Citicoline – An Overview
Citicoline (sometimes called CDP-choline) is a naturally occurring choline source in the body. It is taken as a nootropic supplement for:
- Improved cognition
- Mental function
- Energy and focus
Citicholine is an endogenous nucleotide found in every cell. It is a necessary component of the cell membrane phosphatidylcholine, which is a major component of all neurons.1Fernández-Murray JP1, McMaster CR. Glycerophosphocholine catabolism as a new route for choline formation for phosphatidylcholine synthesis by the Kennedy pathway J Biol Chem. 2005
This nootropic is an excellent source of choline, which is a precursor of acetylcholine (ACh).
ACh is an extremely important neurotransmitter that is necessary for learning, memory, and overall cognitive function.
Low ACh levels can cause problems with memory and other mental functions, eventually leading to cognitive degeneration.
Citicoline has emerged as a treatment for patients with chronic cerebrovascular disorders or memory problems.2Mario Fioravanti and Ann E Buckley. Citicoline (Cognizin) in the treatment of cognitive impairment Clin Interv Aging. 2006
Citicoline is often combined with a member of the racetam family (piracetam, aniracetam, oxiracetam, etc…) for a performance-enhancing nootropic “stack”.
This is one of the most popular uses of citicoline in the nootropics community.
What Does Citicoline Do?
Citicoline for Memory
Citicoline increases levels of ACh, which is heavily associated with memory formation.
This had made it one of the most popular nootropics for memory.
There is a good amount of clinical research showing that it could be effective for this.
In particular, several trials indicate Citicoline is useful for alleviating memory loss due to mild cognitive impairment.
In these trials, patients were suffering some form of pre-dementia difficulty with memory or mental function.
They all point to CDP-Choline as useful for preserving and even improving cognitive abilities in aging patients.3Spiers PA, Myers D, Hochanadel GS, Lieberman HR, Wurtman RJ. Citicoline improves verbal memory in aging Arch Neurol. 1996 4Abad-Santos F, Novalbos-Reina J, Gallego-Sandín S, García AG.. Treatment of mild cognitive impairment: value of citicoline Rev Neurol. 2002 5Fioravanti M, Yanagi M. Cytidinediphosphocholine (CDP-choline) for cognitive and behavioural disturbances associated with chronic cerebral disorders in the elderly Cochrane Database Syst Rev. 2005
Keep in mind that most of the available research focuses on participants with at least mild cognitive dysfunction.
However, the same mechanism that makes it useful in these cases may extend the same benefits to healthy people as well.
Given the amount of anecdotal evidence attesting to this, we suspect it may be the case.
Citicoline for Mood and Depression
There is evidence that citicoline stimulates the release of dopamine neurotransmitters in the brain.
Dopamine is heavily linked to mood, motivation, and depression.
This, along with increasing ACh levels, could help improve feelings of well-being.6Giménez R, Raïch J, Aguilar J. Changes in brain striatum dopamine and acetylcholine receptors induced by chronic CDP-choline treatment of aging mice. Br J Pharmacol. 1991
Many users report more positive feelings in general after supplementing with CDP-Choline for a few weeks or months.
One team of researchers conducted a double-blind trial of citicoline for bipolar and unipolar depression among methamphetamine addicts.
Participants receiving citicoline had a significantly greater reduction in depressive symptoms (but not methamphetamine use) compared to placebo. 7Brown ES, Gabrielson B. A randomized, double-blind, placebo-controlled trial of citicoline for bipolar and unipolar depression and methamphetamine dependence J Affect Disord. 2012
This is an interesting result that lines up with many user’s experiences taking CDP Choline.
We hope to see more studies with patients who are suffering from depression without concurrent drug abuse as well.
Citicoline for Addiction Recovery
Due to its influence on acetylcholine, dopamine, and glutamate neurotransmitter systems, citicoline shows promise as an addiction recovery aid.
It may not only decrease urges to use, but also mitigate some of the physical damage from drug abuse.
In one meta-analysis, Citicoline appears to decrease craving and reduce cocaine use.
Limited data suggest citicoline may also hold promise for alcohol and cannabis dependence and in reducing food consumption.
This is an interesting result and deserves more study.8Nicholas D. Wignall, E. Sherwood Brown Citicoline in Addictive Disorders: A Review of the Literature Am J Drug Alcohol Abuse. 2014
In one study, cocaine users who were treated for only 14 days with citicoline reported increased control over their cocaine use and decreased urges for cocaine.9Renshaw PF1, Daniels S, Lundahl LH, Rogers V, Lukas SE. Short-term treatment with citicoline (CDP-choline) attenuates some measures of craving in cocaine-dependent subjects: a preliminary report Psychopharmacology (Berl). 1999
Another study looked at citicoline in methamphetamine users. Researchers concluded that Citicoline may exert potential neuroprotective effects directly or indirectly because of reductions in drug use.
They were unsure if the neuroprotective effects were due to CDP Choline physically reversing the damage of the meth, or by causing patients to use less, or both.10Yoon SJ1, Lyoo IK, Kim HJ, Kim TS, Sung YH, Kim N, Lukas SE, Renshaw PF. Neurochemical alterations in methamphetamine-dependent patients treated with cytidine-5′-diphosphate choline: a longitudinal proton magnetic resonance spectroscopy study Neuropsychopharmacology. 2010
Patients with a food addiction also saw a reduction in food cravings after supplementing with citicoline.
Researchers concluded that these results “suggest a potential usefulness of citicoline in modulating appetite, but further research is warranted.”11Killgore WD1, Ross AJ, Kamiya T, Kawada Y, Renshaw PF, Yurgelun-Todd DA. Citicoline affects appetite and cortico-limbic responses to images of high-calorie foods Int J Eat Disord. 2010
Citicoline for Alzheimer’s Disease
Citicoline shows a lot of promise as a treatment for Alzheimer’s and related types of dementia.
Research shows that citicoline improves cognitive performance and brain bioelectrical activity patterns in patients with Alzheimer’s.12Alvarez XA, Mouzo R, Pichel V, Pérez P, Laredo M, Fernández-Novoa L, Corzo L, Zas R, Alcaraz M, Secades JJ, Lozano R, Cacabelos R. Double-blind placebo-controlled study with citicoline in APOE genotyped Alzheimer’s disease patients. Effects on cognitive performance, brain bioelectrical activity and cerebral perfusion Methods Find Exp Clin Pharmacol. 1999
It seems that by increasing acetylcholine levels, citicoline can ward off some of the negative effects of Alzheimer’s Disease.
Low ACh levels are one of the hallmarks of this condition, and researchers believe that raising these levels could be beneficial for Alzheimer’s symptoms.13Parnetti L, Mignini F, Tomassoni D, Traini E, Amenta F.. Cholinergic precursors in the treatment of cognitive impairment of vascular origin: ineffective approaches or need for re-evaluation? J Neurol Sci. 200714Blount PJ, Nguyen CD, McDeavitt JT.. Clinical use of cholinomimetic agents: a review J Head Trauma Rehabil. 2002 Aug15Cavun S, Savci V. CDP-choline increases plasma ACTH and potentiates the stimulated release of GH, TSH and LH: the cholinergic involvement. Fundam Clin Pharmacol. 2004
Citicoline for Neuroprotection
Some trials have shown that Citicoline stabilizes cell membranes and reduces the presence of free radicals.
This is because Citicoline can increase phosphatidylcholine, which is a vital component of cell membranes.
It also acts as an antioxidant, clearing of damage caused by free radicals. This can keep the brain healthy as you age.
These actions may also prevent damage caused by stroke.
One meta-analysis showed that treatment with citicoline within the first 24 of moderate to severe stroke increases the probability of complete recovery at 3 months.16Dávalos A, Castillo J, Alvarez-Sabín J, Secades JJ, Mercadal J, López S, Cobo E, Warach S, Sherman D, Clark WM, Lozano R. Oral citicoline in acute ischemic stroke: an individual patient data pooling analysis of clinical trials Stroke. 2002 Dec
Citicoline’s therapeutic action has been attributed to its restoring activity of the phosphatidylcholine levels, which decrease after a stroke.17Adibhatla RM1, Hatcher JF, Larsen EC, Chen X, Sun D, Tsao FH.. CDP-choline significantly restores phosphatidylcholine levels by differentially affecting phospholipase A2 and CTP: phosphocholine cytidylyltransferase after stroke J Biol Chem. 2006 Mar
There is also strong support that supplementing with citicoline in the weeks after a stroke can significantly improve recovery.18Cho HJ, Kim YJ. Efficacy and safety of oral citicoline in acute ischemic stroke: drug surveillance study in 4,191 cases Methods Find Exp Clin Pharmacol. 2009
A metanalysis of the clinical studies performed with this compound confirms citicoline as effective in restoring both the cell lipid structures and some neurotransmitter functions.20Mario Fioravanti1 and Ann E Buckley. Citicoline (Cognizin) in the treatment of cognitive impairmentClin Interv Aging. 2006
CDP choline decreases the level of serotonin and tryptophan and the synthesis rate of serotonin in the midbrain and hypothalamus.
This could prevent or treat Parkinson’s disease.21Martinet M, Fonlupt P, Pacheco H. Effects of cytidine-5′ diphosphocholine on norepinephrine, dopamine and serotonin synthesis in various regions of the rat brain Arch Int Pharmacodyn Ther. 1979
Does Citicoline Help ADHD?
It seems that improving ACh flow can improve some aspects of attention disorders.
One trial found that a mix of citicoline and caffeine had a noticeable effect on the focus and motivation of its participants.22Steven E. Bruce, et al. Improvements in Concentration, Working Memory, and Sustained Attention Following Consumption of a Natural Citicoline-Caffeine Beverage Int J Food Sci Nutr. 2015
There are also many anecdotal reports of citicoline helping with this issue, usually when taken together with a racetam.
Hopefully, we will see more clinical trials in the future about this potentially promising avenue for treating ADHD.
How Citicoline Works In The Brain
Citicoline functions as a precursor of the neurotransmitter acetylcholine (ACh). ACh is one of the most abundant and important neurotransmitters in the brain.23Tayebati SK, Amenta F. Choline-containing phospholipids: relevance to brain functional pathways Clin Chem Lab Med. 2013
This is its primary mode of action when it comes to improving cognition.
CDP Choline plays an important role in neuronal structure and signaling. It may also help preserve the integrity of the neuronal membrane.24Arenth PM, Russell KC, Ricker JH, Zafonte RD. CDP-choline as a biological supplement during neurorecovery: a focused review PM & R. 2011 25Citicoline. Monograph. Altern Med Rev. 2008
According to some research, citicoline may reduce brain glutamate activity and increase dopamine release. This could account for it’s effects on mood.26Hurtado O, Moro MA, Cárdenas A, Sánchez V, Fernández-Tomé P, Leza JC, Lorenzo P, Secades JJ, Lozano R, Dávalos A, Castillo J, Lizasoain I. Neuroprotection afforded by prior citicoline administration in experimental brain ischemia: effects on glutamate transport Neurobiol Dis. 2005
When you take citicoline orally, it has greater than 90% bioavailability. The body rapidly metabolizes it into cytidine and choline.27D’Orlando KJ, Sandage BW Jr. Citicoline (CDP-choline): mechanisms of action and effects in ischemic brain injury Neurol Res. 1995
Cytidine metabolizes into uridine, crosses the blood-brain barrier, and then converts to cytidine triphosphate (CTP).
The choline converts into phosphocholine, which combines with CTP to re-form again as citicoline in the brain. Citicoline and diacylglycerol then form phosphatidylcholine, a critical neural cell membrane.28Silveri MM, Dikan J, Ross AJ, Jensen JE, Kamiya T, Kawada Y, Renshaw PF, Yurgelun-Todd DA. Citicoline enhances frontal lobe bioenergetics as measured by phosphorus magnetic resonance spectroscopy NMR Biomed. 2008
How Much Citicoline Should I Take?
Studies have shown tolerability up to 4000mg/day with no side effects.
However, you should always take the smallest possible effective dose of any nootropic.
Most people see the best results around 500mg-1000mg/day.
Citicoline Potential Side Effects
Citicholine is extremely well tolerated. Rarely, people will experience digestive symptoms (nausea, stomach pain, and diarrhea), or restlessness or fatigue.
Every once in a while, someone reports cardiovascular symptoms, such as low blood pressure or tachycardia. If this happens, discontinue use immediately.
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