A small trial challenges a larger one
STUDY: Bavali Oleyayi MS et al, Neuroscience 2026
STUDY TYPE: Randomized, triple-blind, placebo-controlled pilot trial
FUNDING: Independent
Background
Citicoline is a neuroprotective supplement with evidence in stroke, cognition, and meth/cocaine use disorder. In the brain, it supports membrane repair, promotes acetylcholine and dopamine synthesis, and reduces oxidation and neuroinflammation. Studies in traumatic brain injury, however, have been mixed with positive and negative results.
The Study
- 60 adults with mild-to-moderate traumatic brain injury (Glasgow Coma Scale 9-15) at one hospital in Iran.
- Randomized to citicoline 1,000 mg/day or placebo for 90 days, started within 48 hours, plus standard care.
- Triple-blind; all 60 completed follow-ups.
- Primary outcome: 90-day cognition (Mini-Mental State Exam); secondary: function (Barthel Index, GOS-E).
Results
At 90 days, citicoline patients scored higher on the Mini-Mental State Exam than placebo, 25.2 versus 21.5. Function also improved, with significant differences in overall functioning and activities of daily living (all p < 0.001).
Side Effects
None.
Limitations
Small size, results contradicted by a large trial (COBRIT).
Practice Implications
- Intriguing results, but I’d await further positive trials before acting on this. It is still a mix of positive and negative.
- More promising is its use to improve mood, cognition, and sobriety in cocaine or meth use disorder, and cognition in stroke and age related cognitive decline (target dose 1,000 mg BID). Find lab-tested products here.
—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
