What "the cognitive stack" usually means
In Manila's biohacker and office circles, a cognitive stack means some combination of Semax, Selank and, less often, dihexa or pinealon. The pitch is that each targets a different system, so together they cover focus, mood and memory.
That framing borrows the logic of clinical combination therapy, where two drugs are paired because a trial showed the pair beats either alone. Nothing like that exists here. Every published study of these compounds tests one at a time, and most test it in patients with a diagnosis, not in healthy adults looking for an edge. This page lays out what each single-compound record actually covers, so the gaps in the stack are visible.
Cerebrolysin is included as a reference point: a peptide product with the large trials the others lack, and mostly neutral results.
The evidence, compound by compound
| Compound | What it is | Best human evidence | Population studied | Tested with any other stack member? |
|---|---|---|---|---|
| Semax Stocked locally | 7 amino acid ACTH fragment analogue | 110-person stroke rehabilitation study, no placebo | Stroke patients | No |
| Selank Stocked locally | 7 amino acid tuftsin analogue | Two trials of about 60 patients each vs a benzodiazepine | Anxiety disorders | No |
| Dihexa | Angiotensin IV-derived peptidomimetic | None | None | No |
| Pinealon | 3 amino acid bioregulator | Small reports from one group | Brain injury, elderly | No |
| Cerebrolysin | Pig brain peptide mixture | 1,070-person placebo-controlled stroke trial, neutral | Stroke, dementia | No |
Semax: BDNF in rats, stroke in people
The mechanism that gives Semax its reputation is a 2006 rat study: a single intranasal dose raised hippocampal BDNF protein up to 1.4-fold, trkB receptor activation 1.6-fold, and the rats learned an avoidance task better. That is a clean animal result on a growth factor central to learning.
The human evidence is a 2018 Russian study of 110 people recovering from ischaemic stroke, randomised to Semax plus rehabilitation or rehabilitation alone. Blood BDNF rose with Semax and daily-living scores improved faster in the first month. It had no placebo arm, measured BDNF in blood rather than brain, and has not been replicated outside Russia. Claims about Semax and focus, ADHD or productivity in healthy adults rest on the rat data and on the stroke study's mechanism, not on a trial in the people making the claims.
Selank: anxiety, compared with benzodiazepines
Selank's two clinical studies are in diagnosed anxiety. In 2008, 62 patients with generalised anxiety disorder or neurasthenia were split between Selank and medazepam; anti-anxiety effects were similar, and Selank had an additional anti-fatigue effect. In 2014, 60 patients with anxiety and somatoform disorders compared Selank with phenazepam; the authors reported a pronounced anti-anxiety effect with a mild nootropic effect that lasted about a week after stopping.
Neither trial was placebo-controlled, neither abstract reports doses or adverse-event counts, and both came from the network that developed the peptide. The proposed GABA mechanism is from a 2016 rat gene-expression study. Selank in a cognitive stack is therefore being asked to do something, sharpen a healthy mind, that its own trials never measured.
Dihexa: rats only, and a growth pathway
Dihexa was built to be an orally active, brain-penetrant angiotensin IV analogue, and in 2013 rat studies it reversed scopolamine-induced memory deficits and improved aged rats' performance in a water maze. The 2021 Alzheimer's Drug Discovery Foundation review is blunt: no human studies, no long-term animal safety study, and a widely repeated potency claim against BDNF that was never tested head to head.
The mechanism is the reason to pause. Dihexa amplifies signalling through hepatocyte growth factor and its receptor c-Met, one of the better-known growth and invasion pathways in cancer biology. Boosting that signal daily, on purpose, in a healthy person, is exactly the exposure that would need a toxicology package first. None has been published.
Pinealon: one group, small reports
Pinealon's human reports, including oral use in 72 people with the after-effects of brain injury, come almost entirely from the St Petersburg institute that designed it and appear mostly in Russian-language journals without the design details needed to judge them. Its proposed mechanism, a three amino acid peptide entering the nucleus and binding DNA, has not been confirmed by an outside laboratory.
Cerebrolysin: the cautionary reference point
Cerebrolysin is what a cognitive peptide looks like after it has been through real trials. CASTA randomised 1,070 acute stroke patients in Asia to Cerebrolysin or saline for 10 days and found no difference on its primary combined outcome. The 2023 Cochrane review pooled seven trials with 1,773 participants and found it probably makes little or no difference to death and may increase non-fatal serious adverse events. The Philippine Department of Health's HTA Council reviewed it in 2023 and recommended against government financing.
The point for this page is not that Cerebrolysin is worse than Semax or Selank. It is that when a cognitive peptide finally got large placebo-controlled trials, the effect mostly disappeared. The others have not been put to that test.
What has and has not been studied together
Nothing on this page has been studied with anything else on this page. Specifically:
- No trial has given Semax and Selank together, despite their shared origin and shared Pro-Gly-Pro tail.
- No study has combined dihexa with anything, because no study has given dihexa to a person.
- No study has tested any of these in healthy adults with normal cognition as the primary population.
- The only "combination" in the literature is Semax or Cerebrolysin added to standard stroke rehabilitation, which is a treatment-plus-usual-care design, not a stack.
So a claim that the compounds "work synergistically" has no source. The honest description of the stack is: four single-compound evidence bases of varying quality, none of which addresses the combination, the population or the outcome the stack is sold for. For how each ranks against the others on its own, see best peptides for brain function and Semax vs Selank.
Safety information that does exist
Because there is no combination study, there is no combination safety data. What exists per compound is thin. The Russian literature calls Semax and Selank well tolerated but rarely reports counts; nasal irritation is the plausible local effect for the drops. Dihexa and pinealon have no formal safety data. The US FDA's compounding safety list includes both Semax and Selank, citing immunogenicity risk from aggregation and impurities and insufficient safety information for the proposed routes.
Two further points apply to the stack as sold locally. Research-market powder is not the finished Russian nasal product, so route and formulation differ from anything studied. And stacking several compounds makes it impossible to tell which one caused an effect, good or bad. The side effects hub links each compound's safety section.
Status in the Philippines
None of Semax, Selank, dihexa or pinealon is registered with FDA Philippines; all circulate here as research compounds and none is a controlled substance under RA 9165. Cerebrolysin is registered as a prescription drug but is a hospital infusion, not a home nootropic, and is outside the Philippine National Formulary. Anyone with a diagnosed anxiety disorder, ADHD or cognitive complaint in the Philippines has approved treatments available through a licensed physician, and switching away from a prescribed medicine to an unregistered peptide is the kind of decision that belongs in that consultation. For the sleep half of the same market, see the sleep stack.
Storage
All four research peptides are lyophilised powders that keep best refrigerated and away from light, and at 2 to 8°C once mixed. Dihexa is supplied as a dry powder for which humidity is the main enemy: keep a desiccant in the container. Plan for brownouts with a cooler and ice packs. See the beginner guide for handling basics.
