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Scott E Lukas - One of the best experts on this subject based on the ideXlab platform.

  • Citicoline treatment improves measures of impulsivity and task performance in chronic marijuana smokers a pilot bold fmri study
    International journal of neurology, 2015
    Co-Authors: Staci A Gruber, David M Penetar, Kelly A Sagar, Mary Kathryn Dahlgren, A Gonenc, Nina A Conn, Jeffrey P Winer, Scott E Lukas
    Abstract:

    Objective Citicoline is an endogenous nucleotide that has historically been used to treat stroke, traumatic brain injury, and cognitive dysfunction. Research has also shown that Citicoline treatment is associated with improved cognitive performance in substance-abusing populations. We hypothesized that marijuana (MJ) smokers who received Citicoline would demonstrate improvement in cognitive performance as well as increased neural efficiency during tasks of cognitive control relative to those who received placebo.

  • eight weeks of Citicoline treatment does not perturb sleep wake cycles in cocaine dependent adults
    Pharmacology Biochemistry and Behavior, 2011
    Co-Authors: Bethany K Bracken, David M Penetar, John Rodolico, Elizabeth T Ryan, Scott E Lukas
    Abstract:

    Abstract Background Citicoline (cytidine-5′-diphosphate) is a mononucleotide composed of ribose, cytosine, pyrophosphate, and choline, and is involved in the biosynthesis of the structural phosopholipids of cell membranes. Treatment with Citicoline, improves memory in patients with dementia, and reduces damage to the brain after traumatic brain injury or stroke. Recent research has been conducted to assess whether Citicoline is an effective treatment for cocaine dependence. In cocaine-dependent individuals, withdrawal from cocaine is associated with disturbed sleep, which may contribute to the high rate of relapse to cocaine use. Therefore, it is important to know the impact of Citicoline on the sleep/wake cycle in these individuals in order to rate its overall efficacy. Method In this double-blind, placebo-controlled trial, the effects of Citicoline treatment on the sleep/wake cycles of cocaine dependent participants were assessed. The results of the current study are reported as part of a larger study, consisting of an eight-week treatment period to assess the efficacy of longer-term treatment with Citicoline at decreasing cocaine consumption in cocaine-dependent polydrug using participants. Results In this non-abstinent, cocaine-dependent population, Citicoline had no effect on any of the sleep parameters measured including sleep efficiency, sleep latency, total sleep time, number of waking episodes, time awake per episode, amount of time in bed spent moving, number of sleep episodes, time asleep per episode, and amount of time in bed spent immobile. Conclusions These data suggest that eight weeks of Citicoline administration does not disturb sleep/wake cycles of cocaine-dependent individuals.

  • effects of short term Citicoline treatment on acute cocaine intoxication and cardiovascular effects
    Psychopharmacology, 2001
    Co-Authors: Scott E Lukas, Elena M Kouri, Christina Rhee, Alex Madrid, Perry F. Renshaw
    Abstract:

    Rationale: The majority of pharmacotherapies proposed for cocaine dependence have been marginally effective and frequently have undesirable side effects. We recently demonstrated that short-term treatment with Citicoline decreased self-reported desire to use cocaine in crack cocaine users. Objective: The present study was conducted to assess the safety of Citicoline in combination with cocaine by investigating whether cocaine-induced cardiovascular and behavioral effects and cocaine plasma levels are altered by Citicoline pretreatment. Methods: Eight healthy male and female volunteers who used cocaine on an occasional basis participated in this randomized, placebo-controlled, three-visit study. During all three visits, subjects received an acute intranasal dose of cocaine (0.9 mg/kg) and were continuously monitored for the ensuing 3.5 h. The first visit involved no pretreatment, and visits 2 and 3 were preceded by a 4-day pretreatment period of either Citicoline (1 g/day) or placebo. Results: Citicoline pretreatment did not alter the cardiovascular, physiologic, or subjective effects of acute cocaine. Conclusions: Although Citicoline did not block the acute subjective effects of cocaine in a laboratory environment, the combined use of Citicoline and a moderate dose of intranasal cocaine presented no added risk of cardiovascular effects. Further study is necessary to determine whether this medication (which is currently used to treat strokes) will be a useful adjunct to treat cocaine dependence.

  • short term treatment with Citicoline cdp choline attenuates some measures of craving in cocaine dependent subjects a preliminary report
    Psychopharmacology, 1999
    Co-Authors: Perry F. Renshaw, Sarah L Daniels, Leslie H Lundahl, Veronica W Rogers, Scott E Lukas
    Abstract:

    The administration of cytidine-5′-diphosphate choline (CDP-choline, Citicoline) to animals increases the rate of membrane phospholipid synthesis and elevates brain dopamine levels. Because cocaine dependence has been associated with increases in brain phospholipid precursors, as well as depletion of dopamine within the central nervous system, the present outpatient study was conducted to assess the safety of Citicoline (500 mg bid) and to determine if short-term treatment alters mood states and cocaine craving in subjects with a history of cocaine dependence. In addition, measures of drug craving and mood states after presentation of cocaine-related cues were collected on two occasions: before and after 14 days of double-blind treatment with either Citicoline or placebo. Subjects did not experience any side effects and Citicoline treatment was associated with decreases in self-reported mood states associated with cocaine craving. These preliminary data are encouraging and suggest that Citicoline warrants further study as a promising potential treatment for cocaine abuse and dependence that is devoid of side effects.

Rao Muralikrishna Adibhatla - One of the best experts on this subject based on the ideXlab platform.

  • Citicoline in stroke and TBI clinical trials.
    Nature reviews. Neurology, 2013
    Co-Authors: Rao Muralikrishna Adibhatla
    Abstract:

    The results of recent Citicoline trials by Davalos et al.1 and Zafonte et al.2 showed that Citicoline is not efficacious in treating stroke and TBI, respectively, a view that has been echoed by others,3,4 including a recent News & Views article in this journal (Stroke: Treatment for acute stroke—the end of the Citicoline saga. Nat. Rev. Neurol. 8, 484–485; 2012).5 Studies in rodent models of stroke, however, have indicated that bioavailability of this drug may be an issue that has been repeatedly overlooked in the clinical trials, making it premature to conclude that citico­ line is ineffective. Our and others’ research with animal models strongly suggests that if a liposome formulation had been used, the reported results from the clinical trial would have been different.6–9 Route of administration, bioavailabil­ ity and metabolism of Citicoline are vital factors in stroke and TBI clinical trials. On the basis of absorption and excretion, bio­ availability of Citicoline is believed to be the same between oral and intra venous routes. Animal studies have shown, however, that brain uptake of Citicoline is greater with the intravenous route than with the oral route.7 Citicoline metabolism in humans differs from that in rodents: in rodents, Citicoline administration increases blood plasma levels of cytidine and choline, while in humans blood plasma levels of uridine but not cytidine are increased due to cytidine deaminase in the gastro­ intestinal tract and liver.10 In both humans and rodents, citi coline is metabolized to choline and cytidine triphosphate (CTP) by the liver; after passing through a com­ promised blood–brain barrier (BBB) these two components need to be reassembled by rate­limiting CTP:phosphocholine Citicoline in stroke and TBI clinical trials

  • Citicoline decreases phospholipase a2 stimulation and hydroxyl radical generation in transient cerebral ischemia
    Journal of Neuroscience Research, 2003
    Co-Authors: Rao Muralikrishna Adibhatla, James F Hatcher
    Abstract:

    Neuroprotection by Citicoline (CDP-choline) in transient cerebral ischemia has been demonstrated previously. Citicoline has undergone several Phase III clinical trials for stroke, and is being evaluated for treatment of Alzheimer’s and Parkinson’s diseases. Phospholipid degradation and generation of reactive oxygen species (ROS) are major factors causing neuronal injury in CNS trauma and neurodegenerative diseases. Oxidative metabolism of arachidonic acid (released by the action of phospholipases) contributes to ROS generation. We examined the effect of Citicoline on phospholipase A2 (PLA2) activity in relation to the attenuation of hydroxyl radical (OH) generation after transient forebrain ischemia of gerbil. PLA2 activity (requires mM Ca 2 ) increased significantly (P 0.05) in both membrane (50.2 2.2 pmol/min/mg protein compared to sham 35.9 3.2) and mitochondrial fractions (77.0 1.2 pmol/min/mg protein compared to sham 33.9 1.2) after cerebral ischemia and 2 hr reperfusion in gerbil, which was significantly attenuated (P 0.01) by Citicoline (membrane, 39.9. 2.2 and mitochondria, 41.9 3.2 pmol/min/mg protein). In vitro, Citicoline and its components cytidine and choline had no effect on PLA2 activity, and thus Citicoline as such is not a PLA2 inhibitor. Ischemia/reperfusion resulted in significant OH generation (P 0.01) and Citicoline significantly (P 0.01) attenuated their formation (expressed as 2,3dihydroxybenzoic acid/salicylate ratio; ischemia/24 hr reperfusion, 6.30 0.23; sham, 2.56 0.27; ischemia/24 hr reperfusion Citicoline, 4.85 0.35). These results suggest that Citicoline affects PLA2 stimulation and decreases OH generation after transient cerebral ischemia. © 2003 Wiley-Liss, Inc.

  • Citicoline mechanisms and clinical efficacy in cerebral ischemia.
    Journal of neuroscience research, 2002
    Co-Authors: Rao Muralikrishna Adibhatla, James F Hatcher
    Abstract:

    Citicoline, an intermediate in the biosynthesis of phosphatidylcholine (PtdCho), has shown beneficial effects in various CNS injury models and neurodegenerative diseases. PtdCho hydrolysis by phospholipase A2 (PLA2) after cerebral ischemia and reperfusion yields arachidonic acid (ArAc) and lyso-PtdCho. ArAc oxidative metabolism results in formation of reactive oxygen species and lipid peroxides. Lyso-PtdCho could inhibit activity of cytidine triphosphate-phosphocholine cytidylyltransferase (the rate-limiting enzyme in PtdCho biosynthesis), resulting in impaired PtdCho synthesis. Citicoline significantly increased glutathione levels and attenuated release of ArAc and the loss of PtdCho, cardiolipin, and sphingomyelin following transient cerebral ischemia. These effects could be explained by an effect of Citicoline on PLA2. Based on these observations, a mechanism has been hypothesized. This Mini-Review summarizes recent experimental data on the effects of Citicoline in cerebral ischemia and evaluates several factors that might have hindered efficacy of Citicoline in stroke clinical trials in the United States. Clinical stroke trials of Citicoline in Europe and Japan have demonstrated beneficial effects. U.S. trials shown only marginal effects, which might be due to the 24 hr time window, the dose and route of administration, and the stringency of the primary outcome parameters. Recent evaluation of U.S. clinical data suggests that reduction of infarct growth may be a more sensitive measure of the Citicoline effect than improvement on the NIH Stroke Scale (NIHSS) by ≥7 points. The Citicoline neuroprotective mechanism has not been clearly identified, and its potential in stroke treatment might still be fully recognized in the United States. The clinical efficacy of Citicoline should be examined further in light of the recent phase III stroke clinical trials and experimental data for cerebral ischemia. © 2002 Wiley-Liss, Inc.

  • Citicoline: neuroprotective mechanisms in cerebral ischemia
    Journal of neurochemistry, 2002
    Co-Authors: Rao Muralikrishna Adibhatla, James F Hatcher, Robert J. Dempsey
    Abstract:

    Cytidine-5¢-diphosphocholine (Citicoline or CDP-choline), an intermediate in the biosynthesis of phosphatidylcholine (PtdCho), has shown beneficial effects in a number of CNS injury models and pathological conditions of the brain. Citicoline improved the outcome in several phase-III clinical trials of stroke, but provided inconclusive results in recent clinical trials. The therapeutic action of Citicoline is thought to be caused by stimulation of PtdCho synthesis in the injured brain, although the experimental evidence for this is limited. This review attempts to shed some light on the properties of Citicoline that are responsible for its effectiveness. 2 Our studies in transient cerebral ischemia suggest that Citicoline might enhance reconstruction (synthesis) of PtdCho and sphingomyelin, but could act by inhibiting the destructive processes (activation of phospholipases). Citicoline neuroprotection may include: (i) preserving cardiolipin (an exclusive inner mitochondrial membrane component) and sphingomyelin; (ii) preserving the arachidonic acid content of PtdCho and phosphatidylethanolamine; (iii) partially restoring PtdCho levels; (iv) stimulating glutathione synthesis and glutathione reductase activity; (v) attenuating lipid peroxidation; and (vi) restoring Na + /K + -ATPase activity. These observed effects of Citicoline could be explained by the attenuation of phospholipase A2 activation. Based on these findings, a singular unifying mechanism has been hypothesized. 3 Citicoline also provides choline for synthesis of neurotransmitter acetylcholine, stimulation of tyrosine hydroxylase activity and dopamine release.

  • Citicoline: Mechanisms and Stroke Clinical Trials
    2002
    Co-Authors: Rao Muralikrishna Adibhatla, R J Dempseyj F Hatcher
    Abstract:

    therapeutic action of Citicoline is thought to be due to stimulation of phosphatidylcholine (PtdCho) synthesis in the injured brain, though evidence is unclear [2]. In this regard, Figure 1 needs correction. The biosynthesis of PtdCho from 1,2- diacylglycerol (diglyceride) and CDP-choline forms cytidine 5'- monophosphate as the other product, not monoacylglycerol (monoglyceride). Our studies in transient cerebral ischemia suggest that Citicoline might enhance reconstruction (synthesis) of PtdCho and sphingomyelin, but could inhibit the destructive processes (activation of phospholipases). [2-5] Citicoline neuroprotection may include: preserving cardiolipin and sphingomyelin; preserving arachidonic acid content of PtdCho and phosphatidylethanolamine; partially restoring PtdCho levels; and stimulating glutathione synthesis and glutathione reductase activity. The effects of Citicoline could be explained by the attenuation of phospholipase A2 activation and also to a singular unifying neuroprotective mechanism of this drug [2]. The following points may need to be considered in future clinical trials: Patients were admitted into the clinical studies up to 24 hours after onset of symptoms, a longer timeframe than is used in most clinical trials. [1] Our studies indicate that Citicoline does not provide neuroprotection if the onset of treatment is delayed by 3 hours. Another factor is the percentage of Citicoline that is incorporated into the brain. As noted, all of clinical trials outside the US used IV administration in contrast to the oral route in US trials. It is generally believed that bioavailability is the same between oral and IV methods, but this conclusion was apparently based on absorption and excretion, not delivery of Citicoline to the brain. [6] Animal studies have shown brain uptake of Citicoline (or its metabolites) of only 0.5% with oral dose, which increased to ~2% when administered. IV Liposome encapsulation of Citicoline increased brain uptake of the drug to 23% of the administered dose. [7] In addition, Citicoline metabolism in humans differs from rodents. In rodents, Citicoline administration increases blood plasma levels of cytidine and choline. In humans, blood plasma levels of uridine but not cytidine are increased due to cytidine deaminase in the gastrointestinal tract and liver.[8]. It is believed that uridine must then enter the brain, become phosphorylated to uridine triphosphate, and then converted to cytidine triphosphate. It may be necessary to combine Citicoline with another agent targeted to a different pathway due to the multiple mechanisms contributing to ischemic brain

Wayne M Clark - One of the best experts on this subject based on the ideXlab platform.

  • Stroke: Treatment for acute stroke--the end of the Citicoline saga.
    Nature reviews. Neurology, 2012
    Co-Authors: Wayne M Clark, Tegan D. Clark
    Abstract:

    Over the past two decades, trials of Citicoline for treatment of acute stroke have produced conflicting results. A recent large clinical trial of Citicoline in acute stroke suggests a lack of efficacy of this therapy, seemingly signalling the end to the Citicoline saga.

  • Efficacy of Citicoline as an acute stroke treatment
    Expert opinion on pharmacotherapy, 2009
    Co-Authors: Wayne M Clark
    Abstract:

    Citicoline (cytidine-5′-diphosphocholine or CDP-choline) is a precursor essential for the synthesis of phosphatidylcholine, one of the cell membrane components that is degraded during cerebral ischemia to free fatty acids and free radicals. Animal studies suggest that Citicoline may protect cell membranes by accelerating resynthesis of phospholipids and suppressing the release of free fatty acids, stabilizing cell membranes, and reducing free radical generation. Numerous experimental stroke studies with Citicoline have shown improved outcome and reduced infarct size in both ischemic and hemorrhagic stroke models. Citicoline has been studied worldwide in both ischemic and hemorrhagic clinical stroke with excellent safety and possibly efficacy found in several trials. A meta-analysis of four randomized US clinical Citicoline trials concluded that treatment with oral Citicoline within the first 24 h after a moderate to severe stroke is safe and increases the probability of complete recovery at 3 months. Citi...

  • a phase iii randomized efficacy trial of 2000 mg Citicoline in acute ischemic stroke patients
    Neurology, 2001
    Co-Authors: Wayne M Clark, Lawrence R Wechsler, L A Sabounjian, U E Schwiderski
    Abstract:

    Background: Citicoline may reduce CNS ischemic injury by stabilizing cell membranes and reducing free radical generation. Previous safety and efficacy trials in patients who have had acute strokes suggested that Citicoline may improve neurologic outcome with minimal side effects. Objective: To determine the safety and efficacy of Citicoline treatment in acute stroke patients. Method: An 118-center, randomized, double-blind, efficacy trial in 899 patients compared placebo (n = 446) with Citicoline (n = 453) (1000 mg PO twice a day) for 6 weeks, with a 6-week post-treatment follow-up period. Patients with acute (≤24 hours) ischemic strokes clinically thought to be in the middle cerebral artery territory with NIH Stroke Scale (NIHSS) scores ≥8 were enrolled. Results: Mean time to treatment was 13 hours for both groups and mean age was 67 years for those receiving placebo and 68 years for those receiving Citicoline. Mean baseline NIHSS scores were 14.5 for placebo and 13.9 for Citicoline ( p = 0.06); medians were 14 for placebo and 13 for Citicoline ( p = 0.04). The incidence and type of side effects were similar between the groups. There were no between-group differences on the planned primary analysis, percent of patients with a ≥7-point NIHSS score change at 90 days (placebo 51%, Citicoline 52%). There were no between-group differences on the other planned secondary analyses at 90 days, including mortality. However, post hoc analyses using standard “excellent recovery” measures suggested a possible treatment effect on the modified Rankin 0 or 1 (last observation carried forward: placebo 20%, Citicoline 26%; p = 0.025) as well as a global outcome statistic. Conclusions: Citicoline was safe but ineffective in improving the outcome of patients with acute ischemic stroke as measured by the planned analyses. Post hoc analyses suggest that a modest treatment effect may have been seen if more traditional analyses had been used.

  • A randomized dose-response trial of Citicoline in acute ischemic stroke patients
    Neurology, 1997
    Co-Authors: Wayne M Clark, Steve Warach, L. C. Pettigrew, Richard E. Gammans, L A Sabounjian
    Abstract:

    Citicoline (CDP-choline) is a key intermediary in the biosynthesis of phosphatidylcholine, an important component of the neural cell membrane. It has been shown to produce beneficial effects in both animal models and non-US clinical stroke trials. This study comprised a randomized (3 doses of Citicoline to 1 placebo), vehicle-controlled, double-blind trial at 21 US centers. Treatment was to be started within 24 hours of stroke onset and was continued orally for 6 weeks. Final outcome assessments were at 12 weeks. Two hundred fifty-nine patients were enrolled, with approximately 65 in each of the four groups. Mean time from stroke onset to treatment was 14.5 hours, and there were no significant differences in baseline characteristics between the four groups except for patient weight. A significant difference between the groups, favoring Citicoline treatment, was seen in terms of functional outcome as measured by the Barthel Index and Rankin scale, neurologic evaluation as measured by the National Institutes of Health (NIH) stroke scale, and cognitive function as measured by the Mini Mental Status Examination. When the baseline NIH stroke scale was used as a covariate, both the 500-mg Citicoline group and the 2,000-mg Citicoline group had a significant improvement in terms of the percent of patients who had a favorable outcome on the Barthel Index at 90 days. There were no drug-related serious adverse events or deaths in this study. This study suggests that oral Citicoline can be used safely with minimal side effects in acute stroke treatment. Citicoline appears to improve functional outcome and reduce neurologic deficit with 500 mg of Citicoline appearing to be the optimal dose.

Perry F. Renshaw - One of the best experts on this subject based on the ideXlab platform.

  • chronic Citicoline increases phosphodiesters in the brains of healthy older subjects an in vivo phosphorus magnetic resonance spectroscopy study
    Psychopharmacology, 2002
    Co-Authors: Suzann M Babb, Bruce M. Cohen, Lawrence L Wald, Rosemond A Villafuerte, Staci A Gruber, Deborah A Yurgeluntodd, Perry F. Renshaw
    Abstract:

    Rationale: Phosphatidylcholine (PtdCho) in brain cell membranes decreases with age. Evidence from both animal and in vitro studies indicates that CDP-choline (Citicoline) administration may increase phosphatidylcholine (PtdCho) synthesis and might reverse PtdCho loss. Objectives: We investigated whether oral Citicoline can increase PtdCho synthesis in the brains of older subjects by measuring levels of phosphorus-containing metabolites using proton-decoupled phosphorus magnetic resonance spectroscopy (31P-MRS) before and after Citicoline treatment. Methods: All subjects took 500 mg Citicoline once orally each day for 6 weeks, then took either Citicoline or placebo once orally per day for a second 6-week period. Subjects underwent a 31P-MRS scan at baseline and following 6 and 12 weeks of treatment. Results: Treatment with Citicoline for 6 weeks was associated with a 7.3% increase from baseline levels in brain phosphodiesters (P=0.008), including an 11.6% increase in glycerophosphoethanolamine (P=0.002) and a 5.1% increase in glycerophosphocholine (P=0.137). Subjects who continued to take Citicoline for the second 6-week period did not show significant additional increases in the levels of these metabolites. No changes were seen in other phosphorus-containing metabolites. There was a correlation between improvement on the California Verbal Learning Test and increase in phosphodiesters. Conclusions: The increases in phosphodiesters seen in this study indicate that phospholipid synthesis and turnover were stimulated by 6 weeks of oral Citicoline. These results in humans support previous in vitro and animal studies and suggest that the administration of oral Citicoline may be of use in reversing age-related changes in the brain.

  • Antidepressant-like effects of cytidine in the forced swim test in rats
    Biological Psychiatry, 2002
    Co-Authors: William A. Carlezon, Andrea M. Pliakas, Aimee M. Parow, Michael J. Detke, Bruce M. Cohen, Perry F. Renshaw
    Abstract:

    Background: Altered brain phospholipid metabolism may be involved in the pathophysiology of cocaine dependence and mood disorders. Evidence suggests that Citicoline, a rate-limiting metabolite for phospholipid synthesis, reduces cocaine craving in human addicts. Because antidepressants can reduce cocaine craving, we explored in rats the possibility that Citicoline has antidepressant effects. We also tested the primary metabolites of Citicoline, cytidine and choline. Methods: We examined if Citicoline or metabolites alter immobility in the forced swim test. We used two scoring methods: latency to become immobile, a simple method that identifies antidepressants, and behavioral sampling, a complex method that differentiates antidepressants according to pharmacological mechanisms. Results: Over a range of doses, Citicoline did not affect behavior in the forced swim test. At molar equivalent doses, cytidine dramatically decreased immobility, whereas choline tended to increase immobility. The effects of cytidine resemble those of desipramine, a standard tricyclic antidepressant. None of the treatments affected locomotor activity, and cytidine did not establish conditioned place preferences. Conclusions: Citicoline does not have effects in the forced swim test, but its primary metabolites have opposing effects: cytidine has antidepressant-like actions, whereas choline has prodepressant-like actions. At antidepressant doses, cytidine lacks stimulant and rewarding properties. This is the first report of potential antidepressant effects of cytidine. © 2002 Society of Biological Psychiatry.

  • effects of short term Citicoline treatment on acute cocaine intoxication and cardiovascular effects
    Psychopharmacology, 2001
    Co-Authors: Scott E Lukas, Elena M Kouri, Christina Rhee, Alex Madrid, Perry F. Renshaw
    Abstract:

    Rationale: The majority of pharmacotherapies proposed for cocaine dependence have been marginally effective and frequently have undesirable side effects. We recently demonstrated that short-term treatment with Citicoline decreased self-reported desire to use cocaine in crack cocaine users. Objective: The present study was conducted to assess the safety of Citicoline in combination with cocaine by investigating whether cocaine-induced cardiovascular and behavioral effects and cocaine plasma levels are altered by Citicoline pretreatment. Methods: Eight healthy male and female volunteers who used cocaine on an occasional basis participated in this randomized, placebo-controlled, three-visit study. During all three visits, subjects received an acute intranasal dose of cocaine (0.9 mg/kg) and were continuously monitored for the ensuing 3.5 h. The first visit involved no pretreatment, and visits 2 and 3 were preceded by a 4-day pretreatment period of either Citicoline (1 g/day) or placebo. Results: Citicoline pretreatment did not alter the cardiovascular, physiologic, or subjective effects of acute cocaine. Conclusions: Although Citicoline did not block the acute subjective effects of cocaine in a laboratory environment, the combined use of Citicoline and a moderate dose of intranasal cocaine presented no added risk of cardiovascular effects. Further study is necessary to determine whether this medication (which is currently used to treat strokes) will be a useful adjunct to treat cocaine dependence.

  • short term treatment with Citicoline cdp choline attenuates some measures of craving in cocaine dependent subjects a preliminary report
    Psychopharmacology, 1999
    Co-Authors: Perry F. Renshaw, Sarah L Daniels, Leslie H Lundahl, Veronica W Rogers, Scott E Lukas
    Abstract:

    The administration of cytidine-5′-diphosphate choline (CDP-choline, Citicoline) to animals increases the rate of membrane phospholipid synthesis and elevates brain dopamine levels. Because cocaine dependence has been associated with increases in brain phospholipid precursors, as well as depletion of dopamine within the central nervous system, the present outpatient study was conducted to assess the safety of Citicoline (500 mg bid) and to determine if short-term treatment alters mood states and cocaine craving in subjects with a history of cocaine dependence. In addition, measures of drug craving and mood states after presentation of cocaine-related cues were collected on two occasions: before and after 14 days of double-blind treatment with either Citicoline or placebo. Subjects did not experience any side effects and Citicoline treatment was associated with decreases in self-reported mood states associated with cocaine craving. These preliminary data are encouraging and suggest that Citicoline warrants further study as a promising potential treatment for cocaine abuse and dependence that is devoid of side effects.

Julio J Secades - One of the best experts on this subject based on the ideXlab platform.

  • Citicoline for acute ischemic stroke a systematic review and formal meta analysis of randomized double blind and placebo controlled trials
    Journal of Stroke & Cerebrovascular Diseases, 2016
    Co-Authors: Julio J Secades, José Castillo, Jose Alvarezsabin, Exuperio Dieztejedor, E Martinezvila, Jose Rios, Natalia Oudovenko
    Abstract:

    Background Citicoline is a drug approved for the treatment of acute ischemic stroke. Although evidence of its efficacy has been reported, recently published results of a large placebo-controlled clinical trial did not show differences. This study aims to assess whether starting Citicoline treatment within 14 days after stroke onset improves the outcome in patients with acute ischemic stroke, as compared with placebo. Methods A systematic search was performed to identify all published, unconfounded, randomized, double-blind, and placebo-controlled clinical trials of Citicoline in acute ischemic stroke. Results Ten randomized clinical trials met our inclusion criteria. The administration of Citicoline was associated with a significant higher rate of independence, independently of the method of evaluation used (odds ratio [OR] 1.56, 95% confidence interval [CI] = 1.12-2.16 under random effects; OR 1.20, 95% CI = 1.06-1.36 under fixed effects). After studying the cumulative meta-analysis, and with the results obtained with the subgroup of patients who were not treated with recombinant tissue plasminogen activator (rtPA) (OR 1.63, 95% CI = 1.18-2.24 under random effects; OR 1.42, 95% CI = 1.22-1.66 under fixed effects), our hypothesis of dilution of the effect of Citicoline was confirmed. When we analyzed the effect of Citicoline in patients who were not treated with rtPA and were receiving the highest dose of Citicoline started in the first 24 hours after onset, based on more recent trials, there was no heterogeneity, and the size of the effect has an OR of 1.27 (95% CI = 1.05-1.53). Conclusions This systematic review supports some benefits of Citicoline in the treatment of acute ischemic stroke. But, on top of the best treatment available (rtPA), Citicoline offers a limited benefit.

  • Citicoline for the Treatment of Head Injury: A Systematic Review andMeta-analysis of Controlled Clinical Trials
    Trauma & Treatment, 2014
    Co-Authors: Julio J Secades
    Abstract:

    Background: Citicoline is a neuroprotective/neurorestorative drug used in several countries for the treatment of traumatic brain injury (TBI). After the publication of the controversial COBRIT trial, the use of Citicoline has been questioned in this use, so it has been considered necessary to undertake a systematic review to evaluate if Citicoline is effective in the treatment of patients with traumatic brain injury. Methods: A systematic search was performed on Medline, Embase, and Ferrer databases to identify all published, unconfounded, comparative clinical trials of Citicoline in acute phase head injured patients. Results: 12 controlled trials enrolling 2706 patients were identified. Under the random-effects model, the metaanalysis shows an 1.815 (IC 95% 1.302; 2.530) in favour of Citicoline in the rates of independence, using as a measure the Glasgow Outcome Scale. The effect of Citicoline has been diluted across time in parallel with the improvement of the standard of care of this kind of patient, as demonstrated by the cumulative meta-analysis technique. Conclusion: Formal meta-analysis of comparative trials of Citicoline in TBI shows a beneficial treatment effect, without safety concerns.

  • Citicoline: pharmacological and clinical review, 2006 update.
    Methods and findings in experimental and clinical pharmacology, 2006
    Co-Authors: Julio J Secades, José Luis Lorenzo
    Abstract:

    Cytidine 5'-diphosphocholine, CDP-choline, or Citicoline is an essential intermediate in the biosynthetic pathway of structural phospholipids in cell membranes, particularly phosphatidylcholine. Following administration by both the oral and parenteral routes, Citicoline releases its two main components, cytidine and choline. Absorption by the oral route is virtually complete, and bioavailability by the oral route is therefore approximately the same as by the intravenous route. Once absorbed, Citicoline is widely distributed throughout the body, crosses the blood-brain barrier and reaches the central nervous system (CNS), where it is incorporated into the membrane and microsomal phospholipid fraction. Citicoline activates biosynthesis of structural phospholipids of neuronal membranes, increases brain metabolism, and acts upon the levels of different neurotransmitters. Thus, Citicoline has been experimentally shown to increase norepinephrine and dopamine levels in the CNS. Owing to these pharmacological mechanisms, Citicoline has a neuroprotective effect in hypoxic and ischemic conditions, decreasing the volume of ischemic lesion, and also improves learning and memory performance in animal models of brain aging. In addition, Citicoline has been shown to restore the activity of mitochondrial ATPase and membrane Na+/K+ATPase, to inhibit activation of certain phospholipases, and to accelerate reabsorption of cerebral edema in various experimental models. Citicoline has also been shown to be able to inhibit mechanisms of apoptosis associated to cerebral ischemia and in certain neurodegeneration models, and to potentiate neuroplasticity mechanisms. Citicoline is a safe drug, as shown by the toxicological tests conducted, that has no significant systemic cholinergic effects and is a well tolerated product. These pharmacological characteristics and the action mechanisms of Citicoline suggest that this product may be indicated for treatment of cerebral vascular disease, head trauma (HT) of varying severity, and cognitive disorders of different causes. In studies conducted in the treatment of patients with HT, Citicoline was able to accelerate recovery from post-traumatic coma and neurological deficits, achieving an improved final functional outcome, and to shorten hospital stay in these patients. Citicoline also improved the mnesic and cognitive disorders seen after HT of minor severity that constitute the so-called post-concussional syndrome. In the treatment of patients with acute ischemic cerebral vascular disease, Citicoline accelerates recovery of consciousness and motor deficit, achieves a better final outcome, and facilitates rehabilitation of these patients. The other major indication of Citicoline is for treatment of senile cognitive impairment, either secondary to degenerative diseases (e.g. Alzheimer disease) or to chronic cerebral vascular disease. In patients with chronic cerebral ischemia, Citicoline improves scores in cognitive rating scales, while in patients with senile dementia of the Alzheimer type it stops the course of disease, and neuroendocrine, neuroimmunomodulatory, and neurophysiological benefits have been reported. Citicoline has also been shown to be effective in Parkinson disease, drug addictions, and alcoholism, as well as in amblyopia and glaucoma. No serious side effects have occurred in any series of patients treated with Citicoline, which attests to the safety of treatment with Citicoline.

  • Citicoline in intracerebral haemorrhage a double blind randomized placebo controlled multi centre pilot study
    Cerebrovascular Diseases, 2006
    Co-Authors: Julio J Secades, José Castillo, Rafael Lozano, Antoni Dávalos, Jose Alvarezsabin, Francisco Rubio, Trial Investigators
    Abstract:

    Background: In experimental models Citicoline has shown beneficial effects in intracerebral haemorrhage. Citicoline is a neuroprotectant drug with some beneficial effects in human i

  • Neuroprotection afforded by prior Citicoline administration in experimental brain ischemia: effects on glutamate transport.
    Neurobiology of disease, 2005
    Co-Authors: Olivia Hurtado, Julio J Secades, María A. Moro, Antonio Cárdenas, Veronica Sanchez, Paz Fernández-tomé, Juan C. Leza, Pedro Lorenzo, Rafael Lozano, Antoni Dávalos
    Abstract:

    Background and purpose: Cytidine-5′-diphosphocholine (Citicoline or CDP-choline), an intermediate in the biosynthesis of phosphatidylcholine, has shown beneficial effects in a number of CNS injury models including cerebral ischemia. Citicoline is the only neuroprotectant that has proved efficacy in patients with moderate to severe stroke. However, the precise mechanism by which Citicoline is neuroprotective is not fully known. The present study was designed to search for mechanisms of Citicoline neuroprotective properties using in vivo and in vitro models of brain ischemia. Methods: Focal brain ischemia was produced in male adult Fischer rats by occluding both the common carotid and middle cerebral arteries. Brain glutamate levels were determined at fixed intervals after occlusion. Animals were then sacrificed, and infarct volume and brain ATP levels were measured. As in vitro model of ischemia, rat cultured cortical neurones or astrocytes, isolated or in co-culture, were exposed to oxygen–glucose deprivation (OGD) either in the absence or in the presence of Citicoline (1–100 μM). Viability was studied by measuring LDH release. Glutamate release and uptake, and ATP levels were also determined. Results: Citicoline (0.5, 1 and 2 g/kg i.p. administered 1 h before the occlusion) produced a reduction of the infarct size measured at striatum (18, 27 and 42% inhibition, respectively, n = 8, P < 0.05 vs. ischemia), effect that correlated with the inhibition caused by Citicoline on ischemia-induced increase in glutamate concentrations after the onset of the ischemia. Citicoline also inhibited ischemia-induced decrease in cortical and striatal ATP levels. Incubation of cultured rat cortical neurones with Citicoline (10 and 100 μM) prevented OGD-induced LDH and glutamate release and caused a recovery in ATP levels after OGD, confirming our previous results. In addition, Citicoline (100 μM) caused an increase in glutamate uptake and in EAAT2 glutamate transporter membrane expression in cultured rat astrocytes. Conclusions: Our present findings show novel mechanisms for the neuroprotective effects of Citicoline, which cooperate to decrease brain glutamate release after ischemia.