Cannabidiol-associated hepatotoxicity: A systematic review and meta-analysis.

BACKGROUND: Findings of liver enzyme elevations in recent cannabidiol studies have raised concerns over liver safety. This study aimed to determine the association between cannabidiol use, liver enzyme elevation, and drug-induced liver injury (DILI). METHODS: In this systematic review and meta-analysis, a search of EMBASE, CENTRAL, CINAHL, Clinicaltrials.gov, Medline, medRxiv, and Web of Science of records up to February 2022 was conducted. Clinical trials initiating daily cannabidiol treatment with serial liver enzyme measures were included. The proportion of liver enzyme elevations and DILI were independently extracted from published reports. Pooled proportions and probability meta-analyses were conducted. RESULTS: Cannabidiol use was associated with an increased probability of liver enzyme elevation (N = 12 trials, n = 1229; OR = 5.85 95% CI = 3.84-8.92, p < 0.001) and DILI (N = 12 trials, n = 1229; OR = 4.82 95% CI = 2.46-9.45, p < 0.001) compared to placebo controls. In participants taking cannabidiol (N = 28 trials, n = 1533), the pooled proportion of liver enzyme elevations was 0.074 (95% CI 0.0448-0.1212), and DILI was 0.0296 (95% CI 0.0136-0.0631). High-dose CBD (≥1000 mg/day or ≥20 mg/kg/day) and concomitant antiepileptic drug use were identified as risk factors. No cases were reported in adults using cannabidiol doses <300 mg/day. No cases of severe DILI were reported. CONCLUSIONS: Cannabidiol-associated liver enzyme elevations and DILI meet the criteria of common adverse drug events. Clinicians are encouraged to screen for cannabidiol use and monitor liver function in patients at increased risk.

Art skill-based rehabilitation training for upper limb sensorimotor recovery post-stroke: A feasibility study.

OBJECTIVE: The objective of this study was to assess the feasibility of delivering Art skill-based Rehabilitation Training (ART), a novel upper limb motor training program, to patients with stroke as an adjunct to standard care in an inpatient setting. DESIGN: Feasibility study. SETTING: Inpatient stroke rehabilitation unit at a university hospital. PARTICIPANTS: Thirty-eight patients admitted to a stroke rehabilitation unit with upper limb motor impairment were enrolled in the ART program facilitated by trained non-healthcare professionals between December 2017 and June 2021. INTERVENTION: The ART program included nine, one-hour sessions of supervised tracing and freehand drawing tasks completed with both hands. This program was intended to be delivered at a frequency of three times per week over a duration of 3 weeks or for the length of inpatient stay. MAIN OUTCOME MEASURES: Feasibility outcomes included ART program adherence, acceptability, and safety. RESULTS: Thirty-two (84%) participants with subacute stroke completed the ART program and 30 (79%) were included in the study analysis. Participants completed 93-100% of the ART tasks in a median [IQR] of 8 [6-10] ART sessions over a median [IQR] duration of 15 [7-19] days. ART program facilitators effectively provided upper limb assistance to patients with more severe upper limb impairments. Adherence and acceptability were high and no study-related adverse events occurred. CONCLUSION: The ART program was feasible to deliver and highly acceptable to patients with stroke. Further research is warranted to explore the impact of ART on upper limb sensorimotor function and use.

Cannabis vaporisation: Understanding products, devices and risks.

ISSUES: Vaporisation is a common method of cannabis administration. Inconsistent terminology and jargon regarding vaporisation has led to confusion. The increasing public interest and access to cannabis, combined with possible safety concerns associated with certain cannabis vaping products, warrants improved consumer and public and health care professional knowledge. APPROACH: To improve this knowledge, we conducted a review of the common terminology, regulatory status, products and device types related to cannabis vaporisation. KEY FINDINGS: Cannabis vaporisation devices can be separated into nine types. While vaporisation reduces respiratory risks associated with cannabis combustion, not all vaping products and device types carry the same level of safety. Metered dose inhalers and dried product vaporisers present the lowest safety risk due to a lower risk of toxin exposure and the use of lower tetrahydrocannabinol potency products. IMPLICATIONS: As both vaping and cannabis use increase in popularity, focusing on accurate health education will help facilitate health promotion to encourage lower risk use. The current lack of understanding on risk differences between types of cannabis vaporisation is a missed opportunity for harm reduction. Increased opportunities for public health and health care professional education on different cannabis vaporisation devices and associated risks are warranted. Improvements to health warning labelling may also be beneficial. CONCLUSION: Not all cannabis vaporisation devices and products carry the same level of risk. A better understanding of risk differentiation is needed among consumers and health professionals. Continued research, policy development and health education can lead to safer cannabis vaporisation.

Does acute cannabidiol (CBD) use impair performance? A meta-analysis and comparison with placebo and delta-9-tetrahydrocannabinol (THC).

Cannabidiol (CBD) is widely used and believed to be non-intoxicating, lacking acute performance effects (e.g., non-impairing). However, a synthesis of data has not evaluated this. This meta-analysis synthesized data from controlled human laboratory studies that evaluated if acute CBD use impairs performance. Performance on objective and subjective measures of cognitive and psychomotor function were used as markers for potential performance changes and impairment. Studies were identified through systematic database searches. Adult clinical trials measuring acute CBD effects (within 0-8 h of administration) were included. The primary outcome was the peak mean difference in performance measures between CBD and placebo. A secondary analysis utilizing delta-9-tetrahydrocannabinol (Δ9-THC) as a positive control for comparison to CBD was completed. Pooled Hedges' g estimates were calculated using robust variance estimation (RVE) meta-regression. The omnibus RVE meta-analysis indicated a statistically significant, but small effect size (Hedge's g < 0.2) for impaired performance following acute CBD consumption compared to placebo (N = 16 trials, Hedges' g = 0.122, 95% CI: 0.023-0.221, p = 0.019). Measure type was a significant moderator with larger mean differences between CBD and placebo when subjective measures, specifically self-reported sedation, were used versus objective performance tasks (Hedges' gSubjective = 0.288 versus Hedges' gObjective = 0.048). Δ9-THC had a significantly greater magnitude of impairment compared to CBD (N = 8, Hedges' g = 0.416, 95% CI: 0.017-0.816, p = 0.043). In summary, acute CBD consumption was associated with a small increase in subjective ratings of sedation, but no difference from placebo was observed across multiple domains of objectively assessed cognitive or psychomotor performance. These findings suggest that acute CBD alone is unlikely to significantly impair daily functioning or workplace performance.

A Clinical Framework for Assessing Cannabis-Related Impairment Risk.

Clinicians play an important role in promoting safe and responsible medical cannabis use. One essential component to safe use is considering a patient's risk of neurocognitive impairment. However, there remains a lack of practical guidance on how clinicians can evaluate this risk for medical cannabis patients. Here, a practical framework is presented for clinicians to assess and stratify cannabis-associated impairment risk. The proposed framework is intended to practically guide healthcare providers in gaining a more comprehensive review of a patient's impairment-related factors. This framework can be used to assess impairment risk for patients currently using or considering medical cannabis and is recommended for all patients who perform safety-sensitive duties. Healthcare providers (HCP) managing patient's medical cannabis or those conducting assessments to determine risk of impairment for safety-sensitive workplaces can utilize this framework to stratify patients' risk of impairment. Such assessments can inform patient-specific needs for support, education, and guidance, to ensure cannabis is used safely and responsibly.

Duration of Neurocognitive Impairment With Medical Cannabis Use: A Scoping Review.

While the recreational use of cannabis has well-established dose-dependent effects on neurocognitive and psychomotor functioning, there is little consensus on the degree and duration of impairment typically seen with medical marijuana use. Compared to recreational cannabis users, medical cannabis patients have distinct characteristics that may modify the presence and extent of impairment. The goal of this review was to determine the duration of acute neurocognitive impairment associated with medical cannabis use, and to identify differences between medical cannabis patients and recreational users. These findings are used to gain insight on how medical professionals can best advise medical cannabis patients with regards to automobile driving or safety-sensitive tasks at work. A systematic electronic search for English language randomized controlled trials (RCTs), clinical trials and systematic reviews (in order to capture any potentially missed RCTs) between 2000 and 2019 was conducted through Ovid MEDLINE and EMBASE electronic databases using MeSH terms. Articles were limited to medical cannabis patients using cannabis for chronic non-cancer pain or spasticity. After screening titles and abstracts, 37 relevant studies were subjected to full-text review. Overall, seven controlled trials met the inclusion/exclusion criteria and were included in the qualitative synthesis: six RCTs and one observational clinical trial. Neurocognitive testing varied significantly between all studies, including the specific tests administered and the timing of assessments post-cannabis consumption. In general, cognitive performance declined mostly in a THC dose-dependent manner, with steady resolution of impairment in the hours following THC administration. Doses of THC were lower than those typically reported in recreational cannabis studies. In all the studies, there was no difference between any of the THC groups and placebo on any neurocognitive measure after 4 h of recovery. Variability in the dose-dependent relationship raises the consideration that there are other important factors contributing to the duration of neurocognitive impairment besides the dose of THC ingested. These modifiable and non-modifiable factors are individually discussed.