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Acute effects of MDMA on trust, cooperative behaviour and empathy: A double-blind, placebo-controlled experiment.
Borissova, A, Ferguson, B, Wall, MB, Morgan, CJ, Carhart-Harris, RL, Bolstridge, M, Bloomfield, MA, Williams, TM, Feilding, A, Murphy, K, et al
Journal of psychopharmacology (Oxford, England). 2021;(5):547-555
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Abstract
BACKGROUND 3,4-Methylenedioxymethamphetamine (MDMA) is being actively researched as an adjunct to psychotherapy. It may be beneficial to trust, empathy and cooperative behaviour due to its acute prosocial effects. AIM: To test (a) the acute effects of MDMA on measures of empathy, trust and cooperative behaviour, and (b) subacute changes in mood three days after MDMA administration. METHODS Twenty-five participants (n=7 female), participated in this double-blind, repeated-measures, placebo-controlled experiment. Participants attended two acute sessions, one week apart. Each acute session was followed by a subacute session three days later. Participants received placebo (100 mg ascorbic acid) during one acute session, and MDMA (100 mg MDMA-HCl) at the other, with order counterbalanced. Participants completed the following tasks assessing prosocial behaviour: a trust investment task, a trustworthy face rating task, an empathic stories task, a public project game, a dictator game and an ultimatum game. Participants reported subjective effects. Blood was taken pre-drug, 2 and 4 hours post-drug, and tested for plasma MDMA levels. RESULTS MDMA acutely increased self-reported 'closeness to others' and 'euphoria' and increased plasma concentrations of MDMA. MDMA did not significantly change task-based empathy, trust or cooperative behaviour. Using Bayesian analyses, we found evidence that MDMA and placebo did not differ in their effects on empathy and cooperative behaviour. MDMA did not significantly change subacute mood and this was supported by our Bayesian analyses. CONCLUSION Despite augmentation in plasma MDMA levels and subjective drug effects, we found no increase in prosocial behaviour in a laboratory setting.
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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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Tryptophan depletion predicts lower positive affect in sexual minority men living with HIV who use methamphetamine.
Lee, JY, Glynn, TR, Moskowitz, JT, Fuchs, D, Neilands, TB, Dilworth, SE, Feaster, DJ, Rodriguez, A, Carrico, AW
Journal of neurovirology. 2021;(1):178-182
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Abstract
This longitudinal study with 76 sexual minority men living with HIV who use methamphetamine examined whether dysregulation of essential amino acid precursors for neurotransmitters at baseline predicted positive and negative affect at 15 months. After controlling for covariates including baseline positive affect, a higher baseline kynurenine/tryptophan (K/T) ratio independently predicted lower positive affect at 15 months (β = - 18.31; 95% CI = - 35.35, - 1.27; p = 0.036). Future clinical research should examine whether bio-behavioral interventions targeting tryptophan degradation could optimize treatments for people living with co-occurring HIV and stimulant use disorders.
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Cellular dehydration acutely degrades mood mainly in women: a counterbalanced, crossover trial.
Suh, H, Lieberman, HR, Jansen, LT, Colburn, AT, Adams, JD, Seal, AD, Butts, CL, Kirkland, TM, Melander, O, Vanhaecke, T, et al
The British journal of nutrition. 2021;(10):1092-1100
Abstract
It is unclear if mild-to-moderate dehydration independently affects mood without confounders like heat exposure or exercise. This study examined the acute effect of cellular dehydration on mood. Forty-nine adults (55 % female, age 39 (sd 8) years) were assigned to counterbalanced, crossover trials. Intracellular dehydration was induced with 2-h (0·1 ml/kg per min) 3 % hypertonic saline (HYPER) infusion or 0·9 % isotonic saline (ISO) as a control. Plasma osmolality increased in HYPER (pre 285 (sd 3), post 305 (sd 4) mmol/kg; P < 0·05) but remained unchanged in ISO (pre 285 (sd 3), post 288 (sd 3) mmol/kg; P > 0·05). Mood was assessed with the short version of the Profile of Mood States Questionnaire (POMS). The POMS sub-scale (confusion-bewilderment, depression-dejection, fatigue-inertia) increased in HYPER compared with ISO (P < 0·05). Total mood disturbance score (TMD) assessed by POMS increased from 10·3 (sd 0·9) to 16·6 (sd 1·7) in HYPER (P < 0·01), but not in ISO (P > 0·05). When TMD was stratified by sex, the increase in the HYPER trial was significant in females (P < 0·01) but not in males (P > 0·05). Following infusion, thirst and copeptin (surrogate for vasopressin) were also higher in females than in males (21·3 (sd 2·0), 14·1 (sd 1·4) pmol/l; P < 0·01) during HYPER. In conclusion, cellular dehydration acutely degraded specific aspects of mood mainly in women. The mechanisms underlying sex differences may be related to elevated thirst and vasopressin.
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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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Enhancing Mood, Cognition, and Quality of Life in Pediatric Multiple Sclerosis.
Fernandez-Carbonell, C, Charvet, LE, Krupp, LB
Paediatric drugs. 2021;(4):317-329
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Abstract
Pediatric-onset multiple sclerosis (POMS), representing approximately 5% of all MS cases, affects the central nervous system during its ongoing development. POMS is most commonly diagnosed during adolescence but can occur in younger children as well. For pediatric patients with MS, it is critical to manage the full impact of the disease and monitor for any effects on school and social functioning. Disease management includes not only disease-modifying therapies but also strategies to optimize wellbeing. We review the interventions with the highest evidence of ability to improve the disease course and quality of life in POMS. High levels of vitamin D and a diet low in saturated fat are associated with lower relapse rates. Exercise ameliorates fatigue and sleep. Behavioral strategies for sleep hygiene and mood regulation can also improve fatigue and perceived health. POMS management should be addressed holistically, including assessing overall symptom burden as well as the psychological and functional impact of the disease.
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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.