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1.  Two Sides of the Same Coin: Cannabis Dependence and Mental Health Problems in Help-Seeking Adolescent and Young Adult Outpatients 
The aim of the current study was to delineate the psychiatric profile of cannabis dependent young people (14–29 years old) with mental health problems (N = 36) seeking treatment via a research study. To do so, the Structured Clinical Interview for DSM-IV-TR Axis I Disorders and the Structured Clinical Interview for DSM-IV Childhood Diagnoses were used to obtain DSM-IV diagnoses, while a modified Timeline Followback interview and self-reports were used to measure cannabis use, cannabis-related problems, and impairment. Most individuals had at least two Axis I disorders in addition to cannabis dependence. Anxiety disorders were common, with posttraumatic stress disorder, social phobia, and generalised anxiety disorder accounting for the majority of these diagnoses. On average, young people reported a moderate degree of dependence and functional impairment, and a substantial number of cannabis-related problems. Although both males and females reported using similar quantities of cannabis per month, females reported using cannabis more frequently than males. The current data suggest that young people who present for cannabis use treatment in the context of a mental health issue may have a variety of psychiatric problems that need addressed and that males and females may have slightly different profiles. If cannabis use treatments are to advance for this population, more attention needs to be paid to the complex issues that young people present to treatment with.
doi:10.1007/s11469-012-9378-1
PMCID: PMC3519979  PMID: 23243411
Cannabis use; Cannabis dependence; Comorbidity; Anxiety; Mood disorders; Young people
2.  Aerobic Exercise Training Reduces Cannabis Craving and Use in Non-Treatment Seeking Cannabis-Dependent Adults 
PLoS ONE  2011;6(3):e17465.
Background
Cannabis dependence is a significant public health problem. Because there are no approved medications for this condition, treatment must rely on behavioral approaches empirically complemented by such lifestyle change as exercise.
Aims
To examine the effects of moderate aerobic exercise on cannabis craving and use in cannabis dependent adults under normal living conditions.
Design
Participants attended 10 supervised 30-min treadmill exercise sessions standardized using heart rate (HR) monitoring (60–70% HR reserve) over 2 weeks. Exercise sessions were conducted by exercise physiologists under medical oversight.
Participants
Sedentary or minimally active non-treatment seeking cannabis-dependent adults (n = 12, age 25±3 years, 8 females) met criteria for primary cannabis dependence using the Substance Abuse module of the Structured Clinical Interview for DSM-IV (SCID).
Measurements
Self-reported drug use was assessed for 1-week before, during, and 2-weeks after the study. Participants viewed visual cannabis cues before and after exercise in conjunction with assessment of subjective cannabis craving using the Marijuana Craving Questionnaire (MCQ-SF).
Findings
Daily cannabis use within the run-in period was 5.9 joints per day (SD = 3.1, range 1.8–10.9). Average cannabis use levels within the exercise (2.8 joints, SD = 1.6, range 0.9–5.4) and follow-up (4.1 joints, SD = 2.5, range 1.1–9.5) periods were lower than during the run-in period (both P<.005). Average MCQ factor scores for the pre- and post-exercise craving assessments were reduced for compulsivity (P  = .006), emotionality (P  = .002), expectancy (P  = .002), and purposefulness (P  = .002).
Conclusions
The findings of this pilot study warrant larger, adequately powered controlled trials to test the efficacy of prescribed moderate aerobic exercise as a component of cannabis dependence treatment. The neurobiological mechanisms that account for these beneficial effects on cannabis use may lead to understanding of the physical and emotional underpinnings of cannabis dependence and recovery from this disorder.
Trial Registration
ClinicalTrials.gov NCT00838448]
doi:10.1371/journal.pone.0017465
PMCID: PMC3050879  PMID: 21408154
3.  Predictors of onset of cannabis and other drug use in male young adults: results from a longitudinal study 
BMC Public Health  2014;14(1):1202.
Background
The use of cannabis and other illegal drugs is particularly prevalent in male young adults and is associated with severe health problems. This longitudinal study explored variables associated with the onset of cannabis use and the onset of illegal drug use other than cannabis separately in male young adults, including demographics, religion and religiosity, health, social context, substance use, and personality. Furthermore, we explored how far the gateway hypothesis and the common liability to addiction model are in line with the resulting prediction models.
Methods
The data were gathered within the Cohort Study on Substance Use Risk Factors (C-SURF). Young men aged around 20 years provided demographic, social, health, substance use, and personality-related data at baseline. Onset of cannabis and other drug use were assessed at 15-months follow-up. Samples of 2,774 and 4,254 individuals who indicated at baseline that they have not used cannabis and other drugs, respectively, in their life and who provided follow-up data were used for the prediction models. Hierarchical logistic stepwise regressions were conducted, in order to identify predictors of the late onset of cannabis and other drug use separately.
Results
Not providing for oneself, having siblings, depressiveness, parental divorce, lower parental knowledge of peers and the whereabouts, peer pressure, very low nicotine dependence, and sensation seeking were positively associated with the onset of cannabis use. Practising religion was negatively associated with the onset of cannabis use. Onset of drug use other than cannabis showed a positive association with depressiveness, antisocial personality disorder, lower parental knowledge of peers and the whereabouts, psychiatric problems of peers, problematic cannabis use, and sensation seeking.
Conclusions
Consideration of the predictor variables identified within this study may help to identify young male adults for whom preventive measures for cannabis or other drug use are most appropriate. The results provide evidence for both the gateway hypothesis and the common liability to addiction model and point to further variables like depressiveness or practising of religion that might influence the onset of drug use.
doi:10.1186/1471-2458-14-1202
PMCID: PMC4247759  PMID: 25416140
Onset; Cannabis; Drug use; Male; Young adults
4.  Quantifying the Clinical Significance of Cannabis Withdrawal 
PLoS ONE  2012;7(9):e44864.
Background and Aims
Questions over the clinical significance of cannabis withdrawal have hindered its inclusion as a discrete cannabis induced psychiatric condition in the Diagnostic and Statistical Manual of Mental Disorders (DSM IV). This study aims to quantify functional impairment to normal daily activities from cannabis withdrawal, and looks at the factors predicting functional impairment. In addition the study tests the influence of functional impairment from cannabis withdrawal on cannabis use during and after an abstinence attempt.
Methods and Results
A volunteer sample of 49 non-treatment seeking cannabis users who met DSM-IV criteria for dependence provided daily withdrawal-related functional impairment scores during a one-week baseline phase and two weeks of monitored abstinence from cannabis with a one month follow up. Functional impairment from withdrawal symptoms was strongly associated with symptom severity (p = 0.0001). Participants with more severe cannabis dependence before the abstinence attempt reported greater functional impairment from cannabis withdrawal (p = 0.03). Relapse to cannabis use during the abstinence period was associated with greater functional impairment from a subset of withdrawal symptoms in high dependence users. Higher levels of functional impairment during the abstinence attempt predicted higher levels of cannabis use at one month follow up (p = 0.001).
Conclusions
Cannabis withdrawal is clinically significant because it is associated with functional impairment to normal daily activities, as well as relapse to cannabis use. Sample size in the relapse group was small and the use of a non-treatment seeking population requires findings to be replicated in clinical samples. Tailoring treatments to target withdrawal symptoms contributing to functional impairment during a quit attempt may improve treatment outcomes.
doi:10.1371/journal.pone.0044864
PMCID: PMC3458862  PMID: 23049760
5.  A Genome-Wide Scan for Loci Influencing Adolescent Cannabis Dependence Symptoms: Evidence for Linkage on Chromosomes 3 and 9 
Drug and alcohol dependence  2006;89(1):34-41.
Objective:
Cannabis is the most frequently abused illicit substance among adolescents and young adults. Genetic risk factors account for part of the variation in the development of Cannabis Dependence symptoms; however, no linkage studies have been performed for Cannabis Dependence symptoms. This study aimed to identify such loci.
Method:
324 sibling pairs from 192 families were assessed for Cannabis Dependence symptoms. Probands (13-19 years of age) were recruited from consecutive admissions to substance abuse treatment facilities. The siblings of the probands ranged in age from 12-25 years. A community-based sample of 4843 adolescents and young adults was utilized to define an age- and sex-corrected index of Cannabis Dependence vulnerability. DSM-IV Cannabis Dependence symptoms were assessed in youth and their family members with the Composite International Diagnostic Instrument -Substance Abuse Module. Siblings and parents were genotyped for 374 microsatellite markers distributed across the 22 autosomes (average inter-marker distance = 9.2 cM). Cannabis Dependence symptoms were analyzed using Merlin-regress, a regression-based method that is robust to sample selection.
Results:
Evidence for suggestive linkage was found on chromosome 3q21 near marker D3S1267 (LOD = 2.61), and on chromosome 9q34 near marker D9S1826 (LOD = 2.57).
Conclusions:
This is the first reported linkage study of cannabis dependence symptoms. Other reports of linkage regions for illicit substance dependence have been reported near 3q21, suggesting that this region may contain a quantitative trait loci influencing cannabis dependence and other substance use disorders.
doi:10.1016/j.drugalcdep.2006.11.015
PMCID: PMC1892279  PMID: 17169504
genetics; Cannabis; antisocial behavior; adolescence; linkage study
6.  Cannabis-Related treatment demands in Belgium: a socio-demographic and treatment seeking profile 
Archives of Public Health  2010;67(4):179-193.
Aims
Most people appear to stop using cannabis when getting older, but a certain subgroup becomes cannabis dependent, has problems in various life areas and needs treatment. Our aim is to compare a number of sociodemographic and treatment seeking variables between treatment seekers with primary cannabis problems and those with primary alcohol, opiate, amphetamine or cocaine problems. Understanding how primary canna-bis users seeking treatment differ from other treatment seekers may assist clinicians in better tailoring treatment processes to clients' needs.
Methods
For this purpose, intake information on 1,626 persons seeking treatment in one of 16 treat-ment agencies in the province of Antwerp (Belgium) was registered via an on-line web application. Primary cannabis users seeking treatment were compared with primary alcohol, opiate, amphetamine and cocaine users by means of bivariate analyses (Chi-square tests and analyses of variance), followed by four logistic regression analyses.
Findings
14.5% of all clients used cannabis as their primary drug. Compared to primary alcohol, opiate, amphetamine or cocaine users seeking treatment, cannabis users seeking treatment appeared to be more often male, younger than 30 years old, Belgian and student. They are often referred to treatment by police or justice and 43.6% of them can be considered single-substance users. Multivariate analyses showed that besides age and sex, using no other substances than the primary drug and being registered in outpatient facilities only were significant determinants for being a primary cannabis user seeking treatment.
Conclusions
Primary cannabis users can clearly be differentiated from other drug users seeking treatment. Although cannabis plays an important part in a polydrug use pattern, persons who have cannabis as their primary drug often use only this one substance. Since they regularly have brief contacts with treatment agencies, more research is needed to measure the effect of this brief intervention.
doi:10.1186/0778-7367-67-4-179
PMCID: PMC3436678
Cannabis; Treatment Demand; Substance Abuse Treatment; Drug Use; Demographics
7.  Crosswalk between DSM-IV Dependence and DSM-5 Substance Use Disorders for Opioids, Cannabis, Cocaine and Alcohol 
Drug and alcohol dependence  2013;132(0):387-390.
Background
Ascertaining agreement between DSM-IV and DSM-5 is important to determine the applicability of treatments for DSM-IV conditions to persons diagnosed according to the proposed DSM-5.
Methods
Data from a nationally representative sample of US adults were used to compare concordance of past-year DSM-IV Opioid, Cannabis, Cocaine and Alcohol Dependence with past-year DSM-5 disorders at thresholds of 3+, 4+ 5+ and 6+ positive DSM-5 criteria among past-year users of opioids (n=264), cannabis (n=1,622), cocaine (n=271) and alcohol (n=23,013). Substance-specific 2×2 tables yielded overall concordance (kappa), sensitivity, specificity, positive predictive values (PPV) and negative predictive values (NPV).
Results
For DSM-IV Alcohol, Cocaine and Opioid Dependence, optimal concordance occurred when 4+ DSM-5 criteria were endorsed, corresponding to the threshold for moderate DSM-5 Alcohol, Cocaine and Opioid Use Disorders. Maximal concordance of DSM-IV Cannabis Dependence and DSM-5 Cannabis Use Disorder occurred when 6+ criteria were endorsed, corresponding to the threshold for severe DSM-5 Cannabis Use Disorder. At these optimal thresholds, sensitivity, specificity, PPV and NPV generally exceeded 85% (>75% for cannabis).
Conclusions
Overall, excellent correspondence of DSM-IV Dependence with DSM-5 Substance Use Disorders was documented in this general population sample of alcohol, cannabis, cocaine and opioid users. Applicability of treatments tested for DSM-IV Dependence is supported by these results for those with a DSM-5 Alcohol, Cocaine or Opioid Use Disorder of at least moderate severity or Severe Cannabis Use Disorder. Further research is needed to provide evidence for applicability of treatments for persons with milder substance use disorders.
doi:10.1016/j.drugalcdep.2013.02.036
PMCID: PMC3748225  PMID: 23642316
DSM-IV; DSM-5; substance use disorder; concordance; kappa; diagnosis
8.  12-month follow-up of an exploratory ‘brief intervention’ for high-frequency cannabis users among Canadian university students 
Background
One in three young people use cannabis in Canada. Cannabis use can be associated with a variety of health problems which occur primarily among intensive/frequent users. Availability and effectiveness of conventional treatment for cannabis use is limited. While Brief Interventions (BIs) have been shown to result in short-term reductions of cannabis use risks or problems, few studies have assessed their longer-term effects. The present study examined 12-month follow-up outcomes for BIs in a cohort of young Canadian high-frequency cannabis users where select short-term effects (3 months) had previously been assessed and demonstrated.
Findings
N = 134 frequent cannabis users were recruited from among university students in Toronto, randomized to either an oral or a written cannabis BI, or corresponding health controls, and assessed in-person at baseline, 3-months, and 12-months. N = 72 (54 %) of the original sample were retained for follow-up analyses at 12-months where reductions in ‘deep inhalation/breathholding’ (Q = 13.1; p < .05) and ‘driving after cannabis use’ (Q = 9.3; p < .05) were observed in the experimental groups. Reductions for these indicators had been shown at 3-months in the experimental groups; these reductions were maintained over the year. Other indicators assessed remained overall stable in both experimental and control groups.
Conclusions
The results confirm findings from select other studies indicating the potential for longer-term and sustained risk reduction effects of BIs for cannabis use. While further research is needed on the long-term effects of BIs, these may be a valuable – and efficient – intervention tool in a public health approach to high-risk cannabis use.
doi:10.1186/1747-597X-7-15
PMCID: PMC3504513  PMID: 22538183
Cannabis use; Frequent use; Young adults; Brief interventions; Prevention; Canada
9.  Medial temporal structures and memory functions in adolescents with heavy cannabis use 
Journal of Psychiatric Research  2011;45(8):1055-1066.
Converging lines of evidence suggest an adverse effect of heavy cannabis use on adolescent brain development, particularly on the hippocampus. In this preliminary study, we compared hippocampal morphology in 14 “treatment-seeking” adolescents (aged 18-20) with a history of prior heavy-cannabis use (5.8 joints/day) after an average of 6.7 months of drug abstinence, and 14 demographically matched normal controls. Participants underwent a high-resolution 3D MRI as well as cognitive testing including the California Verbal Learning Test (CVLT). Heavy-cannabis users showed significantly smaller volumes of the right (p< .04) and left (p< .02) hippocampus, but no significant differences in the amygdala region compared to controls. In controls, larger hippocampus volumes were observed to be significantly correlated with higher CVLT verbal learning and memory scores, but these relationships were not observed in cannabis users. In cannabis users, a smaller right hippocampus volume was correlated with a higher amount of cannabis use (r= - .57, p< .03). These data support a hypothesis that heavy-cannabis use may have an adverse effect on hippocampus development. These findings, after an average 6.7 month of supervised abstinence, lend support to a theory that cannabis use may impart long-term structural and functional damage. Alternatively, the observed hippocampal volumetric abnormalities may represent a risk factor for cannabis dependence. These data have potential significance for understanding the observed relationship between early cannabis exposure during adolescence and subsequent development of adult psychopathology reported in the literature for schizophrenia and related psychotic disorders.
doi:10.1016/j.jpsychires.2011.01.004
PMCID: PMC3303223  PMID: 21296361
hippocampus; cannabis; adolescence; magnetic resonance imaging; CVLT; learning and memory
10.  Approach to cannabis use disorder in primary care 
Canadian Family Physician  2014;60(9):801-808.
Objective
To review the clinical features and complications of at-risk cannabis use and cannabis use disorder, and to outline an office-based protocol for screening, identifying, and managing this disorder.
Sources of information
PubMed was searched for controlled trials, observational studies, and reviews on cannabis use among adolescents and young adults; cannabis-related medical and psychiatric harms; cannabis use disorder and its treatment; and lower-risk cannabis use guidelines.
Main message
Physicians should ask all patients about cannabis use. They should ask adolescents and young adults and those at highest risk of cannabis-related harms (those with concurrent psychiatric or substance use disorders) more frequently. Physicians should also ask about cannabis use in patients who have problems that could be caused by cannabis, such as mood disorders, psychosis, and respiratory symptoms. In patients who report cannabis use, physicians should inquire about frequency and amount, tolerance and withdrawal symptoms, attempts to reduce use, and cannabis-related harms. Lower-risk cannabis users smoke, inhale, or ingest cannabis occasionally without evidence of school, work, or social dysfunction; those with problematic use often use cannabis daily or almost daily, have difficulty reducing their use, and have impaired school, work, or social functioning. Physicians should offer all patients with problematic use brief advice and counseling, focusing on the health effects of cannabis and setting a goal of abstinence (some higher-risk groups should not use cannabis at all) or reduced use, and they should provide practical strategies to reduce cannabis use. Physicians should incorporate simple motivational interviewing techniques into the counseling sessions. They should refer those patients who are unable to reduce use or who are experiencing harms from cannabis use to specialized care, while ensuring those patients remain connected to primary care. As well, physicians should give information on lower-risk cannabis use to all cannabis users.
Conclusion
Physicians should screen all patients in their practices at least once for cannabis use, especially those who have problems that might be caused by cannabis. Physicians should screen those at higher risk more often, at least annually. Lower-risk cannabis use should be distinguished from problematic use. Brief counseling should be provided to those with problematic use; these patients should be referred to specialists if they are unable to reduce or cease use.
PMCID: PMC4162694  PMID: 25217674
11.  The Social Context of Cannabis Use: Relationship to Cannabis Use Disorders and Depressive Symptoms among College Students 
Addictive behaviors  2009;34(9):764-768.
Few studies have investigated the association between the social context of cannabis use and cannabis use disorder (CUD). This longitudinal study of college students aimed to: develop a social context measure of cannabis use; examine the degree to which social context is associated with the transition from non-problematic cannabis use to CUD; and, examine the association between social context of cannabis use and depressive symptoms. The analytic sample consisted of 322 past-year cannabis users at baseline. Four distinct and internally consistent social context scales were found (i.e., social facilitation, emotional pain, sex-seeking, and peer acceptance). Persistent CUD (meeting DSM-IV criteria for CUD at baseline and twelve months later) was associated with using cannabis in social facilitation or emotional pain contexts, controlling for frequency of cannabis use and alcohol use quantity. Students with higher levels of depressive symptoms were more likely to use cannabis in an emotional pain or sex-seeking context. These findings highlight the importance of examining the social contextual factors relating to substance use among college students.
doi:10.1016/j.addbeh.2009.05.001
PMCID: PMC2709927  PMID: 19497678
cannabis; marijuana; drug abuse liability; drug addiction; college students; mental health
12.  Cannabis withdrawal in the United States: a general population study 
The Journal of clinical psychiatry  2008;69(9):1354-1363.
Objective
Although cannabis is the most widely abused illicit drug, little is known about the prevalence of cannabis withdrawal, its factor structure, clinical validity and psychiatric correlates in the general population.
Methods
National Epidemiologic Survey on Alcohol and Related Conditions participants were assessed with structured in-person interviews covering substance history, DSM-IV Axis I and II disorders, and withdrawal symptoms after cessation of use. Of these, 2,613 had been frequent cannabis users (≥3 times/week), and a cannabis-only subset (N=1,119) never binge-drank or used other drugs ≥3 times/week.
Results
In the full sample and subset, 44.3% (se 1.19) and 44.2% (se 1.75), respectively, experienced ≥2 cannabis withdrawal symptoms, while 34.4% (se 1.21) and 34.1% (se 1.76), respectively, experienced ≥3 symptoms. The symptoms formed two factors, one characterized by weakness, hypersomnia, and psychomotor retardation, and the second by anxiety, restlessness, depression, insomnia. Both symptom types were associated with significant distress/impairment (p<.01), substance use to relieve/avoid cannabis withdrawal symptoms (p<.01), and quantity of cannabis use (among the cannabis-only users p<.05). Panic (p<.01) and personality disorders (p<.01) associated with anxiety symptoms in both samples, family history of drug problems with weakness symptoms in the subset (p=.01), and depression with both sets of symptoms in the subset (p<.05).
Conclusion
Cannabis withdrawal was prevalent and clinically significant among a representative sample of frequent cannabis users. Similar results in the subset without polysubstance abuse confirmed the specificity of symptoms to cannabis. Cannabis withdrawal should be added to DSM-V and the etiology and treatment implications of cannabis withdrawal symptoms investigated.
PMCID: PMC2777674  PMID: 19012815
cannabis; marijuana; withdrawal; general population; DSM-V
13.  Cannabis Use and Dependence among French Schizophrenic Inpatients 
Background: To assess the prevalence of cannabis use and dependence in a population of schizophrenic inpatients and to compare schizophrenics with and without cannabis consumption.
Methods: One hundred one schizophrenic patients were examined during their first week of hospitalization. They answered the PANNS scale of schizophrenia, the CAGE and the Fagerström questionnaire, and the DSM-IV-TR criteria for cannabis, alcohol, opiates, and nicotine use dependence were checked. We also assessed socio-demographic characteristics, the motive of cannabis consumption, and the number of cannabis joints and alcoholic drinks taken.
Results: The prevalence of cannabis consumption was 33.6% among schizophrenic inpatients. Schizophrenics consuming cannabis were younger than non-schizophrenics (33.3 vs. 44.7 years p < 0.0001), more often male (77 vs. 54%, p = 0.02) and had been hospitalized for the first time in psychiatry earlier (24.3 vs. 31.3 p = 0.003). Eighty-eight percent of cannabis consumers were dependent on cannabis. They were more often dependent on opiates (17 vs. 0%) and alcohol (32 vs. 7.4%, p = 0.001) and presented compulsive buying more often (48 vs. 27%, p = 0.04). Logistic regression revealed that factors associated to cannabis consumption among schizophrenics were cannabis dependence, male gender, pathological gambling, opiate dependence, number of joints smoked each day, and compulsive buying.
Conclusion: 33.6% of the schizophrenic patients hospitalized in psychiatry consume cannabis and most of them are dependent on cannabis and alcohol. Hospitalization in psychiatry may provide an opportunity to systematically identify a dependence disorder and to offer appropriate information and treatment.
doi:10.3389/fpsyt.2014.00082
PMCID: PMC4097102  PMID: 25076916
cannabis; addiction; dependence; alcohol; nicotine; compulsive buying; pathological gambling; alcohol dependence
14.  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.
doi:10.2196/jmir.2256
PMCID: PMC3636012  PMID: 23470329
marijuana; Internet intervention; computer-assisted therapy; addiction; randomized controlled trial
15.  Association of Cannabis Use with Opioid Outcomes among Opioid-Dependent Youth 
Drug and alcohol dependence  2013;132(0):342-345.
Objective
Cannabis use is common among opioid-dependent patients, but studies of its association with treatment outcome are mixed. In this secondary analysis, the association of cannabis use with opioid treatment outcome is assessed.
Methods
In the main study, participants (N=152) aged 15-21 years were randomized to receive psychosocial treatments and either a 12-week course of buprenorphine-naloxone with a dose taper to zero in weeks 9-12, or a 2-week detoxification with buprenorphine-naloxone. Drug use was assessed by self-report and urine drug screen at baseline and during study weeks 1-12. The association between cannabis and opioid use at weeks 4, 8, and 12 was examined using logistic regression models.
Results
Participants reported a median of 3.0 days (range=0-30) cannabis use in the past month; half (50.3%; n=77) reported occasional use, one-third reported no use (33.1%; n=50), and one-sixth reported daily cannabis use (16.6%; n=25). Median lifetime cannabis use was 4.0 years (range=0-11) and median age of initiation of use was 15.0 years (range 9-21). Neither past cannabis use (age of initiation and use in the month prior to baseline) nor concurrent use was associated with level of opioid use.
Conclusions
Overall, cannabis use had no association with opioid use over 12 weeks in this sample of opioid-dependent youth. While cannabis use remains potentially harmful, it was not a predictor of poor opioid treatment outcome.
doi:10.1016/j.drugalcdep.2013.02.030
PMCID: PMC3724203  PMID: 23528523
cannabis use; opioid dependence; buprenorphine; adolescent substance abuse
16.  Self reported cannabis use as a risk factor for schizophrenia in Swedish conscripts of 1969: historical cohort study 
BMJ : British Medical Journal  2002;325(7374):1199.
Objectives
An association between use of cannabis in adolescence and subsequent risk of schizophrenia was previously reported in a follow up of Swedish conscripts. Arguments were raised that this association may be due to use of drugs other than cannabis and that personality traits may have confounded results. We performed a further analysis of this cohort to address these uncertainties while extending the follow up period to identify additional cases.
Design
Historical cohort study.
Setting
1969-70 survey of Swedish conscripts (>97% of the country's male population aged 18-20).
Participants
50 087 subjects: data were available on self reported use of cannabis and other drugs, and on several social and psychological characteristics.
Main outcome measures
Admissions to hospital for ICD-8/9 schizophrenia and other psychoses, as determined by record linkage.
Results
Cannabis was associated with an increased risk of developing schizophrenia in a dose dependent fashion both for subjects who had ever used cannabis (adjusted odds ratio for linear trend of increasing frequency 1.2, 95% confidence interval 1.1 to 1.4, P<0.001), and for subjects who had used only cannabis and no other drugs (adjusted odds ratio for linear trend 1.3, 1.1 to 1.5, P<0.015). The adjusted odds ratio for using cannabis >50 times was 6.7 (2.1 to 21.7) in the cannabis only group. Similar results were obtained when analysis was restricted to subjects developing schizophrenia after five years after conscription, to exclude prodromal cases.
Conclusions
Cannabis use is associated with an increased risk of developing schizophrenia, consistent with a causal relation. This association is not explained by use of other psychoactive drugs or personality traits relating to social integration.
What is already known about this topicUse of cannabis has been associated with an increased risk of developing schizophreniaAlternative explanations for this association include confounding by personality or by use of other drugs such as amphetamines, and use of cannabis as a form of self medication secondary to the disorderWhat this study addsSelf reported cannabis use is associated with an increased risk of subsequently developing schizophrenia, consistent with a causal relationThis association is not explained by sociability personality traits, or by use of amphetamines or other drugsSelf medication with cannabis is an unlikely explanation for the association observed
PMCID: PMC135490  PMID: 12446534
17.  Cannabis Withdrawal is Common among Treatment-Seeking Adolescents with Cannabis Dependence and Major Depression, and is Associated with Rapid Relapse to Dependence 
Addictive behaviors  2008;33(11):1500-1505.
Recently, reports have suggested that cannabis withdrawal occurs commonly in adults with cannabis dependence, though it is unclear whether this extends to those with comorbid depression or to comorbid adolescents. We hypothesized that cannabis withdrawal would be common among our sample of comorbid adolescents and young adults, and that the presence of cannabis withdrawal symptoms would be associated with a self-reported past history of rapid reinstatement of cannabis dependence symptoms (rapid relapse). The participants in this study included 170 adolescents and young adults, including 104 with cannabis dependence, 32 with cannabis abuse, and 34 with cannabis use without dependence or abuse. All of these subjects demonstrated current depressive symptoms and cannabis use, and most demonstrated current DSM-IV major depressive disorder and current comorbid cannabis dependence. These subjects had presented for treatment for either of two double-blind, placebo-controlled trials involving fluoxetine. Cannabis withdrawal was the most commonly reported cannabis dependence criterion among the 104 subjects in our sample with cannabis dependence, being noted in 92% of subjects, using a two-symptom cutoff for determination of cannabis withdrawal. The most common withdrawal symptoms among those with cannabis dependence were craving (82%), irritability (76%), restlessness (58%), anxiety (55%), and depression (52%). Cannabis withdrawal symptoms (in the N=170 sample) were reported to have been associated with rapid reinstatement of cannabis dependence symptoms (rapid relapse). These findings suggest that cannabis withdrawal should be included as a diagnosis in the upcoming DSM-V, and should be listed in the upcoming criteria list for the DSM-V diagnostic category of cannabis dependence.
doi:10.1016/j.addbeh.2008.02.001
PMCID: PMC2565493  PMID: 18313860
18.  Laboratory Profiles of Treatment-Seeking Subjects With Concurrent Dependence on Cannabis and Other Substances: A Comparative Study 
Background:
Cannabis is one of the most widely used illicit drugs in India and worldwide. It is considered to have a minimal effect on physical health.
Objectives:
The aim of this study was to compare the laboratory profiles of treatment-seeking patients who were cannabis dependent, and drug users who concurrently use other substances, with non-users.
Materials and Methods:
Medical records of patients, whose urine was tested for the detection of cannabis within the last year, were considered for the study. The inclusion criteria for the study group were; co-morbid diagnosis of cannabis dependence according to DSM-IV TR criteria, positive urine drug screen for cannabis, and at least one biochemical or hematological examination report during the treatment period. The subjects who underwent all of the above mentioned tests, but who were negative for any psychoactive substance with no past or current history of substance use, were placed in the control group.
Results:
A total of 51 subjects fulfilled the inclusion criteria for the study group and 30 subjects were considered as controls. There was no significant difference found between the demographic profiles of the subject and control groups. The mean duration of cannabis use in the patients was 9.53 ± 8.06 years. Serum levels of; bilirubin, SGOT (serum glutamic oxaloacetic transaminase), SGPT (serum glutamic pyruvic transaminase), total protein, alkaline phosphatase, ESR, and eosinophil counts, were raised in; 13.7%, 15.6%, 33.3%, 17.6%, 37.2%, 75% and 5.8% of subjects, respectively. The relative monocyte count was lower than normal in 92% of cases. Physical complaints were reported in 98% of subjects. The two groups showed significant differences in serum alkaline phosphatase [t (79) = 6.5, P ≤ 0.01], TLC [t (79) = 2.36, P = 0.03] and hemoglobin levels [t (79) = 5.50, P ≤ 0.01].
Conclusions:
Abnormal laboratory parameters were observed in patients with cannabis dependence. The study emphasizes the need for regular physical examinations and laboratory investigations for cannabis users.
doi:10.5812/ijhrba.10993
PMCID: PMC4070163  PMID: 24971286
Cannabis; Urine; Liver Function Tests; Leukocyte Count
19.  Continued cannabis use at one year follow up is associated with elevated mood and lower global functioning in bipolar I disorder 
BMC Psychiatry  2015;15:11.
Background
There is limited knowledge about how environmental factors affect the course of bipolar disorder (BD). Cannabis has been proposed as a potential risk factor for poorer course of illness, but the role of cannabis use has not been studied in a first treatment BD I sample.
Methods
The present study examines the associations between course of illness in first treatment BD I and continued cannabis use, from baseline to one year follow up. Patients (N = 62) with first treatment DSM-IV BD I were included as part of the Thematically Organized Psychosis study (TOP), and completed interviews and self-report questionnaires at both baseline and follow up. Cannabis use within the last six months at baseline and use between baseline and follow up (“continued use”) was recorded.
Results
After controlling for confounders, continued cannabis use was significantly associated with elevated mood (YMRS) and inferior global functioning (GAF-F) at follow up. Elevated mood mediated the effect of cannabis use on global functioning.
Conclusions
These results suggest that cannabis use has clinical implications for the early course of BD by increasing mood level. More focus on reducing cannabis use in clinical settings seems to be useful for improving outcome in early phase of the disorder.
doi:10.1186/s12888-015-0389-x
PMCID: PMC4323143  PMID: 25651990
Cannabis; Bipolar
20.  Two-part random effects growth modeling to identify risks associated with alcohol and cannabis initiation, initial average use and changes in drug consumption in a sample of adult, male twins 
Drug and alcohol dependence  2011;123(1-3):220-228.
Aims
Our aim was to profile alcohol and cannabis initiation and to characterize the effects of developmental and environmental risk factors on changes in average drug use over time.
Design
We fitted a two-part random effects growth model to identify developmental and environmental risks associated with alcohol and cannabis initiation, initial average use and changes in average use.
Participants
1796 males aged 24–63 from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders.
Measurements
Data from three interview waves included self-report measures of average alcohol and cannabis use between ages 15 and 24, genetic risk of problem drug use, childhood environmental risks, personality, psychiatric symptoms, as well as personal, family and social risk factors.
Findings
Average alcohol and cannabis use were correlated at all ages. Genetic risk of drug use based on family history, higher sensation seeking, and peer group deviance predicted both alcohol and cannabis initiation. Higher drug availability predicted cannabis initiation while less parental monitoring and drug availability were the best predictors of how much cannabis individuals consumed over time.
Conclusion
The liability to initiate alcohol and cannabis, average drug use as well as changes in drug use during teenage years and young adulthood is associated with known risk factors.
doi:10.1016/j.drugalcdep.2011.11.015
PMCID: PMC3442360  PMID: 22177896
Alcohol; Cannabis; Initiation; Longitudinal; Risks; Two-part random effects; Latent class; Growth curve; Mixture distributions
21.  Reaching out towards cannabis: approach-bias in heavy cannabis users predicts changes in cannabis use 
Addiction (Abingdon, England)  2011;106(9):1667-1674.
Aims
Repeated drug exposure can lead to an approach-bias, i.e. the relatively automatically triggered tendencies to approach rather that avoid drug-related stimuli. Our main aim was to study this approach-bias in heavy cannabis users with the newly developed cannabis Approach Avoidance Task (cannabis-AAT) and to investigate the predictive relationship between an approach-bias for cannabis-related materials and levels of cannabis use, craving, and the course of cannabis use.
Design, settings and participants
Cross-sectional assessment and six-month follow-up in 32 heavy cannabis users and 39 non-using controls.
Measurements
Approach and avoidance action-tendencies towards cannabis and neutral images were assessed with the cannabis AAT. During the AAT, participants pulled or pushed a joystick in response to image orientation. To generate additional sense of approach or avoidance, pulling the joystick increased picture size while pushing decreased it. Craving was measured pre- and post-test with the multi-factorial Marijuana Craving Questionnaire (MCQ). Cannabis use frequencies and levels of dependence were measured at baseline and after a six-month follow-up.
Findings
Heavy cannabis users demonstrated an approach-bias for cannabis images, as compared to controls. The approach-bias predicted changes in cannabis use at six-month follow-up. The pre-test MCQ emotionality and expectancy factor were associated negatively with the approach-bias. No effects were found on levels of cannabis dependence.
Conclusions
Heavy cannabis users with a strong approach-bias for cannabis are more likely to increase their cannabis use. This approach-bias could be used as a predictor of the course of cannabis use to identify individuals at risk from increasing cannabis use.
doi:10.1111/j.1360-0443.2011.03475.x
PMCID: PMC3178782  PMID: 21518067
Approach avoidance task; approach-bias; cannabis; cannabis use disorder; craving; dependence
22.  A prospective study of cannabis use as a risk factor for non-adherence and treatment dropout in first-episode schizophrenia 
Schizophrenia research  2009;113(2-3):138-144.
Introduction
Although several studies have reported on cannabis use and adherence for first episode of psychosis patients, the findings remain unclear as to whether cannabis use is a risk factor for poor adherence in young people with first-episode schizophrenia. This study was designed to follow patients’ use of cannabis and adherence in a naturalistic setting during the first 12 months of treatment. It examines whether cannabis use is a risk factor for two distinct types of non-adherence: non-adherence to medication and treatment dropout..
Methods
Participants were 112 first-episode schizophrenia patients of diverse backgrounds at two community hospitals, enrolled in of two second-generation antipsychotic medications. a study of differential effectiveness Multiple indicators were used to assess cannabis use and adherence to medication. Patients were encouraged to continue in the study even after periods of treatment refusal or change from study to standardized medication. Study hypotheses were tested using Cox proportional hazards models with cannabis use as a time-varying covariate.
Results
After 12 months, 23 had dropped out and 37 had at some point been non-adherent to medication. Of 34 participants who used cannabis during treatment, 32 had a prior diagnosis of cannabis abuse/dependence and 30 were male. Independently of age, race, socioeconomic status, gender, site, and medication assignment, cannabis use significantly increased hazard of non-adherence by a factor of 2.4 (p < .001) and hazard of dropout by a factor of 6.4 (p = .034).
Conclusion
Results indicate that cannabis use is a risk factor for non-adherence to medication and dropout from treatment. Treatment for first-episode schizophrenia may be more effective if providers address the issue of cannabis use with patients throughout the early years of treatment, especially for those with existing cannabis abuse/dependence.
doi:10.1016/j.schres.2009.04.018
PMCID: PMC2726744  PMID: 19481424
Schizophrenia; adherence; dropout; cannabis; first-episode; substance abuse; compliance
23.  Combining cognitive behavioral therapy and contingency management to enhance their effects in treating cannabis dependence: less can be more, more or less 
Addiction (Abingdon, England)  2012;107(9):1650-1659.
Aims
To evaluate reciprocal enhancement (combining treatments to offset their relative weaknesses) as a strategy to improve cannabis treatment outcomes. Contingency management (CM) with reinforcement for homework completion and session attendance was used as a strategy to enhance cognitive–behavioral therapy (CBT) via greater exposure to skills training; CBT was used as a strategy to enhance durability of CM with rewards for abstinence.
Setting
Community-based out-patient treatment program in New Haven, Connecticut, USA.
Design
Twelve-week randomized clinical trial of four treatment conditions: CM for abstinence alone or combined with CBT, CBT alone or combined with CM with rewards for CBT session attendance and homework completion.
Participants
A total of 127 treatment-seeking young adults (84.3% male, 81.1% minority, 93.7% referred by criminal justice system, average age 25.7 years).
Measurements
Weekly urine specimens testing positive for cannabis, days of cannabis use via the time-line follow-back method.
Findings
Within treatment, reinforcing homework and attendance did not significantly improve CBT outcomes, and the addition of CBT worsened outcomes when added to CM for abstinence (75.5 versus 57.1% cannabis-free urine specimens, F = 2.25, P = 0.02). The CM for abstinence condition had the lowest percentage of cannabis-negative urine specimens and the highest mean number of consecutive cannabis-free urine specimens (3.3, F = 2.33, P = 0.02). Attrition was higher in the CBT alone condition, but random effect regression analyses indicated this condition was associated with the greatest rate of change overall. Cannabis use during the 1-year follow-up increased most rapidly for the two enhanced groups.
Conclusions
Combining contingency management and cognitive–behavioural therapy does not appear to improve success rates of treatment for cannabis dependence in clients involved with the criminal justice system.
doi:10.1111/j.1360-0443.2012.03877.x
PMCID: PMC3509418  PMID: 22404223
Cannabis dependence; cognitive behavioral therapy; contingency management; criminal justice system; randomized clinical trial
24.  DSM-IV criteria-based clinical subtypes of cannabis use disorders: Results from the National Epidemiological Survey on Alcohol and Related Conditions (NESARC)☆ 
Drug and alcohol dependence  2008;96(0):10.1016/j.drugalcdep.2008.02.008.
Prior research documented high homogeneity of alcohol use disorders (AUDs) as clinical entities. However, it is unknown whether this finding extends to other substance use disorders. We investigated this by examining the prevalence of all possible DSM-IV criteria-based clinical subtypes of current and lifetime cannabis use disorders in the general population. The number of possible (i.e., theoretical) clinical subtypes of cannabis abuse and dependence based on different combinations of the DSM-IV criteria was calculated using the combinatorial function. This number was compared with the subtypes actually observed in the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a large U.S. national sample (N= 43,093). Clinical and demographic correlates of the subtypes were examined with χ2 tests whose target population was the United States civilian non-institutionalized population. All DSM-IV cannabis abuse and dependence criteria were assessed with the Alcohol Use Disorder and Associated Disabilities Interview Schedule—DSM-IV Version (AUDADIS-IV). Of all possible cannabis dependence subtypes, 29 (69%) were observed in the 12-month timeframe, and 41 (98%) in the lifetime timeframe. The corresponding numbers of subtypes for cannabis abuse were 12 (75%), current and 15 (100%), lifetime. These findings suggest that, in contrast to alcohol disorders, cannabis use disorders were highly heterogeneous. Future research should investigate whether there are differences in the course and treatment response of these clinical subtypes of cannabis use disorders, and the heterogeneity of other substance use disorders.
doi:10.1016/j.drugalcdep.2008.02.008
PMCID: PMC3850288  PMID: 18420357
Cannabis use disorder; Subtypes; Epidemiological survey; DSM-IV criteria
25.  The Role of Cannabis Use Within a Dimensional Approach to Cannabis Use Disorders 
Drug and alcohol dependence  2008;100(3):221-227.
Context
Cannabis consumption is central to diagnosis of DSM-IV cannabis abuse and dependence; yet, most research on cannabis disorders has focused just on diagnosis or criteria. The present study examines the ability of a frequency and quantity measure of cannabis use as well as cannabis abuse and dependence criteria to discriminate between individuals across the cannabis use disorder continuum.
Method
A representative sample of USA adults in 2001–2002 (N=43,093) were queried about past year frequency of cannabis use and each DSM-IV cannabis abuse and dependence criterion. Factor analysis and item response theory (IRT) models were used to define the relationship between observed responses and the underlying unobserved latent trait (cannabis use disorder severity).
Results
Factor analyses demonstrated a good fit for a one factor model both with and without the cannabis use criterion and no differential criterion functioning was demonstrated across sex. The IRT model including the cannabis use criterion had discriminatory power comparable to the model without the cannabis use criterion and exceeded the informational value of the model without the cannabis use criterion in mild and moderate ranges of the severity continuum.
Discussion
Factor and IRT analyses disprove the validity of the DSM-IV abuse and dependence distinction: A single dimension represented the criteria rather than the two implied by the separate abuse/dependence categories. IRT models identified some dependence criteria to be among the mildest and some abuse criteria to be among the most severe —results inconsistent with the interpretation of DSM-IV cannabis abuse as a milder disorder or prodrome of cannabis dependence. The consumption criterion defined the mild end of the cannabis use disorder continuum and its excellent psychometric properties strongly supported its inclusion as a DSM -V criterion for cannabis use disorders. Additional work is needed to identify candidate consumption criteria across all drugs that apply to the milder end of the severity continuum while also improving overall model performance and clinical diagnostic utility.
doi:10.1016/j.drugalcdep.2008.10.009
PMCID: PMC3153503  PMID: 19062204
Cannabis use disorders; IRT analysis; Cannabis use

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