Effects of cannabidiol on psychosocial stress, situational anxiety and nausea in a virtual reality environment: a protocol for a single-centre randomised clinical trial.

INTRODUCTION: The non-intoxicating plant-derived cannabinoid, cannabidiol (CBD), has demonstrated therapeutic potential in a number of clinical conditions. Most successful clinical trials have used relatively high (≥300 mg) oral doses of CBD. Relatively few studies have investigated the efficacy of lower (<300 mg) oral doses, typical of those available in over-the-counter CBD products. METHODS: We present a protocol for a randomised, double-blind, placebo-controlled, parallel-group clinical trial investigating the effects of a low oral dose (150 mg) of CBD on acute psychosocial stress, situational anxiety, motion sickness and cybersickness in healthy individuals. Participants (n=74) will receive 150 mg of CBD or a matched placebo 90 min before completing three virtual reality (VR) challenges (tasks) designed to induce transient stress and motion sickness: (a) a 15 min 'Public Speaking' task; (b) a 5 min 'Walk the Plank' task (above a sheer drop); and (c) a 5 min 'Rollercoaster Ride' task. The primary outcomes will be self-reported stress and nausea measured on 100 mm Visual Analogue Scales. Secondary outcomes will include salivary cortisol concentrations, skin conductance, heart rate and vomiting episodes (if any). Statistical analyses will test the hypothesis that CBD reduces nausea and attenuates subjective, endocrine and physiological responses to stress compared with placebo. This study will indicate whether low-dose oral CBD has positive effects in reducing acute psychosocial stress, situational anxiety, motion sickness and cybersickness. ETHICS AND DISSEMINATION: The University of Sydney Human Research Ethics Committee has granted approval (2023/307, version 1.6, 16 February 2024). Study findings will be disseminated in a peer-reviewed journal and at academic conferences. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ACTRN12623000872639).

Detection of Δ9 -tetrahydrocannabinol (THC) in oral fluid using two point-of-collection testing devices following oral administration of a THC and cannabidiol containing oil.

Point-of-collection testing (POCT) devices are widely used in roadside and workplace drug testing to identify recent cannabis use by measuring the presence of Δ9 -tetrahydrocannabinol (THC) in oral fluid (OF). However, the performance of POCT devices with oral medicinal cannabis products remains poorly described. In a randomised, double-blinded, crossover trial, adults with insomnia disorder (n = 20) received a single (2 mL) oral dose of oil containing 10 mg THC + 200 mg cannabidiol, or placebo, prior to sleep. Participants were tested with the Securetec DrugWipe® 5S (10 ng/mL THC cut-off) and Dräger DrugTest® 5000 (25 ng/mL THC cut-off) POCT devices at baseline (pre-treatment) and then at 0.5, 10, and 18 h post-treatment. An OF sample, taken at each time point, was also analysed using liquid chromatography-tandem mass spectrometry. Large individual variability in OF THC concentrations was observed 0.5 h post-treatment (range: 0-425 ng/mL; mean (SD) 48.7 (107.5) ng/mL). Both the Securetec DrugWipe® 5S and DrugTest® 5000 demonstrated poor sensitivity to THC at 0.5 h post-treatment (25% and 50%, respectively). At 10 and 18 h post-treatment, all participant OF THC concentrations were below screening cut-offs, and all test results were negative. These findings highlight the relatively poor sensitivity of both devices in detecting recent use of an oral medicinal cannabis product. They also suggest a low probability of obtaining a positive THC result the morning after ('one-off') use. Further research is required to establish the probability of obtaining a positive THC result with regular medicinal cannabis use.

The effect of contact/collision sport participation without concussion on neurometabolites: A systematic review and meta-analysis of magnetic resonance spectroscopy studies.

The aim of this study was to systematically review prior research investigating the effects of contact/collision sport participation on neurometabolite levels in the absence of concussion. Four online databases were searched to identify studies that measured neurometabolite levels in contact/collision sport athletes (without concussion) using proton (1 H) or phosphorus (31 P) magnetic resonance spectroscopy (MRS). All study designs were acceptable for inclusion. Meta-analytic procedures were used to quantify the effect of contact/collision sport participation on neurometabolite levels and explore the impact of specific moderating factors (where sufficient data were available). Narrative synthesis was used to describe outcomes that could not be meta-analysed. Nine observational studies involving 300 contact/collision sport athletes were identified. Six studies (providing 112 effect estimates) employed longitudinal (cohort) designs and three (that could not be meta-analysed) employed case-control designs. N-acetylaspartate (NAA; g = -0.331, p = 0.013) and total creatine (tCr; creatine + phosphocreatine; g = -0.524, p = 0.029), but not glutamate-glutamine (Glx), myo-inositol (mI) or total choline (tCho; choline-containing compounds; p's > 0.05), decreased between the pre-season and mid-/post-season period. Several moderators were statistically significant, including: sex (Glx: 6 female/23 male, g = -0.549, p = 0.013), sport played (Glx: 22 American football/4 association football [soccer], g = 0.724, p = 0.031), brain region (mI: 2 corpus callosum/9 motor cortex, g = -0.804, p = 0.015), and the MRS quantification approach (mI: 18 absolute/3 tCr-referenced, g = 0.619, p = 0.003; and tCho: 18 absolute/3 tCr-referenced, g = 0.554, p = 0.005). In case-control studies, contact/collision sport athletes had higher levels of mI, but not NAA or tCr compared to non-contact sport athletes and non-athlete controls. Overall, this review suggests that contact/collision sport participation has the potential to alter neurometabolites measured via 1 H MRS in the absence of concussion. However, further research employing more rigorous and consistent methodologies (e.g. interventional studies with consistent 1 H MRS pulse sequences and quantifications) is required to confirm and better understand the clinical relevance of observed effects.

Cannabinol (CBN; 30 and 300 mg) effects on sleep and next-day function in insomnia disorder ('CUPID' study): protocol for a randomised, double-blind, placebo-controlled, cross-over, three-arm, proof-of-concept trial.

OBJECTIVE: Insomnia is the most prevalent sleep disorder, with few effective pharmacotherapies. Anecdotal reports and recent preclinical research suggest that cannabinol (CBN), a constituent of Cannabis sativa derived from delta-9-tetrahydrocannabinol, could be an effective treatment. Despite this, the isolated effects of CBN on sleep have yet to be systematically studied in humans. METHODS: The present protocol paper describes a randomised, double-blind, placebo-controlled, single-dose, three-arm, cross-over, proof-of-concept study which investigates the effects of CBN on sleep and next-day function in 20 participants with clinician-diagnosed insomnia disorder and an Insomnia Severity Index Score ≥15. Participants receive a single fixed oral liquid dose of 30 mg CBN, 300 mg CBN and matched placebo, in random order on three treatment nights; each separated by a 2-week wash-out period. Participants undergo overnight sleep assessment using in-laboratory polysomnography and next-day neurobehavioural function tests. The primary outcome is wake after sleep onset minutes. Secondary outcomes include changes to traditional sleep staging, sleep-onset latency and absolute spectral power during non-rapid eye movement (NREM) sleep. Tertiary outcomes include changes to sleep spindles during NREM sleep, arousal indices, absolute spectral power during REM sleep and subjective sleep quality. Safety-related and exploratory outcomes include changes to next-day simulated driving performance, subjective mood and drug effects, postural sway, alertness and reaction time, overnight memory consolidation, pre and post-sleep subjective and objective sleepiness; and plasma, urinary, and salivary cannabinoid concentrations. The study will provide novel preliminary data on CBN efficacy and safety in insomnia disorder, which will inform larger clinical trials. ETHICS AND DISSEMINATION: Human Research Ethics Committee approval has been granted by Bellberry (2021-08-907). Study findings will be disseminated in a peer-reviewed journal and at academic conferences. TRIAL REGISTRATION NUMBER: NCT05344170.

A cross-sectional survey exploring the knowledge, experiences and attitudes of Australian pharmacists toward medicinal cannabis.

BACKGROUND: Australian pharmacists currently dispense a wide range of prescription-only cannabis-based medicines. Recent regulatory changes will expand the role of pharmacists, allowing certain low-dose cannabidiol products to be supplied without a prescription in pharmacies. This harmonises Australia with many other countries where cannabidiol products are readily available to consumers. AIM: To examine Australian pharmacists' experience, knowledge and attitudes towards medicinal cannabis and their preparedness to supply over-the-counter low-dose cannabidiol products. METHOD: We conducted a cross-sectional study using a 51-item on-line questionnaire that was informed by previous surveys of health professionals and assessed for face validity. Australian pharmacists were recruited to complete the survey between May and December 2021, primarily through professional pharmacy organisations. Pharmacists were included in the final dataset if they completed the demographic characteristics section and at least one additional section of the questionnaire. Data were analysed using descriptive and relational statistical tests. RESULTS: There were 272 attempts to complete this survey and 217 responses included in the final dataset. Over half of the respondents (60.0%, 130/217) had dispensed at least one medicinal cannabis prescription during their career and 58.5% (127/217) had received at least one medicinal cannabis enquiry in the last fortnight. Only around half (53.9%, 117/217) felt comfortable supplying medicinal cannabis products and fewer (39.3%, 79/201) were confident discussing cannabis-related enquiries. More than half of the respondents (58.7%, 118/201) supported the provision of low-dose cannabidiol products through pharmacies. Two-thirds (67.8%, 80/118) of respondents achieved relatively low scores (< 60%) in the knowledge component of the survey. Most respondents (94.2%, 178/189) endorsed a need for further training in this area. CONCLUSION: Australian pharmacists tended to support medicinal cannabis availability and improved access to low-dose cannabidiol products via pharmacies. However, results highlight a need for improved training and education of pharmacists around cannabis-based medicines.

The safety and efficacy of low oral doses of cannabidiol: An evaluation of the evidence.

Global interest in the non-intoxicating cannabis constituent, cannabidiol (CBD), is increasing with claims of therapeutic effects across a diversity of health conditions. At present, there is sufficient clinical trial evidence to support the use of high oral doses of CBD (e.g., 10-50 mg/kg) in treating intractable childhood epilepsies. However, a question remains as to whether "low-dose" CBD products confer any therapeutic benefits. This is an important question to answer, as low-dose CBD products are widely available in many countries, often as nutraceutical formulations. The present review therefore evaluated the efficacy and safety of low oral doses of CBD. The review includes interventional studies that measured the clinical efficacy in any health condition and/or safety and tolerability of oral CBD dosed at less than or equal to 400 mg per day in adult populations (i.e., ≥18 years of age). Studies were excluded if the product administered had a Δ9 -tetrahydrocannabinol content greater than 2.0%. Therapeutic benefits of CBD became more clearly evident at doses greater than or equal to 300 mg. Increased dosing from 60 to 400 mg/day did not appear to be associated with an increased frequency of adverse effects. At doses of 300-400 mg, there is evidence of efficacy with respect to reduced anxiety, as well as anti-addiction effects in drug-dependent individuals. More marginal and less consistent therapeutic effects on insomnia, neurological disorders, and chronic pain were also apparent. Larger more robust clinical trials are needed to confirm the therapeutic potential of lower (i.e., <300 mg/day) oral doses of CBD.

How long does a single oral dose of cannabidiol persist in plasma? Findings from three clinical trials.

A growing number of clinical trials (CTs) are investigating the therapeutic potential of cannabidiol (CBD), a non-intoxicating phytocannabinoid found in Cannabis sativa. These CTs often use crossover experimental designs requiring 'washout' (clearance) periods. However, the length of time CBD persists in plasma (its 'window of detection') is unclear and could be significant. Indeed, the structurally related phytocannabinoid, Δ9 -tetrahydrocannabinol (THC), has a long window of detection in plasma. We investigated the extent to which CBD and its major metabolites persist in plasma. Data from three CTs that measured plasma cannabinoid concentrations ≥7 days after administering a single oral dose of CBD were pooled. The CBD doses were as follows: CT #1: 300 mg; CT #2: 200 mg (and 10 mg THC); and CT #3: 15, 300 and 1500 mg (one per treatment session). Thirty-two participants were included in the analysis, 17 of whom (from CT #3) provided repeated measures. Overall, 0% (15 mg), 60% (200 mg), 28% (300 mg) and 100% (1500 mg) of participants had detectable concentrations (i.e., >0.25 ng·ml-1 ) of CBD in plasma ≥7 days post-treatment (some, several weeks post-treatment). A zero-inflated negative binomial mixed-effects regression analysis (R2 m = 0.44; R2 c = 0.73) predicted that, on average, a 13 day washout period would reduce plasma CBD concentrations to 'zero' (i.e., <0.25 ng·ml-1 ) if a single oral dose of 300 mg was consumed. Higher doses require longer washout periods; concomitant medications may also affect clearance. In conclusion, CBD has a long window of detection in plasma. Crossover studies involving CBD should, therefore, be conducted with caution, particularly when higher doses and/or chronic dosing regimens are used.

The "Next Day" Effects of Cannabis Use: A Systematic Review.

Background: Δ9-Tetrahydrocannabinol (THC), the main intoxicating component of cannabis, can cause cognitive and psychomotor impairment. Whether this impairment is still present many hours or even days after THC use requires clarification. Possible "next day" effects are of major significance in safety-sensitive workplaces. We therefore conducted a systematic review of studies investigating the "next day" effects of THC. Methods: Studies that measured performance on safety-sensitive tasks (e.g., driving, flying) and/or neuropsychological tests >8 h after THC (or cannabis) use using interventional designs were identified by searching two online databases from inception until March 28, 2022. Risk of bias (RoB) was evaluated using the relevant Cochrane tools. Results were described in terms of whether THC had a significant effect on performance relative to the primary comparator (i.e., placebo or baseline, as appropriate). Results: Twenty studies (n=458) involving 345 performance tests were reviewed. Most studies administered a single dose of THC (median [interquartile range]: 16 [11-26] mg) and assessed performance between >12 and 24 h post-treatment. N=209/345 tests conducted across 16 published studies showed no "next day" effects of THC. Nine of these 16 studies used randomized, double-blind, placebo-controlled designs. Half (N=8) had "some" RoB, and half (N=8) had a "high" RoB. Notably, N=88 of these 209 tests failed to demonstrate "acute" (i.e., <8 h post-treatment) THC-induced impairment. N=12/345 tests conducted across five published studies indicated negative (i.e., impairing) "next day" effects of THC. None of these five studies used randomized, double-blind, placebo-controlled designs and all were published >18 years ago (four, >30 years ago). Three had "some" RoB, and two had a "high" RoB. A further N=121/345 tests indicated "unclear" "next day" effects of THC with insufficient information provided to assess outcomes. The remaining N=3/345 tests indicated positive (i.e., enhancing) "next day" effects of THC. Conclusions: Some lower quality studies have reported "next day" effects of THC on cognitive function and safety-sensitive tasks. However, most studies, including some of higher quality, have found no such effect. Overall, it appears that there is limited scientific evidence to support the assertion that cannabis use impairs "next day" performance. Further studies involving improved methodologies are required to better address this issue.

Knowledge, experiences, and attitudes of Australian General Practitioners towards medicinal cannabis: a 2021-2022 survey.

BACKGROUND: Medicinal cannabis (MC) products have been available on prescription in Australia for around six years. General practitioners (GPs) are at the forefront of MC prescribing and recent years have seen substantial increases in prescription numbers. This study examined the current knowledge, experiences, and attitudes of Australian GPs around MC. We also compared our findings to those of an earlier 2017 investigation. METHOD: We conducted a cross-sectional study using a 42-item on-line questionnaire adapted from our earlier 2017 survey. The current survey was completed by GPs attending an on-line, multi-topic educational seminar. Australian GPs (n = 505) completed the survey between November 2021 and February 2022. Data were synthesised using descriptive statistics. MC 'prescribers' and 'non-prescribers' responses were compared using Pearson's χ2 tests. RESULTS: While most GPs (85.3%) had received patient enquiries about MC during the last three months, only half (52.3%) felt comfortable discussing MC with patients. Around one fifth (21.8%) had prescribed a MC product. GPs strongly supported MC prescribing for palliative care, cancer pain, chemotherapy-induced nausea and vomiting, and epilepsy, more so than in our 2017 survey. Prescribing for mental health conditions (e.g., depression, anxiety) and insomnia received less support. Opioids, benzodiazepines, and chemotherapy drugs were rated as more hazardous than MC. GPs correctly endorsed concerns around Δ9-tetrahydrocannabinol-related driving impairment and drug-seeking behaviour. However, additional concerns endorsed around cannabidiol causing addiction and driving impairment do not agree with current evidence. Consistent with this, many GPs (66.9%) felt they had inadequate knowledge of MC. CONCLUSION: Acceptance of MC as a treatment option has increased among Australian GPs since 2017. However, there is a clear need for improved training and education of GPs around cannabis-based medicines to provide increased numbers of skilled prescribers in the community.

Effects of Different Sources of Low-Dose Caffeine on Mood/Arousal and Cognitive Performance.

In this study we investigated the effects of variously derived sources of low-dose caffeine on mood/arousal and cognitive performance. Twenty-two participants (15 men, 7 women; M age: 28.2, SD = 9.0 years) undertook five randomized, crossover trials in which they consumed either a water control (CON) or 80 mg of caffeine from one of four sources (coffee [COF], energy drink [END], capsule [CAP], and dissolvable mouth strip [STR]). We measured the participants' perceived efficacy of these varied caffeine sources pre-treatment; and we measured mood/arousal at pre-treatment, and again at 15 and 45 minutes post-treatment. We also measured choice reaction-time at 15 and 45 minutes post-treatment, and participants completed the psychomotor vigilance task (PVT) 45 minutes post-treatment. Caffeine increased participant ratings of alertness and decreased their ratings of tiredness irrespective of source (p's < .05), and all sources of caffeine decreased reaction time on the PVT (p's < .05), with ex-Gaussian distributional analysis localizing this to the tau-parameter, indicating lower variability. However, only the COF source was associated with improved 'overall mood' (p's < .05). Participants expected to perform better on the PVT with COF compared to CON, but there were no other significant associations between source expectancy and performance. In sum, a modest dose of caffeine, regardless of source, positively impacted mood/arousal and cognitive performance, and these effects did not appear to be influenced by expectations.

Effects of Acute Sleep Loss on Physical Performance: A Systematic and Meta-Analytical Review.

BACKGROUND: Sleep loss may influence subsequent physical performance. Quantifying the impact of sleep loss on physical performance is critical for individuals involved in athletic pursuits. DESIGN: Systematic review and meta-analysis. SEARCH AND INCLUSION: Studies were identified via the Web of Science, Scopus, and PsycINFO online databases. Investigations measuring exercise performance under 'control' (i.e., normal sleep, > 6 h in any 24 h period) and 'intervention' (i.e., sleep loss, ≤ 6 h sleep in any 24 h period) conditions were included. Performance tasks were classified into different exercise categories (anaerobic power, speed/power endurance, high-intensity interval exercise (HIIE), strength, endurance, strength-endurance, and skill). Multi-level random-effects meta-analyses and meta-regression analyses were conducted, including subgroup analyses to explore the influence of sleep-loss protocol (e.g., deprivation, restriction, early [delayed sleep onset] and late restriction [earlier than normal waking]), time of day the exercise task was performed (AM vs. PM) and body limb strength (upper vs. lower body). RESULTS: Overall, 227 outcome measures (anaerobic power: n = 58; speed/power endurance: n = 32; HIIE: n = 27; strength: n = 66; endurance: n = 22; strength-endurance: n = 9; skill: n = 13) derived from 69 publications were included. Results indicated a negative impact of sleep loss on the percentage change (%Δ) in exercise performance (n = 959 [89%] male; mean %Δ = - 7.56%, 95% CI - 11.9 to - 3.13, p = 0.001, I2 = 98.1%). Effects were significant for all exercise categories. Subgroup analyses indicated that the pattern of sleep loss (i.e., deprivation, early and late restriction) preceding exercise is an important factor, with consistent negative effects only observed with deprivation and late-restriction protocols. A significant positive relationship was observed between time awake prior to the exercise task and %Δ in performance for both deprivation and late-restriction protocols (~ 0.4% decrease for every hour awake prior to exercise). The negative effects of sleep loss on different exercise tasks performed in the PM were consistent, while tasks performed in the AM were largely unaffected. CONCLUSIONS: Sleep loss appears to have a negative impact on exercise performance. If sleep loss is anticipated and unavoidable, individuals should avoid situations that lead to experiencing deprivation or late restriction, and prioritise morning exercise in an effort to maintain performance.

Effects of cannabidiol on simulated driving and cognitive performance: A dose-ranging randomised controlled trial.

BACKGROUND: Cannabidiol (CBD), a major cannabinoid of Cannabis sativa, is widely consumed in prescription and non-prescription products. While CBD is generally considered 'non-intoxicating', its effects on safety-sensitive tasks are still under scrutiny. AIM: We investigated the effects of CBD on driving performance. METHODS: Healthy adults (n = 17) completed four treatment sessions involving the oral administration of a placebo, or 15, 300 or 1500 mg CBD in a randomised, double-blind, crossover design. Simulated driving performance was assessed between ~45-75 and ~210-240 min post-treatment (Drives 1 and 2) using a two-part scenario with 'standard' and 'car following' (CF) components. The primary outcome was standard deviation of lateral position (SDLP), a well-established measure of vehicular control. Cognitive function, subjective experiences and plasma CBD concentrations were also measured. Non-inferiority analyses tested the hypothesis that CBD would not increase SDLP by more than a margin equivalent to a 0.05% blood alcohol concentration (Cohen's dz = 0.50). RESULTS: Non-inferiority was established during the standard component of Drive 1 and CF component of Drive 2 on all CBD treatments and during the standard component of Drive 2 on the 15 and 1500 mg treatments (95% CIs < 0.5). The remaining comparisons to placebo were inconclusive (the 95% CIs included 0 and 0.50). No dose of CBD impaired cognition or induced feelings of intoxication (ps > 0.05). CBD was unexpectedly found to persist in plasma for prolonged periods of time (e.g. >4 weeks at 1500 mg). CONCLUSION: Acute, oral CBD treatment does not appear to induce feelings of intoxication and is unlikely to impair cognitive function or driving performance (Registration: ACTRN12619001552178).

Effects of Cannabidiol on Exercise Physiology and Bioenergetics: A Randomised Controlled Pilot Trial.

BACKGROUND: Cannabidiol (CBD) has demonstrated anti-inflammatory, analgesic, anxiolytic and neuroprotective effects that have the potential to benefit athletes. This pilot study investigated the effects of acute, oral CBD treatment on physiological and psychological responses to aerobic exercise to determine its practical utility within the sporting context. METHODS: On two occasions, nine endurance-trained males (mean ± SD V̇O2max: 57.4 ± 4.0 mL·min-1·kg-1) ran for 60 min at a fixed intensity (70% V̇O2max) (RUN 1) before completing an incremental run to exhaustion (RUN 2). Participants received CBD (300 mg; oral) or placebo 1.5 h before exercise in a randomised, double-blind design. Respiratory gases (V̇O2), respiratory exchange ratio (RER), heart rate (HR), blood glucose (BG) and lactate (BL) concentrations, and ratings of perceived exertion (RPE) and pleasure-displeasure were measured at three timepoints (T1-3) during RUN 1. V̇O2max, RERmax, HRmax and time to exhaustion (TTE) were recorded during RUN 2. Venous blood was drawn at Baseline, Pre- and Post-RUN 1, Post-RUN 2 and 1 h Post-RUN 2. Data were synthesised using Cohen's dz effect sizes and 85% confidence intervals (CIs). Effects were considered worthy of further investigation if the 85% CI included ± 0.5 but not zero. RESULTS: CBD appeared to increase V̇O2 (T2: + 38 ± 48 mL·min-1, dz: 0.25-1.35), ratings of pleasure (T1: + 0.7 ± 0.9, dz: 0.22-1.32; T2: + 0.8 ± 1.1, dz: 0.17-1.25) and BL (T2: + 3.3 ± 6.4 mmol·L-1, dz: > 0.00-1.03) during RUN 1 compared to placebo. No differences in HR, RPE, BG or RER were observed between treatments. CBD appeared to increase V̇O2max (+ 119 ± 206 mL·min-1, dz: 0.06-1.10) and RERmax (+ 0.04 ± 0.05 dz: 0.24-1.34) during RUN 2 compared to placebo. No differences in TTE or HRmax were observed between treatments. Exercise increased serum interleukin (IL)-6, IL-1ß, tumour necrosis factor-α, lipopolysaccharide and myoglobin concentrations (i.e. Baseline vs. Post-RUN 1, Post-RUN 2 and/or 1-h Post-RUN 2, p's < 0.05). However, the changes were small, making it difficult to reliably evaluate the effect of CBD, where an effect appeared to be present. Plasma concentrations of the endogenous cannabinoid, anandamide (AEA), increased Post-RUN 1 and Post-RUN 2, relative to Baseline and Pre-RUN 1 (p's < 0.05). CBD appeared to reduce AEA concentrations Post-RUN 2, compared to placebo (- 0.95 ± 0.64 pmol·mL-1, dz: - 2.19, - 0.79). CONCLUSION: CBD appears to alter some key physiological and psychological responses to aerobic exercise without impairing performance. Larger studies are required to confirm and better understand these preliminary findings. Trial Registration This investigation was approved by the Sydney Local Health District's Human Research Ethics Committee (2020/ETH00226) and registered with the Australia and New Zealand Clinical Trials Registry (ACTRN12620000941965).

Orally administered cannabidiol does not produce false-positive tests for Δ9 -tetrahydrocannabinol on the Securetec DrugWipe® 5S or Dräger DrugTest® 5000.

Many jurisdictions use point-of-collection (POC) oral fluid testing devices to identify driving under the influence of cannabis, indexed by the presence of Δ9 -tetrahydrocannabinol (THC), an intoxicating cannabinoid, in oral fluid. Although the use of the non-intoxicating cannabinoid, cannabidiol (CBD), is not prohibited among drivers, it is unclear whether these devices can reliably distinguish between CBD and THC, which have similar chemical structures. This study determined whether orally administered CBD produces false-positive tests for THC on standard, POC oral fluid testing devices. In a randomised, double-blind, crossover design, healthy participants (n = 17) completed four treatment sessions involving the administration of either placebo or 15-, 300- or 1500-mg pure CBD in a high-fat dietary supplement. Oral fluid was sampled, and the DrugWipe®-5S (DW-5S; 10 ng·ml-1 THC cut-off) and Drug Test® 5000 (DT5000; 10 ng·mL-1 THC cut-off) devices administered, at baseline (pretreatment) and ~20-, ~145- and ~185-min posttreatment. Oral fluid cannabinoid concentrations were measured using ultra-high performance liquid chromatography-tandem mass spectrometry. Median (interquartile range [IQR]) oral fluid CBD concentrations were highest at ~20 min, quantified as 0.4 (6.0), 15.8 (41.6) and 167 (233) ng·ml-1 on the 15-, 300- and 1500-mg CBD treatments, respectively. THC, cannabinol and cannabigerol were not detected in any samples. A total of 259 DW-5S and 256 DT5000 tests were successfully completed, and no THC-positive tests were observed. Orally administered CBD does not appear to produce false-positive (or true-positive) tests for THC on the DW-5S and DT5000. The likelihood of an individual who is using a CBD (only) oral formulation being falsely accused of DUIC therefore appears low.

The influence of exercise training volume alterations on the gut microbiome in highly-trained middle-distance runners.

The aim of this study was to determine the influence of training volume alterations on diversity and composition of the gut microbiome in a free-living cohort of middle-distance runners. Fourteen highly-trained middle-distance runners (n = 8 men; V˙O2peak = 70.1 ± 4.3 ml·kg·min-1; n = 6 women, V˙O2peak: 59.0 ± 3.2 ml·kg·min-1) completed three weeks of normal training (NormTr), three weeks of high-volume training (HVolTr; a 10, 20 and 30% increase in training volume during each successive week from NormTr), and a one-week taper (TaperTr; 55% exponential reduction in training volume from HVolTr week three). Faecal samples were collected before and immediately after each training phase to quantify alpha-diversity and composition of the gut microbiome. A three-day diet record was collected during each training phase and a maximal incremental running test was completed after each training phase. Results showed no significant changes in nutritional intake, alpha-diversity, or global microbial composition following HVolTr or TaperTr compared to NormTr (p's > 0.05). Following HVolTr, there was a significant decrease in Pasterellaceae (p = 0.03), Lachnoclostridium (p = 0.02), Haemophilus (p = 0.03), S. parasagunis (p = 0.02), and H. parainfluenzae (p = 0.03), while R. callidus (p = 0.03) significantly increased. These changes did not return to NormTr levels following TaperTr. This study shows that the alpha-diversity and global composition of the gut microbiome were unaffected by changes in training volume. However, an increase in training volume led to several changes at the lower taxonomy levels that did not return to pre-HVolTr levels following a taper period.

Are blood and oral fluid Δ9-tetrahydrocannabinol (THC) and metabolite concentrations related to impairment? A meta-regression analysis.

Blood and oral fluid Δ9-tetrahydrocannabinol (THC) concentrations are often used to identify cannabis-impaired drivers. We used meta-analytic techniques to characterise the relationships between biomarkers of cannabis use, subjective intoxication, and impairment of driving and driving-related cognitive skills. Twenty-eight publications and 822 driving-related outcomes were reviewed. Each outcome was measured in concert with one or more biomarkers of cannabis/THC use and/or subjective intoxication. Higher blood THC and 11-OH-THC concentrations, oral fluid THC concentrations and subjective ratings of intoxication were associated with greater impairment in 'other' (mostly occasional) cannabis users (p's<0.05). Blood 11-COOH-THC concentrations were associated with impairment after inhaling, but not orally ingesting, cannabis/THC. However, these 'biomarker-performance' relationships (R) were only very weak (blood THCpost-ingestion: -0.08; blood THCpost-inhalation: -0.10; blood 11-OH-THCpost-ingestion: -0.13), weak (blood 11-OH-THCpost-inhalation: -0.24; oral fluid THCpost-inhalation: -0.36; subjective intoxication: -0.29) or moderate (blood 11-COOH-THCpost-inhalation: -0.43) in strength. No significant biomarker-performance relationships were observed in 'regular' (weekly or more often) cannabis users (p's>0.10), although the analyses were less robust. Blood and oral fluid THC concentrations are relatively poor indicators of cannabis/THC-induced impairment.

Reducing salt intake: a systematic review and meta-analysis of behavior change interventions in adults.

CONTEXT: Prolonged high salt (sodium) intake can increase the risk of hypertension and cardiovascular disease. Behavioral interventions may help reduce sodium intake at the population level. OBJECTIVE: The effectiveness of behavior change interventions to reduce sodium intake in adults was investigated in this systematic review and meta-analysis. DATA SOURCE: The PubMed, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, and EMBASE databases were searched. DATA EXTRACTION: Narrative synthesis and random-effects meta-analyses were used to determine intervention efficacy. A total of 61 trials (46 controlled trials and 15 quasi-experimental studies) were included. RESULTS: Behavior change interventions resulted in significant improvements in salt consumption behavior (eg, decrease in purchase of salty foods; increase in use of salt substitutes), leading to reductions in sodium intake as measured by urinary sodium in 32 trials (N = 7840 participants; mean difference, -486.19 mg/d [95%CI, -669.44 to -302.95]; P < 0.001; I2 = 92%) and dietary sodium in 19 trials (N = 3750 participants; mean difference -399.86 mg/d [95%CI, -581.51 to -218.20]; P < 0.001; I2 = 96%), equivalent to a reduction of >1 g of salt intake daily. Effects were not significantly different based on baseline sodium intakes, blood pressure status, disease status, the use of behavior change theories, or the main method of intervention delivery (ie, online vs face-to-face). CONCLUSION: Behavior change interventions are effective at improving salt consumption practices and appear to reduce salt intake by >1 g/d. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42020185639.

Medical cannabis and driving.

BACKGROUND: Medical cannabis use is increasingly common in Australia. Patients and physicians need to be aware of the important implications that such use may have for driving. OBJECTIVE: The aim of this article is to briefly review the scientific evidence regarding cannabis and driving impairment and discuss current legal issues affecting patients, as well as to update physicians on relevant issues and the best guidance to offer their patients. DISCUSSION: Delta-9-tetrahydrocannabinol (THC) impairs driving performance and can increase crash risk. These effects are more pronounced in people who use THC occasionally and can last for up to eight hours with oral THC products. There is no evidence that cannabidiol (CBD) impairs driving. Patients using THC-containing products should avoid driving and other safety-sensitive tasks (eg operating machinery), particularly during initiation of treatment and in the hours immediately following each dose. Patients may test positive for THC even if they do not feel impaired, and medical cannabis use does not currently exempt patients from mobile (roadside) drug testing and associated legal sanctions.

The impact of post-prandial delay periods on ad libitum consumption of a laboratory breakfast meal.

This study examined the impact of varying the holding time following an ad libitum laboratory breakfast on acute dietary behaviour and subsequent intake. Twenty-four participants (20 females (age: 23.4 ± 6.3 years; body mass index: 23.9 ± 3.9 kg·m-2, mean ± SD)) completed 3 trials following a quasi-randomised, crossover design. Each trial (7-day separation) incorporated a defined post-prandial delay (DPD) period of either zero (no delay), 1 or 3 hours following a buffet breakfast consumed over 30 minutes. Dietary intake outcomes included energy, macronutrient and core food group intakes. On completion of the DPD period, participants left the laboratory and recorded all food/beverages consumed for the remainder of the day. One-way repeated-measures ANOVA assessed all outcomes, with post hoc analysis conducted on significant main effects. Energy and carbohydrate intakes were significantly lower on no delay vs. 1-hour (p = 0.014) and 3-hour (p = 0.06) DPD trials (energy intake: 1853 ± 814 kJ vs. 2250 ± 1345 kJ vs. 1948 ± 1289 kJ; carbohydrates: 68 ± 34 g vs. 77 ± 44 vs. 69 ± 43 g; respectively). DPD periods did not influence the time to consume next meal or energy, macronutrient and core food group intakes for the remainder of the day. Delaying participants from leaving a laboratory alters dietary intake at an ad libitum test meal. The post-meal holding period is an important methodological consideration when planning laboratory studies to assess appetite. Novelty: Delaying participants from leaving a laboratory alters dietary intake at ad libitum breakfast meals. The length of the delay period did not affect dietary intake at ad libitum breakfast meals.