Nootropic Peptides and Smart Drugs Ranked by Evidence
Which nootropic peptide or compound is worth taking?
Bromantane and semax tie at 7.1, and they are the only two in this category scored strong recommend. Selank is third at 6.9 if anxiety rather than focus is the problem. Below them the list splits cleanly into compounds with human evidence and compounds with rodent evidence, and the bottom three have no human trials at all.
- Bromantane 7.1 and semax 7.1 lead. Both are Russian, neither is approved in the West, and both are bought as research chemicals.
- The two highest single use-case scores on the page belong to methylene blue: cognition at 6.8 and memory at 6.5. It ranks ninth.
- Three members have zero human trials of any kind: P21, PE-22-28 and dihexa. They occupy the bottom three positions.
- The compound with the largest human trial base is cerebrolysin, and two independent Cochrane reviews do not confirm the maker-funded results.
- Cost spans $8 to $900 a month. The most expensive member by a factor of ten is cerebrolysin, and it ranks eighth.
- The ranking is the live score. When a member's score moves, this page moves with it.
The Ranking
14 interventions ranked by live BioHarmony score.
Rank 1: Bromantane (Ladasten)
7.1 / 10 🛡 Strong RecommendRussian adamantane actoprotector. Not approved in the West. BioHarmony 7.1, strong recommend.
Rank 1: Semax
7.1 / 10 🛡 Strong RecommendTied for first, and the broadest performer in the category. Semax takes neuroprotection at 6.5 outright, neuroplasticity at 6.0, TBI at 4.5, nerve regeneration at 4.5 and geriatric at 5.0, and it is second on cognition and memory. The mechanism has a coherent story behind it: 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 bromantane when the target is a brain that needs repairing rather than a day that needs powering.
ACTH 4-7 plus PGP heptapeptide. Approved in Russia only. BioHarmony 7.1, strong recommend.
Rank 3: Selank
6.9 / 10 Worth tryingThird, and the answer to a different question than the two above it. Selank is the anxiolytic of the group: it takes anxiety at 6.5, a full point clear of anything else, and ties for stress resilience at 6.0 and mood at 5.5. 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). Pick it over semax 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. BioHarmony 6.9, worth trying.
Rank 4: Piracetam (Nootropil)
6.5 / 10 Worth tryingFourth, and the one whose rank most overstates what you will feel. 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 scores cognition 5.0 and memory 5.0, solidly mid-table, and 1.5 on almost everything else. It ranks fourth on 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 you.
The prototype racetam. A licensed medicine in parts of Europe. BioHarmony 6.5, worth trying.
Rank 5: Pinealon (Glu-Asp-Arg)
6.4 / 10 Worth tryingFifth, and the thinnest human file of any member above the bottom three. 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). It scores 2.5 for cognition and 2.0 for memory, near the bottom of both. Interesting biology, unproven in people.
Khavinson tripeptide (Glu-Asp-Arg). No registered trial anywhere. BioHarmony 6.4, worth trying.
Rank 5: Oxiracetam
6.4 / 10 Worth tryingTied for fifth, and the racetam with the clearest lane. Oxiracetam leans cholinergic and mildly stimulating, and it is the only racetam other than phenylpiracetam with a meaningful energy score at 5.0. It scores cognition 5.0 and memory 5.0, the same as its two siblings, 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. BioHarmony 6.4, worth trying.
Rank 5: Aniracetam
6.4 / 10 Worth tryingTied for fifth, and the one to pick if anxiety is part of the picture. It is the only racetam with a real anxiety score at 5.0, third in the whole category behind selank and bromantane, and 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. BioHarmony 6.4, worth trying.
Rank 8: Cerebrolysin
6.3 / 10 Worth tryingEighth, with 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. BioHarmony 6.3, worth trying.
Rank 9: Methylene Blue
6.1 / 10 Worth tryingNinth on the composite and first on the two use cases most readers came for. Methylene blue holds the top cognition score at 6.8 and the top memory score at 6.5, plus energy 6.8, depression 5.5, longevity 6.0 and healthspan 6.5, more use-case wins than any other member. It ranks ninth because the strong evidence is medical rather than nootropic: it is an FDA-approved methemoglobinemia antidote, and the 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.
FDA-approved redox drug used off-label at microdose. BioHarmony 6.1, worth trying.
Rank 10: Modafinil
5.9 / 10 Worth tryingTenth, and the only prescription member. Modafinil takes energy at 7.0, the highest single score anywhere on this page, plus reaction time at 6.5 and flow state at 5.5. Its sleepiness data in narcolepsy is strong, and that is the indication. In rested healthy adults the cognitive-enhancement effect is small and state-dependent (Battleday and Brem 2015), which is the finding that keeps it at 5.9 rather than in the top three. Pick it for a specific depleted day rather than as a daily cognitive base, and know it is Schedule IV.
Prescription Schedule IV eugeroic. BioHarmony 5.9, worth trying.
Rank 11: Phenylpiracetam (Phenotropil)
5.5 / 10 🤷 NeutralEleventh, and the sharpest short-term tool in the category. It takes reaction time second at 5.0 and energy fourth at 5.3, and it is the racetam people actually feel. What it does not have is durability: the subjective effect fades fast with repeated use, its memory score is 1.5, the lowest of the four racetams, and the direct clinical evidence is one broad class review (Malykh 2010). It is banned by WADA. Pick it for an occasional morning where focus and physical drive have to arrive together, and not as a base.
The most stimulating racetam. Banned in tested sport. BioHarmony 5.5, neutral.
Rank 12: P21 (P021)
5.0 / 10 🤷 NeutralTwelfth, and the first of the three members with no human data at all. 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). That is the cleanest rodent neurogenesis dataset on this page. Three things hold it at 5.0: 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. BioHarmony 5.0, neutral.
Rank 13: PE-22-28
4.9 / 10 🤷 NeutralThirteenth, with one of the cleanest mechanisms in the gray-market peptide world and nothing behind it in humans. 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). It is the only member here whose primary use case is depression, where it scores 2.5. Two problems keep it at 4.9: 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. BioHarmony 4.9, neutral.
Rank 14: Dihexa
4.4 / 10 CautionLast, and the only member scored caution rather than neutral. Dihexa is an angiotensin IV analogue that in rodents drives hippocampal synaptogenesis and rescues memory (Benoist 2011, McCoy 2013, Sun 2021), and it still scores 5.0 for cognition and 5.5 for memory, third-highest memory score on the page, which is why people want it. The caution is the mechanism: it potentiates hepatocyte growth factor signaling at c-Met, and c-Met is 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.
Angiotensin IV analogue acting on c-Met. Zero human trials. BioHarmony 4.4, caution.
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, semax 6.5, modafinil 6.5, bromantane 5.8, then four compounds bunched at 5.0. The 6.8 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, 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 and aniracetam at 5.0. Selank is also the only member whose human evidence is specifically anxiety rather than cognition, tested against a benzodiazepine comparator. |
| Mood | Selank 5.5 | Modafinil 5.5 | A four-way tie at 5.5 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. |
| Energy | Modafinil 7.0 | Methylene Blue 6.8 | The highest single score anywhere on this page, and it belongs to the member ranked tenth. Modafinil's 7.0 is real and it is why people take it. Bromantane at 6.2 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 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, 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. |
| 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 sits at 2.5 or under. If measurable speed rather than subjective clarity is the goal, this row is a short list of two. |
| TBI | Semax 4.5 | Cerebrolysin 4.3 | The lowest-scoring winner in the table, and honestly so. Semax 4.5 and cerebrolysin 4.3 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
Bromantane (Ladasten)
- Efficacy 3.8
- Breadth 3.0
- Evidence 3.3
- Speed 4.0
- Durability 3.9
- Bioindividuality 3.5
- Safety Risk 1.8
- Side Effects 1.7
- Cost 2.5
- Effort 1.9
- Opportunity Cost 1.6
- Dependency 1.4
- Reversibility 1.5
- Energy
- Stress Resilience
- Cognition Focus
- Anxiety
Russian adamantane actoprotector. Not approved in the West. BioHarmony 7.1, strong recommend.
Semax
- Efficacy 3.6
- Breadth 3.8
- Evidence 3.8
- Speed 4.0
- Durability 2.5
- Bioindividuality 2.8
- Safety Risk 1.8
- Side Effects 1.8
- Cost 2.0
- Effort 2.0
- Opportunity Cost 1.8
- Dependency 1.5
- Reversibility 1.2
- Cognition Focus
- Neuroprotection
- Memory
- Neuroplasticity
ACTH 4-7 plus PGP heptapeptide. Approved in Russia only. BioHarmony 7.1, strong recommend.
Selank
- Efficacy 3.7
- Breadth 3.5
- Evidence 3.4
- Speed 4.5
- Durability 2.5
- Bioindividuality 3.5
- Safety Risk 1.8
- Side Effects 1.8
- Cost 2.0
- Effort 2.0
- Opportunity Cost 2.5
- Dependency 1.8
- Reversibility 1.5
- Anxiety
- Stress Resilience
- Mood
- Immune Function
Tuftsin-derived anxiolytic heptapeptide. No Western approval. BioHarmony 6.9, worth trying.
Piracetam (Nootropil)
- Efficacy 2.8
- Breadth 2.9
- Evidence 3.6
- Speed 1.8
- Durability 2.1
- Bioindividuality 2.5
- Safety Risk 1.5
- Side Effects 1.4
- Cost 2.0
- Effort 1.6
- Opportunity Cost 2.0
- Dependency 1.2
- Reversibility 1.3
- Recovery Repair
- Cognition Focus
- Memory
- Pediatric
The prototype racetam. A licensed medicine in parts of Europe. BioHarmony 6.5, worth trying.
Pinealon (Glu-Asp-Arg)
- Efficacy 3.4
- Breadth 2.8
- Evidence 3.2
- Speed 3.0
- Durability 2.6
- Bioindividuality 3.0
- Safety Risk 1.6
- Side Effects 1.6
- Cost 2.6
- Effort 3.2
- Opportunity Cost 2.4
- Dependency 1.6
- Reversibility 1.6
- Neuroprotection
- Cognition Focus
- Neuroplasticity
- Antioxidant
Khavinson tripeptide (Glu-Asp-Arg). No registered trial anywhere. BioHarmony 6.4, worth trying.
Oxiracetam
- Efficacy 3.0
- Breadth 3.0
- Evidence 3.3
- Speed 2.7
- Durability 2.2
- Bioindividuality 2.8
- Safety Risk 1.6
- Side Effects 1.6
- Cost 2.6
- Effort 1.8
- Opportunity Cost 2.2
- Dependency 1.5
- Reversibility 1.4
- Cognition Focus
- Memory
- Energy
- Cardiovascular
Mildly stimulating cholinergic-leaning racetam. BioHarmony 6.4, worth trying.
Aniracetam
- Efficacy 2.9
- Breadth 3.0
- Evidence 3.6
- Speed 2.6
- Durability 1.8
- Bioindividuality 2.6
- Safety Risk 1.6
- Side Effects 1.6
- Cost 2.4
- Effort 1.6
- Opportunity Cost 2.2
- Dependency 1.4
- Reversibility 1.5
- Cognition Focus
- Memory
- Anxiety
- Cardiovascular
Fat-soluble racetam with an anxiolytic lean. BioHarmony 6.4, worth trying.
Cerebrolysin
- Efficacy 3.5
- Breadth 3.8
- Evidence 3.6
- Speed 3.2
- Durability 2.8
- Bioindividuality 3.2
- Safety Risk 2.0
- Side Effects 2.3
- Cost 3.0
- Effort 4.0
- Opportunity Cost 3.0
- Dependency 1.8
- Reversibility 1.6
- Neuroprotection
- TBI
- Cognition Focus
- Memory
Porcine brain-derived peptide mixture, IV or IM. Approved outside the US. BioHarmony 6.3, worth trying.
Methylene Blue
- Efficacy 4.0
- Breadth 3.5
- Evidence 4.2
- Speed 4.5
- Durability 3.0
- Bioindividuality 2.4
- Safety Risk 4.0
- Side Effects 2.2
- Cost 1.8
- Effort 1.3
- Opportunity Cost 1.4
- Dependency 1.2
- Reversibility 1.5
- Mitochondrial
- Cognition Focus
- Energy
- Memory
FDA-approved redox drug used off-label at microdose. BioHarmony 6.1, worth trying.
Modafinil
- Efficacy 4.5
- Breadth 3.6
- Evidence 4.3
- Speed 4.5
- Durability 1.5
- Bioindividuality 3.4
- Safety Risk 4.0
- Side Effects 2.6
- Cost 2.5
- Effort 1.3
- Opportunity Cost 2.5
- Dependency 2.0
- Reversibility 1.5
- Energy
- Cognition Focus
- Reaction Time
- Mood
Prescription Schedule IV eugeroic. BioHarmony 5.9, worth trying.
Phenylpiracetam (Phenotropil)
- Efficacy 3.5
- Breadth 3.0
- Evidence 3.0
- Speed 4.0
- Durability 2.2
- Bioindividuality 2.8
- Safety Risk 2.3
- Side Effects 2.6
- Cost 2.5
- Effort 1.6
- Opportunity Cost 2.2
- Dependency 3.0
- Reversibility 1.8
- Energy
- Cognition Focus
- Reaction Time
- Cold Heat Tolerance
The most stimulating racetam. Banned in tested sport. BioHarmony 5.5, neutral.
P21 (P021)
- Efficacy 3.0
- Breadth 2.8
- Evidence 1.5
- Speed 2.5
- Durability 2.5
- Bioindividuality 2.5
- Safety Risk 2.0
- Side Effects 1.9
- Cost 3.0
- Effort 2.8
- Opportunity Cost 3.2
- Dependency 1.6
- Reversibility 2.0
- Cognition Focus
- Memory
- Neuroprotection
- Neuroplasticity
CNTF-derived peptidomimetic. Zero human trials. BioHarmony 5.0, neutral.
PE-22-28
- Efficacy 3.0
- Breadth 2.5
- Evidence 1.8
- Speed 3.5
- Durability 2.2
- Bioindividuality 2.5
- Safety Risk 2.3
- Side Effects 2.2
- Cost 3.0
- Effort 2.8
- Opportunity Cost 3.0
- Dependency 1.8
- Reversibility 2.0
- Depression
- Mood
- Neuroprotection
- Neuroplasticity
Spadin analogue and TREK-1 blocker. Zero human trials. BioHarmony 4.9, neutral.
Dihexa
- Efficacy 3.0
- Breadth 2.0
- Evidence 2.3
- Speed 3.5
- Durability 2.5
- Bioindividuality 2.5
- Safety Risk 3.3
- Side Effects 2.2
- Cost 2.9
- Effort 2.1
- Opportunity Cost 2.5
- Dependency 1.8
- Reversibility 2.9
- Memory
- Cognition Focus
- Neuroplasticity
- Neuroprotection
Angiotensin IV analogue acting on c-Met. Zero human trials. BioHarmony 4.4, caution.
Cost Comparison
| Intervention | Monthly Cost | Notes |
|---|---|---|
| Cerebrolysin | $500 to $900 | ESTIMATE, priced 2026-09-08, 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 | ESTIMATE, priced 2026-09-08, 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 | ESTIMATE, priced 2026-09-08, 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 | ESTIMATE, priced 2026-09-08, 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 | ESTIMATE, priced 2026-09-08, 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 | ESTIMATE and UNVERIFIED, priced 2026-09-08, 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 | ESTIMATE, priced 2026-09-08, 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 | ESTIMATE, priced 2026-09-08, 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 | ESTIMATE and UNVERIFIED, priced 2026-09-08, 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 | ESTIMATE, priced 2026-09-08, 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 | ESTIMATE and UNVERIFIED, priced 2026-09-08, 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 eighth | 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 and stress resilience 6.0 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, 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 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 and reaction time 6.5, 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 and energy 5.3, the only member other than modafinil that does both. Its memory score is 1.5 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 and healthspan 4.0, the highest geriatric score on the page, and its mechanism is neurotrophic rather than stimulant. Methylene blue's 6.5 healthspan and 6.0 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 and cerebrolysin at 4.3 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, the top score in that row. The one to avoid here is dihexa, which sits third at 5.5 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
- the live BioHarmony overall score
- 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.
The order on this page is the live BioHarmony overall score, read from each member's report when the page renders. It is not an editorial ranking, and nothing about it is fixed. When a member's score changes, the row moves that night.
Ties are shown as ties. Bromantane and semax sit at 7.1, and pinealon, oxiracetam and aniracetam all sit at 6.4. Within a tie the order is by upside total, the sum of the benefit dimensions before risk is subtracted. That is a tiebreak, not a ranking: treat tied members as equivalent.
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 composite and the use-case table together, because they disagree more here than in most categories. Methylene blue ranks ninth and wins six use cases. Modafinil ranks tenth and holds the highest single score on the page. Dihexa ranks last and holds the third-highest memory score. A subrating measures how strong the signal is for that one goal; the composite adds evidence quality, safety, access, cost and practicality on top. When those two numbers disagree, the disagreement is the finding.
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: P21, PE-22-28 and dihexa. 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.
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 fourteenth 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. Bromantane, joint first at 7.1, costs $12 to $30 a month. Dihexa, last at 4.4, costs $30 to $60. Piracetam is the cheapest line on the page and ranks fourth. There is no relationship between what a member costs and where it lands.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 the ranking. Cerebrolysin has the largest human trial base by a wide margin and sits eighth. Modafinil has the strongest regulatory evidence and sits tenth. Bromantane, joint first, rests on a single-country, single-funder literature whose flagship trial was open-label.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 ranks eighth because two independent Cochrane reviews do not confirm the maker-funded results (Ziganshina 2023, Cui 2019). Modafinil ranks tenth because its strong data is about sleepiness in narcolepsy and its healthy-adult cognitive effect is small and state-dependent (Battleday and Brem 2015). A negative or narrow result is information, and it counts.At the other end, three members have no human data at all. 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). That is the difference between a promising mechanism and a result.
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Editorial Verdict
Two members are genuinely recommendable and they answer different questions. Bromantane is for output: a long clean lift with the largest clinical dataset in the category behind it. Semax is for the brain itself: the broadest coverage on the page, with a coherent BDNF mechanism and human evidence in stroke recovery. 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. Methylene blue has the best individual scores on the page and the most serious interaction profile, so it is the one to take to a prescriber first rather than the one to try first.The bottom three are not worth sourcing. P21, PE-22-28 and dihexa have zero human trials between them, dihexa runs through a cancer pathway, and a strong rodent memory score is a reason to follow a literature rather than 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 BioHarmony overall score for each member, resolved when the page loads, so a rescoring of any one report reorders the page that night without an editorial pass.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 movers are the three bottom members, and they would move upward sharply if any of them entered human trials, because access and evidence quality would rise together. The gap between first and last is currently 2.7 points, the widest of any BioHarmony category ranking so far.
Frequently Asked Questions
- What is the best nootropic peptide?
- Semax, at a BioHarmony 7.1, tied with bromantane, which is not a peptide. Semax covers more ground than anything else in the category: it takes neuroprotection at 6.5, neuroplasticity at 6.0, TBI at 4.5 and geriatric at 5.0, and places second on cognition and memory. 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 7.1 and answer different questions. Bromantane is for output: energy 6.2, stress resilience 6.0, and the largest clinical dataset in this category at 728 outpatients. Semax is for the brain itself: neuroprotection, neuroplasticity and memory, on a BDNF mechanism. 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 ninth if it wins the most use cases?
- Because the score weighs more than the size of the signal. Methylene blue holds the top cognition score at 6.8 and the top memory score at 6.5, and those rest on human fMRI from a single 280 mg dose rather than on a cognition outcome trial. 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. Those pull the composite down to 6.1.
- 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 scores 4.4 and is the only member of this ranking marked caution.
- Do the racetams actually work?
- Mildly, and mostly in populations that are not healthy adults. Piracetam, aniracetam and oxiracetam all score 5.0 for cognition and 5.0 for memory, which is mid-table, 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 they rank fourth and fifth despite the modest effect.
- Which one helps with anxiety?
- Selank, at 6.5, 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 and aniracetam third at 5.0. 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?
- P21, PE-22-28 and dihexa, and they occupy the bottom three positions. Everything known about all three comes from mice, rats or cell culture. P21's core mechanism failed its one independent in-vivo replication. 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 score changes. The order is the live BioHarmony overall 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, and the likeliest movers are the bottom three, which would rise sharply if any of them entered human trials.
Evidence Sources
- Observational Treatment of asthenic disorders in patients with psychoautonomic syndrome (2010) 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.
- RCT Ladasten in the treatment of neurasthenia: placebo-controlled comparative study (2009) The only published placebo-controlled bromantane trial. The controlled anchor beneath the larger open-label result.
- Animal study Effects of ladasten on dopaminergic neurotransmission and hippocampal synaptic plasticity in rats (2007) The most rigorous mechanistic work on bromantane, linking dopaminergic transmission to hippocampal plasticity.
- Animal study Cytosine demethylation in the tyrosine hydroxylase gene promoter under the action of ladasten (2006) Epigenetic activation of tyrosine hydroxylase transcription. The mechanism behind bromantane building dopamine synthesis capacity rather than releasing stores.
- Animal study Activation of gene expression for neurotrophins and MAP kinases by ladasten (2012) BDNF and NGF mRNA upregulation, with pERK1/2 up 70 percent at 30 minutes. The neurotrophic half of bromantane's mechanism.
- Observational Multi-laboratory European and Australian surveillance of illicit nootropics (2025) 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.
- Animal study Semax affects BDNF and TrkB expression in rat hippocampus (2006) 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.
- RCT Semax in combination with rehabilitation in post-ischemic stroke patients (2018) 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.
- RCT Effects of Semax on human attention and memory (1996) Small human nootropic-activity signal in healthy subjects. The only direct healthy-adult cognition data semax has, and it is small and old.
- RCT Efficacy and possible mechanisms of Selank in generalized anxiety disorders and neurasthenia (2008) 62 patients; anxiolytic effects similar to medazepam, plus antiasthenic and psychostimulant effects. The anchor for selank's 6.5 anxiety subrating, the highest in this category.
- RCT Comparison of Selank and phenazepam in anxiety disorders (2014) 60 anxiety-spectrum patients; anxiolytic plus mild nootropic effect against a benzodiazepine comparator. The second human signal behind selank's third place.
- Systematic review Peptide-based anxiolytics: molecular aspects of Selank biological activity (2018) GABA-receptor allosteric modulation as the proposed mechanism. Explains why selank produces calm without the sedation and dependence profile of a benzodiazepine.
- Observational Presence of piracetam in cognitive enhancement dietary supplements (2020) Analysis found piracetam, an unapproved drug, present in supplements sold in the US. The sourcing problem in this category is documented, not theoretical.
- Systematic review Piracetam for dementia or cognitive impairment (Cochrane review) (2001) Independent review of the racetam-class evidence in cognitive impairment; unconvinced. The reason all four racetams sit mid-table rather than higher.
- RCT Treatment of acute ischemic stroke with piracetam (PASS) (1997) Large randomized acute-stroke trial. The clinical setting where piracetam has real evidence, and it is not healthy-adult cognition.
- Systematic review Piracetam and piracetam-like drugs: from basic science to novel clinical applications (2010) The broad racetam-class review, and the single main evidence anchor phenylpiracetam has. Four members of this ranking rest partly on this one paper.
- Animal study Aniracetam reduces glutamate receptor desensitization and slows the decay of fast excitatory synaptic currents (1991) The mechanistic basis of the AMPA-modulating racetam arm, measured in hippocampus. Why this class acts the same day and does not compound.
- RCT Senile dementia of the Alzheimer type treated with aniracetam (1987) The clinical trial behind aniracetam's human evidence. A cognitive-decline population, not healthy users, and nearly forty years old.
- Animal study Anxiolytic effects of aniracetam in three mouse models of anxiety (2001) Anxiolytic effects across three separate models. The basis for aniracetam's 5.0 anxiety subrating, third in this category and the only racetam that places in that row.
- Animal study Nootropic drugs positively modulate AMPA-sensitive glutamate receptors in neuronal cultures (1992) The AMPA-modulation evidence oxiracetam's mechanism rests on. Cell culture, not a clinical outcome.
- RCT CASTA: the largest acute ischemic stroke trial of cerebrolysin (2012) 1,070 patients; neutral on its primary global outcome at 90 days. The largest single trial in this whole ranking, and it was negative.
- Systematic review Cerebrolysin for acute ischaemic stroke (Cochrane review) (2023) 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.
- Systematic review Cerebrolysin for vascular dementia (Cochrane review) (2019) 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.
- RCT CARS: cerebrolysin with standardized rehabilitation after stroke (2016) Large arm-recovery effect at day 90 when paired with physical therapy. The strongest positive cerebrolysin result, and it is maker-funded.
- RCT Multimodal randomized functional MR imaging of methylene blue in the human brain (2016) 26 participants; one 280 mg oral dose increased task-related brain activity. The human anchor for methylene blue's category-leading 6.8 cognition subrating, and it is imaging rather than an outcome.
- Observational Methylene blue and serotonin toxicity: inhibition of MAO-A confirms a theoretical prediction (2007) 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.
- Regulatory FDA Drug Safety Communication: serious CNS reactions with methylene blue and serotonergic psychiatric medications (2011) The regulatory warning behind the interaction. Applies to the oral microdose as well as the injectable indication.
- RCT Tau-aggregation inhibitor therapy in mild or moderate Alzheimer's disease: Phase 3 trial (2016) The large LMTX methylthioninium-derivative Phase 3. The most serious clinical test of this chemistry against a cognitive endpoint.
- Systematic review Modafinil for cognitive neuroenhancement in healthy non-sleep-deprived subjects: systematic review (2015) Small and state-dependent cognitive effects in rested healthy adults. The finding that keeps modafinil at tenth despite holding the highest energy score on the page.
- RCT Effects of modafinil on dopamine and dopamine transporters in the male human brain (2009) Human PET study supporting dopamine-transporter engagement. Modafinil's mechanism, which is catecholaminergic rather than neurotrophic.
- Animal study A neurotrophic peptidergic compound enhances learning, memory and neurogenesis in mice (2010) The founding P21 paper: peripherally administered peptide enhanced learning and memory and induced dentate-gyrus neurogenesis in normal adult mice.
- Animal study First independent in-vivo test of P021 in Cdkl5-knockout mice (2024) P021 rescued cells in vitro but failed to raise BDNF or improve neuroanatomy in vivo. The failed independent replication of P21's core mechanism.
- Animal study Spadin, a sortilin-derived peptide, as a new antidepressant (2010) 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.
- Animal study PE-22-28 inhibits human TREK-1 with sub-nanomolar affinity (2017) 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.
- Animal study The TREK-1 blocker spadin potentiates insulin secretion in pancreatic beta cells (2016) 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.
- Animal study Evaluation of metabolically stabilized angiotensin IV analogs as procognitive agents (2013) The main rodent and cell evidence behind dihexa's procognitive claim. Behind its 5.5 memory subrating, third-highest on this page from the member ranked last.
- Animal study Dihexa rescues cognitive impairment and recovers memory in the APP/PS1 mouse via PI3K/AKT signalling (2021) Independent mouse memory-rescue result in an Alzheimer's model. The strongest independent dihexa signal, and it is still a mouse.
- Systematic review Drug development of MET inhibitors in oncology (2008) 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.
- Observational Independent biophysics of the EDR tripeptide and DNA interaction (2019) 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.
- Observational Open-label cohort of 32 polymorbid patients on pinealon (2015) 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.
- Animal study Pinealon restricts reactive-oxygen-species accumulation in cultured neurons (2011) Dose-dependent reduction in ROS accumulation and necrotic cell death under oxidative stress. The cell-level basis for pinealon's neuroprotection score.
- Regulatory FDA: certain bulk drug substances for use in compounding that may present significant safety risks (2026) 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.
Tied for first, and the least familiar molecule on the page to a Western reader. 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. It scores energy 6.2 and stress resilience 6.0. The limits are real: the literature is single-country and single-funder, and the manufacturer let the registration lapse in 2018.