Neuroimaging studies of cannabidiol and potential neurobiological mechanisms relevant for alcohol use disorders: a systematic review.

The underlying neurobiological mechanisms of cannabidiol's (CBD) management of alcohol use disorder (AUD) remains elusive.Aim We conducted a systematic review of neuroimaging literature investigating the effects of CBD on the brain in healthy participants. We then theorise the potential neurobiological mechanisms by which CBD may ameliorate various symptoms of AUD.Methods This review was conducted according to the PRISMA guidelines. Terms relating to CBD and neuroimaging were used to search original clinical research published in peer-reviewed journals.Results Of 767 studies identified by our search strategy, 16 studies satisfied our eligibility criteria. The results suggest that CBD modulates γ-Aminobutyric acid and glutamate signaling in the basal ganglia and dorso-medial prefrontal cortex. Furthermore, CBD regulates activity in regions associated with mesocorticolimbic reward pathways; salience, limbic and fronto-striatal networks which are implicated in reward anticipation; emotion regulation; salience processing; and executive functioning.Conclusion CBD appears to modulate neurotransmitter systems and functional connections in brain regions implicated in AUD, suggesting CBD may be used to manage AUD symptomatology.

A phase II randomised controlled trial of intranasal oxytocin in anorexia nervosa.

BACKGROUND: Anorexia nervosa (AN) is an eating disorder (ED) with high mortality rates and limited response to existing treatments, prompting the need to identify effective agents and adjuncts. There is evidence for an emerging role for the neuropeptide oxytocin (OT) in the pathophysiology of AN, with studies showing a perturbed oxytocinergic system in patients with AN. Preliminary evidence has demonstrated that intranasal OT (IN-OT) can produce anxiolytic effects in AN, as well as reducing concern about eating, and dysfunctional attentional biases related to the disorder. IN-OT is a non-invasive treatment option for AN that requires investigation as an adjunct to nutritional rehabilitation. METHODS: This multi-site study (Trial Registration:ACTRN1261000897460) sought to replicate and extend a previous randomised placebo-controlled pilot trial of repeated dose IN-OT in patients with AN hospitalised for nutritional rehabilitation. Patients with AN (N=61) received daily IN-OT (18 IU twice per day) or placebo for four weeks, whilst undergoing inpatient hospital treatment. Outcome measures included ED psychopathology (primary) as measured by the Eating Disorder Examination (EDE) and Body Mass Index (BMI; secondary). Participants were assessed pre- and post-treatment, and at six months following the intervention. The effects of the first and last doses of IN-OT on responses (anxiety ratings and salivary cortisol) to a high-energy snack were also examined. RESULTS: Sixty-one female inpatients (Mage=24.36,SD=7.87) with an average BMI of 16.24 (range: 11.43-18.55), were recruited into the study. No significant differences were found between placebo and OT groups at any of the time points on the outcomes of interest, but significant improvements in almost all psychological parameters in both groups were evident over time. IN-OT did not significantly reduce anxiety nor salivary cortisol in response to a high-calorie snack. CONCLUSION: This is the largest randomised placebo-controlled trial of repeated dose intranasal OT in people with AN, during refeeding. The therapeutically promising findings of the pilot study were not replicated. Limitations and reasons for the non-replication included relatively large variance, baseline psychopathology scores being higher in this patient group, potential ceiling effects in BMI and ED psychopathology as well as differing comorbidities.

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.

Differences in prescribed medicinal cannabis use by cannabinoid product composition: Findings from the cannabis as medicine survey 2020 (CAMS-20) Australia-wide study.

INTRODUCTION: Prescribed medicinal cannabis (MC) is an increasingly common prescription in Australia for treating pain, anxiety, and sleep disorders. Prescribed MC products generally contain tetrahydrocannabinol (THC) and/or cannabidiol (CBD) in a variety of dose levels and forms. It is unclear whether THC and CBD products are used by patients with different characteristics and for different conditions. OBJECTIVES: To examine consumer experiences of using THC- and CBD-containing prescribed MC products to better understand how they are being used within the Australian context. METHODS: We utilised data collected from an online anonymous cross-sectional survey of individuals (CAMS-20 survey), consisting of Australian residents using cannabis for therapeutic reasons. We focused on a subgroup of participants (N = 546) receiving prescribed MC products. We utilised linear, logistic, and multinomial regression modelling to analyse responses to survey questions based on the cannabinoid profile of the prescribed product. RESULTS: Participants prescribed THC-dominant MC products were statistically more likely to be younger, male, and to prefer inhaled routes of administration than participants using CBD-dominant products who were older, female, and preferred oral routes of administration. Pain and mental health were the most common reasons for all types of prescribed MC, but were more likely to be treated with THC than CBD despite the significantly higher risk of mild to severe drowsiness, dry mouth and eye irritation. Consumer reported effectiveness of prescribed MC was very positive, particularly for THC-containing products. Consumers on opioids and antipsychotics were statistically more likely to be prescribed THC-containing products than products containing CBD only, despite the greater risk of impairment. CONCLUSIONS: This Australia-wide study found clear differences in consumer-reported experiences of prescribed THC- and CBD-containing products. Current prescriptions of these products do not always align with relevant clinical guidance. Educating prescribers around cannabinoid products is essential to ensure optimal prescribing practices and to prevent avoidable drug side effects and interactions.

Driving-related behaviors, attitudes, and perceptions among Australian medical cannabis users: results from the CAMS 20 survey.

Road safety is an important concern amidst expanding worldwide access to legal cannabis. The present study reports on the driving-related subsection of the Cannabis as Medicine Survey 2020 (CAMS-20) which surveyed driving-related behaviors, attitudes, and perceptions among Australian medical cannabis (MC) users. Of the 1063 respondents who reported driving a motor vehicle in the past 12 months, 28% (297/1063) reported driving under the influence of cannabis (DUIC). Overall, 49-56% of respondents said they typically drive within 6 h of MC use, depending on the route of administration (oral or inhaled). Non-medical cannabis (NMC) was perceived to be more impairing for driving than MC. Binary logistic regression revealed associations between likelihood of DUIC and (1) inhaled routes of cannabis administration, (2) THC-dominant products, (3) illicit rather than prescribed use, (4) believing NMC does not impair driving, and (5) not being deterred by roadside drug testing. Overall, these findings suggest there is a relatively low perception of driving-related risk among MC users. Targeted education programs may be needed to highlight the potential risks associated with DUIC, and further research is needed to determine whether driving performance is differentially affected by MC and NMC.

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.

Medical Cannabis Use Patterns for Sleep Disorders in Australia: Results of the Cross-Sectional CAMS-20 Survey.

Introduction: Sleep disorders are the third most common indication for the prescription of medical cannabis products in Australia, after pain and anxiety. While the use of cannabis for medical purposes is growing in Australia, underlying consumer behaviours and patterns of use, particularly around sleep disorders, are poorly understood. Methods: We conducted a subanalysis of the cross-sectional "Cannabis as Medicine Survey" 2020-2021 (CAMS-20) (N = 1600), to explore the characteristics of a sample of Australians who were using prescribed and/or illicit medical cannabis to treat a self-reported sleep disorder. Results: When asked to specify up to seven different conditions they were treating with medical cannabis, a total of 1030 (64%) respondents [mean (SD) 44.9 (13.6) years] selected a sleep disorder, with "insomnia disorder" (85.5%), 'sleep-related movement disorders' (26%) and 'sleep-related breathing disorders' (11.1%) the most common subtypes. Only 165 (16.8%) respondents selected a self-reported sleep disorder as the main health condition being treated. Relative to other health conditions, use of medical cannabis for a self-reported sleep disorder was associated with younger age, increased likelihood of using both prescribed and illicit forms of medical cannabis, inhaled routes of administration, and THC-dominant products. Most respondents reported a reduction in the use of benzodiazepines and alcohol since starting medical cannabis. Binary logistic regression showed that respondents who predominantly used inhaled routes of administration, and concomitant use of medical cannabis for pain, mental health and/or substance use disorder, or a gastrointestinal disorder, were significantly more likely to also use medical cannabis to treat a self-reported sleep disorder. Conclusion: Overall, these results suggest that self-reported sleep disorders are often being treated with medical cannabis alongside other health conditions (often pain or a mental health disorder) and that use of inhaled methods, THC-dominant products, and illicit sources of medical cannabis are common among people with self-reported sleep disorders in Australia.

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.

Tetrahydrocannabinol and Cannabidiol in Tourette Syndrome.

Tetrahydrocannabinol and Cannabidiol in Tourette SyndromeThis randomized controlled crossover trial examined the use of oral tetrahydrocannabinol (THC) with cannabidiol (CBD) to reduce tics in patients with severe Tourette syndrome. Treatment with THC and CBD for 6 weeks led to a significant reduction in tics as measured by the total tic score on the Yale Global Tic Severity Scale, without major adverse effects.

Medical cannabis use in Australia: consumer experiences from the online cannabis as medicine survey 2020 (CAMS-20).

BACKGROUND: Australia has had a framework for legal medicinal cannabis since 2016, yet prior online surveys in 2016 and 2018 indicated that most consumers continued to use illicit medical cannabis products. Regulatory data indicate an increase in the prescription of medicinal cannabis since 2019, and this survey examines consumer experiences of prescribed and illicit medical cannabis (MC) use in Australia. METHODS: A cross-sectional anonymous online survey was administered September 2020 to January 2021. Recruitment via social media, professional and consumer forums, and medical practices. Participant eligibility: ≥ 18 years; used a cannabis product for self-identified medical reason(s) in the past year, and resident in Australia. Outcome measures included consumer characteristics, conditions treated, source and patterns of MC use, and perspectives on accessing MC. RESULTS: Of the 1600 participants (mean age 46.4 ± 14.3 years, 53% male), 62.4% (n = 999) reported using only illicit and 37.6% (n = 601) used prescribed MC in the past year. MC was used on a median of 28 (IQR: 12, 28) of the past 28 days and cost $AUD 74 ± 72 weekly (median = $40, IQR: $7, $100). Prescribed participants were more likely to treat pain conditions than those using illicit MC (52% v 40%, OR = 1.7, 1.3-2.1) and less likely to treat sleep conditions (6% v 11%, OR = 0.5, 0.3-0.8), with mental health conditions also a common indication in both groups (26%, 31%). Prescribed MC was consumed predominately by oral routes (72%), whereas illicit MC was most commonly smoked (41%). Prescribed MC was 'mainly THC' (26%), 'equal THC/CBD' (40%), 'mainly CBD' (31%) and 'uncertain' (3%), while 34% of those using illicit MC were 'uncertain' of the cannabinoid profile. Cost and difficulties finding medical practitioners to prescribe remain significant barriers to accessing prescribed MC, and few (10.8%) described the existing model for accessing prescribed MC as 'straightforward or easy'. CONCLUSIONS: There has been a notable shift from illicit to prescribed MC by many consumers compared to prior surveys. Consumers using prescribed MC reported a range of advantages compared to illicit MC, including safer routes of administration, and greater certainty regarding access and composition of products.

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).

Cannabinoids, Insomnia, and Other Sleep Disorders.

Sleep disturbances are often cited as a primary reason for medicinal cannabis use, and there is increasing clinical interest in the therapeutic potential of cannabinoids in treating sleep disorders. Burgeoning evidence suggests a role of the endocannabinoid system in regulating the circadian sleep-wake cycle, highlighting a potential avenue for developing novel therapeutics. Despite widespread use of cannabis products as sleep aids globally, robustly designed studies verifying efficacy in sleep-disordered populations are limited. Although some study outcomes have suggested cannabinoid utility in insomnia disorder and sleep apnea, most studies to date are limited by small sample sizes, lack of rigorously controlled study designs, and high risk of bias. This critical review summarizes the current evidence for the use of cannabinoids as a treatment for sleep disorders and provides an overview of endocannabinoid modulation of sleep-wake cycles, as well as the sleep-modulating effects of plant-derived cannabinoids such as delta-9-tetrahydrocannbinol, cannabidiol, and cannabinol. The review also discusses practical considerations for clinicians regarding cannabinoid formulations, routes of administration, respiratory concerns, dosing, potential side effects, drug interactions, and effects relevant to driving, tolerance, and withdrawal. Although current interest in, and uptake of, medicinal cannabis use for sleep disorders may have surpassed the evidence base, there is a strong rationale for continued investigation into the therapeutic potential of cannabinoids.

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.

Determination of contaminants in artisanal cannabis products used for childhood epilepsy in the Australian community: A sub-analysis of the 'PELICAN' study.

Despite recent approval of pharmaceutical-grade cannabis products for the treatment of childhood epilepsy, some families continue to use artisanal cannabis products as a way to manage seizures in their children. However, such products are typically of unknown composition and quality, and may therefore pose an unpredictable health risk to the child. In the present analysis, 78 samples of cannabis products collected (as part of a previous study) from families of children with epilepsy (average age 8.8 ± 4.6 years) were analyzed for heavy metals (arsenic, cadmium, lead, and mercury), residual solvents (panel of 19 solvents) and pesticides (panel of 57 pesticides). Due to small sample volumes obtained, only a subset of samples was used in each analysis. Results showed that no cannabis sample exceeded the toxicity limits for heavy metals (n = 51 samples tested). Of the 58 cannabis samples tested for residual solvents, 17 (29%) contained concentrations of ethanol or isopropanol above the generally accepted limit of 5000 parts per million. With the volumes consumed, it was thought unlikely that children were consuming hazardous amounts of residual solvents, although this could not be ruled out in every case. Most samples (n = 31 samples tested) yielded inconclusive results for the pesticides, although one sample contained concentrations of bifenthrin that were 4.9 times higher than the acceptable limit. Overall, these results highlight the need for improved access to quality-assured cannabis products and the education of doctors, patients, and artisanal manufacturers around the contaminant exposure risk in unregulated cannabis products.

Driving-Related Behaviours, Attitudes and Perceptions among Australian Medical Cannabis Users: Results from the CAMS 18-19 Survey.

As the use of cannabis for medical purposes becomes increasingly prevalent, driving under the influence of cannabis (DUIC) is emerging as a major public health issue. Understanding current behaviours, attitudes and perceptions around DUIC in medical cannabis users is an important first step in addressing this issue. Here we present the results from the driving-related subsection of the Cannabis as Medicine 2018-2019 Survey (CAMS18) of current Australian medical cannabis users (n = 1388). Of the 806 respondents who reported driving a motor vehicle in the last month, 34.6% said they typically drive within 3 hours of cannabis use, thereby risking DUIC, while more than 50% waited at least 7 hours before driving. A majority of respondents thought that their medical cannabis use did not affect their driving ability, and most denied any specific effects of cannabis on speeding, risk taking, reaction time, attentiveness or lane departures. A substantial majority (70.9%) felt confident in accurately assessing their own driving ability after using medical cannabis. Binary logistic regression showed that frequency of use and confidence to assess driving ability were strongly related to DUIC behaviour (i.e. driving soon after cannabis use). These results suggest a relatively high prevalence of DUIC and low perception of risk among this sample of medical cannabis users. Further research is needed to better understand the acute and chronic effects of medical cannabis use on driving and the relation between perceived and actual driving ability.

Cannabinoid therapies in the management of sleep disorders: A systematic review of preclinical and clinical studies.

Cannabinoids, including the two main phytocannabinoids Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), are being increasingly utilised as pharmacological interventions for sleep disorders. THC and CBD are known to interact with the endocannabinoid and other neurochemical systems to influence anxiety, mood, autonomic function, and circadian sleep/wake cycle. However, their therapeutic efficacy and safety as treatments for sleep disorders are unclear. The current systematic review assessed the available evidence base using PubMed, Scopus, Web of Science, Embase, CINAHL and PsycInfo databases. A total of 14 preclinical studies and 12 clinical studies met inclusion criteria. Results indicated that there is insufficient evidence to support routine clinical use of cannabinoid therapies for the treatment of any sleep disorder given the lack of published research and the moderate-to-high risk of bias identified within the majority of preclinical and clinical studies completed to-date. Promising preliminary evidence provides the rationale for future randomised controlled trials of cannabinoid therapies in individuals with sleep apnea, insomnia, post-traumatic stress disorder-related nightmares, restless legs syndrome, rapid eye movement sleep behaviour disorder, and narcolepsy. There is a clear need for further investigations on the safety and efficacy of cannabinoid therapies for treating sleep disorders using larger, rigorously controlled, longer-term trials.

The effect of cannabidiol on simulated car driving performance: A randomised, double-blind, placebo-controlled, crossover, dose-ranging clinical trial protocol.

OBJECTIVE: Interest in the use of cannabidiol (CBD) is increasing worldwide as its therapeutic effects are established and legal restrictions moderated. Unlike Δ9 -tetrahydrocannabinol (Δ9 -THC), CBD does not appear to cause cognitive or psychomotor impairment. However, further assessment of its effects on cognitively demanding day-to-day activities, such as driving, is warranted. Here, we describe a study investigating the effects of CBD on simulated driving and cognitive performance. METHODS: Thirty healthy individuals will be recruited to participate in this randomised, double-blind, placebo-controlled crossover trial. Participants will complete four research sessions each involving two 30-min simulated driving performance tests completed 45 and 210 min following oral ingestion of placebo or 15, 300, or 1,500 mg CBD. Cognitive function and subjective drug effects will be measured, and blood and oral fluid sampled, at regular intervals. Oral fluid drug testing will be performed using the Securetec DrugWipe® 5S and Dräger DrugTest® 5000 devices to determine whether CBD increases the risk of "false-positive" roadside tests to Δ9 -THC. Noninferiority analyses will test the hypothesis that CBD is no more impairing than placebo. CONCLUSION: This study will clarify the risks involved in driving following CBD use and assist in ensuring the safe use of CBD by drivers.