Addiction

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

IPD meta-analysis from 3 Australian-New Zealand longitudinal studies (N up to 3.765); daily cannabis use before age 17 associated with aOR=17,95 (95% CI 9,44–34,12) for later cannabis dependence; dose-dependent increase in risk for all adverse outcomes examined.

None of the pharmacotherapies examined (THC preparations, N-acetylcysteine, cannabidiol, anticonvulsants, mood stabilizers) showed significant efficacy for abstinence or reduction of cannabis use compared to placebo.

Cochrane SR on pharmacotherapies for cannabis use disorder; k=37 RCTs evaluated. Primary outcomes: abstinence at end of treatment, withdrawal symptom intensity including craving, adverse effects (AE/SAE), treatment discontinuation due to AE, treatment completion. Comparison: medication vs. placebo/no medication/other medication in cannabis-dependent individuals.

Cannabinoids showed limited efficacy for cannabis withdrawal symptoms, sleep disorders, tic disorders and autistic traits, but no significant effects on anxiety disorders, psychoses, PTSD and opioid disorders; increased risk of adverse effects overall.

Systematic review of k=54 RCTs (n=2.477) on cannabinoids in mental disorders and substance use disorders. CBD+THC combination reduced cannabis withdrawal symptoms (SMD=-0.29, 95% CI -0.57 to -0.02) and weekly cannabis use (SMD=-1.00, 95% CI -1.69 to incomplete). 24 (44%) studies with high risk of bias, quality of evidence for most outcomes low (GRADE).

Moderate evidence for chronic pain and spasticity, low evidence for nausea/vomiting, weight gain and sleep disorders; increased risk of side effects.

Comprehensive JAMA SR across 79 RCTs (n=6.462) on medical cannabis; no sufficient evidence for addiction treatment, moderate evidence for chronic pain/MS spasticity; documents dependence risk and withdrawal symptoms as safety concerns.

Systematic review + meta-analysis on substance use among adolescents <19 years in South Africa (k=30 publications, n=120.041, mean age 16.1). Lifetime prevalences: alcohol 35.09% (95% CI 23.83–48.30), tobacco 26.47% (14.56–33.01), cannabis 10.47% (5.98–17.71); any substance use 13.05% (9.65–17.42). 12-month prevalences: alcohol 17.45% (11.39–25.78), tobacco 11.57% (8.92–14.88), cannabis 6.66% (4.82–9.13). Substantial heterogeneity across studies (I² not numerically reported).

Systematic review on cannabinoids in substance use disorders (opioid, alcohol, cocaine, tobacco, methamphetamine dependence); k=97 studies (n=41.954), 195 endpoint instances across 6 outcomes. 45,6% beneficial findings were concentrated on short-term symptomatic endpoints (craving, withdrawal symptoms, consumption reduction), while sustained therapeutic outcomes (abstinence, relapse prevention, treatment retention) predominantly showed no significant effect (41,0% of all endpoints). For opioid dependence – with the strongest evidence base – no efficacy was demonstrated for sustained outcomes. Design-based weighting scheme (RCT=1.00 to qualitative=0.25); 76,4% of beneficial symptom findings came from weaker study designs.

Some pharmacotherapies show efficacy for individual aspects of CUD, but without sufficiently robust overall evidence for a standard recommendation.

NMA of k=24 RCTs (n=1.912, 74,9% male) on pharmacotherapies for cannabis use disorder; nabilone (d=-4,47 [95% CI -8,15; -0,79]) and topiramate (d=-3,80 [95% CI -7,06; -0,54]) significantly reduced cannabis use vs. placebo; FAAH inhibitors only as a non-significant trend (d=-2,30 [95% CI -4,75; 0,15], CI includes 0); dronabinol improved treatment retention (RR=1,27 [95% CI 1,02; 1,57]); no robust evidence for a single first-line pharmacological therapy.

Endocannabinoid modulators showed efficacy on cannabis use and abstinence, whereas cannabinoid receptor agonists showed only limited or no efficacy.

Systematic review of k=8 RCTs (n=667) on medical cannabinoids in cannabis use disorder (CUD); nabiximols, CBD and PF-04457845 reduced cannabis use and improved abstinence vs. placebo; CB1 agonists (dronabinol, nabilone) showed only limited potential for efficacy. All substances well tolerated.

About one fifth of all cannabis users develop a cannabis use disorder, in regularly using adolescents the risk rises to one third.

SR/MA of 21 studies on prevalence and risk of cannabis use disorders (CUD) among cannabis users: 22% (95% CI 18–26%) met CUD criteria, 13% (10–15%) cannabis dependence (CD). Cohort data show that the risk of developing a CD rises to 33% (22–44%) with regular (weekly/daily) use; increased risk with early onset and frequent use during adolescence.

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, 6 of which on CUD) on cannabis potency and addiction risk; high THC concentration compared to low-potency product consistently associated with increased cannabis use disorder risk; finding on CUD most robust among the mental health outcomes examined (psychosis, anxiety, depression, CUD); recommendation for standardisation of exposure measures for future studies.

CBD shows limited but potential therapeutic effect in selected psychiatric disorders, particularly substance use, psychosis and anxiety.

Systematic review (PRISMA), k=27 RCTs on CBD in psychiatric disorders; conclusion: existing evidence for therapeutic efficacy in substance use disorders (addiction); limited data situation requires larger RCTs for confirmation.

None of the investigated drug classes (SSRIs, buspirone, cannabinoids) showed consistent efficacy in the treatment of CUD.

Systematic review (k=26 trials, PROSPERO CRD42018108064) on pharmacotherapy of cannabis use disorder: moderate evidence that cannabinoids do NOT increase abstinence rate (moderate SOE); low evidence that cannabinoids do not reduce consumption (low SOE) and do not improve treatment retention (low SOE). SSRIs: low-SOE evidence for lack of efficacy; buspirone: no improvement in outcomes. No consistent evidence of increased harm across all substance classes.

CBD monotherapy shows no efficacy for substance use disorders; CBD+THC combination (nabiximols) shows positive effects on cannabis withdrawal and craving, but the evidence for CBD alone is limited and unclear for abstinence and reduction of cannabis, tobacco, alcohol, opioid and other psychoactive substance use.

Umbrella review of k=22 systematic reviews (of which 5 with meta-analysis) on CBD (alone or with THC) in substance use disorders (search up to 15.10.2024); mixed evidence for CBD monotherapy — NO convincing evidence for abstinence, reduction or cessation for cannabis, tobacco, alcohol, opiates; nabiximols (CBD+THC) showed positive effects on cannabis withdrawal symptoms and craving; CBD monotherapy not effective for SUD treatment.

Systematic review & meta-analysis on endocannabinoid system modulators in alcohol use disorder; k=63 preclinical and human studies. Preclinical meta-analyses: CB1R inverse agonists reduced alcohol consumption (SMD=-1.21), CBD likewise (SMD=-0.70), CB1R agonists increased consumption (SMD=+0.66). Human studies: inconsistent, mostly null effects; limited evidence for newer ECS modulators beyond rimonabant/CBD.

Meta-analysis on substance-specific parenting behavior and children's substance use; k=770 studies. Permissive parental attitudes showed the strongest association with substance use (r=.222, 95% CI [.203, .240]), followed by parental use (r=.157, 95% CI [.149, .165]) and parental substance provision (r=.140, 95% CI [.083, .196]). Parental substance-specific control was associated with lower use (r=-.165, 95% CI [-.194, -.135]). Cross-lagged analyses: very small bidirectional associations.

Meta-analysis shows a strong bidirectional association between major depression and cannabis use disorder (MDD prevalence in CUD: 19-22%, CUD prevalence in MDD: 4,6-28,5% depending on setting).

Meta-analysis + meta-regression on the bidirectional association MDD ↔ Cannabis Use Disorder (CUD); k=55 studies, n=3.279.774 (454.547 with CUD, 112.328 with MDD). Current-MDD prevalence in CUD: psychiatric samples 19.24%, community samples 21.65%. Current-CUD prevalence in MDD: psychiatric samples 28.45%, community samples 4.61%. Meta-regression: higher MDD prevalence in older populations and ICD-10 classification (vs. DSM). No publication bias (Egger's test). Sensitivity analyses stable.

CBD shows promise as adjunctive therapy for opioid dependence with reduction of craving and anxiety in clinical studies, but mixed results in preclinical studies with partially absent effects.

Systematic review (k=20 studies: 4 clinical, 16 preclinical) on CBD in opioid use disorder (OUD); clinical sample n=74. Clinical studies showed reduction of craving and alleviation of abstinence-induced anxiety under CBD; preclinically, inhibition of withdrawal symptoms and opioid-rewarding effects in the CPP paradigm (results mixed). Qualitative synthesis due to outcome heterogeneity; risk of bias 'some concerns' (clinical) or 'unclear' (preclinical). PROSPERO: CRD42023401446.

CBD and nabiximols show moderate to weak evidence depending on the psychiatric indication, with the strongest support for cannabis use disorder and schizophrenia.

Systematic review (k=23 studies); grade B recommendation for CBD in cannabis withdrawal and moderate to severe cannabis use disorder (CUD) — moderate evidence for symptom relief; CBD-containing compounds effective for withdrawal symptoms. Evidence base requires larger RCTs.

Systematische Review + Meta-Analyse zu DMT/5-MeO-DMT bei Substanzmissbrauch (1960-2024). Gepoolter Effekt g=0.94 (95% CI: 0.56-1.31, p<0.0001) für Substanzkonsum-Reduktion; Subgruppe Drogen g=1.35 (95% CI: 0.63-2.07, p<0.0001) vs. Alkohol g=0.65 (95% CI: 0.31-0.99, p<0.0001). Mit Psychotherapie g=1.38 (95% CI: 1.06-1.71, p<0.0001) vs. ohne g=0.60 (95% CI: 0.09-1.12, p<0.0001), Subgruppen-Unterschied p=0.0121. Hohe Heterogenität (I²=96.9%), hohes Bias-Risiko.

Alcohol and drug use contribute substantially to the global disease burden, measured in DALYs, YLDs and YLLs across 195 countries.

Global epidemiological SR (195 countries, 1990–2016); cannabis dependence: 22,1 million cases (age-standardised prevalence 289,7/100.000, 95%-UI 248,9–339,1); drug-attributable DALYs globally 31,8 million (95%-UI 27,4–36,6), corresponding to 1,3% of all DALYs; disease burden increases with higher Sociodemographic Index.

Double-blind, placebo-controlled pilot RCT with 40 treatment-seeking cannabis-dependent patients: as-needed self-titrated nabiximols (THC/CBD, Sativex) vs. placebo over 12 weeks, each combined with motivational and cognitive behavioral therapy. Nabiximols was well tolerated, no serious adverse events, adverse event rates showed no difference between arms. The primary endpoint abstinence showed no significant change; cannabis use was reduced under nabiximols (secondary). Limitation: small pilot sample, primary efficacy endpoint negative.

RCT mit n=541 urbanen American Indian/Alaska Native emerging adults (18-25 Jahre) zu kulturell adaptierten Interventionen bei Substanzgebrauch. Beide Gruppen (TACUNA-Workshops vs. HWC usual care) zeigten signifikante Reduktionen: Cannabis-Frequenz (B=-0.44 [SE=0.20] bzw. B=-0.54 [SE=0.21]), positive Alkohol-Screens (B=-0.03 [SE=0.01] bzw. B=-0.02 [SE=0.01]), positive Cannabis-Screens (B nicht vollständig berichtet im Abstract). Primäre Outcomes: Opioid-, Alkohol- und Cannabis-Gebrauch; sekundäre Outcomes: Substanzkonsequenzen, Mental Health, kulturelle Verbundenheit.

The digital treatment (PNC-txt) showed a significantly stronger effect in reducing cannabis use at low exposure to cannabis retail outlets in the activity space, but no significant moderation by residential area exposure.

Secondary analysis of an RCT on digital CUD treatment (Peer Network Counseling-txt) in young adults (n=425, age 18-25). Indirect treatment effect via motivation to change significantly moderated by cannabis retailer exposure in the activity space (β=0.104, 95% CI: 0.010–0.197); treatment effect >3 times stronger at low vs. high retailer exposure. No significant moderation by residential environment exposure (β=0.059, 95% CI: -0.020–0.137).

Nabiximols significantly reduced self-reported cannabis use days compared with placebo (−18,6 days; p=0,02).

RCT n=128 cannabis-dependent patients; nabiximols (up to 86,4 mg THC + 80 mg CBD/day) + counselling vs. placebo over 12 weeks. Nabiximols group had significantly fewer days of illegal cannabis use: 35,0 vs. 53,1 days (difference 18,6 days, 95% CI 3,5–33,7; p=0,02). Drug well tolerated.

Nabiximols significantly reduced cannabis use days and increased the abstinence rate compared to placebo, still 3 months after end of treatment.

RCT n=128 (nabiximols n=61 vs. placebo n=67) in cannabis-dependent individuals, 12 weeks + psychosocial intervention; nabiximols group used cannabis 6,8 fewer days/28 days (p=0,002, CI: 2,1–11,4) at end of treatment and 6,7 fewer days/28 days at 24-week follow-up (p=0,006, CI: 1,4–12,1); abstinence rate 23% vs. 9% (OR=3,0, CI: 1,1–9,1; p=0,035, NNT=8). Treatment benefits persisted >3 months after end of treatment.

Weak evidence for reduction of cannabis abuse in the legal group (10,1 vs. 10,9; p=0,052), but no statistically significant effects on secondary outcomes (depression, anxiety, psychotic symptoms).

n=374 adult cannabis users (Switzerland), randomised to legalised pharmacy access vs. illegal market (6-month follow-up); intervention group showed a tendency toward lower CUDIT-R score (M=10.1 vs. 10.9, β=-0.69, 95% CI [-1.4 to 0.0], p=0.052); subgroup analysis: significant reduction only in users with polysubstance use (p<0.001); no significant differences in depression, anxiety, psychotic symptoms, or amount of use.

CBD 400 mg and 800 mg significantly reduced cannabis use and increased abstinence compared with placebo; CBD was well tolerated with no severe adverse events.

First RCT on CBD in cannabis use disorder (n=82, Lancet Psychiatry): CBD 400 mg vs. placebo reduced THC-COOH:creatinine ratio by -94,21 ng/mL (95%-interval -161,83 to -35,56) and increased abstinence days by +0,48/week (0,15–0,82); CBD 800 mg: -72,02 ng/mL (-135,47 to -19,52). Posterior probability of superiority vs. placebo >0,9995 (400 mg) and >0,9965 (800 mg) respectively. No serious adverse events; 94% treatment adherence.

Nabiximols significantly reduced the severity of cannabis withdrawal and improved treatment retention, but showed no benefit over placebo in reducing long-term cannabis use after discontinuation of medication.

n=51 cannabis-dependent patients, nabiximols (THC/CBD spray) vs. placebo during withdrawal; nabiximols significantly reduces withdrawal symptoms (Cannabis Withdrawal Scale: difference -10.5 points, 95% CI -16.9 to -4.0, p=0.002) and improves treatment retention.

CBD significantly reduced both drug-associated craving and anxiety responses as well as physiological markers (heart rate, cortisol) compared to placebo, with protracted effects 7 days after exposure.

Double-blind RCT in drug-abstinent individuals with heroin use disorder (n=42). CBD (400 or 800 mg daily over 3 days) vs. placebo significantly reduced cue-induced craving and anxiety compared to neutral cues (acute effects at 1h/2h/24h). Protracted effects detectable 7 days after last CBD administration. CBD also lowered cue-induced heart rate and cortisol levels. No significant cognitive effects, no serious adverse events.

Secondary analysis of the CTN-0053 RCT (N-acetylcysteine vs. placebo in Cannabis Use Disorder, n=302); latent class analysis identified 4 craving trajectories over 12 weeks: low craving (41%), moderate-decreasing (38%), moderate-stable (11%), high craving (10%). The high-craving class showed 96% cannabis-positive urine tests and the lowest compliance.

Dronabinol increased treatment retention and reduced withdrawal symptoms, but showed no significant effect on cannabis abstinence versus placebo.

n=156 cannabis-dependent adults, 12-week DB-RCT dronabinol 20 mg 2×/day vs. placebo; primary endpoint abstinence not significant (dronabinol 17,7% vs. placebo 15,6%); treatment retention significantly higher under dronabinol (77% vs. 61%, p=0,02); withdrawal symptoms significantly lower (p=0,02).

The combination dronabinol/lofexidine was not superior to placebo for cannabis abstinence.

n=122 cannabis-dependent adults, dronabinol 20mg 3×/day + lofexidine 0,6mg 3×/day vs. placebo over 11 weeks; no significant difference in 3-week abstinence rate (27,9% medication vs. 29,5% placebo); combination showed no efficacy as treatment for cannabis use disorder.

Cannabis use was not significantly associated with opioid use, craving or withdrawal symptoms.

Exploratory secondary analysis of an RCT (n=272 patients with opioid use disorder), randomized to buprenorphine/naloxone vs. methadone over 24 weeks. Cannabis use (mean 2,3 days/week) showed no significant association with opioid use (β±SE = -0,06±0,04; p=0,15), craving (β±SE = -0,05±0,08; p=0,49) or withdrawal symptoms (β±SE = 0,09±0,1; p=0,36). Bayes factors <0,3 supported the null hypothesis.

CBD 800 mg/day showed no effect versus placebo on cocaine craving or relapse frequency in CUD.

n=78 adults with moderate to severe cocaine use disorder, CBD 800 mg/day vs. placebo (10 days inpatient detoxification + 12 weeks outpatient); craving score increase CBD 4,69 vs. placebo 3,21 (95% CI: -0,33 to 3,04; p=0,069); relapse HR=1,20 (95% CI: 0,65-2,20; p=0,51) — CBD did not significantly reduce craving or relapse risk.

The brief mindfulness intervention showed no significant effects on cannabis frequency, quantity, craving, or other secondary outcomes.

n=66 adults (18-56 years, 19 female) with cannabis use disorder (CUD), randomized 1:1:1 to Mindfulness-Based Intervention (MBI, n=23) vs. Relaxation (n=21) vs. Control (n=22); mean intervention duration 16 days. Primary outcome (Δ cannabis use days baseline→follow-up): NO significant intervention×time effects (F=0.26, FDRp=0.86). Secondary outcomes (Δ grams, craving VAS, mindfulness FFMQ, relaxation VAS): likewise no significant effects. Brief MBI showed NO efficacy in reducing cannabis use in CUD.

Abstinence and reduced frequency of use improve quality of life in CUD, whereas reduction in the amount consumed in grams does not.

RCT (n=62, 11 weeks, double-blind) on lofexidine+dronabinol in cannabis use disorder (CUD); abstinence at end of study significantly associated with higher quality of life (F₁,₄₇=8,34, p=0,006); reduced days of use also significant (F₁,₄₇=9,48, p=0,004); no sex difference as a moderator.

CBD group showed significantly lower cue-induced nucleus accumbens activation and significantly less alcohol craving after stress and alcohol cue exposure as well as during the fMRI task compared to placebo.

n=28 AUD patients, double-blind RCT (ICONIC); CBD 800 mg single dose vs. placebo. CBD reduced bilateral cue-induced nucleus accumbens activation (left: t=4.906, p<0.001, d=1.15; right: t=4.873, p<0.001, d=1.13) as well as alcohol craving after combined stress-/cue-exposure (F=4.516, p=0.043, eta=0.15) and in the fMRI cue-reactivity task (F=6.665, p=0.015, eta=0.23). CBD plasma levels correlated negatively with craving (r=-0.394, p=0.030).

CBD inhalation reduced daily cigarette consumption by ~40% compared to placebo in smokers willing to quit smoking.

Pilot RCT (n=24); CBD inhaler vs. placebo in smokers with desire for nicotine withdrawal. CBD group reduced cigarette consumption by ~40% during the treatment week vs. no change in the placebo group; effect partially maintained at follow-up.

Medical cannabis card led to improved self-reported insomnia symptoms, but to higher incidence and severity of cannabis use disorder and no significant improvement in pain, anxiety or depressive symptoms.

n=269 adults with medical cannabis card, 12-month follow-up shows no significant improvement in pain, insomnia or affective symptoms vs. baseline; risk of cannabis use disorder increased (12% develop CUD).

Nefazodone and bupropion-SR showed no significant effect on cannabis use or withdrawal symptoms compared with placebo.

RCT (n=106) on nefazodone vs. bupropion-SR vs. placebo in cannabis dependence; no significant effect of either drug on cannabis abstinence or withdrawal symptoms. Probability of abstinence increased over time, but independent of medication (negative finding).

CBD showed good tolerability but no superiority over placebo for drinking amount, craving, mood, anxiety or PTSD symptoms in both studies.

Two proof-of-concept RCTs on CBD in alcohol use disorder (AUD): Study 1 (n=27, AUD without PTSD, CBD 600→1200 mg/d vs. placebo, 8 weeks), Study 2 (n=30, AUD+PTSD, CBD 600 mg/d vs. placebo, 6 weeks). CBD well tolerated, but 22,6% of CBD participants had dose-limiting side effects. Both groups showed large reductions in drinking behavior (Cohen's dz>0,9), but no superiority of CBD over placebo for drinking amount, craving, mood, anxiety or PTSD symptoms (p n.s.).

CBD 300 mg/day did not reduce craving and withdrawal symptoms significantly more than placebo.

Exploratory RCT n=31 men with crack cocaine dependence; CBD 300 mg/day vs. placebo over 10 days; craving scores decreased significantly in both groups over 10 days, but no significant difference between CBD and placebo (negative primary endpoint); no effect on anxiety, depression or sleep changes.

Nabilone 2 mg/day did not reduce cannabis use significantly more than placebo.

Pilot RCT (n=18 adults with DSM-IV cannabis dependence); nabilone 2 mg/day vs. placebo over 10 weeks; both groups reduced cannabis use, but no significant difference between nabilone and placebo (p not significant by self-report and urine test). Nabilone well tolerated; 8 adverse events (all mild-moderate) in the nabilone group vs. 6 in the placebo group; no serious adverse events.

CBD significantly reduced cue-induced craving and attentional bias, but showed no effect on all other investigated outcomes.

Pilot RCT (n=10) in opioid dependence (OUD) under buprenorphine/methadone treatment; CBD 600 mg single dose vs. placebo significantly reduced cue-induced craving (0,2 vs. 1,3, p=0,040) and attentional bias toward drug-related cues (-80,4 vs. 100,3, p=0,041); no differences in other outcomes.

High fixed doses of Sativex significantly reduced cannabis withdrawal symptoms, but not craving.

Proof-of-concept RCT (n=9 cannabis-dependent subjects, 8-week ABACADAE crossover design): Sativex (THC/CBD 1:1, up to 108 mg THC/100 mg CBD) in high fixed dosing significantly better than placebo in reducing cannabis withdrawal symptoms (CWS/MWC), but not in craving (MCQ). Self-titrated lower doses showed limited efficacy compared to fixed doses.

Lithium carbonate did not significantly reduce the total withdrawal score compared to placebo.

RCT (n=38 cannabis-dependent adults, inpatient withdrawal treatment for 8 days); lithium carbonate 500 mg 2×/day vs. placebo. Primary outcome (Cannabis Withdrawal Scale total score): no significant group difference (p not significant). Individual symptoms 'nightmares/strange dreams', 'loss of appetite' and 'stomach pain' significantly reduced under lithium. Negative study with a relevant withdrawal population (n<60).

Double-blind, placebo-controlled crossover study in 13 daily cannabis users, who received 0, 30, 60 and 120 mg dronabinol (oral THC) daily over 5 days each. Dronabinol alleviated cannabis withdrawal symptoms in a dose-dependent manner, causing only few side effects and no impairment of cognitive performance; the subjective effect of smoked cannabis remained unchanged, the cannabis-related increase in heart rate was attenuated by 60 and 120 mg. Suggests a possible benefit of dronabinol for the treatment of cannabis use disorder. Major limitation: very small sample size (n=13), short treatment duration.

Placebo-controlled, counterbalanced crossover study with 11 non-treatment-seeking daily cannabis users (inpatient laboratory model) on zolpidem alone and in combination with the cannabinoid nabilone during cannabis withdrawal and a relapse measure. Both conditions reduced withdrawal-related sleep disturbances, but only zolpidem plus nabilone reduced further withdrawal symptoms. Important limitation: very small sample, laboratory setting only, not treatment-seeking.

Cannabis use, need for treatment and THC potency increased considerably in Europe over the decade, indicating growing public health risks.

European surveillance analysis (27 EU countries + UK/NO/TR, 2010–2019): past-month cannabis use prevalence +27% (from 3,1% to 3,9%) among adults; in 13 of 26 countries >20% of users reported high-risk use patterns; treatment entries for cannabis problems rose from 27,0 (95% CI 17,2–36,8) to 35,1 (95% CI 23,6–46,7) per 100.000 adults; THC content in cannabis resin tripled (from 7,6% to 24,1%).

Cannabis withdrawal produces a clinically relevant, temporally defined withdrawal syndrome with onset day 1–3 and duration 4–14 days.

50-day outpatient study (n=18 active users + n=12 ex-users): Cannabis withdrawal syndrome with onset typically day 1-3, peak day 2-6, duration 4-14 days; symptoms: aggression, anxiety, appetite loss, weight loss, irritability, sleep problems, stomach pain. Time course and extent comparable to tobacco and other withdrawal syndromes.