Want to learn everything there is to know about the cognitive enhancer Semax?
This in-depth Semax guide covers everything you need to know about this amazing nootropic peptide.
What is Semax?
Semax peptide is a modified snippet (a small segment of) of a hormone called Adrenocorticotropic Hormone, ACTH [R].
Hormones are oftentimes a collection of bound-up amino acids, the specific amino acids and the order of the amino acid sequence determines the activity of that hormone.
Semax uses only 4 of the 39 amino acids found in the ACTH peptide (called a peptide and not a protein due to the canonical nomenclature of < 50 amino acids defining a peptide).
Semax is a new Russian nootropic researched by the Institute of Molecular Genetics of the Russian Academy of Sciences, with the intention of taking all the neurologically beneficial consequences of administering the ACTH hormone, but without the negative hormonal effects that are not as sustainable as the good, neurologically health-promoting results.
They used a combination of trial and error, and special analysis techniques to infer which amino acids were responsible for the brain-growth effects, and found the shortest working sequence in the 39 amino acid long hormone, which was the first step in inventing the peptide drug Semax.
A Review of Semax Variants
There are several variants of Semax:
The unmodified peptide is 7 amino acids long, easy to synthesis and cheap to acquire yet doesn't last as long in the body as we may want it to.
The effects of N-acetyl Semax on the brain are considered to be the strongest in terms of stimulation and the quintessential properties of it, being energy, mental stamina, and motivation.
N-Acetyl Semax Amidate
N-Acetyl Semax Amidate is considered the best Semax version, probably because it is the most modified form (except Adamax).
The amidate group allows it to last longer in the body, as amidating peptides is used endogenously by the body to extend half-lives. Amidation WILL NOT make peptides more resistant to temperature-induced degradation!
Adamax is a new version of the drug that has THREE different groups attached to it to facilitate absorption and half-life.
On the N-terminus (the left side), we have the familiar acetyl group, whilst the C-terminus is where the surprises are. It features an adamantane group, which itself is amidated, to make it adamidated!
The adamantane group is a large, chunky, lipophilic diamondoid of the simplest kind, which prevents enzymatic degradation of the peptide, making it last longer in the body, whilst also preventing temperature-induced break-down, unlike amidate groups which only helps in the body.
Amidation groups have zero chance of buffering against temperature-induced breakdown.
It is a form of diamond, so it isn't surprising that it's incredibly expensive!
Because of how powerful it is, and its speed of onset, the dosage is far lower than conventional Semax.
50-300 mcg is the usual dose range.
Effects & Benefits
People report a wide range of effects of Semax on the human brain. The most frequently reported Semax benefits are motivation and mood.
What is special about this drug (even when considering the finest of nootropics that aren't common knowledge) is that it is BOTH a powerful neurotrophin releaser AND a positive monoamine modulator and also prevents oxidative stress. Semax has combined effects that aren't replicated by many other synthetic nootropics.
This increase in plasticity is aided by the effect of Semax on dopamine and serotonin neurotransmitters, which work synergistically with high levels of brain-derived neurotrophic factor (BDNF) to encourage activity-dependent AMPA trafficking, which means the circuits that are in heavy use get cognitive priority by being given more of the ultimate currency of excitation in the brain; AMPA receptors.
Here we can see the changes in the all-important levels of neurotrophins, BDNF and NGF.
The Semax dosage was the equivalent of 515 mcg for a 65 kg human. As you can see, at three hours there is a huge spike in NGF in the retina, small increases in the hippocampus and frontal cortex.
Semax is known to rapidly induce BDNF, which could explain why the first time point starts at almost double the control levels.
It’s important to know that human handling is a rich experience for rats, and can increase neurotrophin levels just in itself.
1, brainstem; 2, cerebellum; 3, frontal cortex; 4, hippocampus; 5, retina
This graph compares the expression of NGF between rats that have been intranasally administered Semax compared to those administered water. This does conflict with other studies showing a spike in NGF levels in the brain's frontal cortex... and the retina levels being low in comparison.
1, brainstem; 2, cerebellum; 3, frontal cortex; 4, hippocampus; 5, retina
This graph compares BDNF expression between intranasally water given rats and intranasally given Semax rats.
The drop in prefrontal trophic levels could be because the placebo rats were continuously scared from being picked up by a huge hand and shoved a syringe into a very personal area, which can induce neurotophins itself.
Also, low prefrontal BDNF levels seem advantageous for certain ages and tasks.
Hippocampal BDNF has been shown to be useful in improving a varied collection of cognitive domains [R].
Some data indicate functional significance of a greater functional connectivity to the DMN frontal subcomponent. A phenomenon of this kind is observed as a result of improvement of the cognitive functions due to appropriate training in elderly people [R].
Meta-analysis of the data recorded in the brain of young volunteers has shown that effective cognitive training increases activation of the medial prefrontal cortex, the region located in the DMN frontal subcomponent [R].
The main function of the medial cortex, closely connected to the limbic system and reticular formation, consists in “regulation of brain states, modification of cortical tone, cravings, and affective life”.
The above image gives a clear relationship to the motivational and planning improvements that are present in subjective reportage with Semax, and it’s frontal brain influences.
Semax alone (0.15 and 0.6 mg/kg, i.p.) failed to alter these tissue and extracellular (dopamine) concentrations (data are not shown).
Dopamine is not increased from Semax alone. Serotonin, however, does face a significant rise from the actions of the drug Semax.
The graph shows a rise in serotonin metabolites 2 hours after administration, which continues four hours after. This indicates that serotonin is broken down more because serotonin turnover is greater usually as a result of extra serotonin is being synthesized.
More serotonin can explain the behavioral improvements people report of a more stress-resistant mood and higher energy levels. The arrow signifies the point of Semax administration.
Importantly, the larger Semax dose witnessed a lower increase in serotonin turnover! This persuades us that we should experiment with the dosage sensibly and be aware of the less-is-more phenomena.
This is why people claim that Semax can induce 800% the amount of BDNF [R].
In reality, these neurons came from a postnatal period that is too drastically different from an adult grown brain. Neurons are highly sensitive are reactive to neurotrophins and ligands in general.
Also, this is not the amount of protein, this is the amount of mRNA which does need to be proven to be highly related in glial primary cultures during postnatal day 1 to 2 to be taken as accurately representing the amount of protein actually made.
Indeed, in other studies, the amount of BDNF found after Semax administration is vastly lower than 8-fold [R].
"we used glial primary cultures obtained from the basal forebrain of newborn rats (postnatal days P1±P2)." [R].
The rat brain and human studies have huge variability in the Semax doses used.
For some, it is 500 mcg in humans [R] for treatment of ischemic stroke and brain damage.
It is undeniable that Semax has a huge therapeutic window/dosage range.
The Semax dosage depends on the form of it.
The acetyl version is commonly used between 100 and 900 mcg.
The acetyl-amidate (referred to as NASA) version is commonly used between 200 and 900 mcg.
The original version is used between 50 mcg and 3 mg.
The original, unmodified Semax version has commercial vials that provide 50 mcg drops, and some take a single drop and notice effects.
Who knows how that's possible...
I have used NASA plenty in my time and I do notice that less is more.
Some report hair loss. This is thought to be due to BDNF accelerating hair follicle growth.
If you have a chronic nervous system condition, then it could mean that Semax interacts negatively with it.
One individual with bipolar reported very negative effects.
Semax side-effects are generally very rare.
Semax vs. Selank: What's the Difference?
Semax and Selank are almost entirely different.
Selank is an analog of tuftsin, an immune system peptide that can strongly increase multiple forms of immune system mediated immunity against bacteria, viruses and even tumors [R].
Tuftsin was then given the addition of PGP, a neurotrophic and neuroprotective antioxidant trimer that somehow manages to reliably continue the effects the remainder of the peptide has to its target receptor. PGP is also featured in Semax, and it has some very surprising properties of increasing neurotrophic activity.
Bottom line: Selank is more anxiolytic and stress defeating whilst Semax is more stimulating and motivational in addition to its analgesic effects. For reducing anxiety symptoms and depression disorders, Selank could be the better choice.
Semax vs. Noopept: Which is Better?
I will not consider the differences in ease of access or storage difficulties, only from a practical and neuroscientific evaluation.
Noopept, by promoting VEGF provides lasting and very broad benefits, (perhaps even accounting for its antidepressant effects [R]) and can even potentiate the GABA alpha 5 receptor (After chronic exposure) [R], but...
Semax releases far more BDNF (the statistics of this varies, but in vitro postnatal cells have 8x the amount of BDNF mRNA) and NGF (nerve growth factor) than Noopept, which in-turn means BDNF levels would be more likely to start cascading learning mechanisms, beginning with BDNF's ability to upregulate its own receptor if at high enough concentrations, which could be why TrkB receptors (BDNF's high-affinity, cognate receptor) are found to be higher in rodents given Semax.
Where to Buy Semax?
Semax can be bought in three different manners.
- From a laboratory. Difficult to do unless you know a lot about peptides, professional manners, and own a company/look like you own a company. Larger quantities must be bought, but the prices are the best per mg.
- From a middle man. An online shop, such as WholisticResearch, which only offer the modified versions of Semax, but I recommend people try acetyl-semax first.
- Russia! Mother Russia offers varied strengths of commercialized Semax that is made from their labs and dissolved in water. It isn't always cheap, and sometimes it degrades in transit.
Frequently Asked Questions (FAQ)
Your most pressing questions about Semax answered:
What Is Semax Used for?
Semax treatment stimulates forebrain functions by increasing selective attention at the moment of information reception, improving memory consolidation, reducing anxiety, and raising the learning ability [R].
For general neurological health, and emotional health. It has been even suggested as a universally useful treatment option [R]!
It can be used for neuroprotection against glutamate excitotoxicity: "removal of the C-endPro led to the complete loss of cytoprotective activity of the Semax fragments. PGP demonstrated the highest cytoprotective activity of all peptides tested in the Glu-excitotoxicity model", showing that the C-terminal fragment is responsible for these neuroprotective effects [R].
It can amplify the effects of dopaminergic stimulants and help with depression. In one study, rats were measured in their rotational movements (a bit like repetitive dancing in humans) to assess their dopaminergic activity, and those given amphetamines with Semax had higher rotational behavior [R].
What Is Semax Nasal Spray?
Semax has been given intravenously, subcutaneously, and even sublingually. All of these routes have different qualities, benefits, and drawbacks.
The nose has been seen as an effective delivery mechanism to reclaim neurological health in a huge range of pathologies [R], which can even transport certain medications more efficiently than intravenous administration [R].
This may sound hard to believe but honestly, it's not surprising. Retrograde axonal transport and vagus nerve transport can deliver drugs to the back and front of the brain, whilst giving less chance for the drug to go to other organs.
However, the Semax reviews for intranasal usage are highly varied. Some report stronger effects, others, the opposite. If intranasal is providing nothing, then other administration methods may be better.
Despite all the research the effective use of intranasal treatment, I have never noticed any benefit from intranasal administration of Semax, but that is just me! Selank, however, works better intranasal than injections for me!
Clearly, each peptide has different mechanisms for absorption. The sequence Thr-Lys-Pro-Arg in Selank may be using receptors that are able to internalize the peptide better than Semax' sequence.
The message here is that you are different from everyone else, but don't claim Semax doesn't work until you try two administration methods at least!
How Long Does Semax Last?
The synthetic analog of ACTH 4-7 (not ACTH 4-10) Met-Glu-His-Phe-Pro-Gly-Pro, 'Semax', was designed to prolong some of the effects, was shown to influence animal behavior even 20 hours after administration [R].
Semax users report huge variability in duration. The mode of administration is a variable to consider, as intranasal usually lasts for a shorter period of time, whilst injections last longer. Between 2-10 hours.
How Often Can I Use Semax?
Semax is directed to be used daily for clinical intentions. The lower concentration (0.1%) Semax from Russia is advised to be used for healthy cognition enhancement (such as improving memory, mood and cognition in general) and is also recommended to be used daily.
Is Semax Legal In the US?
Yes, Semax is legal in the United States.
Is Semax Legal In Australia?
Yes, Semax is legal in Australia.