Shaul Lev-Ran

The association between cannabis use and depression: a systematic review and meta-analysis of longitudinal studies

BACKGROUND Longitudinal studies reporting the association between cannabis use and developing depression provide mixed results. The objective of this study was to establish the extent to which different patterns of use of cannabis are associated with the development of depression using meta-analysis of longitudinal studies. METHOD Peer-reviewed publications reporting the risk of developing depression in cannabis users were located using searches of EMBASE, Medline, PsychINFO and ISI Web of Science. Only longitudinal studies that controlled for depression at baseline were included. Data on several study characteristics, including measures of cannabis use, measures of depression and control variables, were extracted. Odds ratios (ORs) were extracted by age and length of follow-up. RESULTS After screening for 4764 articles, 57 articles were selected for full-text review, of which 14 were included in the quantitative analysis (total number of subjects = 76058). The OR for cannabis users developing depression compared with controls was 1.17 [95% confidence interval (CI) 1.05-1.30]. The OR for heavy cannabis users developing depression was 1.62 (95% CI 1.21-2.16), compared with non-users or light users. Meta-regression revealed no significant differences in effect based on age of subjects and marginal difference in effect based on length of follow-up in the individual studies. There was large heterogeneity in the number and type of control variables in the different studies. CONCLUSIONS Cannabis use, and particularly heavy cannabis use, may be associated with an increased risk for developing depressive disorders. There is need for further longitudinal exploration of the association between cannabis use and developing depression, particularly taking into account cumulative exposure to cannabis and potentially significant confounding factors.

Bipolar disorder and co-occurring cannabis use disorders: Characteristics, co-morbidities and clinical correlates

This study examines rates of co-morbid mental disorders and indicators of the course of illness among individuals with bipolar disorder and cannabis use disorders (CUD). Data were drawn from the National Epidemiological Survey of Alcohol and Related Conditions (NESARC Wave 1, 2001-2002), a nationally representative sample of adults living in the United States. Among individuals with lifetime prevalence of bipolar disorder (N=1905) rates of CUD in the past 12 months were 7.2%, compared to 1.2% in the general population. Logistic regression models adjusting for sociodemographic variables indicated that individuals with bipolar disorder and co-occurring CUD were at increased risk for nicotine dependence (Adjusted Odds Ratio (AOR)=3.8), alcohol (AOR=6.6) and drug (AOR=11.9) use disorders, as well as antisocial personality disorder (AOR=2.8) compared to those without CUD. Among individuals with co-occurring CUD, age of onset of bipolar disorder was significantly lower and median number of manic, hypomanic and depressive episodes per year was significantly greater compared to individuals without CUD. Co-occurring CUD is associated with significant co-morbidities and a more severe course of illness among individuals with bipolar disorder. Comprehensive evaluation of patients with bipolar disorder should include a systematic assessment of CUD.

Gender differences in health-related quality of life among cannabis users: Results from the national epidemiologic survey on alcohol and related conditions

BACKGROUND Cannabis is the most widely used illicit substance worldwide. The aim of the present study was to assess self-reported Quality of Life (QoL) among cannabis users in a large representative sample. METHODS We analyzed data from the National Epidemiological Survey of Alcohol and Related Conditions (NESARC, n=43,093). Health-related QoL was assessed using the Short-form 12-item Health Survey (SF-12). The contribution of cannabis use and cannabis use disorders (CUD) to SF-12 scores was assessed using multiple linear regressions models. RESULTS The prevalence of cannabis use and CUD in the last 12 months was 4.1% and 1.5%, respectively. Mean SF-12 mental summary scores were significantly lower (indicating a lower QoL) among female and male cannabis users compared to non-users (by 0.6 standard deviations (SD) and 0.3 SD, respectively), and among females and males with CUD compared to those without CUD (by 0.9 SD and 0.4 SD, respectively). Controlling for sociodemographic variables and mental illness, each joint smoked daily was associated with a greater decrease in mental QoL summary scores in females (0.1 SD) compared to males (0.03 SD). CONCLUSIONS Cannabis use and CUD were associated with lower self-reported mental QoL. Specifically, our findings showed that cannabis use and CUD have a more significant effect on self-reported mental health QoL among female users. Assessing severity of cannabis use and impact of CUD should take into account functional and emotional outcomes. This may particularly aid in detecting the impact of cannabis use and CUD on mental health-related QoL among females.

Cannabis use and cannabis use disorders among individuals with mental illness.

BACKGROUND National epidemiological surveys have reported increased rates of cannabis use and cannabis use disorders (CUDs) among individuals with mental illness. However, this subject has not been sufficiently investigated, particularly given limitations in diagnostic tools used and lack of data pertaining to frequency of cannabis used. OBJECTIVES To examine the prevalence of cannabis use and CUDs among individuals with a wide range of mental illness. METHOD We analyzed data on 43,070 respondents age 18 and above from the National Epidemiologic Survey on Alcohol and Related Conditions, a nationally representative survey conducted from 2001 to 2002. Main outcome measures included rates of cannabis use by frequency (at least weekly and less than weekly use) and DSM-IV CUDs according to the number and type of axis I and axis II psychiatric diagnoses, assessed by the Alcohol Use Disorders and Associated Disabilities Interview Schedule-IV. We estimated the proportion of cannabis used by individuals with mental illness using reported daily dose and frequency of cannabis used by individuals with and without mental illness. RESULTS Rates of weekly cannabis use, less than weekly cannabis use and CUDs among individuals with 12-month mental illness were 4.4%, 5.4% and 4.0%, respectively, compared to 0.6%, 1.1% and 0.4%, respectively, among individuals without any 12-month mental illness (P<0.0001 for all comparisons). The odds ratio for cannabis use among individuals with 12-month mental illness vs. respondents without any mental illness was 2.5, and the odds of having a CUD among individuals with 12-month mental illness were 3.2, after adjusting for sociodemographic variables and additional substance use disorders. Cannabis use and CUDs were particularly associated with bipolar disorder, substance use disorders and specific (anti-social, dependant and histrionic) personality disorders. Persons with a mental illness in the past 12 months represented 72% of all cannabis users and we estimated they consumed 83% of all cannabis consumed by this nationally representative sample. CONCLUSIONS The current study provides further evidence of the strong association between cannabis use and a broad range of primary mental illness. This emphasizes the importance of proper screening for frequent cannabis use and CUDs among individuals with primary mental illness and focusing prevention and treatment efforts on this population.

The association between cannabis use and mood disorders: A longitudinal study

BACKGROUND The association between cannabis use and mood disorders is well documented, yet evidence regarding causality is conflicting. This study explored the association between cannabis use, major depressive disorder (MDD) and bipolar disorder (BPD) in a 3-year prospective study. METHODS Data was drawn from waves 1 and 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). MDD and BPD were controlled at baseline and defined as meeting full criteria in the 12 months prior to the follow-up. Initiation of cannabis use was defined as any cannabis used by former lifetime abstainers in the time period between baseline and follow-up. RESULTS Cannabis use was not significantly associated with increased incidence of MDD (Adjusted Odds Ratio (AOR) for daily use=0.58(0.22-1.51)). Weekly to almost daily cannabis use was associated with increased incidence of BPD ((AOR for weekly to daily use=2.47(1.03-5.92)); daily use was not (AOR=0.52(0.17-1.55)). Baseline MDD was associated with initiation of cannabis use (AOR=1.72(1.1-2.69)). A crude association between baseline BPD and incidence of cannabis use was not maintained in adjusted models (AOR=0.61(0.36-1.04)). LIMITATIONS Lack of information regarding frequency of cannabis use at follow-up and limitations regarding generalization of the results. CONCLUSIONS Our findings do not support a longitudinal association between cannabis use and incidence of MDD. Results regarding the association between cannabis use and incidence of BPD are conflicting and require further investigation. Baseline MDD, but not BPD, may be associated with future initiation of cannabis use. This may have implications for clinical, social and legislative aspects of cannabis use.

Gender differences in prevalence of substance use disorders among individuals with lifetime exposure to substances: results from a large representative sample.

BACKGROUND AND OBJECTIVES Research regarding substance use and substance use disorders (SUDs) shows significant gender differences in prevalence of substance use and dependence. Though lifetime exposure to substances is higher among males, previous reports have not regarded gender differences in prevalence of SUDs among individuals formerly exposed to substances. In addition, though substance abuse is particularly important when exploring gender differences, previous reports have largely focused on rates of transition to substance dependence alone. In this study, we explored gender differences in prevalence of SUDs among individuals with lifetime exposure to substances using a single diagnostic category (abuse or dependence). METHODS We analyzed 11 different categories of substances: heroin, cocaine, cannabis, nicotine, alcohol, hallucinogens, inhalants, sedatives, tranquilizers, opioids, and amphetamines. Data were derived from the National Epidemiologic Survey on Alcohol and Related Conditions (Wave 1, n = 43,093). The impact of gender on prevalence of SUDs among individuals with lifetime exposure to substances was assessed with odds ratios (ORs) using logistic regressions and adjusted for socio-demographic factors. RESULTS Our results show that among individuals with lifetime exposure to substances, males had a significantly higher prevalence of alcohol (OR = 2.95), sedatives (OR = 2.00), cannabis (OR = 1.93), tranquilizers (OR = 1.64), opioids (OR = 1.54), hallucinogens (OR = 1.31), and cocaine (OR = 1.26) use disorders compared with females. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE Using a single broad diagnostic category highlights gender differences in the prevalence of SUDs among individuals with former exposure to substances. Specifically, the significant gender differences found for alcohol, sedatives, and cannabis use disorders may be important for tailoring preventive measures targeted at reducing rates of SUDs among males using these substances.

Varenicline decreases nicotine self-administration and cue-induced reinstatement of nicotine-seeking behaviour in rats when a long pretreatment time is used

Effects of varenicline (Champix), a nicotinic partial agonist, were evaluated on subjective effects of nicotine (drug discrimination), motivation for nicotine taking (progressive-ratio schedule of intravenous nicotine self-administration) and reinstatement (cue-induced reinstatement of previously extinguished nicotine-seeking behaviour). Effects on motor performance were assessed in rats trained to discriminate nicotine (0.4 mg/kg) from saline under a fixed-ratio (FR 10) schedule of food delivery and in rats trained to respond for food under a progressive-ratio schedule. At short pretreatment times (5-40 min), varenicline produced full or high levels of partial generalization to nicotines discriminative-stimulus effects and disrupted responding for food, while there were low levels of partial generalization and no disruption of responding for food at 2- or 4-h pretreatment times. Varenicline (1 and 3 mg/kg, 2-h pretreatment time) enhanced discrimination of low doses of nicotine and to a small extent decreased discrimination of the training dose of nicotine. It also dose-dependently decreased nicotine-taking behaviour, but had no effect on food-taking behaviour under progressive-ratio schedules. Finally, varenicline significantly reduced the ability of a nicotine-associated cue to reinstate extinguished nicotine-seeking behaviour. The ability of varenicline to reduce both nicotine-taking and nicotine-seeking behaviour can contribute to its relatively high efficacy in treating human smokers.

Exploring the Association between Lifetime Prevalence of Mental Illness and Transition from Substance Use to Substance Use Disorders: Results from the National Epidemiologic Survey of Alcohol and Related Conditions (NESARC)

BACKGROUND AND OBJECTIVES The association between substance use disorders (SUDs) and mental illness (MI) has been well established. Previous studies reporting this association in various clinical populations have not taken into account former substance use. This may be important as increased prevalence of substance use among individuals with MI may partially explain the strong association between SUDs and MI. METHODS In this study we included only individuals with previous substance use and explored the association between lifetime diagnosis of MI and transition from substance use to SUDs. Analyses were conducted across six different categories of substances (alcohol, nicotine, cannabis, cocaine, hallucinogens, inhalants) based on a large representative US sample, the National Epidemiologic Survey of Alcohol and Related Conditions (NESARC, n = 43,093). RESULTS Lifetime diagnoses of any MI, and particularly personality disorders and psychotic disorders, were found to be associated with higher prevalence of transition from substance use to SUDs across most categories of substances. This association was particularly strong for nicotine (adjusted OR = 2.95 (2.72-3.20)). CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE This cross-sectional study expands on previous research by highlighting the association between lifetime diagnosis of any MI and increased rates of transition from substance use to SUDs across a range of substances. Longitudinal studies exploring temporal effects of this association are further needed.

Alcohol- or drug-use disorders and motor vehicle accident mortality: A retrospective cohort study

A large body of research has linked alcohol consumption and motor vehicle accidents (MVAs), but far fewer studies have estimated the risk of MVA fatality among drug users. Our study addresses this gap. We identified cohorts of individuals hospitalized in California from 1990 to 2005 with ICD-9 diagnoses of methamphetamine- (n=74,170), alcohol- (n=592,406), opioids- (n=68,066), cannabis- (n=47,048), cocaine- (n=48,949), or polydrug-related disorders (n=411,175), and these groups were followed for up to 16 years. Age-, sex-, and race-adjusted standardized mortality rates (SMRs) for deaths due to MVAs were generated in relation to the California general population. Standardized MVA mortality ratios were elevated across all drug cohorts: alcohol (4.5, 95% CI, 4.1-4.9), cocaine (3.8, 95% CI, 2.3-5.3), opioids (2.8, 95% CI, 2.1-3.5), methamphetamine (2.6, 95% CI, 2-3.1), cannabis (2.3, 95% CI, 1.5-3.2) and polydrug (2.6, 95% CI, 2.4-2.9). Males and females had similar MVA SMRs. Our large, population-based study found elevated risk of MVA mortality across all cohorts of individuals with alcohol- or drug-use disorders. Given that illicit drug users are often unaware of or misperceive the impacts of drug use on safe driving, it may be important for health-service or public-health interventions to address such biases and improve road safety.

The association between cannabis use and anxiety disorders: Results from a population-based representative sample

The cross-sectional association between cannabis use and anxiety disorders is well documented, yet less is known about the longitudinal association between the two. This study explored the association between cannabis use, cannabis use disorders (CUDs) and anxiety disorders in a 3-year prospective study. Data was drawn from waves 1 and 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Anxiety disorders, including generalized anxiety disorder, social anxiety, panic disorder and specific phobias, were controlled for at baseline. Initiation of cannabis use was defined as any cannabis use by former lifetime abstainers in the time period between baseline and follow-up, CUDs were defined as a diagnosis of cannabis abuse or dependence. Results indicate that cannabis use was not associated with increased incidence of any anxiety disorder (Adjusted Odds Ratio (AOR)=1.12(0.63-0.98)). Though heavy cannabis use was associated with increased incidence of social anxiety in most models, this was not fully retained in the final adjusted model (AOR=1.98(0.99-1.98)). Investigation of the association between baseline CUDs and anxiety disorders at follow-up revealed similar results. Any baseline anxiety disorder was not associated with future initiation of cannabis use (AOR=1.03(0.62-1.69)) or onset of a CUD (AOR=0.68(0.41-1.14)), yet individuals with baseline panic disorder were more prone to initiate cannabis use at follow-up (AOR=2.2(1.15-4.18)), possibly as a means of self-medication. Our findings suggest that cannabis use and CUDs are not associated with increased incidence of most anxiety disorders and inversely, most anxiety disorders are not associated with increased incidence of cannabis use or CUDs.