Compounds with a graded row

Ordered by rung, strongest first. The rung rates the study design; the chip beside it says what the study measured. Both are needed.

1. Oxytocin

   human RCT Direct outcome Not approved for this condition

   Who was studied

   healthy women, n=437 pooled from two randomised double-blind placebo-controlled studies, a single 24 IU intranasal dose given either 40 minutes before or immediately after a film paradigm, with recognition tested 7 days later; age not reported in the abstract

   Forced-choice recognition memory did not differ between oxytocin and placebo for any scene type (F(2,401)=0.49, p=0.61), while memory for peri-event details was better than for other details in both arms (p<0.001). A separate randomised double-blind placebo-controlled study in 100 healthy male students gave the same 24 IU dose during an interference-inhibition working-memory task and found no effect on behavioural performance, with differences confined to event-related potential components. Both are single doses in a laboratory paradigm rather than a course of treatment; oxytocin is approved for obstetric use and no regulator has approved it for cognition.

   Source PubMed 2 primary sources read for this row

2. PEA

   human RCT Direct outcome Not approved for this condition

   Who was studied

   healthy young adults, n=39 randomised and completing, 700 mg/day of a formulated palmitoylethanolamide (Levagen+) for 6 weeks in a double-blind placebo-controlled crossover; sex distribution and age range not reported in the abstract

   On the Paired Associates Learning task the palmitoylethanolamide arm made fewer errors (p=0.0287, d=-0.47) while the first-success measure did not reach significance (p=0.142, d=0.54), and serum BDNF rose (p=0.0057, d=0.62). This is a single six-week crossover in 39 people, funded by the ingredient's manufacturer, and the abstract does not list the rest of the battery or which measures did not move, so how much of the test set is being reported cannot be checked. No replication in healthy adults is on file.

   Source PubMed 1 primary source read for this row

3. Testosterone

   human RCT Direct outcome Not approved for this condition

   Who was studied

   cognitively healthy older men aged 60-80, pooled across 14 randomised trials published between 1990 and 2018; men with dementia or mild cognitive impairment were excluded, women were not studied, and the pooled participant total is not stated in the abstract

   A meta-analysis of 14 randomised trials in cognitively healthy older men reported small effects on a global cognitive composite (Hedges g=0.18, 95% CI 0.02 to 0.33), psychomotor speed (g=0.22, 95% CI 0.01 to 0.43) and executive function (g=0.15, 95% CI 0.03 to 0.28), and those are the figures that remain after two trials in which testosterone did not actually rise were removed from the pool. Attention, verbal memory, visuospatial ability and visuospatial memory were also analysed. Individual trials in this population have been null: 237 men aged 60-80 given testosterone undecanoate for 6 months showed no change across eight cognitive instruments, and 46 men aged 65-83 given 200 mg intramuscularly every two weeks for 36 months showed none either. No regulator has approved testosterone for cognition in either sex.

   Source PubMed 3 primary sources read for this row

4. NAD+ Boosting / Precursor Peptides

   human RCT Mechanistic only Not approved for this condition

   Who was studied

   healthy middle-aged adults, n=80, mean age 49.4 plus or minus 6.8 years, randomised to placebo or nicotinamide mononucleotide 300, 600 or 900 mg once daily for 60 days; a second trial gave 36 healthy middle-aged adults 250 mg/day for 12 weeks

   Recorded, and not evidence for this condition

   The dose-ranging trial measured blood NAD+, a six-minute walking test, a blood biological-age calculator, HOMA-IR, SF-36 and safety laboratory values, and the 12-week trial measured NAD+ metabolites and pulse wave velocity. Neither administered a cognitive or memory test, so no study measured cognitive performance in healthy adults and the step from a higher NAD+ concentration to better thinking is a mechanistic argument rather than a result. Where cognition has been measured, it was in people with mild cognitive impairment or subjective cognitive decline, the molecule was nicotinamide riboside rather than nicotinamide mononucleotide, and RBANS and MoCA scores did not change.

   Source PubMed 3 primary sources read for this row

5. Selank

   human observational Mechanistic only Not approved for this condition

   Who was studied

   healthy participants, n=52, allocated to selank, semax or placebo and imaged before dosing and at 5 and 20 minutes; sex, age, dose and route are not reported in the abstract

   Recorded, and not evidence for this condition

   Resting-state functional MRI compared whole-brain connectivity seeded on the amygdala and the dorsolateral prefrontal cortex, and reported different connectivity between the right amygdala and right temporal regions for selank and for semax against placebo. No cognitive or behavioural test was administered, so no study measured cognitive performance in this population. The abstract reports neither randomisation nor blinding, which is why this is graded as observational. A separate trial did administer Stroop and verbal fluency tests alongside selank, but in 70 patients with anxiety disorders rather than in healthy adults.

   Source PubMed 2 primary sources read for this row

6. Semax

   human observational Mechanistic only Not approved for this condition

   Who was studied

   healthy volunteers, n=24 (11 men and 13 women, mean age 43.9 plus or minus 9.5 years), 14 given intranasal 1% semax and 10 given placebo, imaged before dosing and again at 5 and 20 minutes

   Recorded, and not evidence for this condition

   Resting-state functional MRI found a larger rostral, medial frontal cortex subcomponent of the default mode network in the semax group than in the controls. No cognitive or behavioural test was administered, so no study here measured cognitive performance and the step from a network map to sharper thinking is an argument rather than a result. The abstract does not state that allocation was randomised or that anyone was blinded, which is why this is graded as observational rather than as a randomised trial. There is no FDA or EMA marketing authorisation, and no approval anywhere for use by healthy people to improve cognition is on file.

   Source PubMed 1 primary source read for this row

Recorded absences

11 compounds are listed here without a rung. Each row exists to mark a distinction a reader would otherwise draw wrongly, and each says what is missing rather than leaving the compound off the page.

1. Adamax

   No rung — nothing on file to grade Not approved for this condition

   Adamax is sold as a semax-family compound for focus and drive. No study of it in humans or in animals could be located: a PubMed search on the name returns only papers using the unrelated Adamax optimisation algorithm in machine learning. The corpus record carries no citations at all, and nothing measuring attention, memory or any other cognitive outcome exists on file for it.

2. CRH (Corticotropin-Releasing Hormone)

   No rung — nothing on file to grade Not approved for this condition

   Nothing located with an administered dose and a cognitive outcome.

3. Dihexa

   No rung — nothing on file to grade Not approved for this condition

   Dihexa is sold for focus and memory and has never been given to a human being in any published study, so nothing about it has been measured in people at all. The record is rodent and cell work, and the 2014 paper in the Journal of Pharmacology and Experimental Therapeutics behind the procognitive claim carried an expression of concern in 2021 and was retracted in April 2025.

4. GHRH (Growth Hormone-Releasing Hormone)

   No rung — nothing on file to grade Not approved for this condition

   The controlled cognition trials in this family did not use native growth hormone-releasing hormone. The 152-participant randomised, double-blind, placebo-controlled trial of 20 weeks at 1 mg/day, and its magnetic resonance spectroscopy substudy, both administered tesamorelin, a stabilised analogue that is a separate compound in this corpus and holds the record. Nothing retrieved gave native GHRH over a course and measured cognition.

5. GHRP-1

   No rung — nothing on file to grade Not approved for this condition

   No trial has used this compound against this condition; no cognitive endpoint was measured in any GHRP-1 study retrieved.

6. GHRP-2

   No rung — nothing on file to grade Not approved for this condition

   No trial has used this compound against this condition; no cognitive endpoint was measured in any retrieved GHRP-2 study.

7. GHRP-6

   No rung — nothing on file to grade Not approved for this condition

   No trial has used this compound against this condition; no cognitive endpoint was measured outside the ischaemic-injury models recorded under stroke.

8. Hexarelin

   No rung — nothing on file to grade Not approved for this condition

   No trial has used this compound against this condition; no cognitive endpoint was measured in any retrieved hexarelin study.

9. Noopept

   No rung — nothing on file to grade Not approved for this condition

   Noopept is sold as a cognitive enhancer and no trial in healthy adults could be located. The only human reports are two comparative trials against piracetam in patients with cognitive impairment of vascular and traumatic origin, both indexed in PubMed without abstracts, so their design, size, doses and instruments could not be read. It is a proline-containing dipeptide ester rather than a peptide as sold; it is not approved by the FDA or the EMA, and a Russian registration is widely asserted but no regulator document was located.

10. Pinealon

    No rung — nothing on file to grade Not approved for this condition

    Pinealon is positioned for cognitive resilience and no human study of it exists on file. What is on file is a cell-viability experiment and a rat study of hypothalamic noradrenaline under hyperhomocysteinaemia; neither measured cognitive performance, and no trial in healthy adults could be located. Epitalon, the other pineal tetrapeptide in this corpus, is in the same position: cell lines, fruit flies and rodents, with no human cognitive study on file.

11. Vasopressin

    No rung — nothing on file to grade Not approved for this condition

    Small intranasal vasopressin studies exist in social cognition and memory paradigms, but no trial measuring a clinical cognitive outcome against placebo in healthy adults was retrieved that would support a row. Recorded as searched and empty rather than graded.

Checked, and nothing recorded

25 compounds were checked against cognitive performance in healthy adults and produced no gradeable row.

• Angiotensin II — checked, no row on file
• Bombesin — checked, no row on file
• C-Max — checked, no row on file
• Carnosic Acid — checked, no row on file
• Cerebrolysin — checked, no row on file
• Cholecystokinin (CCK) — checked, no row on file
• Cortexin — checked, no row on file
• Dynorphin A — checked, no row on file
• Epitalon — checked, no row on file
• Galantide — checked, no row on file
• Humanin — checked, no row on file
• Irisin — checked, no row on file
• Leu-Enkephalin — checked, no row on file
• Met-Enkephalin — checked, no row on file
• N-Acetylcysteine (NAC) — checked, no row on file
• Nesfatin-1 — checked, no row on file
• Neurotensin — checked, no row on file
• Nociceptin — checked, no row on file
• Orexin-A — checked, no row on file
• P21 — checked, no row on file
• PACAP (Pituitary Adenylate Cyclase-Activating Peptide) — checked, no row on file
• Simonson Alpha 1 — checked, no row on file
• Substance P — checked, no row on file
• VIP — checked, no row on file
• β-Endorphin — checked, no row on file

A compound is here because someone looked and the sources did not support a row — not because nobody looked. Under the rubric, uncertainty resolves to no row, and a row resting on a vendor page or a clinic blog is worse than no row at all.