|Summary sheet: Citicoline|
|Substitutive name||Cytidine diphosphate choline|
|Systematic name||(2R,3S,4R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-ylmethoxy-hydroxyphosphoryl 2-(trimethylazaniumyl)ethyl phosphate|
|Chemical class||Ammonium salt|
|Routes of Administration|
Citicoline (CDP-choline, cytidine 5'-diphosphocholine) is a water soluble nutrient which serves as a precursor to both choline and cytidine within the brain (which later converts to uridine). To humans, choline is an essential nutrient as its role in reducing the risk of neural tube defects, fatty liver disease, and other pathologies have been documented. CDP-choline is one of the three choline-containing phospholipids that can be orally supplemented (the other two being alpha-GPC and phosphatidylcholine).
This supplement is catered towards preventing or treating memory impairments associated with aging because both of the molecules it confers are neuroprotective and potentially enhance learning. This effect may also benefit younger populations as well. It appears to be more efficient than phosphatidylcholine (PC) itself in this role, in part due to also increasing PC synthesis in the brain.
Citicoline has also been implicated in the treatments of cognitive impairments, caused by stroke, vascular dementia, Alzheimer’s disease, Parkinson’s disease, and more.
The potency of this compound is somewhat comparable to that of alpha-GPC. One study has noted an increase in attention with low dose CDP-choline (which needs to be replicated), and CDP-choline may have roles as an anti-addictive compound against both cocaine and (preliminary evidence suggests) food as well.
When taken as a supplement, this compound has nootropic effects. It is readily available and commonly sold for this purpose through the use of online supplement vendors.
Citicoline, or cytidine diphosphate-choline, is a naturally occurring substance found in human cell tissue and synthesized as a sodium salt as a supplement. Its chemical structure is comprised of a cytidine nucleoside attached to a choline group through a diphosphate bridge. Citicoline is a chemical intermediary in the biosynthesis of phosphatidylcholine, a major phospholipid in cell membranes.
The choline subcomponent of citicoline is comprised of a trimethyl ammonium salt with an additional ethanol group attached. In citicoline, the terminal alcohol group is incorporated into the phosphate bridge connecting the choline sub-group to cytidine. Cytidine is a nucleoside made of cytosine bonded to a ribose ring.
CDP-choline breaks down into two key components, choline and cytidine. Choline and its metabolites are needed for three main physiological purposes: structural integrity and signaling roles for cell membranes as well as cholinergic neurotransmission (acetylcholine synthesis). This process essentially allows acetylcholine to accumulate at higher levels than that which it otherwise would. As acetylcholine is involved in the function of memory, this could potentially account for its nootropic effects.
Cytidine is the second metabolite which is a critical step in the synthesis of uridine, which increases the efficiency of phosphatidylcholine. Uridine supplementation also appears to enhance dopamine output from activated neurons without significantly affecting basal levels of dopamine. This could account for its improvements in spatial short-term memory, recognition, recall, attention, and executive functions after prolonged supplementation.
Disclaimer: The effects listed below cite the Subjective Effect Index (SEI), an open research literature based on anecdotal user reports and the personal analyses of PsychonautWiki contributors. As a result, they should be viewed with a healthy degree of skepticism.
It is also worth noting that these effects will not necessarily occur in a predictable or reliable manner, although higher doses are more liable to induce the full spectrum of effects. Likewise, adverse effects become increasingly likely with higher doses and may include addiction, severe injury, or death ☠.
- Appetite suppression
- Stimulation - The stimulation which citicoline presents can be considered as primarily subtle and less than that of caffeine.
- Pain relief - CDP-choline appears to have painkilling effects via the nicotinic acetylcholine receptors in a dosage-dependent manner.
- Body odor alteration - This may occur in some populations, especially those suffering from trimethylaminuria. Choline (a byproduct of CDP-choline) is a precursor to trimethylamine, which some people are not able to break down easily, often resulting in a fishy smell.
- Acuity enhancement - Citicoline may prevent and treat eye damage related to glaucoma.
- Wakefulness - In comparison to Alpha-GPC, Citicoline manifests itself primarily in a mentally stimulating manner over a physical stimulation.
- Dream potentiation
- Focus enhancement
- Addiction suppression - Citicoline has been shown to reduce psychological cravings in cocaine-dependent populations who actively seek substance abuse treatment.
- Memory enhancement
There are currently no anecdotal reports which describe the effects of this compound within our experience index. Additional experience reports can be found here:
Toxicity and harm potential
Citicoline is non-addictive, is not known to cause brain damage, and has an extremely low toxicity relative to dose. Similar to many other nootropics substances, there are relatively few physical side effects associated with acute citicoline exposure. Various studies have shown that in reasonable doses in a careful context, it presents no negative cognitive, psychiatric or toxic physical consequences of any sort.
It is strongly recommended that one use harm reduction practices when using this substance.
Tolerance and addiction potential
Citicoline is not habit-forming and the desire to use it can actually decrease with use. It is most often self-regulating.
Citicoline does not seem to build up an immediate tolerance and becomes stronger with prolonged use due to its long half-life. It is not recommended to take citicoline for extended periods longer than two weeks.
Citicoline is a suspected monoaminergic substance. Citicoline and MAOIs are a potentially dangerous combination. It is likely that MAOIs could increase the effects of Alpha-GPC unpredictably. Taking this chemical while on prescription MAOIs is strongly discouraged.
- Mcglade, E., Locatelli, A., Hardy, J., Kamiya, T., Morita, M., Morishita, K., … Yurgelun-Todd, D. (2012). Improved Attentional Performance Following Citicoline Administration in Healthy Adult Women. Food and Nutrition Sciences, 336103(June), 769–773. https://doi.org/10.4236/fns.2012.36103
- Parisi, V., Coppola, G., Centofanti, M., Oddone, F., Maria Angrisani, A., Ziccardi, L., … Manni, G. (2008). Evidence of the neuroprotective role of citicoline in glaucoma patients. Progress in Brain Research, 173(8), 541–554. https://doi.org/10.1016/S0079-6123(08)01137-0
- Bagdas, D., Sonat, F. A., Hamurtekin, E., Sonal, S., & Gurun, M. S. (2011). The antihyperalgesic effect of cytidine-5’-diphosphate-choline in neuropathic and inflammatory pain models. Behavioural Pharmacology, 22(5–6), 589–598. https://doi.org/10.1097/FBP.0b013e32834a1efb
- Hamurtekin, E., & Sibel Gurun, M. (2006). The antinociceptive effects of centrally administered CDP-choline on acute pain models in rats: The involvement of cholinergic system. Brain Research, 1117(1), 92–100. https://doi.org/10.1016/j.brainres.2006.07.118
- Killgore, W. D. S., Ross, A. J., Kamiya, T., Kawada, Y., Renshaw, P. F., & Yurgelun-Todd, D. A. (2010). Citicoline affects appetite and cortico-limbic responses to images of high-calorie foods. International Journal of Eating Disorders, 43(1), 6–13. https://doi.org/10.1002/eat.20658
- Renshaw, P. F., Daniels, S., Lundahl, L. H., Rogers, V., & Lukas, S. E. (1999). Short-term treatment with citicoline (CDP-choline) attenuates some measures of craving in cocaine-dependent subjects: A preliminary report. Psychopharmacology, 142(2), 132–138. https://doi.org/10.1007/s002130050871
- Zeisel, S. H., Costa, K.-A. da (November 2009). "Choline: an essential nutrient for public health". Nutrition Reviews. 67 (11): 615–623. doi:10.1111/j.1753-4887.2009.00246.x. ISSN 0029-6643.
- Fioravanti, M.; Buckley, A. E. (2006). "Citicoline (Cognizin) in the treatment of cognitive impairment". Clinical Interventions in Aging. 1: 247–251. doi:10.2147/ciia.2006.1.3.247. eISSN 1178-1998. ISSN 1176-9092. OCLC 317918656. PMC . PMID 18046877.
- Jiang, N., Huang, J., Edwards, L. J., Liu, B., Zhang, Y., Beal, C. D., Evavold, B. D., Zhu, C. (January 2011). "Two-Stage Cooperative T Cell Receptor-Peptide Major Histocompatibility Complex-CD8 Trimolecular Interactions Amplify Antigen Discrimination". Immunity. 34 (1): 13–23. doi:10.1016/j.immuni.2010.12.017. ISSN 1074-7613.
- Renshaw, P. F., Daniels, S., Lundahl, L. H., Rogers, V., Lukas, S. E. (18 February 1999). "Short-term treatment with citicoline (CDP-choline) attenuates some measures of craving in cocaine-dependent subjects: a preliminary report". Psychopharmacology. 142 (2): 132–138. doi:10.1007/s002130050871. ISSN 0033-3158.
- Glier, M. B., Green, T. J., Devlin, A. M. (January 2014). "Methyl nutrients, DNA methylation, and cardiovascular disease". Molecular Nutrition & Food Research. 58 (1): 172–182. doi:10.1002/mnfr.201200636. ISSN 1613-4125.
- Killgore, W. D. S., Ross, A. J., Kamiya, T., Kawada, Y., Renshaw, P. F., Yurgelun-Todd, D. A. (2009). "Citicoline affects appetite and cortico-limbic responses to images of high-calorie foods". International Journal of Eating Disorders: NA–NA. doi:10.1002/eat.20658. ISSN 0276-3478.
- Hamurtekin, E., Sibel Gurun, M. (October 2006). "The antinociceptive effects of centrally administered CDP-choline on acute pain models in rats: The involvement of cholinergic system". Brain Research. 1117 (1): 92–100. doi:10.1016/j.brainres.2006.07.118. ISSN 0006-8993.
- Bagdas, D., Sonat, F. A., Hamurtekin, E., Sonal, S., Gurun, M. S. (September 2011). "The antihyperalgesic effect of cytidine-5′-diphosphate-choline in neuropathic and inflammatory pain models". Behavioural Pharmacology. 22 (5 and 6): 589–598. doi:10.1097/FBP.0b013e32834a1efb. ISSN 0955-8810.
- Kashyap, A. S. (1 May 2000). "Fish odour syndrome". Postgraduate Medical Journal. 76 (895): 318a–3318. doi:10.1136/pmj.76.895.318a. ISSN 0032-5473.
- Parisi, V., Coppola, G., Centofanti, M., Oddone, F., Maria Angrisani, A., Ziccardi, L., Ricci, B., Quaranta, L., Manni, G. (2008). "Progress in Brain Research". Evidence of the neuroprotective role of citicoline in glaucoma patients. 173. Elsevier. pp. 541–554. doi:10.1016/S0079-6123(08)01137-0. ISBN 9780444532565.
- McGlade, E., Locatelli, A., Hardy, J., Kamiya, T., Morita, M., Morishita, K., Sugimura, Y., Yurgelun-Todd, D. (2012). "Improved Attentional Performance Following Citicoline Administration in Healthy Adult Women". Food and Nutrition Sciences. 03 (06): 769–773. doi:10.4236/fns.2012.36103. ISSN 2157-944X.
- Tayebati, S. K., Tomassoni, D., Nwankwo, I. E., Di Stefano, A., Sozio, P., Cerasa, L. S., Amenta, F. (1 February 2013). "Modulation of monoaminergic transporters by choline-containing phospholipids in rat brain". CNS & neurological disorders drug targets. 12 (1): 94–103. doi:10.2174/1871527311312010015. ISSN 1996-3181.
- Trabucchi, M., Govoni, S., Battaini, F. (April 1986). "Changes in the interaction between CNS cholinergic and dopaminergic neurons induced by L-alpha-glycerylphosphorylcholine, a cholinomimetic drug". Il Farmaco; Edizione Scientifica. 41 (4): 325–334. ISSN 0430-0920.