Semax is a synthetic polypeptide analog of the natural human hormone fragment, namely adrenocorticotropic hormone fragment 4-10 (ACTH 4-10) (2).

ACTH fragment 4-10 is a peptide fragment from the adrenocorticotropic hormone secreted by the anterior pituitary gland. Interestingly, this fragment does not exhibit any effects characteristic to ACTH itself, but it has a specific effect on the human brain – enhancing one’s memory and attention(3). As an analog, Semax is also said to exhibit similar effects (and more) in the human body which are discussed further in this article.

History

Semax was developed by the Institute of Molecular Genetics, a department of a Russian University in Moscow, and is included in the list of ‘Vital and Essential Drugs List’ in Russia (4).

However, it should be noted that Semax peptide is not yet approved by the US Food and Drug Administration (FDA) (5) and hence only limited study information is available for this medication. Further studies are yet to be conducted to establish drug safety and efficacy profile before its use in the medical field.

For the past 30 years, nootropic medications have been designed with the primary aim to improve cognitive (memory) function. The term nootropic means ‘to monitor the mind’. These medications are also commonly known as “smart drugs” (1).

There are several naturally occurring peptides in our system which perform various biological functions and govern the main regulatory systems in our body, including the nervous system. However, the main drawback of these naturally occurring peptides is their severe instability, i.e., easily degradable by the biological enzymes found in gastrointestinal, cerebrospinal, and other body fluids. Consequently, studies and research is on to synthesize analogs of such peptides, which demonstrate the same biological action and are highly stable in nature.

One such peptide is Semax – it is an analog of a natural human hormone, namely adrenocorticotropic hormone (ACTH), producing similar nootropic effects while being highly stable in nature (2).

How does it work?

Since there is no sufficient data available yet around Semax, there is no confirmed mode of action available yet.

However, there are several theories, based on research studies, on how Semax peptide exhibits its effects in the human system:

Inhibition of Selected Enzymes

Based on this study (6), Semax demonstrated inhibition of selected enzymes in the body which regulate the degradation of enkephalins. Enkephalins are the naturally released neurotransmitters, mainly secreted in the brain, which regulate several biological functions in the body.

In addition to enkephalins, Semax also inhibits several other peptide degrading enzymes secreted in the human serum. Owing to this, Semax maintains an equilibrium of essential peptides in our system, thereby exhibiting the biological effects.

Elevated BDNF Levels

Based on a research study (7), it was found that Semax, similar to psychostimulants, elevated the secretion and release of dopamine as well as increases the levels of brain derived neurotrophic factor (BDNF) in the brain. Consequently, it elevated the attention levels and improved brain development.

One of the causes of attention deficit hyperactivity disorder (ADHD) is the imbalance of these two hormones in the body. Owing to the elevating effects on these hormones by Semax, this peptide exhibits therapeutic potential in treating ADHD.

Modulate Gene Expression

Based on this study (8), Semax has the ability to alter the gene expressions which modulate the human immune system.

Due to its ability to alter the gene expression, the levels of immune cells as well as their mobility are elevated. Amongst all the immune cells, the expression of which was altered the highest by Semax was of genes associated with the encoding of chemokines and immunoglobulins. This is how Semax regulates and promotes the functioning of the vascular system.

What are the benefits?

As previously mentioned, not enough clinical data on human volunteers is available to validate the uses of Semax. However, there are preclinical and animal research studies to suggest below potential uses:

• Neuroprotective effects – may potentially prevent nerve damage
• Nootropic effects – may improve cognitive properties (enhanced memory)
• Protect cardiovascular system – potential use in treatment of stroke
• Potential use in ADHD treatment – due to the ability to increase attention and brain development
• Decrease stress and pain levels

Semax Research Studies and Clinical Trials

Several preclinical and animal research studies conducted to date are briefly summarized below.

Semax Nootropic properties

This initial study (9) was conducted on ACTH hormone and its analogs, including Semax, to determine its nootropic effect in rodents.

After the peptide administration, the levels of 5-hydroxyindoleacetic acid (5-HIAA) were monitored. Semax was administered via intraperitoneal route in the dose of 0.15 mg/kg.

5-HIAA levels elevated by 25% after 2 hours of Semax administration. Whereas the levels increased gradually up to a maximum of 180% within 4 hours of administration. It was noted that the peptide, when administered 20 minutes prior to D-amphetamine, led to significant elevation of 5-HIAA as compared to administering Semax alone.

As a result, Semax demonstrated the ability to enhance striatal release of dopamine neurotransmitters, which thereby results in improved cognitive properties.

Semax Capability to Alternate SSRI Effects at Neonatal Stage

Medications such as selective serotonin reuptake inhibitors (SSRIs) are prescribed to combat depression during pregnancy. These SSRIs then travel via the placenta impacting fetal brain development. The main aim of this study(10) was to expose neonatal rats to SSRI Fluvoxamine and then administer Semax to study its effects.

Rats aged between 1 and 14 days received Fluvoxamine drug, followed by Semax administration on days 15 to 28.

After 28 days, it was noted that upon exposure to Fluvoxamine drug, the rats showed anxiety-like behavior, where they demonstrated impaired response to stress and new items during the first fourteen days. When Semax was administered, these Fluvoxamine induced effects were altered, and the rats demonstrated improved learning abilities and reduction in anxiety. This was because Semax established normal levels of monoamines in the brain, which were initially decreased by the Fluvoxamine drug.

Semax Capability to Modulate Vascular System

In this study (11), the effects of Semax to protect the rat heart from vascular damage after myocardial infarction (MI) was studied.

The rats experiencing myocardial infarction were administered with Semax via intraperitoneal route in the dose of 150 microg/kg body weight on the operating day. Following the operation, rats were administered with Semax for the following 6 days.

On the 28th day, after the myocardial infarction, it was dated that the untreated rats developed cardiac hypertrophy along with decreased arterial blood pressure. These were signs indicating heart failure. Whereas, Semax treated rats showed signs indicating prevention of the diastolic pressure growth in the left ventricle, hence demonstrating beneficial effects on the left ventricle remodeling and prevention of heart failure.

Effects on Neonatal Maternal Deprivation

Maternal deprivation at early age tends to increase anxiety and impaired emotional reactivity of the infant. In this study (12), effects of Semax on adolescent white rats facing maternal deprivation was studied.

Adolescent rats were separated from their mothers for approximately 5 hours per day during postnatal days 1 to 14. From days 15 to 28, these adolescent rats were then administered with intranasal treatment of Semax at a dose of 0.05 milig/kg body weight.

After 28 days, it was found that during the time of maternal deprivation, when Semax was not administered, it led to increased anxiety and boosted physical and emotional reactivity of the rats. Upon Semax administration, these reactions and anxiety were restored at normal levels.

Semax Neuroprotective Properties

This clinical trial (13) was conducted on 100 patients suffering from an ischemic stroke. 30 patients were treated with Semax, along with the conventional therapy, whereas the rest were part of the controlled group treated by conventional therapy.

Depending on the severity of the strokes, 12 mg dose of Semax was given to patients with mild severity whereas 18 mg dose was administered to those with high severity. The duration of the study was between 5 and 10 days.

After administration, it was noted that when Semax was co-administered with the conventional therapy there was some improvement in the restoration rate of damaged neurological functions. All results were analyzed with the help of EEG mapping. This study demonstrated the potential use of Semax in the treatment of neurological disorders and nerve damages, likely in conjunction with current therapy.

Nootropic Effects

A small-scale clinical trial (14) was conducted in Russia where healthy male volunteers, under high stress conditions, were administered with Semax and its effects on the human brain was studied. Volunteers were administered with 0.015 to 0.050 mg/kg body weight dose of Semax via intranasal route.

At the end of the study, after about 24 hours, it was noted that compared to before the volunteers demonstrated increased memory and attention, showing no signs of other negative side effects. This indicated that the peptide could be a well-tolerated therapeutic drug to treat neurological disorders – however, this would require a more robust, high volume study to validate this effect on a larger scale.

Semax Side Effects

Insufficient clinical studies have been conducted to fully demonstrate the side effects of Semax, if any. Currently, based on the data available, the peptide seems to be a well-tolerated medication – however, this needs to be investigated further.

As with other peptides, the common side effects that may occur are:

• Pain, redness, and discomfort at the site of injection
• Nausea
• Vomiting
• Dizziness
• Flu like symptoms
• Fatigue

Semax Peptide Doses, Route of Administration, Dosage

As previously mentioned, Semax is not yet approved by the US FDA for administration. While it is in the list of Essential medications, mainly in Russia, it is yet to be fully investigated on a large scale to be approved by the US FDA. Thus, there is no certain recommendation as to the peptide administration and dosage as Semax safety and efficacy is yet to be fully determined.

Furthermore, some evidence from animal studies (15) suggests that Semax may cause different effects at different doses. For instance, at a low dose of 5 and 50 microg/kg body weight, Semax induced antioxidant effects, while at a high dose of 450 microg/kg body weight, it increased oxidative stress in the body. Hence, an effective dose, dependent on the treatment it is being used for, as per human biological systems, was yet to be determined.

Final Word

Semax is a synthetic peptide analogue of the human hormone called adrenocorticotropic hormone fragment 4-10 (ACTH 4-10). Semax, unlike ACTH, exhibits nootropic and neuroprotective properties, with the demonstrated effects in protecting and restoring vascular functions.

While the mechanism of action of Semax remains unclear, there are various theories to support how the peptide functions. This includes the ability to elevate brain neurotransmitter levels and decrease the neurotransmitter degrading enzyme activities. As a result, Semax increases levels of dopamine in the body which leads to improved brain development, enhanced memory, and attention. What’s more, due to its ability to alter gene expression, this peptide can also lead to vascular protecting effects and restore heart ventricular functions.

All of the above impact of the peptide has been studied extensively in the animals. While small scale clinical trials have been conducted, mainly in Russia, there is no sufficient evidence available yet. Thus, more detailed, robust studies are yet to be conducted to support its continued use across the globe.

Semax online

Currently, Semax is an approved medication in Russia, Ukraine, and most of the UK – however, it is not approved by the US FDA. While studies are ongoing to obtain this approval, it should be noted that not having the US FDA approval does not make this medication illegal. Semax peptide is available online and can be purchased for research purposes.