Association of volatile substance, nitrous oxide and alkyl nitrate use with mental health in UK adolescents.

BACKGROUND: 'Inhalants' have been associated with poorer mental health in adolescence, but little is known of associations with specific types of inhalants. AIMS: We aimed to investigate associations of using volatile substances, nitrous oxide and alkyl nitrates with mental health problems in adolescence. METHOD: We conducted a cross-sectional analysis using data from 13- to 14-year-old adolescents across England and Wales collected between September 2019 and March 2020. Multilevel logistic regression examined associations between lifetime use of volatile substances, nitrous oxide and alkyl nitrates with self-reported symptoms of probable depression, anxiety, conduct disorder and auditory hallucinations. RESULTS: Of the 6672 adolescents in the study, 5.1% reported use of nitrous oxide, 4.9% volatile solvents and 0.1% alkyl nitrates. After accounting for multiple testing, adolescents who had used volatile solvents were significantly more likely to report probable depressive (odds ratio = 4.59, 95% CI 3.58, 5.88), anxiety (odds ratio = 3.47, 95% CI 2.72, 4.43) or conduct disorder (odds ratio = 7.52, 95% CI 5.80, 9.76) and auditory hallucinations (odds ratio = 5.35, 95% CI 4.00, 7.17) than those who had not. Nitrous oxide use was significantly associated with probable depression and conduct disorder but not anxiety disorder or auditory hallucinations. Alkyl nitrate use was rare and not associated with mental health outcomes. Adjustment for use of other inhalants, tobacco and alcohol resulted in marked attenuation but socioeconomic disadvantage had little effect. CONCLUSION: To our knowledge, this study provides the first general population evidence that volatile solvents and nitrous oxide are associated with probable mental health disorders in adolescence. These findings require replication, ideally with prospective designs.

Persistent increased severity of cannabis use disorder symptoms in adolescents compared to adults: a one-year longitudinal study.

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.

Association of cannabis, cannabidiol and synthetic cannabinoid use with mental health in UK adolescents.

BACKGROUND: Cannabis has been associated with poorer mental health, but little is known of the effect of synthetic cannabinoids or cannabidiol (often referred to as CBD). AIMS: To investigate associations of cannabis, synthetic cannabinoids and cannabidiol with mental health in adolescence. METHOD: We conducted a cross-sectional analysis with 13- to 14-year-old adolescents across England and Wales in 2019-2020. Multilevel logistic regression was used to examine the association of lifetime use of cannabis, synthetic cannabinoids and cannabidiol with self-reported symptoms of probable depression, anxiety, conduct disorder and auditory hallucinations. RESULTS: Of the 6672 adolescents who participated, 5.2% reported using of cannabis, 1.9% reported using cannabidiol and 0.6% reported using synthetic cannabinoids. After correction for multiple testing, adolescents who had used these substances were significantly more likely to report a probable depressive, anxiety or conduct disorder, as well as auditory hallucinations, than those who had not. Adjustment for socioeconomic disadvantage had little effect on associations, but weekly tobacco use resulted in marked attenuation of associations. The association of cannabis use with probable anxiety and depressive disorders was weaker in those who reported using cannabidiol than those who did not. There was little evidence of an interaction between synthetic cannabinoids and cannabidiol. CONCLUSIONS: To our knowledge, this study provides the first general population evidence that synthetic cannabinoids and cannabidiol are associated with probable mental health disorders in adolescence. These associations require replication, ideally with prospective cohorts and stronger study designs.

Continuities in maternal substance use from early adolescence to parenthood: findings from the intergenerational cohort consortium.

BACKGROUND: This study assessed the extent to which women's preconception binge drinking, tobacco use and cannabis use, reported prospectively in adolescence and young adulthood, predicted use of these substances during pregnancy and at 1 year postpartum. METHODS: Data were pooled from two intergenerational cohort studies: the Australian Temperament Project Generation 3 Study (395 mothers, 691 pregnancies) and the Victorian Intergenerational Health Cohort Study (398 mothers, 609 pregnancies). Alcohol, tobacco and cannabis use were assessed in adolescence (13-18 years), young adulthood (19-29 years) and at ages 29-35 years for those transitioning to parenthood. Exposures were weekly or more frequent preconception binge drinking (5 + drinks in one session), tobacco use and cannabis use. Outcomes were any alcohol, tobacco and cannabis use prior to awareness of the pregnancy, after awareness of pregnancy (up to and including the third trimester pregnancy) and at 1 year postpartum. RESULTS: Frequent preconception binge drinking, tobacco use and cannabis use across both adolescence and young adulthood were strong predictors of continued use post-conception, before and after awareness of the pregnancy and at 1 year postpartum. Substance use limited to young adulthood also predicted continued use post-conception. CONCLUSIONS: Persistent alcohol, tobacco use and cannabis use that starts in adolescence has a strong continuity into parenthood. Reducing substance use in the perinatal period requires action well before pregnancy, commencing in adolescence and continuing into the years before conception and throughout the perinatal period.

Examining pathways between genetic liability for schizophrenia and patterns of tobacco and cannabis use in adolescence.

BACKGROUND: It is not clear to what extent associations between schizophrenia, cannabis use and cigarette use are due to a shared genetic etiology. We, therefore, examined whether schizophrenia genetic risk associates with longitudinal patterns of cigarette and cannabis use in adolescence and mediating pathways for any association to inform potential reduction strategies. METHODS: Associations between schizophrenia polygenic scores and longitudinal latent classes of cigarette and cannabis use from ages 14 to 19 years were investigated in up to 3925 individuals in the Avon Longitudinal Study of Parents and Children. Mediation models were estimated to assess the potential mediating effects of a range of cognitive, emotional, and behavioral phenotypes. RESULTS: The schizophrenia polygenic score, based on single nucleotide polymorphisms meeting a training-set p threshold of 0.05, was associated with late-onset cannabis use (OR = 1.23; 95% CI = 1.08,1.41), but not with cigarette or early-onset cannabis use classes. This association was not mediated through lower IQ, victimization, emotional difficulties, antisocial behavior, impulsivity, or poorer social relationships during childhood. Sensitivity analyses adjusting for genetic liability to cannabis or cigarette use, using polygenic scores excluding the CHRNA5-A3-B4 gene cluster, or basing scores on a 0.5 training-set p threshold, provided results consistent with our main analyses. CONCLUSIONS: Our study provides evidence that genetic risk for schizophrenia is associated with patterns of cannabis use during adolescence. Investigation of pathways other than the cognitive, emotional, and behavioral phenotypes examined here is required to identify modifiable targets to reduce the public health burden of cannabis use in the population.

Legal status of recreational cannabis and self-reported substitution of cannabis for opioids or prescription pain medication in Canada and the United States.

Aims: With increased liberalization of cannabis policies in North America, there is growing interest in the use of cannabis to manage pain instead of opioids. The objectives of the study were to (1) examine the use of cannabis for pain relief in Canada and the United States (US) in 2018 and 2019; (2) examine the association between recreational cannabis laws and changes in the use of cannabis for pain relief, instead of opioids or prescription pain medication. Methods: Repeat cross-sectional survey data were used from Wave 1 and Wave 2 of the International Cannabis Policy Study conducted in 2018 and 2019 in Canada and the US. Respondents were recruited through commercial panels, aged 16-65, and had ever tried cannabis (N = 44,119). Weighted binary logistic regression models examined the association between the legal status of recreational cannabis and cannabis use for pain relief instead of opioids or prescription pain medication (n = 15,092). Results: Between 14-33% of cannabis consumers in Canada and the US reported using cannabis to manage headaches or pain. Of these consumers, 79% and 78% respondents in Canada; 80% and 83% in US illegal states; and 83% and 84% in US legal states, in 2018 and 2019, respectively, reported cannabis use for pain relief instead of opioids or prescription pain medication. There was little evidence of an association between the legal status of recreational cannabis and cannabis use for pain relief instead of opioids or prescription pain medication, among Canadian (AOR = 0.98, 95% CI: 0.78, 1.22) and US respondents (AOR = 1.11, 95% CI: 0.96, 1.28). Conclusions: Although substitution of cannabis for opioids or prescription pain medication is common among those who use cannabis for pain, there does not seem to be a significant difference according to cannabis legality. Future research should examine cannabis and opioid substitution using different research designs and time frames.

Precursors and correlates of transient and persistent longitudinal profiles of psychotic experiences from late childhood through early adulthood.

BACKGROUND: Psychotic experiences are reported by 5-10% of young people, although only a minority persist and develop into psychotic disorders. It is unclear what characteristics differentiate those with transient psychotic experiences from those with persistent psychotic experiences that are more likely to be of clinical relevance. AIMS: To investigate how longitudinal profiles of psychotic experiences, created from assessments at three different time points, are influenced by early life and co-occurring factors. METHOD: Using data from 8045 individuals from a birth cohort study, longitudinal profiles of psychotic experiences based on semi-structured interviews conducted at 12, 18 and 24 years were defined. Environmental, cognitive, psychopathological and genetic determinants of these profiles were investigated, along with concurrent changes in psychopathology and cognition. RESULTS: Following multiple imputations, the distribution of longitudinal profiles of psychotic experiences was none (65.7%), transient (24.1%), low-frequency persistent (8.4%) and high-frequency persistent (1.7%). Individuals with high-frequency persistent psychotic experiences were more likely to report traumatic experiences, other psychopathology, a more externalised locus of control, reduced emotional stability and conscientious personality traits in childhood, compared with those with transient psychotic experiences. These characteristics also differed between those who had any psychotic experiences and those who did not. CONCLUSIONS: These findings indicate that the same risk factors are associated with incidence as with persistence of psychotic experiences. Thus, it might be that the severity of exposure, rather than the presence of specific disease-modifying factors, is most likely to determine whether psychotic experiences are transient or persist, and potentially develop into a clinical disorder over time.

Psychosocial and pharmacological treatments for cannabis use disorder and mental health comorbidities: a narrative review.

Cannabis is the most widely used illicit drug worldwide, and it is estimated that up to 30% of people who use cannabis will develop a cannabis use disorder (CUD). Demand for treatment of CUD is increasing in almost every region of the world and cannabis use is highly comorbid with mental disorders, where sustained use can reduce treatment compliance and increase risk of relapse. In this narrative review, we outline evidence for psychosocial and pharmacological treatment strategies for CUD, both alone and when comorbid with psychosis, anxiety or depression. Psychosocial treatments such as cognitive behavioural therapy, motivational enhancement therapy and contingency management are currently the most effective strategy for treating CUD but are of limited benefit when comorbid with psychosis. Pharmacological treatments targeting the endocannabinoid system have the potential to reduce cannabis withdrawal and cannabis use in CUD. Mental health comorbidities including anxiety, depression and psychosis hinder effective treatment and should be addressed in treatment provision and clinical decision making to reduce the global burden of CUDs. Antipsychotic medication may decrease cannabis use and cannabis craving as well as psychotic symptoms in patients with CUD and psychosis. Targeted treatments for anxiety and depression when comorbid with CUD are feasible.

Rapid evidence review of harm reduction interventions and messaging for people who inject drugs during pandemic events: implications for the ongoing COVID-19 response.

BACKGROUND: People who inject drugs are at increased health risk in a pandemic due to their greater susceptibility to severe disease and as a consequence of the restrictions put in place to halt the spread of infection. Harm reduction (HR) services, which aim to reduce the negative effects of drug use on health, are likely to be diminished in a pandemic. However, innovative HR interventions and messaging may also develop in response to such a crisis. It is vital to understand the most effective ways to deliver HR in pandemic situations so that guidance can be provided for current and future disruptions to service provision. METHODS: A rapid evidence review was conducted with the aim of exploring what HR interventions and messaging are most effective during a pandemic-type situation. Ten health databases were systematically searched using terms relevant to the research aim. A search was also made of grey literature, including a targeted search of HR messaging from key national and service provider websites. RESULTS: In the initial search, 121 pieces of evidence were identified which, after screening and de-duplication, resulted in 60 for inclusion. The included evidence consists mainly of non-peer reviewed, pre-publication or expert opinion pieces. The rapid findings suggest that HR services should be deemed essential during a pandemic, with staff supported to work safely and social distancing adaptations implemented. Services should be encouraged to operate more flexibly; for instance, in deciding the amounts of take-home supplies of injecting equipment and medications. The evidence on HR communication was very limited but key messages on infection control, uncertain drug supply and accessing services were identified. CONCLUSIONS: This rapid evidence review identifies implications for national policy makers, commissioners and HR service providers. A person-centred rather than disease-centred approach to HR delivered by collaborating partners, as well as prioritizing tailored HR messaging, is recommended. Further research evaluating the delivery of HR services and messaging, particularly focusing on health inequalities, is urgently needed.

A Global Meta-analysis of the Prevalence of HIV, Hepatitis C Virus, and Hepatitis B Virus Among People Who Inject Drugs-Do Gender-Based Differences Vary by Country-Level Indicators?

BACKGROUND: Women-specific factors exist that increases vulnerability to drug-related harms from injection drug use, including blood-borne viruses (BBVs), but gender-based differences in BBV prevalence have not been systematically examined. METHODS: We conducted meta-analyses to estimate country, regional, and global prevalence of serologically confirmed human immunodeficiency virus (HIV), hepatitis C virus (HCV; based on detection of anti-HCV antibody), and hepatitis B virus (HBV; based on detection of HBV surface antigen) in people who inject drugs (PWID), by gender. Gender-based differences in the BBV prevalence (calculated as the risk among women relative to the risk among men) were regressed on country-level prevalence and inequality measures (Gender inequality index, Human development index, Gini coefficient, and high, low or middle income of the country). RESULTS: Gender-based differences varied by countries and regions. HIV prevalence was higher among women than men in sub-Saharan Africa (relative risk [RR], 2.8; 95% confidence interval [CI], 1.8-4.4) and South Asia (RR, 1.7; 95% CI, 1.1-2.7); anti-HCV was lower among women in the Middle East and North Africa (RR, 0.6; 95% CI, .5-.7) and East and Southeast Asia (RR, 0.8; 95% CI, .7-.9). Gender-based differences varied with country-levels of the BBV prevalence in the general population, human development, and income distribution. CONCLUSION: HIV was more prevalent in women who inject drugs as compared to their male counterparts in some countries, but there is variation between and within regions. In countries where women are at higher risks, there is a need to develop gender-sensitive harm-reduction services for the particularly marginalized population of women who inject drugs.

Overlap of heritable influences between cannabis use disorder, frequency of use and opportunity to use cannabis: trivariate twin modelling and implications for genetic design.

BACKGROUND: The genetic component of Cannabis Use Disorder may overlap with influences acting more generally on early stages of cannabis use. This paper aims to determine the extent to which genetic influences on the development of cannabis abuse/dependence are correlated with those acting on the opportunity to use cannabis and frequency of use. METHODS: A cross-sectional study of 3303 Australian twins, measuring age of onset of cannabis use opportunity, lifetime frequency of cannabis use, and lifetime DSM-IV cannabis abuse/dependence. A trivariate Cholesky decomposition estimated additive genetic (A), shared environment (C) and unique environment (E) contributions to the opportunity to use cannabis, the frequency of cannabis use, cannabis abuse/dependence, and the extent of overlap between genetic and environmental factors associated with each phenotype. RESULTS: Variance components estimates were A = 0.64 [95% confidence interval (CI) 0.58-0.70] and E = 0.36 (95% CI 0.29-0.42) for age of opportunity to use cannabis, A = 0.74 (95% CI 0.66-0.80) and E = 0.26 (95% CI 0.20-0.34) for cannabis use frequency, and A = 0.78 (95% CI 0.65-0.88) and E = 0.22 (95% CI 0.12-0.35) for cannabis abuse/dependence. Opportunity shares 45% of genetic influences with the frequency of use, and only 17% of additive genetic influences are unique to abuse/dependence from those acting on opportunity and frequency. CONCLUSIONS: There are significant genetic contributions to lifetime cannabis abuse/dependence, but a large proportion of this overlaps with influences acting on opportunity and frequency of use. Individuals without drug use opportunity are uninformative, and studies of drug use disorders must incorporate individual exposure to accurately identify aetiology.

Incident psychotic experiences following self-reported use of high-potency cannabis: Results from a longitudinal cohort study.

BACKGROUND AND AIMS: High-potency cannabis has been associated with increased risk of psychosis, but a lack of prospective data hinders understanding of causality in this relationship. This study aimed to combine prospective report of cannabis use with retrospective report of potency to infer the potency of cannabis used in adolescence and explore whether use of cannabis, and the use of high-potency cannabis, in adolescence is associated with incident psychotic experiences. DESIGN: Population-based birth cohort study. SETTING: United Kingdom. PARTICIPANTS: n = 5570 participants who reported on any cannabis use (yes/no) age 16 and 18 years, and n = 1560 participants from this group who also retrospectively reported on cannabis potency. MEASUREMENTS: In questionnaires at ages 16 and 18, individuals self-reported lifetime cannabis use, and at age 24, participants reported the type of cannabis they most commonly used in the whole time since first using cannabis. Psychotic experiences were assessed at age 24 years using the semi-structured Psychosis-Like Symptom Interview, with incident defined as new-onset occurring between ages 19 and 24 years. FINDINGS: Use of high-potency cannabis at age 16 or 18 was associated with twice the likelihood of experiencing incident psychotic experiences from age 19-24 (Odds Ratio 2.15, 95% Confidence Intervals 1.13-4.06). There was less evidence for an effect of any cannabis use on incident psychotic experiences (Odds Ratio 1.45, 95% Confidence Intervals 0.94-2.12). CONCLUSIONS: Use of high-potency cannabis appears to be associated with increased likelihood of psychotic experiences.

Does maternal education moderate the relationship between adolescent cannabis use and mental health in early adulthood?

INTRODUCTION: Socioeconomic disadvantage has been associated with cannabis use and poor mental health. It is therefore hypothesised that lower maternal education, a proxy for socioeconomic disadvantage, may increase the risk of cannabis-related mental health and substance use consequences. METHODS: A total of 5099 participants from the Avon Longitudinal Study of Parents and Children reported cannabis use via questionnaires at 16 or 18. Logistic regression was used to examine the relationship between any and regular (weekly or more) adolescent cannabis use with depression, anxiety, psychotic experiences, and problematic cannabis use at age 24. Maternal education was included as an effect modifier. Missing data were addressed through multiple imputation using chained equations. RESULTS: In total, 36.5% of participants reported adolescent cannabis use and, of these, 14% reported regular use. Adolescent cannabis use was associated with an increased likelihood of anxiety and problematic cannabis use; however, there was little evidence of moderation by maternal education. Regular cannabis use was associated with an increased likelihood of problematic cannabis use, with little evidence of moderation by maternal education. There was weak evidence that the association between regular cannabis use and depression (interaction p-value = 0.024) and anxiety (interaction p-value = 0.056) was stronger in people with high maternal education. DISCUSSION AND CONCLUSIONS: Adolescent cannabis use is associated with increased risk of anxiety and cannabis use disorder, but there was insufficient evidence that childhood socioeconomic position (proxied by maternal education) modifies this relationship. Improved public health messages for all adolescents about these risks may be warranted.

Association between cannabis potency and mental health in adolescence.

INTRODUCTION: In legal and illegal markets, high-potency cannabis (>10 % delta-9-tetrahydrocannabinol (THC)) is increasingly available. In adult samples higher-potency cannabis has been associated with mental health disorder but no studies have considered associations in adolescence. METHODS: A population-wide study compared no, low and high potency cannabis using adolescents (aged 13-14 years) self-reported symptoms of probable depression, anxiety, and auditory hallucinations. RESULTS: Of the 6672 participants, high-potency cannabis was used by 2.6 % (n=171) and low-potency by 0.6 % (n=38). After adjustment for sociodemographic factors, tobacco and alcohol use, in comparison to participants who had never used cannabis, people who had used high-potency but not low-potency cannabis were more likely to report symptoms of depression (odds ratio 1.59 [95 % confidence interval 1.06, 2.39), anxiety (OR 1.45, 95 % CI 0.96, 2.20), and auditory hallucinations (OR 1.56, 95 % CI 0.98, 2.47). CONCLUSIONS: High-potency cannabis use is associated with an increased risk of probable mental health disorders. Services and programming to minimise drug harms may need to be adapted to pay more attention to cannabis potency.

Directional Adhesion of Monodomain Liquid Crystalline Elastomers.

Pressure-sensitive adhesives (PSAs) are widely employed in consumer goods, health care, and commercial industry. Anisotropic adhesion of PSAs is often desirable to enable high force capacity coupled with facile release and has typically been realized through the introduction of complex surface and/or bulk microstructures while also maintaining high surface conformability. Although effective, microstructure fabrication can add cost and complexity to adhesive fabrication. Here, we explore aligned liquid crystalline elastomers (LCEs) as directional adhesives. Aligned LCEs exhibit direction-dependent stiffness, dissipation, and nonlinear deformation under load. By varying the cross-link content, we study how the bulk mechanical properties of LCEs correlate to their peel strength and peel anisotropy. We demonstrate up to a 9-fold difference in peel force measured when the LCE is peeled parallel vs perpendicular to the alignment axis. Opportunities to spatially localize adhesion are presented in a monolithic LCE patterned with different director orientations.

Enhanced cannabis timeline followback (EC-TLFB): Comprehensive assessment of cannabis use including standard THC units and validation through biological measures.

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).

Understanding and learning from rural drug service adaptations to opioid substitution therapy during the COVID-19 pandemic: the What C-OST? study.

Introduction: In April 2020, in response to government COVID-19 advice, changes were made to the way English drug services operated. Methadone and buprenorphine were typically dispensed in 1- to 2-week supplies, and key working was conducted by phone/online. Previous studies have examined the impact of these changes on people from urban settings. This study adds the experiences and perspectives of people receiving care from drug services in rural areas and makes suggestions for future emergency planning. Methods: Telephone semi-structured interviews were conducted with 15 people receiving care in Somerset, Wiltshire, and Suffolk, rural counties in England. Reflexive thematic analysis was used. Results: Three overarching themes were found. "Challenges of rural lockdown" (theme 1) describes how rural community challenges, especially reduced or no rural public transport, were experienced. This hampered some OST collections, with consequential drug use. It also impeded connections to loved ones, worsening isolation. For participants who were struggling pre-pandemic, the intersection between this and their experience of revised drug service operations is embodied in "Amplification of Social Disconnection: Cut off and unheard" (theme 2). They felt a lack of support, particularly from remote provision key working. Participants who had supportive relationships and time in the pandemic occupied in ways they found meaningful, and others who struggled with anxiety or depression, found pandemic changes "Fits better with my life" (theme 3). They experienced more freedom for other things, gained support by other means, such as family, or felt more comfortable with remote engagement. A cross-cutting sub-theme "Understandable Interruptions" showed acceptance of pandemic disruptions. Conclusion: National guidance and organizational policy impacted participants in different ways. Those who had supportive relationships and occupied time were better able to make positive use of newfound freedoms and engage with community-level support. In contrast, those who had less stability, including mental health struggles and social isolation, felt cut off and unheard, particularly from key workers. Reduced rural transport was a significant community-level issue, which impeded OST collection and social support. We suggest emergency response plans be created for individuals taking account of their pre-existing personal situations.

High potency cannabis use, mental health symptoms and cannabis dependence: Triangulating the evidence.

BACKGROUND: Cannabis potency (concentration of Δ-9-Tetrahydrocannabinol) has been associated with risks of adverse mental health outcomes and addiction but no studies have triangulated evidence from self-report and objective measures of cannabis potency. We hypothesised that users of high potency cannabis would have higher levels of (a) anxiety, (b) depression and (c) psychosis-like symptoms (d) cannabis dependence than users of lower potency cannabis. METHODS: A cross-sectional study of 410 participants donated a sample of cannabis for analysis of THC concentration and reported their cannabis potency preference. These two exposure measures were investigated for their association with cannabis dependence, depression, anxiety, and psychosis-like symptoms in separate linear/logistic regression models. RESULTS: High potency cannabis preference was associated with a slight increased risk of cannabis dependence after adjusting for confounding, with the exception of cannabis use frequency (OR = 1.16, 95% CI 1.04-1.28). No association was found between THC concentration in cannabis and cannabis dependence. There was weak evidence of a small association between cannabis potency and depression and anxiety. There was no association between high potency cannabis preference or THC concentration in cannabis and psychosis-like symptoms. CONCLUSIONS: Users of cannabis who preferred high potency types might be at increased risk of problematic cannabis use. This should be considered with caution as we were not able to triangulate these results with an objective measure of cannabis potency. More research is needed to understand the association between high potency cannabis use and depression and anxiety.

Adverse childhood experiences and adolescent cannabis use trajectories: findings from a longitudinal UK birth cohort.

BACKGROUND: Adverse childhood experiences (ACEs) are classically defined as physical abuse, sexual abuse, emotional abuse, emotional neglect, bullying, parental substance use or abuse, violence between parents, parental mental health problems or suicide, parental separation, or a parent convicted of criminal offence. Exposure to ACEs can be associated with cannabis use, but no comparisons across all adversities have been made while also considering timing and frequency of cannabis use. We aimed to explore the association between ACEs and cannabis use timing and frequency in adolescence, considering the cumulative number of ACEs and individual ACEs. METHODS: We used data from the Avon Longitudinal Study of Parents and Children, a longitudinal UK birth cohort study. Longitudinal latent classes of cannabis use frequency were derived from self-reported data at multiple timepoints in participants aged 13-24 years. ACEs between ages 0 years and 12 years were derived from prospective and retrospective reports at multiple timepoints by parents and the participant. Multinomial regression was used to analyse the effect of both cumulative exposure to all ACEs and the ten individual ACEs on cannabis use outcomes. FINDINGS: 5212 participants (3132 [60·0%] were female and 2080 [40·0%] were male; 5044 [96·0%] were White and 168 [4·0%] were Black, Asian, or minority ethnic) were included in this study. After adjustment for polygenic risk and environmental risk factors, participants who had 4 or more ACEs at age 0-12 years were at increased risk of early persisting regular cannabis use (relative risk ratio [RRR] 3·15 [95% CI 1·81-5·50]), later onset regular use (1·99 [1·14-3·74]), and early persisting occasional use (2·55 [1·74-3·73]) compared with low or no cannabis use. After adjustment, early persisting regular use was associated with parental substance use or abuse (RRR 3·90 [95% CI 2·10-7·24]), parental mental health problems (2·02 [1·26-3·24]), physical abuse (2·27 [1·31-3·98]), emotional abuse (2·44 [1·49-3·99]), and parental separation (1·88 [1·08-3·27]) compared with low or no cannabis use. INTERPRETATION: Risks for problematic adolescent cannabis use are highest for individuals reporting 4 or more ACEs, and were particularly raised for those with parental substance use or abuse. Public health measures to address ACEs might reduce adolescent cannabis use. FUNDING: The Wellcome Trust, UK Medical Research Council, Alcohol Research UK.

Effect of four-week cannabidiol treatment on cognitive function: secondary outcomes from a randomised clinical trial for the treatment of cannabis use disorder.

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).