GB-115
Cholecystokinin-4 antagonist
GB-115 (Cholecystokinin-4 antagonist) is a cognitive & mood research compound. A dipeptide CCK-B receptor antagonist developed in Russia. CCK-4 reliably induces panic in humans, so blocking that receptor is a rational anxiolytic target that doesn't touch GABA.
GB-115 quick facts
| Reported research dose (Oral) | 6mg daily |
| Route | Oral / intranasal |
| Frequency | Not established — no dosing protocol has been characterized |
| Half-life | Not characterized in published human work |
| Forms | Oral, Nasal |
| Evidence level | Russian preclinical and early clinical work, little of it in English or peer-reviewed internationally |
| Other forms available | Nasal — dosed differently |
Mechanistically appealing — a non-GABAergic anxiolytic without sedation or dependence would be genuinely useful. But essentially all the data sits in Russian-language literature that hasn't been independently replicated, and no Western trial exists. The 6 mg daily on this card is not community folklore, though: it is the effective dose determined by a published dose-finding study in generalized anxiety disorder (Neznamov 2019 — 31 patients, 21 days), and that trial is the only human dosing evidence there is.
How GB-115 works
A dipeptide CCK-B receptor antagonist developed in Russia. CCK-4 reliably induces panic in humans, so blocking that receptor is a rational anxiolytic target that doesn't touch GABA.
Proposed benefits
Researched for focus, memory, neuroprotection, mood and stress resilience.
Where to get GB-115
The evidence for GB-115
Graded by what exists behind each claim.
Human clinical evidence
- The human record is Soviet and post-Soviet clinical work — real patients and real endpoints, published in Russian and rarely replicated to Western standards.
📊 Correlative data
- Very limited use outside Russian research settings. There is almost no community record, which means the clinical tier above is effectively the entire human evidence base for it.
🧪 Theoretical / extrapolated
- A dipeptide cholecystokinin (CCK) antagonist developed at the Russian Institute of Pharmacology. CCK-B receptor activation provokes panic in humans experimentally, so blocking it is a coherent anxiolytic target.
- That mechanism is unusual and interesting — it addresses anxiety without touching GABA, so it predicts no sedation and no dependence liability. It also predicts a narrower effect, since it targets one specific panic pathway.
How to read the Soviet clinical series →
How to read these tiers: they say how much human evidence exists, not how well something works — and ✗ flags harm, never a disappointing trial. How the evidence tiers work →
What GB-115 actually does
The molecule, written out. GB-115 is the amide of N-phenylhexanoyl-glycyl-L-tryptophan Sorokina 2010 Boyko 2007. Strip the name and what is left is a dipeptide, Gly-Trp, wearing a six-carbon phenyl-bearing acyl chain on the nitrogen end and an amide on the carboxyl end. Both termini are blocked. That single design decision is responsible for most of what is unusual about this compound.
What it is a copy of. Cholecystokinin-4 is Trp-Met-Asp-Phe-NH2, the C-terminal tetrapeptide of cholecystokinin and the most reliable experimental panicogen in human research: infuse it and healthy volunteers get panic. GB-115 is described in its own literature as a retro-analog of CCK-4 Kolik 2012 Kolik 2013 — the recognition element rebuilt with the residue order reversed, which is why a Gly-Trp dipeptide can present the same beta-turn as a tetrapeptide does. The design program it came from is explicit about the method: take the beta-turn that carries a regulatory peptide's interaction with its receptor, and build the smallest dipeptide that reproduces that turn. The same program produced noopept from piracetam, dilept from neurotensin and GK-2 from nerve growth factor Gudasheva 2018.
The receptor, tested rather than assumed. The target is the CCK-B (CCK2) receptor, and the pharmacology was checked by dissociation rather than by assertion: activating the CCK-4 type-2 receptor abolished GB-115's anti-anxiety effect in BALB/c mice, GB-115 prevented CCK-4-induced anxiety in C57Bl/6 mice and outbred rats, and in the same experiments the alpha-2 adrenoceptor antagonist yohimbine neither modulated GB-115's effect nor had its own anxiogenic effect prevented by it Kolik 2012. That is a clean result: the effect runs through the cholecystokinin system and not through noradrenaline.
The fact nobody in this market states: CCK-B is the gastrin receptor. CCK2 and the gastrin receptor are the same protein — the receptor gastrin acts on at the parietal cell to drive acid secretion is the receptor this compound is designed to block. So pharmacologically GB-115 is a gastrin-receptor antagonist that happens to be used for anxiety. Nothing in the GB-115 literature reachable for this page reports gastric acid, serum gastrin, or any gastrointestinal endpoint at all. That is an extrapolation from receptor identity rather than a finding, and it is the largest unexamined implication the molecule carries.
And a word the clinical paper uses that deserves attention: low-affinity. The human study describes GB-115 as a low-affinity blocker of central cholecystokinin receptors Neznamov 2019. No binding constant appears in any abstract reachable here, so ‘low-affinity’ is the most precise potency statement that exists for it — which is consistent with a clinical dose of 6 mg a day rather than the micrograms that the receptor-tight peptides elsewhere in this catalog use.
Cell, rodent, human — and where it stops
The receptor step. There is no published binding curve, Ki or Kd. The receptor's involvement rests on the functional dissociation above Kolik 2012 rather than on a radioligand number, which is a real gap in an otherwise unusually complete package.
In rodents, with the doses and the arithmetic that connects them. Orally, anxiolytic effects appeared in outbred mice at 0.1–0.5 mg/kg, in BALB/c mice at 0.1 and 5.0 mg/kg, and in outbred rats at 0.5–0.7 mg/kg, measured in open field and elevated plus maze. The paper states the shift explicitly: the anxiolytic range moves from 0.006–0.100 mg/kg intraperitoneally to 0.1–5.0 mg/kg orally Kolik 2013. That is a 17- to 50-fold penalty for using the gut, and it lines up with the measured bioavailability below — two independent numbers agreeing is rare on this site and worth saying.
The toxicology, which is the most complete in this cohort. No deaths after acute oral dosing at 6000 mg/kg in mice and 3500 mg/kg in rats. Six months of oral dosing in rats and rabbits, males and females, at 0.1 and 10 mg/kg, with no irreversible pathological change in any organ or system. No allergenic, immunotoxic or mutagenic activity, and no effect on generative function or on antenatal and postnatal development of offspring Sorokina 2010.
In humans, and this part corrects something the internet repeats. 31 patients with generalized anxiety disorder (F41.1), 22 women and 9 men, aged 22–53, treated for 21 days with 1 mg tablets. The study's purpose was dose-finding, and it landed on 6 mg daily as the effective dose, with a fast onset, stimulating rather than sedating character, benefit on sleep disturbance and autonomic symptoms, favorable changes in attention and reaction time on a computerized battery, and no initial overactivation of the kind SSRIs and SNRIs produce Neznamov 2019. The 6 mg figure circulating online is therefore not invented — it is the effective dose from a published clinical study, and the catalog entry on this site that says the dosing has no published basis is out of date.
The obstacles.
- n = 31, one center, one country, 21 days. Generalized anxiety disorder has among the highest placebo response rates in psychiatry, and a short open dose-finding study is the design most likely to overstate a drug effect. No placebo-controlled trial has been published Neznamov 2019.
- The formulation is the dose. Three peroral dosage forms of GB-115 were compared against the micronized substance and returned relative bioavailabilities of 53%, 117% and 192% Ivannikova 2014. That is a 3.6-fold spread between presentations of the same compound. ‘6 mg’ is a statement about one tablet made at one institute, not about a quantity of powder in a bag.
- Phenotype dependence, again. The anxiogenic challenges produced an active stress response in rats and C57Bl/6 mice and a freezing response in BALB/c, and GB-115's effects tracked that split Kolik 2012 Kolik 2013. No human study has stratified anyone on anything comparable.
- The comparator problem. For generalized anxiety disorder there are treatments with thousands of randomized participants. This has 31.
GB-115 pharmacokinetics — how much of it actually gets in
What degrades it — and mostly, what does not. The pharmacokinetic study states plainly that the dipeptide is resistant to peptidases Boyko 2007, and the structure says why: the N-terminus is acylated with phenylhexanoic acid rather than free, so aminopeptidases have no handle, and the C-terminus is an amide, so carboxypeptidases have none either. A two-residue peptide capped at both ends is a fundamentally different pharmacokinetic object from an unmodified peptide, and it is why this is the only compound in this cohort that is credibly taken by mouth.
The number, and it is a real measured one. Absolute oral bioavailability 4.65%, determined by HPLC after intravenous and peroral dosing Boyko 2007. Read it both ways. Roughly 19 parts in 20 of a swallowed dose never reaches the circulation intact — and yet 4.65% for a peptide is remarkably high, when the unmodified heptapeptides elsewhere in this catalog have no published oral figure at all because the answer is assumed to be indistinguishable from zero.
The arithmetic that ties the numbers together. If about 5% of an oral dose gets through, an oral dose should need to be around 20 times the injected one for the same effect. The measured shift is 17- to 50-fold Kolik 2013. Two independent experiments, one analytical and one behavioral, agreeing to within a factor of two — that is what a real pharmacokinetic story looks like, and it is worth pointing at precisely because so little else in this catalog has one.
What is missing. No plasma concentration-time curve in a human has been published, so the 6 mg clinical dose is anchored to a clinical response rather than to a measured exposure Neznamov 2019. And the formulation spread means the same 6 mg can deliver 3.6-fold different exposures depending on how the tablet was made Ivannikova 2014.
Routes: what exists and what does not. Every published pharmacokinetic and clinical datum is oral, with intravenous dosing used only as the 100% reference. There is no injectable product and no subcutaneous data of any kind. The intranasal spray a buyer is most likely to encounter has no published pharmacokinetics whatsoever — not a bioavailability, not a plasma level, not an equivalence to the tablet the 6 mg figure came from. Anyone using a nasal product and quoting the clinical dose is combining a number from one route with a delivery system nobody has studied.
What would have to be true, and how you would know it was not
Four predictions, and the second one has never been made for this compound anywhere.
1. Morning cortisol will not move. The target is a cholecystokinin receptor, not the HPA axis. Baseline and 4 weeks; expect a flat line. This matters more here than on most pages because the compound is used for anxiety, and cortisol is the marker people reach for — a flat cortisol with genuine symptom improvement is the expected result, not a contradiction.
2. Serum gastrin should move, and nobody has ever looked. The CCK-B receptor is the gastrin receptor. Blocking it at the parietal cell reduces acid drive, and the standard physiological response to reduced acid drive is a compensatory rise in serum gastrin — the same feedback that makes gastrin climb on a proton-pump inhibitor. So: draw serum gastrin fasting at baseline and after 4 weeks at 6 mg/day. If it rises, this compound is reaching peripheral CCK2 receptors at clinical doses, which is new information about where it acts. If it does not move at all, the drug is either centrally restricted or not achieving receptor occupancy peripherally — also new information. This is a cheap, orderable test and it is the only prediction on this page that could produce a genuinely novel result.
3. A CBC and high-sensitivity CRP should not move — with one reason to draw them anyway. The safety package reports no immunotoxicity, and in the same paper 10 mg/kg suppressed the inflammatory reaction to concanavalin A Sorokina 2010. Both statements are in one document and both are true. At 6 mg in a 70 kg adult — about 0.086 mg/kg, more than a hundred times below that dose — predict no change. A marked fall in CRP would mean the immunological signal seen in rats is larger in people than the dose ratio suggests, and that belongs on the record.
4. The stimulating-yet-sleep-improving claim is internally tense, and actigraphy settles it. The clinical description is a fast anxiolytic effect with stimulating properties that also improved sleep disturbance Neznamov 2019. Those pull in opposite directions. Wear a tracker for two weeks before and across a 21-day course and look at sleep onset latency and total sleep time. If sleep gets worse while anxiety improves, the published profile is not reproducing at the dose being used — which for a nasal product of unknown bioavailability is the most likely explanation.
What nobody has tested yet
Six experiments. The first is the obvious one that the receptor identity demands and nobody has run.
1. Nobody has measured gastrin or gastric acid output on a CCK-B antagonist dosed for weeks. The receptor being blocked is the gastrin receptor. Twenty people, a fasting gastrin before and after 21 days at 6 mg/day, and the field would know whether this compound reaches peripheral CCK2 receptors at its clinical dose. In two decades of work on this molecule it has not been done.
2. There is no published binding constant. ‘Low-affinity blocker’ Neznamov 2019 is the most precise potency description that exists. A radioligand assay against human CCK2 would take a week and would let anybody compare this to every other CCK antagonist ever made.
3. Nobody has published a human plasma concentration. The rat pharmacokinetics are done to a standard Boyko 2007 and the human study measured clinical scales Neznamov 2019. The two have never been joined, so no one can say what exposure 6 mg produces in a person.
4. Nothing at all has been published on the nasal route, which is the form most people will actually buy. Not a bioavailability, not a dose equivalence, not a single measured concentration.
5. No placebo-controlled trial exists, and the indication demands one. A 31-patient open dose-finding study in generalized anxiety disorder Neznamov 2019 is a starting point, not a result. Anxiety is the indication where placebo response is largest, so this is the compound in this cohort where a small blinded trial would change the most.
6. Nobody has tested the opioid interaction the pharmacology predicts. Cholecystokinin acts as an endogenous anti-opioid peptide, so a CCK antagonist would be expected to potentiate opioid analgesia and possibly to alter tolerance. That is extrapolation from receptor pharmacology, clearly labeled as such: no study of GB-115 with an opioid has been published in any species, and the compound is being taken by people who may also be prescribed one.
GB-115 — its own safety story, not its class's
The class block on this page is written for phenibut, trazodone, propranolol and cabergoline — real pharmacological drugs with known receptor problems. GB-115's own story is different, and the first part of it is unusually good news.
1. It has the most complete preclinical safety package of any compound in this cohort, and that deserves to be stated plainly. No lethality at 6000 mg/kg orally in mice or 3500 mg/kg in rats; six months of dosing in two species at 0.1 and 10 mg/kg without irreversible organ change; negative allergenicity, immunotoxicity and mutagenicity testing; and no effect on generative function or on antenatal and postnatal development Sorokina 2010. Most compounds on this site have none of this. Reading a real toxicology package as if it were absent would be as dishonest as inventing one.
2. What that package does not cover. Six months in a rat is not years in a person, and a preclinical study is not a clinical one: the entire human exposure on record is 31 people for 21 days Neznamov 2019. And inside the same safety paper sits a finding that reads the other way — 10 mg/kg suppressed the inflammatory reaction to concanavalin A. ‘No immunotoxicity’ and ‘suppressed an immune reaction’ are both true statements from one document, and the second is not a contradiction of the first so much as a hint that the compound is not inert in the immune system.
3. The stomach is this page's specific unexamined risk. The receptor being antagonized is the gastrin receptor. Long-term suppression of gastrin signaling is not a neutral act in gastroenterology, and there is not one gastrointestinal measurement in the entire published record for this molecule. Anyone with reflux, atrophic gastritis, a history of gastric surgery, or on a proton-pump inhibitor is in exactly the situation nobody has studied.
4. The opioid interaction, labeled as prediction. Cholecystokinin opposes opioid analgesia endogenously, so a CCK antagonist would be predicted to increase an opioid's effect. No study of this combination exists for GB-115.
5. The practical hazard is that the product and the evidence do not match. The evidence is a 1 mg oral tablet made at one institute, at 6 mg/day, in a formulation whose bioavailability differs up to 3.6-fold from other presentations of the same compound Ivannikova 2014. What is on sale is powder or a nasal spray with no published pharmacokinetics. Weighing out ‘6 mg’ of powder is not reproducing the study; it is guessing at an exposure with a number borrowed from a different dosage form.
Sources read for this page
- Boyko SS, Kolyvanov GB, Zherdev VP, Gudasheva TA, Kiryanova EP, Seredenin SB. Experimental study of the pharmacokinetics of a tryptophan-containing dipeptide GB-115. Bulletin of Experimental Biology and Medicine 2007 · PMID 18457023
- Sorokina AV, Alekseeva SV, Nemova EP, Kovalenko LP, Smol'nikova NM, Shipaeva EV, et al. Preclinical safety investigation of GB-115 dipeptide. Eksperimentalnaia i Klinicheskaia Farmakologiia 2010 · PMID 20726348
- Kolik LG, Gudasheva TA, Seredenin SB. Role of the cholecystokinin system in anxiolytic activity of dipeptide GB-115. Bulletin of Experimental Biology and Medicine 2012 · PMID 23113301
- Kolik LG, Konstantinopolsky MA, Ryibina IV, Povarnina PY, Gudasheva TA, Seredenin SB. Anxiolytic activity of dipeptide GB-115 after oral administration. Bulletin of Experimental Biology and Medicine 2013 · PMID 24130989
- Ivannikova EV, et al. Pharmacokinetics of three peroral dosage forms of new dipeptide anxiolytic drug GB-115. Eksperimentalnaia i Klinicheskaia Farmakologiia 2014 · PMID 25322652
- Gudasheva TA. Novel Technologies for Dipeptide Drugs Design and their Implantation. Current Pharmaceutical Design 2018 · PMID 30295186
- Neznamov GG, et al. Results of a clinical study of a new anxiolytic, a blocker of central cholecystokinin receptors. Zhurnal Nevrologii i Psikhiatrii im S S Korsakova 2019 · PMID 31626171
GB-115 — safety, predicted from mechanism
Predicted from mechanism, not from a human safety trial. How that reasoning works →
What the mechanism predicts
Derived from the molecule, not a trial.
- This group acts directly on established CNS receptors — GABA-B (phenibut), serotonergic and histaminergic (trazodone, doxepin), beta-adrenergic (propranolol), dopaminergic (cabergoline, apomorphine). These are pharmacological drugs, not research peptides, and the predicted problems are the known ones for each receptor.
- Phenibut is the one that needs saying plainly: it is physically addictive. GABA-B agonism produces tolerance within days of regular use, and withdrawal is genuinely severe — anxiety, insomnia, tremor, and in heavy users, psychosis and seizures. It is closer to a benzodiazepine than to a nootropic in this respect, and it is sold as though it were the latter.
- Propranolol blunts the physical symptoms of adrenaline. That predicts the useful effect and also the problem — it blunts the training response and masks hypoglycemia.
- Dopamine agonists predict nausea, orthostatic hypotension and, at the doses used in Parkinson's, impulse-control problems. Cabergoline's half-life is very long, so effects persist well past a dose.
What has actually been reported
- Phenibut dependence and withdrawal are well documented in case reports and poison-center data.
- Trazodone: sedation, orthostatic hypotension, and rarely priapism — which is a medical emergency.
- Abrupt propranolol cessation causes rebound tachycardia and hypertension. Do not stop a beta-blocker suddenly.
- Cabergoline at high cumulative doses is associated with cardiac valve changes; at the low doses used for prolactin this has not been shown.
How to reduce the risk
Same mechanism as the prediction.
- For phenibut, the only reliable mitigation is frequency: occasional use does not produce dependence, regular use does. There is no dose that makes daily use safe.
- Taper anything in this group rather than stopping abruptly.
- Take the first dose of anything with orthostatic effects at home, sitting down.
What it does to your bloodwork
A fact about the assay.
- Prolactin if using cabergoline (it is usually why you are). Otherwise blood pressure and heart rate are the monitoring that matters.
Don't run this if
- You already take a sedative, a benzodiazepine, or drink regularly — the CNS depressant effects are additive and this is where respiratory depression comes from.
- You are on an antidepressant and considering trazodone — serotonergic combinations need a prescriber, not a forum.
The honest unknown
- Most of this group is well characterized for its licensed use. What is NOT characterized is the off-label use most people here are making of it, at doses and durations nobody studied.
Not medical advice. If you take prescription medication or have a diagnosed condition, check this with a pharmacist or doctor.
GB-115 — interference & stacking
Predicted from mechanism, not from an interaction study. How mechanism-predicted claims are made →
What GB-115 moves on your bloodwork
Expected direction, not a measured one.
- Comprehensive Metabolic Panel (CMP) — ◆ worth watching
Most of this class has no predicted marker movement at all, and saying so is more useful than listing markers that will not move.
What to do: A baseline liver panel is reasonable for anything taken daily and long-term. Beyond that there is nothing specific to chase.
- How to work up to it, and when not to
- When to take it, and why that window
- Cycle length
- Time off between cycles
- Fasted or fed, and when in the day
- How the forms differ in dose
- Coach Cam's personal notes
- Which compounds push the same lever, and why the dose adds up faster than people count
- What blunts it — the stacks that waste your money
- What compounds the risk, so a side effect arrives sooner than any one of them suggests
- Coach Cam's read on running it alongside the rest of your protocol
Everything above is free and stays free. Skool is where it becomes a plan — GB-115 in an order, with the rest of what you're running.
Unlock in Skool — $10/mo →Bloodwork to run alongside GB-115
Baseline first, then again at 8–12 weeks.
| Marker | What it’s watching for |
|---|---|
| TSH (Thyroid-Stimulating Hormone) | Thyroid disease imitates every cognitive complaint there is |
| Vitamin B12 | Deficiency causes fog long before it causes anemia |
| Methylmalonic Acid (MMA) | Catches the deficiency a normal B12 hides |
| Ferritin | Low iron flattens cognition at levels most labs call fine |
| Vitamin D (25-Hydroxy) | Commonly low, cheap to correct, associated with mood |
The Brain Fog & Cognition panel covers these in one order — 12 markers, $233.06 with the discount applied.
Check results you already have → · All 103 markers A–Z
GB-115 — frequently asked questions
What is GB-115?
GB-115 (Cholecystokinin-4 antagonist) is a cognitive & mood research compound. A dipeptide CCK-B receptor antagonist developed in Russia. CCK-4 reliably induces panic in humans, so blocking that receptor is a rational anxiolytic target that doesn't touch GABA.
Is the full GB-115 protocol on this page?
The reported research dose is on this page, along with how GB-115 works and the evidence behind it. The protocol — how to work up to it, frequency, cycle length, time off, what not to stack it with and Coach Cam's notes — is inside Skool.
What is the half-life of GB-115?
GB-115 has an approximate half-life of Not characterized in published human work, which is part of what determines how often it's dosed.
What forms does GB-115 come in?
GB-115 is available as: Oral, Nasal.
What's the evidence behind GB-115?
Current evidence level: Russian preclinical and early clinical work, little of it in English or peer-reviewed internationally. GB-115 is offered for research purposes only and is not an approved medicine.
What GB-115 is used for
GB-115 appears under 1 goal in the goal router.
Related Cognitive & Mood compounds
Where this goes next
The pages here are the frameworks. The protocols — the dosing, the order to correct things in, the week-by-week schedule and what to retest — are inside Skool.