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.

Kava for the treatment of generalized anxiety disorder RCT: analysis of adverse reactions, liver function, addiction, and sexual effects.

Presently, little is known about a number issues concerning kava (Piper methysticum), including (i) whether kava has any withdrawal or addictive effects; (ii) if genetic polymorphisms of the cytochrome (CYP) P450 2D6 liver enzyme moderates any potential adverse effects; and (iii) if medicinal application of kava has any negative or beneficial effect on sexual function and experience. The study design was a 6-week, double-blind, randomized controlled trial (n = 75) involving chronic administration of kava (one tablet of kava twice per day; 120 mg of kavalactones per day, titrated in non-response to two tablets of kava twice per day; 240 mg of kavalactones) or placebo for participants with generalized anxiety disorder. Results showed no significant differences across groups for liver function tests, nor were there any significant adverse reactions that could be attributed to kava. No differences in withdrawal or addiction were found between groups. Interesting, kava significantly increased female's sexual drive compared to placebo (p = 0.040) on a sub-domain of the Arizona Sexual Experience Scale (ASEX), with no negative effects seen in males. Further, it was found that there was a highly significant correlation between ASEX reduction (improved sexual function and performance) and anxiety reduction in the whole sample.

Does a medicinal dose of kava impair driving? A randomized, placebo-controlled, double-blind study.

OVERVIEW: Increasing concerns over the potentially impairing effects of prescriptive sedative drugs such as benzodiazepines on driving have been raised. However, other alternatives such as natural medicines may also carry similar risks with respect to driving safety. Kava (Piper methysticum) is a psychotropic plant commonly used both recreationally and medicinally in the United States, Australia, and the South Pacific to elicit a physically tranquilizing effect. To date no controlled study has tested a medicinal dose of kava versus placebo and a standard sedative drug on driving ability and driving safety. OBJECTIVE: Due to the need to establish the safety of kava in operating a motor vehicle, we compared the acute effects of the plant extract versus the benzodiazepine oxazepam and placebo using a driving simulator. METHODS: A driving simulator (AusEd) was used by 22 adults aged between 18 and 65 years after being randomly administered an acute medicinal dose of kava (180 mg of kavalactones), oxazepam (30 mg), or placebo one week apart in a crossover design trial. RESULTS: No impairing effects on driving outcomes were found after kava administration compared to placebo. Results on specific driving outcome domains revealed that the oxazepam condition had significantly slower braking reaction time compared to the placebo condition (p =.002) and the kava condition (p =.003). The kava condition had significantly fewer lapses of concentration compared to the oxazepam condition (p =.033). No significant differences were found between conditions for steering deviation, speed deviation, and number of crashes. Results were not modified by driving experience. On the Bond-Lader visual analogue sub-scale of alertness, a significant Treatment × Time interaction (p =.032) was found, with a significant reduction over time for oxazepam decreasing alertness (p <.001), whereas no significant reduction was found in the kava or placebo conditions. CONCLUSION: The results indicate that a medicinal dose of kava containing 180 mg of kavalactones does not impair driving ability, whereas 30 mg of oxazepam shows some impairment. Research assessing larger recreational doses of kava on driving ability should now be conducted.

The acute effects of kava and oxazepam on anxiety, mood, neurocognition; and genetic correlates: a randomized, placebo-controlled, double-blind study.

RATIONALE: Kava (Piper methysticum) is a psychotropic plant medicine with history of cultural and medicinal use. We conducted a study comparing the acute neurocognitive, anxiolytic, and thymoleptic effects of a medicinal dose of kava to a benzodiazepine and explored for the first time specific genetic polymorphisms, which may affect the psychotropic activity of phytomedicines or benzodiazepines. METHODS: Twenty-two moderately anxious adults aged between 18 and 65 years were randomized to receive an acute dose of kava (180 mg of kavalactones), oxazepam (30 mg), and placebo 1 week apart in a crossover design trial. RESULTS: After exposure to cognitive tasks, a significant interaction was revealed between conditions on State-Trait Anxiety Inventory-State anxiety (p = 0.046, partial ŋ² = 0.14). In the oxazepam condition, there was a significant reduction in anxiety (p = 0.035), whereas there was no change in anxiety in the kava condition, and there was an increase in anxiety in the placebo condition. An increase in Bond-Lader "calmness" (p = 0.002) also occurred for the oxazepam condition. Kava was found to have no negative effect on cognition, whereas a reduction in alertness (p < 0.001) occurred in the oxazepam condition. Genetic analyses provide tentative evidence that noradrenaline (SLC6A2) transporter polymorphisms may have an effect on response to kava. CONCLUSION: Acute "medicinal level" doses of this particular kava cultivar in naive users do not provide anxiolytic activity, although the phytomedicine also appears to have no negative effects on cognition.

The acute effects of d-amphetamine and d-methamphetamine on ERP components in humans.

While a number of behavioural studies have been conducted to investigate the acute effects of amphetamines on tasks of attention and information processing, there is currently a scarcity of research concerning their electrophysiological effects in healthy adults. It is also unclear as to whether amphetamines exert effects on stimulus evaluation or response selection. In two studies, independent groups of twenty healthy illicit stimulant users aged between 21 and 32 years were administered 0.42 mg/kg d-amphetamine versus placebo, and 0.42 mg/kg d-methamphetamine versus placebo respectively, and completed an auditory oddball task on two separate testing days. A 62-channel EEG was recorded during the completion of the task, and the effects of amphetamines on N200 and P300 ERP components were analysed. d-amphetamine significantly decreased reaction time, improved accuracy, and reduced the latency of the P300 component relative to placebo, while having no effect on the N200 component. d-methamphetamine had no effect on reaction time, accuracy or the P300 component, but reduced the amplitude of the N200 component, relative to placebo. It was concluded that there is tentative support to suggest that d-amphetamine at a dose of 0.42 mg/kg may enhance speed of information processing while d-methamphetamine at a dose of 0.42 mg/kg may reflect changes to stimulus evaluation.

Examining brain-cognition effects of ginkgo biloba extract: brain activation in the left temporal and left prefrontal cortex in an object working memory task.

Ginkgo Biloba extract (GBE) is increasingly used to alleviate symptoms of age related cognitive impairment, with preclinical evidence pointing to a pro-cholinergic effect. While a number of behavioral studies have reported improvements to working memory (WM) associated with GBE, electrophysiological studies of GBE have typically been limited to recordings during a resting state. The current study investigated the chronic effects of GBE on steady state visually evoked potential (SSVEP) topography in nineteen healthy middle-aged (50-61 year old) male participants whilst completing an object WM task. A randomized double-blind crossover design was employed in which participants were allocated to receive 14 days GBE and 14 days placebo in random order. For both groups, SSVEP was recorded from 64 scalp electrode sites during the completion of an object WM task both pre- and 14 days post-treatment. GBE was found to improve behavioural performance on the WM task. GBE was also found to increase the SSVEP amplitude at occipital and frontal sites and increase SSVEP latency at left temporal and left frontal sites during the hold component of the WM task. These SSVEP changes associated with GBE may represent more efficient processing during WM task completion.

A randomized, controlled trial of meditation for work stress, anxiety and depressed mood in full-time workers.

Objective. To assess the effect of meditation on work stress, anxiety and mood in full-time workers. Methods. 178 adult workers participated in an 8-week, 3-arm randomized controlled trial comparing a "mental silence" approach to meditation (n = 59) to a "relaxation" active control (n = 56) and a wait-list control (n = 63). Participants were assessed before and after using Psychological Strain Questionnaire (PSQ), a subscale of the larger Occupational Stress Inventory (OSI), the State component of the State/Trait Anxiety Inventory for Adults (STAI), and the depression-dejection (DD) subscale of the Profile of Mood States (POMS). Results. There was a significant improvement for the meditation group compared to both the relaxation control and the wait-list groups the PSQ (P = .026), and DD (P = .019). Conclusions. Mental silence-orientated meditation, in this case Sahaja Yoga meditation, is a safe and effective strategy for dealing with work stress and depressive feelings. The findings suggest that "thought reduction" or "mental silence" may have specific effects relevant to work stress and hence occupational health.

Neurocognitive effects of kava (Piper methysticum): a systematic review.

RATIONALE: Kava (Piper methysticum) elicits dose-dependent psychotropic effects and thus may potentially deleteriously affect cognitive performance. Clinical trials have assessed the effects of kava on cognition, however, to our knowledge no systematic review has been conducted in this area. OBJECTIVE: To systematically review the effects of kava on cognition, providing an analysis of the individual study's methodological quality, results and effect sizes. METHODS: A systematic review was conducted of publications up to June 15th 2010, using the electronic databases MEDLINE, PsychINFO, CINAHL, Web of Science and The Cochrane Library. The search criteria involved kava and cognition related terms, e.g. memory and attention. RESULTS: Ten human clinical trials met inclusion criteria (acute n = 7, chronic n = 3). One acute study found that kava significantly improved visual attention and working memory processes while another found that kava increased body sway. One chronic study found that kava significantly impaired visual attention during high-cognitive demand. Potential enhanced cognition may be attributed to the ability of kava to inhibit re-uptake of noradrenaline in the pre-frontal cortex, while increased body sway may be due to GABA pathway modulation. CONCLUSIONS: The majority of evidence suggests that kava has no replicated significant negative effects on cognition.

An examination of the effects of the antioxidant Pycnogenol on cognitive performance, serum lipid profile, endocrinological and oxidative stress biomarkers in an elderly population.

The study examines the effects of the antioxidant flavonoid Pycnogenol on a range of cognitive and biochemical measures in healthy elderly individuals. The study used a double-blind, placebo-controlled, matched-pair design, with 101 elderly participants (60-85 years) consuming a daily dose of 150 mg of Pycnogenol for a three-month treatment period. Participants were assessed at baseline, then at 1, 2, and 3 months of the treatment. The control (placebo) and Pycnogenol groups were matched by age, sex, body mass index, micronutrient intake, and intelligence. The cognitive tasks comprised measures of attention, working memory, episodic memory, and psychomotor performance. The biological measures comprised levels of clinical hepatic enzymes, serum lipid profile, human growth hormone, and lipid peroxidation products. Statistically significant interactions were found for memory-based cognitive variables and lipid peroxidation products, with the Pycnogenol group displaying improved working memory and decreased concentrations of F2-isoprostanes relative to the control group.

The chronic effects of an extract of Bacopa monniera (Brahmi) on cognitive function in healthy human subjects.

RATIONALE: Extracts of Bacopa monniera have been reported to exert cognitive enhancing effects in animals. However, the effects on human cognition are inconclusive. OBJECTIVE: The current study examined the chronic effects of an extract of B. monniera (Keenmind) on cognitive function in healthy human subjects. METHODS: The study was a double-blind placebo-controlled independent-group design in which subjects were randomly allocated to one of two treatment conditions, B. monniera (300 mg) or placebo. Neuropsychological testing was conducted pre-(baseline) and at 5 and 12 weeks post drug administration. RESULTS: B. monniera significantly improved speed of visual information processing measured by the IT task, learning rate and memory consolidation measured by the AVLT (P<0.05), and state anxiety (P<0.001) compared to placebo, with maximal effects evident after 12 weeks. CONCLUSIONS: These findings suggest that B. monniera may improve higher order cognitive processes that are critically dependent on the input of information from our environment such as learning and memory.

An investigation into the acute nootropic effects of Hypericum perforatum L. (St. John's Wort) in healthy human volunteers.

Hypericum perforatum L. (St. John's Wort) is a complex herb that has been used for centuries for its putative medicinal properties, and has current therapeutic relevance as a treatment of mild to moderate depression. Recently, two studies in rodents have suggested that hypericum may also have memory-enhancing effects. It has a complex pharmacology, in that acute administration modulates numerous neurotransmitter systems that have previously been observed to either augment or impair a variety of memory processes in humans. This study aimed to examine whether acute administration of standardized hypericum extract could exert a nootropic effect in normal human subjects. The study employed a double-blind, crossover, repeated-measures design. Twelve healthy young subjects completed the Cognitive Drug Research (CDR) memory battery, following administration of placebo, 900 mg and 1800 mg hypericum (Blackmore's Hyperiforte). The findings suggested that hypericum does not have an acute nootropic effect in healthy humans at these doses. However, there was some evidence for an impairing effect on accuracy of numeric working memory and delayed picture recognition at the higher dose. This observed impairment could be due to a sensitivity of these specific tasks to modulation by neurotransmitters that have been noted to have memory-impairing effects (e.g. y-aminobutyric acid (GABA), serotonin).

Neuropsychological changes after 30-day Ginkgo biloba administration in healthy participants.

Ginkgo biloba extract (EGb) from the world's oldest living tree has been reputed to ameliorate cognitive decline in the elderly and slow cognitive deterioration in patients with dementia of the Alzheimer's type. EGb remains as one of the most popular plant extracts to alleviate symptoms associated with a range of cognitive disorders such as Alzheimer's disease, vascular dementia and age-related amnesic conditions. EGb is known to contain a range of chemically active components that have antagonistic effects on platelet-activating factor, free-radical scavenging activity and direct effects on the cholinergic neurotransmitter system. Recently there has been much speculation, that EGb may act as a 'smart drug' or nootropic agent in the healthy young to improve intelligence. We conducted a 30-d randomized, double-blind, placebo-controlled clinical trial in which 61 participants were administered a battery of validated neuropsychological tests before and after treatment. Statistical analysis indicated significant improvements in speed of information processing working memory and executive processing attributable to the EGb.

The acute effects of an extract of Bacopa monniera (Brahmi) on cognitive function in healthy normal subjects.

The Ayurvedic medicine Bacopa monniera (Brahmi) has been shown to exert cognitive enhancing effects in animals. The current study examined the acute effects of an extract of Bacopa monniera on cognitive function in normal healthy human subjects. The study was a double-blind, placebo-controlled independent group design in which subjects were randomly allocated to one of two treatment conditions, Bacopa monniera (300 mg) (n = 18) or placebo (n = 20). Neuropsychological testing was conducted before and 2 h after drug administration. No significant changes were found on any of the tests. The findings suggest that Bacopa monniera, at least for the dose administered, has no acute effects on cognitive functioning in normal healthy subjects. Copyright 2001 John Wiley & Sons, Ltd.

A preliminary investigation on the acute pharmacodynamic effects of hypericum on cognitive and psychomotor performance.

Research has indicated that the herb St John's Wort (Hypericum perforatum) has comparable efficacy to conventional antidepressants in the treatment of depression. Although clinical studies have demonstrated that hypericum has a superior side-effect profile compared to standard antidepressants, no study has directly compared the cognitive and psychomotor effects of hypericum with those of other antidepressants. The aim of the current study was to examine the acute effects of hypericum on cognitive and psychomotor function, and to compare its effects with those of amitriptyline. Thirteen healthy volunteers received an acute dose of placebo, amitriptyline (25 mg, positive control) or hypericum (900 mg or 1800 mg) in a double-blind, placebo-controlled design. Cognitive and psychomotor tests and subjective measures of sedation were administered before and 1, 2 and 4 hours after drug administration. Amitriptyline impaired performance on a battery of psychological tests, which included critical flicker fusion (CFF), choice reaction time (CRT), digit symbol substitution test (DSST), profile of mood states (POMS) and the line analogue rating scale (LARS), while hypericum had neutral effects on performance in these tests. However, hypericum induced a dose-related impairment on DSST. Current findings suggest that clinical doses of hypericum do not impair attention, sensorimotor function or information processing.

A delivery system for olfactory stimuli.

This paper describes the design of a new method for controlling and administering olfactory stimuli--namely, the hood system. The hood system involves a stream of vaporized odor (at known concentrations) mixed with odorless air and pumped (at a constant flow rate) into an oxygen therapy hood. It is designed to be used with odorants in solution, such as essential oils, as the olfactory stimulus. The use of oxygen therapy hoods allows for the precise control of a constant concentration of odorized air over time, while allowing subjects to breathe normally. The hood system provides a natural administration of olfactory stimuli and the exact determination of the stimulus concentration. The use of this system will allow experimental conditions to be completely defined and results and replication studies to be accurately interpreted. The hood system is portable, cost effective, and constructed from readily available components. It is proposed that the hood system could be adopted to suit a wide range of olfactory research, particularly that in which the effects of chronic exposure to olfactory stimuli on cognition are examined.