Driving performance and ocular activity following acute administration of 10 mg methylphenidate: A randomised, double-blind, placebo-controlled study.

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.

The effect of nightly use of 150 mg cannabidiol on daytime neurocognitive performance in primary insomnia: a randomized controlled pilot trial.

RATIONALE: Cannabidiol (CBD) is increasingly used as a sleep aid for insomnia; yet neurocognitive and subjective state effects following daily therapeutic use are unclear. OBJECTIVES: To measure the effect of daily CBD use on neurocognitive performance and daily subjective mood in a population with primary insomnia. METHODS: This study used a randomized, placebo-controlled, parallel design incorporating a single-blind placebo run-in week followed by a two-week double-blind dosing period, during which participants consumed 150 mg CBD (N = 15) or placebo (N = 15) sublingually 60-minutes daily before bed. Attention, executive function, reasoning, information processing, working and episodic memory were assessed using the CogPro system at the beginning of the placebo run-in, after 1-week and 2-weeks of dosing. Subjective states using visual analogue scales and side effects were recorded daily. RESULTS: Cognitive performance was unaffected by nightly CBD supplementation (all p > 0.05). From baseline to trial conclusion, those receiving CBD reported greater experience of calmness, clear-headedness, coordination and were more likely to report side-effects of dry mouth relative to placebo (all p < 0.05). CONCLUSIONS: Relative to placebo, daytime cognitive functioning following nightly supplementation as a therapeutic aid for primary insomnia was preserved under trial conditions. Results suggested an overall favourable safety profile, with larger controlled trials and thorough analyses of varying insomnia phenotypes necessary to corroborate these findings.

Acute methamphetamine and alcohol usage alters gaze behaviour during driving: A randomised, double-blind, placebo-controlled study.

BACKGROUND: Methamphetamine is frequently co-consumed with alcohol, yet combined effects on visually guided behaviours have not been experimentally assessed. This study examined whether methamphetamine and alcohol-induced changes in gaze behaviour can be accurately detected and indexed during a simulated driving task to establish characteristic patterns relevant to traffic safety. METHODS: In a randomised, placebo-controlled, cross-over study design, the effects of acute oral methamphetamine (0.42 mg/kg) were assessed with and without low doses of alcohol (target 0.04% blood alcohol content) on gaze behaviour during driving. Twenty healthy adults (mean age 29.5 years (SD ± 4.9), 40% female) completed four, 1-h simulated drives with simultaneous eye monitoring using the SensoMotoric Instruments cap-mounted eye tracker over a 4-week experimental paradigm. Gaze entropy measures were used to quantify visual scanning efficiency, expressed as gaze transition entropy and stationary gaze entropy. Fixations, recorded as duration (milliseconds, ms) and rate (count) per minute, were examined in 10-min bins over the duration of the drive. Driving performance was assessed by the standard deviation of lateral position, standard deviation of speed and steering variability. RESULTS: Methamphetamine increased the rate and duration of fixations and produced a less dispersed but more disorganised pattern of gaze during highway driving while preserving performance. Alcohol alone impaired both oculomotor control and driving performance, even when consumed at levels well below the legal limit stipulated in many international jurisdictions. CONCLUSIONS: Methamphetamine-affected drivers display inefficient exploration in a limited visual range during driving. Eye-tracking metrics thus show potential for indexing intoxication due to psychoactive substance usage.

Trait anger as a predictor of dangerous driving behaviour amongst people who use methamphetamine.

INTRODUCTION: Despite increased prevalence of methamphetamine in road trauma, it remains unclear how its use translates to an increased risk of traffic-related harm. Exploration of psychosocial factors may thus help identify relevant predictors of dangerous driving behaviour among people who regularly consume methamphetamine. METHODS: Licenced individuals who report predominant and sustained methamphetamine use (at least 1-time/month for 6 months at heaviest use) were recruited from the Australian community and via targeted campaign (Eastern Health). Psychosocial, substance use and driving behaviour data (Dula Dangerous Driving Index, DDDI) were collected via a secure anonymous online forced-entry survey platform (Qualtrics). RESULTS: Seventy-seven individuals (65.5 % male) aged between 20-50 years [mean = 29.7, ± Standard Deviation (SD) 6.1] were included. Most (90 %) respondents met criteria for problematic methamphetamine use [Severity of Dependency Scale (SDS) score ≥ 5], and 75 % were high-risk alcohol consumers [Alcohol Use Disorders Identification Test (AUDIT-C) score ≥ 4 for men and ≥ 3 for women]. On average, age of first methamphetamine use occurred at 23.3 years (±5.2). A best-possible subset's regression selection method with dangerous driving behaviour as the dependent variable determined the model with three predictors (alcohol use, substance dependence severity and trait anger) as most parsimonious. After controlling for substance use, trait anger strongly and positively predicted dangerous driving behaviour as measured by the DDDI ([F(3,74) = 26.06, p < .001, adjusted R2 = 0.50, Cohens f2 = 0.42). DISCUSSION AND CONCLUSIONS: Trait anger is a strong predictor of risky driving among road users who use methamphetamine. Interactions between stable negative-emotional and situational traffic and driving-related factors may increase risk of harm through greater engagement in risk-taking behaviour.

A randomised, placebo-controlled, double blind, crossover trial on the effect of a 20:1 cannabidiol: Δ9-tetrahydrocannabinol medical cannabis product on neurocognition, attention, and mood.

As cannabinoid-based medications gain popularity in the treatment of refractory medical conditions, it is crucial to examine the neurocognitive effects of commonly prescribed products to ensure associated safety profiles. The present study aims to investigate the acute effects of a standard 1 mL sublingual dose of CannEpil®, a medicinal cannabis oil containing 100 mg cannabidiol (CBD) and 5 mg Δ9-tetrahydrocannabinol (THC) on neurocognition, attention, and mood. A randomised, double-blind, placebo-controlled, within-subjects design assessed 31 healthy participants (16 female, 15 male), aged between 21 and 58 years, over a two-week experimental protocol. Neurocognitive performance outcomes were assessed using the Cambridge Neuropsychological Test Automated Battery, with the Profile of Mood States questionnaire, and the Bond-Lader Visual Analogue Scale used to assess subjective state and mood. CannEpil increased Total Errors in Spatial Span and Correct Latency (median) in Pattern Recognition Memory, while also increasing Efficiency Score (lower score indicates greater efficiency) relative to placebo (all p < .05). Subjective Contentedness (p < .01) and Amicability (p < .05) were also increased at around 2.5 h post dosing, relative to placebo. Drowsiness or sedative effect was reported by 23 % of participants between three to six hours post CannEpil administration. Plasma concentrations of CBD, THC, and their metabolites were not significantly correlated with any observed alterations in neurocognition, subjective state, or adverse event occurrence. An acute dose of CannEpil impairs select aspects of visuospatial working memory and delayed pattern recognition, while largely preserving mood states among healthy individuals. Intermittent reports of drowsiness and sedation underscore the inter-individual variability of medicinal cannabis effects on subjective state. (ANZCTR; ACTRN12619000932167; https://www.anzctr.org.au).

A semi-naturalistic open-label study examining the effect of prescribed medical cannabis use on simulated driving performance.

BACKGROUND: Despite increasing medical cannabis use, research has yet to establish whether and to what extent products containing delta-9-tetrahydrocannabinol (THC) impact driving performance among patients. Stable doses of prescribed cannabinoid products during long-term treatment may alleviate clinical symptoms affecting cognitive and psychomotor performance. AIM: To examine the effects of open-label prescribed medical cannabis use on simulated driving performance among patients. METHODS: In a semi-naturalistic laboratory study, 40 adults (55% male) aged between 23 and 80 years, consumed their own prescribed medical cannabis product. Driving performance outcomes including standard deviation of lateral position (SDLP), the standard deviation of speed (SDS), mean speed and steering variability were evaluated using the Forum8 driving simulator at baseline (pre-dosing), 2.5 h and 5 -h (post-dosing). Perceived driving effort (PDE) was self-reported after each drive. Oral fluid and whole blood samples were collected at multiple timepoints and analysed for THC via liquid chromatography-mass spectrometry. RESULTS: A significant main effect of time was observed for mean speed (p = 0.014) and PDE (p = 0.020), with patients displaying modest stabilisation of vehicle control, increased adherence to speed limits and reductions in PDE post-dosing, relative to baseline. SDLP (p = 0.015) and PDE (p = 0.043) were elevated for those who consumed oil relative to flower-based products. Detectable THC concentrations were observed in oral fluid at 6-h post-dosing (range = 0-24 ng/mL). CONCLUSIONS: This semi-naturalistic study suggests that the consumption of medical cannabis containing THC (1.13-39.18 mg/dose) has a negligible impact on driving performance when used as prescribed.

A systematic review of oculomotor deficits associated with acute and chronic cannabis use.

Driving is a critical everyday task necessitating the rapid and seamless integration of dynamic visually derived information to guide neurobehaviour. Biological markers are frequently employed to detect Δ9-tetrahydrocannabinol (THC) consumption among drivers during roadside tests, despite not necessarily indicating impairment. Characterising THC-specific alterations to oculomotor behaviour may offer a more sensitive measure for indexing drug-related impairment, necessitating discrimination between acute THC effects, chronic use and potential tolerance effects. The present review aims to synthesise current evidence on the acute and chronic effects of THC on driving-relevant oculomotor behaviour. The review was prospectively registered (10.17605/OSF.IO/A4H9W), and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines informed reporting standards. Overall, 20 included articles comprising 12 experimental acute dosing trials, 5 cross-sectional chronic use studies and 3 roadside epidemiological studies examined the effects of cannabis/THC on oculomotor parameters including saccadic activity gaze behaviour, nystagmus, smooth pursuit and eyelid/blink characteristics. Acute THC consumption selectively impacts oculomotor control, notably increasing saccadic latency and inaccuracy and impairing inhibitory control. Chronic cannabis users, especially those with early age of use onset, display enduring oculomotor deficits that affect visual scanning efficiency. The presence of eyelid tremors appears to be a reliable indicator of cannabis consumption while remaining distinct from direct impairment associated with visual attention and motor control. Cannabis selectively influences oculomotor activity relevant to driving, highlighting the role of cannabinoid systems in these processes. Defining cannabis/THC-specific changes in oculomotor control may enhance the precision of roadside impairment assessments and vehicle safety systems to detect drug-related impairment and assess driving fitness.

Cannabidiol for moderate-severe insomnia: a randomized controlled pilot trial of 150 mg of nightly dosing.

STUDY OBJECTIVES: Low-dose cannabidiol (CBD) has become readily available in numerous countries; however, little consensus exists on its efficacy as a sleep aid. This trial explored the efficacy of 150 mg of CBD (n = 15) compared with placebo (n = 15) as a sleep aid in primary insomnia. CBD supplementation was hypothesized to decrease insomnia symptoms and improve aspects of psychological health, relative to placebo. METHODS: Using a randomized, placebo-controlled, parallel design featuring a single-blind placebo run-in week followed by a 2-week double-blind randomized dosing phase, participants consumed the assigned treatment sublingually 60 minutes before bed nightly. Wrist-actigraphy and sleep diaries measured daily sleep. Sleep quality, sleep effort, and well-being were measured weekly over 4 in-laboratory visits. Insomnia severity and trait anxiety were measured at screening and study conclusion. RESULTS: Insomnia severity, self-reported sleep-onset latency, sleep efficiency, and wake after sleep onset did not differ between treatments throughout the trial (all P > .05). Compared with placebo, the CBD group reported greater well-being scores throughout the trial (trial end mean difference = 2.60; standard error: 1.20), transient elevated behavior following wakefulness scores after 1 week of treatment (mean difference = 3.93; standard error: 1.53), and had superior objective sleep efficiency after 2 weeks of treatment (mean difference = 6.85; standard error: 2.95) (all P < .05). No other significant treatment effects were observed. CONCLUSIONS: Nightly supplementation of 150 mg CBD was similar to placebo regarding most sleep outcomes while sustaining greater well-being, suggesting more prominent psychological effects. Additional controlled trials examining varying treatment periods and doses are crucial. CLINICAL TRIAL REGISTRATION: Registry: Australian New Zealand Clinical Trials Registry; Name: Cannabidiol (CBD) treatment for insomnia; URL: https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12620000070932; Identifier: ACTRN12620000070932. CITATION: Narayan AJ, Downey LA, Rose S, Di Natale L, Hayley AC. Cannabidiol for moderate-severe insomnia: a randomized controlled pilot trial of 150 mg of nightly dosing. J Clin Sleep Med. 2024;20(5):753-763.

A Semi-Naturalistic, Open-Label Trial Examining the Effect of Prescribed Medical Cannabis on Neurocognitive Performance.

BACKGROUND AND OBJECTIVES: Medical cannabis use is increasing in Australia and other jurisdictions, yet little is known about the effects of medical cannabis on cognitive function. Findings from studies of non-medical ('recreational') cannabis may not be applicable to patients using prescribed medical cannabis to manage a health condition. METHODS: In this semi-naturalistic, open-label trial, patients with various health conditions attended a single laboratory session in which they self-administered a standard dose of prescribed medical cannabis as per instructions on the pharmacy label. We assessed cognitive performance using the Cambridge Neuropsychological Test Automated Battery (CANTAB) and Druid application (app) prior to and following (CANTAB: + 3 h; Druid: + 3 and 5.5 h) medical cannabis self-administration. We also assessed subjective drug effects prior to and following (1, 2 and 4 h) medical cannabis self-administration using a range of 0-10 cm visual analogue scales ('stoned', 'sedated', 'relaxed', 'comfortable', 'anxious' and 'confident'). Data were analyzed using linear fixed-effect models. RESULTS: Participants (N = 40; 22 females) were prescribed a range of products including orally administered oils (n = 23) and flower for vaporization (n = 17). Participants had a mean (standard deviation [SD]) age of 41.38 (12.66) years and had been using medical cannabis for a mean (SD) of 10.18 (8.73) months. Chronic non-cancer pain was the most common indication for medical cannabis use (n = 20), followed by sleep disorder (n = 18) and anxiety (n = 11). The mean (SD) delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) dose administered by participants was 9.61 (8.52) mg/9.15 (10.11) mg among those using an oil, and 37.00 (24.53) mg/0.38 (1.58) mg among those who vaporized flower, respectively. Participants' performance improved over time on the CANTAB Multitasking Test and Rapid Visual Information Processing test (both p-values <0.001). All other changes in cognitive performance measures over time were non-significant (p > 0.05). Vaporization of flower was associated with significantly stronger subjective feelings of 'stoned' and 'sedated' relative to oils (both p < 0.001). CONCLUSIONS: These findings suggest that prescribed medical cannabis may have minimal acute impact on cognitive function among patients with chronic health conditions, although larger and controlled trials are needed.

Acute administration of alprazolam, alcohol and their combination on cognitive performance and mood: A randomised, double-blind, placebo-controlled study.

BACKGROUND: Recreational co-consumption of benzodiazepines and alcohol is a common practise; yet, the cognitive effects of this combination remain poorly understood. This study aimed to investigate the acute cognitive effects of combining a 1 mg dose of alprazolam with a moderate dose of alcohol (target 0.04% blood alcohol concentration (BAC)) in a non-clinical population. METHODS: In this randomised, double-blind, placebo-controlled, crossover trial, participants completed computerised cognitive assessments and the brief biphasic alcohol effects scale (B-BAES) after consuming 1 mg of alprazolam, both with and without a moderate dose of alcohol (target 0.04% BAC). RESULTS: Among 20 healthy participants (mean age = 28.6, SD ± 4.0 years, 60% female), we found that a peak BAC of 0.03% had no significant impact on cognitive performance. Both the individual use of alprazolam and its combination with alcohol resulted in impaired reaction time, digit vigilance, and verbal, spatial and numeric working memory tasks, although an additive effect when alcohol and alprazolam were consumed together was not evident. The most pronounced cognitive effects occurred at 100 min after dosing, coinciding with increased alprazolam concentrations. Sedative effects were heightened with alcohol, alprazolam and their combination while no stimulative effects were reported. CONCLUSIONS: Our findings highlight the significant implications of a therapeutic dose of alprazolam on impairing cognitive performance. This is particularly relevant considering the frequency of non-medical alprazolam use. Future studies should explore different dosages, administration timings and long-term effects to inform the development of public health policies and guidelines regarding the combined use of alcohol and benzodiazepines.

Driving impairment and altered ocular activity under the effects of alprazolam and alcohol: A randomized, double-blind, placebo-controlled study.

BACKGROUND: Alprazolam, also known by trade-name Xanax, is regularly detected along with alcohol in blood samples of drivers injured or killed in traffic collisions. While their co-consumption is principally legal, policy guidelines concerning fitness-to-drive are lacking and methods to index impairment are underdeveloped. METHODS: In this randomized, double-blind, placebo-controlled, crossover trial, we examined whether legally permissible levels of alcohol [target 0.04% blood alcohol concentration (BAC)], alprazolam (1mg), and their combination impacts driving performance, and whether driving impairment can be indexed by ocular activity. Participants completed a test battery consisting of a 40-minute simulated highway drive with ocular parameters assessed simultaneously, the Karolinska Sleepiness Scale, and a confidence to drive assessment following four separate treatment combinations. The predictive efficacy of ocular parameters to identify alcohol and alprazolam-related driving impairment was also examined. RESULTS: Among 21 healthy, fully licensed drivers (37% female, mean age 28.43, SD ± 3.96), driving performance was significantly impacted by alprazolam, alcohol, and their combination. Linear regression models revealed that the odds of an out-of-lane event occurring increased five-fold under the influence alprazolam alone and when combined with alcohol. An increase in gaze transition entropy (GTE) demonstrated the strongest association with the odds of an out-of-lane event occurring in the same minute, with both microsleeps and fixation rate achieving moderate accuracy across treatments. CONCLUSIONS: Alprazolam and alcohol, alone and in combination, impaired select aspects of vehicle control over time. GTE, microsleeps, and fixation rate show potential as real-time indicators of driving impairment and crash risk associated with alcohol and alprazolam consumption.

Acute neurocognitive and subjective effects of oral methamphetamine with low doses of alcohol: A randomised controlled trial.

BACKGROUND: Methamphetamine is often recreationally co-consumed with alcohol due to desirable off-target effects; however, the acute neurocognitive and subjective consequences of combined use are unclear. METHODS: In a randomised, placebo-controlled, counterbalanced, cross-over study design, the effects of acute oral methamphetamine (0.42 mg/kg) were assessed with and without low doses of alcohol (target 0.04% blood-alcohol concentration, BAC) on subjective intoxication, alertness, physiological outcomes and neurocognition during the ascending and descending phases of the BAC curve. Sixteen healthy adults (mean age = 30.4 years, SD ± 4.4, 67% male) completed four experimental sessions over 4 weeks involving a one-week washout period. RESULTS: Cardiovascular measures [heart rate (beats/minute), blood pressure (mmHg)] were predictably elevated following methamphetamine, but unaffected by combined alcohol use. Methamphetamine and alcohol produce divergent effects on subjective alertness and sedation across time, yet their combination produced predominantly sustained stimulative effects independent of the biphasic alcohol curve. At a peak BAC of 0.029%, alcohol alone impaired performance across most functional neurocognitive domains relative to placebo and methamphetamine only, and the addition of methamphetamine attenuated these effects. Methamphetamine alone produced isolated improvement in psychomotor speed consistent with peak drug effects. CONCLUSION: Methamphetamine combined with alcohol does not substantially alter the physiological or metabolic profile compared to either drug alone. Strong stimulative effects of methamphetamine appear to mask the biphasic sedative and performance effects of low doses of alcohol, which may underlie motivations for co-consumption in recreational settings and increase propensity for harm.

Effect of CannEpil® on simulated driving performance and co-monitoring of ocular activity: A randomised controlled trial.

BACKGROUND: Medicinal cannabis products containing Δ9-tetrahydrocannabinol (THC) are increasingly accessible. Yet, policy guidelines regarding fitness to drive are lacking, and cannabinoid-specific indexations of impairment are underdeveloped. AIMS: To determine the impact of a standardised 1 mL sublingual dose of CannEpil®, a medicinal cannabis oil containing 100 mg cannabidiol (CBD) and 5 mg THC on simulated driving performance, relative to placebo and whether variations in vehicle control can be indexed by ocular activity. METHODS: A double-blind, within-subjects, randomised, placebo-controlled, crossover trial assessed 31 healthy fully licensed drivers (15 male, 16 female) aged between 21 and 58 years (M = 38.0, SD = 10.78). Standard deviation of lateral position (SDLP), standard deviation of speed (SDS) and steering variability were assessed over time and as a function of treatment during a 40 min simulated drive, with oculomotor parameters assessed simultaneously. Oral fluid and plasma were collected at 30 min and 2.5 h. RESULTS: CannEpil did not significantly alter SDLP across the full drive, although increased SDLP was observed between 20 and 30 min (p < 0.05). CannEpil increased SDS across the full drive (p < 0.05), with variance greatest at 20-30 min (p < 0.001). CannEpil increased fixation duration (p < 0.05), blink rate (trend p = 0.051) and decreased blink duration (p < 0.001) during driving. No significant correlations were observed between biological matrices and performance outcomes. CONCLUSIONS: CannEpil impairs select aspects of vehicle control (speed and weaving) over time. Alterations to ocular behaviour suggest that eye tracking may assist in determining cannabis-related driver impairment or intoxication. Australian and New Zealand Clinician Trials Registry, https://anzctr.org.au(ACTRN12619000932167).

Assessment of Medical Cannabis and Health-Related Quality of Life.

Importance: The use of cannabis as a medicine is becoming increasingly prevalent. Given the diverse range of conditions being treated with medical cannabis, as well as the vast array of products and dose forms available, clinical evidence incorporating patient-reported outcomes may help determine safety and efficacy. Objective: To assess whether patients using medical cannabis report improvements in health-related quality of life over time. Design, Setting, and Participants: This retrospective case series study was conducted at a network of specialist medical clinics (Emerald Clinics) located across Australia. Participants were patients who received treatment for any indication at any point between December 2018 and May 2022. Patients were followed up every mean (SD) 44.6 (30.1) days. Data for up to 15 follow-ups were reported. Statistical analysis was conducted from August to September 2022. Exposure: Medical cannabis. Product types and cannabinoid content varied over time in accordance with the treating physician's clinical judgement. Main Outcomes and Measures: The main outcome measure was health-related quality of life as assessed using the 36-Item Short Form Health Survey (SF-36) questionnaire. Results: In this case series of 3148 patients, 1688 (53.6%) were female; 820 (30.2%) were employed; and the mean (SD) age was 55.9 (18.7) years at baseline before treatment. Chronic noncancer pain was the most common indication for treatment (68.6% [2160 of 3148]), followed by cancer pain (6.0% [190 of 3148]), insomnia (4.8% [152 of 3148]), and anxiety (4.2% [132 of 3148]). After commencing treatment with medical cannabis, patients reported significant improvements relative to baseline on all 8 domains of the SF-36, and these improvements were mostly sustained over time. After controlling for potential confounders in a regression model, treatment with medical cannabis was associated with an improvement of 6.60 (95% CI, 4.57-8.63) points to 18.31 (95% CI, 15.86-20.77) points in SF-36 scores, depending on the domain (all P < .001). Effect sizes (Cohen d) ranged from 0.21 to 0.72. A total of 2919 adverse events were reported, including 2 that were considered serious. Conclusions and Relevance: In this case series study, patients using medical cannabis reported improvements in health-related quality of life, which were mostly sustained over time. Adverse events were rarely serious but common, highlighting the need for caution with prescribing medical cannabis.

The Incidence and Temporal Patterns of Use of Amphetamine-Type Stimulant Use in Traffic-Related Ambulance Attendances From 2015 to 2020 in Victoria, Australia.

OBJECTIVE: Amphetamine-type stimulants are increasingly implicated in road trauma incidents. Although ambulances are typically first to attend these emergencies, limited research has used paramedic clinical data to examine the contribution of amphetamine use to road trauma-related ambulance attendances. We describe the clinical and temporal risk profiles associated with amphetamine-related harm in road trauma incidents requiring paramedic attendance in the Australian state of Victoria. METHOD: This cross-sectional, retrospective observational study examined the Victorian component of a national surveillance data set (National Ambulance Surveillance System) of alcohol and other drug (AOD)-related ambulance attendances to determine the incidence and temporal profile of amphetamine use in traffic-related ambulance attendances from January 2015 to December 2020. RESULTS: Throughout the observation period, Victorian paramedics attended 8,163 alcohol, pharmaceutical, or illicit drug-related cases involving a road trauma. More than one quarter (2,161 cases, 27.4%) of these attendances were deemed related to the use of pharmaceutical and/or illicit drugs. Amphetamine alone was involved in nearly one third (640 cases, 29.6%) of non-alcohol-related road trauma attendances, and co-consumption of amphetamine with drugs other than alcohol occurred in more than one third (35.3%) of all AOD-related traffic incidents. Amphetamine-related road trauma attendances predominantly occurred on the weekend (Fri-Sun) during late night/early morning in metropolitan Melbourne. Between 2015 and 2020, the incidence of amphetamine-related road trauma ambulance attendances increased by 86.8%, from 1.1 per 100,000 population in 2015 to 1.9 per 100,000 population in 2020. CONCLUSIONS: Amphetamine-type stimulants are increasingly implicated in road trauma. Co-consumption with other potentially impairing substances reflects a concerning trend of polysubstance use among Victorian drivers.

Cannabinoid treatments for anxiety: A systematic review and consideration of the impact of sleep disturbance.

Cannabidiol's (CBD) safety profile and broad action has made it a popular treatment option for anxiety and co-occurring sleep disturbance. However, its efficacy in healthy and clinical populations, treatment duration, formulation and doses for optimal therapeutic benefits remains unclear. Selected databases were examined from inception to October 2022. Study selection, data extraction and Cochrane Risk of Bias assessments were conducted according to PRISMA guidelines and registered on the PROSPERO database (CRD42021247476) with 58 full-text studies meeting the eligibility criteria and administered CBD only or with Δ-9-tetrahydrocannabinol (THC) across healthy and clinical populations. In healthy populations and certain non-cannabis using clinical populations, CBD had greater anxiolytic effects without prominent effects on sleep. An inverted U-shaped dose relationship, and CBD ratio to THC in combined treatments likely moderated these effects. Mechanistically, observed CBD effects occurred via primary modulation of the endocannabinoid system and secondary regulation of neuroendocrine function. Additional research is needed to understand CBD mechanisms of action across diverse groups.

Effects of psychotropic drugs on ocular parameters relevant to traffic safety: A systematic review.

Driving is a complex neurobehavioural task necessitating the rapid selection, uptake, and processing of visual information. Eye movements that are critical for the execution of visually guided behaviour such as driving are also sensitive to the effects of psychotropic substances. The Embase (via Ovid), EBSCOHost, Psynet, Pubmed, Scopus and Web of Science databases were examined from January 01st, 2000 to December 31st, 2021. Study selection, data extraction and Cochrane Risk of Bias (RoB2) assessments were conducted according to PRISMA guidelines. The review was prospectively registered (CRD42021267554). In total, 36 full-text articles examined the effects of six principal psychotropic drug classes on measures of oculomotor parameters relevant to driving. Centrally depressing substances affect oculomotor responses in a dose-dependent manner. Psychostimulants improve maximal speed, but not accuracy, of visual search behaviours. Inhaled Δ-9-tetrahydrocannabinol (THC) increases inattention (saccadic inaccuracy) but does not consistently affect other oculomotor parameters. Alterations to composite ocular parameters due to psychoactive substance usage likely differently compromises performance precision during driving through impaired ability to select and process dynamic visual information.

The prevalence of alcohol use and risky driving practises among individuals who consume sedatives nonmedically: findings from the NESARC-III.

Background: Worldwide, 1.3 million people die because of a road traffic collision each year, with over half (57.7%) of such deaths in the United States involving a psychoactive substance. The prevalence of drink-drivers is slowly declining; however, the number of drivers under the influence of other drugs, such as sedatives, continues to rise.Objectives: This study aimed to examine alcohol use and risky driving practices among individuals who consume sedatives nonmedically.Methods: A total of 36,309 US adults (48.1% male) who participated in wave 3 (2012) of the National Epidemiologic Survey on Alcohol and Related Conditions were included for analysis.Results: Overall, 827 respondents reported past-year nonmedical sedative use. Almost two-third (64.9%) of these individuals exceeded recommended drinking guidelines and 42.5% met the criteria for a past-year DSM-5 alcohol use disorder. When controlling for demographic, lifestyle, and health factors, they were 1.84 times as likely to drink-drive (95% confidence interval = 1.46-2.33, p < .001) compared to those not using sedatives or using them as prescribed. Among those who reported both drink-driving and driving under the influence of sedatives in the last 12 months, 68.1% met the criteria for a past-year DSM-5 sedative use disorder.Conclusion: Several driving outcomes relevant to road safety, such as driving under the influence of alcohol or sedatives, are impacted by sedative consumption. Given that individuals who consume sedatives nonmedically may be unaware or misperceive the impacts of substance use on safe driving, interventions to reduce such behavior should be targeted among this high-risk group.

Acute effects of amphetamine and related psychostimulants on impulsivity: a systematic review of clinical trials.

Evidence for acute amphetamine effects on behavioural impulsivity in healthy populations remains elusive and, at times, mixed. This review collates and reviews the clinical literature on the acute effects of amphetamines on measures of behavioural impulsivity in healthy adults. Randomised and placebo-controlled clinical trials that assessed behavioural impulsivity following the administration of an acute dose of amphetamine or a related psychostimulant (including amphetamine analogues and methylphenidate) were eligible for inclusion. The EBSCOHost, SCOPUS, PsychNet, Web of Science and ProQuest databases were searched from inception to 26 April 2021. Study selection, data extraction and the Cochrane risk of bias assessments were conducted by two independent reviewers. Reporting follows PRISMA guidelines, and the review was registered a priori on the PROSPERO database (Registration No: CRD42021249861). A total of 20 studies were included, comprising a total of 737 participants. Overall, results indicate that low-moderate doses of amphetamine and related psychostimulants may improve (i.e., reduce) impulsive responding without compromising performance, reflecting enhanced inhibitory control of behaviour. These effects are mild and appear most pronounced in individuals with high baseline impulsivity. This review highlights the need for greater consistency in behavioural task selection and future high-quality and well-designed studies to address current concerns around growing prescription psychostimulant use and misuse.