Semax Breakdown

Semax is a synthetic peptide derived from adrenocorticotropic hormone (ACTH) with a myriad of neurological benefits. Thankfully, for our sake, there are quite a few helpful studies discussing Semax and it's ability to improve brain function, cognition, and recovery, which we will be looking into in this article.

History

In 1982, Semax was developed by a research team from the Institute of Molecular Genetics at the Russian Academy of Sciences in Moscow. It was initially researched for aiding in recovery after strokes, but it was soon discovered that Semax had other properties that could benefit the general population.

Mechanism of Action

Semax's mechanism relies heavily on the alteration of gene transcription [1]. In the literature, the genes that are most affected by Semax administration seem to be those relating to immune system (upregulated), cell differentiation (upregulated), and inflammation (downregulated). It has also been shown to increase the production of brain derived neurotropic factor (BDNF) [3], which plays a valuable role in neuronal development. Though Semax is derived from ACTH, it is entirely devoid of any hormonal activity.

Observed Effects

Semax is commonly used to increase cognition, particularly in the areas of memory retention, reduction of brain fog, and task-specific focus. It is also commonly used to treat "post-exercise brain fog", in which an individual experiences a loss of productivity and ability to focus after completing an exercise session.

In many anecdotal reports, users also experience a reduction in anxiety following Semax administration.

Personally, I have used Semax for both overall focus and to treat brain fog, and it has worked phenomenally for me. Anxiolytic effects seem to be minimal with my specific neurochemistry.

Diving Deeper

Alzheimer's Prevention and Tren?

You may be familiar with the term "amyloid plaque" from trenbolone studies, which showed an aggregation of the toxic compound amyloid beta protein. Well, Alzheimer's Disease specifically is characterized by a buildup of amyloid beta protein in the brain. There is a LOT of scientific jargon regarding Alzheimer's, amyloid protein buildup, and the like, so I'll spare you the rant.

In short, Semax has been shown [5] to decrease aggregation of amyloid beta protein in the brain, making it a potentially neuroprotective compound against Alzheimer's. Interestingly enough, this would also make Semax a good candidate to run alongside trenbolone to prevent some of the neurotoxicity that will inevitably be occurring.

The graph above illustrates the results of the study well. We can see that amyloid beta protein by itself (black line) severely disrupts cell membrane integrity. However, the addition of Semax in a 1:1 ratio to amyloid beta protein decreases the membrane disruption significantly. Adding in copper ions in a 1:1:1 ratio decreases it even further, with the least membrane disruption occurring with a 1:1:5 ratio of AB to copper ions to Semax.

Cognition

Semax has even been shown to be a potential agent for the treatment of ADHD. In research, it has been shown to not only increase levels of BDNF [6], but also augment the effects of stimulants [3], [7], making ADHD drugs like amphetamine (adderall) more effective in practice.

Transcriptional Modulation

In one study [2], researchers analyzed the effects of Semax administration to mice with permanent middle cerebral artery occlusion (pMCAO). In simpler terms, they restricted the blood flow to the brain in these mice, causing devastating neurological effects similar to that which would be caused from a stroke. Researchers found that at both 3 hours post-pMCAO and 24 hours post-pMCAO, Semax significantly upregulated the transcription of genes involving neurological healing. To quote the study, "At that time point [3 hours post-pMCAO], we found a considerable alteration of the expression of genes encoding transcription factors that could set off new signal pathways that allow the correction of the destructive processes that developed after vascular occlusion".

Although we are not mice, nor do we suffer from scientist-induced pMCAO, this may have profound implications for human use. Could Semax be used as a driver for neurological healing factors? Can it potentially decrease neuroinflammation? Could it be used to improve cognition? If so, could we implement it in a way that can be done safely and effectively? The answer to all of these questions is likely yes, and that becomes more apparent as we continue to dive into the research.

Neurotoxicity Reversal and Attenuation

In one study [4], Semax was found to reverse the negative neurological changes following chronic SSRI administration in adolescent rodents. These mice were given Fluvoxamine (an SSRI) immediately after birth for 14 days straight (days 1-14), a time period equivalent to 27-40 weeks in humans.

Unsurprisingly, these mice experienced negative neurological changes: decreased emotional responses to stress, decreased learning capabilities, and increased anxiety. Their monoamine balances were also changed, but this is somewhat to be expected when using a medication that is used to intentionally modulate monoamines (though, really only serotonin specifically).

Administration of Semax for days 15-28 following cessation of Fluvoxamine attenuated the Fluvoxamine-induced anxiety, improved learning capabilities, and normalized monoamine levels to baseline. The rodents that did not use Semax had permanent, lasting changes to these aforementioned processes which did not seem to return to baseline, indicating that Semax was the main culprit of reversing these changes.

This would imply that, at the very least, Semax is only able to reverse negative changes caused by neurologically-altering medications (which is still a big deal, nonetheless). At the most, this could imply that Semax independently increases neurological performance regardless of previously used substances. I believe that the latter is likely the case based on the data we have.

Conclusion

Semax is a relatively safe and innocuous compound that I believe everyone should try. It's neuroprotective, anti-depressant, anti-anxiety, and even anti-ADHD. The only downside of Semax may be the price, as daily administration would get costly. In my opinion, though, wellness and cognition mean more to me than a few bucks here and there.

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Sources

[1] N. F. Miasoedova, V. I. Skvortsova, E. L. Nasonov, E. Iu Zhuravleva, I. A. Grivennikov, E. L. Arsen'eva, I. I. Sukhanov (1999) "Investigation of mechanisms of neuro-protective effect of semax in acute period of ischemic stroke"

[2] Ekaterina V. Medvedeva, Veronika G. Dmitrieva, Oksana V. Povarova, Svetlana A. Limborska, Veronika I. Skvortsova, Nikolay F. Myasoedov,and Lyudmila V. Dergunov (2014) "The peptide semax affects the expression of genes related to the immune and vascular systems in rat brain focal ischemia: genome-wide transcriptional analysis"

[3] Shih-Jen Tsai (2007) "Semax, an analogue of adrenocorticotropin (4–10), is a potential agent for the treatment of attention-deficit hyperactivity disorder and Rett syndrome"

[4] Nataliya Yu. Glazova, Daria M. Manchenko, Maria A. Volodina, Svetlana A. Merchieva, Ludmila A. Andreeva, Vladimir S. Kudrin, Nikolai F. Myasoedov, Natalia G. Levitskaya (2021) "Semax, synthetic ACTH(4–10) analogue, attenuates behavioural and neurochemical alterations following early-life fluvoxamine exposure in white rats"

[5] Michele F.M. Sciacca, Irina Naletova, Maria Laura Giuffrida, and Francesco Attanasio (2022) "Semax, a Synthetic Regulatory Peptide, Affects Copper-Induced Abeta Aggregation and Amyloid Formation in Artificial Membrane Models"

[6] Oleg V Dolotov et al. (2006) "Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus"

[7] Kirill O Eremin et al. (2005) "Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents"