Peptide United

Category

Cognitive Enhancement

Neuropeptides and their synthetic analogs studied for effects on memory, attention, BDNF expression, and stress response. Semax and selank are the most characterized in this class, with documented research from Russian clinical programs spanning several decades.

23 peptides in this category

What are nootropic peptides and how do they work?

Nootropic peptides are neuropeptides or their synthetic analogs that influence brain function through neuroplasticity signaling rather than simple neurotransmitter manipulation. Semax works primarily by upregulating BDNF and TrkB receptors, enhancing neuronal growth and synaptic plasticity. Selank modulates enkephalin metabolism and GABA-A receptor activity to reduce anxiety without sedation. Unlike most small-molecule nootropics, these peptides act on growth factor pathways that support long-term neural structure.

Cognitive-acting peptides work through several mechanisms that differ substantially from small-molecule nootropics. Semax is a synthetic heptapeptide analog of ACTH(4-10) that has been shown to upregulate BDNF and its receptor TrkB in the prefrontal cortex and hippocampus, which may account for its reported effects on attention and working memory in human studies. It was developed and has been clinically used in Russia for stroke recovery and cognitive decline. Selank is a synthetic analog of tuftsin (an immunopeptide) with anxiolytic properties, studied for its interaction with GABA-A receptors and its influence on serotonin and dopamine metabolism without the sedation profile of benzodiazepines.

Other neuropeptides in this category include Dihexa, a hepatocyte growth factor modulator that shows potent pro-cognitive effects in rodent models at extremely low doses, and cerebrolysin, a hydrolysate of porcine brain protein used clinically in parts of Europe and Asia for vascular dementia and Alzheimer's disease. The common thread is interaction with neuroplasticity signaling — BDNF, NGF, or synaptic growth factor pathways — rather than simple monoamine manipulation.

Related terms

Compounds

Peptides in this category

BPC-157

Preclinical

Body Protection Compound 157 · PL 14736

BPC-157 is a 15-amino-acid peptide fragment derived from human gastric juice. It is one of the most extensively researched peptides for tissue repair, demonstrating accelerated healing of tendons, ligaments, muscle, bone, and gut lining in animal models. It appears to upregulate growth hormone receptors and promote angiogenesis at injury sites.

C₆₂H₉₈N₁₆O₂₂ · 1419.55 Da

Healing & RecoveryPain & InflammationCognitive Enhancement

Carnosine

Preclinical

Beta-Alanyl-L-Histidine · L-Carnosine

Carnosine is a naturally occurring dipeptide (β-alanyl-L-histidine) found at high concentrations in skeletal muscle and the brain. It acts as a pH buffer in muscle (reducing acidosis during high-intensity exercise), a powerful antioxidant, an antiglycation agent (preventing protein-sugar crosslinking), and a chelator of zinc and copper. Research explores its role in aging, cognitive decline, autism, and exercise performance.

Anti-Aging & LongevityCognitive EnhancementMuscle & Performance

Cerebrolysin

Approved

FPF 1070

Cerebrolysin is a mixture of neuropeptides and neurotrophic factors derived from porcine brain proteins. It mimics the actions of endogenous neurotrophic factors (NGF, BDNF, CNTF), promoting neuronal survival, synaptogenesis, and neuroplasticity. Approved in multiple countries for Alzheimer's disease, stroke recovery, and TBI, clinical trials show improvements in cognitive function, activities of daily living, and brain MRI outcomes.

NeuroprotectionCognitive Enhancement

Cholecystokinin

Preclinical

CCK · CCK-8

Cholecystokinin (CCK) is a peptide hormone produced by duodenal I-cells and neurons in the CNS. It triggers gallbladder contraction, pancreatic enzyme secretion, and potently suppresses appetite via vagal nerve CCK1 receptors. In the brain, CCK neurons modulate anxiety, pain, memory consolidation, and dopamine release. CCK antagonists are studied for anxiety and pain; CCK agonists for obesity and eating disorders.

Fat Loss & MetabolicCognitive Enhancement

Cortexin

Approved

Cortexin polypeptide complex

Cortexin is a polypeptide complex derived from the cerebral cortex of calves or pigs, containing a mixture of neuropeptides and neurotrophic factors. Approved in Russia for stroke, TBI, epilepsy, and cognitive disorders, it exhibits neuroprotective, nootropic, and anticonvulsant properties. Research supports improvements in cognitive function, reduced neurological deficit after stroke, and accelerated recovery from brain injury. It is conceptually similar to Cerebrolysin but derived from cortical tissue.

NeuroprotectionCognitive Enhancement

CRH

Preclinical

Corticotropin-Releasing Hormone · Corticotropin-Releasing Factor

CRH is a 41-amino-acid neuropeptide produced in the hypothalamus that drives the HPA axis stress response. It stimulates ACTH release from the anterior pituitary, ultimately triggering cortisol secretion. Beyond stress regulation, CRH receptors (CRHR1, CRHR2) are distributed throughout the brain and gut, mediating anxiety, depression, immune function, and GI motility. CRH antagonists are under development for anxiety, depression, and irritable bowel syndrome.

Cognitive Enhancement

Dihexa

Preclinical

N-hexanoic-Tyr-Ile-(6) aminohexanoic amide · PNB-0408

Dihexa is a small peptide derived from angiotensin IV that acts as a potent agonist at the HGF/c-Met receptor system, which mediates synaptogenesis — the formation of new synaptic connections. Animal studies suggest it may be several orders of magnitude more potent than BDNF at promoting synapse formation. Research focuses on Alzheimer's disease, cognitive decline, and traumatic brain injury.

Cognitive EnhancementNeuroprotection

Enkephalins

Preclinical

Leu-Enkephalin · Met-Enkephalin

Enkephalins are endogenous opioid pentapeptides (Met-enkephalin and Leu-enkephalin) acting as natural ligands for delta and mu opioid receptors. They modulate pain, mood, reward, and immune function. Low-dose naltrexone (LDN) works partly by transiently blocking opioid receptors to upregulate enkephalin production. Methionine enkephalin (met-enkephalin) has shown immune-modulating and anti-tumor properties in research, particularly for HIV and cancer.

Pain & InflammationImmune SupportCognitive Enhancement

Galanin

Preclinical

GAL

Galanin is a 29-30 amino acid neuropeptide widely distributed throughout the CNS and peripheral nervous system. It modulates memory, mood, pain, seizures, appetite, and sleep via three receptor subtypes (GALR1–3). Research focuses on its roles in Alzheimer's disease (galanin hyperinnervation of cholinergic neurons), depression, epilepsy, and eating behavior. Both agonists and antagonists have therapeutic potential depending on the target condition.

Cognitive EnhancementPain & InflammationFat Loss & Metabolic

IGF-2

Preclinical

Insulin-like Growth Factor 2 · Somatomedin A

IGF-2 is a 67-amino-acid peptide growth factor closely related to IGF-1, primarily active during fetal and neonatal development. In adults, research highlights its potent cognitive effects — IGF-2 administration after training enhances long-term memory consolidation in rodents by a remarkable degree, acting through IGF2R and mannose-6-phosphate receptors in the hippocampus. It has also emerged as a candidate for treating cognitive deficits in aging and neurodegenerative disease.

Growth Hormone AxisCognitive Enhancement

NAP

Phase II

Davunetide · NAPVSIPQ

NAP (NAPVSIPQ) is an 8-amino-acid neuroprotective peptide derived from activity-dependent neuroprotective protein (ADNP). It stabilizes microtubules by interacting with tubulin, protecting neurons against tau pathology, amyloid toxicity, and oxidative damage. Phase 2 trials in schizophrenia and progressive supranuclear palsy have been completed; research is ongoing for Alzheimer's disease and autism spectrum disorder.

NeuroprotectionCognitive Enhancement

Neuropeptide Y

Preclinical

NPY

Neuropeptide Y (NPY) is a 36-amino-acid peptide and the most abundant neuropeptide in the mammalian CNS, acting through Y1–Y6 receptors. It is a potent orexigenic signal (stimulating appetite and fat storage), anxiolytic agent, vasoconstrictor, and regulator of circadian rhythms. Paradoxically, peripheral NPY promotes fat accumulation while central NPY drives food intake — making it a complex but high-priority metabolic research target.

Cognitive EnhancementFat Loss & MetabolicCardiovascular

Neurotensin

Preclinical

NT · NTS

Neurotensin is a 13-amino-acid neuropeptide found in the brain and GI tract. Centrally, it modulates dopamine circuits, acts as an endogenous antipsychotic-like agent, and is analgesic. Peripherally, it inhibits gastric acid secretion, stimulates pancreatic secretion, and promotes fat absorption. Research explores neurotensin analogs for pain, schizophrenia, Parkinson's disease, and metabolic regulation.

Pain & InflammationFat Loss & MetabolicCognitive Enhancement

Noopept

Approved

N-phenylacetyl-L-prolylglycine ethyl ester · GVS-111

Noopept is a dipeptide-derived nootropic approved in Russia for cognitive disorders and memory impairment. It is hydrolyzed in vivo to release cycloprolylglycine, an endogenous neuropeptide. Research demonstrates neuroprotective, memory-enhancing, and anxiolytic effects, upregulation of BDNF and NGF in the hippocampus and cortex, and potential benefits in Alzheimer's disease models. It is significantly more potent than piracetam on a weight-for-weight basis.

Cognitive EnhancementNeuroprotection

Orexin A

Preclinical

Hypocretin-1 · OXA

Orexin A (Hypocretin-1) is a 33-amino-acid neuropeptide produced exclusively by lateral hypothalamic neurons. It promotes wakefulness, arousal, and energy expenditure via OX1R and OX2R receptors, and its deficiency (due to autoimmune destruction of orexin neurons) is the cause of narcolepsy with cataplexy. Orexin receptor antagonists (suvorexant, lemborexant) are approved for insomnia; orexin agonists are under development for narcolepsy.

Sleep & CircadianCognitive Enhancement

Oxytocin

Approved

Pitocin · the "bonding hormone"

Oxytocin is a 9-amino-acid neuropeptide produced in the hypothalamus and released by the posterior pituitary. Beyond its classic roles in parturition and lactation, research demonstrates effects on social bonding, trust, empathy, fear extinction, and autism spectrum disorder. Intranasal oxytocin research has produced mixed results in clinical trials, but it remains one of the most studied peptides in social neuroscience.

Cognitive EnhancementSexual Health

P21

Preclinical

P21 cognitive peptide

P21 is a peptide fragment derived from CNTF (Ciliary Neurotrophic Factor) designed to activate the STAT3 signaling pathway, which promotes neurogenesis and cognitive function. Animal research demonstrates improved spatial memory, increased hippocampal neurogenesis, and enhanced BDNF expression. It is studied as a non-cytokine CNTF functional mimetic without the systemic side effects of full-length CNTF.

Cognitive EnhancementNeuroprotection

Pinealon

Preclinical

EDR peptide · Glu-Asp-Arg

Pinealon is a synthetic tripeptide (Glu-Asp-Arg) developed by the St. Petersburg Institute of Bioregulation and Gerontology. It is characterized as a pineal gland cytoprotective peptide that penetrates the blood-brain barrier and acts as a transcription factor, regulating gene expression in neuronal cells. Research suggests neuroprotective, antioxidant, and cognition-preserving effects, particularly in aging and hypoxic conditions.

Cognitive EnhancementAnti-Aging & LongevityNeuroprotection

Selank

Approved

Selanc · TP-7

Selank is a synthetic heptapeptide analog of tuftsin developed by the Russian Institute of Molecular Genetics. Approved in Russia for anxiety and cognitive disorders, it exhibits anxiolytic effects comparable to benzodiazepines without sedation or dependence. Research shows it modulates GABA, serotonin, and dopamine systems, enhances BDNF expression, and improves memory consolidation and learning.

C₃₃H₅₇N₁₁O₉ · 751.87 Da

Cognitive EnhancementImmune Support

Semax

Approved

MEHFPGP · Pro8-Gly9-Pro10-ACTH(4–10)

Semax is a synthetic heptapeptide analog of ACTH(4-7) developed in Russia, where it is approved for stroke, TBI, peptic ulcers, and cognitive enhancement. It upregulates BDNF and its receptor TrkB, promotes dopamine and serotonin turnover, and has demonstrated neuroprotective effects in ischemia models. Research highlights improvements in attention, memory, and recovery from neurological injury.

Cognitive EnhancementNeuroprotection

Substance P

Preclinical

SP · NK1 ligand

Substance P is an 11-amino-acid neuropeptide of the tachykinin family and a primary neurotransmitter of pain signaling in the spinal cord. It binds NK1 receptors to mediate neurogenic inflammation, pain hypersensitivity, and emotional processing. NK1 antagonists have been developed for pain, depression (aprepitant), and nausea. Research also implicates substance P in wound healing, immune activation, and neuroinflammation.

Pain & InflammationCognitive Enhancement

TRH

Approved

Thyrotropin-Releasing Hormone · Thyroliberin

TRH is a tripeptide (pGlu-His-Pro-NH2) produced in the hypothalamus that stimulates TSH and prolactin release from the anterior pituitary. Beyond thyroid regulation, TRH has direct CNS effects — it is alerting, antidepressant, neuroprotective, and anticonvulsant. Research explores TRH analogs (taltirelin, approved in Japan) for ALS, spinal cord injury, Alzheimer's disease, and treatment-resistant depression, avoiding thyroid side effects.

Cognitive EnhancementNeuroprotection

Urocortin 1

Phase II

UCN1 · Urocortin

Urocortin 1 (UCN1) is a 40-amino-acid member of the CRH peptide family that activates both CRHR1 and CRHR2 receptors. It has potent cardioprotective effects — improving cardiac contractility, reducing ischemia-reperfusion injury, and stimulating natriuresis — making it a significant heart failure research target. It also modulates anxiety and appetite centrally. Phase 2 trials for chronic heart failure showed improvements in cardiac function.

CardiovascularCognitive Enhancement

Research applications

What researchers are studying

Attention and working memory

Semax has been studied in human subjects in the context of vascular brain lesions, showing improvements in attention and short-term memory retention compared to controls. Its ACTH-analog structure allows it to cross the blood-brain barrier efficiently, and intranasal administration produces rapid CNS distribution, which is why this route is most commonly used in research protocols.

Anxiety modulation without sedation

Selank has been studied in clinical trials in Russia as an anxiolytic, with some data showing effects comparable to benzodiazepines on anxiety measures without the cognitive dampening or dependency risk. It appears to normalize enkephalin metabolism and modulate serotonin transport, producing a calming effect without receptor downregulation seen with GABAergic drugs.

Neuroplasticity and recovery

BDNF upregulation is a central mechanism in several peptides in this category. Higher BDNF expression is associated with synaptic density, long-term potentiation, and resilience to neuronal damage. Semax in particular has been studied for its role in ischemic brain injury recovery, where BDNF induction may help spare penumbral tissue and accelerate functional recovery.

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