Skip to main content
    PeptideAuthority
    Fact-checked by the Peptide Authority Editorial Board · Last reviewed:
    Share:X PostLinkedIn
    Cognitive & Neurological•Updated 2026-02-03•6 min read

    What Is Dihexa? Benefits, Research & Safety

    An angiotensin IV analogue and potent nootropic research compound with dramatic effects on memory and cognitive function in preclinical studies.

    Share:X PostLinkedIn
    Also known as:
    PNB-0408
    N-hexanoic-Tyr-Ile-(6) aminohexanoic amide
    ETheoretical / insufficientUK: Sold as 'research only' (UK)WADA: Sport status unclear

    UK summary: Not a licensed UK medicine. Highly potent in animal cognition models (claimed to be orders of magnitude more potent than BDNF), but zero human safety data. HGF / c-Met pathway it acts on has documented cancer-promotion concerns.

    Quick Facts

    Category
    Cognitive & Neurological
    Half-Life
    Not established in humans; animal pharmacokinetic data limited
    UK Status
    Not licensed. Not available through legitimate pharmaceutical channels. Pure research compound only.
    EU Status
    Not approved by EMA. No authorisation for human use. Research compound status.

    Overview

    Dihexa (PNB-0408) is a small molecule derived from angiotensin IV, developed at Washington State University by researchers seeking to enhance the cognitive effects observed with the angiotensin system. It is one of the most potent nootropic compounds ever studied in preclinical research, with effects on memory and cognition reported at picomolar concentrations. The compound was designed to be orally bioavailable and blood-brain barrier penetrant, addressing limitations of the parent angiotensin IV molecule. Dihexa has shown remarkable efficacy in reversing cognitive deficits in animal models of dementia, including scopolamine-induced amnesia and aged animal models. Dihexa works primarily through hepatocyte growth factor (HGF) system potentiation, promoting the formation of new synaptic connections (synaptogenesis). This mechanism distinguishes it from other nootropic compounds and suggests potential applications in neurodegenerative conditions characterised by synaptic loss. **Critical Note:** Dihexa is an experimental research compound with virtually no human clinical data. Despite impressive preclinical results, safety, dosing, and long-term effects in humans are completely unknown. It is not approved for human use by any regulatory authority.
    Evidence standards summary

    Dihexa — evidence and risk at a glance

    Twenty standard modules scored against the Peptide Authority evidence grading methodology. Missing modules indicate the field has not yet been characterised editorially — treat absences as uncertainty rather than reassurance.

    01Evidence snapshot

    ETheoretical / insufficientOverall grade against our evidence grading methodology.

    Not a licensed UK medicine. Highly potent in animal cognition models (claimed to be orders of magnitude more potent than BDNF), but zero human safety data. HGF / c-Met pathway it acts on has documented cancer-promotion concerns.

    02Human evidence grade

    ETheoretical / insufficientStrength of evidence from published human trials.

    03Preclinical evidence grade

    DAnimal/cell evidence onlyAnimal-model and in-vitro evidence quality.

    04Regulatory status

    • UK: Not licensed. Not available through legitimate pharmaceutical channels. Pure research compound only.
    • EU: Not approved by EMA. No authorisation for human use. Research compound status.
    • Notes: Dihexa has NO regulatory approval anywhere in the world for human use. It remains a research tool compound. Any products marketed for human consumption are not pharmaceutically regulated and may pose serious risks. The compound's potential for misuse due to claimed potency is a concern.

    05Approved medical uses

    None in the UK or EU as a finished medicine. (Or: not yet documented; treat as absence rather than approval.)

    06Unapproved / promotional claims

    • Seven orders of magnitude more potent than BDNF for synapse formation.
    • Reverses age-related cognitive decline.
    • Treats Alzheimer's and Parkinson's disease.
    • Safe long-term nootropic for healthy adults.

    07Common internet claims

    • Marketed as the most powerful nootropic ever discovered.
    • Sold by online retailers as a research-only oral or sublingual dose.
    • Promoted by biohackers for off-label cognitive enhancement.

    08Claim vs evidence

    ClaimEvidenceHuman evidence?Regulatory concernSafer wording
    “Most potent nootropic available”DNoHighHighly potent in animal cognition models; potency in animals is not the same as benefit or safety in humans.
    “Safe for daily use”ENoHighZero systematic human safety data. The HGF / c-Met pathway it activates is implicated in cancer progression — theoretical concern not resolved.
    “Better than prescription cognitive medicines”ENoHighNo human comparative evidence exists.

    09Safety uncertainty score

    Very high

    Effectively no human safety data; safety claims are extrapolations from animal work or anecdote.

    10Known adverse signals

    • Essentially no human safety data.
    • HGF / c-Met activation has theoretical cancer-promotion implications.
    • Unknown effects on tumour growth, particularly in patients with undiagnosed malignancy.
    • Unknown chronic effects on synaptic plasticity.

    11Drug-interaction uncertainty

    High

    Interaction picture sparse; meaningful uncertainty when combined with other medicines.

    12Anti-doping status

    WADA: Sport status unclearWADA strict-liability framing applies.

    13UK legal position

    UK: Sold as 'research only' (UK)

    Not licensed. Not available through legitimate pharmaceutical channels. Pure research compound only.

    Read the full UK legal guide → Research peptides and UK law

    14EU legal position

    Not approved by EMA. No authorisation for human use. Research compound status.

    15What this page cannot tell you

    • Whether a UK-purchased product contains Dihexa at the labelled concentration.
    • Whether oral or sublingual administration produces meaningful CNS exposure.
    • What the cancer risk is from sustained c-Met agonism in any age group.
    • What dose, if any, is safe — there is no licensed reference and no human dose-finding study.

    16Last reviewed

    Last reviewed:

    Next review due:

    Spotted an error or something out of date? Send a correction.

    17Citation quality score

    DAnimal/cell evidence onlyQuality of the sources we cite, graded against the evidence grading methodology.

    18Research gaps

    • No published Phase 1 trials in humans.
    • Long-term oncologic surveillance does not exist.
    • Cognitive outcome data in humans is absent.
    • Pharmacokinetic data in humans is absent.

    19Safer alternatives / established care pathways

    • Sleep, exercise, social engagement — evidence-based cognitive interventions.
    • GP review for adult ADHD assessment if attention is the underlying concern.
    • Memory clinic referral if cognitive decline is the concern.
    • NHS Talking Therapies for mood-driven cognitive complaints.

    Related Safety Centre page → Unlicensed peptide risks

    20Doctor discussion prompts

    Questions to ask a qualified clinician

    These are starter questions you can adapt for a GP, specialist, pharmacist, or anti-doping advisor. The aim is to help you have a better-informed conversation — not to replace one.

    • Is Dihexa a licensed UK medicine?
    • What's the human safety evidence?
    • What theoretical cancer-related concerns exist with HGF / c-Met activation?
    • Should cognitive symptoms I have be investigated for an underlying cause first?

    Discovery & History

    Dihexa was developed at Washington State University by Dr. Joseph Harding and colleagues, researchers who had been studying the cognitive effects of the angiotensin system for decades. The angiotensin system, primarily known for blood pressure regulation, was discovered to have cognitive effects independent of its cardiovascular actions. Angiotensin IV, in particular, was found to enhance memory and learning in animal models. However, angiotensin IV itself is a peptide with poor oral bioavailability and limited brain penetration. The WSU team developed a series of small molecule analogues designed to retain cognitive-enhancing properties while improving drug-like characteristics. Dihexa emerged from this programme as an exceptionally potent compound. Key discoveries included: - Picomolar potency (approximately 7 orders of magnitude more potent than BDNF) - Oral bioavailability - Blood-brain barrier penetration - Ability to reverse cognitive deficits in multiple animal models The compound was patented and licensed for development, with initial interest in Alzheimer's disease and other dementias. However, as of 2026, no human clinical trials have been published, and the compound remains in early research phases.

    Mechanism of Action

    Dihexa exerts its cognitive effects through a unique mechanism involving the hepatocyte growth factor (HGF) system: **Hepatocyte Growth Factor (HGF) System Potentiation** Dihexa's primary mechanism involves enhancing the HGF/c-Met signalling pathway: - HGF is a pleiotropic growth factor involved in neuronal development and plasticity - c-Met is the HGF receptor, expressed in neurons - Dihexa augments HGF-induced c-Met activation - This potentiation occurs at extremely low concentrations (picomolar range) **Synaptogenesis Promotion** Through HGF/c-Met activation, Dihexa promotes: - Formation of new dendritic spines - Increased synaptic connections between neurons - Enhanced neural network connectivity - Potential reversal of synaptic loss in neurodegeneration **Comparison to BDNF** Unlike Semax and other nootropics that work via BDNF: - Dihexa operates through a distinct HGF-mediated pathway - Reported to be ~10 million times more potent than BDNF in synaptogenesis assays - May complement rather than duplicate BDNF-enhancing compounds **AT4 Receptor Independence** Interestingly, while developed from angiotensin IV research: - Dihexa's cognitive effects appear independent of AT4 receptor activation - The HGF mechanism was discovered as the primary pathway - This explains its superior efficacy compared to parent compounds **Blood-Brain Barrier Penetration** Key to Dihexa's potential: - Designed for oral administration - Readily crosses the blood-brain barrier - Achieves effective CNS concentrations

    Researched Benefits

    Based on preclinical and clinical research findings:

    • 1
      Potent memory enhancement in preclinical models
    • 2
      Reversal of scopolamine-induced cognitive deficits
    • 3
      Improved spatial learning and memory in aged animals
    • 4
      Promotion of synaptogenesis and dendritic spine formation
    • 5
      Potential neuroprotective effects in neurodegeneration models
    • 6
      Oral bioavailability with CNS penetration
    • 7
      Effects at extremely low concentrations (picomolar range)

    Claim vs Evidence

    How popular claims about Dihexa stack up against the current research, graded using our public evidence grading methodology.

    ClaimEvidenceHuman evidence?Regulatory concernSafer wording
    “Most potent nootropic available”DNoHighHighly potent in animal cognition models; potency in animals is not the same as benefit or safety in humans.
    “Safe for daily use”ENoHighZero systematic human safety data. The HGF / c-Met pathway it activates is implicated in cancer progression — theoretical concern not resolved.
    “Better than prescription cognitive medicines”ENoHighNo human comparative evidence exists.

    Theoretical Dosing & Protocols

    ⚠️ Educational Only: The following information is derived from research literature and is not a prescription or recommendation. No standardised human dosing exists. Always consult a qualified healthcare professional.
    Theoretical DosageUnknown for humans—no clinical data exists. Animal studies used various concentrations.
    FrequencyUnknown—not established for human use
    DurationUnknown—not established for human use
    NotesCRITICAL: No human dosing protocols exist. Dihexa has not been tested in human clinical trials. Any human use is entirely experimental with unknown risks. The compound's extreme potency makes dosing particularly unpredictable. Do not extrapolate from animal data.

    Administration Routes

    Routes studied in research settings (educational only):

    • Oral (in animal studies)
    • Subcutaneous injection (in some research)
    • Intranasal (anecdotal reports only)
    Half-LifeStability
    Not established in humans; animal pharmacokinetic data limitedStore lyophilised powder at -20°C; solution stability not well characterised

    Safety Profile & Known Risks

    Commonly Reported Side Effects

    • Unknown—no systematic human safety data exists
    • Anecdotal reports vary widely and are unreliable
    • Headache reported anecdotally
    • Sleep disturbances mentioned in user reports

    Rare Risks & Concerns

    • Completely unknown long-term effects
    • Potential for pro-cancer effects (HGF/c-Met pathway involved in some cancers)
    • Possible cardiovascular effects given angiotensin system origins
    • Unknown interactions with other medications
    • Unknown effects on developing brains

    Contraindications

    • Any individual without explicit medical supervision
    • Pregnancy and breastfeeding (absolutely contraindicated)
    • History of cancer (HGF pathway concerns)
    • Cardiovascular disease (angiotensin system involvement)
    • Children and adolescents (brain development concerns)
    • Any individual not involved in formal research

    UK & EU Regulatory Context

    🇬🇧 United Kingdom

    Not licensed. Not available through legitimate pharmaceutical channels. Pure research compound only.

    🇪🇺 European Union

    Not approved by EMA. No authorisation for human use. Research compound status.

    Dihexa has NO regulatory approval anywhere in the world for human use. It remains a research tool compound. Any products marketed for human consumption are not pharmaceutically regulated and may pose serious risks. The compound's potential for misuse due to claimed potency is a concern.

    Clinical Studies Summary

    Cognitive benefits of angiotensin IV and angiotensin-(1-7): A systematic review of experimental studies.

    Studies of cognitive impairment show salutary effects of acute administration of Ang IV and its analogs, as well as AT4R activation. Brain RAS peptides appear most effective administered intracerebroventricularly, close to the time of learning acquisition or retention testing. Ang-(1-7) shows anti-dementia qualities.

    Neurosci Biobehav Rev. 2018View on PubMed

    The development of small molecule angiotensin IV analogs to treat Alzheimer's and Parkinson's diseases.

    In an effort to resolve this issue we have synthesized a number of small molecule AngIV-based compounds that are metabolically stable, penetrate the blood-brain barrier, and facilitate compromised memory and motor systems.

    Prog Neurobiol. 2015View on PubMed

    The Brain Hepatocyte Growth Factor/c-Met Receptor System: A New Target for the Treatment of Alzheimer's Disease.

    Dihexa is a first-in-class compound that is orally active, penetrates the blood-brain barrier, and facilitates memory consolidation and retrieval. This angiotensin-based small molecule may be efficacious as a treatment for AD.

    J Alzheimers Dis. 2015View on PubMed

    Efficiently generate functional hepatic cells from human pluripotent stem cells by complete small-molecule strategy.

    Our current small-molecule-based hepatic generation protocol presents an efficient and cost-effective platform for the large-scale production of functional human hepatic cells for cell-based therapy and drug discovery using.

    Stem Cell Res Ther. 2022View on PubMed

    Small-Molecule-Directed Hepatocyte-Like Cell Differentiation of Human Pluripotent Stem Cells.

    The resulting hepatoblasts are then differentiated to HLCs with N-hexanoic-Tyr, Ile-6 aminohexanoic amide (Dihexa, a hepatocyte growth factor agonist) and dexamethasone. The protocol provides an efficient and reproducible procedure for differentiation of hPSCs into HLCs utilizing small molecules.

    Curr Protoc Stem Cell Biol. 2016View on PubMed

    The Brain Hepatocyte Growth Factor/c-Met Receptor System: A New Target for the Treatment of Alzheimer's Disease.

    Review from the Wright/Harding group covering the HGF/c-Met pathway rationale that motivates the angiotensin-IV-derived peptide (dihexa) programme. Editorial note: the primary Benoist et al. 2014 J Pharmacol Exp Ther paper on this mechanism (PMID 25187433) was subsequently retracted; this Wright & Harding 2015 review covers the same mechanistic ground without that publication's specific claims.

    J Alzheimers Dis. 2015View on PubMed

    Looking for Dihexa?

    Source research-grade Dihexa from a trusted UK supplier — third-party tested with certificate of analysis.

    View at Supplier

    Frequently Asked Questions

    Questions to ask a qualified clinician about Dihexa

    These are starter questions you can adapt for a GP, specialist, pharmacist, or anti-doping advisor. The aim is to help you have a better-informed conversation — not to replace one.

    • Is Dihexa a licensed UK medicine?
    • What's the human safety evidence?
    • What theoretical cancer-related concerns exist with HGF / c-Met activation?
    • Should cognitive symptoms I have be investigated for an underlying cause first?

    UK regulatory & safety context

    Research peptides and UK law

    UK legal reference

    Unlicensed peptide risks

    Safety Centre guide

    Related Research Guides

    Peptides for Cognitive Enhancement

    Read guide

    Peptide Comparisons

    Dihexa vs Semax

    Compare peptides

    Related Peptides

    Selank

    A synthetic peptide based on tuftsin, developed in Russia for anxiolytic and nootropic properties, approved there for anxiety and neurasthenia.

    Learn more

    Semax

    A synthetic peptide based on ACTH, developed in Russia as a nootropic and neuroprotectant, approved there for cognitive disorders and stroke.

    Learn more

    BDNF

    A critical growth factor for brain health, neuroplasticity, and neuronal survival, with implications for depression, memory, and neurodegenerative diseases.

    Learn more

    Explore More Peptides

    Browse our comprehensive database of research-backed peptide profiles.