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Background: Preclinical data have suggested involvement of the endocannabinoid (eCB) system in MDMA-induced memory impairment. Clinical research has shown that blockade of the 5-HT 2 receptor nulls memory impairment during MDMA intoxication. Interestingly, studies have demonstrated that the eCB and the 5-HT system interact. It was hypothesized that MDMA would cause an increase in eCB concentrations together with a decrease in memory performance, and that combining MDMA with a 5-HT 2 receptor blocker ketanserin would lead to a counteraction of the MDMA effects on eCB concentrations and memory., Methods: Twenty healthy recreational polydrug users entered a double-blind placebo-controlled within-subject study. Participants received a pre-treatment (ketanserin 40 mg, placebo) followed 30 min later by a treatment (MDMA 75 mg, placebo). Verbal memory was tested by means of a 30-word learning test. Endocannabinoid concentrations (anandamide (2-AG); N-arachidonylethanolamine (AEA)) were assessed in blood at baseline, before (90 min post-treatment) and after cognitive tests (150 min post-treatment)., Results: Findings showed that MDMA impaired memory 90 min post-treatment in the word learning task. This effect was a replication of previous studies using the same dose of MDMA (75 mg) and the same learning paradigm. Contrary to our hypothesis, MDMA did not affect eCB concentrations, nor did ketanserin block MDMA-induced memory impairment. Ketanserin caused an increase in AEA concentrations, 180 min after administration., Conclusion: Current findings suggest that peripherally measured endocannabinoids are not associated with the verbal memory deficit during MDMA intoxication., Trial Registration Number: NTR3691.

Rationale: A visuospatial episodic memory impairment has recently been identified in irritable bowel syndrome. Increased tryptophan metabolism along the kynurenine pathway has also been reported in irritable bowel syndrome, which may play a role in altered cognitive performance as peripheral kynurenine can cross the blood brain barrier and lead to the production of neuroactive metabolites, which modulate glutamatergic and cholinergic signalling, key neurotransmitter systems involved in cognitive function., Objectives: Utilising the acute tryptophan depletion (ATD) protocol, the aim of this study was to examine if manipulating peripheral levels of tryptophan regulates cognitive performance in irritable bowel syndrome and also to determine for the first time if the ATD protocol alters kynurenine supply to the central nervous system., Methods: In this double-blind, placebo-controlled, crossover design study, nine female patients with irritable bowel syndrome and 14 matched female healthy controls participant completed a range of tests from the CANTAB(®) following ATD and placebo. Plasma tryptophan and kynurenine, self-report measures of gastrointestinal symptoms, mood and arousal were determined pre- and post-treatment on each study day., Results: Following placebo (p = 0.016) but not ATD (p > 0.05), patients with irritable bowel syndrome exhibited impaired visuospatial memory performance (Paired Associates Learning (PAL) test). In addition, ATD significantly decreased (p < 0.001) and placebo significantly increased (p < 0.001) plasma kynurenine levels in both groups., Conclusions: Manipulating peripheral tryptophan and kynurenine levels using ATD modulates hippocampal-mediated cognitive performance in irritable bowel syndrome but not healthy controls. These data may have important implications for reducing cognitive impairment in irritable bowel syndrome.

Rationale: While alcohol intoxication is known to increase disinhibited behavior, the degree to which disinhibition occurs appears to depend on a number of factors including executive functioning ability. However, the neural mechanisms by which individual differences in executive functioning lead to variable degrees of disinhibition remain unclear., Objectives: The aim of the current study was to examine the neural mechanisms by which individual differences in working memory (WM) capacity moderate alcohol-induced disinhibition., Methods: Seventeen heavy-drinking males participated in a within-subjects design in which two sessions were completed: an alcohol session (.82 g/kg) and a control session. Participants completed a go/no-go task while undergoing functional magnetic resonance imaging (fMRI) after ingestion of the control or alcohol beverage. WM capacity was measured using an operation span task., Results: Significant interactions of session and WM capacity emerged in contrasts examining successful response inhibition within superior temporal gyrus and unsuccessful inhibition in regions within the default mode network. In all cases, individuals with low WM capacity demonstrated a relative decrease in blood oxygen level-dependent (BOLD) response during the alcohol compared to control session, whereas the high-WM-capacity group demonstrated relative increases in BOLD response in the alcohol compared to control session., Conclusions: Low WM capacity appears to be associated with decreased neural response to signals indicating a need for behavioral control, an effect that may lead to increased difficulty with inhibiting responses and increased negative consequences from alcohol intoxication.

Rationale: There is potential for multivitamin supplementation to improve cognition in the elderly. This randomized, double-blind, placebo-controlled trial was conducted to investigate the effects of 16 weeks multivitamin supplementation (Swisse Women's 50+ Ultivite ®) on cognition in elderly women., Methods: Participants in this study were 56 community dwelling, elderly women, with subjective complaints of memory loss. Cognition was assessed using a computerized battery of memory and attention tasks designed to be sensitive to age-related declines to fluid intelligence, and a measure of verbal recall. Biochemical measures of selected nutrients, homocysteine, markers of inflammation, oxidative stress, and blood safety parameters were also collected. All cognitive and haematological parameters were assessed at baseline and 16 weeks post-treatment., Results: The multivitamin improved speed of response on a measure of spatial working memory, however benefits to other cognitive processes were not observed. Multivitamin supplementation decreased levels of homocysteine and increased levels of vitamin B(6) and B(12), with a trend for vitamin E to increase. There were no hepatotoxic effects of the multivitamin formula indicating this supplement was safe for everyday usage in the elderly., Conclusion: Sixteen weeks ssupplementation with a combined multivitamin, mineral and herbal formula may benefit working memory in elderly women at risk of cognitive decline.