Adolescence & Development

Adolescent cannabis use is associated with increased risk of depression (OR 1,37), suicidal ideation (OR 1,50) and suicide attempts (OR 3,46) in young adulthood; anxiety disorders show no statistical significance (OR 1,18).

SR of 11 studies (n=23.317 adolescents); adolescent cannabis use associated with increased risk of depression in young adulthood (OR=1.37, 95% CI 1.16-1.62, p0.001), anxiety disorders (OR=1.18, 95% CI 1.10-1.26, p0.001) and suicidality (OR=1.50, 95% CI 1.11-2.03, p0.01).

Frequent cannabis use in adolescence is associated in a dose-dependent manner with far-reaching negative psychosocial consequences into young adulthood.

IPD meta-analysis (N up to 3.765); daily cannabis use before age 17: aOR 0,37 (CI 0,20–0,66) for school completion, 17,95 (CI 9,44–34,12) for cannabis dependence, 7,80 (CI 4,46–13,63) for other illicit drugs, 6,83 (CI 2,04–22,90) for suicide attempt; clear dose-response relationship for all 7 developmental outcomes.

Adolescent cannabis use is associated with increased risk for later anxiety disorders and anxiety symptoms (OR = 2.14).

SR + meta-analysis across k=18 longitudinal studies (n=33.380) on adolescent cannabis use and later anxiety outcomes; meta-analysis of k=6 studies shows increased risk for later anxiety disorders (OR=2.14, 95% CI: 1.37-3.36, p<0.01). Qualitative synthesis of k=12 further studies: 9 of 12 found a significant association between adolescent cannabis use and later anxiety symptoms.

Chronic cannabis use is associated with a significantly smaller hippocampal volume; evidence for further brain structural changes remains inconsistent.

Meta-analysis k=14 imaging studies (n=362 cannabis users vs. n=365 non-users); consistently smaller hippocampus in cannabis users (effect size significant); limited and contradictory evidence for further gray/white matter changes — suggests neurotoxic effect of chronic cannabis use in cannabinoid receptor-rich brain areas.

Cannabis use in adolescence increases psychosis risk later in life (RR = 1,71), with several moderating factors such as age at cannabis onset, frequency of use, childhood trauma and genetic factors.

Systematic review + meta-analysis on adolescent cannabis use and psychosis risk; k=63 studies narrative, k=18 in meta-analysis. Adolescent cannabis use increased psychosis risk (RR=1,71; 95% CI 1,47-2,00; p<0,00001) and predicted earlier psychosis onset. Moderating factors: age of onset, frequency of use, childhood trauma, polysubstance use, genetic factors.

Limited evidence shows differential brain activations and morphological differences with cannabis use, but no consistent negative effects on neuropsychological function in adolescents with ADHD.

Systematic review on cannabis effects on brain structure and function in adolescents/young adults with ADHD; k=11 studies (7 neuroimaging studies incl. fMRI, structural MRI, SPECT). No additive effects or ADHD×cannabis interactions identified on neuropsychological executive function tests. Two studies found negative effects of early cannabis use onset. Limited evidence does not support the hypothesis of harmful effects on neuropsychological tasks in ADHD adolescents.

Cannabis use independently increases the risk of psychosis and schizophrenia by approximately threefold (OR 2,9).

SR + meta-analysis (k=7, OR=2,9; 95% CI 2,4–3,6) on cannabis as a risk factor for psychosis; early cannabis use in adolescence was identified as a distinct vulnerable group — dose-dependent effect on psychotic symptoms in adolescents and persons with high genetic risk.

High cannabis use increases the risk of schizophrenia sixfold, independent of other psychiatric disorders and social background.

Prospective 15-year cohort study (n=45.570 Swedish conscripts); high users (>50 occasions) had RR=6,0 (95% CI 4,0–8,9) for schizophrenia vs. non-users; cannabis confirmed as an independent risk factor after adjustment for other psychiatric disorders and social background.

Cannabis use is associated with significantly increased prodromal psychosis symptoms in adolescents.

Population-based study (n=6.330 adolescents, 15–16 years); cannabis use (n=352; 5,6%) associated with ≥3 prodromal psychosis symptoms (OR=2,23; 95%-CI 1,70–2,94), also after adjustment for covariates including prior behavioural symptoms; dose-response effect demonstrated.

Frequent cannabis use in adolescence significantly increases the risk of psychosis even after controlling for relevant confounders (HR=3,0).

Adolescent cannabis use (age 15–16 years, ≥5 times) in prospective cohort (n=6.534) associated with >3-fold increased psychosis risk up to age 30 after adjustment (HR=3,0, 95% CI 1,1–8,0); onset before the 17th year of life identified as risk modifier.

Cannabis use significantly increases the risk of psychotic symptoms, particularly pronounced in persons with psychosis predisposition.

Prospective cohort study in adolescents and young adults (n=2437, age 14–24 years): Cannabis use in adolescence increased the risk of psychotic symptoms over 4 years (aOR=1.67, 95% CI 1.13–2.46), particularly pronounced in persons with psychosis predisposition (adjusted risk difference 23.8%, p=0.003). Dose-response relationship demonstrated. Indication of specific vulnerability of adolescents with pre-existing risk factors.

Frequent cannabis use in adolescence increases the long-term risk of schizophrenia approximately 3,7-fold compared to non-users.

Adolescent cannabis use (n=50.087 recruits) as a risk factor for later schizophrenia: OR=3,7 (95%-CI 2,3–5,8) with frequent use; 35-year follow-up shows persistently increased risk in heavy users, decline in risk with moderate use over the decades.

The covariation between cannabis use and psychotic experiences is predominantly due to shared environmental factors and not genetic influences.

Population-based twin study (n=4830 pairs, 16-year-olds) on cannabis use in adolescence and psychotic experiences. Cannabis use explains 2-5% of PE variance; association with paranoia and cognitive disorganization fully mediated by shared environmental factors (CE=69-100%). Heritability for cannabis use 37%, for PE 27-54%. Finding relativizes a direct causal cannabis→psychosis pathway in adolescents.

Child abuse and cannabis use interact synergistically and increase the risk for positive psychotic symptoms significantly more than either factor alone.

In 2 population cohorts (n=1.636 + n=4.842) the synergistic psychosis-risk effect of cannabis + childhood traumatization increased with decreasing age [interaction term b=−0.006, 95% CI −0.010 to −0.002, p=0.004]; finding replicated in NEMESIS [χ²(3)=8.08, p=0.04] — cannabis risk particularly elevated in adolescents with trauma exposure.

Adolescent cannabis use is associated with a significantly increased risk of depression and anxiety disorders in adulthood.

Birth cohort study (n=6.325, follow-up 15–33 years); adolescent cannabis use (5.6% adolescents) associated with increased risk of anxiety disorders (HR 2.01, 95% CI 1.15–3.82 for ≥5× use) and depression (HR 1.93–2.02) in adulthood; association persists after adjustment for parental psychiatric history and other substances (p-values not explicit, HR-CIs exclude 1.0).

Cannabis use in adolescence robustly increases the risk of psychotic experiences, tobacco use alone shows no significant association after adjustment.

ALSPAC cohort (n=5.300, JAMA Psychiatry): Early cannabis use in adolescence (onset <16 years) associated with increased psychosis risk (OR=3,70, 95% CI 1,66–8,25 after adjustment); late-onset use (OR=2,97, 95% CI 1,63–5,40); tobacco effects not robust (OR 1,78, 95% CI 0,54–5,88 after adjustment ns); findings demonstrate stronger epidemiological evidence for cannabis risks in adolescents than for tobacco.

Cannabis use shows only weak association with depression after adjustment; association with anxiety disappears after confounder control.

ALSPAC cohort study (n=4.561, measurement cannabis use age 16 → outcomes age 18); adolescent cannabis use → unadjusted OR=1.50 (95%-CI 1.26–1.80) for depression; after full adjustment OR=1.30 (95%-CI 0.98–1.72); no anxiety risk after adjustment. Provides direct risk data for adolescents as primary population.

Longer cannabis use is associated with a significantly increased risk for psychosis-associated outcomes, also after reduction of confounding through sibling-pair analysis.

Birth cohort study (n=3.801, birth years 1981-1984) with sibling-pair analysis. Early cannabis use (≥6 years duration) in adolescents associated with increased risk of psychosis (aOR=2.2), hallucinations (aOR=2.8, 95%-CI=1.9-4.1) and delusional experiences (aOR=4.2) in early adulthood. Sibling-pair design significantly reduces the likelihood of residual confounding by unmeasured factors.

Early onset and frequent cannabis use are associated, independently of other influencing factors, with a significantly increased risk of anxiety and depression in young adulthood.

Birth cohort n=3.239; cannabis onset before age 15 with frequent use at age 21 strongly associated with anxiety/depression symptoms in young adulthood (OR=3,4; 95% CI 1,9–6,1); dose-response pattern: earlier onset = higher risk.

Cannabis increases psychosis risk independently of COMT genotype; a specific gene-environment interaction was not demonstrated.

n=2.630 ALSPAC birth cohort; cannabis use assessed at age 14, psychotic experiences at age 16. Cannabis use increases psychosis risk independently of COMT Val158Met genotype (no significant interaction effect under multiplicative models). Conclusion: risk from cannabis applies to the entire adolescent population, not only a genetically high-risk subgroup.

Daily adolescent cannabis use is associated with increased risk of anxiety disorder at age 29 years, but not consistently with depression.

15-year longitudinal cohort (n=1943, school recruitment, age 14,9–29,1 years): Adolescent daily cannabis use → anxiety disorder at age 29 years (OR=2,5; 95%-CI 1,2–5,2). No consistent association with depression. Effect persists even after cessation of use, which points to long-term consequences of early use for mental health.

Cannabis use significantly increases the risk of incidence and persistence of subclinical psychotic symptoms.

Prospective cohort study (n=1.923, adolescents and young adults, age 14-24 at baseline); cannabis use in adolescence increased the risk of later occurring psychotic symptoms (OR=1,9, 95% CI 1,1–3,1; p=0,021); persistent use doubled the risk of persistent subclinical psychotic symptoms (OR=2,2, 95% CI 1,2–4,2; p=0,016); incidence rate of psychotic symptoms 31% in adolescent users vs. 20% in non-users.

Cannabis use was prospectively associated with panic disorder, but this association was eliminated after controlling for daily cigarette smoking.

Adolescent cohort (n=1.709, baseline age 16,6 years, SD=1,2), followed prospectively into adulthood; cannabis use and dependence in adolescence significantly prospectively associated with development of panic attacks and panic disorder in young adulthood. No incremental effect after controlling for tobacco smoking.

Frequent cannabis use during adolescence significantly increases the risk of depression and anxiety disorders in young adulthood, especially with daily use in girls.

Prospective school cohort study (n=1601, age 14–20 years): Adolescent daily cannabis use in girls → OR=5,6 (95%-KI 2,6–12,0) for depression+anxiety in young adulthood. Weekly use overall: OR≈1,9 (1,1–3,3). Adolescents with daily use carry the highest risk of subsequent mental health conditions; no reverse causation demonstrated.

Cannabis problems in adolescence did not significantly increase the risk of depression in young adulthood in either women or men.

n=1.494 adolescents, longitudinal study age 6–21 years (17 years follow-up), propensity score-adjusted; cannabis problems in adolescence did NOT lead to a significantly increased risk of depression in young adulthood (OR women=0,7, OR men=1,7, both 95% CI include 1,0); provides normative data on adolescent cannabis exposure and psychological development without a demonstrable long-term depression effect.

Regular cannabis use is associated with increased rates of psychosocial adjustment problems, strongest among school-age adolescents.

21-year birth cohort (N=1.265, age 14–21). School-age cannabis use (14–15 yrs) more strongly associated with delinquency, suicidal behaviour and polydrug use than in young adults (20–21 yrs) — significant age-dependent variation (p<0.05). All psychosocial outcomes remained significant after confounder control (p<0.05). Strongest association for other drug use. Implications: school-age cannabis use carries the highest developmental risk.

Chronic cannabis use in adolescence increases the risk of cannabis and alcohol use disorders in young adulthood, but not of depressive or anxiety disorders.

Longitudinal cohort n=1.205 adolescents, cannabis use trajectories across 4 waves; the High-Chronic group had higher delinquency, lower academic achievement, more drug-using friends, and more stressful life events than other trajectory groups. In young adulthood (mean 23,5 years) significantly increased risk of cannabis and alcohol use disorders in the High-Chronic trajectory.

Regular cannabis use in adolescence cumulatively increases the risk of subclinical psychotic symptoms, including paranoia and hallucinations, with a persisting effect after abstinence.

Adolescent cannabis use (n=1.009 boys, age 13–18) → subclinical psychosis symptoms +21% per year of use; paranoia odds +133%, hallucination odds +92% (p<0.05 each); effect still detectable after 1-year abstinence. Early onset and cumulation confirmed as risk factors.

Early cannabis use is associated with more antisocial behavior and substance-related harms in young adulthood, but not with educational or mental health outcomes.

Australian longitudinal study (n=852, 53% female, 6 survey waves age 12–19); three cannabis trajectories: abstainers (62%), early starters (11%), late-occasional users (27%); early starters showed in young adulthood significantly higher frequencies of antisocial behavior, violence, cannabis-related harms and alcohol harms compared to the abstinent group; result supports a prevention focus on early adolescence before age 12.

Only very early cannabis use (≤14 years) is associated with an earlier onset of psychosis; CUD overall shows no significant effect on age of onset of illness.

Retrospective analysis of n=625 first-episode psychosis patients (age 14–29 years); 75% had a cannabis use disorder (CUD). Cannabis use began before psychosis onset in 87,6%. Early CUD onset (≤14 years) was associated with a younger age of onset of illness (F(1)=5,2; p=0,024; partial η²=0,026); earlier age of onset of use predicted earlier age of onset of psychosis (β=−0,49; R²-change=0,25; p<0,001). CUD overall (without further SUD) vs. non-CUD: no significant difference in age of onset of illness.

Prenatal cannabis exposure and early age of onset increase the risk of psychotic symptoms, whereby the mediation pathway via EAOM was not significant.

Prospective cohort study (n=596): early age of onset of cannabis use (EAOM) significantly predicted increased rates of psychotic symptoms in young adulthood (22 years) (p<0,05). In addition, prenatal cannabis exposure (PME) predicted EAOM, suggesting an indirect developmental risk pathway from the prenatal phase to young adulthood.

Adolescent cannabis use significantly increases the risk of depression and suicidality in adulthood, but not the risk of anxiety disorders.

30-year cohort study (n=591, Zurich). Cannabis use in adolescence associated with depression (aOR=1.70, 95%-CI=1.24-2.32) and suicidality (aOR=1.65, 95%-CI=1.11-2.47) in adulthood. Particularly elevated risk with first use ≤15/16 years and with frequent use in adolescence. No significant effect on anxiety disorders (aOR=1.10, 95%-CI=0.82-1.48). All associations controlled independent of substance abuse in adulthood.

Three distinct CUD course types were identified; persistently increasing courses are associated with specific risk factors such as male gender and externalizing disorders.

Prospective longitudinal study (n=816, age 14–30 years); three CUD course classes identified: persistently increasing, maturing out and stable-low; persistent CUD associated with later first diagnosis (η²=0,16, p<0,001) and longer CUD duration (η²=0,26, p<0,001); male gender OR=2,57 (p=0,018) and psychotic experiences (Cohen's d=0,44, p=0,016) as risk factors for the persistently increasing class.

Lifetime cannabis use did not increase the rate of psychosis conversion in clinical high-risk subjects and was associated with better social functioning.

CHR adolescents (age 12–22 years, n=101 CHR+, n=59 HC), follow-up 2,97 years; low to moderate lifetime cannabis use not a significant predictor of psychosis conversion (logistic regression, n=15 converters); no negative effect on social or role functioning — no increased risk with low-to-moderate use.

Cannabis use is significantly associated with an earlier first onset of non-affective psychosis, independent of other substances (HR 2,66).

n=112 patients with first non-affective psychosis; cannabis use in adolescence was significantly associated with earlier psychosis onset (Hazard Ratio 2.66, 95% CI 1.74–4.05, p<0.001); dose-response relationship: the earlier the onset of the most intensive cannabis use, the earlier the psychosis onset (median AOPT 23.5 vs. 33.5 years).

The combination of childhood sexual trauma and early cannabis use significantly increases the risk of psychosis multiplicatively compared to the individual factors alone.

Large community sample (NCS); binary logistic regression; interaction between early cannabis use (<16 years) and childhood sexual trauma on clinically recorded psychosis diagnoses: interaction term OR=6.93 (95%-CI 1.39–34.63, p=.02); in adolescents with early cannabis use (<16 y.), risk from sexual trauma rose to OR=11.96 (95%-CI 2.10–68.22, p=.01). No significant main effect for cannabis alone.

The association between cannabis use and psychotic experiences was considerably attenuated by adjustment for tobacco use and other drug use and lost statistical significance.

ALSPAC cohort (n=1.756 adolescents, 16–18 years): Cannabis use at age 16 was associated with psychotic experiences at age 18 (OR=1,48, 95% CI 1,18–1,86); association attenuated after tobacco adjustment (OR=1,27, 95% CI 0,91–1,76); separability of cannabis and tobacco effects methodologically problematic since nearly all users used cannabis together with tobacco.

Cannabis use and depression/anxiety symptoms show small bidirectional associations, with distinctly stronger associations in LGB adolescents in the sense of possible self-medication.

Longitudinal cohort study (n=1.430 adolescents, age 13–17 yrs, Quebec Longitudinal Study) examined cannabis use risks in adolescence via cross-lagged models. Cannabis at 13 years significantly predicted anxiety symptoms at 15 and 17 years; depression symptoms at 15 years predicted cannabis use at 17 years (bidirectional association, p<0.05 after controlling for alcohol, cigarettes, other drugs). Sexual minorities (LGB) showed substantially larger effects: distinctly stronger depression-15→cannabis-17 association as well as negative association anxiety-15→cannabis-17. Findings point to self-medication dynamics in a vulnerable adolescent subgroup; overall effect sizes small.

Cannabis use in early adolescence is associated with reduced cortical thickness in male adolescents with high polygenic risk score, suggesting an association between cannabis use and genetic schizophrenia risk in brain maturation.

n=1.030 adolescents, early cannabis onset associated with thinner cortical brain maturation in individuals with high polygenic schizophrenia risk score (p0.01), no association in low PRS, supports gene×environment interaction in psychosis risk.

Decrease in cannabis use is accompanied by fewer psychotic experiences, increase by more positive symptoms, but not by negative or depressive symptoms.

Longitudinal study in young adults (N=705, age 18–27 years): Increase in cannabis use significantly associated with an increase in positive psychotic symptoms (β=0,07; p=0,02). Decrease in use associated with a decrease in overall psychotic experiences (β=−0,096; p=0,01). Results consistent with cannabis-induced psychosis vulnerability during the developmental phase of adolescence.

ADHD symptom dimensions, particularly inattention, are independent predictors of more severe cannabis-related outcomes in young adults.

Cross-sectional study in n=376 college students: current and childhood ADHD inattention symptoms independently associated with more severe cannabis outcomes (CUD, craving, problematic use) in young adulthood (p<0,01); childhood hyperactivity-/impulsivity symptoms associated with earlier cannabis initiation (p<0,01). Associations persisted after statistical control for comorbid psychopathology.

Cannabis abuse predicted psychosis conversion, however this effect was confounded by alcohol use and lost strength after adjustment.

Adolescents/young adults (CHR cohort, mean age 18,3 years, N=370); cannabis abuse (CA/CD) vs. no use: significantly higher 2-year psychosis conversion rate (p=0.031); non-impairing use showed no increased conversion effect — differentiated risk profile in adolescents.

Cannabis use increases depressive symptoms only in genetically vulnerable adolescents (5-HTTLPR short allele), not in all.

Longitudinal cohort study (n=310 adolescents, 4 years) on cannabis use and depressive development in adolescence. Early use significantly increases the risk of depressive symptoms – exclusively in genetically vulnerable adolescents (5-HTTLPR short allele). Parallel growth model demonstrates: cannabis → increase in depressive symptoms over time (p<0.05). No reverse causality detectable.

Persistent cannabis use was associated with lower school performance and more externalizing, but not internalizing, symptoms, with the effects no longer significant after controlling for alcohol and tobacco use.

4-year longitudinal study (n=254) on adolescent cannabis use and developmental outcomes: persistent use associated with lower grade point average (β=-0.18, p=0.006), lower SAT score (β=-0.13, p=0.038) and stronger externalizing symptoms (β=0.29, p<0.001) in grade 12. No significant association with internalizing symptoms (β=0.04, p=0.53). Effects no longer significant after controlling for alcohol/tobacco — SES confounding ruled out.

The combination of cannabis use and childhood trauma increases the risk of psychotic symptoms in adolescence beyond the additive measure of both individual risks.

n=211 adolescents (12–15 years), population-based; cannabis use alone and childhood trauma alone each significantly increased the risk of psychotic symptoms; combination of early cannabis use + childhood trauma increased the risk of psychotic symptoms more than expected additively (greater-than-additive interaction). Implication: cannabis prevention in traumatized adolescents as a high-risk group.

Adolescent cannabis use is associated with significant impairments in verbal learning and memory, comparable to deficits seen in adult long-term users.

n=181 adolescents (52 cannabis users, 67 alcohol users, 62 controls, age 16-20 years); cannabis users recalled significantly fewer words (p<0.001), showed impaired learning (p<0.001), retention (p<0.001) and recall (p<0.05); Cohen's d 0.43–0.84 vs. controls. Magnitude of the deficit correlates with duration, amount, frequency and age of onset of cannabis use.

Early onset of cannabis use (before the 16th year of life) is associated with specific, persistent impairments in visual scanning reaction time in adulthood.

Cross-sectional study (n=99 pure cannabis users + n=49 controls, selected from 250 users). Early onset of use (<16 years; n=48) led to significantly prolonged reaction times in visual scanning vs. late-onset users (>16 years; n=51) and controls (p<0.05). Other attention functions (alertness, divided attention, flexibility, working memory) not impaired. The only predictor was age of onset, not total dose or THC levels. Finding supports persistent neurocognitive vulnerability due to peripubertal cannabis use.

Cannabis use correlates with stronger positive symptoms in first-episode psychosis, but abstinence is associated with the best symptomatic improvement after 6 months.

n=110 children and adolescents (9–17 years) with first-episode psychosis; prevalence of cannabis use 29,1% (alcohol 21,8%, cocaine 8,2%). Cannabis use decreased after 6 months (p=0.004). Adolescents with cannabis use initially showed stronger PANSS positive symptomatology (p=0.002); abstinence over the course was associated with the best psychopathological outcome (PANSS total p=0.002). Data demonstrate the relevance of cannabis use for psychopathology and short-term course in adolescent first-episode psychosis.

Increasing cannabis use in adolescence and early adulthood is associated with a range of adverse life outcomes (education, income, employment, life satisfaction).

New Zealand birth cohort up to age 25; increasing cannabis use in adolescence associated with lower educational attainment (p<0,0001), lower income (p<0,01), higher welfare dependence (p<0,0001), higher unemployment (p<0,0001) and lower life satisfaction (p<0,0001) — all associations statistically significant (p<0,05) after adjustment for confounding variables (family structure, mental illness, other substances).

Cannabis users showed a significantly slowed reaction time on the CPT; subclinical ADHD symptoms did not contribute to attention deficits.

n=72 adolescents/young adults (cannabis users n=34, controls n=38); cannabis use significantly associated with slower CPT reaction time (attention); subclinical ADHD symptoms did not predict deficits and did not moderate cannabis effects; attention deficits in cannabis users primarily substance-related.