Semax
Also known as: ACTH(4-7)-PGP, N-Acetyl Semax, NASA (N-Acetyl Semax Amidate), Heptapeptide Semax
Lower numbers = closer to natural. Higher numbers = more enhanced.
Why this rating?
Semax is a nootropic peptide approved in Russia. Per Dolotov et al. (2006) and related studies, it upregulates BDNF 1.4-3x and enhances cognition, memory, and focus. However, it does NOT directly build muscle, burn fat, enhance athletic performance, or raise endogenous anabolic hormones. It is purely for cognitive support. Not WADA prohibited. Rated 1 (basically natty) since it has no effect on the muscular/physique/performance ceiling by any path.
Overview
A synthetic heptapeptide (Met-Glu-His-Phe-Pro-Gly-Pro) derived from ACTH(4-10) with a Pro-Gly-Pro tail for stability. Primary nootropic with cognitive enhancement, focus, and neuroprotection. Significantly upregulates BDNF (1.4x protein, up to 3x mRNA per Dolotov et al. 2006) and modulates NGF expression. Unlike full ACTH, it lacks steroidogenic (adrenal) and melanocyte-stimulating activity, so it does not produce cortisol/HPA stimulation or tanning; some more recent reviews suggest it may still interact with central MC4/MC5 melanocortin receptors, so "no melanocortin activity at all" overstates current evidence. Available as standard Semax, N-Acetyl Semax, and NASA (Amidate) - each progressively more stable.
Important Warnings
- •NOT FDA-approved - approved only in Russia/Ukraine
- •Limited Western peer review of Russian clinical data
- •Effects are subtle and cumulative, not acute
- •Not directly anabolic or performance-enhancing
- •Hair shedding reported anecdotally - monitor if concerned
- •May cause irritability at high doses
- •Avoid late-day dosing - can disrupt sleep
- •Use caution with MAO inhibitors
- •Quality varies significantly between peptide suppliers
- •Individual response varies significantly
Purpose & Use Cases
Cognitive Enhancement
Improves spatial and working memory, learning acquisition/retention, sustained attention, mental clarity. BDNF-mediated neuroplasticity effects.
Neuroprotection
Decreases cortical infarction volume and improves post-ischemic learning/memory retention in rodent stroke models (Romanova et al. 2006); protects against glutamate excitotoxicity. Underlies its Russian clinical approval for stroke and cognitive disorders.
Focus and Mental Energy
Mild stimulant profile via dopamine modulation. Enhanced motivation and drive. Does not cause jitteriness like traditional stimulants.
Training Support
Maintains mental clarity during caloric deficit. May enhance mind-muscle connection (anecdotal). Supports motor learning and skill acquisition.
Benefits
- Upregulates BDNF (1.4x protein, up to 3x mRNA) and modulates NGF expression
- Improved memory, learning, and attention
- Neuroprotective effects demonstrated in stroke models
- Lacks the steroidogenic/melanocyte-stimulating activity of full ACTH (no tanning, no cortisol/HPA stimulation)
- Russian clinical approval with human study data
- No significant HPA axis suppression
- Mild stimulant effect without jitteriness
- Complements Selank for comprehensive cognitive/anxiety support
Good to Know
A Russian-approved nootropic peptide (usually nasal)
Semax is a synthetic heptapeptide derived from a fragment of ACTH(4-10) with a Pro-Gly-Pro tail for stability, dosed intranasally. It is an approved medicine in Russia for cognitive and cerebrovascular indications (including stroke). Its main action is upregulating BDNF (~1.4x protein, up to ~3x mRNA) and modulating NGF expression, supporting neuroplasticity, memory, and focus.
It is an ACTH fragment but does NOT act like ACTH
Despite deriving from ACTH, Semax lacks the steroidogenic (adrenal-stimulating) and melanocyte-stimulating activity of full ACTH (Ponomareva-Stepnaia et al. 1986), so it produces no tanning and no cortisol/HPA stimulation, unlike melanotan or ACTH itself. Some more recent reviews propose it may still interact with central MC4/MC5 melanocortin receptors, so the exact receptor mechanism is not fully settled, but the practical takeaway (no tanning, no HPA hit) holds.
The focus half of the Semax + Selank pair
Semax is the stimulating, dopaminergic focus/drive agent; Selank is the calming/anxiolytic counterpart. Together they are the classic Russian nootropic stack. Because Semax has a mild stimulant profile, dose it in the morning/early afternoon. Late-day dosing can cause insomnia.
Not anabolic: and note the anecdotal hair shedding
Semax does not build muscle, burn fat, or affect the HPTA/hormone panels, so no PCT is involved and it rates a 2. Some users anecdotally report temporary hair shedding (possibly BDNF-related, not confirmed in trials). Effects are subtle and cumulative rather than an acute hit.
Dosage Guidelines
| Route | Typical Dose | Frequency | Cycle |
|---|---|---|---|
| Intranasal | 300 – 600 mcg/day | Intranasal 1-3x daily divided doses. Morning/early afternoon to avoid sleep disruption. | 2 – 4 wk |
| Subcutaneous injection | 500 – 1000 mcg/day | Once daily, subcutaneous | 4 – 8 wk |
Dosing depends on how it's administered. Pick your route in the calculator to score the one you use.
Russian nootropic/clinical practice and community consensus (peptide-vendor and harm-reduction sources, not a controlled trial): 200-600mcg/day split 2-3x, for 10-14 days. NASA (Amidate) is community-reported to be more potent/longer-acting (longer plasma half-life), so lower doses (~100-300mcg/day) are typically used - flag as community-derived, not a head-to-head clinical comparison. Acute stroke protocols use much larger, medically-supervised total course doses (12-18mg over a 5-10 day course per Gusev et al. 1997) that are not comparable to nootropic dosing and should not be self-administered. Cycle 2-4 weeks on, 1-2 weeks off. Despite a plasma half-life of only a few minutes, downstream gene-expression effects have been measured out to 24 hours post-dose.
NOT an official/commercial route - the registered Russian pharmaceutical product is nasal-only. SC injection is a research-chemical/community practice, used because it avoids the variable, individual-dependent absorption of intranasal dosing and bypasses Semax's poor oral bioavailability (it is a peptide, degraded if swallowed). Per peptide-community dosing guides, injectable protocols are extrapolated from intranasal totals rather than derived from independent clinical injection trials - treat this route's numbers as lower-confidence/community-consensus, not clinically validated.
Community/vendor estimates cluster around 2-8 minutes (rapidly cleaved by peptidases); no rigorous published human PK study was located. Despite the short plasma half-life, downstream BDNF/NGF gene-expression changes have been tracked out to 24 hours post single dose (Shadrina et al. 2010).
Side Effects
Nasal Irritation
commonVery common with intranasal use. Dryness, tingling.
Use saline spray between doses. Rotate nostrils.
Headache
uncommonTypically transient during first few days.
Stay hydrated. Reduce dose if persistent.
Hair Shedding (Anecdotal)
uncommonSome users report temporary hair shedding. Mechanism unclear, possibly BDNF-related. Not confirmed in clinical studies.
Discontinue if concerning. Usually temporary if occurs.
Irritability
uncommonPossible at higher doses. May relate to dopamine modulation.
Reduce dose.
Insomnia
uncommonIf taken late in day. Mild stimulant properties.
Avoid evening dosing. Last dose by early afternoon.
General Mitigation Strategies
Generally well-tolerated in Russian clinical use. Mild stimulant profile - avoid late-day dosing. Most side effects are transient and resolve with continued use or dose reduction. Hair shedding is anecdotal and not confirmed in studies. No serious adverse events documented in available literature.
Post Cycle Therapy (PCT)
Does not affect HPT axis. No HPA axis suppression documented. No PCT required. No interference with hormone panels.
How It Works
Upregulates BDNF protein (~1.4x) and mRNA (up to ~3x) and TrkB tyrosine phosphorylation (~1.6x) in hippocampus/cortex (Dolotov et al. 2006); gene-expression effects on BDNF/NGF have been tracked out to 24 hours post-dose (Shadrina et al. 2010; Dmitrieva et al. 2010), though the response is biphasic and NGF changes are regionally variable. One study found NGF expression fell in frontal cortex under some conditions (Agapova et al. 2007). Modulates dopamine turnover in striatum/nucleus accumbens and serotonin in limbic structures. Lacks the steroidogenic/melanocyte-stimulating activity of full ACTH (Ponomareva-Stepnaia et al. 1986); interaction with central MC4/MC5 receptors has been proposed but the precise receptor mechanism is not firmly established. Alters expression of 24+ vascular- and immune-related genes in ischemia models, with immune-related genes accounting for over half of Semax-affected transcripts (Medvedeva et al. 2014).
Fundamentals
Reference on the practices relevant to Semax: how they are done and where they go wrong. Not a recommendation to use it.
Common Stacks
- Semax + Selank - gold standard nootropic/anxiolytic combination
- Semax in AM for focus, Selank any time for calm
- NASA (Amidate) version is most stable/potent - use lower doses
- Avoid late-day dosing to prevent insomnia
- No known interactions with PEDs or PCT compounds
- May complement racetams, modafinil (caution with multiple stimulants)
Legal Status
Used as a prescription drug in Russia for cerebrovascular/cognitive indications, developed by the Institute of Molecular Genetics (Russian Academy of Sciences); added to the official Russian List of Vital & Essential Medicines by government order on 7 December 2011. The exact initial marketing-approval year is not well-documented in English-language sources. Not FDA-approved and not marketed in the US/EU. Not a controlled substance in the USA (sold as a research chemical). Not currently named on the WADA Prohibited List, though see wadaStatus notes for a caveat around its ACTH-fragment origin.
Legal status varies by country and changes over time. This is a general summary, not legal advice.
WADA Status
Semax is not specifically named on the WADA Prohibited List. It is structurally a fragment/analog of ACTH(4-10), and WADA's S2.4 "Corticotrophins" category prohibits ACTH and its analogs, so its status is genuinely ambiguous rather than clearly cleared. In its favor, Semax has been shown to lack the steroidogenic (adrenal-stimulating) activity that makes corticotrophins performance-relevant, and it has no direct muscle-building or athletic-performance effect. Athletes subject to testing should treat this as unresolved and seek a formal ruling/TUE guidance from their anti-doping organization rather than relying on this summary.
References
- Dolotov OV et al. - Semax, an ACTH(4-10) analog, regulates BDNF and trkB in rat hippocampus (Brain Res 2006)
- Medvedeva EV et al. - Semax affects immune/vascular gene expression in rat brain ischemia (BMC Genomics 2014)
- Gusev EI et al. - Effectiveness of Semax in acute ischemic stroke (Zh Nevrol Psikhiatr 1997)
- Ponomareva-Stepnaia, Ashmarin et al. - ACTH(4-10) analog lacks steroidogenic/melanocyte-stimulating activity (Biull Eksp Biol Med 1986)
- Shadrina M et al. - Comparison of temporal dynamics of NGF and BDNF gene expression in rat hippocampus, frontal cortex, and retina under Semax action (J Mol Neurosci 2010)
- Romanova GA et al. - Neuroprotective and antiamnesic effects of Semax during experimental ischemic infarction of the cerebral cortex (Bull Exp Biol Med 2006)