A randomised, placebo-controlled, double blind, crossover trial on the effect of a 20:1 cannabidiol: Δ9-tetrahydrocannabinol medical cannabis product on neurocognition, attention, and mood.

As cannabinoid-based medications gain popularity in the treatment of refractory medical conditions, it is crucial to examine the neurocognitive effects of commonly prescribed products to ensure associated safety profiles. The present study aims to investigate the acute effects of a standard 1 mL sublingual dose of CannEpil®, a medicinal cannabis oil containing 100 mg cannabidiol (CBD) and 5 mg Δ9-tetrahydrocannabinol (THC) on neurocognition, attention, and mood. A randomised, double-blind, placebo-controlled, within-subjects design assessed 31 healthy participants (16 female, 15 male), aged between 21 and 58 years, over a two-week experimental protocol. Neurocognitive performance outcomes were assessed using the Cambridge Neuropsychological Test Automated Battery, with the Profile of Mood States questionnaire, and the Bond-Lader Visual Analogue Scale used to assess subjective state and mood. CannEpil increased Total Errors in Spatial Span and Correct Latency (median) in Pattern Recognition Memory, while also increasing Efficiency Score (lower score indicates greater efficiency) relative to placebo (all p < .05). Subjective Contentedness (p < .01) and Amicability (p < .05) were also increased at around 2.5 h post dosing, relative to placebo. Drowsiness or sedative effect was reported by 23 % of participants between three to six hours post CannEpil administration. Plasma concentrations of CBD, THC, and their metabolites were not significantly correlated with any observed alterations in neurocognition, subjective state, or adverse event occurrence. An acute dose of CannEpil impairs select aspects of visuospatial working memory and delayed pattern recognition, while largely preserving mood states among healthy individuals. Intermittent reports of drowsiness and sedation underscore the inter-individual variability of medicinal cannabis effects on subjective state. (ANZCTR; ACTRN12619000932167; https://www.anzctr.org.au).

Effect of CannEpil® on simulated driving performance and co-monitoring of ocular activity: A randomised controlled trial.

BACKGROUND: Medicinal cannabis products containing Δ9-tetrahydrocannabinol (THC) are increasingly accessible. Yet, policy guidelines regarding fitness to drive are lacking, and cannabinoid-specific indexations of impairment are underdeveloped. AIMS: To determine the impact of a standardised 1 mL sublingual dose of CannEpil®, a medicinal cannabis oil containing 100 mg cannabidiol (CBD) and 5 mg THC on simulated driving performance, relative to placebo and whether variations in vehicle control can be indexed by ocular activity. METHODS: A double-blind, within-subjects, randomised, placebo-controlled, crossover trial assessed 31 healthy fully licensed drivers (15 male, 16 female) aged between 21 and 58 years (M = 38.0, SD = 10.78). Standard deviation of lateral position (SDLP), standard deviation of speed (SDS) and steering variability were assessed over time and as a function of treatment during a 40 min simulated drive, with oculomotor parameters assessed simultaneously. Oral fluid and plasma were collected at 30 min and 2.5 h. RESULTS: CannEpil did not significantly alter SDLP across the full drive, although increased SDLP was observed between 20 and 30 min (p < 0.05). CannEpil increased SDS across the full drive (p < 0.05), with variance greatest at 20-30 min (p < 0.001). CannEpil increased fixation duration (p < 0.05), blink rate (trend p = 0.051) and decreased blink duration (p < 0.001) during driving. No significant correlations were observed between biological matrices and performance outcomes. CONCLUSIONS: CannEpil impairs select aspects of vehicle control (speed and weaving) over time. Alterations to ocular behaviour suggest that eye tracking may assist in determining cannabis-related driver impairment or intoxication. Australian and New Zealand Clinician Trials Registry, https://anzctr.org.au(ACTRN12619000932167).

Examining the Influence of the Human Gut Microbiota on Cognition and Stress: A Systematic Review of the Literature.

The gut microbiota is seen as an emerging biotechnology that can be manipulated to enhance or preserve cognition and physiological outputs of anxiety and depression in clinical conditions. However, the existence of such interactions in healthy young individuals in both non-stressful and stressful environments is unclear. The aim of this systematic review was to examine the relationship between the human gut microbiota, including modulators of the microbiota on cognition, brain function and/or stress, anxiety and depression. A total of n = 25 eligible research articles from a possible 3853 published between October 2018 and August 2021 were identified and included. Two study design methods for synthesis were identified: cross-sectional or pre/post intervention. Few cross-sectional design studies that linked microbiota to cognition, brain activity/structure or mental wellbeing endpoints existed (n = 6); however, correlations between microbiota diversity and composition and areas of the brain related to cognitive functions (memory and visual processing) were observed. Intervention studies targeting the gut microbiota to improve cognition, brain structure/function or emotional well-being (n = 19) generally resulted in improved brain activity and/or cognition (6/8), and improvements in depression and anxiety scores (5/8). Despite inherit limitations in studies reviewed, available evidence suggests that gut microbiota is linked to brain connectivity and cognitive performance and that modulation of gut microbiota could be a promising strategy for enhancing cognition and emotional well-being in stressed and non-stressed situations.

Is poor self-rated sleep quality associated with elevated systemic inflammation in healthy older adults?

OBJECTIVE: Examine subjective sleep quality and inflammation among healthy older adults participating in the Australian Research Council Longevity Intervention (ARCLI). METHODS: Data was taken from a sub-set of 232 participants aged between 60-70 years (M = 65.88 ± SD 4.08 years) who participated in the baseline assessment phase of the Australian Research Council Longevity Intervention (ARCLI) study. Subjective sleep was assessed via the Leeds Sleep Evaluation Questionnaire (LSEQ). Inflammatory markers (TNF-α, IL-1ß, IL-6, IL-10, IL-2, IFN-γ, IL-4, hs-CRP) were derived from whole blood. Correlation and multiple regression analyses were used to examine associations between each of the four sleep outcome variables and inflammatory outcomes, examined as a group and following gender stratification. RESULTS: Difficulties getting to sleep were independently associated with higher IL-2 [F(1,156) = 4.62, adjusted R2 = 0.02, p = 0.03] and IL-1ß [F(1,141) = 8.52, adjusted R2 = 0.05, p = 0.004] (whole group). Difficulties getting to sleep were associated with greater IL-1ß [males: F(1,58) = 7.36, adjusted R2 = 0.097 p = 0.009; females: F (1,81) = 4.25, R2 = 0.038, p = 0.04], and negatively associated with hs-CRP (women) [F (1,129) = 4.71, R2 = 0.028, p = 0.032]. DISCUSSION: Subjective sleep-onset difficulties are associated with systemic inflammation.

Regional Cerebrovascular Reactivity and Cognitive Performance in Healthy Aging.

Cerebrovascular reactivity (CVR) reflects the response of brain blood vessels to vasoactive stimuli, such as neural activity. The current research assessed age-related changes in regional CVR to 5% CO2 inhalation in younger (n = 30, range: 21-45 years) and older (n = 29, range: 55-75 years) adults, and the contribution of regional CVR to cognitive performance using blood-oxygen-level dependent contrast imaging (BOLD) functional magnetic resonance imaging (fMRI) at 3T field strength. CVR was measured by inducing hypercapnia using a block-design paradigm under physiological monitoring. Memory and attention were assessed with a comprehensive computerized aging battery. MRI data analysis was conducted using MATLAB® and SPM12. Memory and attention performance was positively associated with CVR in the temporal cortices. Temporal lobe CVR influenced memory performance independently of age, gender, and education level. When analyzing age groups separately, CVR in the hippocampus contributed significantly to memory score in the older group and was also related to subjective memory complaints. No associations between CVR and cognition were observed in younger adults. Vascular responsiveness in the brain has consequences for cognition in cognitively healthy people. These findings may inform other areas of research concerned with vaso-protective approaches for prevention or treatment of neurocognitive decline.

An investigation of cerebral oxygen utilization, blood flow and cognition in healthy aging.

BACKGROUND: Understanding how vascular and metabolic factors impact on cognitive function is essential to develop efficient therapies to prevent and treat cognitive losses in older age. Cerebral metabolic rate of oxygen (CMRO2), cerebral blood flow (CBF) and venous oxygenation (Yv) comprise key physiologic processes that maintain optimum functioning of neural activity. Changes to these parameters across the lifespan may precede neurodegeneration and contribute to age-related cognitive decline. This study examined differences in blood flow and metabolism between 31 healthy younger (<50 years) and 29 healthy older (>50 years) adults; and investigated whether these parameters contribute to cognitive performance. METHOD: Participants underwent a cognitive assessment and MRI scan. Grey matter CMRO2 was calculated from measures of CBF (phase contrast MRI), arterial and venous oxygenation (TRUST MRI) to assess group differences in physiological function and the contribution of these parameters to cognition. RESULTS: Performance on memory (p<0.001) and attention tasks (p<0.001) and total CBF were reduced (p<0.05), and Yv trended toward a decrease (p = .06) in the older group, while grey matter CBF and CMRO2 did not differ between the age groups. Attention was negatively associated with CBF when adjusted (p<0.05) in the older adults, but not in the younger group. There was no such relationship with memory. Neither cognitive measure was associated with oxygen metabolism or venous oxygenation in either age group. CONCLUSION: Findings indicated an age-related imbalance between oxygen delivery, consumption and demand, evidenced by a decreased supply of oxygen with unchanged metabolism resulting in increased oxygen extraction. CBF predicted attention when the age-effect was controlled, suggesting a task- specific CBF- cognition relationship.

Magnetic resonance imaging for assessment of cerebrovascular reactivity and its relationship to cognition: a systematic review.

BACKGROUND: Cerebrovascular reactivity (CVR) refers to the responsiveness of cerebral vasculature to vasoactive stimuli. CVR is an indicator of brain health and can be assessed using vasodilatory techniques and magnetic resonance imaging (MRI). Using such approaches, some researchers have explored the relationship between CVR and cognition; here we systematically review this work. RESULTS: We extracted information pertaining to: (1) study location and design, participant characteristics, sample sizes, (2) design of vascular challenge, end-tidal CO 2 (etCO 2 ) concentrations (if applicable), (3) MRI protocol, (4) cognitive assessment, (5) CVR values, and outcomes of statistical analyses with cognitive tests. Five studies assessed participants with cognitive impairment compared to controls, one studied patients with multiple sclerosis with or without cognitive impairment compared to controls, one examined patients with moyamoya disease with or without cognitive impairment, two investigated patients with Type 2 diabetes mellitus (T2DM), and one was a cross-sectional study with younger and older healthy adults. Cognition was typically probed using the MMSE and tests of executive function, while a number of vasodilatory techniques were employed. CONCLUSION: CVR was associated with cognition in six of ten studies, but heterogeneity of study samples, designs and vasodilatory methods may have a role in the inconsistent findings. We make recommendations for future research that includes use of a multi-domain cognitive assessment and standardised hypercapnic challenge with MRI.

Acute neurocognitive effects of epigallocatechin gallate (EGCG).

Green tea is reported to have wide ranging beneficial health outcomes across epidemiological studies, which have been attributed to its flavonoid content. We investigated whether the flavonoid epigallocatechin gallate (EGCG) modulates brain activity and self-reported mood in a double-blind, placebo controlled crossover study. Participants completed baseline assessments of cognitive and cardiovascular functioning, mood and a resting state electroencephalogram (EEG) before and then 120 min following administration of 300 mg EGCG or matched placebo. EGCG administration was associated with a significant overall increase in alpha, beta and theta activity, also reflected in overall EEG activity, more dominant in midline frontal and central regions, specifically in the frontal gyrus and medial frontal gyrus. In comparison to placebo the EGCG treatment also increased self-rated calmness and reduced self rated stress. This pattern of results suggests that participants in the EGCG condition may have been in a more relaxed and attentive state after consuming EGCG. This is in keeping with the widespread consumption of green tea for its purported relaxing/refreshing properties. The modulation of brain function due to EGCG is deserving of further controlled human studies.