Semax: The Nootropic Peptide

My personal experience and what you need to know

If you've been around the peptide/biohacking community on twitter for a bit, you've probably at least heard of Semax. You may have even seen me talk about it a bit, but I’ve decided to keep my thoughts to a minimum up to this point. I wanted to take the time to understand its effects, instead of blindly coming out and saying it's the best thing since sliced bread after just a few uses. However, after several months of use, I’m finally ready to share my thoughts and experiences on Semax.

Before that though, I want to dive into Semax as a molecule—as I normally do with nootropic reviews—to explain what it is, what it does, and the different forms available for those who may be curious.

If you're not curious and are only here for my review, go for it. You’ll find it close to the end of this post.

What is Semax?

Simply put, Semax is a synthetic peptide—a short chain of amino acids strung together. More specifically, it is a small fragment of adrenocorticotropic hormone (ACTH), a naturally occurring hormone in the human body that is cleaved from pro-opiomelanocortin (POMC) and is involved in regulation of cortisol.

For my fellow chemistry enjoyers the amino acid sequence is Met-Glu-His-Phe-Pro-Gly-Pro.

Semax was developed in Russia, and is still used there medically. Its primary uses are to treat stroke and other cognitive disorders due to its neuroprotective and neurotrophic effects, which can be useful in the recovery from brain damage by minimizing damage and promoting neuroplasticity. However, Semax is most well known in the West as a nootropic, or cognitive enhancer, that can improve memory, attention, learning, and general mental performance. 

Despite lacking FDA approval, Semax is available online in the United States and other countries as a compound designated “For Research Purposes Only”. (I’ll share my preferred vendor with my subjective experience at the end of the article)

What does Semax do?

While its exact mechanism of action is unknown, Semax has profound neuroprotective and neurotrophic effects. In animals, Semax has been shown to significantly increase levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the frontal cortex and hippocampus shortly after administration [1, 2, 3].

Both BDNF and NGF are powerful modulators of neuroplasticity and promote the growth and survival of neurons. This likely explains why Semax has been shown to improve learning in animals [2, 4], counteract the behavioral effects of chronic stress [5], and aid in the recovery from stroke. The effect on stress is particularly interesting, since chronic stress is known to cause drastic decreases in BDNF. Additionally, Semax has been shown to have nootropic properties in healthy humans, improving attention and short-term memory [6].

Interestingly, Semax has also been shown to prevent the deficits in learning and memory caused by heavy metals in animals [7]. This effect is likely influenced not only by Semax’s positive impact on growth factors, but also its ability to act as an antioxidant, protecting against oxidative stress [7].This adds another layer to Semax’s neuroprotective and restorative potential, which has been shown in animal models of ischemic stroke [8] and in humans [9].

One of Semax’s most unique properties though, is its relationship with dopamine neurotransmission. Administration of Semax alone has no impact on dopamine release in rodents, but when paired with a dopaminergic substance—in the case of this study, amphetamine—dopamine release in the striatum is significantly increased compared to animals that received only amphetamine (Figure 1). Locomotor activity (movement) was also significantly increased by Semax + amphetamine when compared to the group receiving only amphetamine [10]. This indicates that Semax has the ability to potentiate the effects of dopaminergic compounds and further enhance dopamine release in the striatum, leading to increased motivation and drive.

Figure 1: Application of Semax (S) alongside Amphetamine (A) increases dopamine release significantly more than Amphetamine alone

Based on these various effects in vivo, Semax can be labeled as a potent neuroprotective and nootropic compound that can enhance cognition in healthy users, while also possessing the potential to aid in the recovery from neurological damage and promote neuroplasticity. Its impact on neurotrophic factors and monoamine neurotransmission also indicate that Semax may be effective as an antidepressant, given their implications in the pathology of depression, and in combatting the detrimental effects of chronic stress on cognition.

Different forms of Semax

Semax is available in four main chemical forms:

• Semax

• N-Acetyl (NA) Semax

• NA Semax Amidate

• Adamax

All of these contain the original seven amino acid sequence that make up Semax, but the latter three have slight modifications to improve their stability and pharmacokinetic profile. In the NA molecules, an acetyl group is attached to their N-terminus to improve bioavailability and potency. The amide group added to NA Semax Amidate is thought to enhance this further, creating an even more potent molecule. Finally, Adamax is a unique form of Semax with an Adamantane group attached, which may improve stability and bioavailability even further than the NA versions.

Due to their differing structures and potencies, all four versions of Semax have been reported to exert different effect profiles, and the three modified versions are seen to be more potent than basic Semax.

Administration of Semax

As a peptide, Semax does not have great oral bioavailability, so it is commonly administered intranasally (via spray or dropper) or injected subcutaneously. Intranasal administration seems to be as effective as injection, so it's the common recommendation for use in humans due to its ease.

Semax’s half life is only a few minutes when administered intranasal, but it quickly enters the brain and its effects can last for 24 (or more) hours on just a single dose.

My Personal Experience

Over the past 6 months, I’ve been experimenting with the acute use of intranasal NA Semax. By that, I mean that I used it intermittently as opposed to running it every day for a longer amount of time. 

For me, Semax produces a very smooth nootropic feel that kicks in within minutes and lasts all day, potentially lingering into the next day. My mind feels very sharp when I’m on it, and cognitive tasks are less mentally taxing than usual. The feeling it provides me consists of a subtle mental clarity, generally enhanced cognition, improved short-term memory, and increased visual acuity. It’s a similar feeling to that of other compounds that act via neurotrophic factors, but is less outright stimulatory than 4-DMA-7,8-DHF and much more profound than lion’s mane, which gives it a unique feel along with other benefits such as:

Less brain fog after intense exercise - This is an issue that has plagued me for a while, especially on weekends when I choose to lift in the morning. Normally, I’m out of commission mentally for several hours after a workout, but using Semax before (and sometimes after) my workout cuts that mental recovery time significantly. It also improves the quality of my lifts by improving my concentration and mind-muscle connection.

Potentiation of dopaminergics - This is similar to the effect described above where Semax potentiates the dopamine release induced by amphetamine, and it actually translates to my use (even if I take the dopaminergic several hours after Semax). When I’m using Semax, the effects of dopaminergic compounds (mainly caffeine and sabroxy in my case) are greatly enhanced—so much so that I’d express caution when pairing the two because it can easily lead to overstimulation. I’m able to use half the dose of sabroxy I normally do, and it still feels like a huge dose. As a result, this combo has been my go-to for productivity and focus.

Increased libido - Considering my libido is already normal/high, this can be annoying at times, but is welcome at others. This usually takes a few hours to kick in, but can definitely last 24+ hours in my experience. It’s not an overwhelming uptick, but it’s definitely noticeable.

Improved reaction time - This is something that has stuck around even when I’m not using Semax or other neurotrophic nootropics, but is a new phenomena in my life. This is most notable to me when I drop things or knock them off a table. In the past few months, I’ve begun catching things at an alarming rate, which I never did before. Whether or not I can contribute this to Semax entirely is unknown, but it didn’t start until after I started using it.

After realizing that it had potent acute effects for me, I determined that this was how I wanted to use Semax for the time being, as opposed to running a cycle of it (which is still likely better for some use cases, just not necessary for my current goal of acute cognitive enhancement). Although I do still plan to run a cycle in the future.

Concerning dose, I’ve stuck to 300-600mcg per day, either all in the morning or split up between morning and noon, and have had great success with that. I’ve tried 900+mcg several times, but I noticed no more benefit than the lower doses.

I’ve been trialing NA Selank as well, but I only feel like I derive a benefit from it when used in conjunction with Semax as the two are highly synergistic. If I was dealing with anxiety or other mood issues its effects may have been more apparent, but I’m not, so Selank alone hasn’t done much for me. Using the two together though seems to improve the effects I see when using just Semax, especially reducing brain fog after exercise. 

In all, Semax is definitely not a magic bullet for productivity or focus, but it’s definitely been a great tool for me in improving those when I want/need it most. In an acute context, the most useful effects i’ve noticed are the improved mental recovery after a hard workout and the potentiation of dopaminergic compounds, but the uptick in mental clarity and cognition are certainly great as well.

Where to Source Semax (For Research Purposes)

Limitless Life Nootropics has become my preferred source for research peptides.

After experimenting with a few of their products over the past few months, I’ve recently become affiliated with them which means code “neuron” gets you 15% off anything on their site. Their peptides are made in the USA, third-party tested, and they ship quickly, so I trust them as a source.

If you’re interested in researching Semax or its derivatives, you can use the links below and use code “neuron” for a discount.

Semax spray- Link

N-Acetyl Semax spray - Link

N-Acetyl Semax Amidate spray - Link

Adamax spray (currently on sale, code doesn't work) - Link

Conclusion

That’s all for now. If you have any questions or want to recommend a compound for me to do a write up on similar to this one, feel free to comment or DM me on Twitter.

Thanks for reading,

-BowTiedNeuron

Disclaimer

This article is for education purposes only. BowTiedNeuron is not a doctor, and the contents of this article is not medical advice. Always consult your doctor before starting any new supplements, peptides, or health protocols.