Most used for Most used for Brain Health.
Dihexa is a synthetic peptide derived from angiotensin IV and contains six amino acids. It was developed to enhance synaptic connections in the brain and promote neurogenesis. Research suggests it may improve cognitive function and memory in neurodegenerative conditions.
Research use only (not for human use)
Restricted / monitored
Dihexa is a synthetic peptide derived from angiotensin IV, a fragment of the hormone angiotensin II. It is a small molecule consisting of six amino acids, modified to improve stability and ability to cross the blood-brain barrier.
Dihexa is purported to enhance cognitive function by promoting synapse formation and improving communication between brain cells. It is often described as a potential cognitive enhancer that may support memory, learning, and overall brain repair processes.
Dihexa has been shown in animal studies to improve learning and memory in models of cognitive impairment. Studies report restored spatial learning and memory performance in Alzheimer's-model mice after dihexa treatment 1. Dihexa increases dendritic spines and synapse number in hippocampal tissue, changes that correlate with improved behavioral performance on memory tests 2. In neurotrophic assays dihexa produced robust growth-promoting activity that exceeds that of several endogenous trophic factors in vitro 3. Overall, animal data indicate dihexa enhances synaptogenesis and reverses deficits in memory and learning in preclinical models.
Those functional benefits appear to come from pharmacologic activation of hepatocyte growth factor signaling and downstream pathways that support synaptic growth. Multiple studies show dihexa binds HGF or potentiates HGF activity at the c-Met receptor and increases markers of synaptic function such as synaptophysin in affected brain regions 4, 5. This help explains why in rodent Alzheimer’s models these molecular changes accompany recovery of memory tasks, suggesting a link between dihexa-driven synaptogenesis and cognitive improvement 6. In summary, preclinical evidence indicates dihexa promotes synapse formation and restores memory and learning in animal models by activating HGF/c-Met signaling and enhancing synaptic markers.
There is very limited safety data on Dihexa. A review from 2021 notes that no long-term safety studies in animals or humans have been published, and it raises theoretical concerns about activation of the HGF/c-Met signaling pathway (a known oncogenic pathway) which could potentially promote tumorigenesis. Preclinical work does show cognitive benefit in rodent models of disease, but these studies did not extensively report adverse effects, making it difficult to gauge real-world risk 7, 8.
Beyond the theoretical cancer risk, other side-effect concerns are mostly anecdotal or speculative. Some sources mention possible overstimulation of brain circuits (given Dihexa’s potent neurotrophic activity), which might raise risks of maladaptive synaptic changes or dopaminergic side-effects (e.g., mood instability, impulsivity) based on analog literature 9. Additional reported minor effects (without rigorous clinical backing) include mild insomnia, increased irritability, headaches or digestive changes. Because human data are lacking, the full spectrum of negative side-effects remains unknown.
Dihexa is a small peptide derivative of Angiotensin IV that binds with high affinity to Hepatocyte Growth Factor (HGF) and potentiates its receptor c‑Met activation, thereby triggering downstream signalling such as the PI3K/AKT pathway. Through this HGF/c-Met → PI3K/AKT cascade it stimulates synaptogenesis and spinogenesis in hippocampal neurons and enhances synaptic plasticity in animal models of cognitive impairment 10, 11. In transgenic mice modeling Alzheimer’s disease (APP/PS1 mice) dihexa treatment increased synaptophysin expression, preserved neuronal number, reduced neuroinflammation (IL-1β, TNF-α) and improved spatial learning performance 12.
The FDA/NIH substance records and reviews of the literature show Dihexa (PNB-0408; N-hexanoic-Tyr-Ile-(6)-aminohexanoic amide) is a research oligopeptide studied in animals but has no published human clinical-trial approval or FDA marketing approval 13. In sports, the World Anti-Doping Agency Prohibited List forbids non-approved substances (S0) and peptide hormones, growth factors and related substances/mimetics (S2). Dihexa is a small peptide that potentiates hepatocyte growth factor signaling (a growth-factor pathway) and is not an approved therapeutic, so it fits the profile WADA intends to prohibit. So, while Dihexa is not named explicitly on the public WADA records, the rules and categories make it very likely to be treated as a prohibited/performance-enhancing substance in sport.
