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Educational reference only. Nothing on this page constitutes medical advice or encourages personal use of this compound. Always consult a qualified healthcare provider before any decision involving your health.
PE-22-28 is the product of a decade of peptide engineering starting from a serendipitous observation about a protein called sortilin — and the result is a 7-amino-acid fragment with antidepressant potency 333-fold greater than its parent compound.
The story begins not with depression but with neurotrophic factor biology. Sortilin (neurotensin receptor 3, NTSR3) is a multifunctional receptor involved in neurotrophin signaling, lysosomal targeting, and lipoprotein metabolism. The CNRS group in Valbonne (led by Heurteaux and Borsotto) discovered that sortilin's propeptide — a 44-amino-acid fragment released from the protein's extracellular domain — was an endogenous antagonist of the TREK-1 potassium channel. This was an unexpected connection: a peptide derived from a neurotrophin receptor regulating a background potassium channel implicated in depression.
The full 44-amino-acid propeptide was too large for practical development. Structure-activity relationship (SAR) studies progressively narrowed the active sequence. Spadin (PE 12-28) — a 17-amino-acid fragment — was identified in 2010 as the first practical TREK-1-blocking antidepressant candidate. In mouse behavioral models of depression, spadin produced antidepressant effects in 4 days — a timeline of roughly 4-7 times faster than SSRIs in equivalent models. The limitation: spadin's half-life in vivo was approximately 7 hours, limiting its duration of action.
The Valbonne group's next decade of work focused on further truncating spadin to improve stability, potency, and duration. By systematically shortening the sequence and characterizing each fragment's TREK-1 inhibition using patch-clamp electrophysiology on HEK cells expressing human TREK-1, they arrived at PE-22-28 — the 7-amino-acid sequence GVSWGLR that represents the minimal active fragment with equivalent or superior antidepressant activity to the full spadin. PE-22-28's IC50 at human TREK-1 is 0.12 nM — approximately 333-500 times more potent than spadin's 40-60 nM IC50. Its duration of action was extended to approximately 23 hours from spadin's 7 hours. This is the compound the community uses today.
THE CENTRAL TENSION
PE-22-28 represents the most mechanistically novel antidepressant compound in this book. Blocking a potassium channel to increase serotonergic neuron excitability — rather than blocking the reuptake transporter to prevent serotonin clearance — is a genuinely different pharmacological approach to depression. The mouse data shows 4-day antidepressant onset with neurogenesis induction, outperforming SSRIs in speed. The compound is more potent than its parent spadin by 333-fold. And the entire published evidence base — every mouse study, every patch-clamp experiment, every neurogenesis measurement — comes from one research group in Valbonne, France. No independent laboratory has replicated the core antidepressant findings with PE-22-28 specifically. No human has ever been enrolled in a PE-22-28 clinical trial. The community uses it for depression and cognitive enhancement based on mouse behavioral data from a single institution. This is not a critique of the science — the Heurteaux/Borsotto work is published in peer-reviewed journals and is mechanistically coherent. It is an accurate description of the evidence stage.
PE-22-28 is used via two primary routes in the community: SubQ injection and intranasal drops. SubQ: the most common route; standard subcutaneous technique; abdomen or thigh; rotate sites. Intranasal: dissolve in saline to 1mg/mL; deliver 2-3 drops per nostril; theoretically allows direct olfactory pathway brain access with potentially superior CNS delivery; the intranasal route is frequently preferred in the community for nootropic applications given the olfactory shortcut. Oral: unlikely to be bioavailable given rapid peptide degradation in the GI tract; not recommended and not community-standard.
Parameter
SubQ Protocol
Intranasal Protocol
Notes
Starting dose
50-100 mcg
500 mcg (0.5 mg)
SubQ doses are lower; intranasal may require higher volume due to lower bioavailability from mucosal absorption
Standard dose
100-300 mcg
1-2 mg
Community-derived; no human dose-response data exists for either route
Frequency
Once daily
Once daily (AM preferred)
Morning preferred for both — possible mild stimulatory effect
Timing
Morning or AM
Morning or AM
Evening dosing may affect sleep in some users
Reconstitution
BAC water; standard peptide protocol
Normal saline (0.9% NaCl) preferred for nasal; BAC water acceptable
Avoid benzyl alcohol in frequent nasal use
Duration
4-day onset in mice; community reports 1-2 weeks in humans
Similar to SubQ
No human pharmacokinetic data for duration of action
Cycling
Continuous or 4-8 weeks on/2 off
Same
No established protocol; community convention varies
The mouse behavioral data shows antidepressant effect emerging over 4 days of treatment. The community expectation of 4-day antidepressant onset in humans is an extrapolation that may or may not hold. In humans, pharmacokinetics differ substantially from mice: body weight/surface area scaling changes the effective dose; metabolic rate differences affect clearance; human TREK-1 expression may differ in distribution and density from mouse TREK-1; the neurogenesis timeline in adult human hippocampus is longer than in mice. Community reports suggest effects emerging in 1-2 weeks in humans — possibly consistent with a scaled-up timeline from the 4-day mouse onset. Whether the full neurogenesis-mediated antidepressant effects develop on the same timeline in humans as in mice is unknown.
WHAT COMMUNITY USERS REPORT
Community-observed effects at 100-300 mcg SubQ or 1 mg intranasal daily, typically emerging over 1-2 weeks: improved mood and reduction in baseline anxiety; improved verbal fluency and conversational ease; enhanced cognitive clarity (described as 'cleaner' thinking); reduced rumination and intrusive negative thoughts; improved motivation and energy to engage with tasks. These reports are consistent with the proposed mechanism (increased serotonergic tone, neurogenesis, synaptogenesis) but are community-observed and not controlled. The absence of euphoria or intoxication is consistently noted — PE-22-28 does not produce a 'high.' The experience is described as mood normalization rather than mood elevation.
To understand why TREK-1 blockade produces antidepressant effects, you need to understand what TREK-1 does in the brain regions most relevant to mood regulation.
TREK-1 (TWIK-Related potassium channel-1, encoded by the KCNK2 gene) belongs to the two-pore domain (K2P) potassium channel family — so-named because the channel protein contains two pore-forming domains within a single subunit, unlike conventional potassium channels that require four subunits. K2P channels provide a constitutive 'background' or 'leak' potassium current that flows under basal conditions without requiring specific activation. This outward potassium current tends to keep the inside of the cell negatively charged — hyperpolarized — relative to the outside. A hyperpolarized neuron is harder to fire; it requires stronger stimulation to reach the action potential threshold. TREK-1 is therefore a brake on neuronal excitability — its presence makes neurons less likely to fire spontaneously or in response to moderate stimulation.
TREK-1 is expressed throughout the brain including the prefrontal cortex, hippocampus, amygdala, nucleus accumbens, and hypothalamus — all regions implicated in mood regulation. Its most pharmacologically significant expression site for antidepressant purposes is the dorsal raphe nucleus — the primary source of serotonergic projections throughout the brain. Serotonergic neurons in the dorsal raphe project widely to the forebrain structures that regulate mood, anxiety, cognition, and stress response. Their firing rate determines the amount of serotonin released into synaptic terminals throughout the brain. TREK-1 channels in dorsal raphe serotonergic neurons restrain their excitability — suppressing their firing rate and limiting serotonin output. Block TREK-1 in the dorsal raphe and those neurons become more excitable, fire more readily, and release more serotonin throughout the brain. This is the antidepressant mechanism of PE-22-28: increasing serotonin at the source by removing an excitability brake, rather than at the synapse by blocking reuptake.
The strongest preclinical validation of the TREK-1 target comes from genetic studies. TREK-1 knockout mice — mice with the KCNK2 gene deleted and therefore completely lacking TREK-1 channels — develop a phenotype resistant to depression in multiple established behavioral tests. The forced swim test: TREK-1 KO mice show significantly reduced immobility — the proxy measure for depression-like behavior. The tail suspension test: similar result. The chronic unpredictable stress model: TREK-1 KO mice show less anhedonia. The learned helplessness model: reduced helplessness in TREK-1 KO mice. Across multiple independent behavioral models of depression, the absence of TREK-1 consistently produces an antidepressant-like phenotype. This genetic evidence establishes TREK-1 as a mechanistically valid target — before any compound was developed. The pharmacological approach (block TREK-1 with a selective peptide) is conceptually equivalent to the genetic approach (remove TREK-1) for the purpose of demonstrating mechanism.
A critical secondary mechanism of PE-22-28 is hippocampal neurogenesis promotion. The adult hippocampus retains the capacity for neurogenesis — the generation of new neurons — and this capacity is reduced in depression and increased by antidepressant treatments. Multiple classes of antidepressants (SSRIs, SNRIs, MAOIs, ketamine) all increase hippocampal neurogenesis through different upstream mechanisms. The downstream neurogenesis appears to be a shared mediator of antidepressant efficacy that is required for the behavioral effects of many antidepressants. PE-22-28 and its analogues were shown to induce hippocampal neurogenesis after only a 4-day treatment in the mouse studies — a timeline that parallels its rapid behavioral antidepressant onset and is substantially faster than the weeks typically required for SSRI-induced neurogenesis. Additionally, PE-22-28 increased synaptogenesis in mouse cortical neurons, measured by increased PSD-95 expression — PSD-95 is a postsynaptic density protein that scaffolds synaptic connections. Both neurogenesis and synaptogenesis represent structural changes in brain plasticity that may underlie the durability of antidepressant effects.
All significant evidence for PE-22-28 comes from a single research group. This is stated not as a disqualification of the science but as an accurate characterization of its evidentiary status.
Djillani A, Pietri M, Moreno S, Heurteaux C, Mazella J, Borsotto M. (2017). Shortened Spadin Analogs Display Better TREK-1 Inhibition, In Vivo Stability and Antidepressant Activity. Frontiers in Pharmacology. 8:643. PMC5601071. PMID 28955242. This is the primary and essentially only dedicated PE-22-28 paper in the peer-reviewed literature. It established: TREK-1 IC50 of 0.12 nM for PE-22-28 (vs 40-60 nM for spadin) using patch-clamp electrophysiology on HEK293 cells expressing human TREK-1; antidepressant activity in the forced swimming test (significant reduction in immobility time at 4 days); novelty suppressed feeding test: significant reduction in latency to eat (antidepressant behavioral endpoint); hippocampal neurogenesis induction after 4-day treatment; cortical neuron synaptogenesis increase (PSD-95 upregulation); duration of action up to 23 hours (vs 7 hours for spadin). All from the same French institution that developed the compound. Grade C: mouse behavioral models; electrophysiology in cells; single institution; in vivo data is from one group with the compound they developed.
PE-22-28's evidence rests partly on the spadin foundation from the same group. Mazella J, et al. (2010, PLoS Biology): established spadin as a TREK-1 blocker and antidepressant in mice; 4-day treatment equivalent to 21-28 days of SSRI treatment in behavioral models; TREK-1 KO mice depression-resistant. Multiple subsequent papers (Borsotto 2015; Devader 2015; Moha Ou Maati 2012) elaborated the spadin mechanism and therapeutic evidence. This body of work provides the mechanistic context for PE-22-28 but is all from the same Valbonne group. The 'replicated' nature of the evidence is multiple papers from one lab — not independent replication by separate groups.
The TREK-1 target itself has been independently validated by genetic studies from multiple groups. Heurteaux C, et al. (2006, EMBO Journal): original TREK-1 KO antidepressant phenotype paper — from the same group. However, multiple independent groups have since characterized TREK-1 KO biology in different contexts, confirming the channel's role in neuronal excitability and mood regulation at the genetic level. This provides some independent validation that TREK-1 is a legitimate pharmacological target for mood disorders — the specific claim that PE-22-28 blocks this target in humans and produces human antidepressant effects remains unvalidated.
Evidence Type
Compound
Source
Grade
What It Establishes
TREK-1 KO depression resistance
TREK-1 gene knockout mouse
Heurteaux group + some independent work
C (mouse) / D (target validation)
TREK-1 channel restrains antidepressant phenotype — target is valid
PE-22-28 IC50 0.12 nM at hTREK-1
PE-22-28
Djillani 2017 (single lab)
D
Potent in vitro binding at human TREK-1 in overexpressing cells
Antidepressant behavior (FST, NSF)
PE-22-28
Djillani 2017 (single lab)
C — single lab
Antidepressant-like behavior in 4-day mouse treatment
Hippocampal neurogenesis
PE-22-28
Djillani 2017 (single lab)
C — single lab
Neurogenesis increase at 4 days in mouse; mechanistically coherent
Synaptogenesis (PSD-95)
PE-22-28
Djillani 2017 (single lab)
D (cell culture)
Cortical neuron synaptogenesis in vitro
Spadin antidepressant activity
Spadin (parent compound)
Mazella 2010 + multiple Heurteaux group papers
C — single group
Parent compound antidepressant behavior in mice; 4-day onset
Human antidepressant efficacy
PE-22-28
None
No grade — does not exist
No human trial data; efficacy in humans unproven
PE-22-28 is a CNS-active compound that modulates the same serotonergic system as SSRIs, just through a different upstream mechanism. The C4 audit covers mood, cognition, dependency potential, and the depression application specifically.
Depression is a serious psychiatric disorder. Using a research chemical for self-treatment of clinical depression — in place of or alongside physician-prescribed medications — carries specific risks that go beyond the general research chemical concerns. Undiagnosed or undertreated severe depression carries significant risk of self-harm and suicide. Research chemicals have no quality assurance for consistent dosing; an underdosed compound provides no therapeutic effect while the person forgoes effective treatment. An overdosed compound has unknown effects. The community use of PE-22-28 for self-treatment of depression sits at a particularly sensitive intersection: a compelling mechanistic rationale; promising preclinical data; zero human evidence; and an indication where the consequences of treatment failure are potentially serious. This does not mean community use for mood support is categorically inappropriate — mild-to-moderate mood concerns without active suicidal ideation represent a different risk profile from severe depression. The distinction matters and should be made explicitly.
Beyond antidepressant use, PE-22-28 is used in the community as a nootropic — for cognitive enhancement, verbal fluency, and processing speed. The mechanistic basis for cognitive effects: TREK-1 is expressed in hippocampus, prefrontal cortex, and other regions involved in learning and memory; increased neuronal excitability via TREK-1 blockade theoretically enhances synaptic plasticity; the documented neurogenesis and synaptogenesis effects provide a plausible substrate for cognitive improvement. Whether these mouse-model neuroplasticity effects translate to human cognitive enhancement is unknown. Community reports suggest improved clarity and verbal fluency — consistent with the mechanism but not confirmed by controlled data.
TREK-1 is not a reward pathway target — it is not expressed at high density in dopaminergic reward circuits (VTA, nucleus accumbens) in the same way that opioid or dopamine receptors are. The mechanism of PE-22-28 does not produce euphoria, intoxication, or direct reward activation. There is no theoretical basis from the known pharmacology for physical dependence or withdrawal syndrome analogous to benzodiazepines, opioids, or stimulants. Community experience is consistent with this: tolerance and dependence are not reported as concerns. However, psychological habituation to the mood-brightening effects is possible with any mood-modulating compound, and discontinuation after extended use may produce a relative low relative to the elevated baseline — this is community-observed rather than pharmacologically documented. The important distinction: this would be a non-pharmacological psychological adjustment, not a withdrawal syndrome.
The most clinically important drug interaction concern: PE-22-28 + SSRIs. Both increase serotonergic tone through different mechanisms — PE-22-28 increases serotonin production/release; SSRIs reduce serotonin reuptake. Combined, they theoretically increase synaptic serotonin more than either alone. Whether this reaches the level of serotonin syndrome risk at typical doses is unknown — the TREK-1 mechanism operates upstream of the synapse and the combined effect on serotonin tone has not been characterized in any study. Community use of PE-22-28 alongside SSRIs is reported; severe adverse events have not been widely documented from this combination. The theoretical concern exists and should be acknowledged: anyone taking an SSRI, SNRI, or MAOI who adds PE-22-28 should do so with awareness of the additive serotonergic risk and start at the lowest dose.
PE-22-28's safety profile in humans is essentially unknown — no systematic human safety study has been conducted. The preclinical mouse data showed no significant adverse effects at antidepressant doses in behavioral studies. The TREK-1 KO mice do not show increased mortality or gross pathology — removing the channel entirely does not produce severe systemic effects. This suggests that pharmacological blockade of TREK-1 with PE-22-28 is unlikely to cause severe acute systemic toxicity at typical doses. The important caveats: TREK-1 KO mice do show increased sensitivity to cerebral ischemia — the depression-resistance comes with a vulnerability to ischemic injury. Whether this translates to any clinical concern with pharmacological TREK-1 blockade at the doses used by the community is not established but represents a theoretical consideration for anyone with known cerebrovascular disease. Standard precautions: no SSRI/MAOI combination without physician awareness; depression treatment context should involve physician oversight; quality COA verification; liver enzyme monitoring not specifically required based on mechanism but general peptide safety monitoring applies.
Feature
PE-22-28
SSRIs (e.g. fluoxetine)
Primary mechanism
TREK-1 potassium channel blockade — increases dorsal raphe excitability
Serotonin transporter (SERT) blockade — reduces serotonin reuptake at synapse
Site of action
Presynaptic: increases serotonin production/release at dorsal raphe
Postsynaptic: increases serotonin availability in synaptic cleft
Effect on serotonin
More serotonin produced and released
Same serotonin kept in synapse longer
Onset (mouse models)
4 days
21-28 days
Onset (human — extrapolated)
1-2 weeks (community-reported)
2-4 weeks (established)
Neurogenesis
Promotes hippocampal neurogenesis in 4 days (mouse)
Promotes hippocampal neurogenesis — requires weeks
Human evidence
Zero clinical trials
Hundreds of RCTs; FDA-approved
Dependency risk
None established pharmacologically
Discontinuation syndrome documented; not classical addiction
Sexual side effects
None documented (no SERT involvement)
Common — delayed orgasm, reduced libido
Weight
None documented
Variable; often weight gain
Regulatory status
Research chemical
FDA-approved prescription medication
Safety profile
Unknown in humans
Well-characterized across decades of use
PE-22-28 has demonstrated antidepressant-like behavior in mouse models in the forced swimming test and novelty suppressed feeding test — from one research group. These mouse behavioral models are widely used in antidepressant research but are imperfect proxies for human depression. Many compounds that show antidepressant activity in the forced swimming test have failed in human clinical trials. The compound is promising; it is not proven. The distinction matters for anyone considering it as treatment for clinical depression.
PE-22-28 and SSRIs both increase serotonergic tone — but through fundamentally different mechanisms at different anatomical sites. SSRIs work in synapses throughout the brain. PE-22-28 works at the dorsal raphe by changing neuronal excitability. These are not the same mechanism at different speeds. The downstream convergence on increased serotonergic signaling means they share some mechanism of action, but the upstream pharmacology is categorically different. Calling PE-22-28 'a faster SSRI' is a simplification that obscures the mechanistic novelty that makes the compound scientifically interesting.
Mouse-to-human translation of antidepressant effects is the most notoriously unreliable translation in all of psychopharmacology. Dozens of compounds with compelling mouse antidepressant data have failed in human trials. The forced swimming test in particular has been criticized as a test of coping behavior rather than depression per se. The 4-day mouse timeline is a signal — it does not predict the human timeline, which community users report as 1-2 weeks at minimum. The absence of human trials means the 4-day figure cannot be applied to human treatment planning.
PE-22-28 (GVSWGLR, 7 amino acids) is a fragment of spadin (PE 12-28, 17 amino acids). They share the TREK-1 blocking mechanism but are different molecules. PE-22-28 is 333-500x more potent at TREK-1 than spadin and has 3x longer duration of action (23 hours vs 7 hours). Dosing and protocols for spadin do not apply to PE-22-28 due to the potency difference.
Djillani A, Pietri M, Moreno S, Heurteaux C, Mazella J, Borsotto M. (2017). Shortened Spadin Analogs Display Better TREK-1 Inhibition, In Vivo Stability and Antidepressant Activity. Frontiers in Pharmacology. 8:643. PMC5601071. PMID 28955242. doi:10.3389/fphar.2017.00643. [All significant PE-22-28 data: IC50 0.12 nM at hTREK-1; FST and NSF antidepressant behavior at 4 days; hippocampal neurogenesis; cortical synaptogenesis; 23-hour duration of action; single CNRS group, Valbonne France.]
Mazella J, Perez-Sanchez N, Romero F, et al. (2010). Spadin, a sortilin-derived peptide, targeting rodent TREK-1 channels: a new concept in the antidepressant drug design. PLoS Biology. 8(4):e1000355. PMC2854129. PMID 20405001. [Original spadin antidepressant paper; TREK-1 KO depression resistance; 4-day onset vs 21-28 days SSRIs; foundational evidence for the class mechanism.]
Heurteaux C, et al. (2006). Deletion of the background potassium channel TREK-1 results in a depression-resistant phenotype. Nature Neuroscience. 9(9):1134-1141. [Genetic validation of TREK-1 as antidepressant target; TREK-1 KO mice depression-resistant across multiple behavioral models; key independent validation of the target pharmacology.]
Borsotto M, Veyssiere J, Simkin D, Mameli M, Heurteaux C, Mazella J. (2015). Targeting two-pore domain K+ channels TREK-1 and TASK-3 for the treatment of depression: a new therapeutic concept. British Journal of Pharmacology. 172(3):771-784. [Broader TREK-1/TASK-3 antidepressant mechanism review from the same group; contextualizes PE-22-28 in the K2P channel therapeutic landscape.]
PE-22-28 has the most mechanistically novel antidepressant mechanism of any compound in this book — and the least human evidence. Its value is in what it represents pharmacologically, not in what has been proven clinically.
The honest summary: PE-22-28's TREK-1 blocking mechanism is genuinely novel — it operates upstream of SSRI pharmacology, at the level of neuronal excitability rather than synaptic clearance. The target (TREK-1) has been independently genetically validated as an antidepressant target. The compound itself is potent (IC50 0.12 nM), has improved stability over its parent (23 hours), and shows neurogenesis-inducing activity at 4-day treatment in mice. The community experience is broadly positive for mood and cognition. And all of this rests on a single peer-reviewed paper from the group that developed the compound, with zero human data, in a preclinical model class (forced swimming test, novelty suppressed feeding) that has an inconsistent track record of human translation. The compound deserves a clinical trial. It has not received one in 15 years since spadin's identification. Whether this reflects lack of commercial interest, insufficient preclinical replications, or other considerations is unclear.
— End of PE-22-28 —
THE PEPTIDE BIBLE | PE-22-28 | For Research & Educational Purposes Only
PE-22-28: 7-amino-acid synthetic peptide; sequence GVSWGLR (Gly-Val-Ser-Trp-Gly-Leu-Arg); MW ~730 Da. Derived from spadin (PE 12-28), itself a fragment of sortilin/NTSR3 propeptide. Selective TREK-1 potassium channel blocker. TREK-1 BIOLOGY: K2P background potassium channel (KCNK2); constitutive outward K+ current hyperpolarizes neurons; highly expressed in dorsal raphe nucleus (primary serotonin production hub), hippocampus, prefrontal cortex, amygdala; TREK-1 KO mice develop depression-resistant phenotype across multiple behavioral models. MECHANISM: PE-22-28 blocks TREK-1 → removes neuronal hyperpolarization brake → dorsal raphe neurons more excitable → increased serotonin production and release at source (vs SSRIs that block reuptake at synapse). Secondary: hippocampal neurogenesis induction at 4 days; cortical synaptogenesis (PSD-95 upregulation). vs SSRIs: presynaptic mechanism (more serotonin made) vs postsynaptic (same serotonin retained longer). POTENCY: IC50 = 0.12 nM at hTREK-1 (vs spadin 40-60 nM; 333-500x more potent). DURATION: ~23 hours (vs spadin ~7 hours). ONSET (mouse): 4-day antidepressant behavior in FST and NSF. ORIGIN: fragment engineering by Heurteaux/Borsotto/Mazella group, CNRS, Institut de Pharmacologie Moleéculaire et Cellulaire, Université Côte d'Azur, Valbonne, France. EVIDENCE: Primary paper = Djillani et al. 2017 (Front Pharmacol; PMC5601071) — single lab; all in vivo data from developing group; Grade C mouse behavioral models. NO HUMAN TRIALS. NO INDEPENDENT REPLICATION OF PE-22-28 SPECIFICALLY. SSRI CO-ADMINISTRATION: theoretical additive serotonergic risk; inform physician. COMMUNITY PROTOCOL: SubQ 100-300 mcg/day or intranasal 1 mg/day; morning; 1-2 weeks for community-reported effect. REPORTED COMMUNITY EFFECTS: mood improvement, reduced anxiety, improved verbal fluency, cognitive clarity, reduced rumination. SAFETY: no adverse effects in mouse studies; TREK-1 KO mice show increased ischemic sensitivity (theoretical concern); no human safety data. DEPENDENCY: not expected pharmacologically (not a reward pathway target); no withdrawal syndrome documented. WADA: not listed. NO HPTA. NOT C4 dependency concern. DEPRESSION APPLICATION: should not replace physician-supervised treatment for clinical depression. STACK: complements Selank (GABAergic/anxiolytic) and Semax (BDNF/dopaminergic) through non-overlapping mechanisms.
A Structural Modification of Semax With No Published Studies of Its Own. Being Sold as 'The Most Potent Semax Analog.' Every Claim Belongs to Its Parent Compound.
The Compound That Raises NAD+ By Stopping the Body From Destroying It. NNMT: The Enzyme That Wastes Nicotinamide. Fat Loss Without Food Restriction in Mice. The Neelakantan Group's Research Tool Repurposed as a Longevity Drug. Zero Human Trials. 100 mg/Day Community Dose Extrapolated From Mouse IP Injections. The 1-MNA Question: The Metabolite You're Blocking Has Protective Roles in Liver and Kidney. A 2025 Cell/TPS Review Calls for Clinical Translation. Clinics Already Prescribing It Without FDA Ruling on Safety.
Six Human Clinical Trials. 900+ Participants. Safety Indistinguishable From Placebo. Primary Fat Loss Endpoint Failed. WADA Banned. FDA Rejected for Compounding. The Community Uses It Anyway at Doses That Never Worked in the Trials.