Dihexa vs Semax

Side by side

Dihexa Low and semax Medium are often recommended together, or as alternatives, by people looking for compounds that build new brain connections. They differ sharply in how much is known ¹. The table is read from our encyclopedia entries.

Semax: small studies, a Russian approval

Semax is a synthetic ACTH fragment given as nasal drops and approved as a medicine in Russia ¹. In rats a single nasal dose raised hippocampal BDNF by up to 1.4 times and activated its receptor (animal evidence) ². In 110 patients after ischaemic stroke, two courses alongside rehabilitation raised plasma BDNF (human study, not blinded) ³, and an imaging study in 24 healthy adults found brief changes in brain network activity ⁴. That is thin evidence, but it is human evidence.

Dihexa: rodents only, and a mechanism withdrawn

Dihexa was introduced in 2013 as an orally active, brain-penetrant angiotensin IV analogue that reversed memory deficits in rats; that paper carries a 2021 expression of concern on PubMed ⁵. Its claimed mechanism, binding HGF and boosting c-Met, came from papers published in 2011, 2012 and 2014 that PubMed now records as retracted, the 2014 one with a notice in April 2025 ⁶. An independent group found oral dihexa improved memory in Alzheimer's-model mice (animal evidence) ⁷, and in a Huntington's-like rat model it did not help (animal evidence) ⁸. No published study has given dihexa to a person.

BDNF versus c-Met: why the target matters

Both compounds are sold as growth-factor boosters, but the growth factors differ. Semax's studies point to BDNF, a growth factor for nerve connections. Dihexa was promoted as strengthening HGF and its receptor c-Met, and c-Met is a proto-oncogene: a 2021 review describes hyperactive HGF/c-MET signalling as a hallmark of many cancers, involved in growth, spread and drug resistance (review) ⁹. No study has shown that dihexa causes cancer; none has looked. It is a theoretical concern grounded in well-established cancer biology, and it is the main reason researchers worry about dihexa.

The closest human test of the HGF idea

A different HGF/MET modulator, fosgonimeton, reached a 287-person phase 2/3 Alzheimer's trial and missed its primary and secondary endpoints (p = 0.70 on the main combined score), with more people stopping it because of side effects than placebo (human trial) ¹⁰. It is not dihexa, but it is the only large human test of boosting HGF/MET for cognition.

How the differences add up (as of October 3, 2026)

On every measure the comparison favours semax: some human data, an approval in one country, and a mechanism without a known cancer link. Dihexa has no human data, its mechanism papers were retracted, and its target raises a cancer question no one has studied. Neither is FDA-approved. Dihexa is in no FDA compounding category and is due for review by FDA's compounding committee by the end of February 2027; for athletes it falls under WADA's S0, while semax's status is unsettled ¹. Our dihexa safety guide covers the retractions in detail. Doses on this page are those in our entries' sources, not recommendations.

Frequently asked questions

Is dihexa stronger than semax?

Dihexa has only cell and animal data, so there is no human comparison. Semax has small human studies and is approved in Russia; dihexa has never been tested in people.

Is dihexa safe?

Unknown. No human study exists, its mechanism papers were retracted, and its advertised target, c-Met, is a cancer-linked pathway.

Do semax and dihexa work the same way?

No. Semax's studies point to BDNF; dihexa was promoted as boosting HGF and c-Met, though the papers behind that mechanism were retracted.

Related on Grey Peptides

• Dihexa
• Semax
• Dihexa: why researchers worry

Sources

1. Grey Peptides dataset records for dihexa and semax (FDA and compounding status, WADA status, retraction notes, studied doses as sourced on each entry); read October 3, 2026.
2. Dolotov, O. V., et al. (2006). Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus. Brain Res, 1117(1), 54-60. PMID: 16996037
3. Gusev, E. I., et al. (2018). [The efficacy of semax in the tretament of patients at different stages of ischemic stroke]. Zh Nevrol Psikhiatr Im S S Korsakova, 118(3. Vyp. 2), 61-68. PMID: 29798983
4. Lebedeva, I. S., et al. (2018). Effects of Semax on the Default Mode Network of the Brain. Bull Exp Biol Med, 165(5), 653-656. PMID: 30225715
5. McCoy, A. T., et al. (2013). Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents. J Pharmacol Exp Ther, 344(1), 141-54. PMID: 23055539
6. Benoist, C. C., et al. (2025). Retraction notice to "The Procognitive and Synaptogenic Effects of Angiotensin IV-Derived Peptides Are Dependent on Activation of the Hepatocyte Growth Factor/c-Met System" [J Pharmacol Exp Ther 351 (2014) 390-402]. J Pharmacol Exp Ther, 392(4), 103567. PMID: 40312093
7. Sun, X., et al. (2021). AngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in the APP/PS1 Mouse via the PI3K/AKT Signaling Pathway. Brain Sci, 11(11). PMID: 34827486
8. Wells, R. G., et al. (2024). Effects of an Angiotensin IV Analog on 3-Nitropropionic Acid-Induced Huntington's Disease-Like Symptoms in Rats. J Huntingtons Dis, 13(1), 55-66. PMID: 38489193
9. Fu, J., et al. (2021). HGF/c-MET pathway in cancer: from molecular characterization to clinical evidence. Oncogene, 40(28), 4625-4651. PMID: 34145400
10. Porsteinsson, A. P., et al. (2025). Fosgonimeton in mild-to-moderate Alzheimer's disease. J Alzheimers Dis Rep, 9, 25424823251405817. PMID: 41393340

Educational information, not medical advice. Each dose in this guide names its source, an approved label or a published study. 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.