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.

Default Mode Network Modulation by Psychedelics: A Systematic Review.

Psychedelics are a unique class of drug that commonly produce vivid hallucinations as well as profound psychological and mystical experiences. A grouping of interconnected brain regions characterized by increased temporal coherence at rest have been termed the Default Mode Network (DMN). The DMN has been the focus of numerous studies assessing its role in self-referencing, mind wandering, and autobiographical memories. Altered connectivity in the DMN has been associated with a range of neuropsychiatric conditions such as depression, anxiety, post-traumatic stress disorder, attention deficit hyperactive disorder, schizophrenia, and obsessive-compulsive disorder. To date, several studies have investigated how psychedelics modulate this network, but no comprehensive review, to our knowledge, has critically evaluated how major classical psychedelic agents-lysergic acid diethylamide, psilocybin, and ayahuasca-modulate the DMN. Here we present a systematic review of the knowledge base. Across psychedelics there is consistent acute disruption in resting state connectivity within the DMN and increased functional connectivity between canonical resting-state networks. Various models have been proposed to explain the cognitive mechanisms of psychedelics, and in one model DMN modulation is a central axiom. Although the DMN is consistently implicated in psychedelic studies, it is unclear how central the DMN is to the therapeutic potential of classical psychedelic agents. This article aims to provide the field with a comprehensive overview that can propel future research in such a way as to elucidate the neurocognitive mechanisms of psychedelics.

The impact of break duration, time of break onset, and prior shift duration on the amount of sleep between shifts in heavy vehicle drivers.

This study aimed to examine the impact of break duration between consecutive shifts, time of break onset, and prior shift duration on total sleep time (TST) between shifts in heavy vehicle drivers (HVDs), and to assess the interaction between break duration and time of break onset. The sleep (actigraphy and sleep diaries) and work shifts (work diaries) of 27 HVDs were monitored during their usual work schedule for up to 9 weeks. Differences in TST between consecutive shifts and days off were assessed. Linear mixed models (followed by pairwise comparisons) assessed whether break duration, prior shift duration, time of break onset, and the interaction between break duration and break onset were related to TST between shifts. Investigators found TST between consecutive shifts (mean [SD] 6.38 [1.38] h) was significantly less than on days off (mean [SD] 7.63 [1.93] h; p < 0.001). Breaks starting between 12:01 and 8:00 a.m. led to shorter sleep (p < 0.05) compared to breaks starting between 4:01 and 8:00 p.m. Break durations up to 7, 9, and 11 h (Australian and European minimum break durations) resulted in a mean (SD) of 4.76 (1.06), 5.66 (0.77), and 6.41 (1.06) h of sleep, respectively. The impact of shift duration prior to the break and the interaction between break duration and time of break were not significant. HVDs' sleep between workdays is influenced independently by break duration and time of break onset. This naturalistic study provides evidence that current break regulations prevent sufficient sleep duration in this industry. Work regulations should evaluate appropriate break durations and break onset times to allow longer sleep opportunities for HVDs.

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.

Effects of Bacopa monnieri (CDRI 08®) in a population of males exhibiting inattention and hyperactivity aged 6 to 14 years: A randomized, double-blind, placebo-controlled trial.

The current study investigated the efficacy of extract of Bacopa monnieri (BM; CDRI 08®) in reducing levels of inattention and hyperactivity in young children. BM has demonstrated improvements in cognitive outcomes in adults, yet little research is available on its effects in younger populations. A 14-week randomized, double-blind, placebo-controlled clinical trial, with placebo run-in and run-out phases, investigated the effects of BM on behavioural, cognitive, mood, and sleep effects in male children aged 6 to 14 years against placebo. One-hundred and twelve participants were recruited into the trial, with 93 datasets available for analysis. No significant behavioural differences were noted between treatment groups. Cognitive outcomes indicated decreased error-making in children taking CDRI 08® (p = .04) and increased speed of reaction time in those taking placebo (p = .04) at study end. Improvements in cognitive flexibility (p = .01), executive functioning (p = .04), interpersonal problems (p = .02), and sleep routine (p = .04) were noted in those consuming CDRI 08® over placebo. CDRI 08® did not improve behavioural outcomes, but may have cognitive, mood and sleep benefits in children aged 6 to 14 years. Further study is required to support the findings presented here.

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.

Neurotrophins as a reliable biomarker for brain function, structure and cognition: A systematic review and meta-analysis.

Neurotrophins are signalling molecules involved in the formation and maintenance of synapses in the brain. They can cross the blood-brain barrier and be detected in peripheral blood, suggesting they may be a potential biomarker for brain health and function. In this review, the available literature was systematically searched for studies comparing peripheral neurotrophins levels with MRI and cognitive measures in healthy adults. Twenty-four studies were identified, six of which included a neuroimaging outcome. Fifteen studies measuring cognition were eligible for meta-analysis. The majority of studies measured levels of brain-derived neurotrophic factor (BDNF), with few assessing other neurotrophins. Results revealed BDNF is related to some neuroimaging outcomes, with some studies suggesting older age may be an important factor. A higher proportion of studies who had older samples observed significant effects between cognition and neurotrophin levels. When cognitive studies were pooled together in a meta-analysis, there was a weak non-significant effect between BDNF and cognitive outcomes. There was also a high level of heterogeneity between cognitive studies. Results indicated that gender was a notable source of the heterogeneity, but additional studies employing relevant covariates are necessary to better characterise the inter-relationship between circulating neurotrophins and cognition.

Driving Simulator Performance After Administration of Analgesic Doses of Ketamine With Dexmedetomidine or Fentanyl.

PURPOSE/BACKGROUND: As a sole agent, ketamine acutely compromises driving ability; however, performance after coadministration with the adjuvant sedating agents dexmedetomidine or fentanyl is unclear. METHODS/PROCEDURES: Using a randomized within-subject design, 39 participants (mean ± SD age, 28.4 ± 5.8 years) received 0.3 mg/kg bolus followed by 0.15 mg kg h infusion of ketamine (3-hour duration), in addition to either (i) 0.7 µg kg h infusion of dexmedetomidine for 1.5 hours (n = 19; KET/DEX) or (ii) three 25 µg fentanyl injections for 1.5 hours (n = 20; KET/FENT). Whole blood drug concentrations were determined during ketamine only, at coadministration (KET/DEX or KET/FENT) and at 2 hours after treatment. Subjective effects were determined using a standardized visual analog scale. Driving performance was assessed at baseline and at posttreatment using a validated computerized driving simulator. Primary outcomes included SD of lateral position (SDLP) and steering variability (SV). FINDINGS/RESULTS: Administration of ketamine with dexmedetomidine but not fentanyl significantly increased SDLP (F1,18 = 22.60, P < 0.001) and reduced SV (F1,18 = 164.42, P < 0.001) 2 hours after treatment. These deficits were comparatively greater for the KET/DEX group than for the KET/FENT group (t37 = -5.21 [P < 0.001] and t37 = 5.22 [P < 0.001], (respectively). For the KET/DEX group, vehicle control (SV) and self-rated performance (visual analog scale), but not SDLP, was inversely associated with ketamine and norketamine blood concentrations (in nanograms per milliliter). Greater subjective effects were moderately associated with driving deficits. IMPLICATIONS/CONCLUSIONS: Driving simulator performance is significantly compromised after coadministration of analgesic range doses of ketamine with dexmedetomidine but not fentanyl. An extended period of supervised driver abstinence is recommended after treatment, with completion of additional assessments to evaluate home readiness.

When should the driver with a history of substance misuse be allowed to return to the wheel? A review of the substance misuse section of the Australian national guidelines.

Assessing fitness to drive in applicants with a historical or current substance use disorder presents a specific clinical challenge. The Australian guidelines require evidence of remission and absence of cognitive change when considering applications for re-licensing driver or individuals applying to reengage in safety-sensitive work. This paper reviews some of the clinical and biochemical indicators that determine whether a particular person is in 'remission' and meets the criteria for return to driving or other safety-sensitive occupation. It provides an overview of the challenges in establishing an evidence-based approach to determining fitness for safety critical activities. There is no internationally accepted definition of 'remission'. Review of the literature and examination of assessment protocols from other national jurisdictions are available for alcohol and the more important drugs of interest in road safety. Assessing fitness to drive when there is a history of substance misuse and/or substance use disorders is a complex issue that requires assessment of biomarkers, clinical findings and clinical assessment before the person returns to driving. We propose that hair testing provides a reliable and reproducible way to demonstrate remission and provide cost-effective monitoring. Standardised psychological tests could provide a reproducible assessment of the cognitive effects of drug use and suitability to resume driving. We recommend that AustRoads amend the national guidelines to reflect an evidence-based approach to assessing fitness to drive after conviction for offences related to alcohol and drug use.

Recreational stimulants, herbal, and spice cannabis: The core psychobiological processes that underlie their damaging effects.

AIMS: Recreational drugs are taken for their positive mood effects, yet their regular usage damages well-being. The psychobiological mechanisms underlying these damaging effects will be debated. METHODS: The empirical literature on recreational cannabinoids and stimulant drugs is reviewed. A theoretical explanation for how they cause similar types of damage is outlined. RESULTS: All psychoactive drugs cause moods and psychological states to fluctuate. The acute mood gains underlie their recreational usage, while the mood deficits on withdrawal explain their addictiveness. Cyclical mood changes are found with every central nervous system stimulant and also occur with cannabis. These mood state changes provide a surface index for more profound psychobiological fluctuations. Homeostatic balance is altered, with repetitive disturbances of the hypothalamic-pituitary-adrenal axis, and disrupted cortisol-neurohormonal secretions. Hence, these drugs cause increased stress, disturbed sleep, neurocognitive impairments, altered brain activity, and psychiatric vulnerability. Equivalent deficits occur with novel psychoactive stimulants such as mephedrone and artificial "spice" cannabinoids. These psychobiological fluctuations underlie drug dependency and make cessation difficult. Psychobiological stability and homeostatic balance are optimally restored by quitting psychoactive drugs. CONCLUSIONS: Recreational stimulants such as cocaine or MDMA (3.4-methylenedioxymethamphetamine) and sedative drugs such as cannabis damage human homeostasis and well-being through similar core psychobiological mechanisms.

DSM-5 Tobacco Use Disorder and Sleep Disturbance: Findings from the National Epidemiologic Survey on Alcohol and Related Conditions-III (NESARC-III).

INTRODUCTION: The DSM-5 Tobacco use disorder diagnosis incorporates tobacco misuse, addictive behaviors and withdrawal symptomology. Tobacco use is bidirectionally associated with sleep pathology; however, no epidemiological studies have yet evaluated the associations between DSM-5 Tobacco use disorder and self-reported sleep disturbance. The current study aimed to evaluate health, medical and sleep-related factors among individuals within this diagnostic stratum. METHOD: A total of N = 36,177 adults who participated in the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC-III) were included for analyses. The adjusted odd ratios (AOR) for individual classifications of DSM-5 Tobacco use disorder among those with subjective sleep disturbances were used as the primary outcome measure and relevant demographic, clinical and medical factors were considered in all univariate and multivariable analyses. RESULTS: Current and lifetime DSM-5 tobacco use disorder diagnoses were associated with poorer health and medical outcomes and higher rates of subjective sleep disturbances (all p < 0.001). Associations between current and lifetime DSM-5 tobacco use disorder and subjective sleep disturbances were maintained in multivariable analyses following adjustment for a range of health, lifestyle, and psychiatric factors (adjusted OR 1.11, 95%CI 1.00-1.23 and adjusted OR = 1.24, 95%CI 1.15-1.34, respectively); however, these relationships were fully explained by diagnoses of DSM-5 alcohol use disorder. CONCLUSIONS: Data from this large, representative survey indicate that the association between DSM-5 Tobacco use disorder and sleep disturbance is explained by underlying diagnoses of DSM-5 alcohol use disorder. Multifaceted substance abuse treatment protocols may improve treatment outcomes for affected patient groups.

Social and emotional loneliness and self-reported difficulty initiating and maintaining sleep (DIMS) in a sample of Norwegian university students.

Social and emotional loneliness negatively impact several areas of health, including sleep. However, few comprehensive population-based studies have evaluated this relationship. Over 12,000 students aged 21-35 years who participated in the student survey for higher education in Norway (the SHoT study) were assessed. Loneliness was assessed using the Social and Emotional Loneliness Scale. Difficulty initiating and maintaining sleep (DIMS) was assessed by a single-item subjective response on the depression scale of the Hopkins Symptoms Checklist (HSCL-25). Social loneliness was associated with more serious DIMS (unadjusted proportional odds-ratio [OR] = 2.69, 95% CI = 2.46-2.95). This association was attenuated following adjustment for anxiety (adjusted OR = 1.92, 95% CI = 1.75-2.10) and depression (adjusted OR = 1.48, 95% CI = 1.34-1.63), however was not substantially altered when all demographics and psychological distress were accounted for (fully adjusted OR = 1.46, 95% CI = 1.30-1.63). Emotional loneliness was also associated with more serious DIMS (unadjusted proportional OR = 2.33, 95% CI = 2.12-2.57). Adjustment for anxiety (adjusted OR = 1.96, 95% CI = 1.78-2.15) and depression (adjusted OR = 1.64, 95% CI = 1.48-1.80) attenuated, but did not extinguish this relationship in the fully adjusted model (adjusted OR = 1.22, 95% CI = 1.09-1.31). Mediation analyses revealed that the social loneliness-DIMS association was fully attributed to psychological distress, while the emotional loneliness-DIMS association was only partially mediated, and a direct association was still observed. Associations between social and emotional loneliness and subjective DIMS were embedded in a larger pattern of psychological distress. Mitigating underlying feelings of loneliness may reduce potentially deleterious effects on sleep health and psychological wellbeing in young adults.

Reduced memory skills and increased hair cortisol levels in recent Ecstasy/MDMA users: significant but independent neurocognitive and neurohormonal deficits.

OBJECTIVES: The goals of this study were to measure the neurocognitive performance of recent users of recreational Ecstasy and investigate whether it was associated with the stress hormone cortisol. METHODS: The 101 participants included 27 recent light users of Ecstasy (one to four times in the last 3 months), 23 recent heavier Ecstasy users (five or more times) and 51 non-users. Rivermead paragraph recall provided an objective measure for immediate and delayed recall. The prospective and retrospective memory questionnaire provided a subjective index of memory deficits. Cortisol levels were taken from near-scalp 3-month hair samples. RESULTS: Cortisol was significantly raised in recent heavy Ecstasy users compared with controls, whereas hair cortisol in light Ecstasy users was not raised. Both Ecstasy groups were significantly impaired on the Rivermead delayed word recall, and both groups reported significantly more retrospective and prospective memory problems. Stepwise regression confirmed that lifetime Ecstasy predicted the extent of these memory deficits. CONCLUSIONS: Recreational Ecstasy is associated with increased levels of the bio-energetic stress hormone cortisol and significant memory impairments. No significant relationship between cortisol and the cognitive deficits was observed. Ecstasy users did display evidence of a metacognitive deficit, with the strength of the correlations between objective and subjective memory performances being significantly lower in the Ecstasy users.

MDMA, cortisol, and heightened stress in recreational ecstasy users.

Stress develops when an organism requires additional metabolic resources to cope with demanding situations. This review will debate how recreational 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') can increase some aspects of acute and chronic stress in humans. Laboratory studies on the acute effects of MDMA on cortisol release and neurohormone levels in drug-free regular ecstasy/MDMA users have been reviewed, and the role of the hypothalamic-pituitary-adrenal (HPA) axis in chronic changes in anxiety, stress, and cognitive coping is debated. In the laboratory, acute ecstasy/MDMA use can increase cortisol levels by 100-200%, whereas ecstasy/MDMA-using dance clubbers experience an 800% increase in cortisol levels, because of the combined effects of the stimulant drug and dancing. Three-month hair samples of abstinent users revealed cortisol levels 400% higher than those in controls. Chronic users show heightened cortisol release in stressful environments and deficits in complex neurocognitive tasks. Event-related evoked response potential studies show altered patterns of brain activation, suggestive of increased mental effort, during basic information processing. Chronic mood deficits include more daily stress and higher depression in susceptible individuals. We conclude that ecstasy/MDMA increases cortisol levels acutely and subchronically and that changes in the HPA axis may explain why recreational ecstasy/MDMA users show various aspects of neuropsychobiological stress.

Reducing occupational stress with a B-vitamin focussed intervention: a randomized clinical trial: study protocol.

BACKGROUND: Workplace stress in Australia and other western countries has been steadily increasing over the past decade. It can be observed not only in terms of increased compensation claims but also costs due to absenteeism, loss of productivity at work and reduced psychological and physiological health and well-being. Given the cost and pervasive effects of stress in the modern workforce, time efficient and cost-effective interventions capable of reducing occupational stress (or strain) and burnout are urgently required for the improved well-being of stressed employees. One intervention gaining scientific traction is supplementation with nutritional interventions, particularly the B group vitamins. METHODS: This study was developed to examine the effects of B group vitamins on workplace stress and mood variables with a sample of full-time employed older adults who subjectively report feeling stressed. The study is a randomized, double-blind, placebo-controlled, parallel-groups clinical trial where 200 (N = 100/group) participants will be randomized to receive Blackmores® Executive B Stress Formula or placebo daily for a period of 6 months. Participants will be tested at baseline and 6 months post-randomization on workplace stress, cognitive, personality and mood measures, cardiovascular (brachial and aortic systolic and diastolic blood pressures as well as arterial stiffness), biochemical (assays to measure inflammation and safety) as well as genetic assessments (to assess stress processing) and neuroimaging measures (to investigate in vivo mechanisms of action of B vitamins). In addition to this pre- and post- supplementation testing, participants will also complete a battery of self-report questionnaires online to assess their stress and mood once a month for the duration of the study. The primary aim of the study is to investigate the effects of B vitamin supplementation on work related stress. The secondary aims are to explore the mechanisms underpinning any changes in mood or workplace stress due to the B vitamin intervention by examining relationships between cognitive, biological, neuroimaging and cardiovascular variables over 6 months. A subset of 40 participants (N = 20/group) will undergo neuroimaging at baseline and at 6 months using functional magnetic resonance imaging (fMRI) and magnetic resonance spectroscopy (MRS) in order to further explore in vivo mechanisms of action of B vitamins. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR):ACTRN12613000294752.

An acute, double-blind, placebo-controlled cross-over study of 320 mg and 640 mg doses of Bacopa monnieri (CDRI 08) on multitasking stress reactivity and mood.

Little research exists in humans concerning the anxiolytic, antidepressant, sedative, and adaptogenic actions the traditional Ayurvedic medicine Bacopa monnieri (BM) possesses in addition to its documented cognitive-enhancing effects. Preclinical work has identified a number of acute anxiolytic, nootropic, and adaptogenic effects of BM that may also co-occur in humans. The current double-blind, placebo-controlled cross-over study assessed the acute effects of a specific extract of BM (KeenMind® - CDRI 08) in normal healthy participants during completion of a multitasking framework (MTF). Seventeen healthy volunteers completed the MTF, at baseline, then 1 h and 2 h after consuming a placebo, 320 mg BM and 640 mg of BM. Treatments were separated by a 7-day washout with order determined by Latin Square. Outcome measures included cognitive outcomes from the MTF, with mood and salivary cortisol measured before and after each completion of the MTF. Change from baseline scores indicated positive cognitive effects, notably at both 1 h post and 2 h post BM consumption on the Letter Search and Stroop tasks, suggesting an earlier nootropic effect of BM than previously investigated. There were also some positive mood effects and reduction in cortisol levels, pointing to a physiological mechanism for stress reduction associated with BM consumption. It was concluded that acute BM supplementation produced some adaptogenic and nootropic effects that need to be replicated in a larger sample and in isolation from stressful cognitive tests in order to quantify the magnitude of these effects. The study was registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12612000834853).

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.