Key Benefits
Biologic Description
Semax, a synthetic peptide developed in the 1980s by Russian researchers, is authorized in Russia and Ukraine for various indications, including ischemic brain stroke, encephalopathy, optic nerve atrophy, and cognitive disorders like dementia. Its potential benefits extend to neurological conditions such as Alzheimer's, traumatic brain injury (TBI), and stroke.
This peptide, an analog of the ACTH(4-10) peptide derived from adrenocorticotropic hormone (ACTH), is composed of seven amino acids, including a fragment from ACTH (4-7) and a Pro-Gly-Pro fragment. This structure enables Semax to cross the blood-brain barrier, reaching significant concentrations in the central nervous system where it may enhance neuroprotection and cognitive performance. Additionally, modifications like acetylation and amidation lead to the formation of N-Acetyl Semax Amidate, potentially enhancing its stability.
It stimulates neurotrophic factors like Brain-Derived Neurotrophic Factor (BDNF) and Nerve Growth Factor (NGF) in the central nervous system. It also affects serotonin, dopamine, and enkephalin signaling, which could influence mood, stress, cognition, and reward-related behavior. Research indicates that Semax may upregulate both BDNF levels and the corresponding tropomyosin-related kinase B (trkB) receptors in brain cells, vital for cell survival and neuroplasticity.
Despite its promising potential, Semax's clinical studies are limited, and it lacks FDA review or approval. Side effects, risks, and legal status must be considered before use for research purposes.
Studies demonstrate Semax's efficacy in various applications. It has been used in treating glaucomatous optic neuropathy in patients with normalized ophthalmic tone and has shown effectiveness in different stages of ischemic stroke. Its nootropic-like activity in humans has been observed, suggesting benefits in cognitive performance, neuroprotection, and mood regulation.
Clinical data indicate Semax's impact on cognition, with studies showing improved memory test accuracy and changes in the brain's default mode network, hinting at enhanced information processing and memory capabilities. Its potential in mood regulation is explored, with animal studies suggesting anxiolytic and antidepressant effects under stress.
In terms of neuroprotection, Semax has shown promise in stroke patients, with trials reporting improved motor performance and functional independence. It also exhibits anti-inflammatory properties, potentially aiding in conditions like chronic brain ischemia. Its protective effects against various neurotoxins, including alcohol intoxication and neurotoxins related to Parkinson
's disease, have been noted in clinical and pre-clinical trials.
Furthermore, Semax might offer gastroprotective benefits. A study indicated its effectiveness in healing peptic ulcers, with a significantly higher healing rate compared to a placebo. Researchers hypothesize these effects might be due to its influence on blood flow, microcirculation, and vascular permeability, though further research is needed to confirm these mechanisms.
Semax emerges as a multifaceted peptide with potential applications in cognitive enhancement, mood regulation, neuroprotection, and gastroprotection. Its mechanism of action involves interacting with critical neurotrophic factors and neurotransmitters, and it demonstrates promising results in both clinical and pre-clinical studies. Despite its potential, it's important to approach Semax with an understanding of its limited clinical studies, regulatory status, and potential side effects, especially when considering it for research purposes.
Dosage Guidelines
While there are no officially approved dosing guidelines or clinical studies, researchers might consider a regimen of up to 1000mcg daily at the highest. A typical approach could involve administering 500mcg-1000mcg of Semax subcutaneously, depending on the subjects' responsiveness, daily for up to 30 days. For longer studies, a dose of 500mcg daily for up to 60 days may be considered.
500 mcg
Per Day
4 Weeks
Side Effects
Clinical research suggests that intranasal Semax generally exhibits a favorable safety profile with no significant side effects. It has been safely administered in doses ranging from 600mcg to 12mg daily for periods up to 10 consecutive days. Additionally, extended trials, particularly with glaucoma patients using a 0.1% nasal spray for 30 days, have also reported an absence of adverse effects.
There is, however, a study indicating that a dose of 16.0mcg/kg of Semax might produce stimulant-like effects, potentially leading to slightly elevated anxiety levels in healthy individuals. Another area of concern involves the potential adverse effects associated with increased brain-derived neurotrophic factor (BDNF) levels. There's some indication that heightened BDNF might be linked to increased hair loss in men predisposed to baldness, although the direct impact of Semax on this condition remains uncertain.
Regarding the safety of injectable Semax, comprehensive evaluations in clinical settings are lacking, with most existing data derived from animal testing, which have not indicated significant safety concerns. However, given the limited scope of clinical trials, a cautious approach to using Semax is recommended.
For researchers employing Semax, several precautionary measures can help minimize potential risks:
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Optimizing Dosing: It is advisable to start with the lowest effective dose, such as 600mcg daily for intranasal administration or 500mcg daily for subcutaneous injections, adjusting based on the subject’s response and the objectives of the research.
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Hydration: Ensuring that research subjects maintain adequate hydration throughout the duration of the study is important.
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Limiting Other Nootropics: While combining Semax with other nootropics is possible, it may increase the risk of side effects and may not be suitable for all research participants.
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Healthy Diet: Encouraging participants to follow a balanced diet can contribute positively to the study’s outcome.
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Caffeine Intake: Given Semax’s mild stimulant properties, participants should be advised to limit their caffeine intake to reduce the possibility of side effects.
Adherence to these guidelines is crucial for minimizing potential side effects and safeguarding the well-being of participants in research studies involving Semax.
References:
Effects of Semax on the Default Mode Network of the Brain
A greater volume of the default mode network rostral (medial frontal cortex) subcomponent was detected in the Semax group in comparison with controls. Resting state fMRI confirmed Semax effects on the neuronal network of the brain and demonstrated topography of these effects.
Author: I S Lebedeva, Ya R Panikratova, O Yu Sokolov, D A Kupriyanov, A D Rumshiskaya, N V Kost 1, N F Myasoedov
Publication Date: 2018 Sep
On the relationship between the “default mode network” and the “social brain”
The default mode network (DMN) of the brain consists of areas that are typically more active during rest than during active task performance. Recently however, this network has been shown to be activated by certain types of tasks. Social cognition, particularly higher-order tasks such as attributing mental states to others, has been suggested to activate a network of areas at least partly overlapping with the DMN. Here, we explore this claim, drawing on evidence from meta-analyses of functional MRI data and recent studies investigating the structural and functional connectivity of the social brain. In addition, we discuss recent evidence for the existence of a DMN in non-human primates. We conclude by discussing some of the implications of these observations.
Authors: Rogier B. Mars, Franz-Xaver Neubert, MaryAnn P. Noonan, Jerome Sallet, Ivan Toni, and Matthew F. S. Rushworth.
Published: 02 Dec 2019
The efficacy of semax in the tretament of patients at different stages of ischemic stroke
Administration of semax, regardless of the timing of rehabilitation, increased BDNF plasma levels which remained high during the whole study period. In semax- subgroups high BDNF plasma levels were positively correlated with early rehabilitation. Administration of semax and high BDNF levels accelerated the improvement and ameliorated the final outcome of Barthel score index. There was a positive correlation between BDNF plasma levels and Barthel score, as well as a correlation between early rehabilitation and motor performance improvement. The correlation between BDNF plasma levels and Barthel score was modified by the timing of rehabilitation.
Authors: E I Gusev, M Yu Martynov, E V Kostenko, L V Petrova, S N Bobyreva
Published: 2018
Adrenocorticotropic hormone protects learning and memory function in epileptic Kcna1-null mice
ACTH is often successful in controlling the seizures and/or inter-ictal EEG abnormalities, it is unknown whether ACTH possesses other beneficial effects independent of seizure control. We tested whether ACTH can ameliorate the intrinsic impairment of hippocampal-based learning and memory in epileptic Kcna1-null (KO) mice. We found that ACTH - administered in the form of Acthar Gel given i.p. four times daily at a dose of 4 IU/kg (16 IU/kg/day) for 7days - prevented impairment of long-term potentiation (LTP) evoked with high-frequency stimulation in CA1 hippocampus and also restored spatial learning and memory on the Barnes maze test.
Authors: Morris H Scantlebury, Kyoung-Chul Chun, Shun-Chieh Ma, Jong M Rho, Do Young Kim
Published: 2017 Apr
Semax, a Synthetic Regulatory Peptide, Affects Copper-Induced Abeta Aggregation and Amyloid Formation in Artificial Membrane Models
Alzheimer’s disease, the most common form of dementia, is characterized by the aggregation of amyloid beta protein (Aβ). The aggregation and toxicity of Aβ are strongly modulated by metal ions and phospholipidic membranes. In particular, Cu2+ ions play a pivotal role in modulating Aβ aggregation. Although in the last decades several natural or synthetic compounds were evaluated as candidate drugs, to date, no treatments are available for the pathology. Multifunctional compounds able to both inhibit fibrillogenesis, and in particular the formation of oligomeric species, and prevent the formation of the Aβ:Cu2+ complex are of particular interest. Here we tested the anti-aggregating properties of a heptapeptide, Semax, an ACTH-like peptide, which is known to form a stable complex with Cu2+ ions and has been proven to have neuroprotective and nootropic effects. We demonstrated through a combination of spectrofluorometric, calorimetric, and MTT assays that Semax not only is able to prevent the formation of Aβ:Cu2+ complexes but also has anti-aggregating and protective properties especially in the presence of Cu2+. The results suggest that Semax inhibits fiber formation by interfering with the fibrillogenesis of Aβ:Cu2+ complexes.
Authors: Michele F.M. Sciacca, Irina Naletova, Maria Laura Giuffrida, and Francesco Attanasio
Published: 2022 Feb 16