Comprehensive, evidence-based information on Dihexa (PNB-0408) — the HGF/c-Met activating peptide studied for its remarkable effects on synaptogenesis and cognitive function. Honest science. No hype.
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A brief introduction to one of the most intriguing compounds in modern neuroscience research.
Dihexa (PNB-0408) is a synthetic oligopeptide derived from angiotensin IV, originally developed at Washington State University by the research team of Dr. Joseph Harding and Dr. John Wright. Its chemical name is N-hexanoic-Tyr-Ile-(6) aminohexanoic amide, and it carries the molecular formula C27H44N4O5 with a molar mass of 504.672 g/mol.
What makes Dihexa extraordinary among research compounds is its mechanism: it activates the hepatocyte growth factor (HGF)/c-Met receptor pathway in the brain, promoting the formation of new synaptic connections — a process called synaptogenesis. In preclinical studies, Dihexa demonstrated a capacity to drive new dendritic spine formation at concentrations reported to be up to 10 million times more potent than BDNF on a molar basis in specific assay conditions [McCoy et al., 2013].
Originally investigated as a potential therapeutic for Alzheimer's disease, Dihexa has since attracted significant interest from the nootropic and cognitive enhancement community. It is important to note that all current evidence for Dihexa comes from animal and in vitro studies — no completed human clinical trials exist for Dihexa itself, though its prodrug fosgonimeton has undergone clinical testing with mixed results.
Dive deep into every aspect of Dihexa — from molecular mechanisms to UK legal considerations.
How Dihexa activates the HGF/c-Met pathway to promote synaptogenesis, dendritic spine formation, and long-term potentiation.
Read more →Memory, learning, neuroplasticity, neuroprotection — what the preclinical evidence actually says, with honest caveats.
Read more →Animal research doses, anecdotal community protocols, routes of administration, and cycling strategies.
Read more →The c-Met/oncogenic concern, retracted research, WADA status, drug interactions, and who should avoid Dihexa.
Read more →Complete analysis of key studies including the 2014 retraction, LIFT-AD failure, and independent supporting data.
Read more →Dihexa's position under UK law: not controlled, not licensed as a medicine, sold as a research chemical.
Read more →Key milestones in the scientific journey of Dihexa and related compounds.
McCoy et al. publish landmark study demonstrating Dihexa's synaptogenic properties via HGF/c-Met activation at Washington State University [McCoy et al., 2013].
Follow-up study published on Dihexa's cognitive effects. Later retracted due to data fabrication concerns involving Kawas and Harding [Benoist et al., 2014 — RETRACTED].
Comprehensive review of angiotensin IV analogs and their cognitive effects published [Wright & Harding, 2015].
M3 Biotechnology (later Athira Pharma) completes Phase 1 safety trials of fosgonimeton, a prodrug of Dihexa. Deemed safe and well-tolerated.
CEO Leen Kawas resigns amid data falsification allegations. Separately, Sun et al. publish independent supportive data in APP/PS1 mice [Sun et al., 2021].
Fosgonimeton's Phase 2 ACT-AD trial in Alzheimer's patients fails its primary endpoint.
The larger LIFT-AD trial fails both primary and key secondary endpoints, raising questions about the clinical viability of fosgonimeton.
Athira Pharma settles for $4 million with the US Department of Justice related to NIH grants using compromised research data.
Quick answers to the most common questions about Dihexa. See our full FAQ page for 25+ questions.
Dihexa (PNB-0408) is a synthetic peptide derived from angiotensin IV, developed at Washington State University. It activates the HGF/c-Met receptor pathway in the brain, promoting the formation of new synaptic connections (synaptogenesis). In preclinical studies, it has shown remarkable effects on memory and learning in animal models. All current evidence is from animal and cell studies — there are no completed human trials for Dihexa itself. Learn more about Dihexa.
Dihexa is not a controlled substance under the Misuse of Drugs Act 1971 and is not listed under the Psychoactive Substances Act 2016. It is not licensed as a medicine by the MHRA. It occupies a grey area: legal to purchase for research purposes, but it cannot be sold as a medicine or for human consumption. Read our full UK legal analysis.
The honest answer is that we don't know for certain. Dihexa activates the c-Met receptor pathway, which is also involved in certain cancers — creating a theoretical oncogenic concern. There is no long-term human safety data. A key supporting study was retracted due to data fabrication, and the related prodrug fosgonimeton saw adverse events in clinical trials. Those with cancer, precancerous conditions, or compromised immune systems should avoid Dihexa. Read about risks in full.
There is no medically established human dose for Dihexa. Anecdotal community reports typically describe 10–30mg per day taken orally, with 10mg being a common starting point. Cycling protocols (e.g. 90 days on, 30 days off) are reported but not scientifically validated. Oral bioavailability is estimated at approximately 38%. Always consult a healthcare professional before considering any research compound. See the full dosage guide.
Fosgonimeton is a phosphate prodrug of Dihexa — a chemically modified version designed for clinical use via subcutaneous injection. It was developed by Athira Pharma (formerly M3 Biotechnology) for Alzheimer's treatment. While they share a mechanism, they are different molecules with different pharmacokinetics. Fosgonimeton's clinical trial failures do not necessarily mean raw Dihexa is ineffective, as there are important differences in delivery and patient populations. Learn more about fosgonimeton.