Quick Comparison
| Coluracetam | Huperzine A | |
|---|---|---|
| Half-Life | 2-3 hours | 10-14 hours |
| Typical Dosage | Standard: 20-80 mg sublingually, 2-3 times daily. Start at 20 mg to assess sensitivity. Sublingual is strongly preferred for bioavailability. | Standard: 50-200 mcg once or twice daily. Due to the long half-life, cycling is recommended (2 weeks on, 1 week off). Do not combine with prescription acetylcholinesterase inhibitors (donepezil, rivastigmine). |
| Administration | Sublingual (strongly preferred) or oral. Oral bioavailability is limited. | Oral (capsules, tablets). Well-absorbed orally. |
| Research Papers | 1 papers | 10 papers |
| Categories |
Mechanism of Action
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.
Huperzine A
Huperzine A is a potent, selective, and reversible inhibitor of acetylcholinesterase (AChE), binding to the enzyme's active site and preventing hydrolysis of acetylcholine to choline and acetate. By blocking AChE, it increases acetylcholine concentration in the synaptic cleft, prolonging activation of muscarinic (M1-M5) and nicotinic receptors. Huperzine A also blocks NMDA glutamate receptors in a non-competitive, use-dependent manner (similar to memantine), binding to the phencyclidine site within the ion channel and protecting neurons from excitotoxic calcium influx. It shows selectivity for the NR2A and NR2B subunits. Additionally, huperzine A has antioxidant properties, scavenging reactive oxygen species and reducing lipid peroxidation. It may enhance NGF signaling.
Risks & Safety
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.
Huperzine A
Common
Nausea, diarrhea, sweating, muscle twitching.
Serious
Cholinergic crisis at high doses (excessive acetylcholine causing muscle weakness, breathing difficulty).
Rare
Blurred vision, slowed heart rate, seizures.
Full Profiles
Coluracetam →
A racetam that enhances high-affinity choline uptake (HACU) — the rate-limiting step in acetylcholine synthesis. This makes it uniquely effective at boosting acetylcholine levels, which is why users commonly report enhanced color vision, sharper visual perception, and improved memory. It was briefly studied for treatment-resistant depression.
Huperzine A →
A naturally occurring alkaloid extracted from Chinese club moss (Huperzia serrata). It powerfully inhibits acetylcholinesterase — the enzyme that breaks down acetylcholine — resulting in significantly elevated acetylcholine levels in the brain. Used in Chinese medicine for centuries and now studied worldwide for Alzheimer's disease.