
Nootropic Peptides and Smart Drugs Ranked by Evidence
Which nootropic peptide or compound is worth taking?
Ranked by the live Focus and cognition subrating, not the overall score. Methylene blue leads at 6.5–7.0/10 despite a lower overall, 6.0–6.5/10. Bromantane climbs from ninth to fourth. Dihexa ties three racetams here, but its low overall, 4.0–4.5/10, drops it to ninth, a real caution given zero human trials.
- Ranked on the live Focus and cognition subrating, because that is what people actually search a nootropic page to find, not the composite BioHarmony score.
- Methylene blue leads at 6.5–7.0/10, resting on human fMRI from a single 280 mg dose, not a cognition outcome trial. Its own overall is only 6.0–6.5/10.
- Bromantane climbs from ninth on the old memory-ranked order to fourth here at 5.5–6.0/10, much closer to its category-topping overall of 7.0–7.5/10.
- Dihexa ties three racetams at 5.0–5.5/10 but lands ninth once the overall score breaks the tie. That overall, 4.0–4.5/10, is the lowest on the page, and dihexa is the only member here with zero human trials, no human pharmacokinetics, and a mechanism running through a cancer-invasion pathway. The low rank is a real caution, not just a tiebreak quirk.
- Semax and modafinil tie at 6.5–7.0/10. Semax takes second on its higher overall score, 7.0–7.5/10; modafinil is third.
- Three members have zero human trials of any kind: dihexa, P21 and PE-22-28. All three sit in the bottom half of this ranking.
The Ranking
14 interventions, ordered by their live Focus and cognition rating.
Scores are shown as a range because repeat scoring moves by up to ±0.8 on the 0-10 scale; printing one decimal would claim more precision than the method has. The order below is computed from the exact values, so two entries can share a range and still be ranked apart.
How this order works: Focus and cognition first, not the overall number
This page is ordered by each option's Focus and cognition rating: how well it works for that one goal, and nothing else.
The overall BioHarmony number beside it is a different measure. It weighs safety, cost, evidence and practicality across every goal an intervention is used for, so it answers "how good is this thing in general?" rather than "how good is it at this?".
That is why an option with a lower overall BioHarmony number can sit above one with a higher number here. It is the better choice for Focus and cognition, even though the other scores better taken as a whole.
Rank 1: Methylene Blue
Focus and cognition rating 6.5–7.0 / 10Overall BioHarmony 6.0–6.5 / 10 Worth tryingFDA-approved redox drug used off-label at microdose. Focus and cognition 6.5–7.0/10, BioHarmony 6.0–6.5/10, worth trying.
Ranked above options with a higher overall BioHarmony number because it is stronger for Focus and cognition specifically.
Rank 2: Semax
Focus and cognition rating 6.5–7.0 / 10Overall BioHarmony 7.0–7.5 / 10 🛡 Strong RecommendSecond on focus and cognition, tied with modafinil at 6.5–7.0/10 and placing above it on the tiebreak: semax's overall, 7.0–7.5/10, is this category's highest, and the higher overall wins a tie on this metric. Semax is also the broadest performer in the category either way it is measured, taking neuroprotection outright plus strong neuroplasticity, TBI, nerve regeneration and geriatric scores. The mechanism has a coherent story: it upregulates BDNF and TrkB in the hippocampus (Dolotov 2006), and the strongest human evidence is post-stroke rather than healthy-adult cognition, including a 110-patient rehabilitation study (Gusev 2018). Pick it over methylene blue when the target is a brain that needs repairing rather than one specific cognitive lever.
ACTH 4-7 plus PGP heptapeptide. Approved in Russia only. Focus and cognition 6.5–7.0/10, BioHarmony 7.0–7.5/10, strong recommend.
Rank 3: Modafinil
Focus and cognition rating 6.5–7.0 / 10Overall BioHarmony 5.5–6.0 / 10 Worth tryingThird on focus and cognition at 6.5–7.0/10, tied with semax on the score itself but placing behind it because modafinil's overall, 5.5–6.0/10, is lower and the tie breaks on overall. It takes the highest single energy score anywhere on the page, plus a strong reaction-time score, and it is the only prescription member here. Its sleepiness data in narcolepsy is strong, and that is the approved indication; in rested healthy adults the cognitive-enhancement effect is small and state-dependent (Battleday and Brem 2015), which is what keeps its overall well below its cognition-focus number. Pick it for a specific depleted day rather than as a daily cognition base, and know it is Schedule IV.
Prescription Schedule IV eugeroic. Focus and cognition 6.5–7.0/10, BioHarmony 5.5–6.0/10, worth trying.
Ranked above options with a higher overall BioHarmony number because it is stronger for Focus and cognition specifically.
Rank 4: Bromantane (Ladasten)
Focus and cognition rating 5.5–6.0 / 10Overall BioHarmony 7.0–7.5 / 10 🛡 Strong RecommendFourth on focus and cognition at 5.5–6.0/10, a big move up from ninth under the old memory-ranked order, and much closer to where its overall score, 7.0–7.5/10, tied for the highest on the page, would predict. Bromantane is an actoprotector, a Soviet drug class with no Western equivalent, and the flagship trial reported a 76 percent CGI-S responder rate in 728 outpatients with asthenic syndrome (Voznesenskaia 2010). It works by inducing tyrosine hydroxylase expression and demethylating the TH promoter (Vakhitova 2006), with downstream BDNF and NGF upregulation (Salimgareeva 2012), which is why it produces a long clean lift rather than a stimulant spike, an energy and stress-resilience effect that also carries over into focus. The limits are real: the literature is single-country and single-funder, and the manufacturer let the registration lapse in 2018.
Russian adamantane actoprotector. Not approved in the West. Focus and cognition 5.5–6.0/10, BioHarmony 7.0–7.5/10, strong recommend.
Rank 5: Phenylpiracetam (Phenotropil)
Focus and cognition rating 5.0–5.5 / 10Overall BioHarmony 5.5–6.0 / 10 🤷 NeutralFifth on focus and cognition at 5.0–5.5/10, the single biggest climber on this page: it was last on the old memory-ranked order and this metric is exactly what it is known for. Phenylpiracetam is the sharpest short-term tool in the category, with strong reaction-time and energy scores, and it is the racetam people actually feel. What it does not have is durability: the subjective effect fades fast with repeated use, and the direct clinical evidence is one broad class review (Malykh 2010). Its overall is 5.5–6.0/10. It is banned by WADA. Pick it for an occasional morning where focus and physical drive have to arrive together, not as a daily base.
The most stimulating racetam. Banned in tested sport. Focus and cognition 5.0–5.5/10, BioHarmony 5.5–6.0/10, neutral.
Ranked above options with a higher overall BioHarmony number because it is stronger for Focus and cognition specifically.
Rank 6: Piracetam (Nootropil)
Focus and cognition rating 5.0–5.5 / 10Overall BioHarmony 6.5–7.0 / 10 Worth tryingSixth on focus and cognition, tied with aniracetam, oxiracetam and dihexa at 5.0–5.5/10, and first among that four-way tie on the overall tiebreak at 6.5–7.0/10, the highest overall of the group. It is the original nootropic and the deepest-researched racetam, with a clinical case in cortical myoclonus and post-stroke aphasia rather than healthy cognition, and the Cochrane position on dementia and cognitive impairment stays unconvinced (Flicker 2001). It has a long safety record and a low price, roughly $8 to $20 a month. Pick it as the cheapest way to find out whether racetams do anything for your focus specifically.
The prototype racetam. A licensed medicine in parts of Europe. Focus and cognition 5.0–5.5/10, BioHarmony 6.5–7.0/10, worth trying.
Ranked above options with a higher overall BioHarmony number because it is stronger for Focus and cognition specifically.
Rank 7: Aniracetam
Focus and cognition rating 5.0–5.5 / 10Overall BioHarmony 6.0–6.5 / 10 Worth tryingSeventh on focus and cognition, tied with piracetam, oxiracetam and dihexa at 5.0–5.5/10. Its overall, 6.0–6.5/10, matches oxiracetam's exactly, so this pair's order comes down to alphabetical order as the final tiebreak, not to any real difference in the evidence. It is the racetam to pick if anxiety is part of the picture too: the only racetam with a real anxiety subrating, third in the whole category behind selank and bromantane. The mechanism has support: aniracetam reduced glutamate-receptor desensitization and slowed the decay of fast excitatory synaptic currents (Isaacson and Nicoll 1991), with anxiolytic effects across three mouse anxiety models (Nakamura and Kurasawa 2001). The human evidence is older and aimed at senile cognitive disorders (Sourander 1987). It is fat soluble, so it needs to be taken with food.
Fat-soluble racetam with an anxiolytic lean. Focus and cognition 5.0–5.5/10, BioHarmony 6.0–6.5/10, worth trying.
Ranked above options with a higher overall BioHarmony number because it is stronger for Focus and cognition specifically.
Rank 8: Oxiracetam
Focus and cognition rating 5.0–5.5 / 10Overall BioHarmony 6.0–6.5 / 10 Worth tryingEighth on focus and cognition, tied with piracetam, aniracetam and dihexa at 5.0–5.5/10, and just behind aniracetam on the alphabetical tiebreak since both share the same overall, 6.0–6.5/10. Oxiracetam leans cholinergic and mildly stimulating, with a meaningful energy score alongside a cognition-focus subrating that matches two racetam siblings exactly, which tells you how little separates them on measured outcomes. The mechanism evidence is positive AMPA-receptor modulation in neuronal cultures (Copani 1992), and the class-level clinical evidence is the same unconvinced Cochrane position that applies to piracetam. Pair it with choline if you get headaches.
Mildly stimulating cholinergic-leaning racetam. Focus and cognition 5.0–5.5/10, BioHarmony 6.0–6.5/10, worth trying.
Ranked above options with a higher overall BioHarmony number because it is stronger for Focus and cognition specifically.
Ninth on focus and cognition, tied with piracetam, aniracetam and oxiracetam at 5.0–5.5/10, but last in that four-way tie once the overall tiebreak runs: dihexa's overall, 4.0–4.5/10, is the lowest on the entire page, the only member scored caution rather than neutral. That is not just a tiebreak technicality. Dihexa is an angiotensin IV analogue that in rodents drives hippocampal synaptogenesis and rescues memory (Benoist 2011, McCoy 2013, Sun 2021), which is the rodent signal behind its cognition-focus number, but it potentiates hepatocyte growth factor signaling at c-Met, a cancer invasion and metastasis pathway with approved inhibitors built against it (Comoglio 2008). Zero human trials, no human pharmacokinetics, and FDA notes the absence of human exposure data. A strong rodent signal that ties three well-studied racetams is a reason to watch the research, not a reason to be first in humans.
Angiotensin IV analogue acting on c-Met. Zero human trials. Focus and cognition 5.0–5.5/10, BioHarmony 4.0–4.5/10, caution.
Ranked above options with a higher overall BioHarmony number because it is stronger for Focus and cognition specifically.
Rank 10: Selank
Focus and cognition rating 4.5–5.0 / 10Overall BioHarmony 6.5–7.0 / 10 Worth tryingTenth on focus and cognition at 4.5–5.0/10, and the answer to a different question than the compounds above it. Selank is the anxiolytic of the group: it takes the top anxiety subrating in the category by a full point, and ties for stress resilience and mood. A Russian comparator study in 62 patients found anxiolytic effects similar to medazepam without the sedation and dependence profile (Zozulia 2008), and a second trial against phenazepam reported anxiolytic plus mild nootropic effects (Medvedev 2014). Its overall is 6.5–7.0/10. Pick it over the cognition-focus leaders when calm rather than sharpness is the goal. The evidence is geographically narrow and there is no Western replication.
Tuftsin-derived anxiolytic heptapeptide. No Western approval. Focus and cognition 4.5–5.0/10, BioHarmony 6.5–7.0/10, worth trying.
Rank 11: Cerebrolysin
Focus and cognition rating 4.0–4.5 / 10Overall BioHarmony 6.0–6.5 / 10 Worth tryingEleventh on focus and cognition at 4.0–4.5/10, below its own overall of 6.0–6.5/10. It carries by a wide margin the largest human trial base in this category, and that is exactly why it is unresolved rather than recommended. The maker-funded rehabilitation trials are positive: CARS reported a large arm-recovery effect at day 90 (Muresanu 2016) and CAPTAIN II showed a multivariate recovery benefit in moderate-to-severe brain injury (Muresanu 2020). Two independent Cochrane reviews do not confirm it, finding no benefit on death and more non-fatal serious adverse events in stroke (Ziganshina 2023) and very-low-quality evidence in vascular dementia (Cui 2019). It is also an IV or IM course costing $500 to $900.
Porcine brain-derived peptide mixture, IV or IM. Approved outside the US. Focus and cognition 4.0–4.5/10, BioHarmony 6.0–6.5/10, worth trying.
Ranked above options with a higher overall BioHarmony number because it is stronger for Focus and cognition specifically.
Rank 12: Pinealon (Glu-Asp-Arg)
Focus and cognition rating 2.5–3.0 / 10Overall BioHarmony 6.0–6.5 / 10 Worth tryingTwelfth on focus and cognition, tied with P21 at 2.5–3.0/10, and ahead of it on the overall tiebreak: pinealon's overall, 6.0–6.5/10, is higher than P21's own 5.0–5.5/10. Pinealon is a Khavinson tripeptide, and independent biophysics confirms the molecule can enter the DNA major groove and contact guanine (Silanteva 2019), which is a genuinely unusual mechanism. In cultured neurons it restricted reactive-oxygen-species accumulation and reduced necrotic cell death (Khavinson 2011). The only human data is a single uncontrolled open-label cohort of 32 from the lab that created it (Meshchaninov 2015). Interesting biology, unproven cognition in people.
Khavinson tripeptide (Glu-Asp-Arg). No registered trial anywhere. Focus and cognition 2.5–3.0/10, BioHarmony 6.0–6.5/10, worth trying.
Rank 13: P21 (P021)
Focus and cognition rating 2.5–3.0 / 10Overall BioHarmony 5.0–5.5 / 10 🤷 NeutralThirteenth on focus and cognition, tied with pinealon at 2.5–3.0/10 but behind it once the overall tiebreak runs: P21's overall, 5.0–5.5/10, is lower than pinealon's 6.0–6.5/10. P21 is a CNTF-derived peptidomimetic that crosses the blood-brain barrier, and in mice it raises BDNF, lifts hippocampal neurogenesis and lowers tau pathology (Li 2010), the cleanest rodent neurogenesis dataset on this page, and the source of its cognition-focus number. Three things hold its overall down: there are zero human trials, the one independent in-vivo replication failed to reproduce the BDNF effect (Mottolese 2024), and nearly all the positive work comes from the inventor, who co-founded the company commercializing it. Worth following, not worth taking.
CNTF-derived peptidomimetic. Zero human trials. Focus and cognition 2.5–3.0/10, BioHarmony 5.0–5.5/10, neutral.
Fourteenth on focus and cognition at 1.5–2.0/10, the lowest score on this page, despite an overall of 4.5–5.0/10. It has one of the cleanest mechanisms in the gray-market peptide world and nothing behind it in humans for cognition specifically. Blocking TREK-1 is a well-mapped route to a fast antidepressant effect: deleting the gene makes mice resistant to depression (Mazella 2010), and PE-22-28 inhibits human TREK-1 at about 0.12 nanomolar (Djillani 2017), its primary use case is depression, not cognition. Two problems keep its overall down too: the dose response is biphasic in a way that can reverse the effect, and TREK-1 sits in the heart, pancreas and gut too (Hivelin 2016).
Spadin analogue and TREK-1 blocker. Zero human trials. Focus and cognition 1.5–2.0/10, BioHarmony 4.5–5.0/10, neutral.
Best Pick by Use Case
| Use Case | Winner | Runner-Up | Why |
|---|---|---|---|
| Cognition & Focus | Methylene Blue 6.8 | Semax 6.5 | The row this category exists for, and it is tighter than the composite ranking suggests. Methylene blue 6.8/10, semax 6.5/10, modafinil 6.5/10, bromantane 5.8/10, then four compounds bunched at 5.0. The 6.8/10 rests on human fMRI from a single 280 mg dose, not on a cognition outcome trial, and every score in this row should be read that way. |
| Memory | Methylene Blue 6.5 | Semax 6.0 | Dihexa is third at 5.5/10, from a compound with zero human trials that ranks last overall. That gap between a use-case subrating and a composite score is the clearest thing on the page: the subrating measures the strength of the signal, the composite adds what it costs you to act on it. |
| Anxiety | Selank 6.5 | Bromantane (Ladasten) 5.7 | The most decisive row in the table. Selank is a full point clear, and the only other members above 3.5 are bromantane at 5.7/10 and aniracetam at 5.0/10. Selank is also the only member whose human evidence is specifically anxiety rather than cognition, tested against a benzodiazepine comparator. |
| Mood & Emotion | Selank 5.5 | Modafinil 5.5 | A four-way tie at 5.5/10 between selank, modafinil, methylene blue and bromantane, so read this row as a tie rather than a win. They arrive there by four different routes: a peptide anxiolytic, a wakefulness drug, an MAO-A inhibitor and an actoprotector. The next score down is semax at 3.5–4.0/10. |
| Energy & Fatigue | Modafinil 7.0 | Methylene Blue 6.8 | The highest single score anywhere on this page, and it belongs to the member ranked third on this page's focus-and-cognition order. Modafinil's 7.0–7.5/10 is real and it is why people take it. Bromantane at 6.0–6.5/10 is the interesting entry here, because it produces the lift without the stimulant profile that usually comes with it. |
| Depression | Methylene Blue 5.5 | Modafinil 5.0 | Read this row with care. Methylene blue's 5.5–6.0/10 rests partly on it being a genuine MAO-A inhibitor, which is also the reason it interacts dangerously with serotonergic medication. PE-22-28, the only member built specifically as an antidepressant, scores 2.5–3.0/10, because everything it has is in rodents. |
| Neuroprotection | Semax 6.5 | Methylene Blue 6.5 | A dead heat at 6.5, so read this as a tie. Semax gets there through post-stroke human data and BDNF upregulation; methylene blue through mitochondrial redox activity. Cerebrolysin and dihexa follow at 4.5, and the four racetams all sit at 1.5. |
| Neuroplasticity | Semax 6.0 | Dihexa 5.0 | The row where the peptides separate from everything else. Semax, dihexa, bromantane and selank occupy the top four, and all four racetams sit at 1.5. Growing new connections and modulating existing receptors are different jobs, and this row is where that shows. |
| Stress & Resilience | Selank 6.0 | Bromantane (Ladasten) 6.0 | Another dead heat, at 6.0. These two are the category's answer to burnout rather than to sharpness, and both were developed in the same Russian tradition for the same clinical target, asthenic syndrome. Methylene blue is third at 5.5/10. |
| Reaction Time | Modafinil 6.5 | Phenylpiracetam (Phenotropil) 5.0 | The only row where phenylpiracetam places, and it is the reason to own any. Everything below semax at 4.0/10 sits at 2.5 or under. If measurable speed rather than subjective clarity is the goal, this row is a short list of two. |
| Traumatic Brain Injury | Semax 4.5 | Cerebrolysin 4.3 | The lowest-scoring winner in the table, and honestly so. Semax 4.5/10 and cerebrolysin 4.3/10 are the two members with real human brain-injury literature, and cerebrolysin's is the larger and the more contested. Nothing here is a treatment, and brain injury is not a self-directed problem. |
At a Glance
Methylene Blue
- Efficacy Strong
- Breadth Strong
- Evidence Strong
- Speed Exceptional
- Durability Moderate
- Bioindividuality Limited
- Safety Risk High
- Side Effects Low
- Cost premium Low
- Effort Negligible
- Opportunity Cost Negligible
- Dependency Negligible
- Reversibility Low
- Mitochondrial
- Cognition & Focus
- Energy & Fatigue
- Memory
FDA-approved redox drug used off-label at microdose. Focus and cognition 6.5–7.0/10, BioHarmony 6.0–6.5/10, worth trying.
Semax
- Efficacy Strong
- Breadth Strong
- Evidence Strong
- Speed Strong
- Durability Moderate
- Bioindividuality Moderate
- Safety Risk Low
- Side Effects Low
- Cost premium Low
- Effort Low
- Opportunity Cost Low
- Dependency Low
- Reversibility Negligible
- Cognition & Focus
- Neuroprotection
- Memory
- Neuroplasticity
ACTH 4-7 plus PGP heptapeptide. Approved in Russia only. Focus and cognition 6.5–7.0/10, BioHarmony 7.0–7.5/10, strong recommend.
Modafinil
- Efficacy Exceptional
- Breadth Strong
- Evidence Strong
- Speed Exceptional
- Durability Limited
- Bioindividuality Moderate
- Safety Risk High
- Side Effects Moderate
- Cost premium Moderate
- Effort Negligible
- Opportunity Cost Moderate
- Dependency Low
- Reversibility Low
- Energy & Fatigue
- Cognition & Focus
- Reaction Time
- Mood & Emotion
Prescription Schedule IV eugeroic. Focus and cognition 6.5–7.0/10, BioHarmony 5.5–6.0/10, worth trying.
Dihexa
- Efficacy Moderate
- Breadth Limited
- Evidence Limited
- Speed Strong
- Durability Moderate
- Bioindividuality Moderate
- Safety Risk Moderate
- Side Effects Low
- Cost premium Moderate
- Effort Low
- Opportunity Cost Moderate
- Dependency Low
- Reversibility Moderate
- Memory
- Cognition & Focus
- Neuroplasticity
- Neuroprotection
Angiotensin IV analogue acting on c-Met. Zero human trials. Focus and cognition 5.0–5.5/10, BioHarmony 4.0–4.5/10, caution.
Piracetam (Nootropil)
- Efficacy Moderate
- Breadth Moderate
- Evidence Strong
- Speed Limited
- Durability Limited
- Bioindividuality Moderate
- Safety Risk Low
- Side Effects Negligible
- Cost premium Low
- Effort Low
- Opportunity Cost Low
- Dependency Negligible
- Reversibility Negligible
- Recovery & Repair
- Cognition & Focus
- Memory
- Pediatric Use
The prototype racetam. A licensed medicine in parts of Europe. Focus and cognition 5.0–5.5/10, BioHarmony 6.5–7.0/10, worth trying.
Oxiracetam
- Efficacy Moderate
- Breadth Moderate
- Evidence Moderate
- Speed Moderate
- Durability Limited
- Bioindividuality Moderate
- Safety Risk Low
- Side Effects Low
- Cost premium Moderate
- Effort Low
- Opportunity Cost Low
- Dependency Low
- Reversibility Negligible
- Cognition & Focus
- Memory
- Energy & Fatigue
- Cardiovascular
Mildly stimulating cholinergic-leaning racetam. Focus and cognition 5.0–5.5/10, BioHarmony 6.0–6.5/10, worth trying.
Aniracetam
- Efficacy Moderate
- Breadth Moderate
- Evidence Strong
- Speed Moderate
- Durability Limited
- Bioindividuality Moderate
- Safety Risk Low
- Side Effects Low
- Cost premium Low
- Effort Low
- Opportunity Cost Low
- Dependency Negligible
- Reversibility Low
- Cognition & Focus
- Memory
- Anxiety
- Cardiovascular
Fat-soluble racetam with an anxiolytic lean. Focus and cognition 5.0–5.5/10, BioHarmony 6.0–6.5/10, worth trying.
Cerebrolysin
- Efficacy Strong
- Breadth Strong
- Evidence Strong
- Speed Moderate
- Durability Moderate
- Bioindividuality Moderate
- Safety Risk Low
- Side Effects Low
- Cost premium Moderate
- Effort High
- Opportunity Cost Moderate
- Dependency Low
- Reversibility Low
- Neuroprotection
- Traumatic Brain Injury
- Cognition & Focus
- Memory
Porcine brain-derived peptide mixture, IV or IM. Approved outside the US. Focus and cognition 4.0–4.5/10, BioHarmony 6.0–6.5/10, worth trying.
Bromantane (Ladasten)
- Efficacy Strong
- Breadth Moderate
- Evidence Moderate
- Speed Strong
- Durability Strong
- Bioindividuality Strong
- Safety Risk Low
- Side Effects Low
- Cost premium Moderate
- Effort Low
- Opportunity Cost Low
- Dependency Negligible
- Reversibility Low
- Energy & Fatigue
- Stress & Resilience
- Cognition & Focus
- Anxiety
Russian adamantane actoprotector. Not approved in the West. Focus and cognition 5.5–6.0/10, BioHarmony 7.0–7.5/10, strong recommend.
Selank
- Efficacy Strong
- Breadth Strong
- Evidence Moderate
- Speed Exceptional
- Durability Moderate
- Bioindividuality Strong
- Safety Risk Low
- Side Effects Low
- Cost premium Low
- Effort Low
- Opportunity Cost Moderate
- Dependency Low
- Reversibility Low
- Anxiety
- Stress & Resilience
- Mood & Emotion
- Immune Function
Tuftsin-derived anxiolytic heptapeptide. No Western approval. Focus and cognition 4.5–5.0/10, BioHarmony 6.5–7.0/10, worth trying.
P21 (P021)
- Efficacy Moderate
- Breadth Moderate
- Evidence Limited
- Speed Moderate
- Durability Moderate
- Bioindividuality Moderate
- Safety Risk Low
- Side Effects Low
- Cost premium Moderate
- Effort Moderate
- Opportunity Cost Moderate
- Dependency Low
- Reversibility Low
- Cognition & Focus
- Memory
- Neuroprotection
- Neuroplasticity
CNTF-derived peptidomimetic. Zero human trials. Focus and cognition 2.5–3.0/10, BioHarmony 5.0–5.5/10, neutral.
Pinealon (Glu-Asp-Arg)
- Efficacy Moderate
- Breadth Moderate
- Evidence Moderate
- Speed Moderate
- Durability Moderate
- Bioindividuality Moderate
- Safety Risk Low
- Side Effects Low
- Cost premium Moderate
- Effort Moderate
- Opportunity Cost Low
- Dependency Low
- Reversibility Low
- Cognition & Focus
- Neuroprotection
- Neuroplasticity
- Antioxidant
Khavinson tripeptide (Glu-Asp-Arg). No registered trial anywhere. Focus and cognition 2.5–3.0/10, BioHarmony 6.0–6.5/10, worth trying.
PE-22-28
- Efficacy Moderate
- Breadth Moderate
- Evidence Limited
- Speed Strong
- Durability Limited
- Bioindividuality Moderate
- Safety Risk Low
- Side Effects Low
- Cost premium Moderate
- Effort Moderate
- Opportunity Cost Moderate
- Dependency Low
- Reversibility Low
- Neuroprotection
- Mood & Emotion
- Depression
- Neuroplasticity
Spadin analogue and TREK-1 blocker. Zero human trials. Focus and cognition 1.5–2.0/10, BioHarmony 4.5–5.0/10, neutral.
Phenylpiracetam (Phenotropil)
- Efficacy Strong
- Breadth Moderate
- Evidence Moderate
- Speed Strong
- Durability Limited
- Bioindividuality Moderate
- Safety Risk Low
- Side Effects Moderate
- Cost premium Moderate
- Effort Low
- Opportunity Cost Low
- Dependency Moderate
- Reversibility Low
- Energy & Fatigue
- Cognition & Focus
- Reaction Time
- Cold & Heat Tolerance
The most stimulating racetam. Banned in tested sport. Focus and cognition 5.0–5.5/10, BioHarmony 5.5–6.0/10, neutral.
Cost Comparison
| Intervention | Monthly Cost | Notes |
|---|---|---|
| Cerebrolysin | $500 to $900 | Estimated, September 2026 prices, at about 30 mL per day IV. A 4-week dementia course is 20 infusion days at 30 mL, so 60 ten-millilitre ampoules; overseas pharmacy resellers price those at roughly $8 to $14 each. Clinic infusion fees are extra and are not in this figure. Ten times the price of anything else on the page. |
| PE-22-28 | $45 to $138 | Estimated, September 2026 prices, research-vial channel. No validated human dose exists, so this prices one vial per short self-directed course of about a month. Vendors list 8 mg vials from about $55. A price for a protocol nobody has established. |
| Dihexa | $30 to $60 | Community doses of 8 to 12 mg a day sublingual, priced from gray-market vendors 2026-09-08, before the per-lot HPLC and mass-spec testing the report recommends. That testing can cost more than the compound. |
| Selank | $30 to $60 | Priced 2026-09-08, at a 0.15 percent intranasal spray, roughly 1 to 3 sprays per nostril per day. Varies with vendor, concentration and daily dose; third-party testing and cold-chain handling push the top of the band. |
| P21 | $29 to $48 | Estimated, September 2026 prices, research-vial channel, at 100 mcg daily. Vendors list 5 mg vials at roughly $48 to $80, so a month is about 3 mg. Before reconstitution supplies, and for a compound with no human dosing study to price against. |
| Phenylpiracetam | $21 to $42 | Estimated, September 2026 prices, at 100 to 200 mg daily. One vendor lists 60 capsules of 100 mg at $42, so 100 mg a day is about $21 a month and 200 mg about $42. Cycled use costs less, and third-party COA testing is the real added expense. This is the anchor the three racetam estimates below are derived from. |
| Semax | $12 to $60 | Estimated, September 2026 prices, at 300 to 600 mcg a day of a 0.1 percent nasal spray. A pre-mixed 30 mg spray runs $40 to $100; at 300 mcg a day that is $12 to $30 a month, and at 600 mcg it is $24 to $60. One of the cheapest lines on the page, from a joint-first member. |
| Oxiracetam | $15 to $40 | Estimated and unverified, September 2026 prices, at 800 to 2,400 mg daily. No vendor listing was checked for this figure; it is derived from the phenylpiracetam anchor discounted to bulk-powder rates. Treat it as an order of magnitude, not a quote. The report also notes sourcing has become difficult. |
| Modafinil | $18 to $35 | Priced 2026-09-08, at a 200 mg oral tablet. Generic modafinil through a prescription, which makes it the only line on this page that is both cheap and legitimate. Occasional rather than daily use costs proportionally less. |
| Methylene blue | $13 to $40 | Estimated, September 2026 prices, at 0.5 to 5 mg oral. A pharmaceutical-grade or properly compounded solution runs $40 to $120 per vial and lasts months at microdose levels. Aquarium-grade and industrial dye are never acceptable and are not what this price refers to. |
| Bromantane | $12 to $30 | Estimated, September 2026 prices, at 30 mg. Bulk research-chemical powder runs $40 to $100 a gram; a 30 mg pulsed dose taken about ten mornings a month consumes 0.3 g. The joint-first member of this ranking is also one of the two cheapest. |
| Aniracetam | $10 to $25 | Estimated and unverified, September 2026 prices, at 750 to 1,500 mg daily. No vendor listing was checked; derived from the phenylpiracetam anchor discounted to bulk-powder rates. It is fat soluble, so factor in taking it with food rather than on its own. |
| Pinealon | $10 to $15 | Estimated, September 2026 prices, at 100 micrograms. A vendor lists a 20 mg vial at $68, about $3.40 per mg, and the only PMID-anchored dose is 100 mcg a day, or 3 mg a month. Rising to roughly $15 once reconstitution supplies are counted. |
| Piracetam | $8 to $20 | Estimated and unverified, September 2026 prices, at 2.4 to 4.8 g daily. No vendor listing was checked; derived from the phenylpiracetam anchor discounted to bulk-powder rates. The cheapest line on the page and the standard first experiment in this class. |
| The difference | $8 to $900, and the top of the range ranks eleventh | Cerebrolysin costs ten times more than anything else here and it is an infusion course, not a daily capsule. Everything else falls between $8 and $138 a month, which means cost is almost never the deciding variable in this category. Sourcing quality is. Twelve of the fourteen members require a third-party certificate of analysis, and none of the prices quoted include one. |
Who Should Pick What?
Knowledge worker with a demanding output schedule and no clinical problem
Bromantane (Ladasten)
Energy 6.2/10 and stress resilience 6.0/10 from a compound that is not a stimulant, backed by the largest clinical dataset in this category at 728 outpatients. Pulsed rather than daily is how the reports describe it being used, and the honest caveats are that the literature is single-country and the registration lapsed in 2018.
Anxiety is the thing getting in the way, not focus
Selank
Anxiety 6.5/10, a full point clear of everything else on the page, from a peptide tested against a benzodiazepine comparator in 62 patients without the sedation, amnesia or dependence profile. Aniracetam at 5.0/10 is the cheaper and more available second choice if intranasal peptides are not something you want to source.
You want the broadest brain-health effect rather than one lane
Semax
It takes neuroprotection, neuroplasticity, TBI, nerve regeneration and geriatric, and places second on cognition and memory. No other member covers that much ground. The strongest human evidence is post-stroke rather than healthy-adult cognition, so treat the healthy-user case as mechanistically reasonable rather than proven.
Curious about nootropics and unwilling to source a peptide
Piracetam (Nootropil)
The cheapest entry on the page at roughly $8 to $20 a month, the longest safety record, and cognition and memory scores level with its two racetam siblings. It is the standard place to find out whether this class does anything for you at all, and the honest expectation is a mild effect or none.
One depleted day, a deadline, and bad sleep behind you
Modafinil
Energy 7.0–7.5/10 and reaction time 6.5–7.0/10, the two highest scores in those rows, and the sleepiness evidence is genuinely strong. In rested healthy adults the cognitive effect is small and state-dependent, so this is a tool for a specific depleted state rather than a daily base. It is Schedule IV and needs a prescription.
Focus and physical output have to arrive on the same morning
Phenylpiracetam (Phenotropil)
Reaction time 5.0–5.5/10 and energy 5.0–5.5/10, the only member other than modafinil that does both. Its memory subrating is 1.5–2.0/10, the lowest in this category, and the subjective effect fades quickly with repeated use, so it works as an occasional morning tool and fails as a base. It is banned by WADA.
You are trying to protect an aging brain over decades
Semax
Geriatric 5.0–5.5/10 and healthspan 4.0–4.5/10, the highest geriatric score on the page, and its mechanism is neurotrophic rather than stimulant. Methylene blue's 6.5–7.0/10 healthspan and 6.0–6.5/10 longevity are higher but rest on mitochondrial biology rather than on any cognitive-aging outcome, and it carries a real drug-interaction profile. Neither has a long-term cognitive-aging trial.
Recovering from a stroke or a moderate-to-severe brain injury
Tie
Semax at 4.5/10 and cerebrolysin at 4.3/10 are the two members with real human brain-injury literature, and this is a row to take to a clinician rather than to a vendor. Cerebrolysin's positive trials are maker-funded and two independent Cochrane reviews do not confirm them, and it is an IV or IM course that needs a clinic.
You take an SSRI, SNRI or any serotonergic medication
Tie
Not methylene blue, whatever the cognition score says. It is a confirmed MAO-A inhibitor and FDA has issued a drug-safety communication about serious central nervous system reactions when it is combined with serotonergic psychiatric medication. Take the interaction to a prescriber before anything else on this page.
You want the strongest memory effect available
Methylene Blue
Memory 6.5–7.0/10, the top score in that row. The one to avoid here is dihexa, which sits third at 5.5–6.0/10 with zero human trials, no human pharmacokinetics and a mechanism that runs through c-Met, a cancer invasion pathway. A strong rodent memory signal is not a reason to be first in humans.
A drug-tested athlete
Tie
Bromantane has been on the WADA stimulant list since 1997, phenylpiracetam and modafinil are both banned, and most of the peptides fall under the S0 non-approved-substances catch-all. Assume every member of this page is prohibited unless your own federation tells you otherwise in writing.
How This Ranking Is Built
- Ranked by
- Ranked by the live Focus and cognition rating (the Cognition & Focus subrating) This page is ordered by each option's Focus and cognition rating: how well it works for that one goal, and nothing else. The overall BioHarmony number beside it is a different measure. It weighs safety, cost, evidence and practicality across every goal an intervention is used for, so it answers "how good is this thing in general?" rather than "how good is it at this?". That is why an option with a lower overall BioHarmony number can sit above one with a higher number here. It is the better choice for Focus and cognition, even though the other scores better taken as a whole.
- What is included
- Every published BioHarmony intervention report on a synthetic compound whose primary purpose is changing how the brain works: cognition, memory, mood, anxiety or neuroprotection. That takes in the neuropeptides (semax, selank, cerebrolysin, pinealon, P21, PE-22-28, dihexa), the racetams (piracetam, aniracetam, oxiracetam, phenylpiracetam) and the three synthetics that get compared against them (bromantane, methylene blue, modafinil). Botanicals and nutrients are out, because buying a mushroom is a different decision from buying a research peptide. Mitochondrial and longevity compounds that happen to carry a neuroprotection subrating are out. Devices are out. Adding a new report inside this boundary adds a row.
- Kept current
- Positions and scores are read live from each intervention report on every page load, so the order re-renders the moment any member is rescored. Membership is rebuilt nightly against the inclusion rule above.
Ranked by the live Focus and cognition rating (the Cognition & Focus subrating), not the overall BioHarmony score. This page uses bh_overall_for_use_case: the order comes from each member's live bh_subratings[cognition-focus].score, read fresh when the page renders, with bh_overall as the tiebreak when two members share the same subrating and alphabetical order as the final tiebreak if the overall also ties. The overall score shown beside every row is bh_overall — it explains the member's whole-report standing, but it only sets the order when a tie needs breaking.
This is a deliberate change from ranking by the Memory subrating. Cognition and focus is closer to what people actually search a nootropic page to find, and the two orders diverge in real ways. Bromantane climbs from ninth on the memory order to fourth here, much closer to its top-of-page overall score. Phenylpiracetam climbs from last to fifth, the largest single move on the page, because a short, sharp focus effect is exactly what it is built for even though its memory data is thin. Every row ranked above a higher-overall member, or whose tiebreak order needs explaining, carries a note in the commentary.
This ranking covers fourteen members rather than the ten a nootropic-peptide page would carry, and the four extra are the racetams and modafinil. The reason is consistency: phenylpiracetam belongs to this cluster by every measure of how people search and compare, and ranking it while leaving out piracetam, aniracetam and oxiracetam would have been a boundary drawn to suit the page. Modafinil is here for the same reason, and because it is already compared directly against bromantane and dihexa. Botanicals, nutrients and mitochondrial compounds are excluded and named in the boundary above, so you can see what was left out rather than guess.
Read the cognition-focus subrating and the overall together, because they disagree here more than in most categories. A subrating measures how strong the signal is for one goal, focus and cognition specifically; the overall adds evidence quality, safety, access, cost and practicality across every goal a member's report covers. Dihexa is the sharpest case: it ties three well-studied racetams on the ranked subrating, but its overall is the lowest on the page, and that gap is not noise. Dihexa has zero human trials, no human pharmacokinetics, and a mechanism that runs through a cancer-invasion pathway, which is exactly why its overall score pulls it to ninth in that four-way tie rather than letting the shared subrating carry it higher.
Evidence depth is uneven in a way worth stating plainly. Four members carry a full 66 or 67 use-case subrating set, and the other ten carry roughly 15 to 28 each. That is why the mature members appear across more rows, and it is a statement about how much has been measured rather than about biology.
Three members have no human trials of any kind: dihexa, P21 and PE-22-28. A fourth, pinealon, has one uncontrolled cohort of 32 from the lab that invented the molecule. Nothing in those four rows should be read as a human result, including dihexa's cognition-focus score, which rests entirely on rodent data and is the reason it carries a caution rather than a neutral verdict despite sitting in the middle of the pack on the ranked number.
Costs in the table are estimates with a pricing date. Two members have a legitimate channel: methylene blue as a pharmaceutical-grade retail product, and modafinil as a prescription. The other twelve are priced as research chemicals, where purity is vendor-dependent, and the three racetam figures are additionally marked UNVERIFIED because no vendor listing was checked for them.
Research Highlights
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Mechanism Difference
Four mechanisms are represented here and they are not interchangeable. The neuropeptides work through growth factors: semax and selank raise BDNF and TrkB signaling, P21 was designed from ciliary neurotrophic factor, and dihexa potentiates hepatocyte growth factor at c-Met. That arm is trying to grow and protect connections, which is a slow, structural job.The racetams work through glutamate. Piracetam defined a new allosteric binding site on AMPA receptors, aniracetam slows the decay of fast excitatory currents (Isaacson and Nicoll 1991), and oxiracetam adds high-affinity choline uptake. That arm modulates signalling you already have, which is why the effect is felt the same day and does not compound.Bromantane and modafinil work through catecholamines, though by different routes: bromantane induces tyrosine hydroxylase expression and demethylates its promoter (Vakhitova 2006), so it builds dopamine synthesis capacity rather than dumping the stores, while modafinil acts on the dopamine transporter (Volkow 2009). Methylene blue is the outlier: it is a redox compound acting on mitochondrial electron transport, which is why its profile looks metabolic rather than neurological.PE-22-28 is the fourth mechanism on its own, an ion-channel blocker at TREK-1. Reading this ranking as one class getting progressively better misses the point entirely.
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Safety Comparison
The safety profiles here diverge more than in most categories, and the highest-scoring members are not always the safest.Methylene blue is the interaction risk. It is a confirmed MAO-A inhibitor (Ramsay 2007), FDA has issued a drug-safety communication about serious central nervous system reactions when it is combined with serotonergic psychiatric medication, and its report adds a G6PD deficiency contraindication with pre-testing recommended for anyone with ancestral risk. That is a real contraindication list on the member with the top cognition score.Dihexa is the mechanism risk. c-Met is a cancer invasion and metastasis pathway with approved inhibitors developed specifically against it (Comoglio 2008), and dihexa is designed to potentiate signalling through it. That is why it is the only member scored caution.Cerebrolysin is the product risk twice over: it is a porcine brain-derived extract with no single declared active ingredient, and an independent Cochrane review found more non-fatal serious adverse events on treatment than on control in stroke (Ziganshina 2023).Then there is the shared risk. Twelve of the fourteen members have no pharmaceutical-grade option, and a multi-laboratory European surveillance study detected bromantane in illicit nootropic samples, one at 33.2 mg per unit (Vanhee 2025). Buying the wrong thing is the most common harm in this category, ahead of any pharmacology on this page.
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Cost Comparison
Cost is almost never the deciding variable here, and the table shows why. Thirteen of the fourteen members cost between $8 and $138 a month. Cerebrolysin is the exception at $500 to $900, and that is because it is an infusion course of sixty ampoules rather than a daily dose.What that flatness means in practice is that price cannot help you choose, and it tracks nothing about where a member ranks on focus and cognition. Bromantane, one of the two highest overall scores on the page at 7.0–7.5/10, costs $12 to $30 a month and ranks fourth. Dihexa, the lowest overall on the page at 4.0–4.5/10, costs $30 to $60 and ranks ninth despite tying three racetams on the ranked score. Piracetam is the cheapest line on the page and ranks sixth. There is no relationship between what a member costs, its overall score, or where it lands on this cognition-focus-ranked list.The variable that does matter is what you are actually buying. Twelve members require a third-party HPLC and mass-spec certificate of analysis, none of the quoted prices include one, and three of the figures here are marked UNVERIFIED because no vendor listing was checked for them. A $15 compound with a $100 assay is not a $15 compound, and skipping the assay is how people end up dosing something else entirely.
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Evidence Maturity
Sort this category by how much human evidence exists and the order barely resembles this cognition-focus-ranked list. Cerebrolysin has the largest human trial base by a wide margin and sits eleventh. Modafinil has the strongest regulatory evidence of any member and ties for the top score with semax, only placing third because its overall is lower. Bromantane, tied for the highest overall score on the page, rests on a single-country, single-funder literature whose flagship trial was open-label, and it climbs to fourth here specifically because that overall score is high.That is not the scoring model failing. It is the scoring model weighing what the evidence found rather than how much of it there is. Cerebrolysin sits eleventh because two independent Cochrane reviews do not confirm the maker-funded results (Ziganshina 2023, Cui 2019). Modafinil's healthy-adult cognitive effect is small and state-dependent (Battleday and Brem 2015), which is what keeps its overall well below its cognition-focus number. A negative or narrow result is information, and it counts.At the other end, three members have no human data at all: dihexa, P21 and PE-22-28. P21's rodent neurogenesis dataset is the cleanest of any gray-market peptide here, and the one independent in-vivo replication of its core BDNF mechanism failed (Mottolese 2024). Dihexa's rodent signal ties three racetams on the ranked score but its own overall, the lowest on the page, drops it to last in that tie. That is the difference between a promising mechanism and a result, and it is exactly why the tiebreak matters here.
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Editorial Verdict
Two members carry the strong-recommend tier on their overall BioHarmony score and they answer different questions. Bromantane is for output: a long clean lift with the largest clinical dataset in the category behind it, and this page's fourth-place focus and cognition score. Semax is for the brain itself: the broadest coverage on the page, with a coherent BDNF mechanism, human evidence in stroke recovery, and a tied second-place focus and cognition score behind methylene blue. Selank is the third real answer, and the first one if anxiety rather than focus is what is in the way.Below those three the picture is honest rather than exciting. The racetams are cheap, safe and mild, and piracetam is the sensible way to find out whether the class does anything for you. Modafinil is a specific tool for a specific depleted day, and its focus and cognition score is stronger than its narcolepsy-focused reputation suggests. Methylene blue has the best individual scores on the page, including the top focus and cognition subrating, and the most serious interaction profile, so it is the one to take to a prescriber first rather than the one to try first.P21 and PE-22-28 are not worth sourcing: zero human trials, and nothing beyond a rodent or cell-culture signal. Dihexa is the harder case, because its rodent memory data is real and it still runs through a cancer pathway with zero human trials — a strong rodent memory score is a reason to follow the literature, not a reason to be an early human. Cerebrolysin is a clinical question, not a nootropic, and it belongs in a conversation with a neurologist.One thing applies to all fourteen: nothing here outperforms sleep. Every report in this category says a version of the same sentence.
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Ranking Stability
This ranking is not an opinion that gets refreshed quarterly. The order is the live Focus and cognition subrating for each member, resolved when the page loads, so a rescoring of any one report reorders the page that night without an editorial pass. The overall BioHarmony score shown beside every row only breaks a tie on the ranked subrating, which is what makes methylene blue's win at a below-average overall possible, and it is also why dihexa, tied with three racetams on the ranked score, still lands ninth: its overall is the lowest on the page.Expect slow movement. Most of this literature is old and most of it is finished: the racetam trials are from the 1980s and 1990s, semax and selank date to the Soviet peptide program, and bromantane's manufacturer let its registration lapse in 2018. Only three members sit inside an active research program that could produce a new human result, and two of those, P21 and PE-22-28, have not started human trials at all.The likeliest mover is dihexa: its focus and cognition score rests entirely on rodent data, and a single human trial, positive or negative, would move both the score and the tiebreak sharply in either direction. The gap between 6.5–7.0/10 at the top and 1.5–2.0/10 at the bottom is one of the widest spreads of any BioHarmony category ranking so far.
Frequently Asked Questions
- What is the best nootropic peptide?
- Semax, at a BioHarmony 7.0–7.5/10, tied with bromantane, which is not a peptide. Semax covers more ground than anything else in the category: it takes the top neuroprotection subrating, plus strong neuroplasticity, TBI and geriatric scores, and ties for the top focus and cognition score before placing second here on the overall tiebreak. Its strongest human evidence is post-stroke recovery rather than healthy-adult cognition, so the healthy-user case is mechanistically reasonable rather than proven.
- Semax or bromantane?
- They tie at 7.0–7.5/10 on overall BioHarmony score and answer different questions. Bromantane is for output: strong energy and stress-resilience scores, and the largest clinical dataset in this category at 728 outpatients. Semax is for the brain itself: neuroprotection, neuroplasticity and cognition, on a BDNF mechanism, and on this page's focus-and-cognition-ranked order, semax places second while bromantane places fourth, both well up from the old memory-ranked order where bromantane sat ninth. If you want to get through a demanding stretch, bromantane. If you are trying to protect or rebuild cognitive function, semax.
- Why does methylene blue rank first here if its overall BioHarmony score isn't the highest?
- Because this page is ranked by the live Focus and cognition subrating, not the overall score. Methylene blue holds the top score in the category at 6.5–7.0/10, and that rests on human fMRI from a single 280 mg dose rather than on a cognition outcome trial. Its overall BioHarmony score is 6.0–6.5/10, well below bromantane and semax at 7.0–7.5/10 and 7.0–7.5/10, because it is also a confirmed MAO-A inhibitor with an FDA safety communication about combining it with serotonergic psychiatric medication, and it carries a G6PD contraindication. The cognition-focus number measures the strength of the signal; the overall score adds what it costs you to act on it.
- Is dihexa dangerous?
- The concern is mechanistic rather than measured, and nobody can tell you more than that, which is itself the problem. Dihexa potentiates hepatocyte growth factor signalling at c-Met, a pathway that oncology has developed approved inhibitors against because it drives cancer invasion and metastasis. There are zero human trials, no human pharmacokinetics, and FDA notes the absence of human exposure data. It carries an overall BioHarmony score of 4.0–4.5/10, the lowest on this page, and is the only member of this ranking marked caution. Dihexa ties three well-studied racetams on the focus-and-cognition score, 5.0–5.5/10, but that low overall is exactly what drops it to ninth in that tie rather than letting the shared score carry it higher: a strong rodent signal shared with cheap, safe compounds is a reason for caution, not confidence.
- Do the racetams actually work?
- Mildly, and mostly in populations that are not healthy adults. Piracetam, aniracetam and oxiracetam all post the same focus and cognition score, 5.0–5.5/10, mid-table on this page, and the independent Cochrane position on the class in cognitive impairment is unconvinced. Piracetam's real clinical evidence is in cortical myoclonus and post-stroke aphasia. They are cheap and safe, which is why all three still rank ahead of higher-overall members like selank and cerebrolysin on focus and cognition specifically, despite the modest effect.
- Which one helps with anxiety?
- Selank, at 6.5/10, a full point clear of everything else on the page. It was tested against a benzodiazepine comparator in 62 patients and produced similar anxiolytic effects without the sedation, amnesia or dependence profile. Bromantane is second at 5.7/10 and aniracetam third at 5.0/10. All the selank evidence is Russian, with no Western replication and no FDA approval.
- Is cerebrolysin worth the money?
- It costs $500 to $900 a month, ten times more than anything else here, and the answer depends entirely on whether you are recovering from a stroke or brain injury. It has the largest human trial base in this category, the maker-funded rehabilitation trials are positive, and two independent Cochrane reviews do not confirm them, one finding more non-fatal serious adverse events. For healthy cognitive enhancement the data is simply not there.
- Which of these have no human evidence at all?
- Dihexa, P21 and PE-22-28. Everything known about all three comes from mice, rats or cell culture. P21's core mechanism failed its one independent in-vivo replication. Dihexa's rodent signal ties three well-studied racetams on this page's ranked score anyway, which is exactly why the overall score, not the ranked number, is where the zero-human-trials caution belongs. Pinealon is a fourth near-case: its only human data is a single uncontrolled cohort of 32 from the lab that invented it. Nothing in those four rows should be read as a human result.
- Can I stack these?
- People do, and none of the reports in this category can tell you what a stack does, because no combination here has been tested in a human trial. The one combination to actively avoid is methylene blue with any serotonergic drug or supplement, because the MAO-A inhibition is real and FDA has warned about it. Add one thing at a time with a defined outcome, or you will not know which one did anything.
- How often does this ranking change?
- Whenever any member's focus and cognition subrating changes, or when a tied overall score shifts. The order is the live Focus and cognition subrating pulled from each report at render time, and a rescoring reorders the page that night. Expect this category to move slowly: most of the literature is decades old and finished. The likeliest mover is dihexa, whose focus and cognition score rests entirely on rodent data, a single human trial, for or against, would move it and the tiebreak sharply.
Evidence Sources
- Treatment of asthenic disorders in patients with psychoautonomic syndrome 728 outpatients, 50 to 100 mg a day for 28 days; 76.0 percent CGI-S responder rate. The flagship bromantane trial and the largest clinical dataset in this category, and it is open-label.
- Ladasten in the treatment of neurasthenia: placebo-controlled comparative study The only published placebo-controlled bromantane trial. The controlled anchor beneath the larger open-label result.
- Effects of ladasten on dopaminergic neurotransmission and hippocampal synaptic plasticity in rats The most rigorous mechanistic work on bromantane, linking dopaminergic transmission to hippocampal plasticity.
- Cytosine demethylation in the tyrosine hydroxylase gene promoter under the action of ladasten Epigenetic activation of tyrosine hydroxylase transcription. The mechanism behind bromantane building dopamine synthesis capacity rather than releasing stores.
- Activation of gene expression for neurotrophins and MAP kinases by ladasten BDNF and NGF mRNA upregulation, with pERK1/2 up 70 percent at 30 minutes. The neurotrophic half of bromantane's mechanism.
- Multi-laboratory European and Australian surveillance of illicit nootropics Bromantane detected in two illicit samples, one at 33.2 mg per unit. Direct evidence that the gray-market channel in this category carries undeclared active compounds.
- Semax affects BDNF and TrkB expression in rat hippocampus The mechanistic anchor for semax: BDNF and TrkB upregulation in the hippocampus, plus a conditioned-learning signal. Behind its category-leading neuroplasticity subrating of 6.0/10.
- Semax in combination with rehabilitation in post-ischemic stroke patients 110 post-stroke patients; BDNF and rehabilitation outcome direction. The strongest accessible human evidence for semax, and it is a recovery population rather than healthy adults.
- Effects of Semax on human attention and memory Small human nootropic-activity signal in healthy subjects. The only direct healthy-adult cognition data semax has, and it is small and old.
- Efficacy and possible mechanisms of Selank in generalized anxiety disorders and neurasthenia 62 patients; anxiolytic effects similar to medazepam, plus antiasthenic and psychostimulant effects. The anchor for selank's 6.5/10 anxiety subrating, the highest in this category.
- Comparison of Selank and phenazepam in anxiety disorders 60 anxiety-spectrum patients; anxiolytic plus mild nootropic effect against a benzodiazepine comparator. The second human signal behind selank's third place.
- Peptide-based anxiolytics: molecular aspects of Selank biological activity GABA-receptor allosteric modulation as the proposed mechanism. Explains why selank produces calm without the sedation and dependence profile of a benzodiazepine.
- Presence of piracetam in cognitive enhancement dietary supplements Analysis found piracetam, an unapproved drug, present in supplements sold in the US. The sourcing problem in this category is documented, not theoretical.
- Piracetam for dementia or cognitive impairment (Cochrane review) Independent review of the racetam-class evidence in cognitive impairment; unconvinced. The reason all four racetams sit mid-table rather than higher.
- Treatment of acute ischemic stroke with piracetam (PASS) Large randomized acute-stroke trial. The clinical setting where piracetam has real evidence, and it is not healthy-adult cognition.
- Piracetam and piracetam-like drugs: from basic science to novel clinical applications The broad racetam-class review, and the single main evidence anchor phenylpiracetam has. Four members of this ranking rest partly on this one paper.
- Aniracetam reduces glutamate receptor desensitization and slows the decay of fast excitatory synaptic currents The mechanistic basis of the AMPA-modulating racetam arm, measured in hippocampus. Why this class acts the same day and does not compound.
- Senile dementia of the Alzheimer type treated with aniracetam The clinical trial behind aniracetam's human evidence. A cognitive-decline population, not healthy users, and nearly forty years old.
- Anxiolytic effects of aniracetam in three mouse models of anxiety Anxiolytic effects across three separate models. The basis for aniracetam's 5.0/10 anxiety subrating, third in this category and the only racetam that places in that row.
- Nootropic drugs positively modulate AMPA-sensitive glutamate receptors in neuronal cultures The AMPA-modulation evidence oxiracetam's mechanism rests on. Cell culture, not a clinical outcome.
- CASTA: the largest acute ischemic stroke trial of cerebrolysin 1,070 patients; neutral on its primary global outcome at 90 days. The largest single trial in this whole ranking, and it was negative.
- Cerebrolysin for acute ischaemic stroke (Cochrane review) Seven RCTs, 1,773 participants; no benefit on death and more non-fatal serious adverse events on cerebrolysin. The independent finding that holds it at eighth.
- Cerebrolysin for vascular dementia (Cochrane review) Six RCTs, 597 participants; cognitive benefit rated very low quality and all included studies industry-funded. The second independent review that does not confirm the positive results.
- CARS: cerebrolysin with standardized rehabilitation after stroke Large arm-recovery effect at day 90 when paired with physical therapy. The strongest positive cerebrolysin result, and it is maker-funded.
- Multimodal randomized functional MR imaging of methylene blue in the human brain 26 participants; one 280 mg oral dose increased task-related brain activity. The human anchor for methylene blue's category-leading 6.8/10 cognition subrating, and it is imaging rather than an outcome.
- Methylene blue and serotonin toxicity: inhibition of MAO-A confirms a theoretical prediction Mechanistic confirmation that methylene blue inhibits MAO-A. The reason the serotonergic-medication interaction on the top-scoring cognition member is real rather than folklore.
- FDA Drug Safety Communication: serious CNS reactions with methylene blue and serotonergic psychiatric medications The regulatory warning behind the interaction. Applies to the oral microdose as well as the injectable indication.
- Tau-aggregation inhibitor therapy in mild or moderate Alzheimer's disease: Phase 3 trial The large LMTX methylthioninium-derivative Phase 3. The most serious clinical test of this chemistry against a cognitive endpoint.
- Modafinil for cognitive neuroenhancement in healthy non-sleep-deprived subjects: systematic review Small and state-dependent cognitive effects in rested healthy adults. The finding that keeps modafinil's overall well below its focus and cognition subrating, even though modafinil places third on this cognition-focus-ranked page.
- Effects of modafinil on dopamine and dopamine transporters in the male human brain Human PET study supporting dopamine-transporter engagement. Modafinil's mechanism, which is catecholaminergic rather than neurotrophic.
- A neurotrophic peptidergic compound enhances learning, memory and neurogenesis in mice The founding P21 paper: peripherally administered peptide enhanced learning and memory and induced dentate-gyrus neurogenesis in normal adult mice.
- First independent in-vivo test of P021 in Cdkl5-knockout mice P021 rescued cells in vitro but failed to raise BDNF or improve neuroanatomy in vivo. The failed independent replication of P21's core mechanism.
- Spadin, a sortilin-derived peptide, as a new antidepressant Blocks TREK-1 at about 10 nanomolar, raises serotonin neuron firing, and produced antidepressant responses across five behavioural tests. The mechanism PE-22-28 was engineered from.
- PE-22-28 inhibits human TREK-1 with sub-nanomolar affinity About 0.12 nanomolar against 40 to 60 for spadin, with reduced immobility in the forced-swim test and neurogenesis after four days. Every result is rodent or cell.
- The TREK-1 blocker spadin potentiates insulin secretion in pancreatic beta cells A documented metabolic off-target. TREK-1 is expressed outside the brain, which is the uncharacterized risk in a systemic blocker with no human data.
- Evaluation of metabolically stabilized angiotensin IV analogs as procognitive agents The main rodent and cell evidence behind dihexa's procognitive claim. Behind its 5.0–5.5/10 focus and cognition score, tied with three racetams, from the member with the lowest overall BioHarmony score on the page, 4.0–4.5/10, which is what drops it to ninth in that tie.
- Dihexa rescues cognitive impairment and recovers memory in the APP/PS1 mouse via PI3K/AKT signalling Independent mouse memory-rescue result in an Alzheimer's model. The strongest independent dihexa signal, and it is still a mouse.
- Drug development of MET inhibitors in oncology Frames c-Met and HGF as a cancer invasion and metastasis pathway with drugs developed to block it. Dihexa is designed to potentiate the same pathway, which is why it is the only member scored caution.
- Independent biophysics of the EDR tripeptide and DNA interaction NMR, viscosimetry and molecular dynamics showing pinealon's tripeptide can partly enter the DNA major groove and contact guanine. Independent confirmation of an unusual mechanism.
- Open-label cohort of 32 polymorbid patients on pinealon Improved adaptive capacity and slowed biological-age markers, plus a prooxidant signal and lower CD34 progenitor markers. The only human data pinealon has, uncontrolled and from the originating lab.
- Pinealon restricts reactive-oxygen-species accumulation in cultured neurons Dose-dependent reduction in ROS accumulation and necrotic cell death under oxidative stress. The cell-level basis for pinealon's neuroprotection score.
- FDA: certain bulk drug substances for use in compounding that may present significant safety risks The regulatory listing that covers several members here, and which states that human exposure data and key safety information are lacking for dihexa.
Glossary
Quick reference for the medical and technical terms used in this comparison.
- Nootropic Cognitive enhancer
- A compound taken to improve cognition, memory, mood or brain resilience. In this ranking it means synthetic compounds only; botanicals and nutrients are outside the boundary.
- BDNF Brain-Derived Neurotrophic Factor
- The growth factor behind synaptic plasticity and new neuron survival. Semax, selank, bromantane and P21 all act through it, and it is the most-cited mechanism on this page.
- TrkB Tropomyosin receptor kinase B
- The receptor BDNF binds to. Semax upregulates both halves of that pair in the hippocampus, which is the basis of its neuroplasticity score.
- AMPA receptor Glutamate receptor subtype
- The fast excitatory receptor the racetams modulate. Piracetam defined a new allosteric binding site on it, and aniracetam slows the decay of currents through it.
- Actoprotector A Soviet drug class with no Western equivalent
- A compound that raises physical and mental work capacity under stress without stimulant rebound. Bromantane is the prototype, and the class is why it does not feel like caffeine.
- Eugeroic Wakefulness-promoting agent
- A drug that produces alertness without classical stimulant action. Modafinil is the one in this ranking, approved for narcolepsy rather than for cognition.
- TREK-1 Two-pore potassium channel
- The channel PE-22-28 blocks. Deleting it makes mice resistant to depression, which is what put it on the map as an antidepressant target.
- c-Met Hepatocyte growth factor receptor
- The receptor dihexa potentiates, and a cancer invasion and metastasis pathway that oncology has built approved inhibitors against. The reason dihexa is scored caution.
- MAO-A Monoamine Oxidase A
- The enzyme that breaks down serotonin. Methylene blue inhibits it, which is why combining it with serotonergic medication carries an FDA warning.
- CGI-S Clinical Global Impression, Severity
- A clinician-rated severity scale, and the endpoint in bromantane's 728-patient flagship trial where 76 percent were rated responders.
- Asthenic syndrome Clinical fatigue and depletion
- The Russian diagnostic category bromantane and selank were both developed for. It maps loosely onto what a Western reader would call burnout.
- COA Certificate of Analysis
- The third-party HPLC and mass-spec report establishing what is actually in a research-chemical product. Twelve of the fourteen members here require one, and no quoted price includes it.
First on focus and cognition, the metric this page ranks on, and the clearest win on the page. Methylene blue holds the top score at 6.5–7.0/10, plus this category's energy, depression, longevity and healthspan wins, more use-case wins than any other member. It ranks here despite an overall BioHarmony score of only 6.0–6.5/10, well below bromantane and semax at 7.0–7.5/10 and 7.0–7.5/10: the strong evidence behind its cognition number is medical rather than nootropic, an FDA-approved methemoglobinemia antidote whose healthy-user case rests on human fMRI showing increased task-related activity from a single dose (Rodriguez 2016). It is also a real MAO-A inhibitor (Ramsay 2007), which is the interaction to respect.