# Dihexa

Angiotensin-IV analogue claimed as potent synaptogenic; hyped, not evidenced in humans.

- Page: https://peprank.xyz/peptides/dihexa
- Category: Neuroprotection & repair (Research peptide)
- Also known as: PNB-0408; N-hexanoic-Tyr-Ile-(6) aminohexanoic amide
- Routes: Oral / Topical / Injection
- Sequence: YI (N-hexanoyl-Tyr-Ile-(6-aminohexanoic) amide; angiotensin IV derived, largely non-peptidic)
- Safety tier: Strict: Avoid · Balanced: Avoid · Evidence only: Caution
- Risk axes (0 none to 3 severe): Seen harm 1, Mechanism 2, Data gap 3, Silent harm 3, Product 2
- Positive: 50% of 30 graded reports glowing or positive, shrunk toward the 49% all-report average by 8 reports' weight
- Rank: #36 of 61 research peptides
- Graded reports: 30 (Glowing 5, Positive 10, Mixed 3, Nothing 4, Negative 6, Bad reaction 2)
- Evidence: Animal only
- Access: Grey market
- Onset: Oral or transdermal users who feel it describe a lift within an hour or two of the first dose; others build up over 1-2 weeks or feel nothing.
- Lasts: Users report a single dose lasting several days (long half-life), so many dose every few days to weekly rather than daily.
- Cost per month: ≈ €13–53 (at 5–20 mg/day, PGL Chemie at €0.089/mg, trust-3 shop)
- Dose users report: 2.6–4.9 mg/day (median 4.3 mg, n=6), ≈ €7–13 a month at that dose
- Updated: 2026-10-30

**Why Avoid under the strict bar:** Activates the oncogenic HGF/c-Met pathway, has no human safety data, and its foundational studies are under expressions of concern.

## What users report

Polarised: many report energy, faster learning, recall and even chess-rating gains within hours of a dose; others feel nothing even at 30 mg, perhaps 15-25%. Side effects are frequent: insomnia or 3 am waking, or the opposite (exhaustion, dozing off), anger/irritability and emotional flattening. One user reports permanent language interference after months of use and one heard voices falling asleep; commenters also warn of 'aberrant learning' and the cancer mechanism.

**Effects:** energy and mental clarity; faster learning/recall; effects persist between doses (long half-life)

**Downsides:** irritability/anger; no effect for many; dosing confusion across routes

**Risks:** acts on the HGF/c-Met pathway, a well-known oncogenic driver (tumour growth, invasion, angiogenesis); no carcinogenicity data; FDA found no human exposure data at all; the founding research (Harding/Athira) received expressions of concern; the related drug fosgonimeton failed its phase 2/3 Alzheimer's trial (2024); theoretical maladaptive plasticity, made worse when stacked with stimulants

**Typical use:** 5-20 mg/day oral or transdermal (community), often intermittent.

**Getting it:** Research-chemical and peptide vendors sell powder, capsules and DMSO/transdermal solutions; some US telehealth clinics route it through compounding pharmacies (one user paid $355 for 30 days of capsules) despite its FDA Category 2 status.

**Stacked with:** Modafinil or ADHD stimulants (Commonly combined for study sessions; NooTopics regulars call pairing a plasticity drug with stimulants reckless.); Semax / Cerebrolysin / P21 (Grouped in "brain repair" stacks for TBI or burnout, usually run one at a time to tell effects apart.); Eutropoflavin or tropoflavin (TrkB agonists stacked with it by chess and memory self-testers.)

## Risk profile

- **Seen harm 1/3:** FDA found no human exposure data. One first-hand report claims lasting interference with language learning years later, which is isolated and unverifiable; others describe irritability and fatigue.
- **Mechanism 2/3:** Marketed as a potentiator of HGF/c-Met, an oncogenic pathway, but the paper showing that mechanism in vivo was retracted in 2025 and others by the same group carry expressions of concern; the pathway concern remains credible but no longer demonstrated for dihexa.
- **Data gap 3/3:** No human safety data, and no chronic toxicity or carcinogenicity study; the nearest relative, fosgonimeton, failed a 554-patient Alzheimer trial that excluded anyone with recent cancer.
- **Silent harm 3/3:** Tumour promotion through c-Met signalling would be silent and delayed.
- **Product 2/3:** Mostly oral capsules or powder from research-chemical vendors, plus DMSO transdermal solutions; a few inject it.
- **Never if:** Active cancer or a history of cancer; Pregnancy or breastfeeding (no human reproductive data)

## Top reports

- Glowing, memory, 10 mg once weekly in DMSO: “I am on week 5 of a once weekly Dihexa cycle. So far I have noticed major improvements in athletic ability in rock climbing / basketball & ability to learn to drive a Truck and remember things needed to pass the written tests in CDL school.” — [r/Cerebrolysin](https://www.reddit.com/r/Cerebrolysin/comments/tpl9je/dihexa_and_cerebrolysin/)
- Glowing, memory: “It is super-effective for increasing memory acquisition (especially for language or stuff like programming), so effective that I have to avoid filling my brain with trash information for the duration of effects.” — [r/Biohackers](https://www.reddit.com/r/Biohackers/comments/1g8j90p/dihexa_yay_or_nay/lszuru2/)
- Glowing, energy, 10 mg every other day, then 5 mg: “I have been taking Dihexa for the past month. Started at 10mg every other day but dropped it to 5 mg after first week. It’s fucking amazing. It’s giving me energy and i can think so much clearer..” — [r/NooTopics](https://www.reddit.com/r/NooTopics/comments/1rwswj2/dihexa_2_week_report/ob7od5k/)
- Glowing, memory, 2.5 mg with 5 mg Adderall, as needed: “Some times headaches, normally just due to a lack of Choline so I just eat eggs and it goes away, but past that its just insane memory and learning with unbreakable focus, I learned LUA In a week, no joke.” — [r/NooTopics](https://www.reddit.com/r/NooTopics/comments/1lng7lo/clearing_up_some_dihexa_misconceptions/n7v9g64/)
- Glowing, mood, 5 mg in 20 ml DMSO, 2 sprays per wrist: “I feel supreme! My mood went from somber and lazy within an hour or so. I mopped my floors twice. Lots of happy thoughts and excited to share what happened.” — [r/NooTopics](https://www.reddit.com/r/NooTopics/comments/1rwswj2/dihexa_2_week_report/19ri2ndqo2jok/)

## Cheapest in Europe

- [Euro Nootropics](https://euro-nootropics.com/product/dihexa/) (FR): Dihexa powder 1g, €145, €0.14/mg (contents not stated on the page)
- [Euro Nootropics](https://euro-nootropics.com/product/dihexa/) (FR): Dihexa powder 500mg, €87, €0.17/mg (contents not stated on the page)

## Studies

- [McCoy et al. 2013: metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents](https://pubmed.ncbi.nlm.nih.gov/23055539/) (animal, 2013): The founding Dihexa paper; reversed scopolamine- and age-related learning deficits in rats and boosted dendritic spines in culture. The journal attached a notice of concern to it in 2021.
- [Benoist et al. 2014: procognitive and synaptogenic effects of angiotensin IV peptides depend on HGF/c-Met](https://pubmed.ncbi.nlm.nih.gov/25187433/) (animal, 2014): Dihexa's spine-forming and memory effects in rats were blocked by a c-Met antagonist, establishing it as an HGF/c-Met potentiator; same Harding lab.
- [Sun et al. 2021: Dihexa rescues cognitive impairment in the APP/PS1 mouse via PI3K/AKT](https://pubmed.ncbi.nlm.nih.gov/34827486/) (animal, 2021): An independent Chinese group found oral Dihexa improved water-maze memory and reduced neuroinflammation in Alzheimer's-model mice.
- [Effects of an angiotensin IV analog (PNB-0408) on 3-NP Huntington's-like symptoms in rats (2024)](https://pubmed.ncbi.nlm.nih.gov/38489193/) (animal, n=40, 2024): Dihexa did not protect rats from the motor or memory deficits of the mitochondrial toxin 3-NP.
- [Hua et al. 2022: phase 1 trial of fosgonimeton (ATH-1017), a related HGF/MET modulator](https://pubmed.ncbi.nlm.nih.gov/35180125/) (rct, n=88, 2022): The Athira prodrug from the same programme (not Dihexa itself) was well tolerated for up to 9 days in volunteers and Alzheimer's patients.
- [Porsteinsson et al. 2025: fosgonimeton in mild-to-moderate Alzheimer's disease (LIFT-AD, phase 2/3)](https://pubmed.ncbi.nlm.nih.gov/41393340/) (rct, n=287, 2025): Missed its primary and secondary cognitive endpoints at 26 weeks; 14% stopped for adverse events, mostly injection-site reactions. No trial of Dihexa itself exists.

## Sources

- [FDA: Bulk drug substances that may present significant safety risks (Category 2 / withdrawn list, Apr 2026)](https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks)
- [Athira topline: LIFT-AD phase 2/3 fosgonimeton missed primary endpoint (2024)](https://www.sec.gov/Archives/edgar/data/1620463/000095017024102788/atha-ex99_1.htm)
- [Retraction Watch 2021: four papers by Athira CEO earn expressions of concern](https://retractionwatch.com/2021/09/24/four-papers-by-athira-ceo-earn-expressions-of-concern/)