Amie C. Hayley

Rationale: Acute alcohol intoxication impairs cognitive and motor control, elevating risk in safety–critical contexts. While blood alcohol concentration (BAC) quantifies exposure, it does not reflect real-time functional impairment. Mobile, performance-based assessments may offer scalable detection tools, but their sensitivity under controlled alcohol challenge requires further validation. Objectives: To evaluate the sensitivity of a mobile cognitive assessment (DRUID®) to alcohol-induced impairment across low and moderate intoxication levels and examined objective cognitive performance and subjective intoxication within a unified framework. Methods: In a randomised, double-blind, placebo-controlled, within-subjects trial, 30 healthy adults (33% female; aged 23–49 years) completed neurocognitive testing following placebo, low-dose alcohol (mean peak BAC 0.04%), and moderate-dose alcohol (mean peak BAC 0.07%). Cognitive performance was measured using the Cambridge Neuropsychological Test Automated Battery (CANTAB) and DRUID®, while subjective effects were assessed via the Brief Biphasic Alcohol Effects Scale and a single-item intoxication rating. Results: Moderate alcohol intoxication significantly impaired spatial working memory, sustained attention, and psychomotor control (all p < 0.05), and elevated DRUID® impairment scores at 130 min post-dose relative to placebo ( p < 0.001). Low-dose alcohol increased subjective intoxication and sedation (both p < 0.001) without measurable cognitive impairment. Conclusions: Moderate alcohol produced persistent neurocognitive deficits despite dissociation between subjective and objective measures. Findings support performance-based impairment models and highlight mobile cognitive tools such as DRUID® as practical candidates for real-time functional assessment in applied safety settings. Trial registration: ACTRN12623000528651, 19/05/2023.

Background: Stimulant-affected drivers are overrepresented in global road trauma statistics, however, studies to date have not accurately defined how drug consumption contributes to increased risk of road trauma. This study examined whether attitudes toward drug driving predicts dangerous driving behaviour among people who currently use methamphetamine, and whether this differs to individuals with no history of any drug use. Method: Three attitude factors (favourable attitudes toward risks, unfavourable attitudes toward sanctions, and favourable peer attitudes) were explored using an adapted version of attitudes towards drug driving scale and dangerous driving was measured using the Dula Dangerous Driving Index. Results: A multigroup structural equation model indicated that individuals who use methamphetamine report more favourable attitudes toward drug driving compared to those who have never used drugs. Among people who use methamphetamine, a favourable attitude towards drug driving risks predicted higher dangerous driving behaviour scores, while more unfavourable attitudes toward sanctions for drug driving predicted lower scores. Among those with no history of substance use, favourable peer attitudes toward drug driving predicted dangerous driving behaviour. Conclusions: Attitudes towards drug-driving, and their relationship to dangerous driving behaviour differs between those who use methamphetamine and those who do not have a history of substance usage. Targeted campaigns aimed specifically at reducing methamphetamine-related road trauma should challenge general underlying beliefs and attitudes about drug driving, rather than simply the impact of potential sanctions or influence of peers.

Issue: Alcohol hangovers can occur after a single episode of drinking and begin as blood alcohol concentration returns to zero. While hangovers are widely known for their physical symptoms, they also include psychological symptoms such as a depressed mood. These psychological impacts, particularly negative affect (e.g., anxiety, stress), remain less well understood, yet may contribute to maladaptive drinking behaviours and reinforce the cycle of excessive alcohol consumption. Approach: This systematic review, pre‐registered and reported in alignment with Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) and Synthesis without Meta‐analysis guidelines, aimed to comprehensively examine the association between alcohol hangovers and negative affect. Searches were performed in MEDLINE, Embase, PsycNET, Scopus and CINAHL from inception to January 2025. Two independent reviewers screened articles, assessed the risk of bias and extracted data. Key Findings: Twenty‐two studies ( n = 6152; mean age 26.9 years, 57% female) demonstrated a significant association between hangovers and increased negative affect, including anxiety, stress and depression. Maladaptive emotional regulation, avoidant coping styles, repetitive negative thinking and greater baseline anxiety exacerbated these negative experiences, while social support and mental resilience offered potential protective factors. Implications: The findings highlight the clinical importance of addressing psychological factors in alcohol‐related harm. The tendency to return to binge drinking despite negative hangover experiences suggests that psychological factors may perpetuate unhealthy alcohol consumption. Conclusion: This review supports a strong link between alcohol hangovers and heightened negative affect. Effective interventions must address both the reduction of negative affect and the underlying drivers of binge drinking to promote healthier alcohol consumption patterns.

Background and objectives Cannabinoid treatments are commonly used for sleep conditions, but the direct sedating effects of daytime treatment consumption and indirect effects on night-time sleep are unclear. This study measures the direct effects of low-dose cannabinoid treatments on daytime sleepiness and potential indirect night-time sleep effects in healthy adult, novice cannabis users. Methods Using a double-blind, randomised, placebo-controlled cross-over design, participants were orally administered a standardised dose of 1 mL oil containing THC:CBD ratios of either 1:1, 1:16 or a placebo over five weekly in-lab visits. Daytime sleepiness was measured at 40, 135 and 265 min post-dosing using the Karolinska Sleepiness Scale (KSS). Indirect night-time sleep effects on total sleep time (TST), sleep-onset latency (SOL), and number of awakenings after onset were measured using daily wrist-actigraphy and sleep-diary entries during the 7-day washout period between treatments. Results Final analyses (N = 20) showed subjective sleepiness (KSS score) significantly increased (mean difference = 1.9, SE 0.25) from 40 min to 265 min post-treatment (p < 0.001). No significant differences were observed between treatments for KSS. Indirect sleep measures (TST, SOL, number of awakenings) showed no differences between treatments or over time (all p > 0.05). Conclusion Daytime consumption of low-dose cannabinoid oils did not induce direct sleepiness or indirect night-time effects post-dosing among adults. Future studies would benefit from exploring pharmacokinetics and the possibility of treatment amplification of daytime fatigue, mood and cognitive changes to assist the development of therapeutic guidelines for safe daytime medical cannabis use. ANCTR Trial Registration Number ACTRN12622001539729, 13 December 2022, prospectively registered.

Chronic pain is a complex and multidimensional condition that disrupts both physical function and cognitive processing, creating a bidirectional cycle that amplifies symptom burden and complicates clinical management. Cognitive dysfunction, characterized by deficits in memory, attention, and executive function, further impairs treatment adherence and functional recovery. Conventional pharmacologic therapies frequently fail to address this dual burden and are associated with adverse effects, including dependence and cognitive impairment. Neuromodulation has emerged as a promising nonpharmacologic alternative, capable of modulating neuroplastic, neuroinflammatory, and neurotransmitter pathways implicated in both pain and cognitive decline. This narrative review examines the mechanisms and clinical applications of spinal cord stimulation (SCS), transcutaneous electrical nerve stimulation (TENS), and neuromuscular electrical stimulation (NMES), and evaluates emerging innovations such as EcoAI™, an artificial intelligence–driven, non-invasive neuromodulation platform. By integrating physiological and behavioral biomarkers with real-time adaptive therapy, EcoAI and similar technologies represent a shift toward personalized, precision-based interventions. Additional advances in remote patient monitoring (RPM) and closed-loop feedback systems further enhance therapeutic responsiveness and continuity of care. Collectively, these approaches offer a scalable, patient-centered framework for managing chronic pain and its cognitive comorbidities. Future priorities include the development of validated biomarkers, rigorous clinical evaluation of AI-integrated systems, and equitable implementation strategies to ensure broad access to next-generation neuromodulation.

Background: Dexmedetomidine is an α 2-agonist sedative with opioid-sparing properties, is limited by dose-dependent hypotension and bradycardia. Ketamine, an NMDA receptor antagonist, has sympathomimetic effects and may attenuate these cardiovascular effects while contributing analgesia. Whether low-dose ketamine can stabilize dexmedetomidine-induced hemodynamic changes and provide comparable analgesia to an opioid-based regimen is uncertain. Methods: In this open-label trial, we enrolled 41 healthy volunteers aged 18 to 45 years. All participants received a ketamine infusion (0.3 mg/kg bolus, then 0.15 mg/kg/hour for 3 hours). At 90 minutes, participants were randomized to receive either dexmedetomidine (0.7 μg/kg/hour for 90 minutes, KET/DEX group) or fentanyl (three 25 μg boluses, KET/FENT group). The primary outcomes were change in blood pressure and pain tolerance (measured by pressure algometry). Secondary outcomes included heart rate, subjective mood and sedation, and adverse events. Data were analyzed using mixed-effects models and Fisher’s exact tests. Results: Of 41 randomized participants, 39 completed the protocol (KET/DEX, 19; KET/FENT, 20). KET/DEX resulted in greater reductions in systolic blood pressure (mean decrease 35– 40 mm Hg; ~25– 30%) compared to KET/FENT (mean change minimal; between-group P< 0.001). Heart rate declined modestly with KET/DEX but did not differ significantly between groups. Both regimens increased pain tolerance to a similar degree (mean threshold rise ~30– 50 kPa; between-group P=0.80). Participants in the KET/DEX group reported greater sedation and transient negative mood effects (eg, disinterest), while KET/FENT was associated with mild nausea in a minority. Clinically significant hypotension occurred in 4 participants (21%) in the KET/DEX group and in none of the KET/FENT group (P=0.047). All events were transient and responsive to fluid boluses. No respiratory depression occurred in either group. Conclusion: Ketamine plus dexmedetomidine produced analgesia equivalent to ketamine plus fentanyl but with more pronounced hypotension and deeper sedation. The hemodynamic effects of dexmedetomidine were not fully offset by low-dose ketamine. These findings suggest that while ketamine–dexmedetomidine may offer an opioid-sparing alternative, careful dose selection and monitoring are required to ensure tolerability. (Funded by Monash University and Monash Health; ACTRN12617000787381). Clinical Trial Number and Registry Url: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372916.

Objective: To examine the effect of a low dose (10 mg) of methylphenidate on cognitive performance, visuospatial working memory (VSWM) and gaze behaviour capabilities in healthy adults. Methods: This randomised, double‐blind, placebo‐controlled and crossover study examined the effects of 10 mg methylphenidate on cognitive performance, VSWM and gaze behaviour. Fixation duration and rate, gaze transition entropy, and stationary gaze entropy were used to quantify visual scanning efficiency in 25 healthy adults (36% female, mean ± SD age = 33.5 ± 7.8 years, BMI = 24.1 ± 2.9 kg/m ² ). Attention, memory, and reaction time were assessed using the E‐CogPro test battery. Results: Methylphenidate significantly enhanced performance in numeric working memory tasks, reflected by reduced errors and increased accuracy relative to placebo. No significant changes were observed in other cognitive or visual scanning metrics. Conclusions: A low dose of methylphenidate improves limited domains of psychomotor speed and accuracy but does not affect visual scanning efficiency. This suggests limited usefulness as a general pro‐cognitive aid and raises the possibility of a lower threshold of effect for measurable psychostimulant‐induced changes to visual scanning behaviour. Further research is needed to explore these potential dose‐response relationships and effects across diverse populations. Trial Registration: ACTRN12620000499987

Background: Methylphenidate is a routinely prescribed treatment for attention-deficit/hyperactivity disorder with misuse potential owing to its perceived performance-enhancing and euphoric properties. Although clinically effective, there is limited understanding of how methylphenidate affects safety-sensitive tasks such as driving when used by healthy individuals. Aim: Explore the acute effects of 10 mg methylphenidate on driving performance and gaze behaviour. Methods: Twenty-five fully licensed, healthy adults (mean age = 33.5 ± 7.8 years, 64% male) took part in two 40-min simulated highway drives with simultaneous eye movements monitored using a proprietary automotive-grade driver monitoring system (Seeing Machines). Driving performance was assessed using the standard deviation of lateral position, standard deviation of speed and steering variability. Visual scanning efficiency was determined using ocular metrics, such as fixation duration and rate, gaze transition entropy, and stationary gaze entropy, were assessed to determine visual scanning efficiency. Results: Methylphenidate significantly improved driving performance by reducing lane weaving and speed variation, particularly in the latter half of the drive. Although a significant reduction in fixation duration was observed, all other ocular metrics remained unchanged. Conclusions: Methylphenidate mitigates performance decrements typically associated with prolonged and monotonous driving. The absence of pronounced oculomotor effects suggests that a single 10 mg dose of methylphenidate has no deleterious impact on visual scanning behaviour during driving tasks with low-to-moderate cognitive demand. Future research should investigate the effects of methylphenidate under various dosing and driving conditions to better understand its impact. Trial Registration: ACTRN12620000499987.