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Dihexa

Also known as

PNB-0408 · MM-201 (early lab designation in some histories) · N-hexanoic-Tyr-Ile-(6)-aminohexanoic amide · N-hexanoic-tyrosine-isoleucine-(6) aminohexanoic amide · Dihexa peptide · Dihexa oligopeptide · Angiotensin IV analog (Dihexa) · Nle1-Ang IV–derived analog (Dihexa) · HGF/c-Met potentiator (Dihexa discussions) · ATH-1017 / fosgonimeton (related clinical candidate — not identical)

Community talk. May be wrong. Not medical advice. Not a protocol. Not for human or animal use.

Open in the directory ↗
Peptide Some talk Systemic Oral / transdermal / SubQ Cognitive research compounds

Systemic brain-focused discussion—oral or transdermal community products, not local muscle-site dosing; human exposure is unverified.

What people say Dihexa is an experimental angiotensin-IV-derived oligopeptide/peptidomimetic discussed as a nootropic, not an approved drug. Its celebrated HGF/c-Met mechanism literature is compromised by a 2025 retraction and an Expression of Concern, and there is no controlled human safety or efficacy program. Doses people talk about
Lower informal amount~1–3 mg topical (DMSO) or low oral amounts

Community description only; not established as a safe starting amount in humans.

Oral community bands~2–10 mg/day commonly cited; ~10–20 mg daily or every other day also appears; some compilations reach ~45 mg/day

Overlapping forum, clinic and vendor ranges with unverified product identity; the upper end is not a consensus standard.

Transdermal DMSO discussion~1–5 mg in lower reports; broader secondary charts list ~5–20 mg

Vehicle-dependent and unverified; amount does not establish absorption, bioavailability or cross-route equivalence.

SubQ chart discussion~5–10 mg SC daily or every other day for 4–6 weeks

Informal research-chart range; route importance is disputed and no controlled human basis was identified.

Rodent oral studies~1.25–2.0 mg/kg oral in scopolamine work; 1.44 or 2.88 mg/kg daily in APP/PS1 mice

Animal research anchors only; no simple human conversion or community protocol follows.

Marketed unit sizes5 mg capsules, ~8 mg oral tablets or 10 mg units

Product menu sizes do not establish identity, purity or an effective dose.

Every-few-days reports~15–20 mg about every 3 days

Recent anecdotal pattern justified by animal half-life lore; not human PK-guided.

Rows preserve routes, amounts and frequencies without implying a safe start, escalation path, preparation method or cross-route equivalence. Infrequent community pattern: Every other day or a few multi-milligram uses per week. Driven largely by long rat-circulation lore, not measured human pharmacokinetics.

Half-life & effect duration

Half-life in the body
  • IV · ratsAbout 12.7 days
  • Plasma stability testAbout 335 minutes
  • Rat liver stability testAbout 509 minutes
Felt duration people report
  • Positive accountsBrief stimulation or focus; some claim effects across multi-day gaps or for weeks
  • Other accountsNo acute change, or early stimulation followed by no response
Timing context & sources
How it may feel Reports conflict from no noticeable effect or only subtle test-performance changes to transient stimulation, focus, curiosity, headache, anxiety or sleep disruption. Some authors claimed persistence between doses or for weeks, while others reported that an early effect vanished after the first days.
Cycles people discuss Community calendars include two weeks on/two weeks off, longer 4–12-week windows, daily or every-other-day use, and multi-day gaps. These are inconsistent informal patterns driven partly by rat half-life lore, not human dose-ranging or pharmacokinetics. Timing Morning is the preferred slot in retained community reports; evening use is more often linked to insomnia, racing thoughts or vivid dreams. Study or skill practice and adequate sleep feature in these accounts, while no standalone meal rule is established. Stacks Semax, Selank and PE-22-28 are common adjacent cognition compounds, but inspected reports often include modafinil, eutropoflavin or other nootropics. These combinations prevent clean attribution to Dihexa. Access talk Research-chem oral caps, DMSO solutions, and powders dominate Western talk. Watch for Human data gap: No Phase 1 toxicology package or controlled human safety set for Dihexa; “felt fine” ≠ long-term safety.
Related
J-147PE-22-28SemaxSelankNoopept

Tap a line to jump into the full notes. Research only — may be wrong.

Timing context & sources

Half-life in the body

The original Dihexa paper reported a 12.68-day circulating half-life after intravenous administration in adult male rats.

The same research program reported about 335 minutes of plasma stability and about 509 minutes in one pooled rat-liver-microsome set; those are separate ex vivo stability measurements, not the 12.68-day in-vivo endpoint.

Rat intravenous circulation, plasma stability and microsomal degradation cannot establish human oral, transdermal or subcutaneous PK. The paper carries an Expression of Concern, and a related central HGF/c-Met mechanism paper was retracted in 2025.

Felt duration people report

Inspected human reports do not establish a typical duration: some describe no acute change, some transient stimulation or focus, and some claim effects across multi-day gaps or for weeks.

One two-week report, route unspecified, described little subjective change amid modafinil and eutropoflavin despite better chess results. Other users described oral clarity, early stimulation then nonresponse, or persistence between transdermal amounts. A separate Longecity account changed from nearly null oral use to a painful IM attempt and acute intranasal effects.

Unverified products, routes, doses and co-agents; self-selected cognitive benchmarks and strong expectation effects. Claimed persistence cannot be converted into human parent PK or proof of durable synaptogenesis.

  • Reddit r/Nootropics — A brief guide to what really works from someone who has tried everything (opens in a new tab)Single long-form user account describes Dihexa as both effective and risky, with transdermal use, strong early effects, declining intensity over months and several co-exposures or comparisons.High-claim, unblinded multi-nootropic account with unverified product and no objective adjudication; its preparation instructions are not reproduced.
  • Reddit r/NooTopics — Dihexa 2 week report (opens in a new tab)Glittering_Maize2544's OP reports 5 mg daily for two weeks, route unspecified, with little felt change but improved chess results amid occasional modafinil and eutropoflavin. AcanthisittaCheap523 separately confirms oral use after describing a month-long experience; another user reports spaced transdermal persistence. These are different accounts.Self-selected benchmark, brief duration, unverified product and co-agents; thread participants are heterogeneous and do not measure PK.
  • Reddit r/NooTopics — Dihexa experiences and sources (opens in a new tab)Visible replies include slight early stimulation followed by no effect, stimulation limited to the first two days across many later uses, null effects and product-quality concerns. A separate positive-focus reply cannot answer whether it persists; deleted usernames prevent certainty that all deleted replies share one author.Unverified suppliers, routes and exposures; comments are separate users and do not establish one typical effect or duration.
  • Longecity — Dihexa discussion, page 9 (opens in a new tab)Xenix #265 and the nearby follow-up describe a nearly null two-week oral experiment (50 mg/day on an empty stomach) with uncertain product identity, a painful IM attempt, and an acute subjective response after intranasal use. The clearer/more-alive comparison belongs to the intranasal experience, not the oral course; placebo remains unresolved.Old, unverified account with changing routes and uncertain product identity; inspected primary passages establish chronology, not validated cognition, safety or pharmacokinetics.

What people say 14

  • Memory / learning (community): Working memory under load, study retention, easier encoding over multi-week windows — gradual, not day-one stimulant lift. forum
  • Verbal fluency / pattern recognition: Self-reports of faster word access, smoother conversation, and cross-domain idea linking appear repeatedly in nootropic write-ups. anecdote
  • Focus without caffeine buzz: “Cognitive horsepower” or task stickiness without classic stim jitter — sleep debt and stacks still confound. forum
  • Neuroplasticity frame: Sold as structural synapse change (spinogenesis) rather than acute neurotransmitter spike — effects said to lag and sometimes outlast dosing. forum
  • Null / non-responders: Large minority report no subjective change; purity, dose, route, and expectation are the usual forum debates. forum
  • Stack confound: Often co-logged with Semax, Selank, racetams, choline, PE-22-28, or lifestyle upgrades — single-agent credit is shaky. forum
  • 2025–2026 “felt nothing / fake oral” camp: Still loud. DMSO transdermal vs swallowed capsules is the usual argument when a pulse is a dud. forum
  • Scopolamine deficit rescue (rodent): Oral Dihexa (~1.25–2.0 mg/kg class; high oral ~2 mg/kg/day often cited) reversed scopolamine-induced Morris water maze deficits in young rats; treated animals approached vehicle-control acquisition. animal
  • Aged-rat cognition: Same oral protocol improved spatial learning in aged rats with natural cognitive decline — more variable than the scopolamine model. animal
  • APP/PS1 Alzheimer-model mice (independent): Intragastric 1.44 or 2.88 mg/kg once daily for ~3 months (Sun 2021) improved cognitive measures, reduced neuronal-loss signals, and lowered neuroinflammatory markers via PI3K/AKT pathway talk — cleaner independent group than the retracted WSU mechanism set. animal
  • Spinogenesis in culture: Dissociated rat hippocampal neurons showed large increases in dendritic spine density after multi-day Dihexa exposure (roughly three-fold spine counts in classic McCoy-era culture descriptions; picomolar activity range discussed). lab
  • vs BDNF headline: In-vitro neurotrophic/spine assays were marketed as ~seven orders of magnitude more potent than BDNF — assay-specific, not human efficacy. lab
  • Parkinson’s / peripheral-nerve research interest: MJFF-era grant talk and separate preclinical nerve-repair doses (e.g. multi-mg/kg over many weeks in limb-function recovery contexts) are cited in vendor/science summaries — not established human PD therapy. animal
  • Hair-cell / ototoxicity models: In-vitro lateral-line work reports HGF-dependent protection from aminoglycoside ototoxicity at broad concentration bands — niche research, not a community nootropic use. lab

Doses people talk about 15

  • Lower community amount: ~1–3 mg topical (DMSO) or low oral amounts appear in informal discussion focused on headache, anxiety and sleep cost; no controlled human dose-ranging study establishes a safe starting point or escalation sequence. forum
  • Oral daily (most-cited band): ~2–10 mg/day once daily is the modal cognitive-optimization range across wellness/clinic and forum charts. forum
  • Oral higher community/vendor talk: ~10–20 mg once daily or every other day appears on research-chem and compounding-style pages; some blogs compile anecdotal bands up to ~8–45 mg/day — upper end is not a consensus standard and raises unknown-risk talk. forum
  • Transdermal DMSO (classic LongeCity-style): Legacy discussion describes ~1–5 mg, including a frequently repeated ~3–5 mg example dissolved in a few drops of DMSO and applied to the inner forearm until absorbed. This is a historical account, not preparation instructions; absorption and actual product identity are unverified. forum
  • Transdermal broader charts: ~5–20 mg applied to thin skin (forearm, sometimes neck) once daily in secondary dosage guides — absorption highly formulation-dependent. forum
  • EOD / infrequent during “on” phase: Because of long animal circulating half-life lore, some protocols favor every-other-day or a few multi-mg doses per week rather than forever-daily loading. forum
  • Split oral: Minority split a daily total into morning + early afternoon rather than one bolus. forum
  • SubQ research talk: Some charts list ~5–10 mg SC daily or EOD for 4–6 weeks — others argue SC is less central than oral/topical for this molecule; not a settled best route. forum
  • Product unit sizes: Gray-market and clinic menus often sell 5 mg capsules, ~8 mg oral tablets, or 10 mg unit strengths — unit size ≠ proven effective dose. forum
  • Every-few-days camp (2025–2026): Some nootropic logs, citing long circulating half-life lore, use ~15–20 mg every ~3 days instead of daily 5–20 mg. Still anecdote, not PK-guided. forum
  • Intranasal DMSO (minority): A 2025 experiment path described as painful and mucosa-hostile — not a consensus route. anecdote
  • Oral clinic/vendor band: ~5–10 mg/day is frequently listed in informal cognitive-product charts; the label ‘new user’ does not make it a validated or safer human dose. forum
  • Uncertainty: Without third-party testing, labeled mg, salt form, and actual Dihexa content are poorly verified; DMSO solutions add volume/measurement error. forum
  • Framing: Community research-discussion and clinic-marketing ranges only — not advice, prescriptions, or validated human clinical protocols. Gray-market identity/purity make “mg” claims soft. forum
  • Rodent oral efficacy anchors (not human mg): ~1.25–2.0 mg/kg oral (gavage) in scopolamine MWM; Sun 2021 used 1.44 and 2.88 mg/kg IG daily for 3 months in APP/PS1 mice. Simple mg/kg→human allometric conversion is not a community protocol and overstates certainty. animal

How it may feel 9

  • Hours 1–6 (subset): A minority of DMSO/transdermal logs claim faster verbal fluency or “on” within hours — not the dominant pattern and hard to separate from placebo/DMSO feel. anecdote
  • Days 1–7: Little classic stimulant buzz; more common are mild headache, mental pressure, restlessness, vivid dreams, or nothing. forum
  • Days 1–3 (ramp logs): Some trial write-ups note irritability on off-days or vague mental fatigue if consecutive days are pushed hard. anecdote
  • Weeks 1–2: Gradual learning ease, less brain fog, or clearer deep-work blocks more common than day-one magic; first real keep-or-stop checkpoint for many. forum
  • Weeks 2–4: Usual evaluation window on 2-on/2-off templates; decide whether memory/focus edge is real enough to re-run. forum
  • Month 1–2: Some claim focus/memory “sticks” across the cycle; others quit for overstim, anxiety, headache, or null effect. anecdote
  • After stop: Long rodent circulating half-life + synaptogenesis narrative → some report lingering subjective benefit for days to longer; others fade quickly — self-report only. forum
  • Why people pause: Community theory is that new synapses do not vanish when plasma clears — used to justify long offs and to test whether gains persist without redosing. forum
  • Word-finding vs headache: Faster word access and idea-linking are the loud “it’s working” reports; pressure-headache, irritability, and racing thoughts are the loud “too much” reports. forum

Around the dose 8

  • Clock: Morning is the usual slot. Evening dose talk is tied to insomnia, racing thoughts, and vivid dreams. forum
  • Learning load: People who log a “good” pulse often pair it with actual study, language, or skill practice — the synaptogenesis story is use-it-or-it-was-just-a-headache. forum
  • Sleep: Sleep is treated as part of the window, not optional. Logs that skip sleep and chase more mg are the usual overstim / fog posts. forum
  • Training: Not a pre-workout. Normal lifting or cardio stays in the picture as a BDNF-adjacent habit, not a timing rule. forum
  • After the pulse: The 2-on/2-off crowd uses the off window to see if word-finding or memory “stuck” without redosing — that’s the test, not a second compound. forum
  • Choline / stacks: Older LongeCity-style logs add a choline source when racetams are in the mix. Standalone Dihexa does not have a locked meal rule. forum
  • Avoid same-weeks pile-on: High-dose Semax + high-dose Dihexa in the same block is a common “too much neurotrophic noise” warning. forum
  • DMSO handling: Keep the carrier off fabric, pets, and eyes; garlic odor is the solvent, not the peptide. forum

Cycles people discuss 8

  • Most-repeated pulse: 2 weeks on / 2 weeks off remains the classic forum template. forum
  • Persistence test: 2 weeks on → 4+ weeks off to see if subjective benefits stick without redosing (synaptogenesis narrative). forum
  • Broader clinic-style windows: Some dosage guides float 4–12 weeks on with response-based adjustments — still not trial-defined. forum
  • Alternate 4–6 weeks on / equal off: Research-chem SC/oral charts sometimes match off length to on length. forum
  • Avoid open-ended forever daily: Long preclinical circulating half-life + theoretical HGF/c-Met growth/angiogenesis caution → community consensus against indefinite continuous use. forum
  • Re-runs: Common after a subjectively good pulse; no long-term human safety database for repeated gray-market courses. forum
  • Daily vs EOD inside the “on” window: Both appear; long half-life talk pushes some users toward less-than-daily even while “on.” forum
  • Longer plasticity runs: 4–8 weeks on / 2–4 weeks off appears in practitioner and secondary-protocol write-ups for “deeper” cognitive or recovery framing. forum

Timing 9

  • Why infrequent dosing lore: Multi-day circulating t½ in rats is the main scientific-sounding reason community protocols avoid high daily loading forever. forum
  • Time of day: Morning preferred; evening dosing more often linked to insomnia, racing thoughts, or vivid dreams. forum
  • Onset: Multi-day to multi-week change is the default expectation; hour-scale “racetam flash” is not the marketing or typical report pattern. forum
  • Vendor half-life copy: Some marketing restates “~12–13 day half-life” as if it were human — it is rodent IV data. forum
  • Circulating half-life (rat IV): McCoy-era / patent-style PK: Dihexa ~12.68 days t½ after IV administration in adult male Sprague-Dawley rats (noncompartmental modeling) — not human PK. animal
  • Plasma metabolic stability: Often-cited plasma stability t½ ≈ 335–335.5 minutes (McCoy 2013 era) and related microsomal clearance figures (e.g. ~509 min average half-life in one microsome set) — stability metrics, not “you feel it for 335 minutes.” animal
  • Oral / BBB: Described as orally active and BBB-permeable vs parent Ang IV; intact compound retrieved in rat CSF after oral and parenteral treatment in lab/patent narratives. animal
  • Plasticity lag: Subjective effects may lag or outlast measurable plasma presence if structural synaptic change is real — self-report and animal framing, not human PD. anecdote
  • Human gap: No solid published human half-life, bioavailability fraction, Tmax, or clearance for gray-market Dihexa product. trial

More on what it is 9

  • Why people search it: Forums and vendor lore call it a high-potency “synaptogenic” nootropic that rebuilds synaptic hardware rather than giving a stimulant buzz; oral activity is a big differentiator vs classic neuropeptides. forum
  • What it is: Synthetic metabolically stabilized angiotensin-IV–derived oligopeptide (PNB-0408; chemical name N-hexanoic-Tyr-Ile-(6)-aminohexanoic amide) developed from Washington State University Ang IV analog work — research nootropic, not an approved drug. trial
  • Mechanism talk (proposed): Said to bind/dimerize HGF and potentiate HGF/c-Met signaling → dendritic spinogenesis and functional synaptogenesis (hippocampus heavily cited). Core mechanism papers from that program include later-retracted work — treat the pathway story as proposed, not settled clinical fact. animal
  • Potency meme: “~7 orders of magnitude more potent than BDNF” / “10 million× BDNF” traces to in-vitro spine-density assay language (picomolar Dihexa vs higher BDNF concentrations) — not a human outcome and not “millions of times better memory in a living brain.” lab
  • Evidence honesty: Solid rodent scopolamine and aged-rat memory work (McCoy 2013 — paper later under Expression of Concern) plus independent APP/PS1 mouse work (Sun 2021); no large modern human RCTs of Dihexa itself. trial
  • Clinical-class cousin: Athira’s fosgonimeton (ATH-1017 / NDX-1017) grew out of the same HGF/MET commercialization path (described variously as related small-molecule program / prodrug lineage to Dihexa) — LIFT-AD Phase 2/3 Alzheimer’s primary endpoint failed (2024). That is class context, not a Dihexa human trial. trial
  • Not: Not a racetam, stimulant, GH secretagogue, Semax, PE-22-28, FDA-approved AD treatment, or proven human “brain repair” drug. trial
  • Integrity note: Kawas 2012 and Benoist 2014 HGF/c-Met mechanism papers were retracted (2025 notices after WSU misconduct findings involving altered images); McCoy 2013 carries Expression of Concern. Independent animal data still exists but the marketed mechanism story is damaged. trial
  • 2026 compounding calendar: Dihexa acetate came off FDA 503A Category 2 after nomination withdrawal (April 2026). PCAC review is scheduled with LL-37, injectable GHK-Cu, Melanotan II, and PEG-MGF before the end of February 2027 — it was not on the July 2026 seven. FDA staff language has stated it has not identified human exposure data for Dihexa acetate by any route. trial

Stacks 11

  • Semax: Common “acute focus BDNF-style” neighbor while Dihexa is framed as deeper structural memory/cognition; stack or alternate days when overstim appears. forum
  • Selank: Anxiety-modulation / calm clarity pair when Dihexa feels activating or irritable. forum
  • Semax + Selank + Dihexa: Triple cognitive-peptide stack in some protocols — start each alone first is frequent advice. forum
  • Racetam + choline: Older LongeCity-style logs with piracetam-family agents plus choline source. forum
  • PE-22-28 (mini-spadin / TREK-1): Often compared or alternated more than always combined — different mechanism (TREK-1 / BDNF-upregulation talk vs HGF/c-Met). forum
  • Cerebrolysin: Sequenced in some clinic “neuro recovery” frameworks rather than same-day mega-stack. forum
  • NAD+ (IV or other): Cellular-energy add-on in wellness clinic cognitive packages — confounds outcome credit. forum
  • Lifestyle co-factors: Sleep, resistance/aerobic training, and deliberate learning load often get partial credit for good logs. forum
  • Caution — heavy neurotrophic stacking: High-dose Semax + high-dose Dihexa daily is sometimes discouraged (diminishing returns / overstim / “pathway saturation” folklore). forum
  • Caution — multi HGF/c-Met or aggressive growth stacks: Community cancer-pathway talk leads some to avoid piling proliferative-signaling agents. forum
  • TAK-653 / ISRIB co-logs: 2025 NooTopics-style threads sometimes run Dihexa next to other experimental cognition agents — multi-agent, confounded. forum

Access talk 3

  • Research-chem oral caps, DMSO solutions, and powders dominate Western talk. forum
  • Dihexa acetate: Category 2 nomination withdrawn April 2026; PCAC window before end of Feb 2027 with four other peptides. Not FDA-approved. trial
  • Human-data gap: FDA staff language has stated it has not identified human exposure data for Dihexa acetate by any route. trial

Storage notes 2

  • No mix instructions here: STUDresearch does not list reconstitution, diluent volumes, or syringe unit charts. People reconstitute many different ways and vial labels differ — that content creates more confusion than clarity. forum
  • Storage (general talk only): Unopened research products are usually kept cool, dry, and away from light per the seller label. Anything after first use is product-specific — follow the label, not a universal forum SOP. forum

Watch for 15

  • Headache / mental fatigue: Most common community complaint; sometimes “brain fog” or tiredness instead of sharpness — dose, DMSO, or vascular speculation, unproven. forum
  • Irritability / anxiety / overstimulation: Restlessness, agitation, or anxiety in a subset, often framed as dose-dependent; mixed with reports of neutral or improved mood. forum
  • Sleep: Evening dose → insomnia, lighter sleep, racing thoughts; vivid dreams reported in both directions of “good/bad.” anecdote
  • GI: Nausea or mild GI discomfort mainly with oral capsules/powder. forum
  • Appetite: Inconsistent self-reports of appetite up or down — no clear dose curve. anecdote
  • DMSO / skin: Redness, itch, burn, garlic odor, and carrier reactions separate from the peptide itself. forum
  • Blood-pressure speculation: Ang IV structural origin leads some to watch BP subjectively; no human CV dataset for Dihexa. forum
  • HGF/c-Met / oncology theoretical risk: Pathway is proliferative and oncology-relevant; chronic potentiation is a theoretical tumor-support concern. No published study shows Dihexa accelerates cancer in humans; still a major community precaution (esp. active/prior malignancy avoidance talk). forum
  • Source quality: Mislabel, impurity, under/over-fill, and salt/identity variance are structural gray-market risks. forum
  • Reported stop-pattern discussion (anecdote only): Community advice includes pausing when headache, irritability or GI symptoms persist, dropping DMSO routes when skin reactions dominate, and avoiding use with a malignancy history according to personal risk tolerance. These are attributed precautions, not trial stopping rules; the cancer-pathway concern is theoretical. forum
  • DMSO-in-nose/eye: Minority IN-DMSO experiments are described as destructive to mucosa; “do not get this in your eye” is the harm-reduction line. anecdote
  • Mechanism literature damaged: Core HGF/c-Met papers retracted (2025); McCoy 2013 under Expression of Concern — weakens confidence that marketed mechanism and potency claims map cleanly to real-world product use. trial
  • Related clinical failure (class context): Fosgonimeton (ATH-1017) LIFT-AD failed primary/key secondary endpoints in mild–moderate AD (2024) — does not prove Dihexa is unsafe, but undercuts “this pathway will clearly fix human dementia” marketing. trial
  • Human data gap: No Phase 1 toxicology package or controlled human safety set for Dihexa; “felt fine” ≠ long-term safety. trial
  • Feb 2027 PCAC is a review date, not permission to compound. Category 2 nomination withdrawal ≠ 503A listing ≠ FDA approval. trial

Updated: 2026-09-01

Evidence mix Mostly community / anecdote tags Full: every bullet (trial + community). Use Scan for a faster bro-science read.
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