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Pharmacokinetics and Pharmacodynamics of Lysergic Acid Diethylamide Microdoses in Healthy Participants.
Holze, F, Liechti, ME, Hutten, NRPW, Mason, NL, Dolder, PC, Theunissen, EL, Duthaler, U, Feilding, A, Ramaekers, JG, Kuypers, KPC
Clinical pharmacology and therapeutics. 2021;(3):658-666
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Abstract
"Microdoses" of lysergic acid diethylamide (LSD) are used recreationally to enhance mood and cognition. Increasing interest has also been seen in developing LSD into a medication. Therefore, we performed a pharmacokinetic-pharmacodynamic study using very low doses of LSD. Single doses of LSD base (5, 10, and 20 µg) and placebo were administered in a double-blind, randomized, placebo-controlled crossover study in 23 healthy participants. Test days were separated by at least 5 days. Plasma levels of LSD and subjective effects were assessed up to 6 hours after administration. Pharmacokinetic parameters were determined using compartmental modeling. Concentration-subjective effect relationships were described using pharmacokinetic-pharmacodynamic modeling. Mean (95% confidence interval) maximal LSD concentrations were 151 pg/mL (127-181), 279 pg/mL (243-320), and 500 pg/mL (413-607) after 5, 10, and 20 µg LSD administration, respectively. Maximal concentrations were reached after 1.1 hours. The mean elimination half-life was 2.7 hours (1.5-6.2). The 5 µg dose of LSD elicited no significant acute subjective effects. The 10 µg dose of LSD significantly increased ratings of "under the influence" and "good drug effect" compared with placebo. These effects began an average of 1.1 hours after 10 µg LSD administration, peaked at 2.5 hours, and ended at 5.1 hours. The 20 µg dose of LSD significantly increased ratings of "under the influence," "good drug effects," and "bad drug effects." LSD concentrations dose-proportionally increased at doses as low as 5-20 µg and decreased with a half-life of 3 hours. The threshold dose of LSD base for psychotropic effects was 10 µg.
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Effects of Water Restriction and Supplementation on Cognitive Performances and Mood among Young Adults in Baoding, China: A Randomized Controlled Trial (RCT).
Zhang, J, Ma, G, Du, S, Liu, S, Zhang, N
Nutrients. 2021;(10)
Abstract
The brain is approximately 75% water. Therefore, insufficient water intake may affect the cognitive performance of humans. The present study aimed to investigate the effects of water restriction and supplementation on cognitive performances and mood, and the optimum amount of water to alleviate the detrimental effects of dehydration, among young adults. A randomized controlled trial was conducted with 76 young, healthy adults aged 18-23 years old from Baoding, China. After fasting overnight for 12 h, at 8:00 a.m. of day 2, the osmolality of the first morning urine and blood, cognitive performance, and mood were measured as a baseline test. After water restriction for 24 h, at 8:00 a.m. of day 3, the same indexes were measured as a dehydration test. Participants were randomly assigned into four groups: water supplementation group (WS group) 1, 2, or 3 (given 1000, 500, or 200 mL purified water), and the no water supplementation group (NW group). Furthermore, participants were instructed to drink all the water within 10 min. Ninety minutes later, the same measurements were performed as a rehydration test. Compared with the baseline test, participants were all in dehydration and their scores on the portrait memory test, vigor, and self-esteem decreased (34 vs. 27, p < 0.001; 11.8 vs. 9.2, p < 0.001; 7.8 vs. 6.4, p < 0.001). Fatigue and TMD (total mood disturbance) increased (3.6 vs. 4.8, p = 0.004; 95.7 vs. 101.8, p < 0.001) in the dehydration test. Significant interactions between time and volume were found in hydration status, fatigue, vigor, TMD, symbol search test, and operation span test (F = 6.302, p = 0.001; F = 3.118, p = 0.029; F = 2.849, p = 0.043; F = 2.859, p = 0.043; F = 3.463, p = 0.021) when comparing the rehydration and dehydration test. Furthermore, the hydration status was better in WS group 1 compared to WS group 2; the fatigue and TMD scores decreased, and the symbol search test and operation span test scores increased, only in WS group 1 and WS group 2 (p < 0.05). There was no significant difference between them (p > 0.05). Dehydration impaired episodic memory and mood. Water supplementation improved processing speed, working memory, and mood, and 1000 mL was the optimum volume.
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Mental Health in New Mothers: A Randomised Controlled Study into the Effects of Dietary Flavonoids on Mood and Perceived Quality of Life.
Barfoot, KL, Forster, R, Lamport, DJ
Nutrients. 2021;(7)
Abstract
The postnatal period is a significant period of physical, physiological and psychological change for mothers, rendering them particularly vulnerable to changes in mood or disorders such as postnatal depression (PND). Previous interventions with foods high in flavonoids have demonstrated beneficial acute and chronic mood effects in healthy child, adolescent and adult populations. It is unclear whether mood effects persist in populations who are potentially at-risk of developing mood disorders, such as postnatal mothers. This exploratory study investigated the effects of a 2-week daily dietary flavonoid intervention on mood (PANAS-NOW), anxiety (STAI), depressive symptoms (PHQ-8) and perceived quality of life (WHOQOL-BREF) in forty-one new mothers in the 0-12-month postnatal period, before and after flavonoid intervention. Mothers either added high flavonoid foods to their daily diet, or did not include additions following a randomised, between-groups, controlled design. Significant effects were observed in the flavonoid group with mothers reporting lower state anxiety and higher perceived quality of physical health at the 2-week timepoint. These findings suggest that regular dietary consumption of flavonoids may benefit mothers' anxiety and perceived quality of life in the postnatal period. Replication of these results may indicate the potential for dietary flavonoids to promote healthy mood regulation in mothers or prevent the onset or severity of symptoms in postnatal psychological disorders, both of which would be beneficial for women's health services and public mental health.
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Effects of High-Dose, Short-Duration β-Alanine Supplementation on Cognitive Function, Mood, and Circulating Brain-Derived Neurotropic Factor (BDNF) in Recreationally-Active Males Before Simulated Military Operational Stress.
Varanoske, AN, Wells, AJ, Boffey, D, Harat, I, Frosti, CL, Kozlowski, GJ, Gepner, Y, Hoffman, JR
Journal of dietary supplements. 2021;(2):147-168
Abstract
Introduction: β-alanine (BA) supplementation may improve cognition and mitigate symptoms of anxiety and depression associated with aging, neurological disorders, and physical exertion, which has been attributed to increases in brain carnosine and/or brain-derived neurotropic factor (BDNF). BA also provides beneficial effects on cognition, mood, and physical performance during military operations; however, whether BA can attenuate mood disruptions and cognitive dysfunction associated with the anticipatory stress prior to simulated military operations is unknown.Purpose: The present study examined the effects of 14 days of BA (12 g·day-1) supplementation on cognitive function, mood, and circulating BDNF concentrations in recreationally-active, healthy males with limited inflammation and oxidative stress prior to a 24h simulated military operation.Methods: Participants were randomized into BA (n = 10) or placebo (n = 9; PL) for 14 days. Cognitive function, mood, and circulating BDNF were assessed before (PRE) and after (POST) supplementation. Cognition was assessed via multiple object tracking (Neurotracker™), visuomotor reaction time (Dynavision™), mathematical processing (Serial Subtraction Test), and neuropsychological assessments (ANAM™). Mood was assessed using the Profile of Mood States (POMS) questionnaire. After POST testing, subjects underwent a 24h simulated military operation.Results: No change in measures of cognitive function or BDNF concentrations were observed (p > 0.05). However, BA experienced significant reductions (p = 0.046) in subjective feelings of depression, while PL experienced significant reductions (p = 0.021) in feelings of vigor from PRE to POST.Conclusions: High-dose, short-duration BA supplementation does not appear to affect cognitive function or circulating BDNF, but may mitigate the onset of negative mood states in healthy, recreationally-active males prior to a simulated military operation.
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The effects of six months Persicaria minor extract supplement among older adults with mild cognitive impairment: a double-blinded, randomized, and placebo-controlled trial.
Lau, H, Shahar, S, Mohamad, M, Rajab, NF, Yahya, HM, Din, NC, Hamid, HA
BMC complementary medicine and therapies. 2020;(1):315
Abstract
BACKGROUND Persicaria minor extract exhibits antioxidant and anti-inflammatory properties and has potential effects on cognitive function and mood. However, the effects of P.minor on brain activation and biomarkers have not been studied among older adults. This multicentre, randomized, double-blinded, placebo-controlled study aimed to investigate the effect of 6 months P.minor extract supplement (Biokesum®) on cognition, mood, biomarkers, and brain activation among older adults with Mild Cognitive Impairment (MCI). METHOD A total of 36 Malaysian community-dwelling older adults with MCI (60-75-year-old) were randomized into Biokesum® (n = 18) and placebo group (n = 18). Each subject consumed one capsule of Biokesum® (250 mg/capsule) or placebo (maltodextrin, 280 mg/capsule) twice daily for 6 months. Cognitive function and mood were assessed at baseline, 3rd, and 6th-month using neuropsychological tests (MMSE, Digit Span, RAVLT, Digit Symbol, and Visual Reproduction) and Profile of Mood State (POMS) questionnaire. Blood lipid profile, fasting blood glucose, and biomarkers (MDA, LPO, COX-2, iNOS, and BDNF) were measured at baseline and 6th month. By the end of the intervention, there were 30 compliers (Biokesum®: N = 15; Placebo: N = 15) and 6 dropouts. For brain activation assessment, 15 subsamples (Biokesum®: N = 8; Placebo: N = 7) completed N-back and Stroop tasks during fMRI scanning at baseline and 6th month. The dorsolateral prefrontal cortex (Brodmann's area 9 and 46) was identified as a region of interest (ROI) for brain activation analysis using SPM software. RESULTS Two-way mixed ANOVA analysis showed significant improvements in Visual Reproduction II (p = 0.012, partial η2 = 0.470), tension (p = 0.042, partial η2 = 0.147), anger (p = 0.010, partial η2 = 0.207), confusion (p = 0.041, partial η2 = 0.148), total negative subscales (p = 0.043, partial η2 = 0.145), BDNF (p = 0.020, partial η2 = 0.179) and triglyceride (p = 0.029, partial η2 = 0.237) following 6 months of Biokesum® supplementation. Preliminary finding also demonstrated significant improvement at 0-back task-induced right DLPFC activation (p = 0.028, partial η2 = 0.652) among subsamples in Biokesum® group. No adverse events were reported at the end of the study. CONCLUSION Six months Biokesum® supplementation potentially improved visual memory, negative mood, BDNF, and triglyceride levels among older adults with MCI. Significant findings on brain activation at the right DPLFC must be considered as preliminary. TRIAL REGISTRATION Retrospectively registered on 30th August 2019 [ ISRC TN12417552 ].
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Acute and Chronic Effects of Green Oat (Avena sativa) Extract on Cognitive Function and Mood during a Laboratory Stressor in Healthy Adults: A Randomised, Double-Blind, Placebo-Controlled Study in Healthy Humans.
Kennedy, DO, Bonnländer, B, Lang, SC, Pischel, I, Forster, J, Khan, J, Jackson, PA, Wightman, EL
Nutrients. 2020;(6)
Abstract
Green oat (Avena sativa) extracts contain several groups of potentially psychoactive phytochemicals. Previous research has demonstrated improvements in cognitive function following a single dose of these extracts, but not following chronic supplementation. Additionally, whilst green oat extracts contain phytochemicals that may improve mood or protect against stress, for instance species-specific triterpene saponins, to date this possibility has not been examined. The current study investigated the effects of a single dose and four weeks of administration of a novel, Avena sativa herbal extract (cognitaven®) on cognitive function and mood, and changes in psychological state during a laboratory stressor. The study adopted a dose-ranging, double-blind, randomised, parallel groups design in which 132 healthy males and females (35 to 65 years) received either 430 mg, 860 mg, 1290 mg green oat extract or placebo for 29 days. Assessments of cognitive function, mood and changes in psychological state during a laboratory stressor (Observed Multitasking Stressor) were undertaken pre-dose and at 2 h and 4 h post-dose on the first (Day 1) and last days (Day 29) of supplementation. The results showed that both a single dose of 1290 mg and, to a greater extent, supplementation for four weeks with both 430 mg and 1290 mg green oat extract resulted in significantly improved performance on a computerised version of the Corsi Blocks working memory task and a multitasking task (verbal serial subtractions and computerised tracking) in comparison to placebo. After four weeks, the highest dose also decreased the physiological response to the stressor in terms of electrodermal activity. There were no treatment-related effects on mood. These results confirm the acute cognitive effects of Avena sativa extracts and are the first to demonstrate that chronic supplementation can benefit cognitive function and modulate the physiological response to a stressor.
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The Effect of Long-Term Aronia melanocarpa Extract Supplementation on Cognitive Performance, Mood, and Vascular Function: A Randomized Controlled Trial in Healthy, Middle-Aged Individuals.
Ahles, S, Stevens, YR, Joris, PJ, Vauzour, D, Adam, J, de Groot, E, Plat, J
Nutrients. 2020;(8)
Abstract
Cognitive decline is associated with lifestyle-related factors such as overweight, blood pressure, and dietary composition. Studies have reported beneficial effects of dietary anthocyanins on cognition in older adults and children. However, the effect of anthocyanin-rich Aronia melanocarpa extract (AME) on cognition is unknown. Therefore, this study aimed to determine the effect of long-term supplementation with AME on cognitive performance, mood, and vascular function in healthy, middle-aged, overweight adults. In a randomized double-blind placebo-controlled parallel study, 101 participants either consumed 90 mg AME, 150 mg AME, or placebo for 24 weeks. The grooved pegboard test, number cross-out test, and Stroop test were performed as measures for psychomotor speed, attention, and cognitive flexibility. Mood was evaluated with a visual analogue scale, serum brain-derived neurotrophic factor (BDNF) was determined, and vascular function was assessed by carotid ultrasounds and blood pressure measurements. AME improved psychomotor speed compared to placebo (90 mg AME: change = -3.37; p = 0.009). Furthermore, 150 mg AME decreased brachial diastolic blood pressure compared to 90 mg AME (change = 2.44; p = 0.011), but not compared to placebo. Attention, cognitive flexibility, BDNF, and other vascular parameters were not affected. In conclusion, AME supplementation showed an indication of beneficial effects on cognitive performance and blood pressure in individuals at risk of cognitive decline.
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Mindfulness Versus Distraction to Improve Affective Response and Promote Cardiovascular Exercise Behavior.
Gillman, AS, Bryan, AD
Annals of behavioral medicine : a publication of the Society of Behavioral Medicine. 2020;(6):423-435
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Abstract
BACKGROUND Variation in affective response to exercise partially explains high levels of inactivity. Examining ways to improve affective responses to physical activity is, therefore, an important direction for research aiming to promote exercise behavior. PURPOSE This study compares three strategies: mindfulness, distraction, and an associative focus comparison group as potential strategies to improve affective response to exercise and promote exercise behavior. METHODS Seventy-eight insufficiently active individuals (M age 26.82, 74% female) were randomly assigned to one of the following three conditions: (a) mindfulness, (b) distraction, or (c) associative attentional focus. The study was divided into two phases, a laboratory session in which participants learned their assigned strategy and completed a 30 min supervised exercise bout and an at-home intervention in which participants used their assigned strategy while exercising on their own for 2 weeks and filled out daily surveys. RESULTS Seventy-five participants completed the study. The central hypotheses were partially supported. Participants in the mindfulness and distraction conditions maintained more positive affective response to exercise over time compared to participants in the associative focus condition, whose affect became less positive over time (p = .04). Participants in the distraction condition experienced lower perceived exertion during exercise (p = .01). There were no condition differences in self-reported minutes exercised during follow-up, but participants in the mindfulness condition reported exercising for more days during the follow-up compared to the associative focus condition (p = .01). CONCLUSIONS These findings suggest individuals wishing to increase their cardiovascular exercise could engage in mindfulness or distraction in order to make exercise feel less difficult and/or more affectively pleasant.
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Further Evidence of Benefits to Mood and Working Memory from Lipidated Curcumin in Healthy Older People: A 12-Week, Double-Blind, Placebo-Controlled, Partial Replication Study.
Cox, KHM, White, DJ, Pipingas, A, Poorun, K, Scholey, A
Nutrients. 2020;(6)
Abstract
Curcumin (a flavonoid isolated from turmeric) affects several processes involved in neurocognitive aging. We have previously reported that short term (4-weeks) administration of a highly bioavailable curcumin preparation (Longvida©) improved working memory and reduced fatigue and stress reactivity in a healthy older cohort. The present trial (ACTRN12616000484448) was a partial replication study, evaluating similar effects at 4 and 12-weeks Longvida© supplementation. A double-blind, placebo-controlled, parallel-groups trial was conducted. Eighty participants aged 50-80 years (mean = 68.1, SD = 6.34) were randomised to receive Longvida© (400 mg daily containing 80 mg curcumin) or a matching placebo. Assessment took place at baseline then following 4 and 12 weeks treatment. Outcome measures included cognitive performance, mood and biomarkers. Compared with placebo, curcumin was associated with several significant effects. These included better working memory performance at 12-weeks (Serial Threes, Serial Sevens and performance on a virtual Morris Water Maze), and lower fatigue scores on the Profile of Mood States (POMS) at both 4 and 12-weeks, and of tension, anger, confusion and total mood disturbance at 4-weeks only. The curcumin group had significantly elevated blood glucose. These results confirm that Longvida© improves aspects of mood and working memory in a healthy older cohort. The pattern of results is consistent with improvements in hippocampal function and may hold promise for alleviating cognitive decline in some populations.
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Physiological responses to maximal eating in men.
Hengist, A, Edinburgh, RM, Davies, RG, Walhin, JP, Buniam, J, James, LJ, Rogers, PJ, Gonzalez, JT, Betts, JA
The British journal of nutrition. 2020;(4):407-417
Abstract
This study investigated metabolic, endocrine, appetite and mood responses to a maximal eating occasion in fourteen men (mean: age 28 (sd 5) years, body mass 77·2 (sd 6·6) kg and BMI 24·2 (sd 2·2) kg/m2) who completed two trials in a randomised crossover design. On each occasion, participants ate a homogenous mixed-macronutrient meal (pizza). On one occasion, they ate until 'comfortably full' (ad libitum) and on the other, until they 'could not eat another bite' (maximal). Mean energy intake was double in the maximal (13 024 (95 % CI 10 964, 15 084) kJ; 3113 (95 % CI 2620, 3605) kcal) compared with the ad libitum trial (6627 (95 % CI 5708, 7547) kJ; 1584 (95 % CI 1364, 1804) kcal). Serum insulin incremental AUC (iAUC) increased approximately 1·5-fold in the maximal compared with ad libitum trial (mean: ad libitum 43·8 (95 % CI 28·3, 59·3) nmol/l × 240 min and maximal 67·7 (95 % CI 47·0, 88·5) nmol/l × 240 min, P < 0·01), but glucose iAUC did not differ between trials (ad libitum 94·3 (95 % CI 30·3, 158·2) mmol/l × 240 min and maximal 126·5 (95 % CI 76·9, 176·0) mmol/l × 240 min, P = 0·19). TAG iAUC was approximately 1·5-fold greater in the maximal v. ad libitum trial (ad libitum 98·6 (95 % CI 69·9, 127·2) mmol/l × 240 min and maximal 146·4 (95 % CI 88·6, 204·1) mmol/l × 240 min, P < 0·01). Total glucagon-like peptide-1, glucose-dependent insulinotropic peptide and peptide tyrosine-tyrosine iAUC were greater in the maximal compared with ad libitum trial (P < 0·05). Total ghrelin concentrations decreased to a similar extent, but AUC was slightly lower in the maximal v. ad libitum trial (P = 0·02). There were marked differences on appetite and mood between trials, most notably maximal eating caused a prolonged increase in lethargy. Healthy men have the capacity to eat twice the energy content required to achieve comfortable fullness at a single meal. Postprandial glycaemia is well regulated following initial overeating, with elevated postprandial insulinaemia probably contributing.