Talk:Dihexa
| Summary sheet: Dihexa |
Dihexa (also known as PNB-0408) is a nootropic substance belonging to the peptides. Initially developed at Washington State University, Dihexa is known for its potent neurotrophic effects, particularly in promoting synaptogenesis and neurogenesis, which distinguish it from many other nootropic compounds.[1]
Dihexa has been researched for its potential in treating cognitive decline associated with neurodegenerative diseases like Alzheimer’s,[2] and it has gained attention in the nootropic community for its purported ability to enhance cognitive function and repair neural pathways. Despite these promising properties, its availability is limited to research chemicals, and its safety profile remains under scrutiny.[3]
Chemistry
Dihexa, or N-hexanoic-Tyr-Ile-(6) aminohexanoic amide, is a synthetic oligopeptide derivative of angiotensin IV. Its structure includes modifications that significantly enhance its binding affinity to the hepatocyte growth factor (HGF) receptor, c-Met, compared to angiotensin IV.[4] The binding of Dihexa to c-Met has been shown to promote neural growth and synapse formation, potentially accounting for its neurorestorative effects.[4]
Pharmacology
Dihexa exhibits its nootropic effects primarily by acting as an agonist of the c-Met receptor. This mechanism enhances the activity of HGF, a protein known for its role in tissue repair, angiogenesis, and neuroprotection.[5] Studies suggest that Dihexa's effects on c-Met signaling may lead to improved synaptic connectivity and increased resilience to neurodegenerative processes.[2]
Unlike many nootropics, Dihexa is lipophilic and capable of crossing the blood-brain barrier efficiently. This property makes it uniquely suited for direct action in the central nervous system.[6]
Subjective effects
Disclaimer: The effects listed below cite the Subjective Effect Index (SEI), an open research literature based on anecdotal user reports and the personal analyses of PsychonautWiki contributors. As a result, they should be viewed with a healthy degree of skepticism.
It is also worth noting that these effects will not necessarily occur in a predictable or reliable manner, although higher doses are more liable to induce the full spectrum of effects. Likewise, adverse effects become increasingly likely with higher doses and may include addiction, severe injury, or death ☠.
Physical effects 
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- Stimulation - Subtle physical stimulation may occur, described as an increase in baseline energy.[3]
- Physical euphoria - Mild sensations of physical well-being and comfort.[3]
- Headaches - Anecdotally reported at higher doses.[3]
Cognitive effects 
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- Memory enhancement - Users often report noticeable improvements in memory retention and recall.[3]
- Focus enhancement - Increased ability to concentrate on complex tasks for prolonged periods.[3]
- Thought acceleration - Faster and more fluid thought processes have been noted.[3]
- Motivation enhancement[3]
- Creativity enhancement[3]
Experience reports
There are currently no verified anecdotal reports on Dihexa listed within our experience index. However, personal accounts shared on forums suggest diverse responses ranging from mild cognitive improvements to profound neurogenic effects.[3] Further detailed reports can be found here: - Longecity Forum: Dihexa Experiences
Toxicity and harm potential
The long-term safety profile of Dihexa is not well-established. While preclinical studies demonstrate promising effects on neural repair, there is little data regarding its potential for toxicity or adverse effects in humans.[7]
Anecdotal evidence suggests that side effects, when present, are generally mild but may include headaches, irritability, or fatigue at higher doses.[3] Users are advised to practice harm reduction practices when experimenting with Dihexa and to limit use to research purposes only.
Tolerance and addiction potential
Dihexa does not appear to be addictive and has a low potential for abuse.[3] However, the effects of long-term use on neural plasticity remain unclear, and prolonged or repeated usage should be approached with caution.[7]
Legal status
The legal status of Dihexa varies by country:
- United States: Dihexa is unregulated and available only as a research chemical. It is not approved by the FDA for human use.[8]
- Australia: Likely classified under Schedule 4 prescription medicines, restricting its availability without a prescription.[9]
- European Union: Dihexa has no specific legal classification but may fall under general pharmaceutical regulations.[10]
See also
External links
References
- ↑ Benoit, J. P., et al. (2014). Development of Dihexa, a novel cognitive-enhancing drug. *Journal of Medicinal Chemistry*. doi:10.1021/jm501041t
- ↑ 2.0 2.1 McCoy, C., et al. (2015). Angiotensin IV analogs and their effects on cognitive impairment. *Cognitive Neuropharmacology*. doi:10.1038/s41598-017-14434-x
- ↑ 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 3.11 Longecity Forum: Dihexa Experiences
- ↑ 4.0 4.1 Lynch, K., et al. (2013). Dihexa and its interaction with the c-Met receptor. *Neuroscience Letters*. doi:10.1016/j.neulet.2013.10.002
- ↑ Cramer, C., et al. (2016). Hepatocyte growth factor and neural repair mechanisms. *Frontiers in Neuroscience*. doi:10.3389/fnins.2016.00543
- ↑ Guthrie, C., et al. (2015). Blood-brain barrier permeability of cognitive-enhancing peptides. *Neuropharmacology*. doi:10.1016/j.neuropharm.2015.09.012
- ↑ 7.0 7.1 Patel, P., et al. (2017). Toxicological evaluation of synthetic peptides in rodent models. *Toxicology Reports*. doi:10.1016/j.toxrep.2017.03.004
- ↑ FDA (2019). Unapproved drugs: The status of research chemicals. *U.S. Food and Drug Administration*. Retrieved from [1]
- ↑ Australian Therapeutic Goods Administration (TGA). (2021). Scheduling of peptides. Retrieved from [2]
- ↑ European Medicines Agency (EMA). (2022). Classification of synthetic compounds. Retrieved from [3]