Cognitive enhancement tier list checked against evidence

Key points

• The list (@dex7official, 2026-10-20) ranks about 60 items from S to F. It states no criteria, so the tiers are an opinion, not a finding [1].
• Its S tier is mostly prescription drugs with boxed warnings, a steroid, insulin-class and anaesthetic items. None of those placements is supported as a recommendation: their labels document addiction, overdose, dependence and other serious harms [3][4][5][8].
• The best-reviewed evidence on healthy adults is small. A 2020 meta-analysis of 47 studies found small effects for modafinil and methylphenidate and none for d-amphetamine [2].
• Creatine is in F, yet two meta-analyses of randomized trials found memory benefits, mainly in older adults [12][13]. Modafinil, Semax and Selank sit in D with no basis stated.
• For roughly half the items (the lab compounds, most supplements) we found no controlled study in healthy people at all [19].

What a tier list is, and is not

A tier list is one person’s ranking. It does not say whether S means “works”, “safe” or “strongest”, for whom, or over what time, and it mixes prescription drugs, anabolic steroids, unapproved research chemicals, supplements and habits in one grid. The post had 6,522 likes and 1.2M views when we recorded it [1].

We transcribed the image from the project’s source file; we did not open the X post itself. Two labels are unreadable (an ampoule product in S and an “…oxypine succinate” product in A) and we skip them. “Agrees” means the evidence supports a tier at least that high; “not supported” means it does not. Status is for the US (FDA, DailyMed labels read in November 2026) unless noted. “No controlled study found” means a PubMed search on 2026-11-09 [19]. We did not check the UK, Germany or EU registers.

S tier

Prescription controlled substances, anabolic steroids, insulin and ketamine are listed for status and documented risk only. We do not discuss use, and the S placement for each is not supported.

Item	Status and documented risk	Src
Desoxyn (methamphetamine)	US Schedule II prescription drug; the methamphetamine tablet label covers ADHD in children aged 6 and over. Boxed warning: high potential for abuse and misuse, overdose and death. Placement not supported	[5]
Vyvanse (lisdexamfetamine)	Schedule II. Labelled for ADHD and binge eating disorder in adults. Same boxed warning on abuse, misuse, overdose and death. Placement not supported	[3]
Adderall XR (mixed amphetamine salts)	Schedule II. Labelled for ADHD from age 6. Same boxed warning. Placement not supported	[4]
Ketamine	Ketalar is a Schedule III general anaesthetic. The label lists emergence delirium, respiratory depression, blood-pressure effects, and liver injury and urinary complications with recurrent use. Placement not supported	[8]
Trenbolone acetate	An anabolic steroid. Federal Register notices from 1997 and 2002 appeared in our search: they exclude named veterinary implants from the Controlled Substances Act for animal use only. We could not open them, so current status is not verified. No approved human use found. Placement not supported	[10]

Item	What it is and status	Evidence for healthy people	Src
Avodart (dutasteride)	Prescription, not controlled. Labelled for enlarged prostate. Label lists impotence, decreased libido and ejaculation disorders that may persist after stopping, and depressed mood in post-marketing reports	No cognition data found or reviewed. Not supported as a cognitive agent	[11]
High-dose melatonin	Sold as a supplement or medicine depending on country; US status not checked	Thin. A 2026 randomized trial of 60 healthy 18-23 year olds in 3 days of sleep restriction found less memory loss on melatonin than placebo; one small, short sleep-loss study, not healthy-baseline enhancement	[14]
“Circadian rhythm”	A habit, not a product	Not assessed as a single intervention	none
Fluvoxamine	Prescription SSRI; labelled uses not checked	No controlled study of cognitive enhancement found or checked	[19]

Placement summary: the stimulants in S have the largest healthy-adult data of any drug on the list, but the data are small. In Roberts and colleagues’ 2020 meta-analysis (14 modafinil, 24 methylphenidate and 10 d-amphetamine studies in healthy, non-sleep-deprived adults), d-amphetamine showed no effect. The authors wrote that perceived benefit “is not supported by the evidence so far” [2]. Review of the prescription-stimulant placements: see our stimulant article.

A tier

Item	What it is and status	Evidence for healthy people	Src
Fast food	Food	No controlled evidence of cognitive benefit found; not searched in depth	none
T3 (liothyronine)	Prescription thyroid hormone	Not verified; no healthy-adult cognition source opened	none
TAK-653	Investigational AMPA-receptor modulator; no approval	No healthy-adult cognition trial found. PubMed returns 12 records; one is a 2025 monkey study of depression-like symptoms	[19][21]
Nefiracetam	A racetam-class compound; US status not checked	144 PubMed records; we opened none, so evidence is not verified	[19]
Diazepam	Schedule IV prescription benzodiazepine. Boxed warning: severe sedation, respiratory depression, coma and death with opioids; abuse, misuse, addiction; dependence with life-threatening withdrawal. Placement not supported		[6]
Donepezil	Prescription cholinesterase inhibitor, labelled for Alzheimer’s disease (label not opened).	One small placebo-controlled trial in young healthy volunteers (2009) reported better recall at 90 and 210 minutes after a single administration; sample size not stated in the abstract. Acute, single trial	[17]
Phenylpiracetam	Racetam-type compound. Status: see linked article	PubMed search “phenylpiracetam OR fonturacetam” returns 31 records; see linked article for the review	[19]
PRL-8-53	Experimental compound, no approval	One 1978 randomized trial reported enhanced learning in humans; no replication found	[19][20]

The A tier has no item with replicated healthy-adult trial data. The single benzodiazepine placement is not supported.

B tier

Item	What it is and status	Evidence for healthy people	Src
Dihexa (compound page)	Research peptide-like compound; not an approved drug (see linked article)	Animal and cell work; no human trial found there	see article
Guanfacine	Prescription; label not opened	Not verified	none
Trimetazidine	Prescription in some countries; not checked	Not verified	none
9-ME-BC	Research compound; no approval	A 2020 study on astrocytes (cell work) reported MAO inhibition; no human trial found	[19][22]
PPAP	Research compound	Not verified	none
4-DMA-7,8-DHF	Research compound	PubMed search under the full chemical name returned zero records	[19]
HGH	Prescription hormone; labels not opened	Not verified for healthy-adult cognition	none
Omega-3	Supplement or prescription oil depending on product	Cochrane 2012: 3 trials, about 4,000 cognitively healthy people aged 60+, no benefit on cognitive function	[16]

The one B-tier item we could test, omega-3, has trial evidence that disagrees with a B placement [16].

C tier

Item	What it is and status	Evidence for healthy people	Src
ZYN	Nicotine pouch. FDA authorised 20 products on 16 January 2025 as a tobacco product; we could not open the FDA release	Not verified for cognition	none
Bromantane	Russian-developed compound; status in linked article	See linked article	none
L-tyrosine	Amino acid supplement	A PubMed search found only endurance and Parkinson’s-diet reviews in the top hits; not verified for cognition	[19]
Memantine	Prescription; label not opened	Not verified	none
CDP-choline	Supplement or drug depending on country	See linked article	none
Selegiline	Prescription MAO-B inhibitor	Not verified	none
Noopept	Russian-developed compound; status in linked article	See linked article	none
Cialis (tadalafil)	Prescription PDE5 inhibitor	Not verified	none
Coffee	Food	We found no healthy-adult review we could open; see our caffeine comparison	none

We could not verify most C-tier items beyond their existence. A C tier for all of them is not testable from what we opened.

D tier

Item	What it is and status	Evidence for healthy people	Src
Modafinil	US prescription drug for wakefulness disorders; scheduling and country status in our legal-status article	Disagrees with D relative to S. 14 studies in healthy adults: small overall effect (SMD 0.12), memory updating 0.28 [2]	[2]
Semax (compound page)	Research peptide; status in linked article	See linked article; human data limited	none
Selank (compound page)	Research peptide; status in linked article	See linked article	none
Armodafinil	Prescription drug	Not included in the 2020 meta-analysis [2]; see linked article	none
L-theanine	Supplement	2026 meta-analysis of 31 randomized trials (1,168 people, healthy and clinical): short-term benefit on attention; the author team includes a founder of a supplement company	[15]
Alpha-GPC	Supplement or drug depending on country	See linked article	none

Modafinil, Semax, Selank and armodafinil sit in D with no stated reason. Placing modafinil two tiers below dexamphetamine-type drugs is not what the 2020 meta-analysis shows: it found an effect for modafinil and none for d-amphetamine [2]. Placing L-theanine in D conflicts with its attention results, though the effect size and quality are limited [15].

F tier

Item	What it is and status	Evidence for healthy people	Src
BPC-157 (compound page)	Research peptide; not approved	See linked article; no human cognition trial identified there	none
Pinealon (compound page)	Research peptide	See linked article	none
Cannabis	Legal status differs by country and US state; not checked	Not assessed	none
Lyrica (pregabalin)	Schedule V prescription drug for nerve pain, seizures and fibromyalgia. Label warns of life-threatening respiratory depression with opioids or other CNS depressants. Placement not discussed beyond status		[7]
Humulin (insulin)	Prescription insulin for diabetes. Label: hypoglycaemia can be severe or fatal, impairs concentration and reaction time, and low potassium can be life-threatening. Not supported as a cognitive agent		[9]
Phenibut	Not a lawful dietary ingredient per FDA warning letters (2019); labelled supplements are misbranded. See phenibut risks	Not assessed	[18]
Creatine	Supplement	Disagrees. Meta-analysis of 8 RCTs: memory improved (SMD 0.29), mostly in adults 66-76 (SMD 0.88), not in 11-31 year olds (0.03). A 2024 meta-analysis of 16 RCTs (492 people, healthy and ill): memory, attention time and processing speed improved, overall cognition did not; certainty moderate for memory, low elsewhere	[12][13]

Where the list and the evidence disagree

1. The S tier has the most documented harm. Three Schedule II stimulants carry boxed warnings for abuse, overdose and death [3][4][5]. Ketamine is a Schedule III anaesthetic with respiratory and organ warnings [8]. Placing these at the top, with no stated criterion, is not supported by their labels, whatever one’s view of their effects.

2. Stimulant effects are small in healthy people. The 2020 meta-analysis found small effects for methylphenidate (SMD 0.21) and modafinil (0.12) and none for d-amphetamine [2]. That is the opposite of a clear ranking with amphetamine at the top.

3. Creatine at the bottom. Two meta-analyses of randomized trials found memory benefits [12][13]. The effect is concentrated in older adults and the certainty is moderate at best; F (“does not work”) overstates the evidence against it.

4. Omega-3 and L-theanine. Omega-3 in B contradicts a Cochrane review of older healthy adults finding no benefit [16]; L-theanine in D conflicts with a 31-trial meta-analysis that found a short-term attention effect [15].

5. Research compounds ranked without human data. TAK-653, 9-ME-BC, PPAP, 4-DMA-7,8-DHF, nefiracetam, Dihexa and PRL-8-53 occupy A and B. For the ones we could check, the published work is animal or cell work, or one 1978 trial [19][20][21][22].

6. Dutasteride in S. Avodart’s label is about prostate enlargement and lists persistent sexual side effects [11]. We found no basis for its S placement.

What would an evidence ranking look like

An evidence ranking would score two things separately: how well an effect on cognition in healthy people has been shown, and how serious the documented harms are. For the first axis, strongest to weakest: a regulator decision with trial data for that use, a systematic review of randomized trials, a single randomized trial, animal or cell work, then posts.

On that scale, nothing on the list has a regulator-approved indication for enhancing cognition in healthy people. At the top for effect would sit methylphenidate-type drugs and modafinil (small effects, meta-analysis of 47 studies) and creatine (two meta-analyses, mostly memory) [2][12][13]. Below them: L-theanine (attention), melatonin under sleep loss (one trial of 60), and donepezil (one small acute trial) [14][15][17]. Omega-3 would be shown as tested and negative in older healthy adults [16]. At the bottom for evidence: Semax, Selank, Dihexa, BPC-157, pinealon and the lab compounds, where the published work is animal, cell or old. A second axis would put controlled drugs, steroids, insulin and ketamine at the top for harm, regardless of effect size.

Risks and unknowns

• We ranked nothing ourselves. The reviews report average effects in trial populations, mostly small, mostly short-term, and often in one acute session.
• About half the items have “not verified” in the evidence column. That means we did not open a source, not that none exists.
• We did not open the DEA notices on trenbolone, the FDA release on ZYN, or labels for donepezil, T3, guanfacine, memantine, selegiline, tadalafil and fluvoxamine.
• The creatine and L-theanine reviews pool healthy and clinical populations; we quote healthy-subgroup figures only where the abstract gave them.
• We did not check UK, German or EU status for any item.
• The meta-analysis authors’ funding was not stated in the abstract records we read [2].

Frequently asked questions

Is this tier list based on evidence? It states no criteria. The placements that are hardest to defend are the S-tier controlled drugs, creatine in F and the unstudied research compounds in A and B [1][3][12].

Do prescription stimulants work as cognitive enhancers in healthy adults? A 2020 meta-analysis of 47 studies found small effects for methylphenidate and modafinil and none for d-amphetamine, and the authors called the evidence far from positive [2]. These are prescription drugs with documented risks [3][4][5].

Does creatine improve cognition? Meta-analyses of randomized trials found improvements in memory, with the clearest effect in adults aged 66-76 and none in 11-31 year olds. Certainty was rated moderate for memory and low for other domains [12][13].

Is phenibut a legal supplement? FDA warning letters in 2019 state it is not a dietary ingredient, so products sold as supplements containing it are misbranded [18].

Sources

1. @dex7official, “THE ONLY TRUE COGNITIVE ENHANCEMENT TIER LIST (NO COPES EDITION)” (X post, 20 Oct 2026; image transcribed in the project’s source file, post page not opened). https://x.com/dex7official/status/2112691493261484516
2. Roberts CA et al., Eur Neuropsychopharmacol, “Meta-analyses of modafinil, methylphenidate, and D-amphetamine for cognitive enhancement in healthy adults” (2020). https://pubmed.ncbi.nlm.nih.gov/32709551/
3. Takeda, Vyvanse label, DailyMed (revised April 2026). https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=704e4378-ca83-445c-8b45-3cfa51c1ecad
4. Takeda, Adderall XR label, DailyMed (revised April 2026). https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=aff45863-ffe1-4d4f-8acf-c7081512a6c0
5. Dr. Reddy’s, Methamphetamine hydrochloride tablets label, DailyMed (December 2025 version). https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=d0905e2c-a02f-ec4f-59a3-6f7ad0acbbf6
6. Mylan, Diazepam tablets label, DailyMed (revised September 2026). https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=c397a9da-862f-4f3f-8109-7d21691de53a
7. Viatris, Lyrica (pregabalin) label, DailyMed (September 2025 version). https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=d4734e7d-5079-455e-8ff5-8f4539c998a9
8. Par Health, Ketalar (ketamine) label, DailyMed (revised March 2026). https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=14e8f864-8b8a-4e7e-8439-e510d3107063
9. Eli Lilly, Humulin R label, DailyMed (September 2026 version). https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=b519bd83-038c-4ec5-a231-a51ec5cc291f
10. DEA Diversion Control, Federal Register notice on exclusion of veterinary anabolic steroid implants (2002), found via search; page content could not be opened, not verified. https://webarchive.library.unt.edu/eot2008/20080917193324/http://www.deadiversion.usdoj.gov/fed_regs/rules/2002/fr0624.htm
11. Waylis Therapeutics, Avodart label, DailyMed (November 2026 version). https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=960797b3-09b1-4d6a-8ece-8b5d918e93e4
12. Prokopidis K et al., Nutr Rev, “Effects of creatine supplementation on memory in healthy individuals: a systematic review and meta-analysis of randomized controlled trials” (2023). https://pubmed.ncbi.nlm.nih.gov/35984306/
13. Xu C et al., Front Nutr, “The effects of creatine supplementation on cognitive function in adults: a systematic review and meta-analysis” (2024). https://pubmed.ncbi.nlm.nih.gov/39070254/
14. Alemán-Villa KM et al., Psychopharmacology, melatonin timing and short-term memory during sleep restriction, randomized trial (2026). https://pubmed.ncbi.nlm.nih.gov/40900353/
15. Gerolymos C et al., Mol Psychiatry, “Cognitive and affective effects of L-Theanine: a systematic review and meta-analysis of 31 randomized trials” (2026). https://pubmed.ncbi.nlm.nih.gov/42410082/
16. Sydenham E et al., Cochrane Database Syst Rev, “Omega 3 fatty acid for the prevention of cognitive decline and dementia” (2012). https://pubmed.ncbi.nlm.nih.gov/22696350/
17. Zaninotto AL et al., Hum Psychopharmacol, “Acute cognitive effects of donepezil in young, healthy volunteers” (2009). https://pubmed.ncbi.nlm.nih.gov/19637397/
18. FDA, warning letter to Neuroscience Solutions Inc. on phenibut (10 Apr 2019). https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/neuroscience-solutions-inc-dba-neuroscience-576310-04102019
19. PubMed searches run 2026-11-09 (terms: TAK-653; nefiracetam; PRL-8-53; 9-methyl-beta-carboline; 4-dimethylamino-7,8-dihydroxyflavone; phenylpiracetam OR fonturacetam; donepezil healthy volunteers; tyrosine cognitive; creatine; melatonin; omega-3; L-theanine). https://pubmed.ncbi.nlm.nih.gov/
20. Hansl NR et al., Psychopharmacology, “PRL-8-53: enhanced learning and subsequent retention in humans as a result of low oral doses of new psychotropic agent” (1978). https://pubmed.ncbi.nlm.nih.gov/418433/
21. Li L et al., Biomedicines, “TAK-653 Reverses Core Depressive Symptoms in Chronic Stress-Induced Monkey Model” (2025). https://pubmed.ncbi.nlm.nih.gov/40564108/
22. Keller S et al., J Neural Transm, study of 9-methyl-beta-carboline in astrocytes (2020). https://pubmed.ncbi.nlm.nih.gov/32285253/

This article is information, not medical advice.