Neuro & cognitive
PE-22-28
A rodent-stage antidepressant candidate being discussed online as a nootropic peptide.
- How settled this rating is:
- very-low confidence in the current evidence rating
- Routes studied:
- Not established · Subcutaneous injection, Nasal (marketed but never approved)
- Also known as:
- spadin analogue, TREK-1 blocker peptide
- Last reviewed:
- 2026-09-06
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Evidence passport
PE-22-28
A one-screen evidence identity for this compound. These fields describe research maturity, confidence and legal status. They are not a safety guarantee, efficacy percentage or recommendation.
- Evidence level
- L2Animal / lab studies
- Confidence
- Very low confidence in rating
- Regulatory status
- Not approved for this use
- Development status
- Preclinical
Evidence strength
Higher = more and better-quality human evidence. It does not mean the effect is bigger or that the compound works for you.
Higher = more mature, better-documented human safety data. It does not mean the compound is safer than one with a lower number.
The 0-100 values rate the strength and maturity of evidence, not how effective or safe the compound is.
- Evidence base
- Mostly animal and laboratory research
- Furthest established stage
- Preclinical
- Human research maturity
- Preclinical (rodent) on our curated record; no verified completed human trial
- Source curation
- Sources fully curated
Routes recorded
Most of this evidence comes from animals and cells
Overview
Higher = more and better-quality human evidence. It does not mean the effect is bigger or that the compound works for you.
Higher = more animal, tissue or cell research. Preclinical results are a starting point, not proof of a human benefit.
Higher = more mature, better-documented human safety data. It does not mean the compound is safer than one with a lower number.
How to read these scores
Every number here rates the evidence, not the compound. They are editorial 0-100 strength ratings, not percentages, and not a rating out of five stars.
- Human efficacy evidence strength — Higher = more and better-quality human evidence. It does not mean the effect is bigger or that the compound works for you.
- Preclinical evidence strength — Higher = more animal, tissue or cell research. Preclinical results are a starting point, not proof of a human benefit.
- Human safety evidence strength — Higher = more mature, better-documented human safety data. It does not mean the compound is safer than one with a lower number. A score of 80 does not mean “80% safe”.
- Evidence level (L0-L5) — the strongest type of study behind the compound, from anecdote (L0) to large replicated human trials (L5). It is a description of the study evidence, not a quality, safety or recommendation rating.
- Confidence — how likely we think it is that this rating changes as new research lands. Low confidence means the picture is unsettled, not that the compound is bad.
None of these ratings is medical advice, a safety guarantee, or a recommendation to use anything. How we grade evidence.
How far human research has progressed: Preclinical (rodent) on our curated record; no verified completed human trial
Routes & formulations
Marketed / research routes — never approved
Marketed as injectable and nasal preparations. Neither is an approved formulation, and animal-study routes do not validate marketed ones.
Route availability is not evidence of efficacy, and evidence from one route does not transfer to another. The Registry never provides dosing or sourcing information.
Peptide lifecycle
Discovery
Preclinical
Furthest established stage
Phase I
Phase II
Phase III
Approved
Our curated record establishes rodent work only. If a human trial exists, we have not verified it — and we will not describe one that we cannot source.
What it is
A short peptide derived from spadin, developed in academic laboratories to block the TREK-1 potassium channel — a target linked to antidepressant response in rodents.
What people claim
- Fast-acting antidepressant effect
- Neurogenesis and cognitive enhancement
- Safer than conventional antidepressants
What the evidence actually says
The rodent literature is genuinely interesting: TREK-1 blockade produces antidepressant-like behaviour and neurogenesis markers in mice. That is where the evidence stops. There is no verified human trial in our record, which means every claim about mood, cognition or safety in people is extrapolation from mice. Novel target, zero human answers.
Related evidence
Useful next reads based on this compound — not recommendations.
- Related compound
Semax evidence profile
A synthetic heptapeptide derived from an ACTH fragment, registered as nasal drops in Russia and heavily marketed elsewhere as a nootropic.
- Compare
Compare PE-22-28 vs Semax evidence
Same questions, same fields, side by side — including how much human evidence exists.
- Checked claim
Claim review: “Semax is FDA-approved as a nootropic nasal spray.”
A closely related claim we have graded, from Neuro & cognitive.
- Context
Research Desk
How to read animal, early-phase and controlled human studies without over-reading them.
Human evidence
- No completed human trial is verified in our curated record.
- Reports of benefit come from anecdote and marketing, which are not evidence.
Preclinical evidence
- Rodent studies of TREK-1 blockade reporting antidepressant-like behavioural effects and hippocampal neurogenesis markers.
Animal and cell findings are Level 1–2 evidence.
Mechanism and pathways
- Blockade of the TREK-1 two-pore potassium channel, a target implicated in rodent antidepressant response.
- Downstream effects on serotonergic signalling and neurogenesis reported in animals.
Safety and unknowns
- There is no human safety dataset at all.
- Nasal and injectable research-market products carry purity and sterility risks independent of the molecule.
Cancer relevance
This section covers questions raised by how the compound works in the body, plus anything regulators and trial teams keep an eye on. It is not a statement that this compound causes cancer — for most compounds here, no human data exist in either direction.
No established human signal
Regulatory status
Regulatory decisions apply to specific jurisdictions, products, formulations and indications. An approval elsewhere is not automatically an approval in your country.
Check the regulatory note and linked primary sources for jurisdiction-specific details.
Not an approved medicine and not, on our curated record, established in any completed human trial. It is sold as a research chemical and discussed in nootropic and depression communities.
Evidence grade
Documented compound-specific animal or laboratory outcome findings, without qualifying human evidence for the assessed benefit.
What would change our rating?
- A registered, completed human trial with published results.
- Any human pharmacokinetic or safety data at all.
References and sources
Source transparency
A provenance snapshot of this profile. Counts show what kinds of sources are cited, not how much scientific weight each source deserves.
- Last editorial review
- 2026-09-06
- Recently reviewed · 45 days ago
- Linked curated sources
- 1
- Sources still pending
- 0
- External specialist reviews
- 0
- None recorded for this profile
Review provenance
Registry editorial review: Colin Jackson-White, creator and editor, who is not a doctor or clinician. External specialist review is credited only when a named reviewer has completed a review of this exact profile.
Literature-discovery and AI tools may help locate or challenge candidate evidence, but they are not counted as evidence sources here. Registry judgements are tied to the underlying papers, trial records, regulator documents and official study records.
- Peer-reviewedPubMed PMID 28955242 — original peer-reviewed PE-22-28 report (preclinical)PMID: 28955242
Source hierarchy: regulatory documents and trial registries first, peer-reviewed work next, sponsor material flagged as non-independent. We never use supplier or clinic marketing as evidence, and where a verified source has not yet been curated we say so rather than inventing one.
Evidence change history
These entries record changes to our assessment of the published evidence — not changes to the compound itself.
No recorded changes yet. Baseline position set on 2026-09-06.