Semax: the Clarity promoting Insta-Nootropic to become a BDNF Badass
Semax is a heptapeptide, synthetic of an adrenocorticotropic hormone. It is a quintessential smart drug in that it fires up cognition as opposed to wakefulness, focus or motivation. So it will help you work smarter as opposed to harder, which sometimes is exactly what we need.
This article is mostly going to focus on decoding what the human studies are saying about Semax and how this squares up with the anecdotal experiences of Biohackers online. For more of my own personal experiences, thoughts, and comparisons please see the written and video reviews in the sidebar.
It’s been studied worldwide and has been the subject of about 30 articles of human research in the past 10 years that can be found on Pubmed which is relatively small compared to some cognitive enhancers like Piracetam has over 600 articles of human research.
Semax[Title/Abstract] - PubMed - NCBI
PubMed comprises more than 29 million citations for biomedical literature from MEDLINE, life science journals, and…
Probably the most unique feature of Semax is that you take it nasally as opposed to orally as capsule or powder like most Nootropics. Absorption through the olfactory cavity is a much more direct channel to the brain than oral absorption, as anyone who has ever done a line in the bathroom has discovered. A few minutes after depositing drops in your nostrils you’ll notice a heightened sense of focus and a little bit of a cool neurotransmitter rush.
A Californian Biohacker reported
“I agree whole-heartedly with the other member that said there is an almost instant feeling of clarity or clear-headedness. It seems to have a stimulatory and mood elevating effect.”
One of the most distinctive features of Semax to western Biohackers is the Cyrillic text on its bottle and packaging. It’s mainly produced and used in Russia and Ukraine (westerners for some reason are fond of the saying the Ukraine but you’re actually not supposed to say it that way — you don’t say the Germany or the Canada — at least according to my Ukrainian friends) although there’s now a few reputable North American sources of this Slavic molecule.
A Subtle Enabler of Clarity
I read at least several dozen Biohacker reports about Semax and the word that I kept seeing was clarity. Outside of the clinical trials where it is used as a treatment, the effect it seems to imbue consistently is clarity. It imbues a headspace of higher consciousness and maybe an enabler of good decisions. This pseudo-spiritual property is probably due to its anxiolytic property that tempers stress response and reactivity.
A Biohacker taking subcutaneous injections of it reported
“The biggest improvements I’ve noticed is on how clear my mind stays all day long and how I’m not spacey or anything after a night of smoking. Its extremely clear. I’ve noticed huge improvements in clarity of mind before on other noots but nothing like this. I’m also alert throughout the day unless I’m caught up in my own thoughts. Learning seems to have improved slightly and believe me I’ve been using it to my advantage everyday with programming and other hobby’s I have.”
Another Biohacker agreed
“Overall I feel that SEMAX gives one a really clear headspace; however, this has been hard to judge since I have had to pull two all-nighters this week. That being said, this does wonders for keeping one functional during sleep deprivation, and it also seems to be pretty potent in regards to anxiety”
It’s frequently reported as subtle, don’t expect it to be highly stimulating like Piracetam, Modafinil, Nicotine or other drugs that you put in your nose. Its effect on long term memory is not exactly instantaneous, it requires days or weeks of dosing to have a real effect on your long term memory, one Londoner reported
“I understand that some of you guys might be disappointed about Semax. You will probably not feel any effect straight after the administration (unless it’s 1% solution or you are very sensitive)”
It’s very important to take it for a reasonable period of time, otherwise, the effect will be minimal.
Quality of Life
From a 2007 study of 27 Russian patients with motor neuron disease
However, 1% semax significantly improves the total estimate of life quality due to the improvement of emotional state and motivation in [motor neuron disease] patients with the maximal effect on day 10.
The study clarifies that it did not make much of a difference in healing the motor neuron disease itself it did markedly improve people’s outlook on the significant challenge of overcoming their affliction.
However, the study doesn’t clarify if it was double, blind placebo controlled nor does it disclose the funding source or institution that conducted it. So there’s some reason for skepticism but I feel the study does have some relevance because so many anecdotal accounts confirm the effect on quality of life.
[The study of chronic partial denervation and quality of life in patients with motor neuron disease…
Zh Nevrol Psikhiatr Im S S Korsakova. 2007;107(4):29-39. Comparative Study; English Abstract; Randomized Controlled…
One Biohacker, a student at an elite university, reported
“Semax works slowly and progressively but the gains are permanent. You memorize faster and more information you understand concepts and ideas faster, you read faster, your overall thinking processes are enhanced. That’s why i keep saying it is excellent. I have a lot of experience with cerebrolysin and i can say the results of semax are comparable with cerebrolysin’s…
As i said before, it works slowly, but progressively. You will need 2 or 3 days and intense study to start noticing intelligence improvements. ( reading faster, understanding with less effort, etc, etc)”
Another Biohacker in New Jersey reported
“The effects that I subjectively felt included a level of calmness and mental clarity that I have yet to experience since treatment, as well as a slight increase in mental processing speed and memory recall. Overall it was the most powerful nootropic I have tried yet.”
BDNF Mediated Long Term Memory
A European Biohacker on Longecity very articulately explained the connection between long term memory and Semax
“Memory is largely handled and processed at a brain structure called the hippocampus. In order for it to process data (to be memorized) it has to receive data from the sensory organs, vision, hearing, touch, smell etc. This data is transmitted along nerve fibers which in reality are neurons connected end to end with the understanding that on end of a long extension of one neuron (the axon) connects with a short extension of the next neuron (the dendrite) all these extensions originate from the body of the neuron (brain cell).
What complicates matters is that these data are in the form of electrical impulses and that the connection (called a synapse) is not 100%, i.e there is a GAP between the axon and the dendrite. The latter problem is solved by a substance called: neurotransmitters. The are expressed at the gap (called synaptic cleft) so the signal can traverse the gap assisted by this neurotransmitter substance. Examples of neurotransmitters are acetylcholine, serotonine etc . For a memory to be recorded as long term memory, the signal has to pass frequently, much like if you pass through a lawn frequently you will leave a trail of dead grass. This requires synaptic strengthening.
How is this achieved. We got to delve deeper here. Neurotransmitters work by coupling with receptors and thereby transfer the signal on so to say. To strengthen the synaptic passing of the signal we need more receptors and or more synapses. The formation of new synapses is called synaptogenesis. How is this acieved? Well receptors as well as synapses being constructed mainly of protein, we would require protein synthesis, the production of protein which is done by the cell itself (in-house factory). In the process of protein synthesis a factor is needed, its called Brain Derived Neurotrophic Factor (BDNF) for short.
This is where SEMAX comes into the picture, Semax increases the mRNA for BDNF production 500% (five-fold). mRNA or messenger Ribo Nucleic Acid is the molecule that reads the DNA code of the gene that is responsible for BDNF generation. In analogy if you increase your order five-fold at a restaurant for hamburger, you get 5 hamburgers. Boosting synaptic strengthening boosts memory formation long term. That Semax boosts BDNF production is proven in humans suffering from stroke on 160 patients in a double blind controlled trial…”
He went on to relate some more personal experiences
“Personal experience, if you are looking for a rush or hyped up state: Forget it.
If it did, it would be a stimulant and that you don’t want. What you do get is : ability to take on increased mental loads without feeling like a burnt-out candle. When you read you’ll find you retain content much easier, faster and more. I found that after a days work when I start working on private projects like writing a book, I find that I hit the train of thought on the subject much easier, find the correct words to reflect what I want to say quicker. I read longer because it doesn’t tire me like before Semax…
The effect is subtle and becomes apparent gradually, it takes a couple of days…
My personal take is that you can’t put a price on your mental prowess or quality of life. Also on life itself for that matter.”
SEMAX ® and Phenylpiracetam (Phenotropyl) - Brain Health
Page 1 of 4 - SEMAX ® and Phenylpiracetam (Phenotropyl) - posted in Brain Health: I have recently asked one of my…
From a 2010 paper out of Institute of Molecular Genetics in Moscow
Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) gene expression in rat brain and retina was analyzed by real-time polymerase chain reaction. It was revealed that after Semax administration the multidirectional activation of the expression of the genes under investigation in the hippocampus, frontal cortex, and retina was observed. The expression of both neurotrophin genes was decreased in rat hippocampus and retina 20 min after Semax administration and was increased in the frontal cortex. The expression levels of [Nerve growth factor] remained practically constant in the retina at the initial stage, whereas the expression levels of BDNF were significantly increased 90 min after Semax administration.
Comparison of the temporary dynamics of NGF and BDNF gene expression in rat hippocampus, frontal…
J Mol Neurosci. 2010 May;41(1):30-5. doi: 10.1007/s12031-009-9270-z. Epub 2009 Aug 7.
Just a single 2006 Moscow study addresses its effect on cognition
Semax-treated animals showed a distinct increase in the number of conditioned avoidance reactions. We suggest that Semax affects cognitive brain functions by modulating the expression and the activation of the hippocampal BDNF/trkB system.
Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the…
Brain Res. 2006 Oct 30;1117(1):54-60. Epub 2006 Sep 22. Research Support, Non-U.S. Gov't
A Canadian Biohacker taking 500mcg daily reported
“So far the effects are very good: it is very subtle but assist a lot in mental tasks, increase resistance to stress and fatigue and helps with general learning capabilities. I ranked those aspects everyday in my journal and there has been an increase accross the board on those measures.
Also, my working memory has improved as tested by N-Back… I’m a little more fluent when I write papers (I’m a researcher in my university) but nothing grandiose like when using Piracetam.”
As the Canadian said, if cognition is really your priority you will likely do better with the Racetams.
The evidence of it combating fatigue or tiredness is not found in studies but a few Biohackers report a helpful effect. One user reported
“Only on the first few doses I noticed the stimulant like properties. It wasn’t like adderall or caffeine or anything but I just felt awake and alert. I had enough energy to last all day and then some without any feeling of too much energy or being overwhelmed by the energy. Even on my weekend off I didn’t notice a drop in energy levels. Along with better energy levels it also seemed that any fatigue I had vanished. I wasn’t really fatigued at all before Semax but I noticed whatever fatigue I did have was gone.”
From a 2007 Taiwanese paper on treating ADHD and Rett Syndrome
[Semax] has been found to stimulate memory and attention in rodents and humans after intranasal application…
In addition, Semax could improve selective attention and modulate brain development. Since ADHD is likely to be a neurodevelopmental disorder with disturbance in dopamine and BDNF function, it is proposed in this paper that Semax may have good therapeutic potential in ADHD. Furthermore, increased BDNF activity is found to improve Rett syndrome, a severe neurodevelopmental disorder
Semax, an analogue of adrenocorticotropin (4-10), is a potential agent for the treatment of…
Med Hypotheses. 2007;68(5):1144-6. Epub 2006 Sep 25.
Another Russian study suggested that it repairs or optimizes the optic nerve.
Addition of semax to therapeutic complex in patients with diseases of the optic nerve had a favorable impact on the intensity and rate of recovery and improved the visual functions. Semax effectively protected nervous tissue from aftereffects of injury, particularly during the acute stage of optic nerve disease: it stimulated positive changes in the clinical picture, which were evaluated by improvement of visual acuity, extension of the total visual field, increase in the electric sensitivity and conductivity of the optic nerve, and improvement of color vision.
[Evaluation of therapeutic effect of new Russian drug semax in optic nerve disease]. - PubMed …
Vestn Oftalmol. 2000 Jan-Feb;116(1):15-8. Clinical Trial; Comparative Study; Controlled Clinical Trial; English…
A 2012 study of 114 Russian’s concluded
The most pronounced and long-standing (up to 12 months) positive effect on the visual function was documented in the main group.
[The results of the application of the pre-formed physical factors and neuroprotective therapy for…
Vopr Kurortol Fizioter Lech Fiz Kult. 2013 Sep-Oct;(5):29-32. Comparative Study; English Abstract
A very few studies draw a connection between immunomodulatory properties and Semax, but this seems to be limited to how immunomodulation affects ischemic stroke.
Browsing the biohacker reports I could not find substantial evidence that had a desirable effect on the immune system; nobody reporting that it kept them from getting sick or helped appreciably with their autoimmune disorders.
I won’t be trading it anytime soon for Eleuthero or Immune26 as my go-to Immune Biohacking supplement.
From the abstract, that was translated from an older Russian human study
A combined clinical-electrophysiologic study revealed its high efficiency in acute ischemic stroke. A clinical trial was performed of immunobiochemical mechanisms of neuroprotective properties of Semax in acute period of ischemic stroke.
[Investigation of mechanisms of neuro-protective effect of semax in acute period of ischemic…
Zh Nevrol Psikhiatr Im S S Korsakova. 1999;99(5):15-9. Comparative Study; English Abstract
But again this study was on ischemic stroke, so if you don’t have a problem with strokes you probably should not expect much benefit.
Mechanism of Action
According to several science writers, this is another Nootropic with supposedly a mysterious mechanism of action. Likely, this is due to limited human research. However, there are a couple of mechanisms that we know about from animal studies
- It antagonizes the action of the melanocortin receptor.
- It also promotes the expression of brain-derived neurotrophic factor and signaling receptor TrkB in the hippocampus.
- It quickly energizes dopaminergic and serotoninergic brain systems.
- It enhances locomotor behavior elicited by D-amphetamine.
Doing a little math in your head you’ll conclude that it’s kind of a pricey smart drug if you’re going to make a daily habit of it.
0.1% vs 1%
There are two main versions of Semax that vary quite a bit in concentration. One Biohacker reported
“I’ve used both Semax 1% and .1% several times.
The 1% was much more noticeable at first. It produced a heightened sense of smell, and slightly better verbal fluency. I recall the days I have taken it extremely well.
The .1% was less noticable but it functions just the same as a nootropic. I had excellent memory. It paired well with Phelypiracetam OR nicotine. I could remember vocabulary terms, and concepts with ease.
With the .1%, I redosed multiple times throughout the day, it probably is more effective than using the 1% just once a day.”
However, that’s really the only Biohacker report I could find that indicated that there’s much of an effect difference between 0.1% and 1%.
Comin’ straight outta Moscow! This is the real deal. This is the Semax I did my Biohacker report on, my only issue with it is that the little vial is only a 1–2 week supply.
Semax from Ceretropic
In an act of egregious Biohacker cultural appropriation, Ceretropic in the USA has begun producing and distributing pharmaceutical grade Semax. They offer multiple options including a powdered Semax that you have to mix yourself in Bacteriostatic water, if you don’t mind doing a little mixology in your kitchen this seems like the best value for long term Semax usage. Also, they offer cold storage shipping, which is kind of important.
N-Acetyl Semax Amidate
It seems to me that this is the Mercedez-Benz of Semax versions. Biohackers seem to agree that it’s more potent.
One user, a former meth addict reported
“The NA SEMAX Amidate I am using seems like it it beginning to repair my memory. My memory is ten times better than it was before, my priorities are reinforced in my mind every day, but not to an annoying extent, I just get things done plain and simple. Social anxiety is %100 non-existent, fluidity of my conversations with my co-workers and friends is exquisite. I am also beginning to try new social activities.
Still going daily 2 sprays, 1 per nostril, every day when I wake up of the 100mcg SEMAX Amidate. I forgot to mention that my sleep / wake pattern has improved vastly, not sporadic anymore. Clear — headed all day is the way to go.”
Usage & Dosage
It has an effect lasting 4–6 hours although some Biohackers report longer, up to 20 hours.
For some, it really only produces a wow effect after a second dose
“Waited two hours then dosed another 200mcg with an additional cup of coffee and that’s when the magic happened. Mental fatigue vanished, excellent boosts in alertness and clarity without the anxiousness and worsening of my ADD symptoms I often get from other noots like racetams. The effects were apparent for roughly 9 hours and I experienced a gradual, peaceful comedown instead of a crash. It’s now 12 hours since the second dose and my thoughts are still clear, but I think I’ll be able to sleep fine.”
If you’re taking it nasally, as most people do, each dose will be one to two drops per nostril.
Episodic vs Habitual Use
The human research and Biohacker reports indicate that the really beneficial effects on memory via BDNF come after weeks of consistent dosing. However, not everyone is going to be able to afford that, it’s also beneficial if used episodically as a focus and cognition enhancer.
One experienced user recommended
“….my advice to you for effective use would be to use it as needed but dose multiple times in the same day. If I had unlimited funds at my disposal, this would be my approach, use it on days when I need it, multiple times within that day. The days in which I have used Semax multiple times, it seemed to produce the best nootropic effects when dosed multiple times (better recall, clearer thoughts, and as some have mentioned ‘feeling oxygenated’)”
Cold storage is important, store it in your refrigerator. The Semax peptides will break down in water if stored at room temperature. This presents a bit of a concern with shipping, if possible you want to go with climate controlled storage (yes this is a Nootropic that really demands pampering). So I can imagine that if you ordered Semax during the summer time it may sit in hot trucks or warehouses for hours or days and it may not work as advertised. If you’re buying your Semax from a pharmacy and it’s not cold don’t buy it.
However, it does seem to work pretty consistently. I did not come across many Biohacker reports of it being totally useless, so I would not be really concerned about this. All the vendors offer guarantees so if it doesn’t work as advertised you can at least get a replacement.
Some opt to take Semax directly in their bloodstream.
- This is a safe way to take it provided that you mix it with Bacteriostatic water.
- You inject into a muscle, not a vein (which should make you feel like less of a junky).
- You want to cycle injection sites.
Will vary based upon the concentration. However, most people will be taking it nasally in the liquid form.
1–2 drops in each nostril 2 times a day (morning and afternoon). 1 vial lasts for about 7–14 days.
2–4 drops in each nostril 3–4 times a day (morning and afternoon) depending on the severity of stroke or illness.
One Biohacker used it for over 6 months and reported meticulously on its subjective effects, he concluded
“Over the cycle, I noticed a drastic improvement in clarity of thoughts and productivity. It is very subtle but you end up the day and looking back, you realize “sh*t got done!”. I can safely say that many aspects of my life have improved during that time, in terms of cognition for sure but also in general sociability, reduction in stress level, I interact more with my colleagues, my wife and my kids.
I’ve used SEMAX alone as I was tired of “stacking” questionable chemicals and frankly, I don’t feel the need to add anything else to it. Sometimes, I need to stay awake for far longer than I should since my line of work as crazy deadline and is very competitive so I do indulge in the modafinil or phenidate once a month or so and again, SEMAX seems to make the recovery process much easier.”
At least a few Biohackers reported quitting their other Nootropics
“So far semax has been the most subtle but most efficient nootropic I’ve ever taken and I’ve tried a lot. What’s even better is that I’m getting these effects from just the semax alone. But I have to say again, even though I’m getting all these effects, they are very subtle. Its not that I can’t notice them but the improvements are becoming more noticeable everyday.”
“Semax is one of my favorite nootropics. I said this before, and I’ll mention it now, there is a feeling of clearheadedness I get almost immediately after dosing. Whenever I conversed whilst on semax, I had my thoughts collected better and and my vocabulary seemed more extravagant. I recall most of my moments on Semax remarkably well. I’ve used it to study pages of material in combination with phenlypiracetam or nicotine. The recall of the material studied worked well. Possible increase of motivation.
There are two periods of effects. Immediately after taking it and one that persists for over a day. The lasting effect can be attributed to an increase of BDNF.”
A veteran Biohacker in London reported
“I have been taking Semax daily for a while now. In my opinion it is amazing nootropic. My memory has improved a lot, verbal skills are much better, mood is very stable and I am able to stay concentrated on any task much longer.
When I say that my memory has improved, I mean it has improved significantly. My colleagues have noticed that as well.
For example I can now remember most of the roads in London. I don’t need my satnav anymore. Without semax I had to force my self to concentrate on every road, sign and name, otherwise I would not remember anything. Surprisingly I don’t have to do this anymore, I remember everything naturally.”
Perusing the anecdotal reports the side effects are pretty benign. About 15% of the users reported undesirable effects…
- Lack of motivation.
- Tiredness, slowness or lethargy.
- Irritability or moodiness.
Nothing serious. I could not find any cases of catastrophic overdose. The worst overdose case I could find was this guy who just got a major head rush, had an anxiety attack, went for a jog and then needed to take a bath.
Like I said it can have a nearly instant effect, pharmacologically this is an attribute of addictive drugs however, I came across virtual no cases of people developing addictions to it. This stuff seems to be safer than Ritalin, caffeine or Kratom.
From a Russian study of 187 patients
Semax treatment resulted in significant clinical improvement, stabilization of the disease progress and reduced a risk of stroke and transitory ischemic attacks in the disease course. The drug is featured by minor percent of side-effects and is well tolerated by patients, including those of older age groups.
[Semax in prevention of disease progress and development of exacerbations in patients with…
Zh Nevrol Psikhiatr Im S S Korsakova. 2005;105(2):35-40. Comparative Study; Evaluation Studies
As the safety profile is extremely good, the LD50 (the dose at which 50% of the test animals die) is undeterminable. This means that in spite of increasing the dose HUNDREDS of times the therapeutic dose NONE of the animals died. Hence you find that the dosage for every indication is quite flexible.
SEMAX ® and Phenylpiracetam (Phenotropyl) - Page 3 - Brain Health
Page 3 of 4 - SEMAX ® and Phenylpiracetam (Phenotropyl) - posted in Brain Health: By the way, Phenotropil works wonders…
Is another psychoactive peptide developed by the Russian Institute of Molecular Genetics. Biohackers commonly combine the two. It’s the one Semax cofactor that is supported by the published scientific research. An American Biohacker reported
“I had stacked it with selank a few days back, and took a very small dose of ritalin (2.5mg), and went on the most productive 5 hours I had in the last year.”
Selank is a peripheral Nootropic for the sophisticated Biohacker
Selank is an anxiolytic peptide supplement with Nootropic properties.
In combination with the caviar of Racetams.it may make you scary smart. A Biohacker who thoroughly experimented with both reported
“By the way, Phenotropil works wonders when I take it with Semax. Has anyone experienced that or it’s just me?”
Another Russian Racetam, derived from the Czar of Nootropics, Piracetam. It's supposed to be amazing for highly…
No studies have evaluated the two together but a number of Biohackers report them as being a brilliant combination.
Supplementing Nicotine is the secret weapon of elite Biohackers like Dave Asprey and Aubrey Marcus for instant…
It potentiates D-amphetamine. Several Biohackers stacked it with amphetamines like Ritalin and reported that it was overstimulating.
Over the course of researching and writing over fifty of these meta-analysis articles, I’ve read many thousands of Biohacker reports. With Semax, more than any other Nootropic ingredient I’ve researched, I kept coming across Biohackers saying that it’s the best smart drug they’ve ever tried. It is particularly spoken high of in combination with Phenylpiracetam, which is debatably the best Racetam, a true smart drug.
For the risk-averse, on Pubmed, I could only find three clinical trials done and none of them were recent. So it’s a little higher risk Nootropic, if you have a lower risk tolerance as Biohacker, like my friend Justin of Longecity, stick to the Adaptogens and Racetams.
You would expect the 1% to be a 10X better Nootropic than the .1% but none of the Biohacker reports indicate that. So I would recommend (at least the first time you try it) going with the .1% solution and spending the money you save on its cofactors.
If you’re a new Biohacker or a budget Biohacker (a Biohacker ballin’ on a budget?) Semax is probably not for you but if you’re an experienced Biohacker with some money to spend on really taking your cognition to the next level a combination of Semax+Phenyl might really be your own NZT-48.
If I were going to spend my own money on Semax I would go with the powdered N-Acetyl Semax Amidate, mix it myself with Bacteriostatic water and stack it with its cofactors.