Cannabis Use Is Associated With Increased Risk of Cigarette Smoking Initiation, Persistence, and Relapse Among Adults in the United States.

INTRODUCTION: Despite increasing use of cannabis, it is unclear how cannabis use is related to cigarette transitions. This study examined cannabis use and smoking initiation, persistence, and relapse over 1 year among a nationally representative sample of US adults. METHODS: Data were from US adults (≥18 years) who completed two waves of longitudinal data from the Population Assessment of Tobacco and Health Study (Wave 1, 2013-2014; Wave 2, 2014-2015; n = 26 341). Logistic regression models were used to calculate the risk of Wave 2 incident smoking among Wave 1 never-smokers, smoking cessation among Wave 1 smokers, and smoking relapse among Wave 1 former smokers by Wave 1 cannabis use. Analyses were adjusted for age, gender, race/ethnicity, income, and education. RESULTS: Among Wave 1 never-smokers, cannabis use was associated with increased odds of initiation of nondaily (adjusted odds ratio [AOR] = 5.50, 95% confidence limits [CL] = 4.02-7.55) and daily cigarette smoking (AOR = 6.70, 95% CL = 4.75-9.46) 1 year later. Among Wave 1 daily smokers, cannabis use was associated with reduced odds of smoking cessation (AOR = 0.36, 95% CL = 0.20-0.65). Among Wave 1 former smokers, cannabis use was associated with increased odds of relapse to daily and nondaily cigarette smoking (daily AOR = 1.90, 95% CL = 1.11-3.26; nondaily AOR = 2.33, 95% CL = 1.61-3.39). CONCLUSIONS: Cannabis use was associated with increased cigarette smoking initiation, decreased smoking cessation, and increased smoking relapse among adults in the United States. Increased public education about the relationship between cannabis use and cigarette smoking transitions may be needed as cannabis use becomes more common among US adults. IMPLICATIONS: As cannabis use increases in the United States and other countries, an evaluation of the relationships of cannabis use to other health-related behaviors (eg, cigarette smoking) is needed to understand the population-level impact of legalization. Little is known about associations between cannabis use and cigarette smoking transitions (1) using recent longitudinal data, (2) among adults, and (3) examining transitions other than smoking initiation (eg, smoking relapse). Our results suggest that among US adults, cannabis use was associated with increased cigarette smoking initiation among never-smokers, decreased cigarette smoking cessation among current smokers, and increased cigarette smoking relapse among former smokers.

Trends in Daily Cannabis Use Among Cigarette Smokers: United States, 2002-2014.

OBJECTIVES: To estimate changes in the prevalence of daily cannabis use among current, former, and never cigarette smokers from 2002 to 2014 in the United States. METHODS: The National Survey on Drug Use and Health is a nationally representative cross-sectional study conducted annually among persons aged 12 years and older in the United States. RESULTS: Daily cannabis use occurs nearly exclusively among nondaily and daily cigarette smokers compared with former and never smokers (8.03%, 9.01%, 2.79%, 1.05%, respectively). Daily cannabis use increased over the past decade among both nondaily (8.03% [2014] vs 2.85% [2002]; linear trend P < .001) and daily smokers (9.01% [2014]; 4.92% [2002]; linear trend P < .001). Daily cannabis use increased most rapidly among former cigarette smokers (2.79% [2014] vs 0.98% [2002]; linear trend P < .001). CONCLUSIONS: Daily cannabis use occurs predominantly among cigarette smokers in the United States. Daily cannabis use increased among current, former, and never smokers over the past decade, with particularly rapid increases among youth and female cigarette smokers. Future research is needed to monitor the observed increase in daily cannabis use, especially among youths and adults who smoke cigarettes.

Randomised Controlled Trial (RCT) of cannabinoid replacement therapy (Nabiximols) for the management of treatment-resistant cannabis dependent patients: a study protocol.

BACKGROUND: The cannabis extract nabiximols (Sativex®) effectively supresses withdrawal symptoms and cravings in treatment resistant cannabis dependent individuals, who have high relapse rates following conventional withdrawal treatments. This study examines the efficacy, safety and cost-effectiveness of longer-term nabiximols treatment for outpatient cannabis dependent patients who have not responded to previous conventional treatment approaches. METHODS/DESIGN: A phase III multi-site outpatient, randomised, double-blinded, placebo controlled parallel design, comparing a 12-week course of nabiximols to placebo, with follow up at 24 weeks after enrolment. Four specialist drug and alcohol outpatient clinics in New South Wales, Australia. One hundred forty-two treatment seeking cannabis dependent adults, with no significant medical, psychiatric or other substance use disorders. Nabiximols is an oromucosal spray prescribed on a flexible dose regimen to a maximum daily dose of 32 sprays; 8 sprays (total 21.6 mg tetrahydrocannabinol (THC) and 20 mg cannabidiol (CBD)) four times a day, or matching placebo, dispensed weekly. All participants will receive six-sessions of individual cognitive behavioural therapy (CBT) and weekly clinical reviews. Primary endpoints are use of non-prescribed cannabis (self-reported cannabis use days, urine toxicology), safety measures (adverse events and abuse liability), and cost effectiveness (incremental cost effectiveness in achieving additional Quality Adjusted Life Years). Secondary outcomes include, improvement in physical and mental health parameters, substance use other than cannabis, cognitive functioning and patient satisfaction measures. DISCUSSION: This is the first outpatient community-based randomised controlled study of nabiximols as an agonist replacement medication for treating cannabis dependence, targeting individuals who have not previously responded to conventional treatment approaches. The study and treatment design is modelled upon an earlier study with this population and more generally on other agonist replacement treatments (e.g. nicotine, opioids). TRIAL REGISTRATION: Australian and New Zealand Clinical Trial Registry: ACTRN12616000103460 (Registered 1st February 2016).

Rapid elimination of Carboxy-THC in a cohort of chronic cannabis users.

Urinary 11-nor-Δ(9)-tetrahydrocannabinol-9-carboxylic acid (Carboxy-THC) concentrations, normalised to creatinine output, have been demonstrated to be a useful tool in the interpretation of the results of a series of urine tests for cannabis. These tests, often termed historical data, can be used to identify potential chronic cannabis users who may present occupational health and safety risks within the workplace. Conversely, the data can also be used to support employee claims of previous regular, rather than recent, cannabis use. This study aimed at examining the mean elimination of Carboxy-THC in 37 chronic users undergoing voluntary abstinence over a 2-week period. Urine specimens were collected prior to the study and after 1 and 2 weeks of abstinence. Carboxy-THC levels in urine were measured by gas chromatography-mass spectrometry (GC-MS) following alkaline hydrolysis, organic solvent extraction and derivatisation to form its pentafluoropropionic derivative. The creatinine-normalised Carboxy-THC concentrations declined rapidly over the 2 weeks of abstinence period and the majority of chronic cannabis users (73%) reduced their urinary Carboxy-THC levels to below the 15-µg/L confirmatory cutoff within that time. The study further highlights the value of historical urinary Carboxy-THC data as a means of identifying potential occupational health and safety risks among chronic cannabis users.

Psychosocial interventions for cannabis use disorder.

BACKGROUND: Cannabis use disorder is the most commonly reported illegal substance use disorder in the general population; although demand for assistance from health services is increasing internationally, only a minority of those with the disorder seek professional assistance. Treatment studies have been published, but pressure to establish public policy requires an updated systematic review of cannabis-specific treatments for adults. OBJECTIVES: To evaluate the efficacy of psychosocial interventions for cannabis use disorder (compared with inactive control and/or alternative treatment) delivered to adults in an out-patient or community setting. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 6), MEDLINE, EMBASE, PsycINFO, the Cumulaive Index to Nursing and Allied Health Literature (CINAHL) and reference lists of articles. Searched literature included all articles published before July 2015. SELECTION CRITERIA: All randomised controlled studies examining a psychosocial intervention for cannabis use disorder (without pharmacological intervention) in comparison with a minimal or inactive treatment control or alternative combinations of psychosocial interventions. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as expected by The Cochrane Collaboration. MAIN RESULTS: We included 23 randomised controlled trials involving 4045 participants. A total of 15 studies took place in the United States, two in Australia, two in Germany and one each in Switzerland, Canada, Brazil and Ireland. Investigators delivered treatments over approximately seven sessions (range, one to 14) for approximately 12 weeks (range, one to 56).Overall, risk of bias across studies was moderate, that is, no trial was at high risk of selection bias, attrition bias or reporting bias. Further, trials included a large total number of participants, and each trial ensured the fidelity of treatments provided. In contrast, because of the nature of the interventions provided, participant blinding was not possible, and reports of researcher blinding often were unclear or were not provided. Half of the reviewed studies included collateral verification or urinalysis to confirm self report data, leading to concern about performance and detection bias. Finally, concerns of other bias were based on relatively consistent lack of assessment of non-cannabis substance use or use of additional treatments before or during the trial period.A subset of studies provided sufficient detail for comparison of effects of any intervention versus inactive control on primary outcomes of interest at early follow-up (median, four months). Results showed moderate-quality evidence that approximately seven out of 10 intervention participants completed treatment as intended (effect size (ES) 0.71, 95% confidence interval (CI) 0.63 to 0.78, 11 studies, 1424 participants), and that those receiving psychosocial intervention used cannabis on fewer days compared with those given inactive control (mean difference (MD) 5.67, 95% CI 3.08 to 8.26, six studies, 1144 participants). In addition, low-quality evidence revealed that those receiving intervention were more likely to report point-prevalence abstinence (risk ratio (RR) 2.55, 95% CI 1.34 to 4.83, six studies, 1166 participants) and reported fewer symptoms of dependence (standardised mean difference (SMD) 4.15, 95% CI 1.67 to 6.63, four studies, 889 participants) and cannabis-related problems compared with those given inactive control (SMD 3.34, 95% CI 1.26 to 5.42, six studies, 2202 participants). Finally, very low-quality evidence indicated that those receiving intervention reported using fewer joints per day compared with those given inactive control (SMD 3.55, 95% CI 2.51 to 4.59, eight studies, 1600 participants). Notably, subgroup analyses found that interventions of more than four sessions delivered over longer than one month (high intensity) produced consistently improved outcomes (particularly in terms of cannabis use frequency and severity of dependence) in the short term as compared with low-intensity interventions.The most consistent evidence supports the use of cognitive-behavioural therapy (CBT), motivational enhancement therapy (MET) and particularly their combination for assisting with reduction of cannabis use frequency at early follow-up (MET: MD 4.45, 95% CI 1.90 to 7.00, four studies, 612 participants; CBT: MD 10.94, 95% CI 7.44 to 14.44, one study, 134 participants; MET + CBT: MD 7.38, 95% CI 3.18 to 11.57, three studies, 398 participants) and severity of dependence (MET: SMD 4.07, 95% CI 1.97 to 6.17, two studies, 316 participants; MET + CBT: SMD 7.89, 95% CI 0.93 to 14.85, three studies, 573 participants), although no particular intervention was consistently effective at nine-month follow-up or later. In addition, data from five out of six studies supported the utility of adding voucher-based incentives for cannabis-negative urines to enhance treatment effect on cannabis use frequency. A single study found contrasting results throughout a 12-month follow-up period, as post-treatment outcomes related to overall reduction in cannabis use frequency favoured CBT alone without the addition of abstinence-based or treatment adherence-based contingency management. In contrast, evidence of drug counselling, social support, relapse prevention and mindfulness meditation was weak because identified studies were few, information on treatment outcomes insufficient and rates of treatment adherence low. In line with treatments for other substance use, abstinence rates were relatively low overall, with approximately one-quarter of participants abstinent at final follow-up. Finally, three studies found that intervention was comparable with treatment as usual among participants in psychiatric clinics and reported no between-group differences in any of the included outcomes. AUTHORS' CONCLUSIONS: Included studies were heterogeneous in many aspects, and important questions regarding the most effective duration, intensity and type of intervention were raised and partially resolved. Generalisability of findings was unclear, most notably because of the limited number of localities and homogeneous samples of treatment seekers. The rate of abstinence was low and unstable although comparable with treatments for other substance use. Psychosocial intervention was shown, in comparison with minimal treatment controls, to reduce frequency of use and severity of dependence in a fairly durable manner, at least in the short term. Among the included intervention types, an intensive intervention provided over more than four sessions based on the combination of MET and CBT with abstinence-based incentives was most consistently supported for treatment of cannabis use disorder.

Cannabis withdrawal and sleep: A systematic review of human studies.

BACKGROUND: Sleep problems during withdrawal from cannabis use are a common experience. The details regarding how abstinence from cannabis impacts sleep are not well described. This article reviews the literature including a measure of cannabis withdrawal and sleep in humans. METHODS: A literature search using a set of cannabinoid and sleep-related terms was conducted across 8 electronic databases. Human studies that involved the administration of cannabinoids and at least 1 quantitative sleep-related measure were included. Review articles, opinion pieces, letters or editorials, case studies (final N < 8), published abstracts, posters, and non-English articles were excluded. Thirty-six publications were included in the review. RESULTS: Sleep was frequently interrupted during cannabis withdrawal, although the specific mechanisms of disruption remain unclear. CONCLUSIONS: Methodological issues in the majority of studies to date preclude any definitive conclusion on the specific aspects of sleep that are affected.

Cannabis use and its associated disorders: Clinical care.

BACKGROUND: Globally, cannabis is the most widely used and variably regulated illicit drug. The rates of use appeared to be stable in Australia at the time of the 2013 National Drug Strategy Household Survey, but levels of cannabis use disorder are rising and treatment seeking is increasing internationally. OBJECTIVE: This article describes the prevalence of cannabis use, associated disorders (eg harms with early and frequent use), and information on assessment and management. Links to a range of free online and telephone resources are provided. DISCUSSION: Cannabis use is common and around one in 10 people who ever used cannabis will go on to develop a cannabis use disorder diagnosable according to the Diagnostic and statistical manual of mental disorders, fifth edition criteria. Substance use disorders comorbid with mental health conditions are common, and the two should be assessed and treated concurrently. A screening algorithm and review of the evidence for psychosocial interventions, including technological platforms such as web-based and telephone, is provided.

Cannabis smoking and respiratory health: consideration of the literature.

The respiratory health effects from tobacco smoking are well described. Cannabis smoke contains a similar profile of carcinogenic chemicals as tobacco smoke but is inhaled more deeply. Although cannabis smoke is known to contain similar harmful and carcinogenic substances to tobacco smoke, relatively little is understood regarding the respiratory health effects from cannabis smoking. There is a need to integrate research on cannabis and respiratory health effects so that gaps in the literature can be identified and the more consistent findings can be consolidated with the purpose of educating smokers and health service providers. This review focuses on several aspects of respiratory health and cannabis use (as well as concurrent cannabis and tobacco use) and provides an update to (i) the pathophysiology; (ii) general respiratory health including symptoms of chronic bronchitis; and (iii) lung cancer.

Experiences of marijuana-vaporizer users.

BACKGROUND: Using a marijuana vaporizer may have potential harm-reduction advantages on smoking marijuana, in that the user does not inhale smoke. Little research has been published on use of vaporizers. METHODS: In the first study of individuals using a vaporizer on their own initiative, 96 adults anonymously answered questions about their experiences with a vaporizer and their use of marijuana with tobacco. RESULTS: Users identified 4 advantages to using a vaporizer over smoking marijuana: perceived health benefits, better taste, no smoke smell, and more effect from the same amount of marijuana. Users identified 2 disadvantages: inconvenience of setup and cleaning and the time it takes to get the device operating for each use. Only 2 individuals combined tobacco in the vaporizer mix, whereas 15 combined tobacco with marijuana when they smoked marijuana. Almost all participants intended to continue using a vaporizer. CONCLUSIONS: Vaporizers seem to have appeal to marijuana users, who perceive them as having harm-reduction and other benefits. Vaporizers are worthy of experimental research evaluating health-related effects of using them.

Effectiveness of a self-guided web-based cannabis treatment program: randomized controlled trial.

BACKGROUND: Self-help strategies offer a promising way to address problems with access to and stigma associated with face-to-face drug and alcohol treatment, and the Internet provides an excellent delivery mode for such strategies. To date, no study has tested the effectiveness of a fully self-guided web-based treatment for cannabis use and related problems. OBJECTIVES: The current study was a two-armed randomized controlled trial aimed at testing the effectiveness of Reduce Your Use, a fully self-guided web-based treatment program for cannabis use disorder consisting of 6 modules based on cognitive, motivational, and behavioral principles. METHODS: 225 individuals who wanted to cease or reduce their cannabis use were recruited using both online and offline advertising methods and were randomly assigned to receive: (1) the web-based intervention, or (2) a control condition consisting of 6 modules of web-based educational information on cannabis. Assessments of cannabis use, dependence symptoms, and abuse symptoms were conducted through online questionnaires at baseline, and at 6-week and 3-month follow-ups. Two sets of data analyses were undertaken--complier average causal effect (CACE) modeling and intention to treat (ITT). RESULTS: Two thirds (149) of the participants completed the 6-week postintervention assessment, while 122 (54%) completed the 3-month follow-up assessment. Participants in the intervention group completed an average of 3.5 of the 6 modules. The CACE analysis revealed that at 6 weeks, the experimental group reported significantly fewer days of cannabis use during the past month (P=.02), significantly lower past-month quantity of cannabis use (P=.01), and significantly fewer symptoms of cannabis abuse (P=.047) relative to controls. Cannabis dependence symptoms (number and severity) and past-month abstinence did not differ significantly between groups (Ps>.05). Findings at 3 months were similar, except that the experimental group reported significantly fewer and less severe cannabis dependence symptoms (Ps<.05), and past-month quantity of cannabis consumed no longer differed significantly between groups (P=.16). ITT analyses yielded similar outcomes. CONCLUSION: Findings suggest that web-based interventions may be an effective means of treating uncomplicated cannabis use and related problems and reducing the public health burden of cannabis use disorders. TRIAL REGISTRATION: ACTRN12609000856213, Australian New Zealand Clinical Trials Registry.

Evaluating preferences for online psychological interventions to decrease cannabis use in young adults with psychosis: An observational study.

Innovative technology-based solutions have the potential to improve access to clinically proven interventions for cannabis use disorder (CUD) in individuals with first episode psychosis (FEP). High patient engagement with app-based interventions is critical for achieving optimal outcomes. 104 individuals 18 to 35 years old with FEP and CUD from three Canadian provinces completed an electronic survey to evaluate preferences for online psychological intervention intensity, participation autonomy, feedback related to cannabis use, and technology platforms and app functionalities. The development of the questionnaire was informed by a qualitative study that included patients and clinicians. We used Best-Worst Scaling (BWS) and item ranking methodologies to measure preferences. Conditional logistic regression models for BWS data revealed high preferences for moderate intervention intensity (e.g., modules with a length of 15 min) and treatment autonomy that included preferences for using technology-based interventions and receiving feedback related to cannabis use once a week. Luce regression models for rank items revealed high preferences for smartphone-based apps, video intervention components, and having access to synchronous communications with clinicians and gamification elements. Results informed the development of iCanChange (iCC), a smartphone-based intervention for the treatment of CUD in individuals with FEP that is undergoing clinical testing.

Correlates of treatment engagement and client outcomes: results of a randomised controlled trial of nabiximols for the treatment of cannabis use disorder.

INTRODUCTION AND AIMS: There is increasing interest and evidence for the use of cannabinoid medications in the treatment of cannabis use disorder, but little examination of the correlates of successful treatment. This paper is a secondary analysis of a randomised placebo-controlled trial of nabiximols for the treatment of cannabis use disorder (CUD), aiming to identify which client and treatment characteristics impact treatment engagement and outcomes. METHOD: Bayesian multiple regression models were used to examine the impact of age, gender, duration of regular cannabis use, daily quantity of cannabis, cannabis use problems, self-efficacy for quitting, sleep, mental health, pain measures, and treatment group upon treatment engagement (retention, medication dose, and counselling participation) and treatment outcomes (achieving end-of-study abstinence, and a 50% or greater reduction in cannabis use days) among the 128 clients participating in the 12-week trial. RESULTS: Among the treatment factors, greater counselling attendance was associated with greater odds of abstinence and ≥ 50% reduction in cannabis use; nabiximols with greater odds of ≥ 50% reduction and attending counselling, and reduced hazard of treatment dropout; and higher dose with lower odds of ≥ 50% reduction. Among the client factors, longer duration of regular use was associated with higher odds of abstinence and 50% reduction, and lower hazard of treatment dropout; greater quantity of cannabis use with reduced hazard of dropout, greater odds of attending counselling, and higher average dose; greater pain at baseline with greater odds of ≥ 50% reduction and higher average dose; and more severe sleep issues with lower odds of ≥ 50% reduction. Males had lower odds of attending counselling. DISCUSSIONS AND CONCLUSIONS: These findings suggest that counselling combined with agonist pharmacotherapy may provide the optimal treatment for cannabis use disorder. Younger clients, male clients, and clients with sleep issues could benefit from extra support from treatment services to improve engagement and outcomes. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ACTRN12616000103460) https://www.anzctr.org.au.

Mood, sleep and pain comorbidity outcomes in cannabis dependent patients: Findings from a nabiximols versus placebo randomised controlled trial.

BACKGROUND: Mood, sleep and pain problems are common comorbidities among treatment-seeking cannabis-dependent patients. There is limited evidence suggesting treatment for cannabis dependence is associated with their improvement. This study explored the impact of cannabis dependence treatment on these comorbidities. METHODS: This is a secondary analysis from a 12-week double-blind placebo-controlled trial testing the efficacy of a cannabis agonist (nabiximols) against placebo in reducing illicit cannabis use in 128 cannabis-dependent participants. Outcome measurements including DASS-21 (Depression, Anxiety, and Stress subscales); Insomnia Severity Index (ISI); and Brief Pain Inventory (BPI), were performed at weeks 0, 4, 8, 12 and 24. Each was analysed as continuous outcomes and as binary cases based on validated clinical cut-offs. RESULTS: Among those whose DASS and ISI scores were in the moderate to severe range at baseline, after controlling for cannabis use, there was a gradual decrease in severity of symptoms over the course of the trial. BPI decreased significantly until week 12 and then rose again in the post-treatment period during weeks 12-24. Neither pharmacotherapy type (nabiximols vs placebo) nor number of counselling sessions contributed significant explanatory power to any of the models and were excluded from the final analyses for both continuous and categorical outcomes. CONCLUSIONS: Participants in this trial who qualified as cases at baseline had elevated comorbidity symptoms. There was no evidence that nabiximols treatment is a barrier to achieving reductions in the comorbid symptoms examined. Cannabis dependence treatment reduced illicit cannabis use and improved comorbidity symptoms, even when complete abstinence was not achieved.

Reducing Cannabis Use in Young Adults With Psychosis Using iCanChange, a Mobile Health App: Protocol for a Pilot Randomized Controlled Trial (ReCAP-iCC).

BACKGROUND: Cannabis use is the most prevalent among adolescents and young adults; frequent consumption is associated with cannabis use disorder (CUD) and psychosis, with a high prevalence (up to 50%) of CUD in individuals with first-episode psychosis (FEP). Early Intervention Services (EIS) for psychosis include face-to-face psychosocial interventions for CUD, because reducing or discontinuing cannabis use improves clinical and health care service use outcomes. However, multiple barriers (eg, staff availability and limited access to treatment) can hinder the implementation of these interventions. Mobile health (mHealth) interventions may help circumvent some of these barriers; however, to date, no study has evaluated the effects of mHealth psychological interventions for CUD in individuals with FEP. OBJECTIVE: This study describes the protocol for a pilot randomized controlled trial using a novel mHealth psychological intervention (iCanChange [iCC]) to address CUD in young adults with FEP. iCC was developed based on clinical evidence showing that in individuals without psychosis, integrating the principles of cognitive behavioral therapy, motivational interviewing, and behavioral self-management approaches are effective in improving cannabis use-related outcomes. METHODS: Consenting individuals (n=100) meeting the inclusion criteria (eg, aged 18-35 years with FEP and CUD) will be randomly allocated in a 1:1 ratio to the intervention (iCC+modified EIS) or control (EIS) group. The iCC is fully automatized and contains 21 modules that are completed over a 12-week period and 3 booster modules available during the 3-month follow-up period. Validated self-report measures will be taken via in-person assessments at baseline and at 6, 12 (end point), and 24 weeks (end of trial); iCC use data will be collected directly from the mobile app. Primary outcomes are intervention completion and trial retention rates, and secondary outcomes are cannabis use quantity, participant satisfaction, app use, and trial recruiting parameters. Exploratory outcomes include severity of psychotic symptoms and CUD severity. For primary outcomes, we will use the chi-square test using data collected at week 12. We will consider participation in iCC acceptable if ≥50% of the participants complete at least 11 out of 21 intervention modules and the trial feasible if attrition does not reach 50%. We will use analysis of covariance and mixed-effects models for secondary outcomes and generalized estimating equation multivariable analyses for exploratory outcomes. RESULTS: Recruitment began in July 2022, and data collection is anticipated to be completed in July 2024. The main results are expected to be submitted for publication in 2024. We will engage patient partners and other stakeholders in creating a multifaceted knowledge translation plan to reach a diverse audience. CONCLUSIONS: If feasible, this study will provide essential data for a larger-scale efficacy trial of iCC on cannabis use outcomes in individuals with FEP and CUD. TRIAL REGISTRATION: ClinicalTrials.gov NCT05310981; https://www.clinicaltrials.gov/ct2/show/NCT05310981. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/40817.

Young cannabis users in residential treatment: as distressed as other clients.

Doubt remains about the need for residential substance user treatment for young cannabis users. Using a series of validated clinical tools, this study compared 1,221 primarily cannabis-, psychostimulant-, alcohol-, or opioid-dependent young people admitted to an urban/rural Australian residential treatment program between 2001 and 2007. Multinomial logistic regression revealed that the cannabis user group had poorer mental health than the opioid group, poorer social functioning than the alcohol drinking group, and comparably poor functioning otherwise but remained in treatment longer than the psychostimulant and opioid user groups. Residential treatment for primarily cannabis-dependent young people with complex and multiple needs can be supported.

Test-retest reliability and cross-cultural applicability of DSM-5 adopted diagnostic criteria for ketamine use disorders.

BACKGROUND: Despite increasing prevalence of nonmedical ketamine use globally, data on ketamine use disorders, which are classified in the DSM-5 under criteria for phencyclidine, are limited. This study assessed the reliability and applicability of DSM-based diagnostic criteria for ketamine use disorder. METHODS: Participants who used ecstasy were recruited through the Tri-City Study of Club Drug Use, Abuse, and Dependence in St. Louis, Miami, and Sydney. Those who reported using ketamine (lifetime use >5 times) were included in these analyses (n = 205). Participants were interviewed using the computerized Substance Abuse Module for Club Drugs (CD-SAM) at baseline and 7 days later for the reliability of diagnoses and individual diagnostic criteria. RESULTS: Overall, 29.3% met DSM-5 adopted criteria for ketamine use disorder at Time 1. Moderate to excellent test-retest reliability was observed consistently across study sites for any ketamine use disorder (κ = 0.57, Y = 0.61) and severe ketamine use disorder (κ = 0.62, Y = 0.79). Continued use of ketamine despite knowledge of physical or psychological problems was the most frequently endorsed individual criterion (59.0%), followed by reported withdrawal (30.2%) and physically hazardous use (29.8%). All individual criteria had acceptable reliability estimates (κ ≥ 0.41). CONCLUSIONS: Diagnoses of ketamine use disorder can be reliably evaluated using this fully structured diagnostic instrument's questions and algorithm. Ketamine-related withdrawal among people who use ketamine should be re-evaluated. Considering that after-effects of this dissociative anesthetic can last for many hours, it is important to explore a different timeframe for possible withdrawal effects.

Cannabis use among youth in the United States, 2004-2016: Faster rate of increase among youth with depression.

BACKGROUND: Cannabis use has significant negative consequences for youth. Depression is associated with greater cannabis use among adults but less is known about cannabis use and depression among youth. This study investigated whether depression is associated with increased cannabis use among youth in the United States (US), overall and by demographics, and examined trends in cannabis use by depression status among youth from 2004 to 2016. METHODS: Data were from the 2004-2016 National Survey on Drug Use and Health (NSDUH), annual cross-sectional national samples of US persons 12 and older. The analytic sample included respondents aged 12-17 (total combined n=204,102). First, the prevalence of past-month cannabis use by past-year depression status among youth was examined, overall and by demographic subgroups, using pooled data from 2004-2016. Next, linear time trends of past-month cannabis use were assessed by depression status from 2004 to 2016 using logistic regression models with continuous year as the predictor. Models with year-by-depression status interaction terms assessed differential time trends for those with and without depression. RESULTS: From 2004-2016, cannabis use increased both among youth with and without depression. Cannabis use increased significantly more rapidly among youth with (8.45% to 11.65%), compared to without, depression (4.28% to 4.71%). Youth with depression were more than twice as likely to report cannabis use (12.86% versus 6.40%), relative to those without depression. CONCLUSIONS: Cannabis use was more than twice as common and increased more rapidly from 2004 to 2016 among youth with depression compared to youth without depression.

A Web-Based Program for Cannabis Use and Psychotic Experiences in Young People (Keep It Real): Protocol for a Randomized Controlled Trial.

BACKGROUND: Young Australians (16-25 years) have the highest rates of past-month cannabis use in the world. Cannabis use increases the risk of alcohol and other drug disorders and depressive disorders, and has a robust dose-response association with psychotic experiences (PEs) and disorders. PEs are subthreshold positive psychotic symptoms, including delusions and hallucinations, which increase the risk of substance use, depressive or anxiety disorders, and psychotic disorders. Access to effective web-based early interventions targeting both cannabis use and PEs could reduce such risk in young people. OBJECTIVE: The objective of this study is to determine the efficacy and cost-effectiveness of the Keep it Real web-based program compared to an information-only control website among young cannabis users (16-25 years) with PEs. METHODS: Participants are recruited online, and consenting individuals meeting inclusion criteria (aged 16-25 years, who have used cannabis in the past month and experienced PEs in the past 3 months) are automatically randomized to either the Keep it Real web-based program (n=249) or an information-only control website (n=249). Both websites are self-guided (fully automated). The baseline and follow-up assessments at 3, 6, 9, and 12 months are self-completed online. Primary outcome measures are weekly cannabis use, PEs, and the relative cost-effectiveness for quality-adjusted life years. Secondary outcomes include other substance use and related problems, PE-related distress, cannabis intoxication experiences, severity of cannabis dependence, depression/anxiety symptoms, suicidality, and mental well-being and functioning. RESULTS: Recruitment commenced in February 2019, and the results are expected to be submitted for publication in mid-2021. CONCLUSIONS: This study protocol describes a large randomized controlled trial of a new web-based program for young cannabis users experiencing PEs. If effective, the accessibility and scalability of Keep it Real could help reduce growing public health concerns about the significant social, economic, and health impacts of cannabis use. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12618001107213; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374800. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/15803.

Cannabis use among US adults with anxiety from 2008 to 2017: The role of state-level cannabis legalization.

BACKGROUND: Cannabis use is more common among adults with anxiety. Cannabis legalization is occurring rapidly across the United States (US) and individuals may use cannabis to cope with anxiety. This study investigated whether cannabis use across the US has changed differentially by anxiety status and by state cannabis legalization for medical (MML) and/or recreational use (RML). METHODS: Public and restricted-use data from the 2004 to 2017 National Survey on Drug Use and Health, an annual cross-sectional, nationally representative survey of US individuals, were analyzed. The prevalence of past-30-day cannabis use by anxiety status in 2017 was estimated among respondents ages ≥18 (n = 42,554) by sociodemographics and state-level cannabis law. Weighted logistic regressions with continuous year as the predictor for the linear time trend were used to examine the time trends in cannabis use by anxiety and cannabis law status from 2004 to 2017 (total combined analytic sample n = 398,967). RESULTS: Cannabis use was consistently two to three times higher among those with high anxiety compared to those with some or no anxiety and was higher in states with RML compared to MML or no MML/RML. Cannabis use has increased over time among those with and without anxiety overall, in MML states, and in states without MML/RML; with a faster increase in cannabis use among those with high anxiety compared to lower anxiety in states with MML. CONCLUSIONS: Cannabis use is increasing among American adults overall, yet is disproportionately common among Americans with anxiety especially among those residing in states where cannabis has been legalized.

Validation of the Australian Treatment Outcomes Profile for use in clients with cannabis dependence.

INTRODUCTION AND AIMS: The Australian Treatment Outcomes Profile (ATOP) was developed as a clinical tool for monitoring the substance use, health and wellbeing of clients in alcohol and other drug treatment. This is the first psychometric validation of the ATOP in a cannabis-dependent treatment population. DESIGN AND METHODS: A total of 128 individuals with cannabis dependence enrolled in an outpatient randomised controlled trial were administered the ATOP and gold-standard health and wellbeing questionnaires once by clinicians and once by researchers at baseline. Concurrent validity was assessed by testing ATOP Psychological Health, Physical Health and Quality of Life questions against concurrently administered gold-standard questionnaires: the Short Form 36 Health Survey (SF-36), the 21-item Depression, Anxiety and Stress Scale (DASS-21) and the Sheehan Disability Scale (SDS). Interrater reliability was tested by comparing clinician-administered ATOP items at the medical screening interview to the same ATOP items administered by researchers at baseline. RESULTS: ATOP Psychological Health showed moderate to strong correlations with SF-36 Mental Components, SF-36 Mental Health and DASS-21 scores (r = 0.40-0.52) and ATOP Physical Health with SF-36 Physical Components and SF-36 General Health scores (r = 0.36-0.67). The ATOP Quality of Life scale showed moderate agreement with the SDS and six-dimensional health state short form scales (r = 0.38-0.40). ATOP substance use, employment, education and child care items showed good to excellent interrater reliability (Krippendorff's α = 0.62-0.81), and tobacco use, Psychological Health, Physical Health and Quality of Life showed fair to moderate interrater reliability (Krippendorff's α = 0.42-0.53). DISCUSSION AND CONCLUSIONS: The ATOP appears to be valid and reliable when tested in a population with cannabis-dependence, justifying its widespread use in clinical settings.