Synbiotic 2000, a pre + probiotic, reduced comorbid autistic traits and emotion dysregulation in attention deficit hyperactivity disorder (ADHD) patients. Immune activity and bacteria-derived short-chain fatty acids (SCFAs) are microbiota-gut-brain axis mediators. The aim was to investigate Synbiotic 2000 effects on plasma levels of immune activity markers and SCFAs in children and adults with ADHD. ADHD patients (n = 182) completed the 9-week intervention with Synbiotic 2000 or placebo and 156 provided blood samples. Healthy adult controls (n = 57) provided baseline samples. At baseline, adults with ADHD had higher pro-inflammatory sICAM-1 and sVCAM-1 and lower SCFA levels than controls. Children with ADHD had higher baseline sICAM-1, sVCAM-1, IL-12/IL-23p40, IL-2Rα, and lower formic, acetic, and propionic acid levels than adults with ADHD. sICAM-1, sVCAM-1, and propionic acid levels were more abnormal in children on medication. Synbiotic 2000, compared to placebo, reduced IL-12/IL-23p40 and sICAM-1 and increased propionic acid levels in children on medication. SCFAs correlated negatively with sICAM-1 and sVCAM-1. Preliminary human aortic smooth-muscle-cell experiments indicated that SCFAs protected against IL-1β-induced ICAM-1 expression. These findings suggest that treatment with Synbiotic 2000 reduces IL12/IL-23p40 and sICAM-1 and increases propionic acid levels in children with ADHD. Propionic acid, together with formic and acetic acid, may contribute to the lowering of the higher-than-normal sICAM-1 levels.

Background University students are at a higher risk of using cognitive enhancers and psychoactive substances. Depression is associated with a noticeable decline in academic performance and can increase the risk of substance use. Due to sociopolitical issues, the use of cognitive enhancers and psychoactive substances among Palestinians has spread in the last decade. However, depression among tobacco and caffeine users remains underrecognized and neglected. Methodology A self-administrated questionnaire and the Beck Depression Inventory were used to assess the association of depression and the use of cognitive enhancers and psychoactive substances among university students at An-Najah National University in 2020. Results The response rate to the questionnaires was 78.8% (n = 1,051; 38.8% males, 61.2% females). The overall prevalence of depression was high (30.6% males, 34.7% females). The prevalence of cigarette smoking (39.2% males, 3.9% females), waterpipe smoking (43.1% males, 21.6% females), energy drink consumption (59.6% males, 29.7% females), coffee consumption (85.5% for each gender), tea consumption, and chocolate consumption was high, with significant differences in accordance to gender and academic fields. The multinomial logistic regression results revealed that cigarette smokers were more likely to have a higher risk of severe (odds ratio [OR] = 4.5, p = 0.001), moderate (OR = 3.27, p < 0.001), and mild depression (OR = 2.24, p = 0.002) than non-smokers. Severe depression was less prevalent among medical students than health sciences and non-medical students (OR = 0.215, p = 0.015). Moreover, males were less likely to have moderate (OR = 0.5, p = 0.012) and mild (OR = 0.48, p = 0.001) depression than females. Conclusions Overall, the results of this study revealed the high prevalence of depression and the detrimental effects of smoking on students. Moreover, the findings suggest the urgent need to address depression and risk factors among Palestinian university students by educating them about mental health, identifying high-risk students, and offering easily accessible psychological help. Further, it is crucial to broaden the focus of studies to include students from various academic fields instead of focusing on medical students.

BACKGROUND: Acute caffeine ingestion has been associated with improvements in cognitive performance and visual functioning. The main objective of this study was to determine the effects of caffeine intake on dynamic visual acuity (DVA).
METHODS: Twenty-one low caffeine consumers (22.5 ± 1.6 years) took part in this placebo-controlled, double-blind, and balanced crossover study. In two different days and following a random order, participants ingested either caffeine (4 mg/kg) or placebo, and DVA was measured after 60 min of ingesting the corresponding capsule. A recently developed and validated software (moV& test, V&mp Vision Suite, Waterloo, Canada) was used to assess DVA.
RESULTS: We found a greater accuracy for both the horizontal and random motion paths of DVA after caffeine ingestion (p < 0.001 and p = 0.002, respectively). In regard to the speed of the response, our data revealed that caffeine intake was associated with a faster reaction time for horizontally (p = 0.012) but not for randomly (p = 0.846) moving targets. Also, participants reported higher levels of perceived activation after consuming caffeine in comparison to placebo (p < 0.001).
CONCLUSIONS: Our data suggest that caffeine intake (i.e., a capsule containing 4 mg/kg) has an ergogenic effect on DVA, which may be of special relevance in real-word contexts that require to accurately and rapidly detect moving targets (e.g., sports, driving, or piloting).

This study was designed to assess the effects of daily psychostimulant exposure during juvenility and peri-adolescence on brain morphology and functional connectivity using multimodal magnetic resonance imaging. We hypothesized that long-term exposure to methylphenidate would enhance connectivity with the prefrontal cortex. Male rats were given daily injections of either methylphenidate (n=10), dextroamphetamine (n=10) or saline vehicle (n=10) from postnatal day 21 to 42. They were imaged between postnatal day 43 and 48. Voxel-based morphometry, diffusion weighted imaging, and resting state functional connectivity were used to quantify brain structure and function. Images from each modality were registered and analyzed, using a 3D MRI rat atlas providing site-specific data over 171 different brain areas. Following imaging, rats were tested for cognitive function using novel object preference. Long-lasting psychostimulant treatment was associated with only a few significant changes in brain volume and measures of anisotropy compared to vehicle. Resting state functional connectivity imaging revealed decreased coupling between the prefrontal cortex, basal ganglia and sensory motor cortices. There were no significant differences between experimental groups for cognitive behavior. In this exploratory study, we showed that chronic psychostimulant treatment throughout juvenility and preadolescence has a minimal effect on brain volume and gray matter microarchitecture, but significantly uncouples the connectivity in the cerebral/basal ganglia circuitry.

Psychostimulants are first-line pharmacological treatments for attention deficit hyperactivity disorder (ADHD), although symptom reduction varies widely between patients and these individual differences in treatment response are poorly understood. The authors sought to examine whether the resting-state functional connectivity within and between cingulo-opercular, striato-thalamic, and default mode networks was associated with treatment response to psychostimulant medication, and whether this relationship changed with development.
Patients with ADHD (N=110; 196 observations; mean age at first observation, 10.83 years, SD=2.2) and typically developing control subjects (N=142; 330 observations; mean age at first observation, 10.49 years, SD=2.81) underwent functional neuroimaging on up to five occasions during development (age range, 6-17 years). For patients, symptoms were assessed on and off psychostimulant medication (methylphenidate-based treatments: N=132 observations, 67%; amphetamine-based treatments: N=64 observations, 33%) using the Diagnostic Interview for Children and Adolescents for parents. Linear mixed-effects models examined whether resting-state connectivity was associated with treatment response and its interaction with age. Comparisons with typically developing control subjects were performed to contextualize any significant associations.
Resting-state connectivity within the cingulo-opercular network was associated with a significant interaction between treatment response and age. Specifically, worse responses to treatment compared with better responses to treatment among patients and compared with typically developing control subjects were associated with an atypical increase in cingulo-opercular connectivity with increasing age from childhood to adolescence.
This work delineates how resting-state connectivity may be associated over development with response to psychostimulants in ADHD. Functioning and development within the cingulo-opercular network may warrant further investigation as a contributor to differential response to psychostimulants.

UNASSIGNED: University students, who are at risk of eating disorders (ED), are more liable to use cognitive enhancers and psychostimulants to improve their cognitive functions and lose weight. ED in Palestinian male students is a neglected health issue. We aimed to investigate the prevalence and the association between ED and cognitive enhancers, and psychostimulants use among An-Najah National University students (ANNU).
UNASSIGNED: In a cross-sectional study conducted in 2020 at ANNU, 1047 students completed anonymous surveys for cognitive enhancers practice, the Eating Attitude Test-26 (EAT-26), Sick, Control, One, Fat and FOOD (SCOFF) screening tests.
UNASSIGNED: The prevalence of ED among ANNU students was 21.2% based on EAT-26 (17.1% in males, 23.8% in females) and 31.5% based on SCOFF (24.0% in males, 36.3% in females). The binary logistic regression revealed that students at risk to have ED were water-pipe smokers (OR: 1.471, p-value 0.047), especially males, while students who were less likely to have ED were males (OR: 0.341, p-value<0.001), coffee users (OR: 0.581, p-value 0.014) and chocolate users (OR: 0.530, p-value 0.041) than nonusers. Moreover, the risk of ED increased with increasing body mass index (p-value<0.01). Clinical medical students showed the lowest prevalence (11.1%) compared to preclinical (22.5%), health sciences (23.7%), and non-medical students (20.9%) (p-value 0.059).
UNASSIGNED: Our findings highlight water-pipe smoking as a significant health problem in males with ED, which may require unique treatment and prevention strategies. Moreover, coffee and chocolate consumption were associated with decreased risk of ED, only among males. The gender-gap in ED prevalence was very narrow compared to international results. These results prompt the need to focus on both genders in future studies instead of females. They also suggest the urgent need to address ED among Palestinian university students by educating students about mental health, identifying high-risk students, and offering easily accessible psychological help.

Mephedrone (4-methylmethcathinone) is a synthetic cathinone with psychostimulant properties which remains one of the most popular new psychoactive substances (NPS). It is frequently used orally and/or intranasally. To date, no studies have evaluated the acute effects and pharmacokinetics after self-administration of mephedrone orally (ingestion) and intranasally (insufflation) in naturalistic conditions. An observational study was conducted to assess and compare the acute pharmacological effects, as well as the oral fluid (saliva) concentrations of mephedrone self-administered orally and intranasally. Ten healthy experienced drug users (4 females and 6 males) self-administered a single dose of mephedrone, orally (n = 5, 100-200 mg; mean 150 mg) or intranasally (n = 5, 50-100 mg, mean 70 mg). Vital signs (blood pressure, heart rate, and cutaneous temperature) were measured at baseline (0), 1, 2, and 4 h after self-administration. Each participant completed subjective effects questionnaires: A set of Visual Analogue Scales (VAS), the 49-item Addiction Research Centre Inventory (ARCI), and Evaluation of the Subjective Effects of Substances with Abuse Potential (VESSPA-SSE) at baseline, 1, 2, and 4 h after self-administration. Oral fluid and urine were collected during 4 h. Both routes of mephedrone self-administration enhanced ratings of euphoria and well-being effects and increased cardiovascular effects in humans. Although it was at times assessed that the oral route produced greater and larger effects than the intranasal one, concentrations of mephedrone in oral fluid and also the total amount of mephedrone and metabolites in urine showed that concentrations of mephedrone are considerably higher when self-administered intranasally in comparison to orally. Controlled clinical trials are needed to confirm our observational results.

2,5-Dimethoxy-4-ethylphenethylamine (2C-E) is psychedelic phenylethylamine, with a chemical structure similar to mescaline, used as new psychoactive substance (NPS). It inhibits norepinephrine and serotonin uptake and, more relevant, acts as a partial agonist of the serotonin 2A (5-HT2 A), 2B (5-HT2 B), and (5-HT2 C) receptors. Consumers have reported that 2C-E induces mild-moderate psychedelic effects, but its pharmacology in humans, including pharmacological effects and pharmacokinetics, have not yet studied. To assess the acute effects of 2C-E on physiological and subjective effects and evaluate its pharmacokinetics, an observational study was carried-out. Ten recreational users of psychedelics self-administered a single oral dose of 2C-E (6.5, 8, 10, 15, or 25 mg). Blood pressure and heart rate were evaluated at baseline, 2, 4, and 6 h post-administration. Three rating scales were administered to evaluate subjective effects: a set of Visual Analog Scales (VAS), the 49-item short form version of the Addiction Research Centre Inventory (ARCI), and the Evaluation of the Subjective Effects of Substances with Abuse Potential (VESSPA-SSE) at baseline, 2, 4, and 6 h after self-administration. To assess 2C-E concentrations oral fluid (saliva) was collected during 6 h. 2C-E induced primarily alterations in perceptions, hallucinations, and euphoric-mood. Saliva maximal concentrations were achieved 2 h after self-administration. Administration of oral 2C-E at recreational doses produces a group of psychedelic-like effects such to 2C-B and other serotonin-acting drugs.

BACKGROUND: This study investigated the dental health problems and saliva characteristics of children under psychostimulant therapy for attention-deficit hyperactivity disorder (ADHD).
METHODS: One hundred and twenty children aged 7-12 years were divided into three groups. Groups 1-2 comprised children diagnosed with ADHD: those who had not yet started psychostimulant therapy (Group 1) and those already receiving long-term psychostimulant therapy (Group 2). Group 3 comprised healthy, nonmedicated children. Possible side effects of psychostimulants were investigated at the beginning of study in Group 2 and after 3 months drug use in Group 1. Bruxism and dental erosion prevalence, salivary Streptococcus mutans count, buffering capacity, and stimulated salivary flow rate (SSFR) were measured, and salivary α-amylase, calcium, total protein, and proline-rich acidic protein (PRAP) levels were quantified in the beginning of the study. Data were analyzed using the Kruskal-Wallis test.
RESULTS: The most frequently reported side effects of psychostimulants were decreased appetite, dry mouth, and increased fluid consumption. The prevalence of bruxism and dental erosion was higher in Groups 1 and 2 than in Group 3, but the differences were not significant (P > 0.05). In Group 2, subjective dry mouth feel was reported by 32.5% of patients and 17.5% had a very low SSFR. Salivary α-amylase, calcium, total protein, and PRAP levels were lower in Group 2 than the others, but the differences were not significant (P > 0.05).
CONCLUSIONS: ADHD and psychostimulant therapy do not appear to be significantly related to decreasing SSFR or protective saliva components against dental caries. However, a systematic investigation of the long-term safety of psychostimulants is needed. The most effective method of maintaining dental health of children with ADHD is frequent appointments focusing on oral hygiene practices accompanied by dietary analyses.

Delay-discounting procedures involving choice between small immediate rewards and large delayed rewards are used to study impulsivity in rodents. Improving existing procedures may provide new insights into the neurobiological mechanisms underlying decision-making processes.
To develop a novel delay-discounting procedure that adjusts the delay value within individual sessions based on the rat\'s most recent choices.
Compared to previously developed procedure, we required a more consistent demonstration of preference, five consecutive choices of the large or small reward, a criterion that is more likely to reflect deliberate choice by the animal, as opposed to two consecutive choices. In addition, delays were changed in steps of 5 s (rather than 1 s), because 5-s increments should be more easily discriminated and may produce a more distinct effect on choice. We characterized the procedure behaviorally by manipulating the duration of the session and the consecutive choice criterion, and we investigated the stability of the behavior upon interruption of training. We also characterized the procedure pharmacologically by investigating the effects of dopaminergic compounds.
Our procedures allowed obtaining two complementary measures of delay discounting: (1) the percentage of choices of the delay option and (2) the mean adjusting delay, an index of the delay that animals choose more frequently. We found that our procedure rapidly establishes a baseline of choice behavior that remains stable over time and is highly sensitive to manipulations of the dopaminergic system.
This procedure may provide a useful tool for investigating the neurobiology of inter-temporal choice and decision-making.