Cannabis Experiences Questionnaire Research Articles

Overshadowing and salience attribution in relation to cannabis use

Aberrant attentional salience has been implicated in the cannabis-psychosis association. Here, history and frequency of cannabis use were examined against changes in overshadowing (OS), a cue competition paradigm that involves salience processing. Additionally, we examined the association between OS and alternative measures of aberrant salience, as well as schizotypy, in a non-clinical adult sample.280 participants completed an online geometry learning-based OS task, while a subset (N = 149) also completed the Salience Attribution Task (SAT) measure of aberrant salience. All completed the Schizotypal Personality Questionnaire (SPQ), Aberrant Salience Inventory (ASI), and the modified Cannabis Experience Questionnaire (CEQmv). Differences across OS and SAT performance stages and between cannabis use groups were assessed using mixed ANOVAs. Multiple regression and correlational analyses assessed the relationships between OS and SAT task metrics and SPQ and ASI subscale scores.Current cannabis users had significantly lower OS scores during the testing phase relative to those who do not use cannabis, at medium effect sizes. Schizotypy or ASI scores did not mediate this relationship. In the SAT, current cannabis users presented significantly higher implicit aberrant salience relative to non-users. Scores in the first training phase of the OS task significantly predicted higher explicit aberrant and adaptive salience scores in the SAT.These data indicate an association between regular cannabis use and abnormalities in cue competition effects in a healthy adult sample. Comparisons of OS and SAT cast new light on putative overlapping mechanisms underlying performance across different measures of salience.

The role of cannabis and salience alterations in determining the severity of psychotic symptoms: a multi-centric, cross-sectional study on adolescent and adult cohorts

IntroductionThe aim of this project is to study to which extent salience alterations influence the severity of psychotic symptoms. However, rather than studying them individually, we decided to focus on their interplay with two additional variables, that is: observing their effect in a vulnerability phase (adolescence) and with another added, well-recognized risk factor (cannabis use).The reason for this study design lies in the fact that, in our opinion, it is fundamental to observe the trajectory of psychotic symptoms over a continuum; however, rather than adopting a longitudinal approach, we decided to structure it as a cross-sectional study confronting patients from two age brackets - adolescence and adulthood.ObjectivesThe primary purpose of this study was to assess a difference between THC-abusing and non-abusing patients in adolescent and adult cohorts, using the Italian version of the psychometric scale “Aberrant Salience Inventory” (ASI), and the possible correlation with more severe psychotic symptoms. The employment of several different psychometric scales and the inclusion of a variegated cohort allowed to pursue multiple secondary objectives.MethodsWe recruited 192 patients, subsequently divided into six subgroups based on age and department of recruitment (whether adolescent or adult psychiatric or neurologic units - the latter serving as controls). Each individual was administered a set of questionnaires and a socio-demographic survey; the set included: Aberrant Salience Inventory (ASI), Community Assessment of Psychic Experiences (CAPE), Positive and Negative Syndrome Scale (PANSS), Montgomery-Asberg Depression Rating Scale (MADRS), Mania Rating Scale (MRS), Hamilton Anxiety Scale (HAM-A), Association for Methodology and Documentation in Psychiatry (AMDP) and Cannabis Experience Questionnaire (CEQ).ResultsThe data analysis showed statistically significant (p<0.05) differences between adolescents and adults with psychotic symptoms in all of the three scales of PANSS and in MADRS. These two groups were homogenous for both cannabis use and ASI score. The intra-group comparison (either adolescent or adult) showed a hierarchical pattern in the scores of psychometric scales according to the diagnostic subgroup of allocation: patients with psychotic symptoms showed an higher level of psychopathology in all measures when compared to patients from the psychiatric unit without psychotic symptoms, which in turn scored higher than the patients from the neurologic unit.Image:ConclusionsThe results of the present study may suggest that when salience alterations occur in adolescents with cannabis exposure, we might observe worsened positive and negative psychotic symptoms; their influence might be relevant also in other domains, especially regarding the depressive and anxiety spectrums.Disclosure of InterestNone Declared

Spanish versions and validation of a series of rating scales and visual analogue scales to assess the subjective effects of cannabis

Cannabis is being legalized for medical and recreational purposes all around the world. However, the understanding of the psychological effects of cannabis is still limited, and it has been previously linked to mental disorders such as schizophrenia. Lately, new scales have been created and adapted to measure its psychological effects. The aim of this study is to create Spanish versions of some of these scales and test their psychometric characteristics. One hundred sixteen participants were recruited from Cannabis Social Clubs (CSC) in Barcelona, Spain. Participants under the effects of their own cannabis completed the Cannabis Experience Questionnaire–modified version (CEQ-mv), Addiction Research Centre Inventory-18 (ARCI-18), Psychotomimetic States Inventory (PSI) and Visual Analogue Scales (VAS). Questionnaires were completed in the CSC, providing a naturalistic setting for the study. Exploratory factor analysis and internal consistency were analyzed. PSI was reduced from a 6-factor to a 4-factor model with adequate to low reliability, ARCI-18 was reduced from a 3-factor to a 2-factor model with good reliability, and VAS were reduced from a 4-factor to a 3-factor model, also with good reliability. These questionnaires showed adequate reliability and can be used in future studies to test the subjective effects of cannabis in clinical and naturalistic settings.

Influence of cannabis use on incidence of psychosis in people at clinical high risk.

Evidence for case-control studies suggests that cannabis use is a risk factor for the development of psychosis. However, there have been limited prospective studies and the direction of this association remains controversial. The primary aim of the present study was to examine the association between cannabis use and the incidence of psychotic disorders in people at clinical high risk of psychosis. Secondary aims were to assess associations between cannabis use and the persistence of psychotic symptoms, and with functional outcome. Current and previous cannabis use were assessed in individuals at clinical high risk of psychosis (n = 334) and healthy controls (n = 67), using a modified version of the Cannabis Experience Questionnaire. Participants were assessed at baseline and followed up for 2 years. Transition to psychosis and persistence of psychotic symptoms were assessed using the Comprehensive Assessment of At-Risk Mental States criteria. Level of functioning at follow up was assessed using the Global Assessment of Functioning disability scale. During follow up, 16.2% of the clinical high-risk sample developed psychosis. Of those who did not become psychotic, 51.4% had persistent symptoms and 48.6% were in remission. There was no significant association between any measure of cannabis use at baseline and either transition to psychosis, the persistence of symptoms, or functional outcome. These findings contrast with epidemiological data that suggest that cannabis use increases the risk of psychotic disorder.

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

AbstractBackgroundChildhood 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.MethodsData 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.ResultsThe 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.ConclusionsHarmful 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.

Effect of D2R, NMDAR and CB1R genetic variants associated with cannabis use and childhood trauma in first-episode psychosis in a Brazilian population

IntroductionGene-environment interactions increase psychosis risk (Gayer-Anderson et al. Soc Psychiatry Psychiatr Epidemiol 2020; 55(5):645-657). However, identifying the genetic variants involved and how they interact with environmental risk factors underlying psychosis remains challenging.ObjectivesTo investigate whether there are gene-environment interactions in the relationships of childhood trauma, lifetime cannabis use, and single nucleotide variants (SNVs) of dopamine D2 receptor (D2R: DRD2), N-methyl-d-aspartate receptor (NMDAR: GRIN1, GRIN2A and GRIN2B) and cannabinoid receptor type 1 (CB1R: CNR1) with psychosis.MethodsIn a population-based case-control study nested in an incident study (STREAM, Brazil) (Del-Ben et al. Br J of Psychiatry 2019; 215(6):726-729), part of the EU-GEI consortium (Gayer-Anderson et al. Soc Psychiatry Psychiatr Epidemiol 2020; 55(5):645-657), 143 first-episode psychosis patients and 286 community-based controls of both sexes aged between 16 and 64 years were included over a period of 3 years. Twenty-three SNVs of D2R (rs1799978, rs7131056, rs6275), NMDAR (GRIN1: rs4880213, rs11146020; GRIN2A: rs1420040, rs11866328; GRIN2B: rs890, rs2098469, rs7298664), and CB1R genes (CNR1: rs806380, rs806379, rs1049353, rs6454674, rs1535255, rs2023239, rs12720071, rs6928499, rs806374, rs7766029, rs806378, rs10485170, rs9450898), were genotyped from peripheral blood DNA using a custom Illumina HumanCoreExome-24 BeadChip. Environmental adversities were evaluated using the Cannabis Experience Questionnaire (Di Forti et al. The Lancet Psychiatry 2009; 6(5):427–436) and the Childhood Trauma Questionnaire (Grassi-Oliveira et al. Rev Saude Publica 2006; 40(2):249-55). Associations between SNVs and environmental risk factors were performed using the nonparametric multifactor dimensionality reduction software (version 3.0.2).ResultsSingle locus analysis showed no association among the 23 SNVs with psychosis; however, gene-environment analysis was significant for the polymorphic loci rs12720071 and rs7766029 in CNR1. The best association models were the two-factor representing by the combination of CNR1 rs12720071 with lifetime cannabis use (p<0.001), and CNR1 rs12720071 with childhood trauma (p<0.05), both suggesting an increased risk of psychosis. Additionally, when considering the interaction of both environmental factors in the same model, we found CNR1 rs7766029 to be associated with psychosis (p<0.001).ConclusionsOur study supports the hypothesis of gene-environment interactions for psychosis involving the T allele carriers of CNR1 SNVs (rs12720071 and rs7766029), childhood trauma and lifetime cannabis use in psychosis.Disclosure of InterestNone Declared

Development and initial validation of a reliable German self-report measure to assess acute cannabis intoxication-effects (CanTox-17).

ObjectivesBoth positive and negative including psychotic‐like cannabis intoxication effects are well‐established. Yet, consequences for consumption patterns, addictive behavior or psychotic developments are poorly researched in general, in Germany not at all. Thus, objective was to develop the first German‐language questionnaire operationalizing acute cannabis intoxication effects, based on the original “Cannabis Experience Questionnaire” (CEQ).MethodsAfter expert translation of the CEQ, items related to acute intoxication effects were presented to a sample of 537 cannabis users. Four‐ and five‐factorial solutions of explorative factor analysis with a randomly split sub‐sample 1 were cross‐validated by confirmatory factor analysis on sub‐sample 2.ResultsAfter content review of factors and analysis of external validity, a 17 item four‐factorial model was approved. Factors are (1) “paranoia/dysphoria”, (2) “confusion/disorientation”, (3) “euphoria/creativity”, (4) “psychosis‐like/loss of reality”. Model fit is satisfactory (RMSEA = 0.058, SRMR = 0.065, CFI = 0.929, TLI = 0.914). Correlations with corresponding external measures support construct validity.ConclusionsThe present questionnaire is a time‐efficient, valid and reliable instrument. Thus, predictors of different cannabis intoxication effects can be analysed for the first time in German‐speaking area, as well as their significance for substance use or psychosis risk.

Immune regulatory gene polymorphisms, frequent cannabis use, and psychosis: implications to Treg hypofunction

IntroductionWe have previously shown that the association between frequent cannabis use and psychosis is more likely in subgroups with low-grade inflammation than subgroups without (PMID: 33736715). The role of immune-related polymorphisms remains unknown.ObjectivesTo explore whether polymorphisms affecting the function of key immune regulatory proteins moderate the association between cannabis and psychosis, namely: ENTPD1 and NT5E, involved in the synthesis of CD39, CD73, respectively, and anti-inflammatory adenosine; CTLA4 and FOXP1, essential for Treg functional capacity.MethodsWe genotyped blood samples from 283 community-based controls and 140 recent-onset psychosis patients in Brazil (EU-GEI consortium, Ribeirão Preto/SP) for twelve polymorphisms (ENTPD1: rs3814159, rs3176891, rs10748643; NT5E: rs9444348, rs2295890; CTLA4: rs3087243, rs231775, rs5742909, rs4553808; FOXP1: rs6803008, rs6786408, rs830599; Illumina Human Core Exome-24). Cannabis frequency (daily, less than daily, never) was assessed by self-report (Cannabis Experience Questionnaire). Binary logistic regression models (OR,95%CI) included case status as the outcome, genotype (dominant model), cannabis frequency, and an interaction term between the two as exposure, adjusting for confounders (age, sex, ethnicity, tobacco smoking).ResultsWe found significant interactions between cannabis use and polymorphisms for ENTPD1 (rs3814159), NT5E (rs9444348), and FOXP1 (rs6786408). Less than daily or daily use were, in a dose-response fashion, only associated with psychosis in those with the variant and heterozygous genotypes; less than daily: ENTPD1 AG/GG (3.34,1.71-6.50); NT5E AG/AA (3.71,1.87-7.33); FOXP1 AC/CC (2.98,1.54-5.77); daily: ENTPD1 AG/GG (16.81;5.89-47.96); NT5E AG/AA (21.20,6.81-66.01); FOXP1 AC/CC (13.75,5.22-36.21).ConclusionsVariation in genes that affect Treg function appears to modify the effect of cannabis consumption on psychosis in keeping with Treg hypofunction hypothesis (PMID:33713699).DisclosureNo significant relationships.

Latent inhibition, aberrant salience, and schizotypy traits in cannabis users

Aberrant salience processing may underlie the link between cannabis and psychosis, as posited in individuals with schizophrenia or high schizotypy. We investigated the relative effects of cannabis use, schizotypy status, and self-reported aberrant salience experiences on salience processing, measured using a latent inhibition (LI) task (Granger et al., 2016), in a non-clinical population.A university sample of 346 participants completed the Schizotypal Personality Questionnaire (SPQ), Aberrant Salience Inventory (ASI) the modified Cannabis Experience Questionnaire (CEQmv) and the LI task. Regression models and parallel (Bayesian and frequentist) t-tests or ANOVA (or non-parametric equivalents) examined differences in LI based on lifetime or current cannabis use (frequent use during previous year), as well as frequency of use. Mann-Whitney U tests assessed differences in SPQ and ASI scores based on current cannabis use.Neither lifetime nor current cannabis use was associated with significant change in LI scores. Current cannabis use was associated with both higher ‘Disorganised’ and ‘Cognitive-perceptual’ SPQ dimension scores and higher total and sub-scale ASI scores. No association was observed between LI score and SPQ total and dimension scores. Higher scores on ‘Senses sharpening’ and the ‘Heightened cognition’ ASI subscales predicted decreased LI scores. These data support previous findings of no association between cannabis use and abnormality in other associative learning tasks in young non-clinical populations, and elaborate the previously demonstrated association between self-reported cannabis use, schizotypy and aberrant salience. The association between dimensions of ASI and LI performance suggests this task may have potential as an experimental measure of aberrant salience.

Tobacco and Alcohol and Cannabis Experience Questionnaires. Greek translation and test-retest reliability.

The Tobacco and Alcohol Questionnaire (TAQ) and the Cannabis Experience Questionnaire (CEQ) are two instruments employed in the evaluation of substance use. The First Episode Psychosis (FEP) study in Athens employed two versions of those questionnaires, as part of a battery of psychometric tools, detecting environmental and genetic factors associated with FEP and addressed specifically to the distinctive characteristics of patients with FEP. The goal of the present study is to present those two versions, regarding their content, their use in international research, their translation in Greek, and their test-retest reliability. The two questionnaires were translated by two independent translators and administered to 32 subjects with FEP twice, in order to be tested for test-retest reliability. Cohen's kappa was used to measure agreement between qualitative variables and ICC between quantitative variables. Significant agreement was found between the two measurements in all items of the TAQ version and almost all items of the CEQ version. Our study is an indication that both translations are reliable, although a more thorough test of their psychometric properties is needed. Both might be used in the Greek research field as part of a broad package of psychometric tools, specifically addressed to patients with FEP.

Cannabis Use, Schizotypy and Kamin Blocking Performance

Cannabis use has been associated with increased risk for a first episode of psychosis and inappropriate assignment of salience to extraneous stimuli has been proposed as a mechanism underlying this association. Psychosis-prone (especially schizotypal) personality traits are associated with deficits in associative learning tasks that measure salience allocation. The aim of this study was to examine the relationship between history of cannabis use and Kamin blocking (KB), a form of selective associative learning, in a non-clinical sample. Additionally, KB was examined in relation to self-reported schizotypy and aberrant salience scale profiles. A cross-sectional study was conducted in 307 healthy participants with no previous psychiatric or neurological history. Participants were recruited and tested using the Testable Minds behavioural testing platform. KB was calculated using Oades' “mouse in the house task”, performance of which is disrupted in schizophrenia patients. Schizotypy was measured using the Schizotypal Personality Questionnaire (SPQ), and the Aberrant Salience Inventory (ASI) was used to assess self-reported unusual or inappropriate salience. The modified Cannabis Experience Questionnaire (CEQm) was used to collect detailed history of use of cannabis and other recreational drugs. Regression models and Bayesian t-tests or ANOVA (or non-parametric equivalents) examined differences in KB based on lifetime or current cannabis use (frequent use during previous year), as well as frequency of use among those who had previously used cannabis. Neither lifetime nor current cannabis use was associated with any significant change in total or trial-specific KB scores. Current cannabis use was associated with higher Disorganised SPQ dimension scores and higher total and sub-scale values for the ASI. A modest positive association was observed between total KB score and Disorganised SPQ dimension scores, but no relationships were found between KB and other SPQ measures. Higher scores on “Senses Sharpening” ASI sub-scale predicted decreased KB score only in participants who have not engaged in recent cannabis use. These results are discussed in the context of our understanding of the effects of long-term cannabis exposure on salience attribution, as well as inconsistencies in the literature with respect to both the relationship between KB and schizotypy and the measurement of KB associative learning phenomena.

Are researchers getting the terms used to denote different types of recreational cannabis right?\u2014a user perspective

BackgroundWhile current cannabis research has advanced our understanding into the effects of its individual components, there is a pressing need to identify simple terminology that is understood in the same way by researchers and users of cannabis. Current categorisation in research focuses on the two main cannabinoids: delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD); and two different species of cannabis: indica and sativa. Recreational cannabis has also been categorised by researchers as ‘skunk’ or ‘hash’. Focusing on individuals who use cannabis frequently, this study aimed to identify views on current terms used to denote different types of cannabis and to identify terms validated by participants. These views were extracted from responses of the Cannabis Experiences Questionnaire (CEQ), a widely used instrument in the literature.MethodsWe qualitatively analysed 236 free-text responses from Question 23 of the CEQ survey (using Iterative Categorisation) relating to categorization and consumption methods. Data was used from a previous study (Sami et al., Psychol Med 49:103–12, 2019), which recruited a convenience sample of 1231 participants aged 18 years and above who had previously used cannabis.ResultsRegarding type of cannabis used, specific strain names (n = 130), concentrates (n = 37), indica/sativa (n = 22) and THC/CBD terms (n = 22) were mentioned. Other terms used were hybrids (n = 10), origins of specific strains (n = 17), edibles (n = 8), and herbal cannabis (n = 7). Regarding problems with specific terms, participants were skeptical about terms such as skunk and super skunk (n = 78) preferring terms like THC/CBD, indica/sativa, specific marketed strains and references to preparation methods.ConclusionsThe results suggest a disparity between the common terms used by researchers in academia and those used by cannabis consumers. While there are advantages and limitations of using these terms to bridge views of researchers and individuals who use cannabis, this study underscores the importance of formally assessing chemical constituents rather than relying on self-report data and of incorporating cannabis user views on current terms used in research, potentially also incorporating descriptors of preparation and consumption methods.

The independent and combined effects of cannabis use and systemic inflammation during the early stages of psychosis: exploring the two-hit hypothesis.

Cannabis consumption is a modifiable risk factor associated with psychosis, but not all cannabis users develop psychosis. Animal studies suggest that an antecedent active immune system interacts with subsequent cannabis exposure and moderates the cannabis-psychosis association, supporting the two-hit hypothesis. The clinical investigations are few, and it is unclear if the immune system is a biological candidate moderating the cannabis-psychosis association or whether cannabis increases inflammation, which in turn, augments psychosis likelihood. We explored the mediating and moderating role of blood inflammation using PROCESS macro. We used data from a cross-sectional study, including 153 first-episode psychosis patients and 256 community-based controls. Participants answered the Cannabis Experience Questionnaire (cannabis frequency, age of onset, and duration), and plasma cytokines were measured [interleukin (IL)-1β, IL-6, IL-4, IL-10, tumour necrosis factor-α (TNF-α), interferon-γ (IFN-γ), transforming growth factor-β (TGF-β); multiplex]. We computed an inflammatory composite score (ICS) to represent the systemic inflammatory state. Confounders included sex, age, ethnicity, educational level, body mass index, tobacco smoking, lifetime use of other drugs, and antipsychotic treatment. Mediation: Cannabis consumption was not associated with increased inflammation, thus not supporting a mediating effect of inflammation. Moderation: Daily use and age of onset <17 interacted significantly with the ICS to increase the odds of psychosis beyond their individual effects and were only associated with psychosis among those scoring medium-high in the ICS. Immune dysregulation might be part of the pathophysiology of psychosis, not explained by cannabis use or other confounders. We provide the first and initial evidence that immune dysregulation modifies the cannabis-psychosis association, in line with a two-hit hypothesis.

S118. TRANSDIAGNOSTIC SYMPTOM DIMENSIONS OF PSYCHOSIS AND THE PREDICTIVE ROLE OF PREMORBID ADJUSTMENT AND COGNITIVE CHARACTERISTICS IN THE MULTINATIONAL EU-GEI STUDY

BackgroundA symptom dimension approach may best examine the heterogeneous expression of psychosis. However, whether and how premorbid predisposition and cognitive factors explain phenotypes variation is still debated. This study aimed to test the predictive value of combined cognition and premorbid adjustment on transdiagnostic symptom dimensions in a large sample of people suffering from the first episode of psychosis (FEP).MethodsFEP patients were part of the EUGEI study. Psychopathology was rated using the OPerational CRITeria system. Multidimensional item response modelling estimate a bifactor model of psychosis by Mplus, composed of a general factor and five specific symptom dimensions. WAIS-brief version measured IQ, and Premorbid Adjustment Scale estimated premorbid social (SF) and academic adjustment (AF). We set a multivariate analysis of the covariance having symptom-dimensions as the output and SF, AF, and IQ as the main predictors, adjusted by age, gender, country, and ethnicity. Since lifetime frequency of cannabis use related to both premorbid and cognitive characteristics, and symptom dimensions, it was added as an independent predictor, collected by the Cannabis Experience Questionnaire. Sensitivity analyses were run with IQ subtests.ResultsThe sample included 785 FEP patients [61.2% (N=481) males; Mean age=33.8 (12.3)]. IQ [Pillai=0.019, F(6, 765)=2.52; p=0.020] and SF [Pillai=0.032, F(6, 765)=4.26; p<0.001] had a discriminant effect on the bifactor model as a whole, whereas AF did not [Pillai=0.007, F(6, 765)=0.93; p=0.468]. Cannabis use had a marginally effect [Pillai=0.027, F(12, 1532)=1.76; p=0.049].Positive symptoms were slightly predicted by a lower IQ (B=-0.005, 95% C.I. -0.01, 0.0, p=0.038) and sensitivity analysis revealed the role of a worse processing speed (B=-0.04, 95% C.I. -0.07, -0.01, p=0.003) and working memory (B=-0.02, 95% C.I. -0.05, -0.04, p=0.013) abilities in this relationship. Negative symptoms were higher in subjects with a worse SF (B=-0.12, 95% C.I. -0.18, -0.06, p<0.001) and a lower IQ (B=-0.005, 95% C.I. -0.01, -0.001, p=0.014), due to a lower perceptual reasoning (B=-0.02, 95% C.I. 0.04, 0.003, p=0.023). On the opposite, manic symptoms were more present if patients had better SF (B=0.07, 95% C.I. 0.01, 0.14, p=0.023) and IQ (B=0.005, 95% C.I. 0.0, 0.009, p=0.030), particularly, a higher perceptual reasoning (B=0.02, 95% C.I. 0.04, 0.008, p=0.014). Lower SF predicted depressive symptoms (B=-0.09, 95% C.I. -0.15, -0.03, p=0.032). The model was not predictive of general and disorganization symptoms. Cannabis use had an effect on positive symptoms (F(2, 770)=4.9, p=0.011); that means, patients who smoked cannabis everyday had higher positive symptoms than occasional (M_difference=0.27, 95% C.I. 0.01, 0.52, p=0.034) and never-users (M_difference=0.25, 95% C.I. 0.02, 0.48, p=0.021).DiscussionThe opposed relationship between premorbid sociability and an IQ, particularly its “hold” perceptual-reasoning sub-test – linked to an early coherent self-construction – with manic and negative symptoms, suggests divergent neurodevelopmental trajectories among patients endorsing these different phenotypes. On the other hand, the specific predictive value for positive symptoms of lower processing speed and working memory – well-recognised cognitive markers in psychosis – implies an encoding problem. Worse premorbid sociability but not low general cognition predicted depressive symptoms, thus suggesting a difference between mood downregulation and flat affect, often unrecognised. The cannabis-effect on positive symptoms was expected; this analysis suggests its possible interaction with cognitive characteristics, which deserves further attention.

O9.3. CANNABIS CONSUMPTION INCREASES RISK OF PSYCHOSIS IN A SUBGROUP OF PATIENTS WITH HIGH PERIPHERAL BLOOD INFLAMMATION

BackgroundAssociations between cannabis use and psychotic outcomes are consistently reported. Increased innate immune markers have also been suggested as risk factors for psychosis; nevertheless, no study has ever tested whether augmented blood inflammation could be a possible biological mechanism underlying the association between cannabis use and psychosis. We investigated: i) which patterns of peripheral blood cytokines (innate and adaptive immune markers) would be associated with the strongest effect on odds of psychosis; and ii) whether the contribution of cannabis use (lifetime use: yes/no; frequency of use: non-users, less than daily use; daily use) on risk of psychosis would vary between subgroups with low- or high-inflammation.MethodsThe Schizophrenia and Other Psychoses Translational Research: Environment and Molecular Biology (STREAM) is an epidemiological and case-sibling-control study, conducted in Ribeirão Preto catchment area (São Paulo, Brazil) between April 2012 and March 2015, which integrates the international multicentre consortium EU-GEI. We recruited 153 first-episode psychosis patients and 256 community-based controls aged between 16–64 years. Participants answered the Cannabis Experience Questionnaire and plasma cytokines (IL-1β, IL-6, TNF-α, IFN-γ, IL-4, IL-10, TGF-β) were measured by Multiplex. We firstly investigated which patterns of peripheral blood innate and adaptive immune markers would contribute to the strongest effect on the odds of psychosis. To do that, the sample was divided into quartiles according to cytokine’s percentile distribution (reference group: minimum value – 25th percentile; lower group: 25th – 50th percentile; middle group: 50th – 75th percentile; and upper group: 75th percentile – maximum value). We next investigated whether the effects of the different patterns of cannabis use (lifetime and frequency of use) on the risk of psychosis would differ between subgroups classified as low- or high-inflammatory, using the median (50th percentile) of each cytokine as the cut-off value. All the binary logistic regression analyses were correct for the effects of confounders (gender, age, ethnicity, years of education, body mass index, tobacco smoking, and recreational drugs).ResultsMore than 60% of the patients were classified as high-inflammatory, whereas in the control group, around the same percentage was classified as low-inflammatory. After adjusting for confounders, we observed a dose-response relationship between the percentile’s distribution of IL-10, IL-6, TNF-α, TGF-β and risk of psychosis, with participants classified in the upper percentile having the highest odds ratio when compared with the reference group. The adjusted odds ratio (adj ORs) and 95% CIs range for each cytokine were the following: IL-10 from 4.68 (2.02–10.85) to 11.86 (5.01–28.11), IL-6 from 3.74 (1.61–8.69) to 9.62 (4.15–22.31); TNF-α from 2.18 (1.01–4.73) to 6.88 (3.12–15.17); TGF-β from 2.17 (1.01–4.67) to 3.20 (1.50–6.80). Lifetime cannabis use only increased risk of psychosis in the high-inflammatory subgroup (adj ORs, 95% CIs: IL10: 4.66, 1.62–13.39; IL-6: 2.75, 1.05–7.21). Daily use increased the risk of psychosis even further, and only in the high-inflammatory but not in the low-inflammatory subgroup (adj OR, 95% CIs: IL-10: 14.09, 2.26–87.93; TNF-α: 6.16, 1.28–29.74; IL-6: 4.68, 1.08–20.36), with the exception of TGF-β, for which the effects were seen in the low-subgroup (adj OR, 95% CI: 5.23, 1.17–23.42).DiscussionThe existence of distinct inflammatory profiles indicates possible biological predisposition facilitating immune activation. This would translate into a higher vulnerability to the effects of cannabis use, especially daily use, on risk of psychosis.

S92. REASONS TO START SMOKING CANNABIS: A CASE CONTROL-ANALYSIS FROM THE EUGEI STUDY

BackgroundStudies have shown that cannabis can increase the risk of psychosis from 1.7 to 3.9 times. Both frequency and potency seem to contribute to differences in the incidence of psychosis across Europe. Despite this evidence, sceptics argue that that the association between cannabis use and psychotic disorders could be explained by: (a) subjects who start experiencing psychosis use cannabis as a form of self-medication; (b) the co-morbid effect of other psychotogenic drugs (e.g., amphetamines); or (c) there is a common genetic vulnerability between cannabis use and psychosis. Thus, we aim to analyse: 1) reported reasons to start using cannabis, 2) if these predict differences in patterns of use (frequency and potency), 3) the association of both reasons to start and pattern of use with PRS for Schizophrenia, as it can explain whether patients with a higher genetic burden also start smoking cannabis after experiencing a higher psychological discomfort.MethodsUsing data from the multicentric EUGEI First-Episode Psychosis (FEP) case-control study we examined differences in reasons to start using cannabis between cases and controls. Data were obtained from the Cannabis Experiences Questionnaire modified version. Logistic regression models were used to test if reason to start predicted different patterns of use. Finally, we used regression to test if Polygenic risk scores for schizophrenia (SZ PRS) explained variance in reasons to start.ResultsUp to 85% of controls compared to 68% of FEP started using cannabis because either friends or family were using it. Instead, 18% of cases started using cannabis to feel better compared 5% of controls, reporting the 13.4% of cases and 10.3% of controls having start due to “other reasons”. Regression models showed that being a case was positively associated with starting use in order to feel better (RRR 4.67, z=7.58, p<0.001), remaining significant after adjusting for gender, age, ethnicity or site. We did not find evidence of an association between start using cannabis “to feel better” and potency nor in cases or controls. We found an association for both cases and controls between those who started smoking to feel better and the frequency of use following a gradient from “more than once a week” to “daily”. Using cannabis “to feel better” was associated with a 4 times increase in the risk (RRR=4.45 95% CI 1.85 – 10.72) of using it daily in controls and 3 times increase (RRR= 3.11 95% CI 1.81 – 5.35) in FEP. Multinomial regression showed that reasons to start did not change according to Schizophrenia PRS, with those starting because a family member was using cannabis (RRR =1 95% CI 0.38 – 2.62) and those starting to feel better (RRR = 1.05 95% CI 0.47 – 2.33) not being at higher polygenic risk compared with those starting because their friends were using cannabis.DiscussionThese preliminary findings show that a higher proportion of patients with psychosis than controls start using cannabis as a way to make them feel better, although they are a minority. Furthermore, both cases and controls that started smoking “to feel better” presented higher chances to start smoking more frequently. Lastly, PRS did not predict the reasons to start smoking cannabis.

Does cannabis use predict psychometric schizotypy via aberrant salience?

Cannabis can induce acute psychotic symptoms in healthy individuals and exacerbate pre-existing psychotic symptoms in patients with schizophrenia. Inappropriate salience allocation is hypothesised to be central to the association between dopamine dysregulation and psychotic symptoms. This study examined whether cannabis use is associated with self-reported salience dysfunction and schizotypal symptoms in a non-clinical population. 910 University students completed the following questionnaire battery: the cannabis experience questionnaire modified version (CEQmv); schizotypal personality questionnaire (SPQ); community assessment of psychic experience (CAPE); aberrant salience inventory (ASI). Mediation analysis was used to test whether aberrant salience mediated the relationship between cannabis use and schizotypal traits. Both frequent cannabis consumption during the previous year and ASI score predicted variation across selected positive and disorganised SPQ subscales. However, for the SPQ subscales ‘ideas of reference’ and ‘odd beliefs’, mediation analysis revealed that with the addition of ASI score as a mediating variable, current cannabis use no longer predicted scores on these subscales. Similarly, cannabis use frequency predicted higher total SPQ as well as specific Positive and Disorganised subscale scores, but ASI score as a mediating variable removed the significant predictive relationship between frequent cannabis use and ‘odd beliefs’, ‘ideas of reference’, ‘unusual perceptual experiences’, ‘odd speech’, and total SPQ scores. In summary, cannabis use was associated with increased psychometric schizotypy and aberrant salience. Using self-report measures in a non-clinical population, the cannabis-related increase in selected positive and disorganised SPQ subscale scores was shown to be, at least in part, mediated by disturbance in salience processing mechanisms.

F100. FACTOR STRUCTURE OF THE CANNABIS EXPERIENCES QUESTIONNAIRE IN A FIRST-EPISODE PSYCHOSIS SAMPLE

BackgroundThe Cannabis Experiences Questionnaire (CEQ) was developed to measure the subjective experiences of cannabis use both during and after intoxication. Despite the need to better understand the nature of the complex and significant relationship between cannabis use and early psychosis, this questionnaire has rarely been used in individuals with first-episode psychosis.MethodsWe conducted a set of factor analyses using CEQ data from 194 first-episode psychosis patients who used cannabis, in order to uncover the underlying factor structure of the questionnaire and thus the overarching types of psychological experiences during/after using cannabis in young people with psychotic disorders.ResultsConfirmatory factor analyses were performed on the 2 full-scale CEQ factor structures identified in the literature and neither model fit the data within acceptable levels. Using all 56 CEQ items, an exploratory factor analysis (EFA) model was fit with an oblique rotation. Models with 3, 4, and 5 factors were further explored to identify underlying factors. The final 4-factor EFA model provided the best fit. It included 47 items (3 items had multiple loadings and 6 items did not load on any factor), with names given, based on item composition, as follows: Factor 1 (Distortions of Reality and Self-Perception) included 18 items (α = 0.89), Factor 2 (Euphoria Effects) included 16 items (α = 0.89), Factor 3 (Slowing and Amotivational Effects) included 7 items (α = 0.81), and Factor 4 (Anxiety and Paranoia Effects) included 6 items (α = 0.79).DiscussionOur derived factor structure differed from those stemming from previous EFAs using different samples (eg, healthy individuals with varying degrees of schizotypy). The inconsistency might be best explained by the different populations sampled, ranging from healthy individuals who have smoked cannabis at least once to individuals with schizophrenia who smoked it regularly. Specifically, differences could be related to variations in how cannabis affects healthy individuals as well as those with schizotypy, as opposed to those with emerging or frank psychosis. Elucidating the underlying factor structure of the CEQ in first-episode psychosis samples could help researchers move towards a deeper understanding of the types of experiences associated with cannabis intoxication among young adults with first-episode psychosis and could inform the development of programs designed to reduce use, improve the course of illness, and possibly delay or prevent the onset of psychotic symptoms in those at risk.

T110. FIRST EPISODE PSYCHOTIC PATIENTS WITH A HISTORY OF FREQUENT CANNABIS USE EXPRESS MORE POSITIVE SYMPTOMS AT ILLNESS ONSET THAN THOSE WHO NEVER USED CANNABIS

BackgroundRobust evidence has demonstrated that cannabis use increases the risk to develop psychotic disorders. However, a limited number of studies have investigated if and how cannabis use influences psychopathology profiles at first episode psychosis (FEP).Based on the evidence that dopamine dysfunction contributes to explain positive symptoms in psychosis, and that the main cannabis’ psychoactive component, Δ9-Tetrahydrocannabinol (THC), modulates the dopamine system, we hypothesise that: 1) positive symptoms at FEP are more common among psychotic patients who used cannabis compared with never users; 2) this association is a dose-response relationship.MethodsWe analyzed a sample of 1130 FEP patients as part of the EUGEI study, recruited across six countries. The MRC Socio-demographic Schedule was used to collect sociodemographic information. Psychopathology was assessed with the OPerational CRITeria (OPCRIT), and symptom items were analyzed using Mplus to estimate a multidimensional model of psychosis. The Cannabis Experience Questionnaire modified version (CEQmv) was administered to collect information on cannabis, and different patterns of use were computed based on frequency of consumption and type of cannabis, as a proxy of exposure to THC.ResultsThe lifetime rate of cannabis use was 63%. Fifty-five percent of cannabis users consumed mostly high-potency cannabis, and 46% showed a daily frequency. Mixed-effects linear regression revealed that frequency of cannabis use was associated with the positive symptom dimension score. Daily users of high-potency cannabis presented with the strongest association (Β=0.19, 95%CI=0.02–0.38), even after gender, age, ethnicity, other drug use, and study site were controlled for.DiscussionOur results show that patients with a history of daily use of high potency cannabis express more positive symptoms at psychosis onset, even after taking into account other substance use and relevant sociodemographic factors.

Psychotic-like experiences with cannabis use predict cannabis cessation and desire to quit: a cannabis discontinuation hypothesis.

Evidence suggests that cannabis-induced psychotic-like experiences may be a marker of psychosis proneness. The effect of such experiences on cannabis use has not systematically been examined. We undertook a mixed-methods online survey of 1231 cannabis users (including 926 continued users) using the Cannabis Experiences Questionnaire. We examined the effect of psychotic-like and pleasurable experiences on cessation of cannabis and intention to quit. Socio-demographic variables, cannabis use parameters and substance misuse history were included as covariates. Free-text data explored subjective reasons for changes in use. Cessation of cannabis use was associated with greater psychotic-like experiences [p &lt; 0.001, Exp(B) 1.262, 95% confidence interval (CI) 1.179-1.351], whilst continued cannabis users were more likely to report pleasurable experiences [p &lt; 0.001, Exp(B) 0.717, 95% CI 0.662-0.776]. Intention to quit cannabis in continued users was associated with greater psychotic-like experiences [p &lt; 0.003, Exp(B) 1.131, 95% CI 1.044-1.225], whilst intention to not quit was significantly associated with increased pleasurable experiences [p &lt; 0.015, Exp(B) 0.892, 95% CI 0.814-0.978]. Whereas former users clearly ascribed cessation to negative experiences, continued users who expressed intention to quit less readily ascribed the intention to negative experiences. Elucidation of psychotic-like experiences may form the basis of a therapeutic intervention for those who wish to quit. Cessation in those with cannabis-induced psychotomimetic experiences may offset the risk for the development of a psychotic disorder, in this higher risk group.