Picamilon

Nicotinoyl-GABA

Picamilon (Nicotinoyl-GABA) is a cognitive & mood research compound. Niacin + GABA conjugate — crosses the BBB then splits, delivering GABA (calm) plus niacin (cerebral blood flow).

How Picamilon works

Niacin + GABA conjugate — crosses the BBB then splits, delivering GABA (calm) plus niacin (cerebral blood flow).

Proposed benefits

Researched for focus, memory, neuroprotection, mood and stress resilience.

Where to get Picamilon

The evidence for Picamilon

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

• Used in Russia for cerebrovascular conditions and anxiety. The FDA ruled in 2015 that it does not qualify as a dietary supplement in the US, removing it from that market — a regulatory classification decision, not a safety finding.
• Reported experience is a mild anxiolysis without sedation.

🧪 Theoretical / extrapolated

• GABA covalently bound to niacin. GABA itself barely crosses the blood-brain barrier, which is why oral GABA does little; the niacin conjugate is designed to carry it across, where it is then cleaved into both parts.
• That predicts the dual effect reported — GABAergic calm plus niacin's vasodilation — and it is a genuinely clever bit of prodrug design regardless of how strong the end result is.

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 Picamilon actually does

Picamilon is one amide bond: the carboxyl of nicotinic acid joined to the amino group of gamma-aminobutyric acid. C10H12N2O3, 208.22 Da as the free acid, 230.2 Da as the sodium salt most products actually contain. Capping GABA's amine is not cosmetic — free GABA is a zwitterion carrying both a positive ammonium and a negative carboxylate, and it is that permanent charge pair which makes oral GABA a poor traveller. Acylate the amine and the molecule becomes a simple mono-anion with an aromatic ring attached, which is a different physicochemical object entirely.

The 2023 result that should change how this compound is described. Santillo and Sprando screened picamilon against 50 safety-related biological targets — receptors, ion channels, enzymes and transporters — using two computational prediction tools and an in-vitro binding panel at 10 µM. Both computational tools predicted no binding to any target tested, and the in-vitro measurements found weak or no binding across the whole panel; despite structural similarity to other GABA analogs, picamilon showed a distinct — that is, empty — binding profile Santillo 2023. Take that seriously in both directions. It means the intact molecule is not a GABA-receptor ligand, not a niacin-receptor ligand, and not anything else on a standard safety panel. Whatever picamilon does, it does only after being cut in half. It is a prodrug in the strict sense, and this is the first time that has been shown by exclusion rather than assumed.

What has to cut it, and why that is not an esterase. The bond is a secondary amide between an aryl carboxylic acid and a primary alkylamine. Amide bonds are orders of magnitude more stable in plasma than the ethyl esters that carry other nootropics — the compound is not falling apart in the blood the way noopept's ester does. Cleavage needs an amidase or acylase, and the identity of that enzyme, and the tissue it sits in, is the single fact that decides whether this molecule is a brain-delivery device or an expensive way to take niacin. It has never been established.

What the two halves do once free. GABA acts at GABA-A chloride channels and GABA-B G-protein-coupled receptors. Nicotinic acid acts at HCA2 (GPR109A), the receptor on epidermal Langerhans cells whose activation releases prostaglandin D2 and produces the niacin flush, and on adipocytes where it suppresses lipolysis. Every discussion of picamilon describes the GABA arm and leaves out the second one, which is a mistake: HCA2 is where the dose-dependent, immediately observable, entirely falsifiable part of this compound's pharmacology lives.

And a finding nobody has followed up. In an outpatient study, picamilon treatment was accompanied by a fall in elevated ADMA concentrations and in the ADMA/MMA and (ADMA+SDMA)/MMA ratios, alongside increased linear cerebral blood-flow velocity, reduced intima-media thickness and a reduced resistance index Danilov 2024. ADMA is asymmetric dimethylarginine, the endogenous competitive inhibitor of endothelial nitric oxide synthase. If that result is real, the vascular mechanism of this compound is not ‘niacin dilates vessels’ but less inhibition of eNOS — a completely different claim, and one attached to an assay anybody can order.

Cell, rodent, human — and where it stops

In vitro. 50 targets, 10 µM, nothing binds Santillo 2023. That is the entire modern in-vitro record for this molecule, and its value is negative information: it rules out a direct receptor action rather than demonstrating one.

The rodent rung is missing, and that is worth saying plainly. The claim that picamilon crosses the blood-brain barrier intact and is then hydrolyzed in brain tissue rests on Soviet-era work that is not indexed in English, and the 2023 target screen is the first modern characterization of any kind Santillo 2023. So the chain runs tube → gap → human, and the missing rung is the one that would tell you where the molecule splits.

In humans, and there are two 2024 studies, both open. The outpatient study randomized 44 people aged 46–67 with stage I chronic cerebral ischemia into two arms: 50 mg orally three times a day for 60 days, or 100 mg intramuscularly daily for 10 days then 50 mg three times a day for 50 days. Across the whole sample MoCA went 24.9 → 26.5 → 28.3 (p=0.022 then p<0.001), the Fedin neurological score fell from 11.9±8.3 to 6±6.1 and then to 2.77±4.43, sleep quality improved in 50% by visit 3 and 84% by visit 4, autonomic function normalized in 29%, adverse events ran below 8.6%, and the ADMA changes above were recorded Danilov 2024. The second study was an open cohort of 50 patients aged 51–69 with stage II disease given 200 mg intravenously daily for 10 days then 50 mg three times a day for 60 days; MoCA improved significantly, sleep normalized in 81%, the Fedin score fell from 17.4±9.34 to 5.31±5.71, and tolerability was 98% Danilov 2024.

The obstacles, and the first one is fatal to the effect size. (1) Neither study was blinded and neither had a placebo group. An open design with MoCA administered four times to the same person produces a practice effect of roughly the magnitude being reported; a 3.4-point rise across four sittings without a control arm cannot be separated from learning the test. (2) Both studies front-load a parenteral dose nobody outside Russia uses — 100 mg intramuscularly or 200 mg intravenously, daily for 10 days — and the pure-oral arm, while it also improved, has no control either Danilov 2024. (3) The trials ran 60 days; the compound is used acutely. Almost everyone taking picamilon takes it for a specific afternoon, and there is no acute-dose human study at all. (4) The 10 µM negative screen forces the mechanism question back one step Santillo 2023: if the intact molecule binds nothing, then the amount of GABA and the amount of nicotinic acid actually liberated, and where, is the mechanism — and no one has measured either in a person.

The number that reframes the whole product. Hydrolysis of 100 mg of picamilon (0.48 mmol) yields 49.5 mg of GABA and 59.1 mg of nicotinic acid; 200 mg yields 99 mg and 118 mg. So the trials' oral regimen, 150 mg/day, delivers about 74 mg of GABA and 89 mg of niacin a day. Compare that with the plain GABA capsules people buy, which are dosed at 500 to 3,000 mg. Picamilon delivers less GABA than a GABA supplement. Its entire argument therefore has to be about where the GABA is released, not how much — and that is precisely the fact nobody has established.

Picamilon pharmacokinetics — how much of it actually gets in

The catalog says ‘Short (~hours)’. The interesting pharmacokinetics here are stoichiometric rather than temporal.

What degrades it, and why the answer is unusual. Not plasma esterases — there is no ester. An amide between nicotinic acid and GABA needs enzymatic amide hydrolysis, and mammalian amidases are far more selective and far less abundant than the carboxylesterases that dismantle ester prodrugs within minutes. That is the mechanistic reason picamilon can survive an oral course at all, and it is also why the release rate is the unknown: a bond that is hard to break is a bond whose breaking site and speed determine everything.

The stoichiometry, which is the number to carry away. Complete hydrolysis of 1 mmol of picamilon consumes 1 mmol of water and releases 1 mmol of nicotinic acid (123.11 Da) and 1 mmol of GABA (103.12 Da). Per 50 mg capsule that is 29.6 mg of niacin and 24.8 mg of GABA; per 200 mg, 118 mg and 99 mg. If your product is picamilon sodium rather than the free acid, subtract about 10% from both because the counter-ion is dead weight. The niacin figure is the one that matters practically: immediate-release nicotinic acid produces flushing in many people at doses as low as 30–50 mg, so a 200 mg picamilon dose carries niacin well above the usual flush threshold in a form that reportedly does not flush — which is itself evidence about the hydrolysis rate, and is discussed as a prediction below.

The oral barrier and first pass. At intestinal pH the free acid is a mono-anion; anions do not cross the enterocyte by passive diffusion in quantity, so a carrier is implied and none has been identified. Whatever crosses reaches the portal vein first, and the liver extracts nicotinic acid avidly — so if hydrolysis happens anywhere before or inside the hepatocyte, the liver sees more of the niacin arm than the brain ever will. That single asymmetry explains both why the flush is muted and why the hepatic cautions that belong to high-dose niacin are the ones worth importing here rather than the neurological ones.

Route. This site lists oral at 50–200 mg. Both 2024 trials began parenterally — 100 mg intramuscularly or 200 mg intravenously, daily for 10 days Danilov 2024 Danilov 2024 — which bypasses the first-pass asymmetry entirely and is therefore not a stronger version of the oral protocol but a mechanistically different one.

What would have to be true, and how you would know it was not

Four predictions. The second is designed to embarrass the mechanism if the mechanism is wrong.

1. ADMA should fall, and this is the one worth running. The outpatient study reported reduced ADMA and reduced ADMA/MMA ratios alongside improved flow velocity and reduced intima-media thickness Danilov 2024. It is an open study and it has never been replicated, which makes it the most interesting unconfirmed result picamilon has. Order ADMA and SDMA at baseline and at 8 weeks on 150 mg/day; keep arginine intake, blood pressure medication and kidney function stable across the window, because all three move ADMA harder than this will. If ADMA does not move, the endothelial story collapses and what is left is a slow-release niacin with a small GABA payload.

2. Against the mechanism: 200 mg on an empty stomach should not flush. That dose carries 118 mg of nicotinic-acid equivalent, which as immediate-release niacin would flush a large fraction of people within 30 minutes. Sit with it for 45 minutes and watch your forearms and ears. Absence of any flush is evidence that the niacin arm is not reaching the skin as free nicotinic acid, and therefore evidence against the popular claim that picamilon ‘splits into both parts’ systemically. A flush, conversely, means the hydrolysis is fast and peripheral, which undermines the brain-delivery claim from the other side. Both answers are informative and neither has been published.

3. The lipid panel and uric acid should stay flat. Nicotinic acid lowers triglycerides, raises HDL and raises urate — at grams per day, not at 89 mg. Prediction: on 150 mg/day of picamilon, a lipid panel and uric acid at 12 weeks look exactly like baseline. If they move, either the product contains more than the label says or hydrolysis is far more complete and systemic than anyone thinks — and given that 75% of declared quantities in this product category were found inaccurate Cohen 2021, the first explanation deserves checking before the second.

4. MoCA will not move in a healthy person, and the trials do not claim it will. Both 2024 studies enrolled patients with a cerebrovascular diagnosis and used an open design Danilov 2024 Danilov 2024. In an intact adult the instrument ceilings. Naming this here is the point: the compound's human evidence is entirely in impaired populations and entirely unblinded, so there is currently no test a healthy user could run that would count as confirmation.

What nobody has tested yet

Five experiments. The first two are cheap enough that their absence is genuinely strange.

1. Nobody has measured plasma GABA and plasma nicotinic acid after an oral picamilon dose in a human. Both assays are routine. One six-person time course after 200 mg would show whether the molecule is cleaved at all, how fast, and in what proportion — which is the entire mechanism, reduced to one afternoon in a clinical pharmacology unit. More than fifty years after the compound was first synthesized, it has not been done in the open literature.

2. Nobody has run the flush-threshold comparison. Escalating picamilon doses against equimolar immediate-release nicotinic acid doses, same subjects, crossover, flush intensity and onset time as the endpoint. It directly measures the hydrolysis rate using nothing but a stopwatch and a skin, and it would settle the ‘does it split’ argument that every forum thread on this compound runs into.

3. Nobody has identified the amidase. Which enzyme hydrolyzes the nicotinoyl-GABA bond, and whether it lives in the gut wall, the liver, the blood or the brain, is unpublished. Recombinant human amidase panels exist. The answer decides whether the whole prodrug rationale is correct or whether picamilon is mostly excreted intact.

4. Nobody has replicated the ADMA finding under blinding. It is a single open study of 44 people Danilov 2024, and it is the only biochemical mechanism result picamilon has in a human. A 40-person placebo-controlled crossover with ADMA as the primary endpoint would either give this compound a real mechanism or close the question.

5. Nobody has run a blinded trial of any kind. Two studies in 2024, 94 patients between them, no placebo arm in either Danilov 2024 Danilov 2024. For a drug that has been in clinical use since the 1980s that is an extraordinary state of affairs, and it is the reason the honest summary of picamilon's efficacy is ‘unknown’ rather than ‘modest’.

Picamilon — its own safety story, not its class's

The class block is written for GABAergics that cause dependence. Picamilon is not one of those, and its actual risk story is different in four ways.

1. The strongest safety datum picamilon has is a negative screen, and a page that only listed risks would hide it. Fifty safety-related targets, 10 µM, weak or no binding on any of them, and no predicted binding from either computational tool Santillo 2023. That is genuinely reassuring about off-target pharmacology of the intact molecule, and it is better evidence of the absence of receptor-level trouble than most compounds in this catalog can produce.

2. The risk that does exist belongs to the niacin half. At the top of the site's range, 200 mg carries 118 mg of nicotinic-acid equivalent. Flushing, itch and a warm head-rush are the expected effects of that arm and are harmless; what belongs on a longer-course label is that nicotinic acid at sustained higher intakes raises hepatic enzymes and urate. At 89 mg/day, the trial dose, that is unlikely. At the doses people escalate to when they feel nothing, the arithmetic changes, and the marker that notices is a liver panel and uric acid rather than anything neurological.

3. The supply problem is measured, not speculated. Picamilon was one of five unapproved drugs found in cognitive-enhancement supplements bought online; across those products 75% of declared quantities were inaccurate, some drugs were present but unlabelled, others were labeled but not detected, and consumers following the serving size were exposed to pharmaceutical quantities up to four-fold above typical pharmacologic doses Cohen 2021. A European and Australian market surveillance study across 12 official medicines control laboratories documented 159 samples and 34 distinct molecules over 2020–2024, 69% of them from the illegal market Vanhee 2025. The FDA's 2015 decision that picamilon does not qualify as a dietary supplement is a classification, not a toxicology finding — but its practical consequence is that any US product containing it is one that should not, which is exactly the population those analyses sampled.

4. The failure mode is a null, not an injury. Given the empty 10 µM screen, the unmeasured hydrolysis, the small delivered GABA mass and the absence of a single blinded trial, the most likely thing to go wrong with picamilon is that a person spends two months on it for an anxiety or sleep problem that had a treatable cause. Name it, because it is more probable than any pharmacological harm on this page.

Sources read for this page

• Santillo MF, Sprando RL. Picamilon, a γ-aminobutyric acid (GABA) analogue and marketed nootropic, is inactive against 50 biological targets. Basic & Clinical Pharmacology & Toxicology 2023;132(4):355-358 · PMID 36668678
• Danilov AB, Shindryaeva NN, Borodulina IV, Lunegov TD. Integrative assessment of the effectiveness and safety of outpatient use of Picamilon. Zhurnal Nevrologii i Psikhiatrii im. S.S. Korsakova 2024;124(7):119 · PMID 39113452
• Danilov AB, Shindryaeva NN, Borodulina IV, Lunegov TD, Kristeleva DA. Clinical efficacy and safety of Picamilon in patients with progressive chronic cerebral ischemia. Zhurnal Nevrologii i Psikhiatrii im. S.S. Korsakova 2024;124(8):71 · PMID 39269299
• Cohen PA, Avula B, Wang YH, Zakharevich I, Khan I. Five Unapproved Drugs Found in Cognitive Enhancement Supplements. Neurology: Clinical Practice 2021;11(3):e303-e307 · PMID 34484905
• Vanhee C, Deconinck E, George M, Hansen A, Hackl A, Wollein U, El-Atma O, Beerbaum N, Aureli F, Borioni A, et al. The Occurrence of Illicit Smart Drugs or Nootropics in Europe and Australia and Their Associated Dangers: Results from a Market Surveillance Study by 12 Official Medicines Control Laboratories. Journal of Xenobiotics 2025;15(3):88 · PMID 40558871

Picamilon — safety, predicted from mechanism

Picamilon — interference & stacking

Bloodwork to run alongside Picamilon

Baseline first, then again at 8–12 weeks.

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Picamilon — frequently asked questions

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