Persistent increased severity of cannabis use disorder symptoms in adolescents compared to adults: a one-year longitudinal study.

Adolescence is a developmental period characterised by increased vulnerability to cannabis use disorder (CUD). However, previous investigations of this vulnerability have relied on cross-sectional comparisons and lack a detailed assessment of cannabis quantity, a potentially important confounding factor. Here, we aimed to investigate the one-year course of CUD in adolescents compared to adults who currently use cannabis, adjusting for a comprehensive measure of cannabis quantity. Data are from a one-year observational longitudinal study (CannTeen) of adolescents and adults who currently used cannabis regularly with five waves of assessment at 3-monthly intervals, based in London, UK. Participants were n = 70 adults (26-29, 45.7% female), who did not regularly use cannabis when they were under age 18, and n = 76 adolescents (16-17, 50.0% female). The exposure was adolescent (compared to adult) frequent cannabis use. The primary outcome was CUD symptoms measured using the cannabis use disorder identification test revised (CUDIT-R) at five time points. Models were adjusted for cannabis quantity using mean weekly standard THC units (one unit = 5 mg THC). Other covariates included gender, and whether each session occurred before or during the COVID-19 pandemic. In models adjusted for pre-registered covariates, adolescents scored 3.7 points higher on the CUDIT-R compared to the adult group across the 5 assessment waves (3.66 95% CIs 1.99, 5.34). There was also evidence of a linear reduction in symptoms over time in both groups (-0.47, 95%CIs -0.67, -0.27). Adolescents had persistently increased CUD symptoms compared to adults across the 12-month period. This association was robust after adjusting for the quantity of cannabis consumed and other covariates.

Applying machine learning to international drug monitoring: classifying cannabis resin collected in Europe using cannabinoid concentrations.

In Europe, concentrations of ∆9-tetrahydrocannabinol (THC) in cannabis resin (also known as hash) have risen markedly in the past decade, potentially increasing risks of mental health disorders. Current approaches to international drug monitoring cannot distinguish between different types of cannabis resin which may have contrasting health effects due to THC and cannabidiol (CBD) content. Here, we compared concentrations of THC and CBD in different types of cannabis resin collected in Europe (either Moroccan-type, or Dutch-type). We then tested the ability of machine learning algorithms to classify the type of cannabis resin (either Moroccan-type, or Dutch-type) using routinely collected monitoring data on THC and CBD. Finally, we applied the optimal algorithm to new samples collected in countries where the type of cannabis resin was unknown, the UK and Denmark. Results showed that overall, Dutch-type samples had higher THC (Hedges' g = 2.39) and lower CBD (Hedges' g = 0.81) than Moroccan-type samples. A Support Vector Machine algorithm achieved classification accuracy exceeding 95%, with little variation in this estimate, good interpretability, and plausibility. It made contrasting predictions about the type of cannabis resin collected in the UK (94% Moroccan-type; 6% Dutch-type) and Denmark (36% Moroccan-type; 64% Dutch-type). In conclusion, we provide proof-of-concept evidence for the potential of machine learning to inform international drug monitoring. Our findings should not be interpreted as objective confirmatory evidence but suggest that Dutch-type cannabis resin has higher THC concentrations than Moroccan-type cannabis resin, which may contribute to variation in drug markets and health outcomes for people who use cannabis in Europe.

Instant Detection of Synthetic Cannabinoids on Physical Matrices, Implemented on a Low-Cost, Ultraportable Device.

Synthetic cannabinoids (SCs) make up a class of novel psychoactive substances (NPS), used predominantly in prisons and homeless communities in the U.K. SCs can have severe side effects, including psychosis, stroke, and seizures, with numerous reported deaths associated with their use. The chemical diversity of SCs presents the major challenge to their detection since approaches relying on specific molecular recognition become outdated almost immediately. Ideally one would have a generic approach to detecting SCs in portable settings. The problem of SC detection is more challenging still because the majority of SCs enter the prison estate adsorbed onto physical matrices such as paper, fabric, or herb materials. That is, regardless of the detection modality used, the necessary extraction step reduces the effectiveness and ability to rapidly screen materials on-site. Herein, we demonstrate a truly instant generic test for SCs, tested against real-world drug seizures. The test is based on two advances. First, we identify a spectrally silent region in the emission spectrum of most physical matrices. Second, the finding that background signals (including from autofluorescence) can be accurately predicted is based on tracking the fraction of absorbed light from the irradiation source. Finally, we demonstrate that the intrinsic fluorescence of a large range of physical substrates can be leveraged to track the presence of other drugs of interest, including the most recent iterations of benzodiazepines and opioids. We demonstrate the implementation of our presumptive test in a portable, pocket-sized device that will find immediate utility in prisons and law enforcement agencies around the world.

Photochemical Fingerprinting Is a Sensitive Probe for the Detection of Synthetic Cannabinoid Receptor Agonists; toward Robust Point-of-Care Detection.

With synthetic cannabinoid receptor agonist (SCRA) use still prevalent across Europe and structurally advanced generations emerging, it is imperative that drug detection methods advance in parallel. SCRAs are a chemically diverse and evolving group, which makes rapid detection challenging. We have previously shown that fluorescence spectral fingerprinting (FSF) has the potential to provide rapid assessment of SCRA presence directly from street material with minimal processing and in saliva. Enhancing the sensitivity and discriminatory ability of this approach has high potential to accelerate the delivery of a point-of-care technology that can be used confidently by a range of stakeholders, from medical to prison staff. We demonstrate that a range of structurally distinct SCRAs are photochemically active and give rise to distinct FSFs after irradiation. To explore this in detail, we have synthesized a model series of compounds which mimic specific structural features of AM-694. Our data show that FSFs are sensitive to chemically conservative changes, with evidence that this relates to shifts in the electronic structure and cross-conjugation. Crucially, we find that the photochemical degradation rate is sensitive to individual structures and gives rise to a specific major product, the mechanism and identification of which we elucidate through density-functional theory (DFT) and time-dependent DFT. We test the potential of our hybrid "photochemical fingerprinting" approach to discriminate SCRAs by demonstrating SCRA detection from a simulated smoking apparatus in saliva. Our study shows the potential of tracking photochemical reactivity via FSFs for enhanced discrimination of SCRAs, with successful integration into a portable device.

Anhedonia, Apathy, Pleasure, and Effort-Based Decision-Making in Adult and Adolescent Cannabis Users and Controls.

BACKGROUND: Cannabis use may be linked with anhedonia and apathy. However, previous studies have shown mixed results, and few have examined the association between cannabis use and specific reward sub-processes. Adolescents may be more vulnerable than adults to harmful effects of cannabis. This study investigated (1) the association between non-acute cannabis use and apathy, anhedonia, pleasure, and effort-based decision-making for reward; and (2) whether these relationships were moderated by age group. METHODS: We used data from the "CannTeen" study. Participants were 274 adult (26-29 years) and adolescent (16-17 years) cannabis users (1-7 d/wk use in the past 3 months) and gender- and age-matched controls. Anhedonia was measured with the Snaith-Hamilton Pleasure Scale (n = 274), and apathy was measured with the Apathy Evaluation Scale (n = 215). Effort-based decision-making for reward was measured with the Physical Effort task (n = 139), and subjective wanting and liking of rewards was measured with the novel Real Reward Pleasure task (n = 137). RESULTS: Controls had higher levels of anhedonia than cannabis users (F1,258 = 5.35, P = .02, η p2 = .02). There were no other significant effects of user-group and no significant user-group*age-group interactions. Null findings were supported by post hoc Bayesian analyses. CONCLUSION: Our results suggest that cannabis use at a frequency of 3 to 4 d/wk is not associated with apathy, effort-based decision-making for reward, reward wanting, or reward liking in adults or adolescents. Cannabis users had lower anhedonia than controls, albeit at a small effect size. These findings are not consistent with the hypothesis that non-acute cannabis use is associated with amotivation.

Cannabis use as a potential mediator between childhood adversity and first-episode psychosis: results from the EU-GEI case-control study.

BACKGROUND: Childhood adversity and cannabis use are considered independent risk factors for psychosis, but whether different patterns of cannabis use may be acting as mediator between adversity and psychotic disorders has not yet been explored. The aim of this study is to examine whether cannabis use mediates the relationship between childhood adversity and psychosis. METHODS: Data were utilised on 881 first-episode psychosis patients and 1231 controls from the European network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) study. Detailed history of cannabis use was collected with the Cannabis Experience Questionnaire. The Childhood Experience of Care and Abuse Questionnaire was used to assess exposure to household discord, sexual, physical or emotional abuse and bullying in two periods: early (0-11 years), and late (12-17 years). A path decomposition method was used to analyse whether the association between childhood adversity and psychosis was mediated by (1) lifetime cannabis use, (2) cannabis potency and (3) frequency of use. RESULTS: The association between household discord and psychosis was partially mediated by lifetime use of cannabis (indirect effect coef. 0.078, s.e. 0.022, 17%), its potency (indirect effect coef. 0.059, s.e. 0.018, 14%) and by frequency (indirect effect coef. 0.117, s.e. 0.038, 29%). Similar findings were obtained when analyses were restricted to early exposure to household discord. CONCLUSIONS: Harmful patterns of cannabis use mediated the association between specific childhood adversities, like household discord, with later psychosis. Children exposed to particularly challenging environments in their household could benefit from psychosocial interventions aimed at preventing cannabis misuse.

The association between reasons for first using cannabis, later pattern of use, and risk of first-episode psychosis: the EU-GEI case-control study.

BACKGROUND: While cannabis use is a well-established risk factor for psychosis, little is known about any association between reasons for first using cannabis (RFUC) and later patterns of use and risk of psychosis. METHODS: We used data from 11 sites of the multicentre European Gene-Environment Interaction (EU-GEI) case-control study. 558 first-episode psychosis patients (FEPp) and 567 population controls who had used cannabis and reported their RFUC.We ran logistic regressions to examine whether RFUC were associated with first-episode psychosis (FEP) case-control status. Path analysis then examined the relationship between RFUC, subsequent patterns of cannabis use, and case-control status. RESULTS: Controls (86.1%) and FEPp (75.63%) were most likely to report 'because of friends' as their most common RFUC. However, 20.1% of FEPp compared to 5.8% of controls reported: 'to feel better' as their RFUC (χ2 = 50.97; p < 0.001). RFUC 'to feel better' was associated with being a FEPp (OR 1.74; 95% CI 1.03-2.95) while RFUC 'with friends' was associated with being a control (OR 0.56; 95% CI 0.37-0.83). The path model indicated an association between RFUC 'to feel better' with heavy cannabis use and with FEPp-control status. CONCLUSIONS: Both FEPp and controls usually started using cannabis with their friends, but more patients than controls had begun to use 'to feel better'. People who reported their reason for first using cannabis to 'feel better' were more likely to progress to heavy use and develop a psychotic disorder than those reporting 'because of friends'.

Acceptability of integrating smoking cessation treatment into routine care for people with mental illness: A qualitative study.

INTRODUCTION: Improving Access to Psychological Therapies (IAPTs) Services could offer smoking cessation treatment to improve physical and psychological outcomes for service users, but it currently does not. This study aimed to understand participants' views and experiences of receiving a novel smoking cessation intervention as part of the ESCAPE trial (intEgrating Smoking Cessation treatment As part of usual Psychological care for dEpression and anxiety). We used the Capability, Opportunity and Motivation Model of Behaviour (COM-B) to understand the (i) acceptability of the integrated smoking cessation treatment, (ii) views of psychological well-being practitioners' (PWPs) ability to deliver the smoking cessation treatment and (iii) positive and negative impacts of smoking cessation treatment. METHODS: This was a qualitative study embedded within a feasibility randomized-controlled trial (ESCAPE) in primary care services in the United Kingdom (IAPT). Thirty-six participants (53% female) from both usual care and intervention arms of the ESCAPE trial, including both quitters and nonquitters, were interviewed using semi-structured interviews. Data were analysed using a framework approach to thematic analysis, using the COM-B as a theoretical frame. RESULTS: Psychological Capability: Integrated smoking cessation treatment was acceptable and encouraged participants to reflect on their mental health. Some participants found it difficult to understand nicotine withdrawal symptoms. MOTIVATION: Participants were open to change during the event of presenting to IAPT. Some described being motivated to take part in the intervention by curiosity, to see whether quitting smoking would help their mental health. Physical Opportunity: IAPT has a natural infrastructure for supporting integrated treatment, but there were some barriers such as session duration and interventions feeling segmented. Social Opportunity: Participants viewed PWPs as having good interpersonal skills to deliver a smoking cessation intervention. CONCLUSION: People with common mental illness generally accepted integrated smoking cessation and mental health treatment. Smoking cessation treatment fits well within IAPT's structure; however, there are barriers to implementation. PATIENT OR PUBLIC CONTRIBUTION: Before data collection, we consulted with people with lived experience of smoking and/or mental illness and lay public members regarding the aims, design and interview schedules. After analysis, two people with lived experience of smoking and mental illness individually gave feedback on the final themes and quotes.

Legal sourcing of ten cannabis products in the Canadian cannabis market, 2019-2021: a repeat cross-sectional study.

BACKGROUND: One of the objectives of cannabis legalization in Canada is to transition consumers from the illegal to the legal market. Little is known about how legal sourcing varies across different cannabis product types, provinces, and frequency of cannabis use. METHODS: Data were analyzed from Canadian respondents in the International Cannabis Policy Study, a repeat cross-sectional survey conducted annually from 2019 to 2021. Respondents were 15,311 past 12-month cannabis consumers of legal age to purchase cannabis. Weighted logistic regression models estimated the association between legal sourcing ("all"/ "some"/ "none") of ten cannabis product types, province, and frequency of cannabis use over time. RESULTS: The percentage of consumers who sourced "all" their cannabis products from legal sources in the past 12 months varied by product type, ranging from 49% of solid concentrate consumers to 82% of cannabis drink consumers in 2021. The percentage of consumers sourcing "all" their respective products legally was greater in 2021 than 2020 across all products. Legal sourcing varied by frequency of use: weekly or more frequent consumers were more likely to source "some" (versus "none") of their products legally versus less frequent consumers. Legal sourcing also varied by province, with a lower likelihood of legal sourcing in Québec of products whose legal sale was restricted (e.g., edibles). CONCLUSION: Legal sourcing increased over time, demonstrating progress in the transition to the legal market for all products in the first three years of legalization in Canada. Legal sourcing was highest for drinks and oils and lowest for solid concentrates and hash.

The Effect of Conflicting Public Health Guidance on Smokers' and Vapers' E-cigarette Harm Perceptions.

BACKGROUND: E-cigarettes are increasingly being viewed, incorrectly, as more harmful than cigarettes. This may discourage smokers from switching to e-cigarettes. One potential explanation for these increasingly harmful attitudes is conflicting information presented in the media and online, and from public health bodies. AIMS AND METHODS: In this prospectively registered online study, we aimed to examine the impact of conflicting public health information on smokers' and vapers' e-cigarette harm perceptions. Daily UK smokers who do not vape (n = 334) and daily UK vapers (n = 368) were randomized to receive either: (1) a consistent harm reduction statement from two different public health bodies (Harm Reduction), (2) a consistent negative statement about e-cigarette harms from two different public health bodies (Negative), (3) a harm reduction statement from one public health body and a negative statement from another (Conflict), and (4) a statement of the risks of smoking followed by a harm reduction statement from one public health body and a negative statement from another (Smoking Risk + Conflict). Participants then answered questions regarding their perceptions of e-cigarette harm. RESULTS: The Negative condition had the highest e-cigarette harm perceptions, significantly higher than the Smoking Risk + Conflict condition (MD = 5.4, SE = 1.8, p < .016, d = 0.3 [CI 0.73 to 10.04]), which did not differ from the Conflict condition (MD = 1.5, SE = 1.8, p = .836, d = 0.1 [CI -3.14 to 6.17]). The Conflict condition differed from the Harm Reduction condition, where harm perceptions were lowest (MD = 5.4, SE = 1.8, p = .016, d = 0.3 [CI 0.74 to 10.07]). CONCLUSIONS: These findings are the first to demonstrate that, compared to harm reduction information, conflicting information increases e-cigarette harm perceptions amongst vapers, and smokers who do not vape. IMPLICATIONS: This research provides the first empirical evidence that conflicting information increases smokers' and vapers' e-cigarette harm perceptions, compared to harm reduction information. This may have a meaningful impact on public health as e-cigarette harm perceptions can influence subsequent smoking and vaping behavior. Conflicting information may dissuade smokers, who have the most to gain from accurate e-cigarette harm perceptions, from switching to e-cigarettes. These findings indicate that public health communications that are consensus-based can lower harm perceptions of e-cigarettes, and have the potential to reduce morbidity and mortality attributable to tobacco smoking.

Drug Use Changes at the Individual Level: Results from a Longitudinal, Multisite Survey in Young Europeans Frequenting the Nightlife Scene.

BACKGROUND: Monitoring emerging trends in the increasingly dynamic European drug market is vital; however, information on change at the individual level is scarce. In the current study, we investigated changes in drug use over 12 months in European nightlife attendees. METHOD: In this longitudinal online survey, changes in substances used, use frequency in continued users, and relative initiation of use at follow-up were assessed for 20 different substances. To take part, participants had to be aged 18-34 years; be from Belgium, Italy, the Netherlands, Sweden, or the UK; and have attended at least 6 electronic music events in the past 12 months at baseline. Of 8,045 volunteers at baseline, 2,897 completed the survey at both time points (36% follow-up rate), in 2017 and 2018. RESULTS: The number of people using ketamine increased by 21% (p < 0.001), and logarithmized frequency of use in those continuing use increased by 15% (p < 0.001; 95% CI: 0.07-0.23). 4-Fluoroamphetamine use decreased by 27% (p < 0.001), and logarithmized frequency of use in continuing users decreased by 15% (p < 0.001, 95% CI: -0.48 to -0.23). The drugs with the greatest proportion of relative initiation at follow-up were synthetic cannabinoids (73%, N = 30), mephedrone (44%, N = 18), alkyl nitrites (42%, N = 147), synthetic dissociatives (41%, N = 15), and prescription opioids (40%, N = 48). CONCLUSIONS: In this European nightlife sample, ketamine was found to have the biggest increase in the past 12 months, which occurred alongside an increase in frequency of use in continuing users. The patterns of uptake and discontinuation of alkyl nitrates, novel psychoactive substances, and prescription opioids provide new information that has not been captured by existing cross-sectional surveys. These findings demonstrate the importance of longitudinal assessments of drug use and highlight the dynamic nature of the European drug landscape.

Cannabis and Mental Health: Adverse Outcomes and Self-Reported Impact of Cannabis Use by Mental Health Status.

Background: Cannabis can induce negative outcomes among consumers with mental health conditions. This study examined medical help-seeking behavior, patterns of adverse effects, and perceived impacts of cannabis among consumers with and without mental health conditions. Methods: Data came from the International Cannabis Policy Study, via online surveys conducted in 2018. Respondents included 6,413 past 12-month cannabis consumers aged 16-65, recruited from commercial panels in Canada and the US. Regression models examined differences in adverse health effects and perceived impact of cannabis among those with and without self-reported past 12-month experience of anxiety, depression, PTSD, bipolar disorder, psychosis. Results: Overall, 7% of past 12-month consumers reported seeking medical help for adverse effects of cannabis, including panic, dizziness, nausea. Help-seeking was greater for those with psychosis (13.8%: AOR = 1.78; 1.11-2.87), depression (8.9%: AOR = 1.57; 1.28-1.93), and bipolar disorder (10.1%: AOR = 1.53; 1.44-2.74). Additionally, 54.1% reported using cannabis to manage symptoms of mental health, with higher rates among those with bipolar (90.8%) and PTSD (90.7%). Consumers reporting >1 condition were more likely to perceive positive impacts on friendships, physical/mental health, family life, work, studies, quality of life (all p < .001). Consumers with psychosis were most likely to perceive negative effects across categories. Conclusion: For conditions with substantial evidence suggesting cannabis is harmful, greater help-seeking behaviors and self-perceived negative effects were observed. Consumers with mental health conditions generally perceive cannabis to have a positive impact on their lives. The relationship between cannabis and mental health is disorder specific and may include a combination of perceived benefits and harms.

Keep off the grass? Cannabis, cognition and addiction.

In an increasing number of states and countries, cannabis now stands poised to join alcohol and tobacco as a legal drug. Quantifying the relative adverse and beneficial effects of cannabis and its constituent cannabinoids should therefore be prioritized. Whereas newspaper headlines have focused on links between cannabis and psychosis, less attention has been paid to the much more common problem of cannabis addiction. Certain cognitive changes have also been attributed to cannabis use, although their causality and longevity are fiercely debated. Identifying why some individuals are more vulnerable than others to the adverse effects of cannabis is now of paramount importance to public health. Here, we review the current state of knowledge about such vulnerability factors, the variations in types of cannabis, and the relationship between these and cognition and addiction.

Psychosocial and pharmacological treatments for cannabis use disorder and mental health comorbidities: a narrative review.

Cannabis is the most widely used illicit drug worldwide, and it is estimated that up to 30% of people who use cannabis will develop a cannabis use disorder (CUD). Demand for treatment of CUD is increasing in almost every region of the world and cannabis use is highly comorbid with mental disorders, where sustained use can reduce treatment compliance and increase risk of relapse. In this narrative review, we outline evidence for psychosocial and pharmacological treatment strategies for CUD, both alone and when comorbid with psychosis, anxiety or depression. Psychosocial treatments such as cognitive behavioural therapy, motivational enhancement therapy and contingency management are currently the most effective strategy for treating CUD but are of limited benefit when comorbid with psychosis. Pharmacological treatments targeting the endocannabinoid system have the potential to reduce cannabis withdrawal and cannabis use in CUD. Mental health comorbidities including anxiety, depression and psychosis hinder effective treatment and should be addressed in treatment provision and clinical decision making to reduce the global burden of CUDs. Antipsychotic medication may decrease cannabis use and cannabis craving as well as psychotic symptoms in patients with CUD and psychosis. Targeted treatments for anxiety and depression when comorbid with CUD are feasible.

Acute effects of cannabis on speech illusions and psychotic-like symptoms: two studies testing the moderating effects of cannabidiol and adolescence.

BACKGROUND: Acute cannabis administration can produce transient psychotic-like effects in healthy individuals. However, the mechanisms through which this occurs and which factors predict vulnerability remain unclear. We investigate whether cannabis inhalation leads to psychotic-like symptoms and speech illusion; and whether cannabidiol (CBD) blunts such effects (study 1) and adolescence heightens such effects (study 2). METHODS: Two double-blind placebo-controlled studies, assessing speech illusion in a white noise task, and psychotic-like symptoms on the Psychotomimetic States Inventory (PSI). Study 1 compared effects of Cann-CBD (cannabis containing Δ-9-tetrahydrocannabinol (THC) and negligible levels of CBD) with Cann+CBD (cannabis containing THC and CBD) in 17 adults. Study 2 compared effects of Cann-CBD in 20 adolescents and 20 adults. All participants were healthy individuals who currently used cannabis. RESULTS: In study 1, relative to placebo, both Cann-CBD and Cann+CBD increased PSI scores but not speech illusion. No differences between Cann-CBD and Cann+CBD emerged. In study 2, relative to placebo, Cann-CBD increased PSI scores and incidence of speech illusion, with the odds of experiencing speech illusion 3.1 (95% CIs 1.3-7.2) times higher after Cann-CBD. No age group differences were found for speech illusion, but adults showed heightened effects on the PSI. CONCLUSIONS: Inhalation of cannabis reliably increases psychotic-like symptoms in healthy cannabis users and may increase the incidence of speech illusion. CBD did not influence psychotic-like effects of cannabis. Adolescents may be less vulnerable to acute psychotic-like effects of cannabis than adults.

Association of extent of cannabis use and psychotic like intoxication experiences in a multi-national sample of first episode psychosis patients and controls.

BACKGROUND: First episode psychosis (FEP) patients who use cannabis experience more frequent psychotic and euphoric intoxication experiences compared to controls. It is not clear whether this is consequent to patients being more vulnerable to the effects of cannabis use or to their heavier pattern of use. We aimed to determine whether extent of use predicted psychotic-like and euphoric intoxication experiences in patients and controls and whether this differs between groups. METHODS: We analysed data on patients who had ever used cannabis (n = 655) and controls who had ever used cannabis (n = 654) across 15 sites from six countries in the EU-GEI study (2010-2015). We used multiple regression to model predictors of cannabis-induced experiences and to determine if there was an interaction between caseness and extent of use. RESULTS: Caseness, frequency of cannabis use and money spent on cannabis predicted psychotic-like and euphoric experiences (p ⩽ 0.001). For psychotic-like experiences (PEs) there was a significant interaction for caseness × frequency of use (p < 0.001) and caseness × money spent on cannabis (p = 0.001) such that FEP patients had increased experiences at increased levels of use compared to controls. There was no significant interaction for euphoric experiences (p > 0.5). CONCLUSIONS: FEP patients are particularly sensitive to increased psychotic-like, but not euphoric experiences, at higher levels of cannabis use compared to controls. This suggests a specific psychotomimetic response in FEP patients related to heavy cannabis use. Clinicians should enquire regarding cannabis related PEs and advise that lower levels of cannabis use are associated with less frequent PEs.

Daily use of high-potency cannabis is associated with more positive symptoms in first-episode psychosis patients: the EU-GEI case-control study.

BACKGROUND: Daily use of high-potency cannabis has been reported to carry a high risk for developing a psychotic disorder. However, the evidence is mixed on whether any pattern of cannabis use is associated with a particular symptomatology in first-episode psychosis (FEP) patients. METHOD: We analysed data from 901 FEP patients and 1235 controls recruited across six countries, as part of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study. We used item response modelling to estimate two bifactor models, which included general and specific dimensions of psychotic symptoms in patients and psychotic experiences in controls. The associations between these dimensions and cannabis use were evaluated using linear mixed-effects models analyses. RESULTS: In patients, there was a linear relationship between the positive symptom dimension and the extent of lifetime exposure to cannabis, with daily users of high-potency cannabis having the highest score (B = 0.35; 95% CI 0.14-0.56). Moreover, negative symptoms were more common among patients who never used cannabis compared with those with any pattern of use (B = -0.22; 95% CI -0.37 to -0.07). In controls, psychotic experiences were associated with current use of cannabis but not with the extent of lifetime use. Neither patients nor controls presented differences in depressive dimension related to cannabis use. CONCLUSIONS: Our findings provide the first large-scale evidence that FEP patients with a history of daily use of high-potency cannabis present with more positive and less negative symptoms, compared with those who never used cannabis or used low-potency types.

Characterising heterogeneity in the use of different cannabis products: latent class analysis with 55 000 people who use cannabis and associations with severity of cannabis dependence.

BACKGROUND: As new cannabis products and administration methods proliferate, patterns of use are becoming increasingly heterogeneous. However, few studies have explored different profiles of cannabis use and their association with problematic use. METHODS: Latent class analysis (LCA) was used to identify subgroups of past-year cannabis users endorsing distinct patterns of use from a large international sample (n = 55 240). Past-12-months use of six different cannabis types (sinsemilla, herbal, hashish, concentrates, kief, edibles) were used as latent class indicators. Participants also reported the frequency and amount of cannabis used, whether they had ever received a mental health disorder diagnosis and their cannabis dependence severity via the Severity of Dependence Scale (SDS). RESULTS: LCA identified seven distinct classes of cannabis use, characterised by high probabilities of using: sinsemilla & herbal (30.3% of the sample); sinsemilla, herbal & hashish (20.4%); herbal (18.4%); hashish & herbal (18.8%); all types (5.7%); edibles & herbal (4.6%) and concentrates & sinsemilla (1.7%). Relative to the herbal class, classes characterised by sinsemilla and/or hashish use had increased dependence severity. By contrast, the classes characterised by concentrates use did not show strong associations with cannabis dependence but reported greater rates of ever receiving a mental health disorder diagnosis. CONCLUSIONS: The identification of these distinct classes underscores heterogeneity among cannabis use behaviours and provides novel insight into their different associations with addiction and mental health.

Acute effects of cannabinoids on addiction endophenotypes are moderated by genes encoding the CB1 receptor and FAAH enzyme.

Understanding genetic factors that contribute to cannabis use disorder (CUD) is important, but to date, findings have been equivocal. Single-nucleotide polymorphisms (SNPs) in the cannabinoid receptor 1 gene (CNR1; rs1049353 and rs806378) and fatty acid amide hydrolase (FAAH) gene (rs324420) have been implicated in CUD. Their relationship to addiction endophenotypes such as cannabis-related state satiety, the salience of appetitive cues, and craving after acute cannabinoid administration has not been investigated. Forty-eight cannabis users participated in a double-blind, placebo-controlled, four-way crossover experiment where they were administered treatments in a randomized order via vaporization: placebo, Δ9 -tetrahydrocannabinol (THC) (8 mg), THC + cannabidiol (THC + CBD) (8 + 16 mg), and CBD (16 mg). Cannabis-related state satiety, appetitive cue salience (cannabis and food), and cannabis craving were assessed each day. Participants were genotyped for rs1049353, rs806378, and rs324420. Results indicated that CNR1 rs1049353 GG carriers showed increased state satiety after THC/THC + CBD administration in comparison with placebo and reduced the salience of appetitive cues after THC in comparison with CBD administration; A carriers did not vary on either of these measures indicative of a vulnerability to CUD. CNR1 rs806378 CC carriers showed greater salience to appetitive cues in comparison with T carriers, but there was no evidence for changes in state satiety. FAAH rs324420 A carriers showed greater bias to appetitive cues after THC, in comparison with CC carriers. FAAH CC carriers showed reduced bias after THC in comparison with CBD. No SNPs modulated craving. These findings identify candidate neurocognitive mechanisms through which endocannabinoid system genetics may influence vulnerability to CUD.

Value-based decision-making of cigarette and nondrug rewards in dependent and occasional cigarette smokers: An FMRI study.

Little is known about the neural functioning that underpins drug valuation and choice in addiction, including nicotine dependence. Following ad libitum smoking, 19 dependent smokers (smoked≥10/day) and 19 occasional smokers (smoked 0.5-5/week) completed a decision-making task. First, participants stated how much they were willing-to-pay for various amounts of cigarettes and shop vouchers. Second, during functional magnetic resonance imaging, participants decided if they wanted to buy these cigarettes and vouchers for a set amount of money. We examined decision-making behaviour and brain activity when faced with cigarette and voucher decisions, purchasing (vs not purchasing) cigarettes and vouchers, and "value signals" where brain activity correlated with cigarette and voucher value. Dependent smokers had a higher willingness-to-pay for cigarettes and greater activity in the bilateral middle temporal gyrus when faced with cigarette decisions than occasional smokers. Across both groups, the decision to buy cigarettes was associated with activity in the left paracingulate gyrus, right nucleus accumbens, and left amygdala. The decision to buy vouchers was associated with activity in the left superior frontal gyrus, but dependent smokers showed weaker activity in the left posterior cingulate gyrus than occasional smokers. Across both groups, cigarette value signals were observed in the left striatum and ventromedial prefrontal cortex. To summarise, nicotine dependence was associated with greater behavioural valuation of cigarettes and brain activity during cigarette decisions. When purchasing cigarettes and vouchers, reward and decision-related brain regions were activated in both groups. For the first time, we identified value signals for cigarettes in the brain.