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A single dose of psilocybin, a psychedelic that acutely causes distortions of space-time perception and ego dissolution, produces rapid and persistent therapeutic effects in human clinical trials1-4. In animal models, psilocybin induces neuroplasticity in cortex and hippocampus5-8. It remains unclear how human brain network changes relate to subjective and lasting effects of psychedelics. Here we tracked individual-specific brain changes with longitudinal precision functional mapping (roughly 18 magnetic resonance imaging visits per participant). Healthy adults were tracked before, during and for 3 weeks after high-dose psilocybin (25 mg) and methylphenidate (40 mg), and brought back for an additional psilocybin dose 6-12 months later. Psilocybin massively disrupted functional connectivity (FC) in cortex and subcortex, acutely causing more than threefold greater change than methylphenidate. These FC changes were driven by brain desynchronization across spatial scales (areal, global), which dissolved network distinctions by reducing correlations within and anticorrelations between networks. Psilocybin-driven FC changes were strongest in the default mode network, which is connected to the anterior hippocampus and is thought to create our sense of space, time and self. Individual differences in FC changes were strongly linked to the subjective psychedelic experience. Performing a perceptual task reduced psilocybin-driven FC changes. Psilocybin caused persistent decrease in FC between the anterior hippocampus and default mode network, lasting for weeks. Persistent reduction of hippocampal-default mode network connectivity may represent a neuroanatomical and mechanistic correlate of the proplasticity and therapeutic effects of psychedelics.

Methylphenidate (MPH) is highly efficacious in reducing symptoms of attention-deficit/hyperactivity disorder (ADHD) in children. Generally increased doses are found to result in better symptom control; however, it remains unclear whether this pattern can be observed at the individual level, given the large heterogeneity in individual dose-response relationships and observed placebo responses. A double-blind, randomized, placebo-controlled cross-over trial was used to compare weekly treatment with placebo and 5, 10, 15 and 20 mg of MPH twice daily on parent and teacher ratings of child ADHD symptoms and side effects. Participants were 5-13-year-old children with a DSM-5 diagnosis of ADHD (N = 45). MPH response was assessed at group and individual levels and predictors of individual dose-response curves were examined. Mixed model analysis showed positive linear dose-response curves at group level for parent and teacher rated ADHD symptoms and parent rated side effects, but not for teacher rated side effects. Teachers reported all dosages to improve ADHD symptoms compared to placebo, while parents only reported > 5 mg/dose as effective. At the individual level, most (73-88%) children, but not all, showed positive linear dose-response curves. Higher severity of hyperactive-impulsive symptoms and lower internalizing problems, lower weight, younger age and more positive opinions towards diagnosis and medication partly predicted steeper linear individual dose-response curves. Our study confirms that increased doses of MPH yield greater symptom control at a group level. However, large interindividual variation in the dose-response relationship was found and increased doses did not lead to greater symptom improvement for all children. This trial was registered in the Netherlands trial register (# NL8121).

Introduction: Nociplastic pain (NP), classified as a third type of pain alongside nociceptive and neuropathic pain, is chronic pain arising from the amplification of nociceptive stimuli through central sensitization, despite the absence of tissue damage, sensory nerve damage, or disease. An important clinical feature of NP is that it is not only associated with pain but also with sensory hypersensitivity to sound and light and cognitive dysfunction, including mood and attention disorders. Recent studies have suggested that depression and developmental disorders, such as attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), coexist with NP at high frequency. Additionally, cognitive impairment in individuals with NP may be associated with these psychiatric comorbidities. However, to our knowledge, there are no reports on (1) multidimensional evaluation and diagnostic details of abdominal NP in adults with ADHD/ASD; (2) how ADHD drugs and antidepressants are administered when ADHD and depression coexist with NP; and (3) how central sensitization, brain function, and family relationship problems underlying NP are altered by treatments of ADHD and depression. Case presentation: Herein, we present the case of a 51-year-old woman with abdominal NP. She developed severe right lower abdominal pain and underwent a thorough medical examination; however, the physical, medical cause remained unknown, making treatment challenging. Additionally, she took time off work as she began to complain of insomnia and anxiety. She was referred to our pain center, where a diagnosis of depression, ADHD, and ASD was confirmed, and treatment with ADHD medication was initiated. While ADHD medications alone did not yield sufficient improvement, a combination of methylphenidate and the antidepressant venlafaxine eventually led to improvements in abdominal NP, depression, ADHD symptoms, central sensitization, and family relationship issues. During treatment, cerebral blood flow in the anterior cingulate, prefrontal, and parietal cortices also improved. Conclusion: The treatment of comorbid depression is important while treating NP, and venlafaxine may be effective, especially in cases of comorbid ADHD/ASD. Screening for developmental disorders and depression is required in patients with abdominal NP. [ABSTRACT FROM AUTHOR]

In this retrospective cohort study, we compared neonatal and maternal outcomes after exposure of different psychopharmacological classes of drugs. Both psychiatric diseases and pharmacological treatment of these are associated with lower birth weights, lower APGAR scores, and NICU admission. Therefore, we tried to rule out the role of psychotropics as if no differences were found between pharmacological classes, the lower birthweights might not be attributable to these. We divided our groups in exposed to atypical antipsychotic drugs, Selective Serotonin Reuptake Inhibitors (SSRI), Tricyclic Antidepressants (TCA), benzodiazepines, and different combinations of psychotropic drugs. The last group included SSRIs combined with benzodiazepines, methylphenidate, lithium, and classic antipsychotic drugs. We used univariate regression analysis to see which factors from our rich dataset including pharmacological class, are associated with birth weight, APGAR scores, gestational age, and NICU admission. The significant associations from univariate analyses were further analyzed using ancova analysis or logistic regression where applicable. We found no clinically relevant differences in neonatal and maternal outcomes between the different exposed pharmacological classes. However, our dataset may have been too small to draw firm conclusions. [ABSTRACT FROM AUTHOR]

Introduction There have been substantial increases in the use of Schedule II stimulants in the United States. Schedule II stimulants are the gold standard treatment for attention-deficit hyperactivity disorder (ADHD), but also carry the risk of addiction. Since the neurocognitive deficits seen in ADHD resemble those of chronic cannabis use, and the rise in stimulant use is incompletely understood, this study sought to determine if recreational cannabis (RC) legalization increased distribution rates of Schedule II stimulants. Methods The distribution of amphetamine, lisdexamfetamine, and methylphenidate were extracted from the ARCOS database of the Drug Enforcement Administration. The three-year population-corrected slopes of distribution before and after RC sales were evaluated. Results Total stimulant distribution rates were significantly higher in states with RC sales after (p =0.049), but not before (p =0.221), program implementation compared to states without RC. Significant effects of time (p <0.001) and RC sales status (p =0.045) were observed, while time x RC sales status interaction effects were not significant (p =0.406). Discussion RC legalization did not contribute to a more pronounced rise in Schedule II stimulant distribution in states. Future studies could explore the impact of illicit cannabis use on stimulant rates and the impact of cannabis sales on distribution rates of non-stimulant ADHD pharmacotherapies and ADHD diagnoses. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to compare the approval of medicines for attention deficit/hyperactivity disorder (ADHD) for pediatric patients across five countries. Method: A document analysis was completed, using the drug labeling for ADHD medicines from five countries; United Kingdom, Australia, New Zealand, Canada and United States (US). Comparisons of available formulations and approval information for ADHD medicine use in pediatric patients were made. Results: The US had the highest number of approved medicines and medicine forms across the studied countries (29 medicine forms for 10 approved medicines). Approved age and dosage variations across countries and missing dosage information were identified in several drug labeling. Conclusions: The discrepancies in approval information in ADHD medicine drug labeling and differing availability of medicine formulations across countries suggest variations in the management of ADHD across countries. The update of drug labeling and further research into reasons for variability and impact on practice are needed. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to investigate the variables that may affect treatment continuation in children aged 6 to 12 years who were newly diagnosed with ADHD. Methods: A total of 132 children diagnosed with ADHD and their parents participated in the study. Sociodemographic and clinical risk factors affecting continuation of treatment were examined using logistic regression analysis. Results: Multiple model examination revealed that greater age increased the risk of treatment discontinuation 1.824 times (p =.003) while a lower total length of paternal education increased the risk of discontinuation (1/0.835) 1.198 times (p =.022). Other variables emerging as significant in the univariate model lost that significance in the multiple model. Conclusions: Understanding the variables associated with medication discontinuation in ADHD in different populations and taking these variables into account in the development of health policies, will be useful in improving the long-term devastating effects of the disorder. [ABSTRACT FROM AUTHOR]

ObjectiveMethodsResultsConclusionsAttention Deficit Hyperactivity Disorder (ADHD) is one of the most common mental disorders in children. Evidence regarding the impact of probiotics supplementation in ADHD children is limited and controversial. Thus, this study aimed to assess the effect of probiotics as an adjunctive therapy with Ritalin among ADHD children and adolescents.This study was a triple-blind, randomized controlled trial of 60 Iranian ADHD patients aged four to sixteen. The participants were randomly assigned to receive probiotics supplements containing both Lactobacillus plantarum PTCC 1896™ (A7) and Bifidobacterium animalis subsp. Lactis (BB-12®) (n = 30) or placebo (n = 30) for 8 weeks. ADHD symptoms were assessed using Conners’ Parent Rating Scale (CPRS) and Integrated Visual and Auditory Continuous Performance Test (IVA/CPT) at baseline and during the study.This study showed a significant decrease in the CPRS total score after 4 weeks of intervention in the probiotic group (baseline: 43.96 ± 21.52; fourth week: 37.22 ± 23.01; p = 0.01). However, no significant finding was found for the total score of the CPRS after 8 weeks. Moreover, at the end of the study, a significant increase was observed in score of auditory response control in the probiotic versus the placebo group (probiotic: 91.55 ± 16.69; placebo: 80.55 ± 17.43; p = 0.02).Probiotics supplementation with Ritalin may have some beneficial effects among ADHD children and adolescents, such as improving auditory response control and total score of CPRS. However, further clinical trials are required to clarify the impact of probiotics on ADHD. [ABSTRACT FROM AUTHOR]

The co-occurrence Oppositional Defiant Disorder (ODD) in children and adolescents with Attention Deficit Hyperactivity Disorder (ADHD) has been associated to difficulties in regulating adverse states, elevated functional impairment, deficits in Executive Functions and high risk for psychopathology. Recent studies have shown that ODD is a negative predictor of a positive response to methylphenidate (MPH) treatment for ADHD symptoms in children and adolescents and that patients with a diagnosis of comorbid ADHD and ODD are less likely to respond favorably to pharmacological treatment with MPH. We conducted a naturalistic study to understand the clinical characteristics of drug-naïve children and adolescents with ADHD that influence the response to MPH by measuring the effect on attention. Specifically, we investigated whether a single dose of MPH differently affects the performance of 53 children and adolescents with ADHD with or without ODD comorbidity. In addition, participant characteristics such as symptom severity, functional impairment, and associated behavioral and emotional symptoms at baseline were examined to better understand what aspects affect the response to MPH. We found that a single dose of MPH improved the attention of children and adolescents with ADHD without ODD more than those with comorbid ADHD and ODD, resulting in reduced reaction times. Our findings indicated that children and adolescents with comorbid ADHD and ODD and those with ADHD alone did not exhibit differences in measures of attention prior to taking MPH, nor in demographic variables (age, intelligence quotient, gender), clinical characteristics related to symptom severity, and adaptive behaviors. However, we observed differences between the two groups in certain behavioral aspects, including the Dysregulation Profile and disruptive behaviors. Assessing symptoms in combination with the presence of ADHD can be beneficial in determining which individuals would derive the greatest benefits from treatment. [ABSTRACT FROM AUTHOR]

The literature emphasizes the importance of addressing the misuse of ADHD medications as a potential significant healthcare issue within the general population. Nevertheless, there are no systematic reviews that specifically examine whether the misuse of psychostimulant medication among clinical populations diagnosed with ADHD who are undergoing prescribed stimulant therapy is a rational concern or a false myth. This systematic review was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 Statement. We searched PubMed databases for articles indexed up to 12th July 2023, without language restrictions. Our systematic search generated 996 unique articles. After a full-text revision, 13 studies met the eligibility criteria and were included in the systematic review. In the 50% of the study on the adult population, the reported prevalence of stimulant misuse was 0%. In other studies, the range of stimulant misuse rates varied from 2% to 29%, with no available data specifically focusing on the youth population. It has been noted that misuse of prescribed stimulant treatment is linked with particular subject characteristics, such as older age, prior or more frequent use of ADHD medication, use of short-acting medication, and a history of alcohol/substance misuse diagnosis. Despite certain limitations, our study highlights that while a significant proportion of individuals undergoing psychostimulant treatment for ADHD follow their prescribed medication regimens without resorting to misuse behaviors, there is variability in adherence, with occurrences of misuse behaviors. The misuse of prescribed ADHD treatment appears to be associated with distinct subject characteristics, underscoring the importance for tailored interventions addressing the specific requirements of these individuals to attain optimal treatment outcomes while mitigating misuse risks. [ABSTRACT FROM AUTHOR]

To compare safety and efficacy of centanafadine versus methylphenidate hydrochloride extended release (ER; Concerta) in adults with ADHD. Without head-to-head trials, anchored matching-adjusted indirect comparisons (MAIC) of adverse event rates reported across trials and mean change from baseline in Adult ADHD Investigator Symptom Rating Scale (AISRS) score between centanafadine and methylphenidate hydrochloride ER were conducted. Pooled patient-level data from two centanafadine trials (NCT03605680/NCT03605836) and aggregate data from one published methylphenidate hydrochloride ER trial (NCT00937040) were used. Characteristics of individual patients from the centanafadine trials were matched to aggregate baseline characteristics from the methylphenidate hydrochloride ER trial using propensity score weighting. A sensitivity analysis assessed the robustness of the results to the capping of extreme weights (i.e. >99th percentile). Compared with methylphenidate hydrochloride ER, centanafadine was associated with significantly lower risk of dry mouth (risk difference [RD] in percentage points: −11.95), initial insomnia (−11.10), decreased appetite (−8.05), anxiety (−5.39), palpitations (−5.25), and feeling jittery (−4.73) though a significantly smaller reduction in AISRS score (4.16-point). In the sensitivity analysis, the safety results were consistent with the primary analysis but there was no significant difference in efficacy between centanafadine and methylphenidate hydrochloride ER. In this MAIC, centanafadine had better safety and possibly lower efficacy than methylphenidate hydrochloride ER. While safety results were robust across analyses, there was no efficacy difference between centanafadine and methylphenidate hydrochloride ER in the sensitivity analysis. Considering its favorable safety profile, centanafadine may be preferred among patients for whom treatment-related adverse events are a concern. [ABSTRACT FROM AUTHOR]

Methylphenidate (MPD) remains a cornerstone pharmacological intervention for managing ADHD, yet its increasing usage among ordinary youth and adults outside clinical contexts necessitates a thorough investigation into its developmental effects. This study seeks to simultaneously investigate the behavioral and neuronal changes within the dorsal raphe (DR) nucleus, a center of serotonergic neurons in the mammalian brain, before and after the administration of varying doses of acute and chronic MPD in freely behaving young and adult rats implanted with DR recording electrodes. Wireless neuronal and behavioral recording systems were used over 10 consecutive experimental days. Eight groups were examined: saline, 0.6, 2.5, and 10.0 mg/kg MPD for both young and adult rats. Six daily MPD injections were administered on experimental days 1 to 6, followed by a three-day washout period and MPD re-administration on experimental day 10 (ED10). The analysis of neuronal activity recorded from 504 DR neurons (DRNs) in young rats and 356 DRNs in adult rats reveals significant age-dependent differences in acute and chronic MPD responses. This study emphasizes the importance of aligning electrophysiological evaluations with behavioral outcomes following extended MPD exposure, elucidating the critical role of DRNs and serotonin signaling in modulating MPD responses and delineating age-specific variations in young versus adult rat models. [ABSTRACT FROM AUTHOR]

Attention deficits are frequently reported within the clinical autism population. Despite not being a core diagnostic feature, some aetiological theories place atypical attention at the centre of autism development. Drugs used to treat attention dysfunction are therefore increasingly prescribed to autistic patients, though currently off‐label with uncertain efficacy. We utilised a rodent‐translated touchscreen test of sustained attention in mice carrying an autism‐associated R451C mutation in the neuroligin‐3 gene (Nlgn3R451C). In doing so, we replicated their cautious but accurate response profile and probed it using two widely prescribed attention‐modulating drugs: methylphenidate (MPH) and atomoxetine (ATO). In wild‐type mice, acute administration of MPH (3 mg/kg) promoted impulsive responding at the expense of accuracy, while ATO (3 mg/kg) broadly reduced impulsive responding. These drug effects were absent in Nlgn3R451C mice, other than a small reduction in blank touches to the screen following ATO administration. The absence of drug effects in Nlgn3R451C mice likely arises from their altered behavioural baseline and underlying neurobiology, highlighting caveats to the use of classic attention‐modulating drugs across disorders and autism subsets. It further suggests that altered dopaminergic and/or norepinephrinergic systems may drive behavioural differences in the Nlgn3R451C mouse model of autism, supporting further targeted investigation. [ABSTRACT FROM AUTHOR]

Background Parkinson's disease (PD) is a common neurodegenerative disorder in older adults that is associated with neuroinflammation, oxidative stress, and characterized by loss of dopaminergic cells. Illicit stimulants increase oxidative stress and are associated with increased risk of PD. Prescription stimulants are similar in mechanism to illicit stimulants, yet their influence on PD is not well described. This study aims to determine if prescription stimulants influence risk of PD among older adults with attention-deficit and hyperactivity disorder (ADHD). Methods We implemented a retrospective observational cohort design utilizing the TriNetX database which sources from the electronic health records of 57 healthcare organizations. Inclusion criteria were ADHD diagnosis and age ≥50. Those exposed to stimulants and the unexposed controls were matched based on demographics and known risk factors for PD. The outcome of interest was the incidence of PD over a 30-year follow-up period. We utilized TriNetX software for hazard ratio (HR) analysis. Results Among the 59,471 individuals treated with prescription stimulants 131 of them developed PD, and there were 272 individuals who developed PD that were not prescribed stimulants. This analysis yielded a HR of 0.419 (HR = 0.419 [95% CI 0.34, 0.516], P = 0.0013). Conclusion Illicit stimulants are associated with increased risk of PD, but this study suggests prescribed stimulants may not impart that same risk. The reduced risk in this cohort may be due to protection from illicit substance use and oxidative stress, however additional study exploring the relationship between prescription stimulants and PD is warranted. [ABSTRACT FROM AUTHOR]