Medicinal cannabis for treating post-traumatic stress disorder and comorbid depression: real-world evidence.

BACKGROUND: Cannabis-based medicinal products (CBMPs) are increasingly being used to treat post-traumatic stress disorder (PTSD), despite limited evidence of their efficacy. PTSD is often comorbid with major depression, and little is known about whether comorbid depression alters the effectiveness of CBMPs. AIMS: To document the prevalence of depression among individuals seeking CBMPs to treat PTSD and to examine whether the effectiveness of CBMPs varies by depression status. METHOD: Data were available for 238 people with PTSD seeking CBMP treatment (5.9% of the treatment-seeking sample) and 3-month follow-up data were available for 116 of these. Self-reported PTSD symptoms were assessed at treatment entry and at 3-month follow-up using the PTSD Checklist - Civilian Version (PCL-C). The probable presence of comorbid depression at treatment entry was assessed using the nine-item Patient Health Questionnaire (PHQ-9). Additional data included sociodemographic characteristics and self-reported quality of life. RESULTS: In total, 77% met screening criteria for depression, which was associated with higher levels of PTSD symptomatology (mean 67.8 v. 48.4, F(1,236) = 118.5, P < 0.001) and poorer general health, quality of life and sleep. PTSD symptomatology reduced substantially 3 months after commencing treatment (mean 58.0 v. 47.0, F(1,112) = 14.5, P < 0.001), with a significant interaction (F(1,112) = 6.2, P < 0.05) indicating greater improvement in those with depression (mean difference 15.3) than in those without (mean difference 7). CONCLUSIONS: Depression is common among individuals seeking CBMPs to treat PTSD and is associated with greater symptom severity and poorer quality of life. Effectiveness of CBMPs for treating PTSD does not appear to be impaired in people with comorbid depression.

Feasibility of a cannabidiol-dominant cannabis-based medicinal product for the treatment of long COVID symptoms: A single-arm open-label feasibility trial.

AIMS: To conduct a single-arm open-label feasibility trial of the safety and tolerability of a full-spectrum cannabidiol (CBD)-dominant cannabis-based medicinal product for treating the symptoms of long COVID. METHODS: The treatment phase ran for a total of 21 weeks, followed by ~3 weeks without the study drug. Participants received up to 3 mL of MediCabilis 5% CBD Oil (50 mg CBD/mL, <2 mg δ-9-tetrahydrocannabinol/mL) per day orally. Monthly patient-reported outcome measures of common symptoms and daily self-report of symptoms were collected via a smartphone app. Key measures of heart rate, activity, sleep and oxygen saturation were assessed using wearable technology. RESULTS: Twelve (1 male, 11 female) individuals diagnosed with long COVID were recruited into the trial. All participants adhered to the treatment protocol for the duration of the study and there were no serious adverse events. Response rates for the research assessments were high with over 90% completion of patient-reported outcome measures and daily self-report. CONCLUSION: The study drug was safe and well-tolerated, demonstrating feasibility of CBD-dominant cannabis-based medicinal products in individuals diagnosed with long COVID. However, there were limitations in research design related to recruitment strategy demonstrating a lack of feasibility in the approach implemented in this study. Future work with larger samples and incorporating a control group are required to test the efficacy of this treatment.

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.

Adolescent substance use and high school noncompletion: exploring the nature of the relationship using a discordant twin design.

BACKGROUND AND AIMS: Previous studies have demonstrated associations between substance use and reduced educational attainment; however, many were unable to account for potential confounding factors like genetics and the rearing environment. In the few studies that controlled for these factors, the substances assessed were limited to alcohol, cannabis, and tobacco. To address these limitations, we examined the relationship between adolescent use of seven kinds of substances, the number of additional substances used, and high school noncompletion within a large sample of Australian twins. DESIGN: A series of two-level generalized mixed effects logistic regressions were conducted to examine associations between adolescent substance use and high school noncompletion. SETTING: Australia. PARTICIPANTS: A total of 9579 adult Australian twins from two cohorts of the Australian Twin Registry. MEASUREMENTS: Assessments of high school completion, childhood major depression, conduct disorder symptoms, substance use initiation, demographics, and parental educational attainment using the Australian version of the Semi-Structured Assessment for the Genetics of Alcoholism. FINDINGS: There were unique within-twin-pair effects of use of sedatives (odds ratio [OR] = 22.39 [95% confidence interval (CI) = 1.18-423.48]) and inhalants/solvents (OR = 10.46 [95% CI = 1.30-84.16]) on high school noncompletion. The number of substances used in adolescence was strongly associated with high school noncompletion across all discordant twin models (ORs from 1.50-2.32, Ps < 0.03). CONCLUSIONS: In Australia, adolescent substance use appears to be associated with early school dropout, with the effects of any given substance largely because of the confounding factors of parental education, childhood conduct disorder symptoms, and use of other substances. Sedatives and inhalants/solvents have effects on high school noncompletion that cannot be explained by polysubstance use or familial factors.

The value of real world evidence: The case of medical cannabis.

Randomised controlled trials (RCTs) have long been considered the gold standard of medical evidence. In relation to cannabis based medicinal products (CBMPs), this focus on RCTs has led to very restrictive guidelines in the UK, which are limiting patient access. There is general agreement that RCT evidence in relation to CBPMs is insufficient at present. As well as commercial reasons, a major problem is that RCTs do not lend themselves well to the study of whole plant medicines. One solution to this challenge is the use of real world evidence (RWE) with patient reported outcomes (PROs) to widen the evidence base. Such data increasingly highlights the positive impact medical cannabis can have on patients' lives. This paper outlines the value of this approach which involves the study of interventions and patients longitudinally under medical care. In relation to CBMPs, RWE has a broad range of advantages. These include the study of larger groups of patients, the use of a broader range and ratio of components of CBMPs, and the inclusion of more and rarer medical conditions. Importantly, and in contrast to RCTs, patients with significant comorbidities-and from a wider demographic profile-can also be studied, so providing higher ecological validity and increasing patient numbers, whilst offering significant cost savings. We conclude by outlining 12 key recommendations of the value of RWE in relation to medical cannabis. We hope that this paper will help policymakers and prescribers understand the importance of RWE in relation to medical cannabis and help them develop approaches to overcome the current situation which is detrimental to patients.

"Flower Power": Controlled Inhalation of THC-Predominant Cannabis Flos Improves Health-Related Quality of Life and Symptoms of Chronic Pain and Anxiety in Eligible UK Patients.

In November 2018, the UK's Home Office established a legal route for eligible patients to be prescribed cannabis-based products for medicinal use in humans (CBPMs) as unlicensed medicines. These include liquid cannabis extracts for oral administration ("oils") and dried flowers for inhalation ("flos"). Smoking of CBPMs is expressly prohibited. To date, THC-predominant cannabis flowers remain the most prescribed CBPMs in project Twenty21 (T21), the first multi-center, prospective, observational UK cannabis patient registry. This observational, prospective data review analyzes patient-reported outcome measures (PROMS) collected by T21 associated with the inhalation of KHIRON 20/1, the most prescribed CBPM in the project. PROMS collected at baseline and at subsequent 3-month follow-up included health-related quality of life (HRQoL), general mood, and sleep. Condition-specific measures of illness severity were performed with the Brief Pain Inventory Short Form (BPI-SF) and the Generalized Anxiety Disorder 7-Item Scale (GAD-7). Participants (N = 344) were mostly males (77.6%, average age = 38.3) diagnosed mainly with chronic pain (50.9%) and anxiety-related disorders (25.3%). Inhalation of KHIRON 20/1 was associated with a marked increase in self-reported HRQoL, general mood, and sleep (N = 344; p < 0.001). Condition-specific assessments showed significant improvements in pain severity (T = 6.67; p < 0.001) and interference (T = 7.19; p < 0.001) in patients using KHIRON 20/1 for chronic pain (N = 174). Similar results were found for patients diagnosed with anxiety-related disorders (N = 107; T = 12.9; p < 0.001). Our results indicate that controlled inhalation of pharmaceutical grade, THC-predominant cannabis flos is associated with a significant improvement in patient-reported pain scores, mood, anxiety, sleep disturbances and overall HRQoL in a treatment-resistant clinical population.

An Epidemiologic, Longitudinal, and Discordant-Twin Study of the Association Between Gambling Disorder and Suicidal Behaviors.

Gambling disorder is associated with suicidal behaviors, but it is not clear whether the association is due to common etiologic factors or to gambling disorder being causally related to suicidality. This question was examined from epidemiologic, longitudinal, and discordant twin study perspectives. The results suggested that the causes of the association with disordered gambling differed for suicidal ideation, plan, and attempt, and differed for men and women. The association of suicidal thoughts with disordered gambling was non-causally explained by common genetic influences among women (but not men). Conversely, there was evidence consistent with a potentially causal influence of disordered gambling on suicide attempt among men (but not women), which might have been related to gambling-related financial problems. The use of monetary data to identify individuals experiencing financial harms associated with their gambling may represent a more practicable target for screening, intervention, and prevention and may reduce gambling-related financial crises, thereby warding off a potential gambling-related suicide attempt.

Characteristics of People Seeking Prescribed Cannabinoids for the Treatment of Chronic Pain: Evidence From Project Twenty 21.

Background: Prescribed cannabinoids are now legal in the UK and increasingly being used for a variety of conditions, with one of the most frequent conditions being chronic pain. This paper describes the characteristics of individuals seeking prescribed cannabinoids for the treatment of chronic pain in Project Twenty 21, a UK based real world data registry of prescribed cannabis patients. Method: By 1st November 2021 data were available for 1,782 people who had sought treatment with medical cannabis as part of Project Twenty 21. The most common diagnosis among this cohort was chronic pain with 949 (53.5%) of the cohort reporting a primary condition related to chronic pain. Medical and self-report data on the characteristics of these patients, their health status and type/s of cannabinoid/s prescribed are summarized in this report. Results: Of the 949 people reporting chronic pain as a primary condition 54.7% were male and their average age was 42.0 years (range = 18-84). Patients reported a low quality of life and high levels of comorbidity: people reported an average of 4.6 comorbid conditions with the most common comorbid conditions including anxiety, depression, insomnia and stress. A range of cannabinoid products were prescribed with the most common products being classified as high THC flower (48.5%). The majority of patients also reported using at least one other prescribed medication (68.7%). Conclusions: Consistent with findings in other national and international databases, chronic pain was the most common primary condition in this real world study of prescribed cannabinoids. There was considerable variation in the types of chronic pain, comorbid pathology and in the characteristics of products being prescribed to treat these conditions. Together, this evidence supports the utility of real world evidence, as opposed to clinical trial approaches to studying the potential benefits of prescribed cannabinoids in treating chronic pain.

Differences in Alcohol and Other Drug Use and Dependence Between Transgender and Cisgender Participants from the 2018 Global Drug Survey.

Purpose: The purpose of this study was to compare five gender groups (cisgender women, cisgender men, transgender women, transgender men, people with nonbinary/other identities) on measures of use of and dependence on seven substances. Methods: A two-stage approach to assessing gender allowed 126,648 participants from the 2018 Global Drug Survey (GDS) to be classified to one of these five gender groups. Participants were asked to disclose use of each substance in the preceding 12 months. The Alcohol Use Disorders Identification Test and the Severity of Dependence Scale were used to assess dependence. Multivariable logistic regression generated odds ratios (ORs) to measure the association between gender and each substance use/dependence outcome, with cisgender women as the reference group. Results: The sample comprised 43,331 cisgender women, 81,607 cisgender men, 215 transgender women, 254 transgender men, and 1241 people with nonbinary/other identities. Relative to cisgender women, nonbinary/other participants reported greater odds of last 12-month use of all substances (adjusted odds ratio [AOR] = 1.66-2.30), except alcohol (lower odds; AOR = 0.42), and greater odds of dependence on cannabis (AOR = 2.39), 3,4-methylenedioxymethamphetamine (AOR = 1.64) and alcohol (AOR = 3.28), adjusting only for age (all p < 0.05). Conclusion: Transgender 2018 GDS respondents, particularly those with nonbinary/other identities, had greater odds of reporting most substance use outcomes than cisgender women. These findings suggest that a nuanced approach to gender reporting in surveys and treatment centers is required to understand the needs of transgender people who use substances.

Substance use in psychiatric crisis: relationship to violence.

BACKGROUND: Substance use and psychiatric illness, particularly psychotic disorders, contribute to violence in emergency healthcare settings. However, there is limited research regarding the relationship between specific substances, psychotic symptoms and violent behaviour in such settings. We investigated the interaction between recent cannabinoid and stimulant use, and acute psychotic symptoms, in relation to violent behaviour in a British emergency healthcare setting. METHODS: We used electronic medical records from detentions of 1089 individuals under Section 136 of the UK Mental Health Act (1983 amended 2007), an emergency police power used to detain people for 24-36 h for psychiatric assessment. The relationship between recent cannabinoids and/or stimulant use, psychotic symptoms, and violent behaviour, was estimated using logistic regression. FINDINGS: There was evidence of recent alcohol or drug use in 64.5% of detentions. Violent incidents occurred in 12.6% of detentions. Psychotic symptoms increased the odds of violence by 4.0 [95% confidence intervals (CI) 2.2-7.4; p < 0.0001]. Cannabinoid use combined with psychotic symptoms increased the odds of violence further [odds ratios (OR) 7.1, 95% CI 3.7-13.6; p < 0.0001]. Recent use of cannabinoids with stimulants but without psychotic symptoms was also associated with increased odds of violence (OR 3.3, 95% CI 1.4-7.9; p < 0.0001). INTERPRETATION: In the emergency setting, patients who have recently used cannabinoids and exhibit psychotic symptoms are at higher risk of violent behaviour. Those who have used both stimulants and cannabinoids without psychotic symptoms may also be at increased risk. De-escalation protocols in emergency healthcare settings should account explicitly for substance use.

Clinical withdrawal symptom profile of synthetic cannabinoid receptor agonists and comparison of effects with high potency cannabis.

Synthetic cannabinoid receptor agonists (SCRAs) may be used as an alternative to natural cannabis; however, they may carry a greater risk of problematic use and withdrawal. This study aimed to characterise the withdrawal symptom profile of SCRAs and compare their profile of effect with high-potency herbal cannabis. Global Drug Survey data (2015 and 2016) were used to access a clinically relevant sample of people reporting use of SCRAs >10 times in the past 12-months, a previous SCRA quit attempt, and lifetime use of high-potency herbal cannabis. Participants completed an 11-item SCRA withdrawal symptom checklist and compared SCRAs and high-potency herbal cannabis on their onset and duration of effects, speed of the development of tolerance, severity of withdrawal, and difficulty with dose titration. Participants (n = 284) reported experiencing a mean of 4.4 (95% CI: 4.1, 4.8) withdrawal symptoms after not using SCRAs for >1 day; most frequently reported were sleep issues (59.2%), irritability (55.6%), and low mood (54.2%). Withdrawal symptoms were significantly associated with frequency (>51 vs. 11-50 times per year: IRR = 1.43, 95% CI: 1.16, 1.77, p = 0.005) and quantity (grams per session: IRR = 1.13, 95% CI: 1.05, 1.22, p = 0.001) of SCRA use. Compared to high-potency herbal cannabis, SCRAs were rated as having a faster onset and shorter duration of effects, faster development of tolerance, and more severe withdrawal (p's < 0.001). In conclusion, SCRA withdrawal symptoms are more likely to occur after greater SCRA exposure. The effects of SCRA indicate a more severe withdrawal syndrome and a greater risk of problematic use than natural cannabis.

Patients' beliefs towards contingency management: Target behaviours, incentives and the remote application of these interventions.

INTRODUCTION: Contingency management interventions are among the most efficacious psychosocial interventions in promoting abstinence from smoking, alcohol and substance use. The aim of this study was to assess the beliefs and objections towards contingency management among patients in UK-based drug and alcohol services to help understand barriers to uptake and support the development and implementation of these interventions. METHODS: The Service User Survey of Incentives was developed and implemented among patients (N = 181) at three UK-based drug and alcohol treatment services. Descriptive analyses were conducted to ascertain positive and negative beliefs about contingency management, acceptability of different target behaviours, incentives and delivery mechanisms including delivering incentives remotely using technology devices such as mobile telephones. RESULTS: Overall, 81% of participants were in favour of incentive programs, with more than 70% of respondents agreeing with the majority of positive belief statements. With the exception of two survey items, less than a third of participants agreed with negative belief statements. The proportion of participants indicating a neutral response was higher for negative statements (27%) indicating greater levels of ambiguity towards objections and concerns regarding contingency management. DISCUSSION AND CONCLUSIONS: Positive beliefs towards contingency management interventions were found, including high levels of acceptability towards a range of target behaviours, incentives and the use of technology devices to remotely monitor behaviour and deliver incentives. These findings have implications for the development and implementation of remote contingency management interventions within the UK drug treatment services.

Are prescription misuse and illicit drug use etiologically distinct? A genetically-informed analysis of opioids and stimulants.

BACKGROUND: Drug classes are grouped based on their chemical and pharmacological properties, but prescription and illicit drugs differ in other important ways. Potential differences in genetic and environmental influences on the (mis)use of prescription and illicit drugs that are subsumed under the same class should be examined. Opioid and stimulant classes contain prescription and illicit forms differentially associated with salient risk factors (common route of administration, legality), making them useful comparators for addressing this etiological issue. METHODS: A total of 2410 individual Australian twins [Mage = 31.77 (s.d. = 2.48); 67% women] were interviewed about prescription misuse and illicit use of opioids and stimulants. Univariate and bivariate biometric models partitioned variances and covariances into additive genetic, shared environmental, and unique environmental influences across drug types. RESULTS: Variation in the propensity to misuse prescription opioids was attributable to genes (41%) and unique environment (59%). Illicit opioid use was attributable to shared (71%) and unique (29%) environment. Prescription stimulant misuse was attributable to genes (79%) and unique environment (21%). Illicit stimulant use was attributable to genes (48%), shared environment (29%), and unique environment (23%). There was evidence for genetic influence common to both stimulant types, but limited evidence for genetic influence common to both opioid types. Bivariate correlations suggested that prescription opioid use may be more genetically similar to prescription stimulant use than to illicit opioid use. CONCLUSIONS: Prescription opioid misuse may share little genetic influence with illicit opioid use. Future research may consider avoiding unitary drug classifications, particularly when examining genetic influences.

Retrospectively assessed subjective effects of initial opioid use differ between opioid misusers with opioid use disorder (OUD) and those who never progressed to OUD: Data from a pilot and a replication sample.

Attempts to identify opioid users with increased risk of escalating to opioid use disorder (OUD) have had limited success. Retrospectively assessed subjective effects of initial opioid misuse were compared in a pilot sample of opioid misusers (nonmedical use ≤60 times lifetime) who had never met criteria for OUD (N = 14) and heroin-addicted individuals in treatment for OUD (N = 15). Relative to opioid misusers without a lifetime OUD diagnosis, individuals with OUD reported greater euphoria and other positive emotions, activation, pruritus, and internalizing symptoms. Consistent with these findings, proxy Addiction Research Center Inventory (ARCI) Amphetamine Group, and Morphine Benzedrine Group scale mean item scores were significantly higher in those with OUD. Replication was attempted in opioid misusers with (N = 25) and without OUD (N = 25) who were assessed as part of an ongoing genetic study. We observed similar significant between-group differences in individual subjective effect items and ARCI scale mean item scores in the replication sample. We, thus confirm findings from prior reports that retrospectively assessed subjective responses to initial opioid exposure differ significantly between opioid users who do, and do not, progress to OUD. Our report extends these findings in comparisons limited to opioid misusers. Additional research will be necessary to examine prospectively whether the assessment of subjective effects after initial use has predictive utility in the identification of individuals more likely to progress to OUD.

The continuity of effect of schizophrenia polygenic risk score and patterns of cannabis use on transdiagnostic symptom dimensions at first-episode psychosis: findings from the EU-GEI study.

Diagnostic categories do not completely reflect the heterogeneous expression of psychosis. Using data from the EU-GEI study, we evaluated the impact of schizophrenia polygenic risk score (SZ-PRS) and patterns of cannabis use on the transdiagnostic expression of psychosis. We analysed first-episode psychosis patients (FEP) and controls, generating transdiagnostic dimensions of psychotic symptoms and experiences using item response bi-factor modelling. Linear regression was used to test the associations between these dimensions and SZ-PRS, as well as the combined effect of SZ-PRS and cannabis use on the dimensions of positive psychotic symptoms and experiences. We found associations between SZ-PRS and (1) both negative (B = 0.18; 95%CI 0.03-0.33) and positive (B = 0.19; 95%CI 0.03-0.35) symptom dimensions in 617 FEP patients, regardless of their categorical diagnosis; and (2) all the psychotic experience dimensions in 979 controls. We did not observe associations between SZ-PRS and the general and affective dimensions in FEP. Daily and current cannabis use were associated with the positive dimensions in FEP (B = 0.31; 95%CI 0.11-0.52) and in controls (B = 0.26; 95%CI 0.06-0.46), over and above SZ-PRS. We provide evidence that genetic liability to schizophrenia and cannabis use map onto transdiagnostic symptom dimensions, supporting the validity and utility of the dimensional representation of psychosis. In our sample, genetic liability to schizophrenia correlated with more severe psychosis presentation, and cannabis use conferred risk to positive symptomatology beyond the genetic risk. Our findings support the hypothesis that psychotic experiences in the general population have similar genetic substrates as clinical disorders.

Temporal trends in smoking and nicotine dependence in relation to co-occurring substance use in the United States, 2005-2016.

BACKGROUND: Despite an overall decline in tobacco use in the United States, secular trends of smoking and nicotine dependence with co-occurring substance use are not well characterized. METHODS: We examined self-reported tobacco and other substance use in 22,245 participants age 21-59 in the United States from six waves of the National Health and Nutrition Examination Survey (NHANES). Using Joinpoint regression, we assessed secular trends of smoking and nicotine dependence as a function of co-occurring use of alcohol, prescription opioids, marijuana/hashish, cocaine/heroin/methamphetamine, or other injection drug use. Multivariable logistic regressions were fitted to identify the potential risk factors. RESULTS: During 2005-2016, the prevalence of current smoking decreased (without co-occurring substance use: 17.0 %-12.7 %; with co-occurring use of one substance: 35.3 % to 24.6 %; with co-occurring use of two or more substances: 53.8 %-42.2 %), and moderate-to-severe nicotine dependence decreased as well (8.0 %-4.2 %, 16.0 %-8.8 %, and 23.9 %-15.7 %, respectively). Smoking and nicotine dependence were more likely in those with co-occurring use of one substance (current smoking: odds ratio [OR] = 2.22, 95 % confidence interval [CI] = 2.01-2.45); nicotine dependence: OR = 1.88, 95 % CI = 1.63-2.17) and in those with co-occurring use of two or more substances (current smoking: OR = 5.25, 95 % CI = 4.63-5.95; nicotine dependence: OR = 3.24, 95 % CI = 2.72-3.87). CONCLUSIONS: Co-occurring substance use was associated with smaller reductions in tobacco use, over time, and with increased odds of nicotine dependence. This suggests that co-occurring substance users should be regarded as a tobacco-related disparity group and prioritized for tobacco control interventions.

The Relationship Between Childhood Physical and Sexual Abuse and Adolescent Cannabis Use: A Systematic Review.

Background: Among adolescents, cannabis use is a health concern due to associations with drug addiction and mental health disorders across the life course. It has been shown that childhood maltreatment is associated with drug addiction in adulthood. However, a better understanding of the relationship between maltreatment and drug use may improve targeted prevention and interventions. The aim of this systematic review is to describe the association between exposure to childhood maltreatment, specifically physical and sexual abuse, with adolescent cannabis use. Methods: A systematic search strategy was applied to Embase, PsycINFO, and Ovid MEDLINE(R) databases. Methods followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Abstract and title screening was performed to identify papers which reported an estimate of the association between childhood physical or sexual abuse and adolescent cannabis use. Full text screening of each paper was performed, and data were extracted and study quality assessed. Weighted means meta-analysis was performed on studies reporting odds ratios as effect estimates. Results: Of 8,780 screened articles, 13 were identified for inclusion. Eight papers received a quality rating score indicating lower risk of bias. Eleven papers reported the relationship between childhood sexual abuse and adolescent cannabis use; effect estimates ranged from AOR 0.53-AOR 2.18 (weighted mean OR 1.29, 95% CI 1.08-1.49). The relationship between childhood physical abuse and adolescent cannabis use was reported in 7 papers; effect estimates ranged from AOR 1.25-AOR 1.87 (weighted mean OR 1.39, 95% CI 1.12-1.66). Differences in the strength of the evidence were observed by the method of exposure ascertainment, and there was some evidence of differences in association by gender, age of cannabis initiation, and the severity of the abuse. Conclusions: This systematic review indicates childhood physical or sexual abuse may increase risk of adolescent-onset cannabis use. Few studies considered variation in timing of onset, or by gender. Adolescent cannabis use precedes is strongly associated with increased risk of negative mental health outcomes; further exploration of adolescent cannabis use's place on the causal pathway between childhood abuse and adult mental health problems is warranted to improve intervention.

Cannabis use in adolescence and risk of psychosis: Are there factors that moderate this relationship? A systematic review and meta-analysis.

Background: Previous research has reported increased risk for psychosis among individuals who use cannabis during adolescence. We conducted a systematic review and meta-analysis to investigate the interaction between adolescent cannabis use and other factors in moderating risk for psychosis later in life. Method: We searched four electronic databases in June 2020 for articles that assessed adolescent cannabis use, had psychosis as an outcome and analyzed for the association between adolescent cannabis use and psychosis. Analysis was done using random-effects meta-analysis and narrative synthesis. Results: A total of 63 studies were included in the narrative review and 18 studies were included in the meta-analysis. Adolescent cannabis use was found to increase risk for psychosis (RR = 1.71 (95%CI, 1.47-2.00, p < 0.00001) and predict earlier onset of psychosis. The following factors moderate the relationship between cannabis use and the risk of psychosis: age of onset of cannabis use, frequent cannabis use, exposure to childhood trauma, concurrent use of other substances and genetic factors. Conclusion: Adolescent cannabis use is associated with an increased risk for psychosis later in life. In addition, there are factors that moderate this relationship; therefore there is a need for research to assess the interaction between these factors, adolescent cannabis use and psychosis risk.

A latent class analysis of cannabis use products in a general population sample of adolescents and their association with paranoia, hallucinations, cognitive disorganisation and grandiosity.

Adolescents have access to a wide range of cannabis products with patterns of use becoming increasingly diverse. This study aimed to identify subgroups of adolescents in the general population who use similar types of cannabis and their association with psychotic experiences. Data on cannabis use were obtained from 467 adolescents aged between 16 and 17 years. Latent class analysis (LCA) identified groups of adolescents based on the type of cannabis used in the past 12 months. Univariate analysis explored differences in socio-demographics, substance use and mental health symptoms between groups. Multivariate analysis examined associations between class membership and psychotic experiences controlling for frequency and amount of cannabis. Finally, we explored the association between motives for cannabis and class membership using multi-nominal logistic regression. LCA identified 3 classes of adolescents: (i) herbal only (47.9%); (ii) skunk only (20.8%) and (3) mixed use (31.3%). Relative to non-users, skunk only use was associated with a 2-fold increase in paranoia (OR = 2.45, 95% CI = 1.29-4.63), along with, sleep disturbance and anxiety. Monthly cannabis use and consuming 2 or more joints on one occasion was associated with a 2-fold increase in hallucinations (OR = 2.2; 95% CI = 1.0-4.8 and OR = 1.9; 95% CI = 1.2-3.2), but did not reach the Bonferroni corrected p-value. Expansion and conformity motives differentiated the mixed cannabis class from the herbal only class. The findings suggest that different subgroups of cannabis users exist in adolescence as defined by the type of cannabis consumed and are differentially related to psychotic experiences and motives for use.