hemorphins: cupping draws out and breaks down hemoglobin beta-subunit under the skin, which would release hemorphins that engage opioid-receptor signalling — framing hemorphin as both a candidate mechanism and a potential biomarker for assessing cupping (a hypothesis review).
No Established Human Dose
Hemorphins are peptides the body makes when hemoglobin is broken down; none has been given to people as a treatment. The work is in cells and animals (often with synthetic analogs) at experimental amounts that do not carry over to people, and the human studies only measure natural hemorphin levels. No regulator has approved any dose, and no published human dose exists, so no amount is printed here.
What this rests on: PMID 3743640, PMID 32798365, PMID 39767696.
Educational information, not medical advice. The doses on this page come from approved labels, published studies and, where no study exists, amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
What a Buyer Needs to Know
What is sold, how it is mixed, stored and taken, and what is known about its safety, quality and legal status. Each part names its source. Where we have none, it says unknown.
What is sold
Unknown: we hold no label and no published test that says what forms or vial sizes Hemorphin (Hemorphins) is sold in. A vial's own label is a seller's claim, not a source.
Mixing a vial: a worked example
Unknown: no human dose of Hemorphin (Hemorphins) has been established (see No Established Human Dose below), so there is no amount to work out. The reconstitution calculator does the arithmetic for any vial, water and dose.
Storage before and after mixing
Unknown: no label or published stability study on file says how to store Hemorphin (Hemorphins), before or after mixing. The mixing guide sets out the general rules, with their sources: keep a mixed vial in the fridge, and use it promptly, as the bacteriostatic water label says of any drug dissolved in it. The 28 days often quoted is the limit for an opened multiple-dose vial from a manufacturer, an outer limit set for sterility, not a time a mixed solution has been shown to keep. Nobody has published how long Hemorphin (Hemorphins) stays intact once mixed.
How it is taken
Unknown: with no established human dose, there is no established way of taking Hemorphin (Hemorphins). What the human studies gave and how is set out under No Established Human Dose.
What to expect, and when
How long it stays in the body: a half-life of short; small endogenous peptides, with many stabilised analogs made. After about five half-lives almost none is left.
When effects appear: unknown; no source on this page gives a time to effect for Hemorphin (Hemorphins). Results reported in the studies are under Published Research.
Source: half-life: PMID 32798365.
Side effects, and when to stop or get help
From the Side Effects section: No human adverse-event data exist: no published study has administered a hemorphin to people as a treatment; They act on opioid receptors AND the renin-angiotensin (blood-pressure) system, so effects on pain AND blood pressure would both be expected considerations — a mechanistic inference, not human data; Raised hemorphin levels mark hemoglobin breakdown and have been associated with sepsis and shock (PMID 39767696) — a biomarker signal, not a drug safety profile; Material sold online as 'hemorphin', 'LVV-hemorphin-7' or 'valorphin' is an unregulated research chemical. Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Hemorphin (Hemorphins). Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“Hemorphins are endogenous peptides that have not been given to people as drugs, so there is no human safety profile; the points below reflect that research status and their biology”).
Interactions
Unknown: a PubMed search for human interaction studies of Hemorphin (Hemorphins) (reviewed 2026-11-07) found none. Unknown is not the same as safe to combine.
Every peptide's record, with its source: the interaction matrix.
Checking what you bought
Unknown: no published independent test of Hemorphin (Hemorphins) products is in our lab-results database yet, so how products sold under this name measure up is not known.
To read a certificate of analysis, paste it into the COA decoder. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: Research Chemical (Not drugs: Drugs@FDA and the openFDA label endpoint hold no record, and FDA GSRS and ChEMBL hold no drug record for hemorphin peptides (hemorphin-7, LVV-hemorphin-7, valorphin) (searched November 7, 2026)). Sport: Not on the 2026 List.
Country by country ↓ · Regulatory tracker
Source: this entry's approval status and the WADA Prohibited List, as in Legal Status below.
Side Effects & Contraindications
Reported Side Effects
Hemorphins are endogenous peptides that have not been given to people as drugs, so there is no human safety profile; the points below reflect that research status and their biology.
Contraindications & Cautions
Hemorphins have no approved use and no label. These points reflect their research status.
Legal Status
Hemorphins are endogenous hemoglobin-derived peptides studied as research compounds; they are not drugs and are not approved in any country.
Frequently Asked Questions
?What are hemorphins?
Opioid peptides released when hemoglobin's beta-chain is broken down. They share a Tyr-Pro-Trp-Thr core and include hemorphin-7, LVV-hemorphin-7, VV-hemorphin-7 and valorphin (PMID 3743640).
?Why are they called 'atypical' opioids?
Because beyond binding opioid receptors they also act on the renin-angiotensin blood-pressure system — inhibiting ACE and modulating the angiotensin II type-1 receptor (PMID 33379211) — which classic opioid peptides do not.
?Are they used in medicine?
No. Hemorphins are studied as endogenous regulators and as biomarkers (e.g. LVV-hemorphin-7 rises in sepsis, PMID 39767696), but none is an approved drug and none has been given to people as a treatment.
?Can I buy them?
Material sold online as hemorphin, LVV-hemorphin-7 or valorphin is an unregulated research chemical. Grey Peptides lists no sellers and recommends no source; this page records the published science.
References
- [mechanism] Brantl V, et al. "Novel opioid peptides derived from hemoglobin: hemorphins." Eur J Pharmacol, 1986;125(2):309-10. PMID: 3743640.
- [mechanism] Ali A, et al. "Insights into the Interaction of LVV-Hemorphin-7 with Angiotensin II Type 1 Receptor." Int J Mol Sci, 2020;22(1). PMID: 33379211.
- [animal] Assenov B, et al. "Antinociceptive Effects of VV-Hemorphin-5 Peptide Analogues Containing Amino phosphonate Moiety in Mouse Formalin Model of Pain." Protein Pept Lett, 2021;28(4):442-449. PMID: 32798365.
- [animal] Todorov PT, et al. "Synthesis, characterization and anticonvulsant activity of new azobenzene-containing VV-hemorphin-5 bio photoswitch." Amino Acids, 2019;51(3):549-563. PMID: 30604096.
- [clinical-trial] Wu YK, et al. "Association of LVV-Hemorphin-7 with Sepsis and Shock: Roles of Cathepsin D and G in Hemoglobin Metabolism in a Prospective ICU Cohort Study." Biomedicines, 2024;12(12). PMID: 39767696.
- [review] Song C, et al. "Hemorphin-Based Analgesia: A Mechanism of Cupping Technique?." J Pain Res, 2023;16:1751-1754. PMID: 37273272.
- [other] Hemorphins are opioid peptides released by proteolysis of the hemoglobin beta-chain, first described by Brantl and colleagues in 1986; members share the core Tyr-Pro-Trp-Thr sequence extended at either end (e.g. hemorphin-7 YPWTQRF, LVV-hemorphin-7 LVVYPWTQRF), as described in the discovery paper and studies carded on this page (read November 7, 2026).
- [other] US FDA, Drugs@FDA and the openFDA label endpoint, searched November 7, 2026: no application and no label record for hemorphin peptides (hemorphin-7, LVV-hemorphin-7, VV-hemorphin-5/valorphin). They are endogenous hemoglobin-derived peptides studied in research, not drugs; FDA GSRS and ChEMBL hold no drug record for them.
Sources & Citations
The six studies carded above were read from their PubMed records on November 7, 2026. The hemorphin family's origin from hemoglobin, its core sequences, its opioid and renin-angiotensin (ACE / AT1R) actions, the valorphin analogs for pain and seizures, the LVV-hemorphin-7 sepsis biomarker association, and the cupping hypothesis are from the discovery paper, review and studies carded here; the absence of US approval or a drug record from Drugs@FDA, openFDA, FDA GSRS and ChEMBL was checked the same day. The related spinal peptide spinorphin is a hemoglobin fragment too. Grey Peptides sells nothing and links to no vendor.
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