Dihexa
What do these badges mean?
Evidence tier
- AHuman-validated — Human trials showing positive results and good safety.
- BAnimal-grade — No human trials yet, but solid animal/preclinical evidence of effect and safety.
- CAnecdotal — No human or animal trials — only anecdotal/observational reports.
- DInsufficient evidence — No or insufficient evidence (encyclopedia only — never recommended by the builder).
Safety light
- 🟢 Green — Only mild, manageable side effects; reasonable safety data.
- 🟡 Yellow — Needs active management, has a meaningful contraindication/interaction, or has thin long-term data.
- 🔴 Red — Risk of a hospital-level event — treat with serious caution.
Browse-only — not on the protocol builder's curated shortlist, so the builder won't recommend it.
What is it?
Dihexa (N-hexanoic-Tyr-Ile-(6)-aminohexanoic amide) is a synthetic six-amino-acid peptide derivative of angiotensin IV — the C-terminal fragment of angiotensin II. It was developed by Dr. Joseph Harding’s lab at Washington State University around 2011. The lipophilic, blood-brain-barrier-crossing structure makes it one of the rare peptides that’s actually orally active.
Dihexa sits in a different mechanistic category from the two best-evidenced Russian nootropic peptides, Semax and Selank, both of which work through fast-onset BDNF/NGF-upregulating receptor signaling. Dihexa is claimed instead to build new neural architecture directly — synaptogenesis rather than upregulating the brain’s existing repair signaling. That’s the pitch. The integrity status of the underlying claim is the reason this article exists.
What does it do in my body?
Dihexa is claimed to bind hepatocyte growth factor (HGF) with very high affinity and to potentiate HGF activity at its receptor c-Met, which is proposed to drive synaptogenesis — the physical formation of new synaptic connections between neurons.
The retraction — and what it means
The foundational paper has been retracted.
- Benoist CC, Kawas LH, et al. (Harding group) — Journal of Pharmacology and Experimental Therapeutics 2014, 351(2):390-402 — PMID 25187433 — RETRACTED 2025 (retraction PMID 40312093). Expression of Concern issued September 2021.
This is the paper that established Dihexa’s claimed HGF/c-Met mechanism and the widely-circulated claim that “Dihexa is seven orders of magnitude more potent than BDNF.” That number — and the entire mechanism case it rests on — traces back to this single retracted paper. The retraction was preceded by an Expression of Concern in 2021, then formalized in 2025.
What this means in practice: the marketing claim that Dihexa is the most potent nootropic ever discovered is built on a foundation that’s been pulled out from under it. Every peptide-info site and forum that still reproduces the “7 orders of magnitude vs BDNF” line is reproducing a claim from a retracted study. Most of those sites have not updated. OHM’s position: lead with the retraction. Being the credible source that reports the integrity story honestly is the play here, not amplifying the hype.
The follow-up Dihexa literature (also primarily from the Harding group) what’s still standing post-retraction. Beyond Benoist 2014, there are zero completed human trials for Dihexa.
How can it help me?
- Where the science stands: Foundational mechanism paper RETRACTED (2025); zero completed human trials; no independent replication located
The full evidence — every human, animal, and lab study, graded — is one tap away: use the See the deeper science → toggle at the top.
Is it dangerous? What are the side effects?
The safety database is essentially empty. This is the most important caveat — Dihexa is billed by some sources as “the most potent nootropic ever discovered” but the underlying mechanism paper is retracted and there is no meaningful human safety record.
Theoretical concerns worth taking seriously:
- The HGF/c-Met pathway is also a driver in multiple cancers — uncontrolled stimulation is a biologically plausible cancer-promotion risk oncology literature. Hard contraindication for active malignancy or cancer history.
- Angiotensin-pathway off-target effects on the cardiovascular system — unknown.
Regulatory status: Not FDA-approved. Not a controlled substance. PCAC review July 23-24, 2026: Dihexa is one of 12 peptides going to the FDA’s Pharmacy Compounding Advisory Committee for 503A re-evaluation. Even a positive vote would clear it for compounding only — not full FDA drug approval — and given the mechanism retraction plus the empty human safety database plus the HGF/c-Met cancer concern, Dihexa remains a low-confidence compound regardless of the PCAC outcome.
The Alyve / vendor picture. Dihexa is not sold through any of OHM’s affiliate vendors (Alyve, US Pure Peptides, or BioLongevity) at this time — it is, at most, a low-priority roadmap candidate given the retraction, the empty human safety database, and the HGF/c-Met cancer concern. The supply-chain trust story that anchors OHM’s other peptide content (US-manufactured, third-party COA, >99% purity) only works if the underlying molecule is one OHM is confident in — and Dihexa isn’t there yet.
Typical dosing
Talk to your medical provider before starting any protocol. That said, here are the doses most people commonly use — shared for educational purposes so you can have an informed conversation. These peptides are sold for research use only and are not FDA-approved drugs, and this isn't medical advice.
These numbers come from forum convergence, not from clinical trials — there is no validated dose-finding study for Dihexa in humans.
- Oral: 8-45 mg/day (wide community range).
- Subcutaneous: 2-5 mg/day.
- Cycle: No validated cycle length.
Sequencing rule (holds independent of the mechanism controversy). The operational rule for any synaptogenic compound is the same regardless of which specific molecule sits at the end of the chain: clear neuroinflammation first, then add the synaptogenic compound — never the reverse. A brain running hot with neuroinflammation doesn’t respond the way a clean brain does; you risk wasting the compound and masking what’s actually driving the cognitive issue. Clear the inflammation, get mitochondria functioning, hormones optimized — only then layer in a synaptogenic compound like Dihexa. This is the same logical pattern as the SS-31 → MOTS-c sequencing rule and is good general practice for layered cognitive protocols.
What should I avoid combining — and what's synergistic?
Dihexa doesn't have a dedicated stacking protocol in our notes — the interactions that matter most are in the safety section above. For how people combine it with other peptides, the deeper-science view has the full detail.
How can I buy this?
We don't have a verified affiliate source for Dihexa yet, so there's no coupon or vendor link here — we won't point you to a seller we haven't vetted. When buying any research-use-only peptide, the single biggest variable is the supply chain: insist on a vendor that publishes third-party Certificates of Analysis (COAs) confirming identity and >99% purity. Working with a peptide-literate clinician is one solid route — see our provider directory — or check back as our verified sources list grows.
A synthetic angiotensin IV derivative once billed as “the most potent nootropic ever discovered” — a claim that traces entirely to a foundational mechanism paper that has since been retracted. OHM leads with that fact rather than the hype.
| Class | Angiotensin IV analog (synthetic hexapeptide-derivative) |
| Sequence | N-hexanoic-Tyr-Ile-(6)-aminohexanoic amide |
| Mechanism (one line, claimed) | Binds hepatocyte growth factor (HGF), potentiates HGF at its receptor c-Met → synaptogenesis (new synapse formation) |
| Evidence base | Foundational mechanism paper RETRACTED (2025); zero completed human trials; no independent replication located |
| Safety record | Essentially no human safety database; theoretical HGF/c-Met cancer-promotion concern |
| Regulatory status | Not FDA-approved; not a controlled substance; under FDA PCAC 503A re-evaluation July 23-24, 2026 |
What it is
Dihexa (N-hexanoic-Tyr-Ile-(6)-aminohexanoic amide) is a synthetic six-amino-acid peptide derivative of angiotensin IV — the C-terminal fragment of angiotensin II. It was developed by Dr. Joseph Harding’s lab at Washington State University around 2011. The lipophilic, blood-brain-barrier-crossing structure makes it one of the rare peptides that’s actually orally active.
Dihexa sits in a different mechanistic category from the two best-evidenced Russian nootropic peptides, Semax and Selank, both of which work through fast-onset BDNF/NGF-upregulating receptor signaling. Dihexa is claimed instead to build new neural architecture directly — synaptogenesis rather than upregulating the brain’s existing repair signaling. That’s the pitch. The integrity status of the underlying claim is the reason this article exists.
How it works
Dihexa is claimed to bind hepatocyte growth factor (HGF) with very high affinity and to potentiate HGF activity at its receptor c-Met, which is proposed to drive synaptogenesis — the physical formation of new synaptic connections between neurons.
The retraction — and what it means
The foundational paper has been retracted.
- Benoist CC, Kawas LH, et al. (Harding group) — Journal of Pharmacology and Experimental Therapeutics 2014, 351(2):390-402 — PMID 25187433 — RETRACTED 2025 (retraction PMID 40312093). Expression of Concern issued September 2021.
This is the paper that established Dihexa’s claimed HGF/c-Met mechanism and the widely-circulated claim that “Dihexa is seven orders of magnitude more potent than BDNF.” That number — and the entire mechanism case it rests on — traces back to this single retracted paper. The retraction was preceded by an Expression of Concern in 2021, then formalized in 2025.
What this means in practice: the marketing claim that Dihexa is the most potent nootropic ever discovered is built on a foundation that’s been pulled out from under it. Every peptide-info site and forum that still reproduces the “7 orders of magnitude vs BDNF” line is reproducing a claim from a retracted study. Most of those sites have not updated. OHM’s position: lead with the retraction. Being the credible source that reports the integrity story honestly is the play here, not amplifying the hype.
The follow-up Dihexa literature (also primarily from the Harding group) what’s still standing post-retraction. Beyond Benoist 2014, there are zero completed human trials for Dihexa.
What the research shows
Outside of the retracted Benoist 2014 paper, there is no separately-cited Dihexa evidence base in the source material for this article — the entire mechanism case (HGF/c-Met binding, synaptogenesis, the “7 orders of magnitude more potent than BDNF” figure) traces to that single retracted study. Follow-up Harding-group papers reportedly exist but which ones are still standing post-retraction, and with what integrity status, is. There are zero completed human trials.
0035 categorization pass grade: C/yellow (cognitive cluster).
Real-world protocol
The doses and schedules here are for educational and informational purposes only. These peptides are sold for research use only and are not FDA-approved drugs. This is not medical advice. Consult a qualified physician before beginning any protocol.
These numbers come from forum convergence, not from clinical trials — there is no validated dose-finding study for Dihexa in humans.
- Oral: 8-45 mg/day (wide community range).
- Subcutaneous: 2-5 mg/day.
- Cycle: No validated cycle length.
Sequencing rule (holds independent of the mechanism controversy). The operational rule for any synaptogenic compound is the same regardless of which specific molecule sits at the end of the chain: clear neuroinflammation first, then add the synaptogenic compound — never the reverse. A brain running hot with neuroinflammation doesn’t respond the way a clean brain does; you risk wasting the compound and masking what’s actually driving the cognitive issue. Clear the inflammation, get mitochondria functioning, hormones optimized — only then layer in a synaptogenic compound like Dihexa. This is the same logical pattern as the SS-31 → MOTS-c sequencing rule and is good general practice for layered cognitive protocols.
Side effects & management
The safety database is essentially empty. This is the most important caveat — Dihexa is billed by some sources as “the most potent nootropic ever discovered” but the underlying mechanism paper is retracted and there is no meaningful human safety record.
Theoretical concerns worth taking seriously:
- The HGF/c-Met pathway is also a driver in multiple cancers — uncontrolled stimulation is a biologically plausible cancer-promotion risk oncology literature. Hard contraindication for active malignancy or cancer history.
- Angiotensin-pathway off-target effects on the cardiovascular system — unknown.
Regulatory status
Not FDA-approved. Not a controlled substance. PCAC review July 23-24, 2026: Dihexa is one of 12 peptides going to the FDA’s Pharmacy Compounding Advisory Committee for 503A re-evaluation. Even a positive vote would clear it for compounding only — not full FDA drug approval — and given the mechanism retraction plus the empty human safety database plus the HGF/c-Met cancer concern, Dihexa remains a low-confidence compound regardless of the PCAC outcome.
The Alyve / vendor picture. Dihexa is not sold through any of OHM’s affiliate vendors (Alyve, US Pure Peptides, or BioLongevity) at this time — it is, at most, a low-priority roadmap candidate given the retraction, the empty human safety database, and the HGF/c-Met cancer concern. The supply-chain trust story that anchors OHM’s other peptide content (US-manufactured, third-party COA, >99% purity) only works if the underlying molecule is one OHM is confident in — and Dihexa isn’t there yet.
Technical & analytical reference (chemistry & QC)
| Field | Value |
|---|---|
| Molecular formula | C27H44N4O5 |
| Average MW | 504.66 g/mol (PubChem CID 129010512) — the often-circulated 474.64 figure is wrong |
| CAS | 1401708-83-5 |
| Sequence | N-hexanoyl-Tyr-Ile-NH-(CH2)5-NH2 |
| PubChem CID | 129010512 |
Sources
- primary source, including the Benoist 2014 retraction (PMID 25187433 → retraction PMID 40312093).
- baseline grading (C/yellow ).
- Jones (2026), cited in the source cluster (no dedicated raw digest filename given there) — source of the neuroinflammation-first sequencing rule; note the original source itself positions Dihexa as “among the most compelling preclinical results in the entire neuropeptide space” and does not surface the Benoist 2014 retraction. OHM’s position, anchored in the retraction record above, stays the more skeptical read of the mechanism case while preserving the useful sequencing wisdom.
- Migrated from
cognitive-peptides-cluster.md(retired) — 2026-07-16.
Related: Pinealon · Cortagen · Semax · Selank · MOTS-c · BPC-157.
Sources & references
- primary source, including the Benoist 2014 retraction (PMID 25187433 → retraction PMID 40312093).
- baseline grading (C/yellow ).
- Jones (2026), cited in the source cluster (no dedicated raw digest filename given there) — source of the neuroinflammation-first sequencing rule; note the original source itself positions Dihexa as “among the most compelling preclinical results in the entire neuropeptide space” and does not surface the Benoist 2014 retraction. OHM’s position, anchored in the retraction record above, stays the more skeptical read of the mechanism case while preserving the useful sequencing wisdom.
- Migrated from
cognitive-peptides-cluster.md(retired) — 2026-07-16.
Related: Pinealon · Cortagen · Semax · Selank · MOTS-c · BPC-157.