Cannabis Use Disorder (CUD) affects 50 million individuals worldwide and is associated with alterations in brain reward pathways. Mindfulness-based interventions (MBIs) show promise in reducing substance use and aberrant brain function in substance use disorders (SUD), but the effects on CUD or brain reward function have not been investigated. To examine whether a 2-week MBI vs. active control (i.e., closely matched relaxation) and passive control (i.e., no intervention) affected brain reward function in CUD using the Monetary Incentive Delay fMRI task, 49 individuals with moderate-to-severe CUD were randomised to: a 2-week MBI (n = 18), active control condition (n = 15), or passive control condition (n = 16), and assessed before and after the intervention. The effect of intervention-by-time was analysed using an exploratory whole-brain approach and a priori regions-of-interest approach (ROIs; ventral striatum, dorsal caudate, putamen, insula, cingulate, and orbitofrontal cortices). Whole-brain results revealed significant intervention-by-time effects. Post-MBI, there was: decreased cerebellum activity while anticipating monetary cues, increased parietal activity while receiving monetary wins, and decreased fusiform/superior frontal gyri (SFG) activity while receiving monetary wins. Post-relaxation, activity increased in several regions (i.e., hippocampus, insula, parietal cortex, fusiform, and SFG) during the receipt of monetary wins. Post-no intervention, activity increased in the cerebellum while anticipating monetary cues, and decreased in other areas (i.e., parietal cortex, hippocampus, and insula) while receiving monetary wins. There were no significant intervention-by-time effects using the ROI approach. Overall, MBI, matched relaxation, and no intervention may share changes in partially overlapping brain regions in distinct directions.

BACKGROUND:Population data on cannabis use-beyond prevalence and frequency of use-in the UK is lacking, yet needed to inform harm reduction messaging about cannabis. This study examined (a) recreational and medical cannabis use; (b) cannabis product use; (c) cannabis risk perceptions via three different routes of administration; (d) how product use and risk perceptions vary by reasons for use and higher risk use. METHODS:Data were from UK respondents of the 2023 International Cannabis Policy Study. National surveys included 3444 UK residents and 1590 people who consumed cannabis in the past year aged 16-65. Weighted logistic regression examined associations between product use, risk perceptions and reasons for use. RESULTS:50.9% of people who reported consuming cannabis reported doing so for recreational reasons only, 12.1% for medical reasons only, and 31.3% for both reasons. Dried flower was the most consumed product both in the past year (68%). Edibles (38.9%), vape oils (30.5%) and hash (27.5%) were the next commonly consumed products. People who consumed cannabis in the past year that screened positive for higher risk use were more likely to report consuming non-flower products (AOR 3.15, 95% CI 2.17, 4.58) than only dried flower. There were a higher percentage of respondents-regardless of whether they consumed cannabis or not-that reported perceiving consuming edibles daily as low or very low risk than smoking or vaping cannabis daily. CONCLUSIONS:There is diversity in the UK cannabis market in terms of the reasons for use and the products consumed. Understanding product use beyond just 'cannabis' and risk perceptions across different routes of administration is important for informing harm reduction messaging and evaluating policies to minimise harm and maximise benefit from both recreational and medical cannabis.

BACKGROUND AND AIMS:Lower risk guidelines for safer levels of cannabis use could help to reduce the health burden posed by cannabis use disorder (CUD). We aimed to estimate risk thresholds for CUD based on delta-9-tetrahydrocannabinol (THC) consumption using standard THC units (1 unit = 5 mg THC). DESIGN:Data from the CannTeen study, a longitudinal observational study consisting of five assessments over a 12-month period. SETTING:London, UK. PARTICIPANTS:Participants were n = 65 adults aged 26-29 (46% female, 70.77% white ethnicity) and n = 85 adolescents aged 16-17 (56% female, 65.48% white ethnicity). All participants reported at least one use of cannabis during the 12-month study period. MEASUREMENTS:Mean weekly standard THC units were estimated using the Enhanced Cannabis Timeline Followback, a comprehensive and validated assessment of quantity, frequency and potency of cannabis consumed. This was administered at 3-month intervals and averaged over a 12-month period. Past 12-month diagnosis of CUD using The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) was assessed at the final follow-up. Receiver operating characteristic curve models estimated the extent to which weekly standard THC unit consumption could discriminate no CUD from any CUD (mild, moderate or severe), and no CUD from moderate/severe CUD, in adults and adolescents separately. Risk thresholds were selected based on cut-offs that maximised sensitivity and specificity. FINDINGS:Discrimination accuracy of weekly standard THC units on CUD was good, with area under the curve > 0.70 for all models. Optimal cut-offs for risk of any CUD (versus no CUD) were 8.26 units per week for adults and 6.04 units per week for adolescents. For risk of moderate/severe CUD (versus no CUD) optimal cut-offs were 13.44 units per week for adults and 6.45 units per week for adolescents. CONCLUSIONS:Weekly cannabis consumption based on standard delta-9-tetrahydrocannabinol (THC) units appears to show good discrimination accuracy of cannabis use disorder at different severities and in different age groups. Safer levels of cannabis use, defined by low weekly standard THC unit consumption, could be recommended in lower risk cannabis use guidelines.

Global shifts towards the liberalisation of cannabis policies have increased the potency of cannabis products, alongside their accessibility, diversity, and the number of inexperienced cannabis consumers. There is a lack of systematic evidence on the subjective effects of cannabis' main psychoactive compound, Δ9-tetrahydrocannabinol (THC). We systematically reviewed and meta-analysed data from 41 randomised, double-blind, and placebo-controlled experimental studies on the acute subjective effects of THC in 1020 healthy individuals with infrequent cannabis use (<2 weekly; <100 lifetime). Pairwise meta-analyses estimating the mean difference of peak subjective effects between THC and placebo showed greater feelings of high, anxiety, and tiredness (all p < 0.001), lower alertness and contentedness (both p < 0.01), and no difference on calmness (p = 0.414). Meta-regressions of dose were stratified by inhaled and oral administration. Greater inhaled THC dose increased feeling high (b=1.06, p = 0.0024) and contentedness (b=1.06, p = 0.025), and decreased calmness (b=-0.96, p = 0.048); with no change in anxiety (b=-0.03, p = 0.845), tiredness (b=0.39, p = 0.129), or alertness (b=0.11, p = 0.837). Variability meta-analyses showed that greater inhaled dose of THC produced greater consistency between individuals in feeling high (b=-0.05, p = 0.021) and contentedness (b=-0.04, p < 0.0001). On a 100-point scale, inhaling 5 mg THC resulted in: increased high, anxiety, tiredness, and calmness by 34.3 (95%CI: 30.8-37.7), 14.4 (95%CI: 12.8-16.0), 26.3 (95%CI: 23.8-28.8), 4.5 (95%CI: -0.3-9.3), respectively; decreased alertness and contentedness by 40.2 (95%CI: -45.4--34.9) and 71.0 (95%CI: -75.7--66.4), respectively. Oral dose was not associated with any subjective effects (p > 0.05), although variability meta-analyses showed that greater oral dose of THC produced greater consistency between individuals in alertness (b=-0.13, p = 0.049). This evidence can inform public health efforts to guide consumers on the expected subjective effects of THC.

AIM:Our primary aim was to conduct a network meta-analysis (NMA) for the effectiveness, safety and acceptability of all psychosocial interventions and all pharmacotherapies for cannabis use disorder (CUD). METHODS:We conducted a NMA of studies identified from two completed systematic reviews examining the effectiveness, safety and acceptability of pharmacotherapies and psychosocial interventions for CUD in people aged ≥16 years. Outcomes were level of cannabis use, abstinence, adverse events and treatment completion. RESULTS:Fifty-seven studies were eligible for NMA. Depending on outcome, NMAs of psychosocial interventions included 6-16 studies (445-2287 participants), and NMAs of pharmacotherapies included 5-36 studies (260-3106 participants). Results are described relative to minimum clinically meaningful difference [mean difference (MD) ± 0.05, odds ratio (OR) ≤ 0.8 or ≥1.25]. Evidence for pharmacological interventions reducing cannabis use was very uncertain. However, low-certainty evidence suggested that dialectical behavioural/acceptance and commitment therapies [DBT/ACT; MD -0.18, 95% credible interval (-0.26 to -0.09)] and cognitive-behavioural therapy with motivation enhancement (MET-CBT) with contingency management [CM; MD -0.15 (-0.23 to -0.07)] reduced use frequency relative to a nonspecific comparator. Interventions including CM also supported abstinence (very low certainty). Limited, low-certainty evidence indicated that cannabidiol [OR 2.91 (0.45 to 27.98)], N-acetylcysteine [OR 1.30 (0.55 to 3.74)] and varenicline [OR 4.85 (0.65 to 48.26)] promoted abstinence compared with placebo, although cannabidiol was associated with adverse events [OR 1.58 (0.26 to 8.98)]. Very low-certainty evidence suggested mixed-action antidepressants, benzodiazepines, bupropion and buspirone also had more adverse events than placebo, without any indication of effectiveness. Very low-certainty evidence indicated that DBT/ACT and CM improved treatment completion. In contrast, MET-CBT, with/without affect management, reduced completion, relative to a nonspecific comparator. Low-certainty evidence suggested N-acetylcysteine [OR 1.29 (0.76 to 2.19)] and delta-9-tetrahydrocannabinol preparations [OR 1.32 (0.89 to 1.97)] increased treatment completion, while fatty acid amide hydrolase inhibitor [OR 0.80 (0.40 to 1.58)] and selective serotonin reuptake inhibitors [OR 0.56 (0.29-1.04)] reduced it, relative to placebo. CONCLUSIONS:There is some evidence that dialectical behavioural/acceptance and commitment therapies, contingency management alone or with cognitive-behavioural therapy with motivation enhancement, N-acetylcysteine, cannabidiol or varenicline may facilitate abstinence, reduce use and/or support treatment completion for cannabis use disorder. Some interventions may have unfavourable effects on those outcomes, relative to placebo or nonspecific comparators. While safety data for psychosocial interventions is lacking, several pharmacotherapies may be associated with adverse events. These findings should be interpreted with caution as all evidence is low- to very-low-certainty due to imprecise or heterogeneous treatment effects and high risk of bias in some study results.

BACKGROUND:In recent decades, the potency of cannabis resin increased globally, raising concerns, as higher potency has been associated with increased risk of psychiatric harms at the individual level. The aim here was to examine whether changes over time in the potency of seized cannabis resin samples were associated with psychiatric harms at the population level. METHODS:Data on ∆-9-tetrahydrocannabinol (THC) concentration in seized cannabis resin were obtained from forensic departments in Denmark (2000-2022), the country reporting the highest potency in Europe. Data on admissions to cannabis treatment, incidence of cannabis-induced psychosis, and dual diagnosis (schizophrenia and cannabis use disorder) were obtained from national registers. Time-dependent associations between potency and the outcomes were examined with mixed-effects linear regression models and associations across age and sex were explored. Candidate time lags were 0-10 years. RESULTS:THC concentration increased almost fourfold: mean 8.3-31.2% from 2000 to 2022. In fully adjusted models, THC was positively associated with first-time cannabis treatment entry at lags of 0-6, strongest at year 0 (p < 0.0001); incidence of cannabis-induced psychosis at lags of 0-4, strongest at year 0 (p < 0.0001); and incidence of dual diagnosis at lags of 0-1, strongest at year 0 (p < 0.01). No positive associations were found in unadjusted models. Subgroup analyses indicated associations in older patients and women. CONCLUSIONS:Potency of seized cannabis resin increased almost fourfold from 2000 to 2022. Changes in cannabis potency were positively associated with psychiatric harms at the population level across all outcomes.

The British Association for Psychopharmacology guidelines for the management of substance dependence focus primarily on the pharmacological aspects of treatment. A group of international experts from a wide range of disciplines reviewed the current evidence in their field, considered the strength of the evidence and discussed the clinical implications at a consensus meeting. The guidelines focus on the pharmacological management of dependence on alcohol, benzodiazepines, ‘z-drugs’, γ-hydroxybutyrate (GHB), gabapentinoids, opioids, nicotine, cannabis and synthetic cannabinoids, cocaine, amphetamine and methamphetamine, dissociative drugs and their analogues. They are based on the available evidence and make recommendations to aid clinical decision making, as well as highlighting the gaps in the current evidence-base.

The UK legalised medical cannabis in 2018, yet little is known about people accessing cannabis legally via prescription or those using cannabis for medical purposes without a prescription. This study aimed to estimate: 1) the percentage of people who use cannabis medically with and without a prescription; 2) the sources used to obtain cannabis; 3) the products used; and 4) the associations between monthly or more frequent (MMF) product use and medical cannabis use status. National repeat cross-sectional surveys conducted in September-November 2023 and 2024. UK. People aged 16-65 who used cannabis in the past 12 months (n=4,414). Inferential statistics compared outcomes by medical cannabis use status. Multivariable regression analyses estimated associations between MMF product use and medical cannabis use status. Overall, 13.0% of people reported receiving a medical cannabis prescription, 36.4% reported medical use without a prescription, and 50.6% reported no medical use. Cannabis was sourced through diverse routes; only 10.7% of people with prescriptions obtained all their cannabis from a legal medical prescription. People with a medical prescription had a higher probability of reporting MMF use of oils or liquid drops (aRR=3.51; 95% CI: 2.73-4.52), oil or liquid capsules (aRR=2.63; 1.99-3.47), vape oils (aRR=2.40; 2.03-2.84), edibles (aRR=2.41; 2.01-2.90), cannabis drinks (aRR=3.39; 2.69-4.26), solid concentrates (aRR=3.10; 2.29-4.21), hash or kief (aRR=1.82; 1.44-2.30), and topicals (aRR=3.42; 2.58-4.51) than people who did not report medical use, after adjusting for covariates. People who ever asked for a medical prescription and people with a medical prescription in the past year had a higher probability of screening positive for high-risk use. Over one in ten people who use cannabis in the UK report a medical cannabis prescription, yet a third reported medical use without a prescription. With only a minority obtaining all their cannabis legally, many rely on illegal sources, suggesting prescriptions may not meet the needs of those reporting use for medical purposes. People with prescriptions show a higher probability of frequent use of processed, higher-potency products, and meeting a threshold for high-risk use. Healthcare encounters during medical cannabis prescribing should discuss risks related to potency, product type, and adverse effects such as cannabis use disorder.

BACKGROUND:The presence of cannabidiol (CBD) in cannabis may alter cannabinoid pharmacokinetics, however previous research has produced mixed results. Furthermore, no prior research has explored how cannabinoid pharmacokinetics are moderated by age. AIM:Using vaporised and inhaled cannabis, we aimed to (1) examine the effect of CBD on the plasma concentration of delta-9-tetrahydrocannabinol (THC) and its metabolites, and (2) compare cannabinoid plasma pharmacokinetics in adolescents and adults. METHODOLOGY:We conducted a randomised, double-blind, placebo-controlled, cross-over study. We compared the effects of three vaporized, weight-adjusted cannabis preparations: 'THC-alone' (8mg THC/75kg), 'THC+CBD' (8mg THC and 24mg CBD/75kg) and placebo, in 48 participants, aged 16-17-years and 26-29-years. Blood samples were taken prior to inhalation, then 20, 30, and 160min after inhalation began. Thirty-five participants had complete pharmacokinetic datasets, which were analysed. Plasma was analysed for concentrations of THC, 11-hydroxy-THC (OH-THC) and 11-Nor-9-carboxy-THC (COOH-THC), CBD, 7-hydroxy-cannabidiol (OH-CBD) and 7-carboxy-cannabidiol (COOH-CBD). RESULTS:The 'THC+CBD' condition produced significantly greater THC, OH-THC, and COOH-THC plasma levels than the 'THC-alone' condition, in terms of natural-log-transformed area-under-the-curve (AUC) and peak concentration (Cmax) values, with the exception of Cmax for OH-THC. Geometric mean ratios showed the 'THC+CBD' condition led to higher THC plasma levels. There was no strong evidence of age-related differences. CONCLUSION:The presence of CBD in vaporised cannabis increased circulating levels of THC and THC-metabolites. However, further research is needed to understand discrepancies across studies regarding the impact of CBD on THC pharmacokinetics.

Cannabis use often begins in adolescence and young adulthood, when anxiety, depression, psychosis, and bipolar disorder typically first develop. Young people aged in their mid-teens to mid-twenties who engage in daily cannabis use and develop a cannabis use disorder have a higher prevalence of these mental disorders. We assessed the coherence of evidence from epidemiological, genetic, experimental, and preclinical studies to assess relationships between daily cannabis use and the increased incidence, prevalence, and persistence of psychosis, bipolar disorder, anxiety, depression, and suicidal behaviours. We found credible evidence that daily cannabis use is a contributory cause of psychosis. There were fewer high quality epidemiological and genetic studies of bipolar disorder. The role of cannabis use in depression, anxiety, and suicidality was less certain because associations were modest and could reflect self-medication, shared risk factors, or bidirectional relationships. A high priority should be given to developing effective interventions for cannabis use disorders in people with mental disorders.

BACKGROUND:The United Kingdom legalized medical cannabis in 2018, yet little is known about people using cannabis medically with and without a prescription. This study aimed to estimate: 1) the percentage of people reporting using cannabis medically with and without a prescription; 2) the sources; 3) products used; and 4) associations between frequent product use and medical cannabis status. METHODS:Data were from national repeat cross-sectional surveys conducted in 2023 and 2024. UK participants were aged 16-65 who used cannabis in the past 12 months (n = 4,414). Multivariable regression analyses estimated associations between outcomes and medical cannabis status. RESULTS:Overall, 12.9% of respondents reported receiving a medical cannabis prescription, 35.9% reported medical use without a prescription, and 51.2% reported no medical use. Cannabis was sourced through diverse routes; only 10.9% of people with prescriptions obtained all their cannabis from a prescription. Respondents with a prescription had a higher probability of reporting frequent use of drops, capsules, vape oils, edibles, drinks, solid concentrates, hash/kief, and topicals (aRRs = range between 1.82 and 3.51)) and a higher probability of screening positive for high-risk use (aRR = 3.09; 2.51-3.79) than respondents who did not use medically. CONCLUSIONS:People with medical cannabis prescriptions show a higher probability of frequent use of processed products and of meeting a threshold for high-risk use. Healthcare encounters during medical cannabis prescribing should discuss risks related to products, potency, and adverse effects such as cannabis use disorder.

Background Cannabis use is common in people with psychosis and is associated with poor outcomes. Aims To assess insight into cannabis use disorder, perceptions about how cannabis use influences mental health and the desire to change cannabis use among people with psychotic disorders. Method Adults with a psychotic disorder and comorbid cannabis use disorder were asked about the impact of cannabis use on their illness and their desire to change cannabis use. Cannabis use disorder was determined using DSM-5 criteria. Participants completed the Substance Use Awareness and Insight Scale. Results Sixty-two participants (mean age: 42 years; 95% male; 65% Black ethnicity; 85% severe DSM-5 cannabis use disorder) completed the study. The mean total Substance Use Awareness and Insight Scale score was 4.8 (s.d.: 2.1), with subdomain scores of 3.7 (s.d.: 2.8) for general illness awareness, 6.2 (s.d.: 2.8) for symptom attribution, 3.5 (s.d.: 2.9) for awareness of need for treatment and 5.6 (s.d.: 3.8) for awareness of negative consequences. Fifty-eight per cent said that cannabis use made their mental health ‘better’, whereas only 15% said it made it ‘worse’; 27% reported that cannabis made their psychotic symptoms ‘better’, and 21% said it made them ‘worse’. Nevertheless, more than half the sample (53%) said they wanted to reduce or stop using cannabis. Conclusions Many people with psychotic disorders have impaired insight into cannabis use disorder or believe that cannabis improves their mental health; these factors may contribute to persistent use in this population. Interventions that improve insight may help to address ambivalence and support those already wishing to reduce use.

Substance use has been associated with blunted brain responses to non-drug rewards, but findings in people who use cannabis are mixed. Adolescents may be uniquely vulnerable to cannabis-related disruption to reward processing due to ongoing neuromaturation, but longitudinal research is lacking. In this longitudinal fMRI study, we compared brain measures of reward anticipation in 46 adolescents (16–17 years) and adults (26–29 years) who used cannabis (1–7 days/week) and 50 age-matched controls with the Monetary Incentive Delay task at baseline and 12-month follow-up. Region of interest (ROI) analyses adjusted for cigarette/roll-up use, depression, and risk-taking found that reward anticipation activity decreased in the right (p = 0.05, ηp2 = 0.04) and left (p = 0.02, ηp2 = 0.05) ventral striatum from baseline to follow-up in participants who used cannabis compared with control participants. These effects remained in unadjusted models and when including only participants who consistently used or abstained from cannabis during the study period. There were no significant interactions between the cannabis user-group and age-group, or between the user-group, age-group, and time. There were also no cannabis user-group main or interaction effects in full sample ROI analyses for the thalamus, insula, or supplementary motor area, or in exploratory whole-brain analyses. The current results suggest that cannabis use may be associated with reductions in non-drug reward anticipation activity in the ventral striatum, a key part of the brain’s reward system. However, there was no evidence of adolescent resilience or vulnerability to cannabis-related changes in brain reward anticipation activity.

Cannabis policies vary from strict prohibition to commercialised legalisation and are rapidly evolving worldwide. Here, we reviewed evidence for associations between international cannabis policy changes from 2000-25 and cannabis use, cannabis use disorder, and other psychiatric disorders. Commercialised legal markets for non-medical use in Canada and the USA were associated with increased prevalence of cannabis use and cannabis use disorder in adults and increases in cannabis potency since legalisation. There was no consistent evidence for associations between policy change and the prevalence or incidence of psychotic disorders. Commercialised legalisation was associated with an increase in hospital admissions for psychosis, and for psychotic disorders comorbid with cannabis use disorder. Poorly regulated legal access to medical cannabis, in the absence of efficacy and safety data, could increase risk of harm. Policies that limit commercialisation, such as strictly regulated legalisation of medical or non-medical supply, were not as strongly associated with cannabis use or psychiatric disorders, but long-term evaluation is needed. There was little evidence that decriminalisation of non-medical cannabis in Europe, Africa, Oceania, and Asia was associated with cannabis use or psychiatric disorders.