Lifestyle and mood correlates of cardiometabolic risk in people with serious mental illness on second-generation antipsychotic medications.

INTRODUCTION: Cardiovascular morbidity and mortality are high in people with serious mental illness (SMI). This problem is mediated, at least in part, by metabolic side effects of second-generation antipsychotics (SGAs) and by unhealthy lifestyle behaviors. We asked whether oral glucose tolerance testing (oGTT) or hemoglobin A1c (HbA1c) is superior in identifying people with SMI at high cardiometabolic risk and whether this risk is shaped by mood, cognition, or lifestyle habits. METHODS: We evaluated 40 patients with schizophrenia, schizoaffective, or bipolar disorder receiving SGAs by oGTT, HbA1c, comprehensive metabolic and lipid panels, and CRP. Mood was assessed using the Patient Health Questionnaire (PHQ-9), and cognition was assessed using the Saint Louis University Mental Status examination. Diet was assessed using the UK Diabetes and Diet Questionnaire (UKDDQ), and physical activity was assessed using daily step counts. RESULTS: Most patients had prediabetes (preDM) or diabetes mellitus (DM), 72.5% by oGTT, and 52.5% by HbA1c criteria. Pulse rates and insulin resistance indices (Homeostatic Model Assessment of Insulin Resistance, HOMA IR; Matsuda) were significantly different between patients classified as normal or with preDM/DM, using either oGTT or HbA1c criteria. Patients with preDM/DM by HbA1c but not oGTT criteria also had higher waist/hip ratios, triglyceride, and CRP levels (p<0.05). A strong negative correlation was found between average daily step counts and CRP levels (rho = -0.62, p<0.001). Higher UKDDQ scores, or unhealthier diet habits, were associated with higher fasting plasma glucose (rho = 0.28, p = 0.08), triglyceride levels (rho = 0.31, p = 0.05), and insulin resistance (HOMA IR: rho = 0.31, p = 0.06). Higher PHQ-9 scores correlated with lower 2h-oGTT glucose levels (rho = -0.37, p<0.05). CONCLUSIONS: OGTT screening is superior to HbA1c screening in detecting preDM and DM early. Patients identified with preDM/DM by oGTT or HbA1c screening are insulin-resistant and have higher pulse rates. Abdominal obesity, unfavorable lipid profiles, and higher CRP levels were noted in patients screened by HbA1c, but not by oGTT. Low physical activity, low depression scores, and unhealthy diet habits were associated with higher CRP and higher glucose and triglyceride levels, respectively. Future studies should assess the impact of specifically tailored individual lifestyle counseling and medical management interventions in this high-risk population.

Acute effects of cannabigerol on anxiety, stress, and mood: a double-blind, placebo-controlled, crossover, field trial.

Cannabigerol (CBG) is a phytocannabinoid increasing in popularity, with preclinical research indicating it has anxiolytic and antidepressant effects. However, there are no published clinical trials to corroborate these findings in humans. The primary objective of this study was to examine acute effects of CBG on anxiety, stress, and mood. Secondary objectives were to examine whether CBG produces subjective drug effects or motor and cognitive impairments. A double-blind, placebo-controlled cross-over field trial was conducted with 34 healthy adult participants. Participants completed two sessions (with a one-week washout period) via Zoom. In each, they provided ratings of anxiety, stress, mood, and subjective drug effects prior to double-blind administration of 20 mg hemp-derived CBG or placebo tincture (T0). These ratings were collected again after participants ingested the product and completed an online survey (T1), the Trier Social Stress Test (T2), a verbal memory test and the DRUID impairment app (T3). Relative to placebo, there was a significant main effect of CBG on overall reductions in anxiety as well as reductions in stress at T1. CBG also enhanced verbal memory relative to placebo. There was no evidence of subjective drug effects or impairment. CBG may represent a novel option to reduce stress and anxiety in healthy adults.

Effects of open-label transdermal nicotine antidepressant augmentation on affective symptoms and executive function in late-life depression.

BACKGROUND: Late-life depression (LLD) is characterized by a poor response to antidepressant medications and diminished cognitive performance, particularly in executive functioning. There is currently no accepted pharmacotherapy for LLD that effectively treats both mood and cognitive symptoms. This study investigated whether transdermal nicotine augmentation of standard antidepressant medications benefitted mood and cognitive symptoms in LLD. METHODS: Nonsmoking participants aged 60 years or older with unremitted LLD on stable SSRI or SNRI medications (N = 29) received transdermal nicotine patches up to a 21 mg daily dose over 12 weeks. Clinical measures assessed depression severity, secondary affective symptoms, and cognitive performance. Nicotine metabolite concentrations were obtained from blood samples. RESULTS: Depression severity significantly decreased over the trial, with a 76 % response rate and 59 % remission rate. Change in depression severity was positively associated with nicotine exposure. Participants also exhibited improvement in self-reported affective symptoms (apathy, insomnia, rumination, and generalized anxiety symptoms), negativity bias, and disability. Executive function test performance significantly improved, specifically in measures of cognitive control, as did subjective cognitive performance. Adverse events were generally mild, with 75 % of the sample tolerating the maximum dose. CONCLUSION: The current study extends our previous pilot open-label trial in LLD, supporting feasibility and tolerability of transdermal nicotine patches as antidepressant augmentation. Although preliminary, this open-label study supports the potential benefit of transdermal nicotine patches for both mood and cognitive symptoms of LLD. Further research, including definitive randomized, blinded trials, is warranted to confirm these findings and explore long-term risk and benefit. TRIAL REGISTRATION: The study was registered with clinicaltrials.gov (NCT04433767).

Placebo treatment affects brain systems related to affective and cognitive processes, but not nociceptive pain.

Drug treatments for pain often do not outperform placebo, and a better understanding of placebo mechanisms is needed to improve treatment development and clinical practice. In a large-scale fMRI study (N = 392) with pre-registered analyses, we tested whether placebo analgesic treatment modulates nociceptive processes, and whether its effects generalize from conditioned to unconditioned pain modalities. Placebo treatment caused robust analgesia in conditioned thermal pain that generalized to unconditioned mechanical pain. However, placebo did not decrease pain-related fMRI activity in brain measures linked to nociceptive pain, including the Neurologic Pain Signature (NPS) and spinothalamic pathway regions, with strong support for null effects in Bayes Factor analyses. In addition, surprisingly, placebo increased activity in some spinothalamic regions for unconditioned mechanical pain. In contrast, placebo reduced activity in a neuromarker associated with higher-level contributions to pain, the Stimulus Intensity Independent Pain Signature (SIIPS), and affected activity in brain regions related to motivation and value, in both pain modalities. Individual differences in behavioral analgesia were correlated with neural changes in both modalities. Our results indicate that cognitive and affective processes primarily drive placebo analgesia, and show the potential of neuromarkers for separating treatment influences on nociception from influences on evaluative processes.

Engaging Mood Brain Circuits with Psilocybin (EMBRACE): a study protocol for a randomized, placebo-controlled and delayed-start, neuroimaging trial in depression.

BACKGROUND: Major depressive disorder (MDD) is a leading cause of disability worldwide across domains of health and cognition, affecting overall quality of life. Approximately one third of individuals with depression do not fully respond to treatments (e.g., conventional antidepressants, psychotherapy) and alternative strategies are needed. Recent early phase trials suggest psilocybin may be a safe and efficacious intervention with rapid-acting antidepressant properties. Psilocybin is thought to exert therapeutic benefits by altering brain network connectivity and inducing neuroplastic changes that endure for weeks post-treatment. Although early clinical results are encouraging, psilocybin's acute neurobiological effects on neuroplasticity have not been fully investigated. We aim to examine for the first time how psilocybin acutely (intraday) and subacutely (weeks) alters functional brain networks implicated in depression. METHODS: Fifty participants diagnosed with MDD or persistent depressive disorder (PDD) will be recruited from a tertiary mood disorders clinic and undergo 1:1 randomization into either an experimental or control arm. Participants will be given either 25 mg psilocybin or 25 mg microcrystalline cellulose (MCC) placebo for the first treatment. Three weeks later, those in the control arm will transition to receiving 25 mg psilocybin. We will investigate whether treatments are associated with changes in arterial spin labelling and blood oxygenation level-dependent contrast neuroimaging assessments at acute and subacute timepoints. Primary outcomes include testing whether psilocybin demonstrates acute changes in (1) cerebral blood flow and (2) functional brain activity in networks associated with mood regulation and depression when compared to placebo, along with changes in MADRS score over time compared to placebo. Secondary outcomes include changes across complementary clinical psychiatric, cognitive, and functional scales from baseline to final follow-up. Serum peripheral neurotrophic and inflammatory biomarkers will be collected at baseline and follow-up to examine relationships with clinical response, and neuroimaging measures. DISCUSSION: This study will investigate the acute and additive subacute neuroplastic effects of psilocybin on brain networks affected by depression using advanced serial neuroimaging methods. Results will improve our understanding of psilocybin's antidepressant mechanisms versus placebo response and whether biological measures of brain function can provide early predictors of treatment response. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06072898. Registered on 6 October 2023.

Characterizing reward and relief/habit drinking profiles in a study of naltrexone, varenicline, and placebo.

INTRODUCTION: This study aims to clarify differences in mood, craving, and treatment response between reward and relief/habit individuals in a study of naltrexone, varenicline, and placebo. We hypothesized that relief/habit individuals would have a poorer mood during early abstinence and higher levels of alcohol craving than reward individuals. We hypothesized that reward individuals would demonstrate better drinking outcomes on naltrexone versus placebo. METHODS: Data were culled from a randomized, double-blind, placebo-controlled human trial of 53 individuals (18F/16M) with alcohol use disorder randomized to varenicline (n = 19), naltrexone (n = 15), or matched placebo (n = 19). In this 6-day practice quit trial, participants attempted to abstain from drinking and completed daily diaries. Participants were classified into reward or relief/habit subgroups based on self-reported motivation for drinking. Multilinear models tested differences in mood and alcohol craving between reward and relief/habit individuals. General linear models tested differences between reward and relief/habit individuals' drinking outcomes on each medication versus placebo. RESULTS: Relief/habit individuals showed decreases in positive mood and increases in negative mood over the quit attempt across medications, compared to reward individuals (P's < .05). Reward individuals' tension decreased on naltrexone, while relief/habit individuals' tension remained stable (F = 3.64, P = .03). Reward individuals in the placebo group had higher percent days abstinent than relief individuals in the placebo group (P < .001). DISCUSSION: This study suggests relief/habit individuals' mood worsens during early abstinence. Our finding that reward individuals' tension decreased on naltrexone and increased on placebo may suggest a clinical response to the medication.

Acute, dose-response effects of guayusa leaf extract on mood, cognitive and motor-cognitive performance, and blood pressure, heart rate, and ventricular repolarization.

PURPOSE: We conducted a randomized, double-blind, placebo-controlled crossover trial in young adults to examine the dose-dependent (600 mg versus 1200 mg), acute effects of consumption of an Ilex guayusa tea extract (GLE) on mood, cognitive and motor-cognitive performance, as well as its acute cardiovascular effects. METHODS: Twenty-five adults (mean ± SD, age = 28 ± 7 y; 9 M/16 F) completed familiarization and then three randomly ordered experimental visits where they consumed either 600 mg (GLE600) or 1200 mg (GLE1200) GLE or placebo (PLA). Following supplement consumption, participants completed a mood state survey, assessments of perceived jitteriness, energy, and focus, and neurocognitive and motor-cognitive testing. Blood pressure (BP), heart rate, and QT interval length were determined before and after supplementation. RESULTS: GLE600 significantly improved total mood disturbance (mean ± SE difference = -6.9 ± 2.6 au, p = 0.034), fatigue-inertia (-2.84 ± 0.89 au, p = 0.008), perceived energy (+13.00 ± 4.49 au; p = 0.02), motor speed (+4.52 ± 1.42 au, p = 0.008), and psychomotor speed (+7.20 ± 2.16 au, p = 0.005) relative to PLA. GLE1200 also improved psychomotor speed (+5.08 ± 2.16 ms, p = 0.045) and uniquely increased motor-cognitive performance as reflected by a decrease in reaction time (-0.106 ± 0.04 ms, p = 0.026) during a neurocognitive hop test. The effect of GLE on jitteriness was both dose- and sex-dependent. Jitteriness increased with increasing GLE dose in women only (p < 0.001). Both GLE600 and GLE1200 similarly increased systolic and diastolic BP by 4-5 mmHg (p ≤ 0.022). Neither GLE600 nor GLE1200 acutely influenced QTc length (p = 0.31). CONCLUSIONS: The goal of GLE supplementation should be considered when selecting a dosing strategy. Lower dosages of GLE (e.g. 600 mg) appear to optimize cognitive and mood-related outcomes while limiting side-effects such as jitteriness in women, and higher dosages may be necessary (e.g. 1200 mg) to promote improvements in motor-cognitive performance.

Kavalactones support motivation to move during intensive training in males preparing for military special operations forces.

BACKGROUND: Military special operators, elite athletes, and others requiring uninterrupted optimal performance currently lack options for sleep and mood support without performance-inhibiting effects. Kavalactones, derived from the root of the kava plant (Piper methysticum Forst), have been shown to elevate mood and wellbeing by producing a feeling of relaxation without addiction or cognitive impairment. METHODS: In this placebo-controlled, crossover study (NCT05381025), we investigated the effects of 2 weeks of kavalactones use on cortisol (diurnal salivary), sleep (RSQ-W; Restorative Sleep Questionnaire, Weekly), mood (DASS-21; Depression Anxiety Stress Scale-21), and motivation state to expend (Move) or conserve (Rest) energy (CRAVE; Cravings for Rest and Volitional Energy Expenditure, Right Now) in a cohort of 15 healthy, physically fit young males engaged in a rigorous, two-a-day preparation class for special operations forces qualification. RESULTS: Cortisol, sleep, and mood were within normal, healthy parameters in this cohort at baseline. This remained unchanged with kavalactones use with no significant findings of clinical interest. However, a statistically similar, positive slope for within-group Move scores was seen in both groups during kavalactones loading (first group Move slope 2.25, second group Move slope 3.29, p = 0.299). This trend was seen regardless of order and with no apparent effects on the Rest metric (all p ≥ 0.05). Moreover, a significant between-group difference appeared after 1 week of kavalactones use in the first phase (p = 0.044) and persisted through the end of the first loading period (p = 0.022). Following the 10-day washout, this between-groups divergence remained significant (p = 0.038) but was reversed by 1 week after the crossover (p = 0.072), with Move scores once again statistically similar between groups and compared to baseline at study end. Furthermore, the group taking kavalactones first never experienced a significant decrease in Move motivation state (lowest mean score 21.0, highest 28.6, all p ≥ 0.05), while the group receiving kavalactones in the last 2 weeks of the study had Move scores that were statistically lower than baseline (lowest mean score 8.6, highest 25.9, all p ≤ 0.05) at all time points but the last (p = 0.063) after 2 weeks of kavalactones exposure. CONCLUSIONS: We report a novel finding that kavalactones may support performance by maintaining or rescuing the desire to expend energy in the context of significant physical and mental strain in well-conditioned individuals, even in a context of already normal cortisol, sleep, and mood.

Combined Effect of Red Wine and Mocha Pot Coffee in Mild Vascular Cognitive Impairment.

OBJECTIVES: Moderate daily mocha pot coffee intake has been associated with better mood and cognition in patients with mild vascular cognitive impairment (VCI). Similarly, moderate red wine consumption has shown protective effects on cognitive disorders, including Alzheimer's disease and vascular dementia. The aim of this study was to explore the synergistic relation between red wine and coffee intake on mood and cognitive status in mild VCI patients at risk for dementia. METHODS: A total of 300 non-demented older patients with mild VCI were asked for coffee and red wine consumption and administered with the 17-items Hamilton Depression Rating Scale (HDRS), the Mini Mental State Examination (MMSE), and the Stroop Color-Word Interference Test (Stroop T), as well as the Activities of Daily Living (ADL) and the Instrumental ADL to measure their mood status, cognitive performance, and functional independence. Linear regression models were used to test the association between variables. RESULTS: Moderate wine drinkers tended to show the best Stroop T score at any level of coffee consumption; conversely, heavy wine consumers performed worse at the Stroop T, especially in patients reporting high coffee intake. Moderate drinkers of both coffee and wine showed the lowest HDRS scores. Finally, a progressive increase in MMSE score was evident with increasing coffee consumption, which peaks when combined with a moderate wine consumption. CONCLUSIONS: Daily mocha pot coffee and red wine intake seem to be synergistically associated with global cognition, executive functioning, and mood status in patients with mild VCI; the association was not linear, resulting in a protective direction for moderate intake and detrimental for heavy consumption. Future studies are needed to further corroborate the present findings and the potential long-term protective effects of these dietary compounds over time.

The Affective Bias Test and Reward Learning Assay: Neuropsychological Models for Depression Research and Investigating Antidepressant Treatments in Rodents.

The Affective Bias Test (ABT) quantifies acute changes in affective state based on the affective biases they generate in an associative reward learning task. The Reward Learning Assay (RLA) provides a control assay for the ABT and reward-induced biases generated in this model are sensitive to changes in core affective state. Both tasks involve training animals to associate a specific digging substrate with a food reward. Animals learn to discriminate between two digging substrates placed in ceramic bowls, one rewarded and one unrewarded. In the ABT, the animal learns two independent substrate-reward associations with a fixed reward value following either an affective state or drug manipulation, or under control conditions. Affective biases generated are quantified in a choice test where the animals exhibit a bias (make more choices) for one of the substrates which is specifically related to affective state at the time of learning. The ABT is used to investigate biases generated during learning as well as modulation of biases associated with past experiences. The RLA follows a similar protocol, but the animal remains in the same affective state throughout and a reward-induced bias is generated by pairing one substrate with a higher value reward. The RLA provides a control to determine if drug treatments affect memory retrieval more generally. Studies in depression models and following environmental enrichment suggest that reward-induced biases are sensitive to core changes in affective state. Each task offers different insights into affective processing mechanisms and may help improve the translational validity of animal studies and benefit pre-clinical drug development. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Bowl digging and discrimination training Basic Protocol 2: The reward learning assay Basic Protocol 3: The affective bias test - new learning Basic Protocol 4: The affective bias test - modulation of affective biases associated with past experiences.

Acute and Repeated Ashwagandha Supplementation Improves Markers of Cognitive Function and Mood.

BACKGROUND: Ashwagandha has been reported to reduce stress and attenuate cognitive decline associated with inflammation and neurodegeneration in clinical populations. However, the effects as a potential nootropic nutrient in younger populations are unclear. This study examined the effects of liposomal ashwagandha supplementation on cognitive function, mood, and markers of health and safety in healthy young men and women. METHODS: 59 men and women (22.7 ± 7 yrs., 74.9 ± 16 kg, 26.2 ± 5 BMI) fasted for 12 h, donated a fasting blood sample, and were administered the COMPASS cognitive function test battery (Word Recall, Word recognition, Choice Reaction Time Task, Picture Recognition, Digit Vigilance Task, Corsi Block test, Stroop test) and profile of mood states (POMS). In a randomized and double-blind manner, participants were administered 225 mg of a placebo (Gum Arabic) or ashwagandha (Withania somnifera) root and leaf extract coated with a liposomal covering. After 60-min, participants repeated cognitive assessments. Participants continued supplementation (225 mg/d) for 30 days and then returned to the lab to repeat the experiment. Data were analyzed using a general linear model (GLM) univariate analysis with repeated measures and pairwise comparisons of mean changes from baseline with 95% confidence intervals (CI). RESULTS: Ashwagandha supplementation improved acute and/or 30-day measures of Word Recall (correct and recalled attempts), Choice Reaction Time (targets identified), Picture Recognition ("yes" correct responses, correct and overall reaction time), Digit Vigilance (correct reaction time), Stroop Color-Word (congruent words identified, reaction time), and POMS (tension and fatigue) from baseline more consistently with several differences observed between groups. CONCLUSION: Results support contentions that ashwagandha supplementation (225 mg) may improve some measures of memory, attention, vigilance, attention, and executive function while decreasing perceptions of tension and fatigue in younger healthy individuals. Retrospectively registered clinical trial ISRCTN58680760.

Effects of Acute Guarana (Paullinia cupana) Ingestion on Mental Performance and Vagal Modulation Compared to a Low Dose of Caffeine.

Guarana (GUA), a Brazilian seed extract, contains caffeine and other bioactive compounds that may have psychoactive effects. To assess the acute effects of GUA compared to a low dose of caffeine (CAF) on cognitive and mood parameters, twenty participants completed a double-blind, crossover experiment where they ingested capsules containing the following: (1) 100 mg CAF, (2) 500 mg GUA containing 130 mg caffeine, or (3) placebo (PLA). Cognitive tests (Simon and 2N-Back Task) were performed at the baseline (pre-ingestion) and 60 min after ingestion. The response time for the cognitive tests and heart rate variability were unaffected (p > 0.05) by treatment, although 2N-Back was overall faster (p = 0.001) across time. The accuracy in the 2N-Back Task showed a significant interaction effect (p = 0.029) due to higher post-ingestion versus pre-ingestion levels (p = 0.033), but only with the PLA. The supplements also had no effect on cognitive measures following physical fatigue (n = 11). There was an interaction effect on perceived mental energy, where the pre-ingestion of GUA had lower mental pep ratings compared to post-ingestion (p = 0.006) and post-exercise (p = 0.018) levels. Neither the acute ingestion of GUA nor low dose of CAF influenced cognitive performance or provided consistent benefit on mood or mental workload through vagal modulation. Additional investigations are beneficial to determining the lowest effective dose for CAF or GUA to influence mood and/or cognitive performance.

Chronic administration of caffeine, modafinil, AVL-3288 and CX516 induces time-dependent complex effects on cognition and mood in an animal model of sleep deprivation.

OBJECTIVE: Caffeine and modafinil are used to reverse effects of sleep deprivation. Nicotinic alpha-7 receptor and AMPA receptor positive allosteric modulators (PAM) are also potential substances in this context. Our objective is to evaluate the effects of caffeine, modafinil, AVL-3288 (nicotinic alpha-7 PAM) and CX516 (AMPA receptor PAM) on cognition and mood in a model of sleep deprivation. METHOD: Modified multiple platform model is used to sleep-deprive mice for 24 days, for 8 h/day. Vehicle, Modafinil (40 mg/kg), Caffeine (5 mg/kg), CX516 (10 mg/kg), and AVL3288 (1 mg/kg) were administered intraperitoneally daily. A cognitive test battery was applied every six days for four times. The battery that included elevated plus maze, novel object recognition, and sucrose preference tests was administered on consecutive days. RESULTS: Sleep deprivation decreased novel object recognition skill, but no significant difference was found in anxiety and depressive mood. Caffeine administration decreased anxiety-like behavior in short term, but this effect disappeared in chronic administration. Caffeine administration increased memory performance in chronic period. AVL group showed better memory performance in short term, but this effect disappeared in the rest of experiment. Although, in the modafinil group, no significant change in mood and memory was observed, anhedonia was observed in the chronic period in vehicle, caffeine and modafinil groups, but not in AVL-3288 and CX-516 groups. CONCLUSION: Caffeine has anxiolytic effect in acute administration. The improvement of memory in chronic period may be associated with the neuroprotective effects of caffeine. AVL-3288 had a short-term positive effect on memory, but tolerance to these effects developed over time. Furthermore, no anhedonia was observed in AVL-3288 and CX516 groups in contrast to vehicle, caffeine and modafinil groups. This indicates that AVL-3288 and CX516 may show protective effect against depression.

Levilactobacillus brevis SG031 modulates mood-related behaviors and attenuates stress-related sleep disturbance and autonomic dysfunction via gut microbiota modulation in Wistar-Kyoto rats.

AIMS: The probiotic bacterium Levilactobacillus brevis (L. brevis) has been proposed as a potential solution to manage mood disorders and alleviate stress-related sleep disturbances. However, the underlying mechanisms of its effects have not been fully elucidated. The aim of this study was to explore the impact and potential mechanisms of L. brevis SG031 supplementation on anxiety/depression-like behaviors and stress-induced changes in sleep patterns and sleep-related autonomic function. MAIN METHODS: Male Wistar-Kyoto rats were administered low, medium, or high doses of L. brevis SG031 or a vehicle for 4 weeks, followed by behavioral tests to evaluate anxiety and depression. After an additional 2 weeks of SG031 or vehicle administration, a cage-exchange paradigm was performed with 24-hour physiological signal measurements under different stress conditions. Fecal samples were collected to construct a 16S rRNA library and assess fecal short-chain fatty acids (SCFAs). KEY FINDINGS: High-dose SG031 administration yielded reduced depression-like responses and enhanced social interaction in behavioral tests. It also exhibited a protective effect against stress-induced sleep disturbance characterized by decreased sleep time, increased awake time, and autonomic dysfunction during sleep. Fecal examination indicated that high-dose SG031 administration exerted beneficial effects on gut health by maintaining the gut microbial abundance, preserving stability of the microbial composition, and enriching the gut with SCFAs, which were associated with improvements in sleep and autonomic function. SIGNIFICANCE: These findings collectively underscore the multifaceted potential of SG031 in addressing mental health and stress-related sleep challenges through the modulation of the gut microbiota.

Effects of medical cannabis use on physical and psychiatric symptoms across the day among older adults.

INTRODUCTION: Older adults are increasingly using medical cannabis (MC). It is unclear if therapeutic effects increase problematic use patterns. The current study addresses this issue by examining symptom trajectories across the day and using trajectories to predict problematic use. METHODS: One-hundred six older adults (age range 55-74) who endorsed medical conditions approved for treatment using MC were recruited online. Participants received six text messages/day to assess momentary symptoms for 15 days. RESULTS: Participants provided 5,156 momentary assessments across 1,106 use days. Symptom trajectories were examined across the day. There was a decline in all symptoms following use. Negative affect, pain, and nausea evinced momentary negative reinforcement associations with cannabis intoxication. Momentary negative reinforcement was associated with adverse cannabis outcomes. Declines in post-use trauma symptoms and momentary negative reinforcement effects for negative affect were both associated with cannabis use disorder symptoms. DISCUSSION: These data suggest that MC may be effective in reducing common symptom clusters. However, the negative reinforcing effect (i.e., the link between use and symptom relief at the event level) may complicate the therapeutic nature (i.e., symptom reduction). Identifying interventions to maximize benefits while minimizing costs may increase the efficacy and safety of MC in older adults.

Reduced threat avoidance but increased stress induced approach bias in women taking oral contraceptives.

Recent research has increasingly acknowledged the impact of oral contraceptives on affective behavior and stress responses; however, the underlying mechanisms are still not well understood. Studies have previously shown that steroid hormones modulate automatic approach and avoidance behavior. Here, we thus investigated the effects of oral contraceptives on approach and avoidance behavior and whether these effects are modulated by stress. The study comprised 130 female participants, half of whom were using oral contraceptives, while the other half were not using any hormonal contraception (NC). The participants completed the Approach Avoidance Task (AAT), which measures automatic approach and avoidance behavior to socio-affective signals. The AAT was run once before and once after a stress manipulation using the Socially Evaluated Cold Pressor Test. OC users showed absent avoidance behavior to social threat signals and a stress-induced increase in approach behavior to positive social signals. The latter was found in particular in women taking androgenic acting OC, demonstrating that different OC preparations need to be taken into account in research on OC effects. However, OC and NC group did not differ in their cortisol stress response. Overall, the results suggest that OC usage impacts on approach and avoidance behavior to social signals, which might also contribute to the development of affective side effects.

A positive affect intervention alters leukocyte DNA methylation in sexual minority men with HIV who use methamphetamine.

OBJECTIVE: This epigenomics sub-study embedded within a randomized controlled trial examined whether an evidenced-based behavioral intervention model that decreased stimulant use altered leukocyte DNA methylation (DNAm). METHODS: Sexual minority men with HIV who use methamphetamine were randomized to a five-session positive affect intervention (n = 32) or an attention-control condition (n = 21), both delivered during three months of contingency management for stimulant abstinence. All participants exhibited sustained HIV virologic control - an HIV viral load less than 40 copies/mL at baseline and six months post-randomization. The Illumina EPIC BeadChip measured leukocyte methylation of cytosine-phosphate-guanosine (CpG) sites mapping onto five a priori candidate genes of interest (i.e., ADRB2, BDNF, FKBP5, NR3C1, OXTR). Functional DNAm pathways and soluble markers of immune dysfunction were secondary outcomes. RESULTS: Compared to the attention-control condition, the positive affect intervention significantly decreased methylation of CpG sites on genes that regulate ß2 adrenergic and oxytocin receptors. There was an inconsistent pattern for the direction of the intervention effects on methylation of CpG sites on genes for glucocorticoid receptors and brain-derived neurotrophic factor. Pathway analyses adjusting for the false discovery rate (padj < 0.05) revealed significant intervention-related alterations in DNAm of Reactome pathways corresponding to neural function as well as dopamine, glutamate, and serotonin release. Positive affect intervention effects on DNAm were accompanied by significant reductions in the self-reported frequency of stimulant use. CONCLUSIONS: There is an epigenetic signature of an evidence-based behavioral intervention model that reduced stimulant use, which will guide the identification of biomarkers for treatment responses.

Pain and withdrawal are common among patients receiving medications for opioid use disorder and associated with pain catastrophizing, negative affect, and poor sleep.

Substantial percentages of persons receiving medications for opioid use disorder (MOUD) continue to experience clinically significant levels of pain and opioid withdrawal, which may pose barriers to reducing opioid use. Continued pain, in particular, may increase the risk for psychiatric problems and poorer treatment retention, especially with a lack of adequate care for pain. The goals of these analyses were to characterize the prevalence of, and patient-level variables associated with, pain and opioid withdrawal, as well as utilization of related coping strategies and treatments. Participants were 18 years of age or older and received methadone or buprenorphine for opioid use disorder (n = 179). Participants completed this survey in person, within their MOUD clinic. Participants completed patient-level and demographic questions as well as measures of pain, withdrawal, utilization of related coping strategies, and pain treatment. Numerous participants endorsed chronic pain (41.9%) or opioid withdrawal (89.4%) and indicated reliance upon over-the-counter medications and prayer for pain management. Multiple linear regression models showed greater pain catastrophizing and negative affect accounted for variability in pain severity and pain interference, as well as opioid withdrawal. Persons who slept less and endorsed chronic pain also reported greater pain severity and interference, and pain interference was higher with increased age. These and previous findings combine to further highlight the detrimental role that pain catastrophizing and negative affect can play in pain perception and withdrawal, but also represent promising treatment targets to facilitate pain and withdrawal management and improved quality of life. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Caffeine Attenuates Exacerbated Central Fatigue during Moderate-Intensity Cycling Exercise in Women with Fibromyalgia.

PURPOSE: To compare the development of fatigability during a moderate-intensity cycling exercise between women with fibromyalgia (FM) and control women (CON) after acute ingestion of caffeine and placebo. METHODS: Ten FM and 10 CON women performed a 30-min moderate-intensity cycling exercise 1 h after the ingestion of a capsule containing either caffeine or a placebo. Fatigability and its central and peripheral determinants were determined via changes from pre- to post-15 and post-30 min of exercise in maximal voluntary isometric contractions, voluntary activation (VA), and quadriceps potentiated twitch torque ( Qtw-pot ), respectively. Heart rate, muscle oxygen saturation, perceptive responses, mood state, localized and widespread pain, and sleepiness were also monitored during and after exercise. RESULTS: There was a time versus group interaction for maximal voluntary isometric contraction and VA ( P < 0.001) but not for Qtw-pot ( P = 0.363), indicating a greater rate of fatigability development, mainly caused by central mechanisms, in the FM than in the CON group. There was also a main effect of condition for VA ( P = 0.011), indicating that caffeine attenuates central mechanisms of fatigability in both groups. Caffeine ingestion also increased muscle oxygenation, perceived vigor, and energy, and decreased leg muscle pain, sleepiness, and perceived fatigue in both groups. However, caffeine improved perceived pleasure/displeasure and exercise adherence likelihood only in the FM group. CONCLUSIONS: Compared with CON, women with FM present a greater rate of fatigability during exercise, mainly of central origin. Caffeine seems to be a promising bioactive to counteract the central mechanisms of fatigability and improve the exercise experience among FM women.

Effect of MDMA-assisted therapy on mood and anxiety symptoms in advanced-stage cancer (EMMAC): study protocol for a double-blind, randomised controlled trial.

BACKGROUND: Symptoms of anxiety and depression are common in patients with terminal illness and multiple challenges exist with timely and effective care in this population. Several centres have reported that one dose of the serotonergic psychedelic psilocybin, combined with therapeutic support, improves these symptoms for up to 6 months in this patient group. Drawing upon related therapeutic mechanisms, 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy may have the potential to achieve similar, positive mental health outcomes in this group. Preliminary evidence also supports the tolerability of MDMA-assisted therapy for anxiety and depression in advanced-stage cancer. METHODS: Up to 32 participants with advanced-stage cancer and associated depression and anxiety will be randomised in a 1:1 ratio into one of two blinded parallel treatment arms. The intervention group will receive 120 mg (+ 60 mg optional supplemental dose) MDMA-assisted therapy. The psychoactive control group will receive 20 mg oral (+ 10 mg optional supplemental dose) methylphenidate-assisted therapy. For each medication-assisted therapy session, participants will undergo two 90-min therapeutic support sessions in the week preceding, and one 90-min support session the day after the experimental session. A battery of measures (mood, anxiety, quality of life, mystical experience, spiritual wellbeing, attitudes towards death, personality traits, holistic health and wellbeing, connectedness, demoralisation, expectations, qualitative data and safety measures) will be assessed at baseline and through to the end of the protocol. Participants will be followed up until either 12 months post-randomisation or death, whichever occurs first. DISCUSSION: This study will examine the effect of MDMA-assisted therapy on symptoms of anxiety and depression in advanced-stage cancer. Potential therapeutic implications include establishing the safety and effectiveness of a novel treatment that may relieve mental suffering in patients with life-threatening illness. TRIAL REGISTRATION: Trial registered on Australian New Zealand Clinical Trials Registry. REGISTRATION NUMBER: ACTRN12619001334190p. Date registered: 30/09/2019. URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378153&showOriginal=true&isReview=true.