The effects of multivitamin supplementation on mood and general well-being in healthy young adults. A laboratory and at-home mobile phone assessment.

Previous research has suggested that multivitamin (MV) supplementation may be associated with beneficial effects for mood and general well-being, although treatment durations have typically been less than 90 days, samples have often been restricted to males only and acute effects have not been adequately differentiated from chronic effects. In the current study a MV supplement containing high levels of B-vitamins was administered daily to 138 healthy young adult participants between the ages of 20 and 50 years over a 16-week period. Chronic mood measures (GHQ-28, POMS, Chalder fatigue, PILL, Bond-Lader and custom visual analogue scales) were administered pre-dose at baseline, 8- and 16-weeks. Changes in Bond-Lader and VAS in response to a multi-tasking framework (MTF) were also assessed at 8- and 16-weeks. For a subset of participants, at-home mobile-phone assessments of mood were assessed on a weekly basis using Bond-Lader and VAS. No significant treatment effects were found for any chronic laboratory mood measures. In response to the MTF, a significant treatment x time interaction was found for STAI-S, with a trend towards a greater increase in stress ratings for male participants in the MV group at 16 weeks. However, this finding may have been attributable to a larger proportion of students in the male MV group. In contrast, at-home mobile-phone assessments, where assessments were conducted post-dose, revealed significantly reduced stress, physical fatigue and anxiety in the MV group in comparison to placebo across a number of time points. Further research using both acute and chronic dosing regimens are required in order to properly differentiate these effects.

The neurocognitive effects of Hypericum perforatum Special Extract (Ze 117) during smoking cessation.

The efficacy and tolerability of current treatments for smoking cessation are relatively poor. More research is required to address the biological mechanisms underpinning nicotine withdrawal and drug treatments for smoking cessation. We assessed the neurocognitive effects of Remotiv® (Hypericum perforatum Special Extract - Ze 117), Nicabate CQ Nicotine Replacement therapy (NRT) and combined NRT/HP during conditions of smoking abstinence in 20 regular smokers aged between 18 and 60 years over a period of 10 weeks during smoking cessation. A Spatial Working Memory (SWM) task was completed at baseline, 4 weeks prior to quitting, as well as at the completion of the study, following the 10 weeks of treatment. Brain activity was recorded during the completion of the SWM task using Steady-State Probe Topography. Reaction time and accuracy on the SWM task were not found to be significantly different between treatment groups at retest. Differences in SSVEP treatment profiles at retest are discussed, including stronger SSVEP Amplitude increase in posterior-parietal regions for the HP and NRT groups and greater fronto-central SSVEP Phase Advance in the HP group.

Neurocognitive and mood effects of alcohol in a naturalistic setting.

OBJECTIVE: The current pilot study aimed to assess the effects of drinking alcohol in a naturalistic setting on aspects of performance. METHODS: Thirty individuals were approached and tested individually in a university campus bar. They provided details regarding alcoholic drinks consumption. Each was breathalysed before and after completion of a computerised test battery administered on a handheld device. The battery consisted of visual analogue mood scales, a series of alcohol-sensitive psychomotor and cognitive tests. RESULTS: There were highly significant correlations between measured blood alcohol concentrations, estimated units of alcohol consumed and scores on a 'sober-drunk' VAS (p < 0.001 in all cases). For performance, there was a characteristic alcohol-associated shift in the speed/accuracy trade-off (SATO), which was reflected as significantly more errors with less effect on speed across several measures (including maze performance and Serial Sevens). Individuals who were more intoxicated were also significantly less alert. CONCLUSIONS: The data suggest that controlled laboratory tests into the effects of alcohol intoxication may have ecological validity, with SATO shifts amongst the characteristic impairments seen in both controlled and naturalistic settings.

Hair MDMA samples are consistent with reported ecstasy use: findings from a study investigating effects of ecstasy on mood and memory.

AIMS: Our group has conducted several Internet investigations into the biobehavioural effects of self-reported recreational use of MDMA (3,4-methylenedioxymethamphetamine or Ecstasy) and other psychosocial drugs. Here we report a new study examining the relationship between self-reported Ecstasy use and traces of MDMA found in hair samples. METHODS: In a laboratory setting, 49 undergraduate volunteers performed an Internet-based assessment which included mood scales and the University of East London Drug Use Questionnaire, which asks for history and current drug use. They also provided a hair sample for determination of exposure to MDMA over the previous month. RESULTS: Self-report of Ecstasy use and presence in hair samples were consistent (p < 0.00001). Both subjective and objective measures predicted lower self-reported ratings of happiness and higher self-reported stress. Self-reported Ecstasy use, but not presence in hair, was also associated with decreased tension. CONCLUSION: Different psychoactive drugs can influence long-term mood and cognition in complex and dynamically interactive ways. Here we have shown a good correspondence between self-report and objective assessment of exposure to MDMA. These data suggest that the Internet has potentially high utility as a useful medium to complement traditional laboratory studies into the sequelae of recreational drug use.

Improved cognitive performance and mental fatigue following a multi-vitamin and mineral supplement with added guaraná (Paullinia cupana).

Guaraná (Paullinia cupana) extracts are most commonly used in Western markets as putatively psychoactive food and drink additives. This double-blind, randomised, placebo-controlled, parallel groups study assessed the acute effects of either a vitamin/mineral/guaraná supplement or placebo drink in 129 healthy young adults (18-24 years). Participants completed a 10min version of the Cognitive Demand Battery (comprising: Serial 3s and Serial 7s subtraction tasks, a Rapid Visual Information Processing (RVIP) task, 'mental fatigue' scale). Thirty minutes following their drink participants made six consecutive completions of the battery (i.e. 60 min). The vitamin/mineral/guaraná combination resulted in improved task performance, in comparison to placebo, in terms of both increased speed and accuracy of performing the RVIP task throughout the post-dose assessment. The increase in mental fatigue associated with extended task performance was also attenuated by the supplement. This research supports previous findings demonstrating guaraná's cognition enhancing properties and provides evidence that its addition to a multi-vitamin-mineral supplement can improve cognitive performance and reduce the mental fatigue associated with sustained mental effort.

Acute cognitive effects of standardised Ginkgo biloba extract complexed with phosphatidylserine.

Recent data suggest that the complexation of standardised Ginkgo biloba extract (GBE) with soy-derived phospholipids enhances the bioavailability of GBE's active components. The current study therefore aimed to assess the comparative cognitive and mood effects of a low dose of GBE and products complexing the same extract with either phosphatidylserine or phosphatidylcholine. The study utilised a placebo-controlled, multi-dose, double-blind, balanced-crossover design. Twenty-eight healthy young participants received 120 mg GBE, 120 mg GBE complexed with phosphatidylserine (Virtiva), 120 mg GBE complexed with phosphatidylcholine and a matching placebo, on separate days 7 days apart. Cognitive performance was assessed using the Cognitive Drug Research (CDR) computerised test battery and Serial Subtraction tasks immediately prior to dosing and at 1, 2.5, 4 and 6 h thereafter. The primary outcome measures were the four aspects of cognitive performance, which have previously been derived by factor analysis of CDR subtests. Levels of terpenoids (bilobalide, ginkgolide A and ginkgolide B) were concomitantly assessed in plasma samples taken pre-dose and at 3 and 6.5 h post-dose.In keeping with previous research utilising the same methodology, 120 mg of GBE was not associated with markedly improved performance on the primary outcomes. However, administration of GBE complexed with phosphatidylserine resulted both in improved secondary memory performance and significantly increased speed of memory task performance across all of the post-dose testing sessions. Enhancement following GBE complexed with phosphatidylcholine was restricted to a modest improvement in secondary memory performance which was restricted to one post-dose time point. All three treatments were associated with improved calmness. There were no significant differences in post-dose levels of terpenoids between the Ginkgo containing treatments, although this latter finding may be attributable to methodological factors. Complexation with phosphatidylserine appears to potentiate the cognitive effects associated with a low dose of GBE. Further research is required to identify whether this effect is due to the complexation of the extracts, their mere combination, or the separate psychopharmacological actions of the two extracts.

A double-blind, placebo-controlled, multi-dose evaluation of the acute behavioural effects of guaraná in humans.

The present study aimed to systematically assess acute, dose-related behavioural effects of an extract of guaraná plant for the first time in humans. This double-blind, counterbalanced, placebo-controlled study (n=26) assessed the acute mood and cognitive effects throughout the day of four different doses (37.5 mg, 75 mg, 150 mg and 300 mg) of a standardised guaraná extract (PC-102). Assessment included the Cognitive Drug Research computerized test battery and Bond-Lader mood scales. Guaraná improved secondary memory performance and increased alert and content mood ratings. The two lower doses produced more positive cognitive effects than the higher doses. This research supports previous findings of cognitive improvements following 75 mg guaraná and provides the first exploration of different dose effects of guaraná in humans. The findings suggest that the effects cannot be attributed to caffeine alone.

The glycaemic effects of single doses of Panax ginseng in young healthy volunteers.

The results of two acute placebo-controlled, double-blind cross-over studies assessing the effect of Panax ginseng (G115) on blood glucose levels are reported. In study 1, thirty participants received three treatments: placebo; 200 mg G115; 400 mg G115. In study 2, twenty-seven participants received four treatments: placebo (0 mg ginseng and 30 mg saccharin); ginseng (200 mg ginseng and 30 mg saccharin); placebo-glucose (0 mg ginseng and 25 g oral glucose); ginseng-glucose (200 mg ginseng and 25 g oral glucose). Blood glucose levels were measured at baseline (at 09.00 hours after an overnight fast) and then 60, 90 (study 1 only) and 120 min post-dose. Both studies demonstrated that G115 alone significantly lowers fasting blood glucose levels. Conversely, in study 2 there was a significant drink x ginseng interaction suggesting opposing glycaemic effects of ginseng under fasting and raised blood glucose conditions. These data have implications for the use of ginseng in individuals with poor gluco-regulation.

Dancing hot on Ecstasy: physical activity and thermal comfort ratings are associated with the memory and other psychobiological problems reported by recreational MDMA users.

BACKGROUND: Non-drug factors such as ambient temperature can heighten the adverse effects of MDMA (3,4-methylendioxymethamphetamine) in animals. We assessed whether dancing and feeling hot on Ecstasy would be associated with more psychobiological problems in recreational users. METHODS: In an internet study, 206 unpaid participants (modal age 16-24) reported that they had used recreational Ecstasy/MDMA. They completed a drug use questionnaire, the Prospective Memory Questionnaire (PMQ), questions about dancing and feeling hot when on Ecstasy, and psychobiological problems afterwards. RESULTS: Those who danced 'all the time' when on Ecstasy, reported significantly more PMQ memory problems than the less intensive dancers. Prolonged dancing was also associated with more complaints of depression, memory problems, concentration and organizational difficulties afterwards. Feeling hot when on Ecstasy was associated with poor concentration in the comedown period, and with mood fluctuation and impulsivity off-drug. PMQ long-term problems demonstrated a significant curvilinear relationship with thermal self-ratings; more memory problems were noted by those who felt very hot, and by those who did not feel hot when on Ecstasy. CONCLUSIONS: Non-drug factors such as dancing and feeling hot are associated with the incidence of psychobiological problems reported by recreational Ecstasy/MDMA users.

MDMA polydrug users show process-specific central executive impairments coupled with impaired social and emotional judgement processes.

In recent years working memory deficits have been reported in users of MDMA (3,4-methylenedioxymethamphetamine, ecstasy). The current study aimed to assess the impact of MDMA use on three separate central executive processes (set shifting, inhibition and memory updating) and also on "prefrontal" mediated social and emotional judgement processes. Fifteen polydrug ecstasy users and 15 polydrug non-ecstasy user controls completed a general drug use questionnaire, the Brixton Spatial Anticipation task (set shifting), Backward Digit Span procedure (memory updating), Inhibition of Return (inhibition), an emotional intelligence scale, the Tromso Social Intelligence Scale and the Dysexecutive Questionnaire (DEX). Compared with MDMA-free polydrug controls, MDMA polydrug users showed impairments in set shifting and memory updating, and also in social and emotional judgement processes. The latter two deficits remained significant after controlling for other drug use. These data lend further support to the proposal that cognitive processes mediated by the prefrontal cortex may be impaired by recreational ecstasy use.

Differential experiences of the psychobiological sequelae of ecstasy use: quantitative and qualitative data from an internet study.

Previous work provided preliminary evidence that different patterns of use among ecstasy users may impact on perceived side-effects. Participants recruited via an ecstasy-related bulletin board differed in their responses compared to those recruited via other means. The present investigation compares self-reports of psychobiological difficulties among ecstasy users recruited either via a bulletin board or by alternative methods. Qualitative data included reports of any negative or positive changes attributable to ecstasy use and reasons for cessation of use. An Internet-based design was utilized and 209 volunteers completed the study, 117 of whom were recruited via a bulletin board devoted to discussion of ecstasy. Psychobiological difficulties attributable to ecstasy use varied, with mood fluctuation the most common. Differences between the two groups in the extent to which these problems were reported was found. Bulletin board recruits were less likely to report anxiety or poor concentration, but more likely to report tremors/twitches. For the whole sample, lifetime use was associated more with psychobiologial problems, although this pattern was stronger and more pervasive for the non-bulletin board participants. Bulletin board recruits were more aware of possible negative psychological effects and were more likely to report adopting harm reduction strategies. From the qualitative data three negative consequences of use were identified, the most common of which was "psychological problems". In support of the quantitative findings the likelihood of reporting psychological problems increased with lifetime exposure to ecstasy in both recruitment conditions but interestingly this did not appear to impact on reasons for cessation of use. Participants also reported a number of effects that they regarded as beneficial. Future research should also take these aspects of use into account.

Self-rated everyday and prospective memory abilities of cigarette smokers and non-smokers: a web-based study.

The present study examined self-ratings of two aspects of everyday memory performance: long-term prospective memory-measured by the prospective memory questionnaire (PMQ), and everyday memory-measured by the everyday memory questionnaire (EMQ). Use of other substances was also measured and used as covariates in the study. To ensure confidentiality and to expand the numbers used in previous studies, an Internet study was carried out and data from 763 participants was gathered. After controlling for other drug use and strategy use, the data from the PMQ revealed that smokers reported a greater number of long-term prospective memory errors than non-smokers. There were also differences between light and heavier smokers in long-term prospective memory, suggesting that nicotine may have a dose-dependent impact upon long-term prospective memory performance. There was also a significant ANOVA group effect on the EMQ, although the trend for more memory errors amongst the heavier smokers was statistically only borderline (p=.057). These findings suggest there are selective memory deficits associated with smoking and that long-term prospective memory deficits should be added to the growing list of problems associated with cigarette use.

Positive modulation of mood and cognitive performance following administration of acute doses of Salvia lavandulaefolia essential oil to healthy young volunteers.

Members of the Sage family, such as Salvia officinalis and Salvia lavandulaefolia, have a long history of use as memory-enhancing agents coupled with cholinergic properties that may potentially be relevant to the amelioration of the cognitive deficits associated with Alzheimer's disease. The current study utilised a placebo-controlled, double-blind, balanced, crossover design in order to comprehensively assess any mood and cognition modulation by S. lavandulaefolia. Twenty-four participants received single doses of placebo, 25 microl and 50 microl of a standardised essential oil of S. lavandulaefolia in an order dictated by a Latin square. Doses were separated by a 7-day washout period. Cognitive performance was assessed prior to the day's treatment and at 1, 2.5, 4 and 6 h thereafter using the Cognitive Drug Research (CDR) computerised test battery. Subjective mood ratings were measured using Bond-Lader visual analogue scales. The primary outcome measures were scores on the five cognitive factors that can be derived by factor analysis of the task outcomes from the CDR battery. The results showed that administration of S. lavandulaefolia resulted in a consistent improvement for both the 25- and 50-microl dose on the 'Speed of Memory' factor. There was also an improvement on the 'Secondary Memory' factor for the 25-microl dose. Mood was consistently enhanced, with increases in self-rated 'alertness', 'calmness' and 'contentedness' following the 50-microl dose and elevated 'calmness' following 25 microl. These results represent further evidence that Salvia is capable of acute modulation of mood and cognition in healthy young adults. The data also suggest that previous reports of memory enhancement by Salvia may be due to more efficient retrieval of target material.

Improved cognitive performance in human volunteers following administration of guarana (Paullinia cupana) extract: comparison and interaction with Panax ginseng.

Extracts from the plant guarana (Paullinia cupana) feature as putatively stimulating ingredients in a number of foods, drinks and dietary/herbal supplements. To date, little research in humans has examined the potential psychoactive effects of these extracts. Extracts of Panax ginseng, which are often sold in combination with guarana, contain similar potentially active components, and have been shown to modulate cognitive performance. In this double-blind, counterbalanced, placebo-controlled study, the cognitive and mood effects of separate single doses of: 75 mg of a dried ethanolic extract of guarana (approx 12% caffeine), 200 mg of Panax ginseng (G115), and their combination (75 mg/200 mg), were assessed in 28 healthy young (18-24) participants. On each day of the study (separated by a 7-day washout), cognitive performance and subjective mood were assessed pre-dose and at 1, 2.5, 4 and 6 h post-dose using the Cognitive Drug Research computerised assessment battery, Serial subtraction tasks and Bond-Lader mood scales. In comparison to placebo, all three treatments resulted in improved task performance throughout the day. In the case of guarana, improvements were seen across 'attention' tasks (but with some evidence of reduced accuracy), and on a sentence verification task. While also increasing the speed of attention task performance, both ginseng and the ginseng/guarana combination also enhanced the speed of memory task performance, with little evidence of modulated accuracy. Guarana and the combination, and to a lesser extent ginseng, also led to significant improvements in serial subtraction task performance. These results provide the first demonstration in humans of the psychoactive effects of guarana, and confirmation of the psychoactive properties of ginseng. Given the low caffeine content (9 mg) of this dose of guarana extract, the effects are unlikely to be attributable to its caffeine content.

Salvia lavandulaefolia (Spanish sage) enhances memory in healthy young volunteers.

Sage (Salvia) has a longstanding reputation in British herbal encyclopaedias as an agent that enhances memory, although there is little evidence regarding the efficacy of sage from systematized trials. Based on known pharmacokinetic and binding properties, it was hypothesised that acute administration of sage would enhance memory in young adult volunteers. Two experiments utilised a placebo-controlled, double-blind, balanced, crossover methodology. In Trial 1, 20 participants received 50, 100 and 150 microl of a standardised essential oil extract of Salvia lavandulaefolia and placebo. In Trial 2, 24 participants received 25 and 50 microl of a standardised essential oil extract of S. lavandulaefolia and placebo. Doses were separated by a 7-day washout period with treatment order determined by Latin squares. Assessment was undertaken using the Cognitive Drug Research computerised test battery prior to treatment and 1, 2.5, 4 and 6 h thereafter. The primary outcome measures were immediate and delayed word recall. The 50 microl dose of Salvia essential oil significantly improved immediate word recall in both studies. These results represent the first systematic evidence that Salvia is capable of acute modulation of cognition in healthy young adults.

Electroencephalograph effects of single doses of Ginkgo biloba and Panax ginseng in healthy young volunteers.

Both Ginkgo biloba and Panax ginseng exert a number of physiological effects and have been shown to modulate aspects of cognitive performance. Whilst a number of studies have examined ginkgo's effects on electroencephalograph (EEG) recordings, to date, none have investigated the EEG effects of ginseng. In this double-blind, placebo-controlled, balanced crossover experiment, the effects of single doses of G. biloba (360 mg GK501), P. ginseng (200 mg G115), and an identical placebo, on auditory-evoked potentials, contingent negative variation (CNV), and resting power within the delta, theta, alpha, and beta wavebands, were assessed in 15 healthy volunteers. Each participant was assessed on three separate occasions 4 h after consuming that day's treatment. The order of presentation of the treatments was dictated by a Latin square with 7 days between testing sessions. The results showed that ginseng led to a significant shortening of the latency of the P300 component of the evoked potential. Both ginseng and ginkgo also led to significant reductions in frontal 'eyes closed' theta and beta activity, with additional reduction for ginseng in the alpha waveband. These findings demonstrate for the first time that P. ginseng can directly modulate cerebroelectrical activity, and that these effects are more pronounced than those following G. biloba.

Modulation of mood and cognitive performance following acute administration of single doses of Melissa officinalis (Lemon balm) with human CNS nicotinic and muscarinic receptor-binding properties.

Melissa officinalis (Lemon balm) is a herbal medicine that has traditionally been attributed with memory-enhancing properties, but which is currently more widely used as a mild sedative and sleep aid. In a previous study it was demonstrated that a commercial Melissa extract led to dose-specific increases in calmness, and dose-dependent decrements in timed memory task performance. However, the extract utilized in that study did not exhibit in vitro cholinergic receptor-binding properties. The current study involved an initial screening of samples of M. officinalis for human acetylcholinesterase inhibition and cholinergic receptor-binding properties. The cognitive and mood effects of single doses of the most cholinergically active dried leaf were then assessed in a randomized, placebo-controlled, double-blind, balanced crossover study. Following the in vitro analysis, 20 healthy, young participants received single doses of 600, 1000, and 1600 mg of encapsulated dried leaf, or a matching placebo, at 7-day intervals. Cognitive performance and mood were assessed predose and at 1, 3, and 6 h postdose using the Cognitive Drug Research computerized assessment battery and Bond-Lader visual analog scales, respectively. In vitro analysis of the chosen extract established IC(50) concentrations of 0.18 and 3.47 mg ml(-1), respectively, for the displacement of [(3)H]-(N)-nicotine and [(3)H]-(N)-scopolamine from nicotinic and muscarinic receptors in the human cerebral cortex tissue. However, no cholinesterase inhibitory properties were detected. The most notable cognitive and mood effects were improved memory performance and increased 'calmness' at all postdose time points for the highest (1600 mg) dose. However, while the profile of results was overwhelmingly favorable for the highest dose, decrements in the speed of timed memory task performance and on a rapid visual information-processing task increased with decreasing dose. These results suggest that doses of Melissa officinalis at or above the maximum employed here can improve cognitive performance and mood and may therefore be a valuable adjunct in the treatment of Alzheimer's disease. The results also suggest that different preparations derived from the same plant species may exhibit different properties depending on the process used for the sample preparation.

Effects of alcohol on subjective ratings of prospective and everyday memory deficits.

BACKGROUND: Research has shown that heavy alcohol use has a detrimental effect on retrospective memory. Less is known about the effect of alcohol on everyday memory. METHODS: This study examined self-ratings of two aspects of memory performance: prospective memory (for example, forgetting to pass on a message) and everyday memory (measured by cognitive failures, such as telling someone a joke that you have told them before). To ensure anonymity and expand on the numbers of participants used in previous studies, data were collected by using the Internet. Data from 763 participants remained after data screening. RESULTS: After controlling for other drug and strategy use, there was clear evidence that differential use of alcohol was associated with impairments in the long-term aspect of prospective memory and with an increased number of cognitive failures. CONCLUSIONS: These results support and extend the findings of previous research: our findings are consistent with the idea that heavy use of alcohol does have a significant and negative effect on everyday cognitive performance. Possible causes of these impairments are discussed.