Dihexa
Dihexa is a gray-market angiotensin IV analog with rodent synaptogenesis and memory data, including McCoy 2013 and Sun 2021, but zero human trials, no human pharmacokinetics, and FDA-noted absence of human exposure data.
Dihexa scored 3.8 / 10 (⚠️ Proceed with caution) on the BioHarmony scale as a Substance → Research Compound.
What It Is
Dihexa is a synthetic angiotensin IV analog developed as a procognitive research compound. The basic claim is simple: dihexa may help neurons form new synapses by potentiating hepatocyte growth factor signaling at the c-Met receptor, with AT4 / IRAP biology connecting the angiotensin system to memory-related pathways.
The scientific case is still almost entirely animal and cell work. Benoist 2011 reported hippocampal synaptogenesis and spatial-memory effects in rats, McCoy 2013 evaluated metabolically stabilized angiotensin IV analogs as procognitive agents, and Sun 2021 reported memory rescue in APP / PS1 mice. That makes dihexa interesting as a research tool. It does not make dihexa a validated human nootropic.
The risk side is unusually important because c-Met is not a casual wellness pathway. HGF / c-Met signaling appears throughout oncology biology, and MET inhibitors exist because aberrant MET activation can support cancer growth, invasion, and metastasis. Comoglio 2008 frames MET as an oncology drug target, while Mathieu 2022 summarizes FDA approvals of capmatinib and tepotinib for MET-altered lung cancer. In practice, dihexa sits in a difficult category: mechanistically compelling, clinically untested, and operating near a pathway that medicine often tries to inhibit in cancer.
Regulators have not cleared up the uncertainty. FDA's dihexa substance record identifies the molecule, but the record itself says UNII availability does not imply regulatory review or approval. FDA's compounding materials state that the agency has not identified human exposure data for dihexa acetate and lacks important safety information. That is why this report holds the v0.x score at 4.7 / 10 despite the attractive cognitive story.
Terminology
- Angiotensin IV: A peptide fragment of the angiotensin system. Angiotensin IV analogs are studied for memory and hippocampal effects in animal models.
- AT4 receptor: The binding site originally associated with angiotensin IV. Albiston 2001 identified this site as IRAP.
- IRAP: Insulin-regulated aminopeptidase, a membrane enzyme that also functions as the AT4 binding site.
- HGF: Hepatocyte growth factor, a growth factor that signals through the c-Met receptor and affects survival, migration, repair, and tumor biology.
- c-Met / MET: A receptor tyrosine kinase activated by HGF. MET dysregulation is targeted by oncology drugs such as capmatinib and tepotinib.
- Synaptogenesis: Formation of new synaptic connections between neurons. This is dihexa's claimed central mechanism.
- Dendritic spine density: A structural proxy for synaptic connectivity. Higher spine density can suggest more potential synaptic contacts.
- Morris water maze: A rodent spatial-learning and memory task used in aging and neurodegeneration models.
- APP / PS1 mouse: A transgenic Alzheimer's-disease mouse model used to study amyloid-related cognitive impairment.
- PNB-0408 / ATH-1001: Alternate identifiers listed for dihexa in FDA substance records.
- Gray-market: Sold outside approved human-use channels, often as a research chemical with no cGMP manufacturing or clinical consumer protections.
- cGMP: Current Good Manufacturing Practice, the quality standard expected for regulated pharmaceutical manufacturing.
- HPLC: High-performance liquid chromatography, a lab method used to check identity and purity.
- Mass spectrometry: An analytical method used to confirm molecular identity and detect contaminants or degradation products.
- IND: Investigational New Drug application, the FDA filing usually required before clinical testing of a new drug in humans.
- WADA: World Anti-Doping Agency. The 2026 prohibited list covers HGF and growth-factor modulators, creating athlete risk for dihexa.
Dosing & Protocols
Dosing information is summarized from published research and community reports. This is not a prescribing guide. Consult a healthcare provider before starting any protocol.
View 3 routes and 3 protocols
Routes & Forms
| Route | Form | Clinical Range | Community Range |
|---|---|---|---|
| Oral capsule (gray-market) | Capsule or prefilled vendor capsules sold as a research chemical | No clinical human range established | 5-15 mg/day oral |
| Sublingual powder (gray-market) | Loose powder held under the tongue | No clinical human range established | 8-45 mg/day sublingual |
| Intranasal (gray-market, speculative) | Powder or improvised nasal preparation | No clinical human range established | 5-10 mg/day intranasal, speculative |
Protocols
Starter / cautious Anecdotal
- Dose
- 8-12 mg/day sublingual
- Frequency
- Daily
- Duration
- 2-4 weeks
Lower-end community protocol for first-time users testing subjective tolerability. Short duration is a risk-control choice, not a validated pharmacology decision.
Intermediate / typical Anecdotal
- Dose
- 15-30 mg/day sublingual
- Frequency
- Daily
- Duration
- 4-8 weeks
Commonly reported community midpoint. No RCT, pharmacokinetic, or long-term safety data supports this exposure.
Max reported (no safety data) Anecdotal
- Dose
- 40-50 mg/day sublingual
- Frequency
- Daily
- Duration
- 4-8 weeks
Upper-end community exposure reported by heavy users. Higher dose with the same unknown cancer-pathway risk profile is worse, not better. Included for documentation, not endorsement.
Use-Case Specific Dosing
| Use Case | Dose | Notes |
|---|---|---|
How this score is calculated →
Upside contribution: 1.65
| Dimension | Weight | Score | Visual | Weighted |
|---|---|---|---|---|
| Efficacy | 25% | 1.5 | 0.375 | |
| Breadth of Benefits | 15% | 1.5 | 0.225 | |
| Evidence Quality | 25% | 1.2 | 0.300 | |
| Speed of Onset | 10% | 2.5 | 0.250 | |
| Durability | 10% | 2.0 | 0.200 | |
| Bioindividuality Upside | 15% | 2.0 | 0.300 | |
| Total | 1.650 |
Upside Rationale
Dihexa has its best upside when the user matches Dihexa to the evidence-backed lane instead of treating it as a broad wellness shortcut. The upside is narrow but real: Dihexa has unusually interesting preclinical synaptogenesis and memory data. The compound targets angiotensin IV and HGF/MET-adjacent signaling, which makes the mechanism more specific than generic stimulant-style focus support. That specificity is also why the report does not score Dihexa like a casual supplement. The most useful anchors are McCoy 2013 and Sun 2021, because they explain both the signal and the boundary around that signal. For readers, the so-what is simple: Dihexa is worth considering when the expected benefit can be observed in a concrete marker, symptom, lab, or performance measure. Dihexa is weaker when the goal is vague optimization with no baseline and no follow-up.
Efficacy (1.5/5.0): Dihexa efficacy remains weak because no human efficacy trial exists. The strongest positive evidence is still preclinical: McCoy 2013 reported synaptogenic activity in rat and cell models, Benoist 2011 reported rodent spatial-memory effects, and Sun 2021 reported APP / PS1 mouse cognitive rescue. That is enough to justify continued research interest. It is not enough to support a high human nootropic score. Wells 2024 adds a recent negative animal signal in a Huntington's-like rat model, which tempers the idea that dihexa broadly rescues neurodegenerative dysfunction.
Breadth of Benefits (1.5/5.0): Dihexa breadth is narrow. The documented upside is clustered around hippocampal synaptogenesis, spatial memory, APP / PS1 mouse cognition, and one peripheral nerve-repair animal model. Weiss 2021 studied stem cells, G-CSF, and/or dihexa in a rat sciatic nerve damage-repair model, but that does not establish broad neuroregeneration in humans. There is no cardiovascular, metabolic, immune, skin, hormonal, endurance, pain, or longevity evidence. HGF / c-Met signaling has broad tissue biology, but in this report that breadth counts more as safety complexity than as a benefit.
Evidence Quality (1.2/5.0): Dihexa evidence quality is very low because the human evidence base is empty. Track 1 found no eligible 2024-2026 human RCT, systematic review, or meta-analysis with n >= 100 for dihexa / PNB-0408. Track 2 corrected several citation problems: Benoist 2011, Albiston 2001, and Comoglio 2008 needed corrected PMIDs; the Ali label should be Sun 2021; the Seyedsadjadi label should be Weiss 2021. The audit could not verify that McCoy 2013 itself is retracted, so this report does not label that paper as retracted.
Speed of Onset (2.5/5.0): Dihexa speed is entirely anecdotal in humans. Gray-market users report subjective cognitive sharpness, verbal recall, pattern recognition, and vivid dreams within 1-3 days. Rodent work suggests synaptogenesis and memory effects unfold over days to weeks, but that is not a validated human onset timeline. Fast subjective effects are also the easiest class of nootropic signal to confuse with placebo, sleep disruption, expectation, or stimulant-like arousal. A 2.5 preserves the v0.x score because fast onset is plausible but not objectively demonstrated.
Durability (2.0/5.0): Dihexa durability is unknown. If synaptogenesis translated cleanly into humans, some structural neural changes could persist beyond dosing. That is the optimistic case. The conservative case is stronger: no washout study exists, no human longitudinal data exists, and community reports often describe effects fading after discontinuation. Durability also has an asymmetric tail. If a growth-factor pathway meaningfully affected tumor biology in a vulnerable user, the consequence would not be easily reversible. The score stays at 2.0 because possible structural persistence is balanced by almost no evidence.
Bioindividuality (2.0/5.0): Dihexa responder patterns are unmapped. No human trial has stratified users by age, sex, APOE genotype, cognitive baseline, neurodegenerative status, inflammatory state, sleep, medications, cancer risk, or route. The likely user base is small, self-selected, expectation-heavy, and exposed to uncertain product identity. Bioindividuality may be large because HGF / c-Met signaling and neuroplasticity vary by context, but no data tells us who benefits, who does not respond, or who is harmed. Nick has not personally run a cycle, so there is no first-person response signal to add.
Downside contribution: 3.31 (safety risks weighted extra)
| Dimension | Weight | Score | Visual | Weighted |
|---|---|---|---|---|
| Safety Risk | 30% | 3.5 | 1.050 | |
| Side Effect Profile | 15% | 2.0 | 0.300 | |
| Financial Cost | 5% | 2.5 | 0.125 | |
| Time/Effort Burden | 5% | 2.5 | 0.125 | |
| Opportunity Cost | 5% | 3.0 | 0.150 | |
| Dependency / Withdrawal | 15% | 1.5 | 0.225 | |
| Reversibility | 25% | 2.0 | 0.500 | |
| Total | 2.475 | |||
| Harm subtotal × 1.4 | 2.905 | |||
| Opportunity subtotal × 1.0 | 0.400 | |||
| Combined downside | 3.305 | |||
| Baseline offset (constant) | −1.340 | |||
| Effective downside penalty | 1.965 |
Downside Rationale
Dihexa's main downside is not one isolated risk; it is the mismatch between marketing certainty and the actual evidence base. The downside dominates the score. Dihexa has no human trials, no practical human pharmacokinetic map, no long-term safety record, and a theoretical cancer-signaling concern because MET biology is tied to invasion and metastasis pathways. The gray-market supply chain adds identity, purity, and dosing uncertainty. FDA 2026 is the anchor that keeps the safety discussion honest, while McCoy 2013 helps define where the benefits are strongest. The practical move is to treat Dihexa as a targeted experiment, not a default habit. That means checking contraindications, product quality, dose, medication conflicts, and the opportunity cost of skipping better-supported basics before assigning Dihexa a permanent role.
Safety Risk (3.5/5.0): Dihexa safety risk is the dominant downside because c-Met is a validated oncology pathway. Comoglio 2008 describes MET inhibitors as oncology drug-development targets, and Wu 2021 reviews capmatinib in MET-dysregulated lung cancer. Dihexa does not have a carcinogenicity study, a Phase 1 safety study, or human long-term exposure data. FDA's compounding page states that it has not identified human exposure data for dihexa acetate and lacks important safety information. The risk remains theoretical for dihexa, but it is grounded in real pathway biology.
Side Effect Profile (2.0/5.0): Dihexa side effects are poorly characterized. Community reports mention headache, anxiety, overstimulation, insomnia, and vivid dreams. These are usually described as mild or manageable, but the dataset is uncontrolled and contaminated by unknown product identity. A bad reaction could come from dihexa, an impurity, a degradation product, a mislabeled compound, or dose error. There is no adverse-event registry, no trial table, no frequency estimate, and no route-specific side-effect profile. The score stays at 2.0 because reported acute side effects are not severe, while uncertainty is high.
Financial Cost (2.5/5.0): Dihexa sticker cost is moderate, typically around $30-60/month at reported community doses. The real cost is quality control. A responsible user would need third-party HPLC and mass spectrometry on each lot, plus careful storage and vendor due diligence. Those steps can cost more than the compound itself. Paying $50/month for an unverified research chemical is not the same as paying $50/month for a regulated supplement with identity testing and consumer protections.
Time / Effort Burden (2.5/5.0): Dihexa effort is moderate because the daily act is simple but the safe-use overhead is not. Users must choose among oral, sublingual, and intranasal routes without human pharmacokinetic guidance. Sublingual powder requires milligram-scale measuring, and consumer scales are unreliable in that range. The sourcing burden is larger: vendor screening, lot verification, purity testing, storage, cycle planning, and a conservative stop rule. The compound is easy to take and hard to responsibly validate.
Opportunity Cost (3.0/5.0): Dihexa opportunity cost is high because safer cognitive interventions exist. Creatine, sleep extension, aerobic training, resistance training, bacopa, meditation, light exposure, and medical workups for fatigue or cognitive decline all have better human risk characterization. Choosing dihexa means allocating risk budget to a gray-market growth-factor-modulating compound without human safety data. The mechanism is distinct, which prevents the opportunity score from being worse, but for most users this is a poor first-line cognitive-enhancement choice.
Dependency / Withdrawal (1.5/5.0): Dihexa dependency risk appears low but unstudied. There is no known reward-pathway mechanism, no opioid-like withdrawal model, and no documented withdrawal syndrome in the available animal or community record. Functional dependence is still possible if a user comes to rely on perceived cognitive sharpness during demanding work. Tolerance and rebound have not been measured. The score stays at 1.5 because there is no strong dependency signal, but the absence of human discontinuation data prevents a lower score.
Reversibility (2.0/5.0): Dihexa reversibility is mixed. Short-term subjective effects appear to fade after stopping based on community reports, and no acute irreversible pharmacology has been shown. The concern is structural and pathway-level reversibility. If synaptogenesis meaningfully translates to humans, the desired neural changes may persist. If chronic HGF / c-Met modulation accelerates a malignancy in a susceptible user, that outcome is not cleanly reversible. The normal case may be reversible; the tail case is not. That asymmetry justifies the preserved 2.0 score.
Verdict
Dihexa is a 3.8/10 fit for experimenters looking at cognition through a high-risk research-chemical lens, not people who want a normal nootropic, not a clinically proven memory drug. The cleanest evidence anchors are McCoy 2013, which supports rodent and cell procognitive activity, and Sun 2021, which reported APP/PS1 mouse memory rescue. FDA 2026 adds useful context: states human exposure data and key safety information are lacking. The practical gap is the same one that shows up across the report: mechanism and early outcomes are more convincing than broad real-world certainty. In practice, Dihexa belongs after the basics, works best when the target is specific, and deserves tracking around benefits, side effects, interactions, and cost before it becomes a standing protocol.
✅ Best for: Researchers and informed self-experimenters specifically studying neurodegenerative mechanisms, not general productivity seekers. The least-unreasonable use case would be a short, carefully documented cycle in someone with a specific cognitive or neurodegenerative hypothesis, medical oversight, third-party identity and purity testing, no cancer risk factors, no competitive-sport constraints, no pregnancy or pediatric exposure, and no prescription-medication complexity. Even then, dihexa is better framed as a research-risk decision than a supplement recommendation.
❌ Avoid if: You have any personal cancer history, strong family cancer predisposition, pregnancy, lactation, pediatric exposure, cardiovascular disease, active unexplained symptoms, or current prescription medications. Avoid dihexa if you compete in drug-tested sport because WADA's 2026 list covers HGF and growth-factor modulators even though dihexa is not named. Also avoid it if you want a normal nootropic stack. The evidence base is preclinical, dosing is unvalidated, sourcing is gray-market, and the safety downside is too large for casual use.
Use Case Breakdown
The overall BioHarmony score reflects the intervention's primary evidence profile. These subratings are independent assessments per use case.
Cognition / Focus: 5.0/10
Score: 5.0/10Dihexa cognition focus earns 5.0/10 because McCoy 2013 anchors the most relevant signal. Dihexa fits cognition focus only as a research-chemical hypothesis around synaptogenesis and memory circuits, not as a proven human nootropic. The score stays bounded because the evidence is preclinical and lacks human safety, dose-response, and outcome data. In practice, Dihexa is most defensible when someone tracks memory testing, sleep, anxiety, blood pressure, and any adverse neurological changes instead of relying on a vague before-and-after feeling. Dihexa is less convincing when the basics are ignored or when the use case needs fast, proven clinical treatment. That makes this a high-caution cognition experiment with clear stop rules.
Memory: 5.5/10
Score: 5.5/10Dihexa memory earns 5.5/10 because McCoy 2013 anchors the most relevant signal. Dihexa fits memory only as a research-chemical hypothesis around synaptogenesis and memory circuits, not as a proven human nootropic. The score stays bounded because the evidence is preclinical and lacks human safety, dose-response, and outcome data. In practice, Dihexa is most defensible when someone tracks memory testing, sleep, anxiety, blood pressure, and any adverse neurological changes instead of relying on a vague before-and-after feeling. Dihexa is less convincing when the basics are ignored or when the use case needs fast, proven clinical treatment. That makes this a high-caution cognition experiment with clear stop rules.
Neuroplasticity: 5.0/10
Score: 5.0/10Dihexa neuroplasticity earns 5.0/10 because McCoy 2013 anchors the most relevant signal. Dihexa fits neuroplasticity only as a research-chemical hypothesis around synaptogenesis and memory circuits, not as a proven human nootropic. The score stays bounded because the evidence is preclinical and lacks human safety, dose-response, and outcome data. In practice, Dihexa is most defensible when someone tracks memory testing, sleep, anxiety, blood pressure, and any adverse neurological changes instead of relying on a vague before-and-after feeling. Dihexa is less convincing when the basics are ignored or when the use case needs fast, proven clinical treatment. That makes this a high-caution cognition experiment with clear stop rules.
| Use Case | Score | Summary |
|---|---|---|
| ○ Neuroprotection Primary | 4.5 | HGF / c-Met synaptogenesis is neuroprotective in theory, and APP / PS1 mouse data from Sun 2021 supports a disease-model signal. Cancer-pathway concern and no human data cap confidence. |
| ○ Nerve Regeneration Primary | 3.5 | One animal repair signal exists: Weiss 2021 studied stem cells, G-CSF, and/or dihexa in a rat sciatic nerve damage-repair model. This is not standalone human nerve-regeneration evidence. |
| ○ Traumatic Brain Injury | 3.0 | Neurotrophic and synaptogenic mechanisms could matter after brain injury, but no direct TBI study exists for dihexa. This remains speculative despite the memory-model literature. |
Frequently Asked Questions
What is dihexa and how does it actually work mechanistically?
Dihexa is a synthetic angiotensin IV analog claimed to increase synapse formation through HGF / c-Met signaling and AT4 / IRAP biology. Albiston 2001 identified AT4 as IRAP, while McCoy 2013 reported synaptogenic activity in rat and cell models. The catch: this is not a human-proven nootropic mechanism. It is a growth-factor pathway with real oncology relevance.
What did the main dihexa animal studies actually show?
The main positive signal is preclinical memory and synaptogenesis. Benoist 2011 reported hippocampal synaptogenesis and spatial-memory effects in rats, McCoy 2013 reported metabolically stabilized angiotensin IV analog activity, and Sun 2021 reported APP / PS1 mouse memory rescue. None of these establishes human benefit.
Why are there no human trials on dihexa specifically?
There are no published human trials for dihexa itself. The clinical-development path moved toward related HGF / MET-modulating candidates, but those data cannot be transferred to dihexa. FDA's compounding page says it has not identified human exposure data for dihexa acetate. That means no human pharmacokinetics, no maximum tolerated dose, no long-term safety program, and no validated route.
What do gray-market users and biohackers report subjectively?
Gray-market users commonly report faster recall, sharper verbal fluency, pattern recognition, and vivid dreams within 1-3 days. Some also report headaches, anxiety, overstimulation, and insomnia. These reports are uncontrolled, unblinded, and confounded by product-identity uncertainty. They are useful for hypothesis generation only. No Cogstate, CANTAB, imaging, biomarker, or clinician-rated human dataset confirms the subjective effect.
How serious is the cancer concern with c-Met activation?
The cancer concern is serious enough to drive the caution score. c-Met is not an obscure pathway: Comoglio 2008 frames MET / HGF as an oncology drug-development target, and Mathieu 2022 summarizes FDA approvals of capmatinib and tepotinib for MET-altered lung cancer. Dihexa has no carcinogenicity study to show chronic HGF / c-Met modulation is safe.
How do people source dihexa and what are the sourcing risks?
Dihexa is usually sold by gray-market research-chemical vendors, often labeled not for human consumption. The supply chain is a separate risk from the molecule: identity, purity, degradation, contaminants, and dosing accuracy may all be unknown. Responsible verification would require independent HPLC and mass spectrometry. Without that, a product labeled dihexa may not be dihexa, or may contain unwanted impurities.
What are the hard contraindications for dihexa?
Avoid dihexa if you have any personal cancer history, strong family cancer predisposition, pregnancy, lactation, pediatric exposure, cardiovascular disease, or current prescription medications. Competitive athletes should also avoid it unless they obtain written anti-doping clearance because the WADA prohibited list covers HGF and growth-factor modulators. The absence of human interaction data makes ordinary medication stacking impossible to risk-stratify.
What is the actual legal and regulatory status of dihexa in the US?
Dihexa has an FDA substance identity record, but that is not approval. The FDA GSRS record states that UNII availability does not imply regulatory review or approval. The FDA 503A update removed dihexa acetate from Category 2 because the nomination was withdrawn, with later PCAC consultation planned. That is a process update, not human-use clearance.
How fast should dihexa work if it works at all?
The only human onset timeline is anecdotal: users report subjective focus and vivid dreams within 1-3 days. Rodent synaptogenesis and memory effects are described over days to weeks in Benoist 2011 and related preclinical work. No human trial has measured onset, dose-response, washout, or persistence, so any practical timeline is speculative.
How This Score Could Change
BioHarmony scores are living assessments. New research, regulatory changes, or personal context can shift the score up or down. These are the most likely scenarios that would change this intervention's rating.
| Scenario | Dimensions changed | New score |
|---|---|---|
| Independent human RCT shows objective cognitive benefit with clean short-term safety | Evidence 1.2 to 2.5; Efficacy 1.5 to 3.0 | 5.0 / 10 Neutral |
| Human Phase 1 shows clean pharmacokinetics, tolerability, biomarkers, and no concerning growth-factor signal | Evidence 1.2 to 2.5; Safety 3.5 to 2.5 | 5.2 / 10 Neutral |
| Long-term animal carcinogenicity study shows tumor promotion or accelerated metastasis | Safety 3.5 to 4.5; Reversibility 2.0 to 3.0 | 3.5 / 10 Skip |
| Fosgonimeton Phase 3 succeeds but no dihexa-specific human data appears | Evidence 1.2 to 2.0; Efficacy 1.5 to 2.5 | 4.7 / 10 Caution |
| 2024-2026 negative animal findings replicate across additional neurodegeneration models | Efficacy 1.5 to 1.1; Breadth 1.5 to 1.2 | 3.7 / 10 Caution |
| FDA or WADA issues explicit warning against human or athlete use | Safety 3.5 to 4.0; Opportunity 3.0 to 3.5 | 3.6 / 10 Skip |
Key Evidence Sources
- McCoy AT et al. 2013 - Evaluation of metabolically stabilized angiotensin IV analogs as procognitive / antidementia agents, JPET. Rat/cell preclinical evidence for dihexa-related synaptogenic and procognitive activity; audit confirmed PMID 23055539.
- Benoist CC et al. 2011 - Facilitation of hippocampal synaptogenesis and spatial memory by C-terminal truncated Nle1-angiotensin IV analogs, JPET. Rodent hippocampal synaptogenesis and spatial-memory study; audit corrected the PubMed link to PMID 21719467.
- Albiston AL et al. 2001 - Evidence that the angiotensin IV (AT4) receptor is the enzyme insulin-regulated aminopeptidase, J Biol Chem. Mechanistic AT4 / IRAP identity paper; audit corrected the PubMed link to PMID 11707427.
- Wright JW, Harding JW 2008 - The angiotensin AT4 receptor subtype as a target for memory dysfunction associated with Alzheimer's disease, Drugs of the Future. Originating-lab review of AT4 cognitive-target rationale; not clinical validation of dihexa.
- Sun X et al. 2021 - AngIV-Analog Dihexa rescues cognitive impairment and recovers memory in the APP / PS1 mouse via PI3K / AKT signaling, Brain Sciences. Independent mouse Alzheimer's-model signal; audit corrected the author label from Ali to Sun.
- Weiss JB et al. 2021 - Stem cell, G-CSF and/or dihexa to promote limb function recovery in a rat sciatic nerve damage-repair model, Annals of Medicine and Surgery. Rat peripheral nerve-repair model in a combined MSC / G-CSF / dihexa context; audit corrected author/year from Seyedsadjadi 2022.
- Comoglio PM et al. 2008 - Drug development of MET inhibitors in oncology, Nature Reviews Drug Discovery. Frames MET / HGF as a cancer invasion and metastasis pathway and oncology drug target; audit corrected PMID 18511928.
- Wells L et al. 2024 - Effects of an angiotensin IV analog on 3-nitropropionic-acid-induced Huntington's disease-like symptoms in rats, Journal of Huntington's Disease. Recent animal-only signal found by audit: PNB-0408 / dihexa did not protect against motor, weight, or cognitive deficits in 40 rats.
- FDA GSRS 2026 - DIHEXA substance record, UNII 9WYX65A5C2. FDA substance identity record lists DIHEXA, PNB-0408, ATH-1001, and notes UNII availability does not imply regulatory review or approval.
- FDA 2026 - Certain bulk drug substances for use in compounding that may present significant safety risks. FDA page states it has not identified human exposure data for dihexa acetate and lacks important safety information.
- FDA 2026 - Bulk drug substances nominated for use in compounding under Section 503A, updated April 22, 2026. FDA update says dihexa acetate was removed from Category 2 because the nomination was withdrawn, with PCAC consultation planned before February 2027.
- WADA 2026 - Prohibited List. 2026 list in force from 2026-01-01; growth factors and growth-factor modulators include HGF and related regenerative-capacity modulators.
- Mathieu LN et al. 2022 - FDA approval summary: capmatinib and tepotinib for metastatic NSCLC harboring MET exon 14 skipping mutations or alterations, Clinical Cancer Research. FDA oncology approval summary confirming MET inhibitor drug approvals for MET-altered lung cancer.
- Wu YL et al. 2021 - Capmatinib for patients with NSCLC with MET exon 14 skipping mutations: review of preclinical and clinical studies, Cancer Treatment Reviews. Review explains MET receptor biology and aberrant activation mechanisms in cancer.
- Hsu R et al. 2023 - The development and role of capmatinib in MET-dysregulated non-small cell lung cancer, Cancers. Clinical oncology review supporting the safety-context point that c-Met is a druggable cancer pathway.
Holistic Evidence Profile
Evidence on this intervention is summarized across three complementary streams: contemporary clinical research, pre-RCT-era pharmacology and observational use, and the traditional medical systems that documented it first. Convergence across streams signals higher confidence; divergence is surfaced honestly.
Modern Clinical Research
Confidence: Low
Citations: McCoy 2013, Benoist 2011, Sun 2021, Weiss 2021, Wells 2024, FDA 2026, Comoglio 2008, Mathieu 2022
Pre-RCT-Era Pharmacology and Use
Confidence: Limited
Citations: Albiston 2001, Wright 2008, McCoy 2013, FDA 2026
Traditional Medicine Systems
Confidence: Low
Holistic Evidence for Dihexa
The lenses diverge rather than converge. Modern science offers a small preclinical signal and a clear safety concern; the historical lens shows a narrow academic research lineage that did not become a dihexa clinical program; the traditional lens is absent. The honest synthesis is that dihexa is interesting enough to study and too under-characterized to recommend for routine human use.
What to Track If You Try This
These are the data points that matter most while running a 30-day Experiment with this intervention.
How to read this section
- Pre
- Test or score before starting the protocol. Anchors a baseline.
- During
- Track while running the protocol so you can see if anything is changing.
- Post
- Re-test after a full cycle to confirm the change held.
- Up
- The marker should rise. For most positive outcomes, that is a good sign.
- Down
- The marker should fall. For most positive outcomes, that is a good sign.
- Stable
- The marker should hold steady. Big swings in either direction are a yellow flag.
- Watch
- Direction depends on dose, timing, and your baseline. Pay close attention to the trend.
- N/A
- No expected direction. The entry is there to anchor a baseline reading.
- Primary
- The Pulse dimension most likely to shift. Track this first.
- Secondary
- Also relevant, but a smaller or less consistent shift. Track if Primary is unclear.
Bloodwork to Order
Open These Markers In Your Dashboard
- ALT Baseline (pre-protocol) During | Expected Stable
- AST During | Expected Stable
- hs-CRP During | Expected Watch
Pulse Dimensions to Watch
- Drive During | Expected Up | Primary
- Energy During | Expected Up | Secondary
- Calm During | Expected Watch | Tertiary
Subjective Signals (Daily Voice Card)
- Memory Recall Scale 1-5 | During | Expected Up
- Anxiety Or Agitation Scale 1-5 | During | Expected Watch
- Sleep Disruption Scale 1-5 | During | Expected Watch
Red Flags: Stop and Consult
- Severe agitation, mania, or insomnia
- New neurological symptoms
Other interventions for Cognition & Focus
See all ratings →📊 How BioHarmony scoring works
BioHarmony translates a weighted expected-value calculation into a reader-facing 0–10 score. Tier bands: Skip 0–3.6, Caution 3.7–4.7, Neutral 4.8–5.7, Worth Trying 5.8–6.9, Strong Recommend 7.0–7.9, Top-tier 8.0+.
Harm-type downsides (safety risk, side effects, reversibility, dependency) carry a 1.4× precautionary multiplier. Harm weighs more than benefit. Opportunity-type downsides (financial cost, time/effort, opportunity cost) are subtracted at face value.
Use case subratings are independent assessments of how well the intervention addresses specific health goals. They are not components of the overall score. Each subrating reflects the scorer's judgment based on use-case-specific evidence, safety, and effect sizes.
Every dimension is evaluated on a 1–5 scale, and the baseline (1) is subtracted before weighting. A perfect intervention with zero downsides contributes zero penalty rather than a residual floor, so top-tier scores are actually reachable.
EV = Upside − Downside
EV = 0.650 − 1.965 = -1.315
Formula v0.5 maps EV = 0 to score 5.0. Above neutral, 1 EV point equals 1 score point. Below neutral, 1 EV point equals about 0.71 score points, so EV = −7 reaches 0.0 while EV = +5 reaches 10.0. Both sides use the full 5-point half-scale.
Score = 5 + (-1.315 / 7) × 5 = 4.1 / 10
