Effects Of Modafinil Research Articles

Cognition Enhancement by Modafinil: A Meta-Analysis

Currently, there are a number of pharmaceuticals available that have potential to enhance cognitive functioning, some of which may ultimately be considered for such use in military operations. Some drugs with potential for cognition enhancement have already been studied for use in military operations specific to their primary effect in sleep regulation (i.e., dextroamphetamine, modafinil, caffeine). There is considerable information available on many of these drugs. However, considerations for military appropriateness must be based on proficient research (e.g., randomly controlled trial design). A meta-analysis was conducted to summarize the current state of knowledge of these potentially cognition-enhancing drugs. The analysis only included studies which met inclusion criteria relevant to military research. The results of the literature review reveal a gap in research of the enhancement properties of the drugs of interest. The results yielded three studies (all of which studied modafinil) that met the criteria. The meta-analysis of these three studies revealed a relatively weak pooled effect of modafinil on some aspects of cognitive performance in normal, rested adults. While the results of this study support the efficacy of modafinil, the main finding is the large literature gap evaluating the short- and long-term effects of these drugs in healthy adults.

A Randomized, Double-Blind, Placebo-Controlled Trial of Modafinil for the Treatment of Apathy in Individuals With Mild-to-Moderate Alzheimer’s Disease

This study examined the effects of modafinil on apathetic symptomatology, performance of activities of daily living (ADLs), and caregiver burden in individuals with Alzheimer's disease (AD). 23 participants with a diagnosis of mild-to-moderate probable AD according to National Institute of Neurologic and Communicative Disorder and Stroke-Alzheimer's Disease and Related Disorders criteria were randomized into the experimental (modafinil 200 mg daily) or control (placebo) groups. All participants were also receiving stable doses of a cholinesterase inhibitor medication. Participants completed assessments at baseline and after 8 weeks of treatment. Outcome measures included family report measures of apathy, ADL performance, and caregiver burden, as well as direct assessment of ADL performance. The study was conducted at a private psychiatric hospital in Rhode Island from September 2005 until September 2007. Both the experimental and control groups showed reductions in apathy on the Frontal Systems Behavior Scale between baseline and final assessments (F1,20 = 18.017, P < .001, η2 = 0.474), and there was no significant additional reduction in apathy with modafinil (F1,20 = 0.008, P = .932, η2 = 0.000). Groups did not show significant changes in caregiver report of ADL performance over time (F1,19 = 0.268, P = .611). The correlation between change in apathy and change in caregiver burden was not significant (r = 0.355, P = .053), but there was a trend toward improved levels of apathy being related to decreased levels of caregiver burden. The addition of modafinil to the standard of care treatment (cholinesterase inhibitor medication) did not result in significant additional reductions in apathy or improvements in ADL functioning. The reduction in reported apathy observed in both groups between baseline and final assessments was likely due to placebo effect. However, reductions in perceived apathetic symptomatology were correlated with reductions in reported caregiver distress and burden. Larger studies with more statistical power are needed to confirm the absence of significant effects. ClinicalTrials.gov identifier: NCT01172145.

Differential effects of modafinil, methamphetamine, and MDMA on agonistic behavior in male mice

The aim of the present study was to compare the behavioral effects of modafinil, an atypical psychostimulatory acting and cognitive-function improving drug, with the effects of the psychostimulants methamphetamine (MET) and MDMA (3,4-methylenedioxymethamphetamine, or “ecstasy”) in a model of mouse agonistic behavior. This model enables the observation of ethologically well-defined sociable, timid, aggressive, and locomotor behavioral acts and postures. Singly-housed male mice (isolates) were separated into 4 groups. The observations were performed in 4 sessions, 1week apart. In each interaction, singly-housed mice were paired with non-aggressive group-housed partners for 4min in a neutral environment. The isolates received, in a Latin square design, either a) a vehicle or modafinil at doses 2.0, 10.0, or 50.0mg/kg; or b) a vehicle or MET at doses 1.0, 5.0, or 10.0mg/kg; or c) a vehicle or MDMA at doses 2.5, 10.0, or 30.0mg/kg. The isolates were categorized as timid or aggressive according to their behavior in the control interaction (vehicle pre-treatment). Elements of locomotor, sociable, aggressive, and timid behavior were evaluated (one-way ANOVA).In the aggressive mice, no change in the sum of aggressive behavior was measured following modafinil administration, while both methamphetamine and MDMA produced dose-dependent inhibition of aggression (p<0.01). The substantial difference in the tested drug effects on agonistic behavior was an increased occurrence of sociable acts (p<0.01) accompanied by a simultaneous increase of timid acts (p<0.01) recorded after MDMA, but not after modafinil or methamphetamine administration. In the timid mice, at least some doses of modafinil decreased timidity (p<0.01) and increased aggression (p<0.01) with no effect on sociability. Administration of MDMA increased timid activities (p<0.01). Both MDMA and MET decreased sociability (p<0.01).

Neurophysiological effects of modafinil on cue-exposure in cocaine dependence: A randomized placebo‐controlled cross-over study using pharmacological fMRI

ObjectiveEnhanced reactivity to substance related cues is a central characteristic of addiction and has been associated with increased activity in motivation, attention, and memory related brain circuits and with a higher probability of relapse. Modafinil was promising in the first clinical trials in cocaine dependence, and was able to reduce craving in addictive disorders. However, its mechanism of action remains to be elucidated. In this functional magnetic resonance imaging (fMRI) study therefore, cue reactivity in cocaine dependent patients was compared to cue reactivity in healthy controls (HCs) under modafinil and placebo conditions. MethodsAn fMRI cue reactivity study, with a double-blind, placebo-controlled cross-over challenge with a single dose of modafinil (200mg) was employed in 13 treatment seeking cocaine dependent patients and 16 HCs. ResultsIn the placebo condition, watching cocaine-related pictures (versus neutral pictures) resulted in higher brain activation in the medial frontal cortex, anterior cingulate cortex, angular gyrus, left orbitofrontal cortex, and ventral tegmental area (VTA) in the cocaine dependent group compared to HCs. However, in the modafinil condition, no differences in brain activation patterns were found between cocaine dependent patients and HCs. Group interactions revealed decreased activity in the VTA and increased activity in the right ACC and putamen in the modafinil condition relative to the placebo condition in cocaine dependent patients, whereas such changes were not present in healthy controls. Decreases in self-reported craving when watching cocaine-related cues after modafinil administration compared to the placebo condition were associated with modafinil‐induced increases in ACC and putamen activation. ConclusionsEnhanced cue reactivity in the cocaine dependent group compared to healthy controls was found in brain circuitries related to reward, motivation, and autobiographical memory processes. In cocaine dependent patients, these enhanced brain responses were attenuated by modafinil, mainly due to decreases in cue‐ reactivity in reward‐related brain areas (VTA) and increases in cue reactivity in cognitive control areas (ACC). These modafinil‐induced changes in brain activation in response to cocaine-related visual stimuli were associated with diminished self-reported craving. These findings imply that in cocaine dependent patients, modafinil, although mainly known as a cognitive enhancer, acts on both the motivational and the cognitive brain circuitry.

Reduced EDSS progression in multiple sclerosis patients treated with modafinil for three years or more compared to matched untreated subjects

BackgroundModafinil is a wakefulness-promoting drug used to treat narcolepsy, obstructive sleep apnoea, and shift-work sleep disorder. Modafinil has also been used for the treatment of fatigue and excessive sleepiness in other neurological disorders including multiple sclerosis, psychiatric disorders, and for cognitive enhancement. Recent preclinical studies suggest a potential neuroprotective effect of modafinil in neurodegenerative diseases. Therefore, we investigated its neuroprotective potential in multiple sclerosis. ObjectiveTo retrospectively assess disease progression in a group of MS patients that had received treatment with modafinil, and a matched group that received no treatment with modafinil. MethodsWe assessed the expanded disability status scale (EDSS) score change, over at least three years, in 30 patients with MS treated with modafinil, and in 90 patients who did not receive modafinil. The two groups were matched for initial EDSS, age, sex, type of disease, disease duration, duration of follow-up, and concomitant disease modifying therapies. Statistical analysis was performed using a general linear regression model. ResultsIn relapsing-remitting (RR) patients treated with modafinil there was no significant EDSS change over the follow-up period. In RR patients not treated with modafinil, the mean EDSS increased significantly (0.94; p=0.0001) over the follow-up period. Independent of modafinil treatment status, our model indicated an additional mean EDSS increase of 1.1 point (p=0.0002) for progressive patients i.e. mean EDSS change was 1.1 point for modafinil treated, and 1.1+0.94=2.04 points for modafinil-untreated patients. ConclusionOur results support the hypothesis that modafinil has neuroprotective potential, and may play a role in the treatment of multiple sclerosis. A prospective study will need to confirm this finding.

Using the Test of Variables of Attention to Determine the Effectiveness of Modafinil in Children With Attention-Deficit Hyperactivity Disorder (ADHD): A Prospective Methylphenidate-Controlled Trial

The efficacy of modafinil in comparison with methylphenidate in treatment of pediatric attention-deficit hyperactivity disorder (ADHD) has not been thoroughly investigated. This study compared the effect of modafinil versus methylphenidate on continuous attention task in children with ADHD, using the Test of Variables of Attention. Twenty-eight participants completed a baseline test followed by administration of a single dose of either methylphenidate or modafinil, after which the test was repeated. The test was performed a third time, after each subject received a dose of the medication not previously administered. Comparison of scores showed mean baseline, postmethylphenidate, and postmodafinil scores of -2.04, 0.017, and 0.09, respectively. No difference was found between improvements observed with either medication (P < .05). Adverse events for both agents were mild and self-limited, including abdominal pain, diarrhea, and hyposomnia. The authors conclude that modafinil is as effective as methylphenidate; however, a larger scale long-term study is required to confirm these results.

Retinoic acid as target for local pharmacokinetic interaction with modafinil in neural cells

While the biological importance of the cytochrome P450 system in the liver is well established, much less is known about its role in the brain and drug interactions at the level of brain cells have hardly been investigated. Here, we show that modafinil, a well-known inducer of hepatic CYP enzymes, also increases CYP3A4 expression in human-derived neuron-like SH-SY5Y cells. Upregulation of CYP3A4 by modafinil was associated with increased retinoic acid (RA) degradation, which could be blocked by specific CYP3A4 inhibitor erythromycin. In turn, reduced RA levels in culture medium during modafinil treatment resulted in decreased neuronal differentiation of SH-SY5Y cells as assessed by intracellular neurotransmitter concentrations and proliferative activity. Again, this differentiation-impeding effect of modafinil on SH-SY5Y cells was antagonized by erythromycin. Similarly, modafinil treatment of the murine GL261 glioma cell line resulted in increased proliferative activity. This was associated with upregulation of RA-degrading CYP26A1 in GL261 cells. Taken together, our results indicate that psychopharmacological agents such as modafinil may directly act on CYP enzymes in neural tissue. These kinds of drug effects may become highly relevant especially in the context of biomolecules such as RA whose local metabolism in brain is under tight spatial and temporal control.

Modafinil inhibits KCa3.1 currents and muscle contraction via a cAMP-dependent mechanism

Modafinil has been used as a psychostimulant for the treatment of narcolepsy. However, its primary mechanism of action remains elusive. Therefore, we examined the effects of modafinil on KCa3.1 channels and vascular smooth muscle contraction. KCa3.1 currents and channel activity were measured using a voltage-clamp technique and inside-out patches in mouse embryonic fibroblast cell line, NIH-3T3 fibroblasts. Intracellular adenosine 3′,5′-cyclic monophosphate (cAMP) concentration was measured, and the phosphorylation of KCa3.1 channel protein was examined using western blotting in NIH-3T3 fibroblasts and/or primary cultured mouse aortic smooth muscle cells (SMCs). Muscle contractions were recorded from mouse aorta and rat pulmonary artery by using a myograph developed in-house. Modafinil was found to inhibit KCa3.1 currents in a concentration-dependent manner, and the half-maximal inhibition (IC50) of modafinil for the current inhibition was 6.8±0.7nM. The protein kinase A (PKA) activator forskolin also inhibited KCa3.1 currents. The inhibitory effects of modafinil and forskolin on KCa3.1 currents were blocked by the PKA inhibitors PKI14–22 or H-89. In addition, modafinil relaxed blood vessels (mouse aorta and rat pulmonary artery) in a concentration-dependent manner. Modafinil increased cAMP concentrations in NIH-3T3 fibroblasts or primary cultured mouse aortic SMCs and phosphorylated KCa3.1 channel protein in NIH-3T3 fibroblasts. However, open probability and single-channel current amplitudes of KCa3.1 channels were not changed by modafinil. From these results, we conclude that modafinil inhibits KCa3.1 channels and vascular smooth muscle contraction by cAMP-dependent phosphorylation, suggesting that modafinil can be used as a cAMP-dependent KCa3.1 channel blocker and vasodilator.

Practical Use and Risk of Modafinil, a Novel Waking Drug

ObjectivesModafinil is a waking drug prescribed to narcolepsy patients, but its usage among healthy individuals is increasing to enhance their alertness or to mitigate fatigue. This study was conducted to investigate practical use and toxic effects on neuro-immune interaction of modafinil.MethodsThis study reviewed the significance of psychoactive drugs, and discussed the benefits and risks of the application of modafinil, which seems to be ideal as an anti-psychotic or anti-fatigue agent.ResultsModafinil is known to have less or no adverse effects than those found in traditional psychostimulants such as amphetamine, methylphenidate or cocaine. It can be applied as an anti-psychotic or anti-fatigue agent. However, the waking mechanism of modafinil is yet to be fully revealed. Recent studies reported that modafinil may be subject to abuse and addiction. In addition prolonged sleeplessness induces stress responses and impairs immune function.ConclusionsModafinil can be used by anyone, who wishes to work late, stay awake, enhance their cognitive reactions, or brighten their moods. Users may already be under a great level of stress, i.e. cancer patients or soldiers in a battle field. A psychoneuroimmunological approach is thus needed to investigate the multi-functional effects of modafinil.

COMT Val158Met, BDNF Val66Met, and OPRM1 Asn40Asp and Methamphetamine Dependence Treatment Response

COMT Val158Met, BDNF Val66Met, and OPRM1 Asn40Asp and Methamphetamine Dependence Treatment Response

Effect of Pharmacological Enhancement on the Cognitive and Clinical Psychomotor Performance of Sleep-Deprived Doctors

To investigate the effect of modafinil 200 mg on the performance of a cohort of healthy male doctors after 1 night of supervised sleep deprivation. Sleep-deprived and fatigued doctors pose a safety risk to themselves and their patients. Yet, because of the around-the-clock nature of medical practice, doctors frequently care for patients after periods of extended wakefulness or during circadian troughs. Studies suggest that a group of substances may be capable of safely and effectively reversing the effects of fatigue. However, little work has been done to investigate their role within our profession. We conducted a parallel, double-blind, randomized, and placebo-controlled study to investigate the effect of pharmacological enhancement on performance doctors. Thirty-nine healthy male resident doctors received either lactose placebo (n = 19) or modafinil 200 mg (n = 20) after 1 night of sleep deprivation. A selection of CANTAB neuropsychological tests was used to assess higher cognitive function. Clinical psychomotor performance was assessed using the Minimally Invasive Surgical Trainer Virtual Reality. Assessments were carried out between 6.00 AM and approximately 8.00 AM. Modafinil improved performance on tests of higher cognitive function; participants in the modafinil group worked more efficiently when solving working memory (F1,38 = 5.24, P = 0.028) and planning (F1,38 = 4.34, P = 0.04) problems, were less-impulsive decision makers (F1,37 = 6.76, P = 0.01), and were more able to flexibly redirect their attention (F1,38 = 4.64, P = 0.038). In contrast, no improvement was seen in tests of clinical psychomotor performance. Our results suggest that fatigued doctors might benefit from pharmacological enhancement in situations that require efficient information processing, flexible thinking, and decision making under time pressure. However, no improvement is likely to be seen in the performance of basic procedural tasks.

Acute Modafinil Effects on Attention and Inhibitory Control in Methamphetamine-Dependent Humans

Individuals who are methamphetamine dependent exhibit higher rates of cognitive dysfunction than healthy people who do not use methamphetamine, and this dysfunction may have a negative effect on the success of behavioral treatments for the disorder. Therefore, a medication that improves cognition, such as modafinil (Provigil), may serve as a useful adjunct to behavioral treatments for methamphetamine dependence. Although cognitive-enhancing effects of modafinil have been reported in several populations, little is known about the effects of modafinil in methamphetamine-dependent individuals. We thus sought to evaluate the effects of modafinil on the cognitive performance of methamphetamine-dependent and healthy individuals. Seventeen healthy subjects and 24 methamphetamine- dependent subjects participated in this randomized, double-blind, placebo-controlled, crossover study. Effects of modafinil (200 mg, single oral dose) were assessed on participants' performance on tests of inhibitory control, working memory, and processing speed/attention. Across subjects, modafinil improved performance on a test of sustained attention, with no significant improvement on any other cognitive tests. However, within the methamphetamine-dependent group only, participants with a high baseline frequency of methamphetamine use demonstrated a greater effect of modafinil on tests of inhibitory control and processing speed than those participants with low baseline use of methamphetamine. Although modafinil produced limited effects across all participants, methamphetamine-dependent participants with a high baseline use of methamphetamine demonstrated significant cognitive improvement on modafinil relative to those with low baseline methamphetamine use. These results add to the findings from a clinical trial that suggested that modafinil may be particularly useful in methamphetamine-dependent subjects who use the drug frequently.

A placebo-controlled study of the modafinil added to risperidone in chronic schizophrenia

In recent years, evidence suggests that modafinil may be useful for certain symptom domains of schizophrenia, especially for the negative and cognitive symptoms. However, the results are not consistent. This study was designed to investigate the effect of modafinil added to risperidone in patients with chronic schizophrenia in a double blind and randomized clinical trial. Participants were inpatients males (35) and females (11), ages 20-49 years at two teaching psychiatric hospital in Iran. All patients were in the active phase of the illness and met DSM-IV-TR criteria for schizophrenia. Patients were allocated in a random fashion 23 patients to risperidone 6 mg/day plus modafinil 200 mg/day and 23 patients to risperidone 6 mg/day plus placebo. The principal measure of outcome was the positive and negative syndrome scale (PANSS). Patients were assessed by a psychiatrist at baseline and after 2, 4, 6 and 8 weeks after the start of medication. The modafinil group had significantly greater improvement in the negative symptoms as well as PANSS total scores over the 8-week trial. Therapy with 200 mg/day of modafinil was well tolerated and no clinically important side effects were observed. The present study indicates modafinil as a potential adjunctive treatment strategy for treatment of schizophrenia particularly the negative symptoms. Nevertheless, results of larger-controlled trials are needed before recommendation for broad clinical application can be made.

Effects of modafinil on cognitive functions in first episode psychosis

Cognitive impairments are important determinants of functional outcome in psychosis, which are inadequately treated by antipsychotic medication. Modafinil is a wake-promoting drug that has been shown to improve attention, memory and executive function in the healthy population and in patients with schizophrenia. We aimed to establish modafinil's role in the adjunctive treatment of cognitive impairments in the first episode of psychosis, a time when symptoms may be more malleable than at chronic stages of the disease. Forty patients with a first episode of psychosis participated in a randomised, double-blind, placebo-controlled crossover design study assessing the effects of a single dose of 200mg modafinil on measures of executive functioning, memory, learning, impulsivity and attention. Modafinil improved verbal working memory (d = 0.24, p = 0.04), spatial working memory errors (d = 0.30, p = 0.0004) and strategy use (d = 0.23, p = 0.03). It also reduced discrimination errors in a task testing impulsivity. Modafinil showed no effect on impulsivity measures, sustained attention, attentional set-shifting, learning or fluency. Modafinil selectively enhances working memory in first episode psychosis patients, which could have downstream effects on patients' social and occupational functioning.

Effects of Modafinil on Sleep–Wake Cycles in Larval Zebrafish

We describe, for the first time, the effects of the wakefulness-promoting drug modafinil on sleep and wakefulness in larval zebrafish. Modafinil is currently used to treat narcolepsy, hypersomnia, and shift-work disorder by increasing wakefulness. Tolerance and dependence are limited with modafinil use, differentiating it from common stimulants; however, the neural mechanisms of action of modafinil are still unknown. Zebrafish, a low-cost, prolific, and genetically tractable animal model, have recently become a key model in sleep research. Zebrafish express circadian rhythms, sleep homeostasis, and sleep pressure, and, in addition, respond to common hypnotics and stimulants in a manner similar to mammals. Therefore, in the current experiment we characterize the effects of modafinil on sleep-wake cycles in larval zebrafish as a first step to gaining further insight into the neural mechanisms underlying the effects of modafinil. We show that modafinil modulates sleep-wake activity in larval zebrafish in a manner consistent with what would be predicted from mammalian data. Modafinil increases wakefulness by lengthening wake-bouts, an effect that likely restricted to the night (lights-off). These results validate the use of zebrafish as an animal model for the study of sleep and provide a means for dissecting the neural mechanisms of modafinil, and, more broadly, sleep disorders.

Modafinil for the treatment of methamphetamine dependence

Aim Modafinil was tested for efficacy in decreasing use in methamphetamine-dependent participants, compared to placebo. Methods This was a randomized, double-blind, placebo-controlled study, with 12 weeks of treatment and a 4-week follow-up. Eight outpatient substance abuse treatment clinics participated in the study. There were 210 treatment-seekers randomized, who all had a DSM-IV diagnosis of methamphetamine dependence; 68 participants to placebo, 72 to modafinil 200 mg, and 70 to modafinil 400 mg, taken once daily on awakening. Participants came to the clinic three times per week for assessments, urine drug screens, and group psychotherapy. The primary outcome measure was a methamphetamine non-use week, which required all the week's qualitative urine drug screens to be negative for methamphetamine. Results Regression analysis showed no significant difference between either modafinil group (200 or 400 mg) or placebo in change in weekly percentage having a methamphetamine non-use week over the 12-week treatment period ( p = 0.53). Similarly, a number of secondary outcomes did not show significant effects of modafinil. However, an ad-hoc analysis of medication compliance, by urinalysis for modafinil and its metabolite, did find a significant difference in maximum duration of abstinence (23 days vs. 10 days, p = 0.003), between those having the top quartile of compliance (>85% of urines were positive for modafinil, N = 36), and the lower three quartiles of modafinil 200 and 400 mg groups ( N = 106). Conclusions Although these data suggest that modafinil, plus group behavioral therapy, was not effective for decreasing methamphetamine use, the study is probably inconclusive because of inadequate compliance with taking medication.

Addictive potential of modafinil and cross‐sensitization with cocaine: a pre‐clinical study

Repeated or even a single exposure to drugs of abuse can lead to persistent locomotor sensitization, which is the result of an abundance of neuroplastic changes occurring within the circuitry involved in motivational behavior and is thought to play a key role in certain aspects of drug addiction. There is substantial controversy about the addictive potential of modafinil, a wake-promoting drug used to treat narcolepsy that is increasingly being used as a cognitive enhancer and has been proposed as a pharmacotherapy for cocaine dependence. Male mice were used to investigate the ability of modafinil to induce locomotor sensitization after repeated or single administration in mice. Bidirectional cross-sensitization with cocaine and modafinil-induced conditioned place preference were also evaluated. Both repeated and single exposure to moderate and high doses of modafinil produced a pronounced locomotor sensitization that cross-sensitized in a bidirectional way with cocaine. Remarkably, when cocaine and modafinil were repeatedly administered sequentially, their behavioral sensitization was additive. Supporting these behavioral sensitization data, modafinil produced a pronounced conditioned place preference in the mouse. Taken together, the present findings provide pre-clinical evidence for the addictive potential of modafinil. Our data also strongly suggest that similar neural substrates are involved in the psychomotor/rewarding effects of modafinil and cocaine.

Chronic modafinil effects on drug-seeking following methamphetamine self-administration in rats

Acute administration of the cognitive enhancing drug, modafinil (Provigil®), reduces methamphetamine (Meth) seeking following withdrawal from daily self-administration. However, the more clinically relevant effects of modafinil on Meth-seeking after chronic treatment have not been explored. Here, we determined the impact of modafinil on Meth-seeking after chronic daily treatment during extinction or abstinence following Meth self-administration. Rats self-administered intravenous Meth during daily 2-h sessions for 14 d, followed by extinction sessions or abstinence. During this period, rats received daily injections of vehicle, 30, or 100 mg/kg modafinil and were then tested for Meth-seeking via cue, Meth-primed, and context-induced reinstatement at early and late withdrawal time-points. We found that chronic modafinil attenuated relapse to a Meth-paired context, decreased conditioned cue-induced and Meth-primed reinstatement, and resulted in enduring reductions in Meth-seeking even after discontinuation of treatment. Additionally, we determined that only a very high dose of modafinil (300 mg/kg) during maintenance of self-administration had an impact on Meth intake. These results validate and extend clinical and preclinical findings that modafinil may be a viable treatment option for Meth addiction.

Cognitive difficulties among patients with cancer receiving chemotherapy affects quality of life: A University of Rochester Clinical Community Oncology Program study of 439 patients.

9119 Background: Cognitive difficulties affect up to 75% of cancer patients receiving chemotherapy, and these difficulties linger in up to 35% of survivors years after treatment. The extent to which cognitive difficulties affect quality of life (QOL) in patients receiving chemotherapy is not well-understood. Methods: We examined levels of memory and concentration difficulty in 439 patients undergoing chemotherapy who were enrolled in a randomized trial assessing effects of modafinil on cancer-related fatigue conducted through the University of Rochester Clinical Community Oncology Program (CCOP). Memory and concentration were assessed via the Fatigue Symptom Checklist (FSCL) from those that completed the measure at cycles 2, 3, and 4 of chemotherapy. QOL (i.e., general activity, mood, normal work, and enjoyment of life) items were assessed by the Brief Fatigue Inventory (BFI). Spearman’s rho correlations were used to determine the strength of the relationship between cognitive function and QOL. Logistic regression was used to predict associations between memory and concentration at cycle 2 and 3 with cycle 4 and was also used to predict associations between memory and concentration difficulty at cycle 2 with interference in QOL at cycle 4. Results: Concentration and memory difficulty at cycles 2 and 3 were both significant predictors of concentration and memory difficulty at cycle 4 (OR range=1.94 to 9.08; all p <0.05). At cycles 2, 3, and 4, problems with memory and concentration were significantly correlated with interference in all QOL items assessed (r values range=0.160 to 0.365, all p <0.05). Concentration difficulty at cycle 2 was significantly predictive of interference in all QOLs items at cycle 4 (OR range=2.23 to 3.34; all p <0.05). Memory difficulty at cycle 2 was only significantly predictive of interference in mood at cycle 4 (OR=2.05, p <0.05) and not other items (OR range=1.33 to 2.13; p >0.05). Conclusions: Our results suggest that cognitive difficulties in cancer patients receiving chemotherapy are associated with reductions in QOL. Further research on the long-term effects of cognitive difficulties on QOL are needed.

Attenuated methamphetamine induced neurotoxicity by modafinil administration in mice

Methamphetamine (METH) is a highly addictive drug that might induce neurotoxicity. Clinical trials have reported that modafinil, a wake-promoting agent used to treat sleep disorders, may have some efficacy for the treatment of psychostimulant addiction. In this study we tested possible neuroprotective effects of modafinil after toxic METH administration in mice. We evaluated the effect of modafinil (two injections of either 90 or 180 mg/kg) and METH binge (3 × 7 mg/kg i.p. injections, 3-h apart) coadministration on DA striatal content, TH immunoreactivity in striatal areas and spontaneous locomotor activity. We also investigated acute locomotor activity and stereotypy profile in mice treated with a single METH dose (2 and 7 mg/kg) pretreated with modafinil (90 and 180 mg/kg). We found that mice treated with a METH binge showed a marked decrease in DA and dopaminergic metabolites as well as lower levels of TH immunoreactivity in the dorsal striatum. Pretreatment with modafinil (both 90 and 180 mg/kg) attenuated these effects but did not prevent METH induced decrease in locomotion. We also found that groups that received the combination of both modafinil and single dose METH showed a decrease in total distance traveled in an open field compared with METH groups. We observed an increment in the time mice expended doing stereotypic movements (continuous sniffing) in the group that received the combination of both METH and modafinil (i.e., decreasing locomotion). Our results suggest a possible protective role of modafinil against METH acute striatal toxicity.