Semax
Semax — evidence, nootropic claims & status

Class: peptide
Synonyms: Semax
ACTH(4-7) analog (also written ACTH(4-10) analog)
sequence Met-Glu-His-Phe-Pro-Gly-Pro (MEHFPGP). INCI: none
Function tags: neuro / cognitive
neuroprotection
BDNF (research context)
Overall evidence grade: B
WADA prohibited: no
Last updated: 2026-07-13

In brief: Semax is a synthetic heptapeptide analog of an ACTH fragment and an approved neuroprotective/nootropic drug in Russia (since 1994). Its strongest evidence is for ischemic-stroke recovery — multiple Russian randomized trials and routine clinical use — but that evidence is Russian and not independently replicated to Western standards, and the popular "cognitive enhancement in healthy people" use is much weaker than the stroke use. It does not stimulate cortisol, and it is not approved in the US or EU.

## Identity a synthetic **heptapeptide** (7 amino acids, < 40 aa → peptide) — the ACTH(4-7) active fragment (Met-Glu-His-Phe) with a **C-terminal Pro-Gly-Pro** extension added for metabolic stability. Developed at the Institute of Molecular Genetics, Russian Academy of Sciences (1980s). Crucially, despite being ACTH-derived, the (4-7/4-10) fragment **does not stimulate cortisol/adrenal steroidogenesis** (that requires ACTH 1-24). ## Development & history - Semax was engineered in the **1980s** at the **Institute of Molecular Genetics, Russian Academy of Sciences**, out of a Soviet programme studying **ACTH fragments** for cognition and neuroprotection. Adding the **Pro-Gly-Pro** tail to the ACTH(4-7) fragment both stabilised the molecule and stripped its hormonal (cortisol-releasing) activity.
- It was **registered as a drug in Russia in 1994**, first for cerebrovascular disease (ischemic stroke), with cognitive and optic-nerve indications added later. It remains a **Russia/CIS-approved** medicine and is now under US compounding review (July 2026). ## Mechanism (as proposed) Semax is proposed to upregulate **BDNF** and **NGF** (with increased TrkB signalling), modulate dopamine/serotonin/acetylcholine systems, and provide neuroprotection during ischemia and against oxidative/neuroinflammatory injury — while, unlike parent ACTH, **not** triggering cortisol release. Much of the mechanistic detail is from animal work; the stroke-recovery use is better substantiated than the healthy-cognition use.

Evidence grades by outcome:
outcome: Ischemic-stroke recovery (on-label in Russia)
grade: C
base: Multiple Russian RCTs; routine use added to standard stroke care
effect: Improved recovery / functional outcomes / lower mortality reported
caveat: Strongest use, but Russian-only, no Western replication; trial methodology varies from FDA/EMA standards
outcome: BDNF/NGF upregulation & neuroprotection (mechanism)
grade: B
base: Consistent rodent studies (e.g. single intranasal dose ↑BDNF; Romanova 2006 ↓infarct volume)
effect: Robust in animals
caveat: Animal/in-vitro; does not by itself prove the human cognitive claims
outcome: Cognitive enhancement in healthy adults (the popular use)
grade: D
base: Extrapolated; few direct RCTs
effect: Suggestive
caveat: The healthy-user "nootropic" case is far weaker than the stroke case — the opposite of how it's marketed
outcome: Optic-nerve disease
grade: D
base: Small Russian trials
effect: Suggestive
caveat: Small, regional
outcome: Antidepressant / anxiety / stress
grade: D
base: Preclinical + some Russian data
effect: Suggestive
caveat: Early; interestingly, the PGP fragment alone shows activity
outcome: Marketed "limitless-style" cognitive enhancement
grade: F
base: None rigorous
effect: Not demonstrated
caveat: Not supported by rigorous evidence in healthy people
outcome: Safety
base: Approved drug in Russia (intranasal), broad clinical use
effect: Generally well tolerated
caveat: Long-term / Western safety data limited

Legal status:
region: EU
status: Not approved
note: Not approved; not eligible for magistral/officinal compounding (no Ph. Eur. monograph).
region: US
status: Not FDA-approved (under review)
note: Not FDA-approved. On the PCAC agenda for 24 July 2026 (day two, with DSIP/Epitalon), with cerebral ischemia as the reviewed indication; removed from Category 2 in April 2026; FDA's pre-meeting briefing documents proposed not adding it to the 503A Bulks List. Advisory only; no final rule.
region: INT
status: Approval limited to Russia/CIS
note: Approval limited to Russia/CIS.

Cosmetic claims:

Note: Research / reference — not for sale. No dosing, reconstitution, or administration is published (intentional). Neutral scientific reference only. Unlike most compounds in this register, Semax is an approved prescription drug in Russia — so the honest task is to credit real clinical standing and flag its limits.
Status note: US review status evolving — re-check the July PCAC outcome and any Federal Register rule

Sources:
(Original development — Institute of Molecular Genetics, Russian Academy of Sciences; Russian regulatory registration, 1994.)
Romanova GA, et al. (Semax reduces infarct volume after photoinduced cortical ischemia in rats.) 2006.
Eremin KO, et al. (Semax activates dopaminergic and serotonergic systems.) 2005.
(Russian clinical trials of Semax in acute ischemic stroke — cite specific trials before publishing.)
Independent reviews framing the evidence (Russian data, no Western RCT replication; stroke > nootropic).