Dependence Risk

High-potency cannabis increases the risk of psychosis and cannabis use disorder, while the association with depression and anxiety remains inconsistent.

Systematic review (k=20 studies, of which 6 on cannabis use disorder/CUD) on the influence of cannabis potency (THC concentration) on dependence risk; higher cannabis potency was associated with increased CUD risk compared to lower potency; evidence for CUD and psychosis risk most consistent; heterogeneous findings for depression and anxiety.

Earlier age at cannabis use onset is associated with cannabis use disorder and negative consequences of cannabis use, but with mixed findings for other substance use problems.

Systematic review of k=16 prospective studies on age of first cannabis use and later substance problems. Earlier first use was significantly associated with cannabis use disorder (CUD) and cannabis-negative consequences; mixed findings for other substance problems (e.g. alcohol). The CUD association remained independent of frequency of use. Only 1 study with low risk of bias, 7 with moderate, 8 with high/very high risk.

In the domain "problematic cannabis use" an association with higher-potency cannabis was suggested; in other areas findings were less consistent, but tended toward worse outcomes with higher potency.

Systematic review on high-potency cannabis and health; k=42 studies from 4.545 screened records. Potency categories: 1-9% THC, 10-19%, 20-30%, kief/resin (~30-50%), concentrates (≥60%). Suggestive association between higher potency and 'problem cannabis use'; inconsistent findings in Mental Health, Other Substance Use. Therapeutic outcomes limited and mixed. GRADE certainty: 'very low'. Need for prospective studies on cardiorespiratory, cancer, pre-/perinatal outcomes.

Cannabis use disorder is associated with small to moderate cognitive impairments in 10 of 13 cognitive domains, particularly in verbal learning/memory, processing speed and working memory.

Meta-analysis on cognitive deficits in Cannabis Use Disorder. Small-to-moderate impairments in 10 of 13 cognitive domains; most affected: verbal learning/memory, processing speed and working memory (d=0.4-0.5). Verbal fluency and attention least impaired. No association between potential moderators and global cognition.

Prevalence of cannabis use rose from 4,1% (2001-2002) to 9,5% (2012-2013); prevalence of cannabis disorders rose from 1,5% to 2,9%, but risk among users fell from 35,6% to 30,6%.

n=36.309 US adults (NESARC 2001–2002 vs. 2012–2013), prevalence of cannabis use disorder rose from 1.5% to 2.9% (p0.001); increase particularly among older adults (≥65 years: +250%) and ethnic minorities; no decrease in disorder rate despite legalization.

Cannabis use was significantly associated with increased risk of substance use disorders (OR 6,2), but not with mood or anxiety disorders.

n=34.653, NESARC-III prospective cohort over 3 years; cannabis use associated with increased risk of psychiatric disorders incl. depression (aOR=1.49, 95% CI 1.14-1.94, p0.01), also after adjustment for baseline psychopathology.

Frequent and early-onset cannabis use in adolescence markedly increases the risk of problematic use and dependence in young adulthood.

10-year cohort study (n=1.943 adolescents, 78% follow-up at 24 years): 34% reported cannabis use in adolescence; of the adolescent cannabis users, 37% continued to use weekly at age 24, 20% met DSM-IV criteria for cannabis dependence. Persistent adolescent use and concurrent tobacco use as well as ongoing mental health problems significantly increased the risk of problematic use in adulthood.

High-potency cannabis use is associated with more frequent use, cannabis problems and anxiety disorders, but shows no connection to depression or alcohol misuse.

Longitudinal cohort study (ALSPAC, n=1.087, age 24 years); high-potency cannabis use associated with increased problematic cannabis use (AOR=4,08; 95%-CI 1,41–11,81) and increased frequency of use (AOR=4,38; 95%-CI 2,89–6,63) compared to low-potency use; 13% of respondents used high-potency cannabis.

Early cannabis use (before 17 years) was associated with 2,1- to 5,2-fold increased odds of subsequent use of other drugs, alcohol dependence and drug abuse/dependence, independent of genetic and shared environmental factors.

n=311 twin pairs, early cannabis use (before the 17th year of life) associated with increased risk of later use of other drugs (OR=2.1–5.2 depending on substance, p0.05); the gateway hypothesis is supported by co-twin control.

Frequency of use is the more robust predictor of problematic cannabis use, while THC potency in concentrates was partially associated with more favorable health measures.

Cross-sectional (N=300 adult recreational users, Colorado); higher frequency of cannabis use of flower and concentrates (not edibles) significantly associated with more pronounced problematic use (dependence, withdrawal, craving); after controlling for total frequency and CBD potency, higher THC concentrate strength remained associated with less withdrawal. Frequency — not potency — is the more robust predictor of dependence risk.

Cannabis use had no significant influence on treatment retention or medical-psychological outcomes in MMT.

Prospective 1-year cohort study (n=283 MMT patients, n=196 after 1 year of follow-up) at an Israeli methadone clinic; cannabis lifetime prevalence 75%, current abuse 25%; cannabis users had NO significantly worse treatment retention, no increased psychological distress and no increased HIV/HCV risk behavior vs. non-users — no negative influence on MMT outcome.

High-potency cannabis use is associated with significantly higher dependence severity, particularly among younger users.

UK population survey on cannabis potency and dependence severity; frequent high-potency cannabis (skunk) use significantly predicted higher dependence severity [b=0.254, 95%-KI 0.161–0.357, p<0.001], effect enhanced in younger users [interaction b=−0.006, p=0.004]; low-potency cannabis not associated with dependence (p>0.2).

Cannabis dependence was associated with 2,5-2,9-fold higher odds for suicidal ideation and suicide attempt; early cannabis use (before 17 years) showed increased suicide attempt rates, but no MDD association after genetic control.

n=311 twin pairs discordant for cannabis dependence; increased risk for major depression (OR=2.8, 95% CI 1.5-5.3) and suicidal ideation in cannabis-dependent twins; genetically controlled risk association.

TriNetX cohort study across 10 neurological diseases including neuropathy; cannabis abuse associated with significantly higher emergency department visits (neuropathy: 25.8% vs. 19.3% without cannabis) and increased pain prevalence over 3-year follow-up. Propensity score matching applied.

Psychosocial interventions effectively reduce cannabis use, lasting abstinence remains rare; no approved pharmacotherapy available.

Narrative review (Nature Reviews) on cannabis use disorder (CUD): ~10% of the 193 million cannabis users worldwide develop CUD; psychosocial therapies (CBT, MET, contingency management) significantly reduce use; no approved pharmacotherapies; legalization may increase CUD prevalence through availability of stronger products.