Rachel Lees

Background and aims: Lower risk guidelines for safer levels of cannabis use could help to reduce the health burden posed by cannabis use disorder (CUD). We aimed to estimate risk thresholds for CUD based on delta‐9‐tetrahydrocannabinol (THC) consumption using standard THC units (1 unit = 5 mg THC). Design: Data from the CannTeen study, a longitudinal observational study consisting of five assessments over a 12‐month period. Setting: London, UK. Participants: Participants were n = 65 adults aged 26–29 (46% female, 70.77% white ethnicity) and n = 85 adolescents aged 16–17 (56% female, 65.48% white ethnicity). All participants reported at least one use of cannabis during the 12‐month study period. Measurements: Mean weekly standard THC units were estimated using the Enhanced Cannabis Timeline Followback, a comprehensive and validated assessment of quantity, frequency and potency of cannabis consumed. This was administered at 3‐month intervals and averaged over a 12‐month period. Past 12‐month diagnosis of CUD using The Diagnostic and Statistical Manual of Mental Disorders , Fifth Edition (DSM‐5) was assessed at the final follow‐up. Receiver operating characteristic curve models estimated the extent to which weekly standard THC unit consumption could discriminate no CUD from any CUD (mild, moderate or severe), and no CUD from moderate/severe CUD, in adults and adolescents separately. Risk thresholds were selected based on cut‐offs that maximised sensitivity and specificity. Findings: Discrimination accuracy of weekly standard THC units on CUD was good, with area under the curve > 0.70 for all models. Optimal cut‐offs for risk of any CUD (versus no CUD) were 8.26 units per week for adults and 6.04 units per week for adolescents. For risk of moderate/severe CUD (versus no CUD) optimal cut‐offs were 13.44 units per week for adults and 6.45 units per week for adolescents. Conclusions: Weekly cannabis consumption based on standard delta‐9‐tetrahydrocannabinol (THC) units appears to show good discrimination accuracy of cannabis use disorder at different severities and in different age groups. Safer levels of cannabis use, defined by low weekly standard THC unit consumption, could be recommended in lower risk cannabis use guidelines.

Clinical guidelines recommend collecting reports from multiple informants when identifying and diagnosing challenges in children. The current study examined parent–teacher discrepancies in rating of autistic children’s adaptive functioning and how these related to children’s executive functions. Participants ( n = 194) were a subsample of autistic children (mean age = 9.2 years; 86% male) from the Pathways in ASD cohort. We used latent profile analysis to characterise profiles based on both parent and teacher reports of adaptive functioning levels. We tested links between these profiles and indices of children’s executive function and other clinical correlates. Four profiles were characterised: a lower adaptive functioning-parent higher profile, in which parents reported relatively higher scores than teachers ( n = 45), an intermediate adaptive functioning profile ( n = 70) and a higher adaptive functioning profile ( n = 39; both characterised by similar ratings between informants) and finally, a higher adaptive functioning-teacher higher profile, in which teachers reported relatively higher scores than parents ( n = 40). The higher adaptive functioning-teacher higher profile showed fewer teacher-rated executive function challenges and higher IQ compared to the other profiles. Characterising profiles facilitates interpretation of informant discrepancies and identification of clinical correlates to inform clinical decision-making. Lay Clinicians are advised to collect reports from multiple informants (e.g., parents and teachers), when making assessments about the wellbeing of autistic children. Parents and teachers observe children in different environments (home vs. school); therefore, collecting both reports can give a fuller account of a child’s strengths and challenges. In this investigation, we looked at parent and teacher reports of autistic children’s adaptive functioning, an important body of skills necessary for children to navigate daily life including practical, communication and conceptual skills. Currently, we know little about child characteristics associated with informant discrepancies, which means that it is a challenge to identify which children are most likely to display behaviour differently across contexts. We grouped n = 194 children based on the level of adaptive functioning reported by both their parent and teachers, and we compared the groups on key characteristics. We identified four groups: a lower adaptive functioning group with higher parent scores ( n = 45), an intermediate group with similar scores from both informants ( n = 70), a higher adaptive functioning group with similar scores from both informants ( n = 39) and a higher adaptive functioning group with higher teacher scores ( n = 40). Our findings indicate that many children display adaptive functioning skills differently across contexts, across levels of adaptive functioning skills. We found that children across groups differed on IQ, autistic traits and teacher-rated executive functioning. These findings can help clinicians identify and evaluate autistic children that might be likely to demonstrate different adaptive functioning skills in different environments, which could help with assessment and treatment planning.

Background & Aims: Lower risk guidelines for safer levels of cannabis use could help to reduce the health burden posed by cannabis use disorder (CUD). We aimed to estimate risk thresholds for CUD based on delta-9-tetrahydrocannabinol (THC) consumption using standard THC units (1 unit = 5mg THC). Design: Data from the CannTeen study, a longitudinal observational study consisting of five assessments over a 12-month period. Setting: London, UK. Participants: Participants were n = 65 adults aged 26-29 (46% female, 70.77% white ethnicity) and n = 85 adolescents aged 16-17 (56% female, 65.48% white ethnicity). All participants reported at least one use of cannabis during the 12-month study period and completed an assessment of DSM-5 CUD symptoms at the final follow up. Measurements: Mean weekly standard THC units were estimated using the Enhanced Cannabis Timeline Followback, a comprehensive assessment of quantity, frequency and potency of cannabis consumed. This was administered at 3-month intervals and averaged over a 12-month period. Past 12-month diagnosis of DSM-5 CUD was assessed at the final follow-up. Receiver operating characteristic curve models estimated the extent to which weekly standard THC unit consumption could discriminate no CUD from any CUD (mild, moderate, or severe), and no CUD from moderate/severe CUD, in adults and adolescents separately. Risk thresholds were selected based on cut-offs that maximised sensitivity and specificity. Findings: Discrimination accuracy of weekly standard THC units on CUD was good, with area under the curve > 0.70 for all models. Optimal cut-offs for risk of any CUD (versus no CUD) were 8.26 units per week for adults and 6.04 units per week for adolescents. For risk of moderate/severe CUD (versus no CUD) optimal cut-offs were 13.44 units per week for adults and 6.45 units per week for adolescents. Conclusions: Standard THC units show good discrimination accuracy of CUD at different severities and in different age groups. Safer levels of cannabis use, defined by low weekly standard THC unit consumption, could be recommended in lower risk cannabis use guidelines.

Background: Adolescence is a key developmental period associated with an increased risk of experiencing cannabis-related problems. Identifying modifiable risk factors prior to the onset of cannabis use could help inform preventative interventions. Method: Analysis nested within a UK prospective birth cohort study, the Avon Longitudinal Study of Parents and Children. Participants (n = 6,049) provided data on cannabis use and symptoms of cannabis problems using the Cannabis Abuse Screening Test at two or more time points between the ages of 15–24 years. Risk factors included internalizing and externalizing disorders assessed at age 10 years, and cognitive function assessed at age 8 years via short-term memory, emotion recognition, divided attention, and listening comprehension. Results: Participants were mostly female (59.1%) and white (95.73%). Five patterns of adolescent cannabis use problems were identified using longitudinal latent class analysis: stable-no problems (n = 5,157, 85%), early-onset high (n = 104, 2%), late-onset high (n = 153, 3%), early onset low (n = 348, 6%), and late-onset low (n = 287, 5%). In adjusted models, externalizing disorders were associated with early-onset high [RR, 95% CI: 2.82 (1.72, 4.63)], late-onset high [RR, 95% CI: 1.62 (1.02, 2.57)], and early-onset low [RR, 95% CI: 1.82 (1.30, 2.55)] compared to the stable-no problems class. Internalizing disorders were associated with late-onset low only [RR, 95% CI: .50 (.26, .96)], and short-term memory with late-onset high only [RR, 95% CI: 1.09 (1.01, 1.18) compared to the stable-no problems class. Conclusions: Childhood externalizing disorders were consistently associated with increased risk of problematic patterns of cannabis use over adolescence, particularly early-onset and high levels of problems.

Background: Observational studies consistently report associations between tobacco use, cannabis use and mental illness. However, the extent to which this association reflects an increased risk of new-onset mental illness is unclear and may be biased by unmeasured confounding.Methods: A systematic review and meta-analysis (CRD42021243903). Electronic databases were searched until November 2022. Longitudinal studies in general population samples assessing tobacco and/or cannabis use and reporting the association (e.g. risk ratio [RR]) with incident anxiety, mood, or psychotic disorders were included. Estimates were combined using random-effects meta-analyses. Bias was explored using a modified Newcastle–Ottawa Scale, confounder matrix, E-values, and Doi plots.Results: Seventy-five studies were included. Tobacco use was associated with mood disorders (K = 43; RR: 1.39, 95% confidence interval [CI] 1.30–1.47), but not anxiety disorders (K = 7; RR: 1.21, 95% CI 0.87–1.68) and evidence for psychotic disorders was influenced by treatment of outliers (K = 4, RR: 3.45, 95% CI 2.63–4.53; K = 5, RR: 2.06, 95% CI 0.98–4.29). Cannabis use was associated with psychotic disorders (K = 4; RR: 3.19, 95% CI 2.07–4.90), but not mood (K = 7; RR: 1.31, 95% CI 0.92–1.86) or anxiety disorders (K = 7; RR: 1.10, 95% CI 0.99–1.22). Confounder matrices and E-values suggested potential overestimation of effects. Only 27% of studies were rated as high quality.Conclusions: Both substances were associated with psychotic disorders and tobacco use was associated with mood disorders. There was no clear evidence of an association between cannabis use and mood or anxiety disorders. Limited high-quality studies underscore the need for future research using robust causal inference approaches (e.g. evidence triangulation).

Adolescence is a developmental period characterised by increased vulnerability to cannabis use disorder (CUD). However, previous investigations of this vulnerability have relied on cross-sectional comparisons and lack a detailed assessment of cannabis quantity, a potentially important confounding factor. Here, we aimed to investigate the one-year course of CUD in adolescents compared to adults who currently use cannabis, adjusting for a comprehensive measure of cannabis quantity. Data are from a one-year observational longitudinal study (CannTeen) of adolescents and adults who currently used cannabis regularly with five waves of assessment at 3-monthly intervals, based in London, UK. Participants were n = 70 adults (26–29, 45.7% female), who did not regularly use cannabis when they were under age 18, and n = 76 adolescents (16–17, 50.0% female). The exposure was adolescent (compared to adult) frequent cannabis use. The primary outcome was CUD symptoms measured using the cannabis use disorder identification test revised (CUDIT-R) at five time points. Models were adjusted for cannabis quantity using mean weekly standard THC units (one unit = 5 mg THC). Other covariates included gender, and whether each session occurred before or during the COVID-19 pandemic. In models adjusted for pre-registered covariates, adolescents scored 3.7 points higher on the CUDIT-R compared to the adult group across the 5 assessment waves (3.66 95% CIs 1.99, 5.34). There was also evidence of a linear reduction in symptoms over time in both groups (−0.47, 95%CIs −0.67, −0.27). Adolescents had persistently increased CUD symptoms compared to adults across the 12-month period. This association was robust after adjusting for the quantity of cannabis consumed and other covariates.

Aims: The aims of this study were to present an enhanced cannabis timeline followback (EC‐TLFB) enabling comprehensive assessment of cannabis use measures, including standard tetrahydrocannabinol (THC) units, and to validate these against objectively indexed urinary 11‐nor‐9‐carboxy‐tetrahydrocannabinol (THC‐COOH) concentrations.Design: We used cross‐sectional baseline data from the ‘CannTeen’ observational longitudinal study.Setting: The study was conducted in London, UK.Participants: A total of 147 participants who used cannabis regularly took part in the study (n = 71 female, n = 76 male; mean age = 21.90, standard deviation = 5.32).Measurements: The EC‐TLFB was used to calculate frequency of cannabis use, method of administration, including co‐administration with tobacco, amount of cannabis used (measured with unaided self‐report and also using pictorial aided self‐report) and type of cannabis product (flower, hash) which was used to estimate THC concentration (both from published data on THC concentration of products and analysis of cannabis samples donated by participants in this study). We calculated total weekly standard THC units (i.e. 5 mg THC for all cannabis products and methods of administration) using the EC‐TLFB. The outcome variable for validation of past week EC‐TLFB assessments was creatinine‐normalized carboxy‐tetrahydrocannabinol (THC‐COOH) in urine.Findings: All measures of cannabis exposure included in this analysis were positively correlated with levels of THC‐COOH in urine (r = 0.41–0.52). Standard THC units, calculated with average concentrations of THC in cannabis in the UK and unaided self‐report measures of amount of cannabis used in grams showed the strongest correlation with THC‐COOH in urine (r = 0.52, 95% bias‐corrected and accelerated = 0.26–0.70).Conclusions: The enhanced cannabis timeline followback (EC‐TLFB) can provide a valid assessment of a comprehensive set of cannabis use measures including standard tetrahydrocannabinol units as well as and traditional TLFB assessments (e.g. frequency of use and grams of cannabis use).

Rationale: Chronic cannabis use is associated with impaired cognitive function. Evidence indicates cannabidiol (CBD) might be beneficial for treating cannabis use disorder. CBD may also have pro-cognitive effects; however, its effect on cognition in people with cannabis use disorder is currently unclear. Objectives: We aimed to assess whether a 4-week CBD treatment impacted cognitive function. We hypothesised that CBD treatment would improve cognition from baseline to week 4, compared to placebo. Methods: Cognition was assessed as a secondary outcome in a phase 2a randomised, double-blind, parallel-group and placebo-controlled clinical trial of 4-week daily 200 mg, 400 mg and 800 mg CBD for the treatment of cannabis use disorder. Participants had moderate or severe DSM-5 cannabis use disorder and intended to quit cannabis use. Our pre-registered primary cognitive outcome was delayed prose recall. Secondary cognitive outcomes were immediate prose recall, stop signal reaction time, trail-making task performance, verbal fluency and digit span. Results: Seventy participants were randomly assigned to placebo (n = 23), 400 mg CBD (n = 24) and 800 mg CBD (n = 23). A 200 mg group was eliminated from the trial because it was an inefficacious dose at interim analysis (n = 12) and was not analysed here. For the primary cognitive outcome, there was no effect of CBD compared to placebo, evidenced by a lack of dose-by-time interaction at 400 mg (0.46, 95%CIs: − 1.41, 2.54) and 800 mg (0.89, 95%CIs: − 0.99, 2.81). There was no effect of CBD compared to placebo on secondary cognitive outcomes, except backwards digit span which increased following 800 mg CBD (0.30, 95%CIs: 0.02, 0.58). Conclusions: In this clinical trial for cannabis use disorder, CBD did not influence delayed verbal memory. CBD did not have broad cognitive effects but 800 mg daily treatment may improve working memory manipulation. Clinical trial registration: The trial was registered with ClinicalTrials.gov (NCT02044809) and the EU Clinical Trials Register (2013–000,361-36).