Citicoline

Scientific Name(s): Cytidine 5′-diphosphocholine, Cytidine diphosphate-choline
Common Name(s): CDP-choline, Citicoline

Medically reviewed by Drugs.com. Last updated on Feb 14, 2022.

Clinical Overview

Use

There is mounting evidence for choline's place in therapy for stroke, brain and spinal cord injury, cognitive deficits, and glaucoma; however, results in clinical trials have been inconsistent.

Dosing

Oral dosages of 250 to 2,000 mg daily have been evaluated in adolescents and adults in clinical trials. Lower doses (100 mg twice daily) have been used in short-term trials (6 weeks) with combination therapy in patients with major depressive disorder.

Contraindications

Contraindications have not been identified.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking at dosages above those usually taken nutritionally.

Interactions

None well documented.

Adverse Reactions

Citicoline was well tolerated in clinical trials. Adverse effects may include GI disturbances, transient headaches, hypotension, tachycardia, bradycardia, and restlessness.

Toxicology

Studies in humans are limited.

Source

Citicoline is found in all animal and plant cell membranes. It is available commercially in its free-base form or as a sodium salt.1

History

Citicoline is widely available internationally as a supplement, which was originally developed in Japan for the treatment of cerebrovascular disorders. Use of citicoline has been extended to include treatment of chronic conditions, although further research is needed.2

Chemistry

Citicoline is a phospholipid composed of ribose, pyrophosphate, cytosine, and choline. It is water-soluble and highly bioavailable.3 Citicoline is produced endogenously as an intermediate in the production of phosphatidylcholine from choline and is then hydrolyzed in the small intestine to make choline and cytidine available for further biosynthesis.4

Uses and Pharmacology

Supplementation with citicoline increases choline stores available for other biosynthetic pathways. Citicoline appears to decrease glutamate levels in the brain and increase adenosine triphosphate, which in turn offers protection against ischemic neurotoxicity. Increased glucose metabolism in the brain and cerebral blood flow has also been demonstrated, as well as increased availability of the neurotransmitters acetylcholine, norepinephrine, and dopamine.4, 5

Cocaine dependence

Clinical data

Studies have investigated a role for citicoline in substance addiction and among patients with bipolar disorder.25, 26 A 12-week, double-blind, parallel-group, randomized, placebo-controlled trial (n = 130) in adults with bipolar disorder and cocaine dependence reported a significant early treatment effect in favor of citicoline (500 mg/day titrated up every 2 weeks to 2,000 mg/day by week 6) compared to placebo.34

Cognition

Animal data

Accelerated resynthesis of phospholipids and subsequent protection of cell membranes in the presence of citicoline have been suggested as a possible mechanism of action, based on animal studies. Labeled phospholipid from radioactively labeled citicoline has been shown to cross the blood-brain barrier. Studies in rats with cognitive impairment have been conducted, and im...