Association of Cannabis Use in Adolescence and Risk of Depression, Anxiety, and Suicidality in Young Adulthood – A Systematic Review and Meta-analysis

Gabriella Gobbi, Tobias Atkin, Tomasz Zytynski, Shouao Wang, Sorayya Askari, Jill Boruff,  Mark Ware, Naomi Marmorstein, Andrea Cipriani, Nandini Dendukuri, Nancy Mayo

JAMA Psychiatry, 2019, 76, 4, 426-434.

doi:10.1001/jamapsychiatry.2018.4500

Published online February 13, 2019. Corrected on March 13, 2019.

https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2723657?guestAccessKey=c2ffca43-46c1-4563-8949-c1625bfbdefa&utm_source=silverchair&utm_medium=email&utm_campaign=article_alert-jamanetwork&utm_content=weekly_highlights&utm_term=051919

 

IMPORTANCE : Cannabis is the most commonly used drug of abuse by adolescents in the world. While the impact of adolescent cannabis use on the development of psychosis has been investigated in depth, little is known about the impact of cannabis use on mood and suicidality in young adulthood.

OBJECTIVE : To provide a summary estimate of the extent to which cannabis use during adolescence is associated with the risk of developing subsequent major depression, anxiety, and suicidal behavior.

DATA SOURCES : Medline, Embase, CINAHL, PsycInfo, and Proquest Dissertations and These were searched from inception to January 2017.

STUDY SELECTION : Longitudinal and prospective studies, assessing cannabis use in adolescents younger than 18 years (at least 1 assessment point) and then ascertaining development of depression in young adulthood (age 18 to 32 years) were selected, and odds ratios (OR) adjusted for the presence of baseline depression and/or anxiety and/or suicidalit were extracted.

DATA EXTRACTION AND SYNTHESIS : Study qualitywas assessed using the Research Triangle Institute item bank on risk of bias and precision of observational studies. Two reviewers conducted all review stages independently. Selected data were pooled using random-effects meta-analysis.

MAIN OUTCOMES AND MEASURES : The studies assessing cannabis use and depression at different points from adolescence to young adulthood and reporting the corresponding OR were included. In the studies selected, depression was diagnosed according to the third or fourth editions of Diagnostic and Statistical Manual of Mental Disorders or by using scales with predetermined cutoff points.

RESULTS : After screening 3142 articles, 269 articles were selected for full-text review, 35 were selected for further review, and 11 studies comprising 23 317 individuals were included in the quantitative analysis. The OR of developing depression for cannabis users in young adulthood compared with nonusers was 1.37 (95%CI, 1.16-1.62; I2 = 0%). The pooled OR for anxiety was not statistically significant: 1.18 (95%CI, 0.84-1.67; I2 = 42%). The pooled OR for suicidal ideation was 1.50 (95%CI, 1.11-2.03; I2 = 0%), and for suicidal attempt was 3.46 (95%CI, 1.53-7.84, I2 = 61.3%).

CONCLUSIONS AND RELEVANCE : Although individual-level risk remains moderate to low and results from this study should be confirmed in future adequately powered prospective studies, the high prevalence of adolescents consuming cannabis generates a large number of young people who could develop depression and suicidality attributable to cannabis. This is an important public health problem and concern, which should be properly addressed by health care policy.

 

Cannabis is the world’s most widely used illicit drug, with 3.8% of the global population having used cannabis in the past year.(1) Prevalence of use as a fraction of the world’s population has remained stable since the 1990s,(1) although patterns in individual countries are changing,with the percent age of individuals aged 18 to 29 years in the United States who reported using cannabis in the past year roughly doubling between 2001 to 2002 and 2012 to 2013, from10.5%to 21.2%.2  Among US adolescents from 1991 to 2011, the prevalence of cannabis was high,with 20.9% of adolescents reporting use in the past month(3); additionally, about 7% of US high school seniors are daily or near-daily users of cannabis.(4) In Canada, among youth aged 15 to 19 years, the rate of past-year cannabis use in 2015 was 20.6%.(5) Similarly, in Australia, 4%of adolescents aged 14 to 19 years use cannabis weekly (6); in England, 4% of adolescents aged 11 to 15 years used cannabis in the last month.(7) It is estimated that 87.6 million adults in the European Union (aged 15 to 64 years), or 26.3%of this age group, have tried cannabis during their lives.(8) Last year, prevalence rates among individuals aged 15 to 34 years range from 3.5% in Hungary to 21.5% in France.( 8)

The main pharmacologically active cannabinoid in the cannabis plant (Cannabis sativa or indica) is Δ-9 tetrahydrocannabinal (THC), which mediates most of its psychoactive and mood-related effects and also has addictive properties. The regular use of cannabis during adolescence is of profound concern(9) as use in this age group is associated with an increased likelihood of deleterious consequences, such as diminished scholastic achievement, lower degree attainment and school abandonment, liability to addiction,(10) earlier onset of psychosis,(11) and neuropsychological decline.(12) Furthermore, in the general population, there is substantive evidence for statistical associations between cannabis use and increased risk of motor vehicle crashes; the development of psychoses with the highest risk among the most frequent and high potency cannabis users; increased cannabis use frequency and the progression to developing problem cannabis use; adverse birth outcome in the offspring of mothers with cannabis smoking habits; and worse respiratory symptoms and more frequent chronic bronchitis episodes with long-term cannabis smoking.(9,13)

Little attention has been specifically paid in the public health discourse as to the impact of adolescent cannabis use on the risk of developing depressive symptoms and mood disorders, even though researchers have published on this topic since the 1970s.(14) Some clinical studies have found a larger effect in women,(15) while the rate of depression in adulthood may remain elevated even when cannabis use is stopped after adolescence.(16) Moreover, many preclinical studies in laboratory animals have also reported an association between pubertal exposure to cannabinoids and adult-onset depressive symptoms, in addition to elucidating the neurobiological mechanisms of this observed effect.(17-19) The adolescent brain is indeed still under development and psychotropic drugs used at this time may thus alter the physiological neurodevelopment, especially of the frontal cortex and limbic system.(20,21)

To date and to our knowledge, there has been no systematic review or meta-analysis summarizing the association of cannabis use during adolescence on the risk of depression in young adulthood. A meta analysis published in 2014 examined the association of cannabis use and depression (22) but this study included youth and adults and therefore did not estimate the specific risk of use during adolescence. The study also did not consider the risk of suicidal behavior and the comorbid anxiety often associated with depression. Two other systematic reviews and meta-analyses (23,24) analyzed the association between cannabis and depression, but those studies likewise focused on use in the general population (adolescents and adults) and thus could not study the window of risk in adolescence.

The goal of this investigation is to systematically review and analyze longitudinal prospective cohort studies that measured cannabis use during adolescence (18 years and younger) and evaluate the risk of depression, anxiety, and suicidality during young adulthood (aged 18 to 32 years). Given the high percentage of depression in adolescents smoking cannabis at the baseline, only longitudinal prospective cohort studies controlling for baseline depression were included in the study.

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