Quick Comparison

Citicoline (CDP-Choline)Coluracetam
Half-Life56-71 hours (sustained release characteristics)2-3 hours
Typical DosageStandard: 250-500 mg daily. Clinical studies use 500-2000 mg daily. Take in the morning — mildly stimulating. Cognizin is the most studied form. Can be split into 2 doses. Often combined with racetams to provide the choline needed for enhanced acetylcholine turnover.Standard: 20-80 mg sublingually, 2-3 times daily. Start at 20 mg to assess sensitivity. Sublingual is strongly preferred for bioavailability.
AdministrationOral (capsules, powder). Cognizin branded form is most studied. Take in the morning.Sublingual (strongly preferred) or oral. Oral bioavailability is limited.
Research Papers10 papers1 papers
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Mechanism of Action

Citicoline (CDP-Choline)

Citicoline (CDP-choline) is hydrolyzed in the gut by alkaline phosphatase to choline and cytidine-5'-monophosphate, which are absorbed separately and reassembled in the brain via the Kennedy pathway. Choline feeds two critical pathways: (1) Acetylcholine synthesis via choline acetyltransferase (ChAT) — the primary memory and learning neurotransmitter acting at muscarinic and nicotinic receptors. (2) Phosphatidylcholine synthesis via CTP:phosphocholine cytidylyltransferase — the structural component of neuronal membranes and synaptic vesicles. Cytidine is dephosphorylated to uridine, converted to UTP, and supports RNA synthesis and CDP-choline formation for synapse formation. Citicoline also activates SIRT1 (possibly via NAD+ modulation) and increases brain norepinephrine and dopamine (mechanism unclear — may enhance synthesis or release). It is the only choline source providing both cholinergic and membrane-building support in one molecule.

Coluracetam

Coluracetam's primary mechanism is enhancement of high-affinity choline uptake (HACU) in hippocampal neurons — the rate-limiting step in acetylcholine synthesis. HACU is mediated by the high-affinity choline transporter (CHT1/SLC5A7), which coluracetam upregulates or potentiates, increasing the Vmax of choline transport into presynaptic terminals. By making this process more efficient, coluracetam increases acetylcholine production and vesicular packaging via the vesicular acetylcholine transporter (VAChT) even when choline levels are normal. This enhances cholinergic transmission in the hippocampus, cortex, and retina — explaining reports of enhanced color vision and visual acuity. Coluracetam also has minor AMPA receptor positive allosteric modulation. The compound was studied for treatment-resistant depression, possibly through cholinergic modulation of mood circuits.

Risks & Safety

Citicoline (CDP-Choline)

Common

Headache (especially with racetams — indicates too much cholinergic stimulation), nausea, diarrhea.

Serious

None documented at standard doses.

Rare

Insomnia, blurred vision.

Coluracetam

Common

Headache, fatigue, brain fog at high doses.

Serious

Very limited human safety data — studied only in small trials.

Rare

Anxiety, irritability, suicidal ideation was reported in one clinical trial participant.

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