Increased Posterior Cingulate Functional Connectivity Following 6-Month High-Dose B-Vitamin Multivitamin Supplementation: A Randomized, Double-Blind, Placebo-Controlled Trial.

B vitamins are essential for optimal brain and body function, and are particularly important for cortical metabolic processes that have downstream effects on mitigating oxidative stress. Oxidative stress has been linked to poor psychological outcomes including psychological distress, which has wide-reaching implications for the community and the workplace. Given work-related stress has been associated with poor mental health outcomes, high-dose B vitamin supplementation may be effective in improving brain function and psychological outcomes via attenuation of oxidative stress. This randomized, double-blind, placebo-controlled study investigated psychological outcomes following 6-month supplementation of a high-B-vitamin multivitamin in a large sample of healthy adults (n = 108, aged 30-70 years), as well as changes in default mode network functional connectivity in a subset of the original sample (n = 28). Improvements in occupational stress, general health, perceived stress, depressive symptoms, and mood profiles were identified for both active and placebo groups over time (p < 0.05 corrected). Seed-based functional connectivity analysis centered on the posterior cingulate cortex (PCC) showed that connectivity between the PCC and the caudate increased for the active treatment group, but decreased for the placebo group (p < 0.05 corrected). These findings reveal a substantial intervention effect for both active and placebo treatments, which could in part be associated with a placebo effect in subjective measures. There was, however, a significant treatment effect in the objective measure of functional connectivity, suggesting that reduced psychological stress and high-B-vitamin multivitamin supplementation may lead to an increase in DMN and caudate functional connectivity, which might reflect a strengthening of neurocircuitry within areas associated with reward and emotion at rest. Future studies should consider a placebo run-in methodology to reduce the placebo effect on the subjective measures of stress.

Risky driving behaviours among stimulant drug users and the role of aggression: findings from a national survey.

BACKGROUND AND AIMS: Stimulant drug users have a greater prevalence of risky driving behaviour. This study aimed to assess how far this association remains after adjusting for aggressiveness. DESIGN: Cross-sectional interview study assessing associations between measures of risky driving behaviours as outcomes, measures of stimulant drug use as predictors and a measure of aggressiveness as a covariate. SETTING: United States. PARTICIPANTS: Data were drawn from wave 3 (2012-13) of the National Epidemiological Survey on Alcohol and Related Conditions (NESARC-III) (n = 36 309 aged ≥ 18 years). MEASUREMENTS: Stimulant drug use, past-year DSM-5 stimulant use disorder, aggression and measures of risky driving were assessed using face-to-face interviews conducted using the Alcohol Use Disorder and Associated Disabilities Interview Schedule (AUDADIS-5) and the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5). FINDINGS: Overall, 2714 (8.3%) respondents indicated life-time stimulant use, and 112 (0.3%) met criteria for past-year DSM-5 stimulant use disorder. More than 10% of ongoing stimulant users and one-third of respondents with DSM-5 stimulant use disorder reported stimulant-specific driving under the influence of drugs (DUID) in the past-year (both P < 0.0001). Adjusted for demographics and independent of aggression, life-time stimulant users reported increased likelihood of driving [adjusted odds ratio (aOR) = 3.00, 95% confidence interval (CI) = 2.63-3.42] or speeding under the influence of drugs (aOR = 3.39, 95% CI = 3.01-3.82) and licence revocation (aOR = 2.16, 95% CI = 1.87-2.50) (all P < 0.0001). Past-year DSM-5 stimulant use disorder was associated with all outcomes (aOR = 5.48, 95% CI = 2.95-10.18 and aOR = 3.87, 95% CI = 2.23-6.70, respectively, all P < 0.0001), except licence revocation (aOR = 1.72). CONCLUSIONS: Stimulant use appears to be positively associated with risky driving behaviours after adjusting for aggressiveness.

The acute and residual effects of escalating, analgesic-range doses of ketamine on driving performance: A simulator study.

Ketamine hydrochloride elicits potent psychotomimetic and neurobehavioural effects which make it incompatible with driving; however, the direct effect on driving performance is yet to be assessed. Using an open label, within-subjects protocol, 15 males and 5 females (mean age = 30.8 years) were administered three fixed, stepwise increasing sub-anaesthetic doses of intravenous (IV) ketamine solution [(i) 8 mg/h IV infusion plus 30 mg bolus, (ii) 12 mg/h IV infusion and (iii) 20 mg/h infusion]. Whole blood ketamine and norketamine concentrations were determined at each treatment step and at 2 h post-infusion. Driving performance was assessed at baseline, at each treatment step and at 2 h post-treatment using a validated computerised driving simulator. Standard Deviation of Lateral Position (SDLP) and Steering Variability (SV) were assessed. Linear Fixed Effect Modelling indicated a main effect for time (dose) for SDLP (F[4,72] = 33.22, p < 0.0001) and SV (F[4,72] = 4.65, p < 0.002). Post-hoc analyses revealed significant differences from baseline at each treatment step for SDLP (all p < 0.001), and for 12 mg/h treatment step for SV (p = 0.049). Post-treatment driving performance returned to baseline levels. Weak positive linear associations were observed between SDLP and whole blood ketamine concentrations (R2 = 0.11, ß = 29.96, p = 0.001) and norketamine (R2 = 0.09, ß = 28.87, p = 0.003). These findings suggest that even under highly controlled conditions, ketamine intoxication significantly alters simulated driving performance. At the highest dose, ketamine produced changes to SDLP considered incompatible with safe driving, highlighting how ketamine consumption may translate to an increased risk of road trauma.

Detection of delta-9-tetrahydrocannabinol (THC) in oral fluid, blood and urine following oral consumption of low-content THC hemp oil.

Hemp-derivative (Cannabis sativa L.) food products containing trace levels of Δ-9-tetrahydrocannabinol (THC) are proposed for consumption in Australia and New Zealand; however, it is unclear whether use of these products will negatively affect existing drug screening protocols. This double-blind, within-subjects, cross-over trial assessed 35 adults (17 male; 18 female), aged 22-52 years [Mean=30.7, Standard Deviation (S.D)±7.6]. Low dose THC oil [5mL bearer sesame oil containing 10mg/kg THC (0.046mg THC per 5mL dose)]; high dose THC oil [5mL bearer sesame oil containing 20mg/kg THC (0.092mg THC per 5mL dose)]; and a placebo oil (THC negative) was consumed during a three-week protocol. The Securetec Drugwipe® II Twin device assessed THC presence (cut-off 20ng/mL) in oral fluid at baseline, at 5, 30, 60, 120 and 240min post-treatment. Blood was drawn at baseline, 30, 120 and 240min post-treatment, and urine at baseline and 240min post-treatment. No THC was detected in oral fluid, blood or urine samples at any time-point following consumption of the low or high THC dose. Trace concentrations of 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid (THCa) were detected in blood 4-h after consumption of the high THC treatment (M=0.0001mg/L) and in urine at 4-h post consumption of both low and high THC treatments (M=0.0001mg/L and 0.0004mg/L, respectively). Consumption of low-content THC oil does not result in positive biological assessments. It is therefore highly unlikely that ingestion of products containing these levels of THC will negatively impact existing region-specific drug driving enforcement protocols.

An evaluation of the sensitivity of the standardised field sobriety tests to detect the presence of amphetamine.

RATIONALE: The Standardised Field Sobriety Tests (SFSTs), designed and validated to assess impairment associated with alcohol intoxication, are currently being employed by the Victoria Police (Australia) for the identification of driving impairment associated with drugs other than alcohol. OBJECTIVES: The aim of this study was to evaluate whether the SFSTs are a sensitive measure for identifying the presence of dexamphetamine and methamphetamine. METHODS: Three studies each employed a repeated-measures, counterbalanced, double-blind placebo-controlled design. In each study, 20 healthy volunteers completed two treatment conditions: either 0.42 mg/kg d,l-dexamphetamine and placebo, 0.42 mg/kg d,l-methamphetamine and placebo, or 0.42 mg/kg d-methamphetamine and placebo. Performance was assessed using the SFSTs, consisting of the Horizontal Gaze Nystagmus test, the Walk and Turn test, and the One Leg Stand test. Blood and saliva samples were obtained before and immediately after the administration of the SFSTs (120 and 170 min post drug administration). RESULTS: At 120 and 170 min post drug administration, d,l-dexamphetamine blood levels were 83.16 and 98.42 ng/ml, respectively; d,l-methamphetamine levels were 90 and 95 ng/ml, respectively; and d-methamphetamine blood levels were 72 and 67 ng/ml, respectively. None of the three amphetamine doses impaired performance on the SFSTs. Using the SFSTs, the presence of dexamphetamine was identified in 5% of cases, d-methamphetamine in 5%, and d,l-methamphetamine in 0% of cases. CONCLUSIONS: Under these conditions, the SFSTs are not a sensitive measure for detecting the presence of low levels of amphetamine.

Hemispheric asymmetries for visual and auditory temporal processing: an evoked potential study.

Lateralization for temporal processing was investigated using evoked potentials to an auditory and visual gap detection task in 12 dextral adults. The auditory stimuli consisted of 300-ms bursts of white noise, half of which contained an interruption lasting 4 or 6 ms. The visual stimuli consisted of 130-ms flashes of light, half of which contained a gap lasting 6 or 8 ms. The stimuli were presented bilaterally to both ears or both visual fields. Participants made a forced two-choice discrimination using a bimanual response. Manipulations of the task had no effect on the early evoked components. However, an effect was observed for a late positive component, which occurred approximately 300-400 ms following gap presentation. This component tended to be later and lower in amplitude for the more difficult stimulus conditions. An index of the capacity to discriminate gap from no-gap stimuli was gained by calculating the difference waveform between these conditions. The peak of the difference waveform was delayed for the short-gap stimuli relative to the long-gap stimuli, reflecting decreased levels of difficulty associated with the latter stimuli. Topographic maps of the difference waveforms revealed a prominence over the left hemisphere. The visual stimuli had an occipital parietal focus whereas the auditory stimuli were parietally centered. These results confirm the importance of the left hemisphere for temporal processing and demonstrate that it is not the result of a hemispatial attentional bias or a peripheral sensory asymmetry.