Association of Cannabis Use in Adolescence and Risk of Depression, Anxiety, and Suicidality in Young Adulthood

In the paper

“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.”

What the sources say

• ?Could not verify

  The indexed copy’s Search Strategy and Selection Criteria section concerns breast and cervical cancer, not cannabis or depression. Searches for cannabis, depression, and an adolescent window of risk returned no relevant passage. The supplied source title also does not match the text held in the indexed copy, so this copy cannot verify the attribution. (LLM, conf=0.75)

  cites [23] 23. Moore TH, Zammit S, Lingford-Hughes A, et al. Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review. Lancet. 2007;370(9584):319-328. doi:10.1016/S0140-6736 (07)61162-3 sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [24] 24. Degenhardt L, Hall W, Lynskey M. Exploring the association between cannabis use and depression. Addiction. 2003;98(11):1493-1504. doi:10.1046/j. 1360-0443.2003.00437.x source

In the paper

“The Medline strategy was developed with input from the research team and then peer reviewed by a second librarian using the PRESS standard.27”

What the sources say

• Supported

  The paper presents the PRESS evidence-based checklist as a tool for peer review of electronic search strategies (main text, Table 1 discussion). The citation identifies the standard used; it does not attribute the citing team's Medline-search process to this paper. (LLM, conf=0.91)

  cites [27] 27. McGowan J, Sampson M, Lefebvre C. An evidence based checklist for the peer review of electronic search strategies (PRESS EBC). Evid Based Libr Inf Pract. 2010;5(1):149-154. doi:10. 18438/B8SG8R source

In the paper

“Another study 69 found an increased risk of depression among adolescents who possessed the short allele of the serotonin transporter gene (5-HTTLPR genotype) (S/S), evincing an interaction between genetics and an environmental exposure (cannabis).”

What the sources say

• Partly supported

  Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [69] 69. Otten R, Engels RC. Testing bidirectional effects between cannabis use and depressive symptoms: moderation by the serotonin transporter gene. Addict Biol. 2013;18(5):826-835. doi:10.1111/j.1369-1600.2011.00380.x sourceExperimental — accuracy not yet measured

In the paper

“The cohort with the highest OR for depression 46 was entirely reanalyzed using both the classical methods for factors adjustment (multivariate regression analysis) and using the propensity score adjusted regression meth-ods to better estimate the differences in the distribution of the confounding variables 67 using SAS, version 9.4 (SAS Institute Inc).”

What the sources say

• Partly supported

  The Results report an odds ratio of 2.95 for later major depression in the Minnesota twin cohort, supporting its identification as a cohort with a depression OR. Our copy does not establish that this was the highest OR among cohorts. The reanalysis using multivariable and propensity-score-adjusted regression is described in the citing sentence as the citing authors’ own work, not as a method used by this source. (LLM, conf=0.77)

  cites [46] 46. Marmorstein NR, Iacono WG. Explaining associations between cannabis use disorders in adolescence and later major depression: a test of the psychosocial failure model. Addict Behav. 2011; 36(7):773-776. doi:10.1016/j.addbeh.2011.02.006 sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [67] 67. Schneeweiss S, Rassen JA, Glynn RJ, Avorn J, Mogun H, Brookhart MA. High-dimensional propensity score adjustment in studies of treatment effects using health care claims data. Epidemiology. 2009;20(4):512-522. doi:10.1097/EDE. 0b013e3181a663cc

In the paper

“these differences may constitute the neurobiological underpinning of the cognitive and behavioral deficits that are observed in humans.9”

What the sources say

• Supported

  In “Effect on Brain Development” (page unavailable), the paper says altered brain connectivity may help explain IQ declines associated with frequent marijuana use from adolescence into adulthood. In “Possible Role as Gateway Drug” (page unavailable), it suggests that changes in dopamine reactivity could help explain later susceptibility to drug abuse and addiction. Both are hedged neurobiological explanations for cognitive or behavioral effects in humans. (LLM, conf=0.86)

  cites [9] 9. Volkow ND, Baler RD, Compton WM, Weiss SR. Adverse health effects of marijuana use. N Engl J Med. 2014;370(23):2219-2227. doi:10.1056/ NEJMra1402309 source

In the paper

“Another study supported a self-medication hypothesis in male individuals, in which adolescents with higher depressive symptoms at baseline used more cannabis.59”

What the sources say

• Supported

  The Results report that, among males, higher depressive symptoms were associated with a later increase in marijuana-use frequency. The Discussion interprets this finding as support for males self-medicating depressive symptoms with marijuana. The claim’s reference to baseline symptoms is a reasonable paraphrase of that temporal relationship. (LLM, conf=0.90)

  cites [59] 59. Wilkinson AL, Halpern CT, Herring AH. Directions of the relationship between substance use and depressive symptoms from adolescence to young adulthood. Addict Behav. 2016;60:64-70. doi:10.1016/j.addbeh.2016.03.036 source

In the paper

“Adolescent rats treated with THC also have fewer synaptic contacts during adulthood and reduced efficiency of hippocampal networks 75”

What the sources say

• ?Could not verify

  The Introduction and Discussion describe THC-related structural changes in rats’ nucleus accumbens, but do not report fewer synaptic contacts in adulthood or reduced hippocampal-network efficiency. Searches for adolescent THC exposure, synaptic contacts, and hippocampal-network efficiency found no passage addressing those outcomes. The Discussion’s report of no hippocampal effects in one rat study does not establish a contradiction for the adolescent-treatment claim. (LLM, conf=0.76)

  cites [75] 75. Gilman JM, Kuster JK, Lee S, et al. Cannabis use is quantitatively associated with nucleus accumbens and amygdala abnormalities in young adult recreational users. J Neurosci. 2014;34(16): 5529-5538. doi:10.1523/JNEUROSCI.4745-13.2014 sourceExperimental — accuracy not yet measured

In the paper

“Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline for reporting of systematic reviews were followed and fulfilled.29”

What the sources say

• Supported

  The PRISMA Statement section identifies this paper as the source of a reporting guideline for systematic reviews and meta-analyses, comprising a 27-item checklist and a four-phase flow diagram. The citing authors’ statement that they followed and fulfilled it describes their own review, not a finding attributed to this source. (LLM, conf=0.92)

  cites [29] 29. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097. doi:10.1371/journal.pmed.1000097 source

In the paper

“Other studies likewise found significant positive associations between cannabis use during adolescence and later anxiety and depression paralleled by academic unpreparedness, delinquency, and poorer academic performance.36”

What the sources say

• Partly supported

  The Abstract Findings and Results (Effects of use on wave 7 outcomes; page not provided) report significant associations between greater adolescent marijuana use and academic unpreparedness, delinquency, poorer academic performance, and poorer mental health in high school. The Methods (Measures; page not provided) say the mental-health scale primarily reflects anxiety and depression, but the paper does not report separate significant associations for anxiety and depression. (LLM, conf=0.86)

  cites [36] 36. D'Amico EJ, Tucker JS, Miles JN, Ewing BA, Shih RA, Pedersen ER. Alcohol and marijuana use trajectories in a diverse longitudinal sample of adolescents: examining use patterns from age 11 to 17 years. Addiction. 2016;111(10):1825-1835. doi:10. 1111/add.13442 sourceExperimental — accuracy not yet measured

In the paper

“Some of the detrimental effects of cannabis on behavior seem more pronounced in females in both animals 19 and humans, 15 although this finding remains controversial.”

What the sources say

• ?Not checked — no full text of the sourcecites [19] 19. Rubino T, Parolaro D. The impact of exposure to cannabinoids in adolescence: insights from animal models. Biol Psychiatry. 2016;79(7):578-585. doi:10.1016/j.biopsych.2015.07.024 source
• Supported

  The citation to this paper is attached to the human finding, not the animal finding. In “Cannabis and depression in young adults,” the paper reports that the association between cannabis use and depression and anxiety was clearest in females, with a significant interaction between sex and daily use. The paper treats a harmful effect as a possible explanation rather than establishing causation, consistent with the citing sentence’s cautious wording. (LLM, conf=0.90)

  cites [15] 15. Patton GC, Coffey C, Carlin JB, Degenhardt L, Lynskey M, Hall W. Cannabis use and mental health in young people: cohort study. BMJ. 2002;325 (7374):1195-1198. doi:10.1136/bmj.325.7374.1195 source

In the paper

“The 6 cannabis trajectory groups were not significantly different on year-1 health-related variables but differed on all 10-year mental health outcomes tested, including depression and anxiety.”

In the paper

“There is evidence that younger users of cannabis (aged 14 to 15 years) were at significantly higher risk of suicidal behaviors, although, overall, the association between cannabis use and depression did not vary with age 42”

What the sources say

• ?Not checked — no full text of the sourcecites [42] 42. Fergusson DM, Horwood LJ, Swain-Campbell N. Cannabis use and psychosocial adjustment in adolescence and young adulthood. Addiction. 2002;97(9):1123-1135. doi:10.1046/j.1360-0443. 2002.00103.x source

In the paper

“This study failed to support a link between using cannabis as an adolescent and later depression in male or female individuals but found instead a positive association between tobacco and depression.”

In the paper

“Twenty-four longitudinal studies did not report OR poolable data or reported the same cohorts and were thus not included in the meta-analysis”

In the paper

“A total of 11 articles met the inclusion criteria for the metaanalysis (Figure 1): 7 for depression 10,16,34,38,[44][45][46] ; 3 for anxiety, 16,38,44 3 for suicidal ideation, 41,47,57 and 3 for suicide attempts.10,54,57”

In the paper

“The pooled OR among studies from the United States was 1.54 (95% CI, 1.20-1.98);the pooled OR among studies from other countries was 1.24 (95% CI, 0.99-1.56;P = .21).”

In the paper

“The new OR was 1.40 (95% CI, 1.17-1.67)and remained significant.”

In the paper

“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.”

What the sources say

• ?Not checked — no full text of the sourcecites [22] 22. Lev-Ran S, Roerecke M, Le Foll B, George TP, McKenzie K, Rehm J. The association between cannabis use and depression: a systematic review and meta-analysis of longitudinal studies. Psychol Med. 2014;44(4):797-810. doi:10.1017/ S0033291713001438 source

In the paper

“The study also did not consider the risk of suicidal behavior and the comorbid anxiety often associated with depression.”

What the sources say

• ?Not checked — no full text of the sourcecites [22] 22. Lev-Ran S, Roerecke M, Le Foll B, George TP, McKenzie K, Rehm J. The association between cannabis use and depression: a systematic review and meta-analysis of longitudinal studies. Psychol Med. 2014;44(4):797-810. doi:10.1017/ S0033291713001438 source

In the paper

“Database search strategies complied with the Institute of Medicine standards 25 and were not limited by language or by year of publication.”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [25] 25. Eden J, Levit L, Berg A, Morton S. Finding What Works in Health Care: Standards for Systematic Reviews. Washington, DC: National Academies Press; 2011.

In the paper

“One set of sensitive analysis was done to rule out possible cohorts' overlap.”

In the paper

“The effect size is modest, but considering that 20.9% of adolescents in the United States report monthly use of cannabis 3 and 7% of US high school seniors are daily or neardaily users, 4 the consequences of cannabis use during adolescence are magnified in young adulthood.”

What the sources say

• ?Not checked — no full text of the sourcecites [3] 3. Choo EK, Benz M, Zaller N, Warren O, Rising KL, McConnell KJ. The impact of state medical marijuana legislation on adolescent marijuana use. J Adolesc Health. 2014;55(2):160-166. doi:10.1016/j. jadohealth.2014.02.018 source
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [4] 4. Johnston LD. OMP, Bachman J, Schulenberg J. Monitoring the Future National Results on Drug Use: 2012 Overview. Ann Arbor, Michigan: Institute for Social Research, University of Michigan; 2013.

In the paper

“When multiple studies were found reporting on the same population cohort at different time points, only the study reporting the longest follow-up was chosen.”

In the paper

“This meta-analysis shows that cannabis consumption in adolescence is associated with increased risk of developing major depression in young adulthood and suicidality, especially suicidal ideation.”

In the paper

“and are mostly characterized by a decrease in volume (hippocampus, amygdala, prefrontal cortex) or greater gray matter density in cannabis users than in controls in the left nucleus accumbens extending to subcallosal cortex, hypothalamus, sublenticular extended amygdala, and left amygdala.74”

What the sources say

• ?Not checked — no full text of the sourcecites [74] 74. Lorenzetti V, Solowij N, Yücel M. The Role of cannabinoids in neuroanatomic alterations in cannabis users. Biol Psychiatry. 2016;79(7):e17-e31. doi:10.1016/j.biopsych.2015.11.013

In the paper

“Two reviewers (T.A. and T.Z.) independently assessed all titles and abstracts along with full texts of potentially relevant articles.”

In the paper

“Only longitudinal prospective cohort studies reporting outcome data about cannabis use (baseline) and depression (follow-up) and adjusting for depression and/or anxiety and/or suicidality at baseline were included in the metaanalysis (eTable 1 in the Supplement).”

In the paper

“Only studies reporting adjusted OR for basal depression or anxiety or suicidality were included in the metaanalysis.”

In the paper

“controlled and adjusted for the following confounding factors: age, sex, and depres-sion and/or anxiety at baseline.”

In the paper

“Additional studies further demonstrate the neurobiological and the pathophysiological depressionlike behavior of adolescent rats when exposed to cannabinoids.19”

What the sources say

• ?Not checked — no full text of the sourcecites [19] 19. Rubino T, Parolaro D. The impact of exposure to cannabinoids in adolescence: insights from animal models. Biol Psychiatry. 2016;79(7):578-585. doi:10.1016/j.biopsych.2015.07.024 source

In the paper

“Animal studies have demonstrated that cannabis consumption during adolescence produces an increase in anhedonia and anxiety in adulthood, paralleled by a decrease in serotonin (a neurotransmitter linked to depression) and an increase in norepinephrine (a neurotransmitter linked to anxiety).17”

What the sources say

• ?Not checked — no full text of the sourcecites [17] 17. Bambico FR, Nguyen N-T, Katz N, Gobbi G. Chronic exposure to cannabinoids during adolescence but not during adulthood impairs emotional behaviour and monoaminergic neurotransmission. Neurobiol Dis. 2010;37(3):641- 655. doi:10.1016/j.nbd.2009.11.020 source

In the paper

“Studies have also demonstrated that, following long-term adolescent cannabinoid exposure, dopamine neurons become less responsive to the stimulating action of cannabinoids and a long-lasting cross-tolerance for morphine, cocaine, and amphetamine occur.18”

What the sources say

• ?Not checked — no full text of the sourcecites [18] 18. Pistis M, Perra S, Pillolla G, Melis M, Muntoni AL, Gessa GL. Adolescent exposure to cannabinoids induces long-lasting changes in the response to drugs of abuse of rat midbrain dopamine neurons. Biol Psychiatry. 2004;56(2):86-94. doi:10.1016/j. biopsych.2004.05.006 source

In the paper

“This study also is consistent with the greater part of research on brain imaging literature demonstrating the negative influence of cannabis in brain plasticity during the development.”

In the paper

“Interestingly, most of these studies reported a positive correlation between adolescent cannabis use and later depression, 15,[30][31][32][33][34][35][36][37]40,42,43,[49][50][51][52][53]61 reinforcing the results of the meta-analysis.”

In the paper

“The risk of bias of the included articles was assessed using the Research Triangle Institute item bank on risk of bias and precision of observational studies.63”

What the sources say

• ?Not checked — no full text of the sourcecites [63] 63. Viswanathan M, Berkman ND. Development of the RTI item bank on risk of bias and precision of observational studies. J Clin Epidemiol. 2012;65(2): 163-178. doi:10.1016/j.jclinepi.2011.05.008 source

In the paper

“The association between cannabis and suicidal behavior was previously reported by Borges et al. 70”

What the sources say

• ?Not checked — no full text of the sourcecites [70] 70. Borges G, Bagge CL, Orozco R. A literature review and meta-analyses of cannabis use and suicidality. J Affect Disord. 2016;195:63-74. doi:10. 1016/j.jad.2016.02.007 source

In the paper

“Parental level of education, socioeconomic status, alcohol consumption, and cigarette smoking were also controlled for in almost all included studies.”

In the paper

“the findings in this meta-analysis suggest that cannabis is a serious public health concern”

In the paper

“Thus, the content of THC in”

In the paper

“It was also not possible to evaluate the exact quantity of cannabis consumed among adolescents in individual studies since they used measures of frequency of use and rather than the precise quantity.”

In the paper

“Furthermore, the potency of cannabis has generally increased since 1980, 76 and potency varies across geographic location.8”

What the sources say

• ?Not checked — no full text of the sourcecites [76] 76. Rubino T, Realini N, Braida D, et al. Changes in hippocampal morphology and neuroplasticity induced by adolescent THC treatment are associated with cognitive impairment in adulthood. Hippocampus. 2009;19(8):763-772. doi:10.1002/ hipo.20554 source
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [8] 8. European Drug Report 2018: Trends and Developments. Luxembourg: European Monitoring Centre for Drugs and Drug Addiction; 2018.