Development and initial validation of the cannabis-related psychosis risk literacy scale (CPRL): a multinational psychometric study.

BACKGROUND: Public education efforts to address and reduce potential harms from cannabis use in Arab countries are either slow or inexistent, and do not follow the steadily increasing trends of cannabis use in Arab youth. Several decades of research on substance use, it can be suggested that being aware of, and knowing about, psychosis risk related to cannabis can at least limit the consumption of the substance. Motivated by a lack of measures specifically designed to measure literacy about cannabis-related psychosis risk in younger populations, and based on an extensive literature review, we aimed to create and validate a new self-report scale to assess the construct, the Cannabis-related Psychosis Risk Literacy Scale (CPRL), in the Arabic language. METHOD: A cross-sectional study was carried-out during the period from September 2022 to June 2023, enrolling 1855 university students (mean age of 23.26 ± 4.96, 75.6% females) from three Arab countries (Egypt, Kuwait and Tunisia). RESULTS: Starting from an initial pool of 20 items, both Exploratory Factor Analysis and Confirmatory Factor Analysis suggested that the remaining 8 items loaded into a single factor. The scale demonstrated good internal consistency, with both McDonald omega and Cronbach's alpha values exceeding 0.7 (omega = 0.85 / alpha = 0.85). The CPRL showed measurement invariance across gender and country at the configural, metric, and scalar levels. Concurrent validity of the CPRL was established by correlations with less favourable attitudes towards cannabis (r = -.14; p <.001). In addition, higher literacy levels were found in students who never used cannabis compared to lifetime users (4.18 ± 1.55 vs. 3.44 ± 1.20, t(1853) = 8.152, p <.001). CONCLUSION: The newly developed CPRL scale offers a valid and reliable instrument for assessing and better understanding literacy about cannabis-related psychosis risk among Arabic-speaking young adults. We believe that this new scale is suitable as a screening tool of literacy, as an instrument for measuring the effect of public education interventions aimed at promoting cannabis-related psychosis risk literacy among young people, and as a research tool to facilitate future studies on the topic with a wider application.

Development and validation of the Cannabis Exposure in Pregnancy Tool (CEPT): a mixed methods study.

BACKGROUND: Evidence of associations between prenatal cannabis use (PCU) and maternal and infant health outcomes remains conflicting amid broad legalization of cannabis across Canada and 40 American states. A critical limitation of existing evidence lies in the non-standardized and crude measurement of prenatal cannabis use (PCU), resulting in high risk of misclassification bias. We developed a standardized tool to comprehensively measure prenatal cannabis use in pregnant populations for research purposes. METHODS: We conducted a mixed-methods, patient-oriented tool development and validation study, using a bias-minimizing process. Following an environmental scan and critical appraisal of existing prenatal substance use tools, we recruited pregnant participants via targeted social media advertising and obstetric clinics in Alberta, Canada. We conducted individual in-depth interviews and cognitive interviewing in separate sub-samples, to develop and refine our tool. We assessed convergent and discriminant validity internal consistency and 3-month test-retest reliability, and validated the tool externally against urine-THC bioassays. RESULTS: Two hundred fifty four pregnant women participated. The 9-item Cannabis Exposure in Pregnancy Tool (CEPT) had excellent discriminant (Cohen's kappa = -0.27-0.15) and convergent (Cohen's kappa = 0.72-1.0) validity; as well as high internal consistency (Chronbach's alpha = 0.92), and very good test-retest reliability (weighted Kappa = 0.92, 95% C.I. [0.86-0.97]). The CEPT is valid against urine THC bioassay (sensitivity = 100%, specificity = 82%). CONCLUSION: The CEPT is a novel, valid and reliable measure of frequency, timing, dose, and mode of PCU, in a contemporary sample of pregnant women. Using CEPT (compared to non-standardized tools) can improve measurement accuracy, and thus the quality of research examining PCU and maternal and child health outcomes.

Prenatal delta-9-tetrahydrocannabinol exposure alters fetal neurodevelopment in rhesus macaques.

Prenatal cannabis use is associated with adverse offspring neurodevelopmental outcomes, however the underlying mechanisms are relatively unknown. We sought to determine the impact of chronic delta-9-tetrahydrocannabinol (THC) exposure on fetal neurodevelopment in a rhesus macaque model using advanced imaging combined with molecular and tissue studies. Animals were divided into two groups, control (n = 5) and THC-exposed (n = 5), which received a daily THC edible pre-conception and throughout pregnancy. Fetal T2-weighted MRI was performed at gestational days 85 (G85), G110, G135 and G155 to assess volumetric brain development. At G155, animals underwent cesarean delivery with collection of fetal cerebrospinal fluid (CSF) for microRNA (miRNA) studies and fetal tissue for histologic analysis. THC exposure was associated with significant age by sex interactions in brain growth, and differences in fetal brain histology suggestive of brain dysregulation. Two extracellular vesicle associated-miRNAs were identified in THC-exposed fetal CSF; pathway analysis suggests that these miRNAs are associated with dysregulated axonal guidance and netrin signaling. This data is indicative of subtle molecular changes consistent with the observed histological data, suggesting a potential role for fetal miRNA regulation by THC. Further studies are needed to determine whether these adverse findings correlate with long-term offspring neurodevelopmental health.

Vaporized D-limonene selectively mitigates the acute anxiogenic effects of Δ9-tetrahydrocannabinol in healthy adults who intermittently use cannabis.

BACKGROUND: Cannabis contains hundreds of chemical constituents beyond delta-9-tetrahydrocannabinol (THC), which is believed to drive most of its acute pharmacodynamic effects. The entourage effect theory asserts that non-THC constituents can impact acute cannabis effects, but few empirical studies have systematically evaluated this theory in humans. This study assessed whether the cannabis terpenoid d-limonene mitigates the acute anxiogenic effects of THC. METHODS: Twenty healthy adults completed nine, double-blind outpatient sessions in which they inhaled vaporized THC alone (15mg or 30mg), d-limonene alone (1mg or 5mg), the same doses of THC and d-limonene together, or placebo; a subset of participants (n=12) completed a tenth session in which 30mg THC+15mg d-limonene was administered. Outcomes included subjective drug effects, cognitive/psychomotor performance, vital signs, and plasma THC and d-limonene concentrations. RESULTS: When d-limonene was administered alone, pharmacodynamic outcomes did not differ from placebo. Administration of 15mg and 30mg THC alone produced subjective, cognitive, and physiological effects typical of acute cannabis exposure. Ratings of anxiety-like subjective effects qualitatively decreased as d-limonene dose increased and concurrent administration of 30mg THC+15mg d-limonene significantly reduced ratings of "anxious/nervous" and "paranoid" compared with 30mg THC alone. Other pharmacodynamic effects were unchanged by d-limonene. D-limonene plasma concentrations were dose orderly, and concurrent administration of d-limonene did not alter THC pharmacokinetics. CONCLUSIONS: D-limonene selectively attenuated THC-induced anxiogenic effects, suggesting this terpenoid could increase the therapeutic index of THC. Future research should determine whether this effect extends to oral dose formulations and evaluate the interactions between other cannabis terpenoids or cannabinoids and THC.

The association between prenatal cannabis use and congenital birth defects in offspring: A cumulative meta-analysis.

OBJECTIVE: To examine the association between prenatal cannabis use and structural birth defects in exposed offspring. METHODS: In line with the preregistered protocol (PROSPERO: CRD42022368623), we systematically searched PubMed/Medline, CINHAL, EMBASE, Web of Science, ProQuest, Psych-Info, and Google Scholar for published articles until 25 January 2024. The methodological quality of the included studies was appraised by the Newcastle-Ottawa Quality Assessment Scale (NOS). A meta-analysis was carried out to report the pooled effect estimates from the included studies. We further performed subgroup, leave-one-out sensitivity, and meta-regression analyses, which increased the robustness of our findings. RESULTS: In this cumulative meta-analysis, thirty-six observational studies, consisting of 18 case-control and 18 cohort studies, with 230, 816 cases of birth defects and 18,049,013 controls (healthy babies) were included in the final analysis. We found that offspring exposed to maternal prenatal cannabis are at greater risks of a wide range of structural birth defects: cardiovascular/heart [OR = 2.35: 95 % CI 1.63 - 3.39], gastrointestinal [OR = 2.42: 95 % CI 1.61 - 3.64], central nervous system [OR = 2.87: 95 % CI 1.51 - 5.46], genitourinary [OR = 2.39: 95 % CI 1.11 - 5.17], and any (unclassified) birth defects [OR = 1.25: 95 % CI 1.12 - 1.41]. CONCLUSION: The findings from the current study suggest that maternal prenatal cannabis exposure is associated with a higher risk of different forms of structural birth defects in offspring. The findings underscore the significance of implementing preventive strategies, including enhanced preconception counselling, to address cannabis use during pregnancy and mitigate the risk of birth defects in offspring.

Understanding cannabis use and mental health difficulties in context with women's experiences of stressful events and social health issues in pregnancy: The Aboriginal Families Study.

BACKGROUND: Few population-based data sources fully recognise the intersections between stressful events, social health issues, and cannabis use in pregnancy, and little is known about sequelae for women's mental health. METHODS: We draw on two waves of population-based data for 344 families participating in the Aboriginal Families Study longitudinal cohort. We examine women's mental health in the first year postpartum and when children were aged 5-9 years in context with life experiences and use of cannabis in pregnancy. OUTCOMES: One in five women (19·5%) used cannabis during pregnancy (with or without co-use of tobacco). Within this group of women, 88·3% experienced 3 or more (3+) stressful events or social health issues. Psychological distress (Kessler-5 scale, K-5) in the year postpartum was substantially higher amongst women who had used cannabis or experienced 3+ stressful events or social health issues. High proportions of women met criteria for support and referral for depression and/or anxiety (52·5% of women who had used cannabis compared to 20·9% amongst women who had neither used cannabis nor tobacco; 43·2% of women who had experienced 3+ stressful events or social health issues compared to 15·6% amongst women who had not indicated these experiences). Similar patterns of psychological distress, depressive (9-item adapted Personal Health Questionnaire, aPHQ-9) and anxiety symptoms (7-item Generalised Anxiety Disorder score, GAD-7) were evident when the study children were aged 5-9 years. INTERPRETATION: Amongst women who had used cannabis in pregnancy, a high burden of psychological distress, depression, and anxiety is evident in the postpartum period and as their children turn 5-9 years. The overlay of stressful events and social health issues and the high proportion of women meeting criteria for referral for mental health assessment and support indicate an urgent need to offer women opportunities for safe disclosure of cannabis use and opportunities to access sustained holistic services. Reducing the harms of cannabis use on Aboriginal and Torres Strait Islander families must be coupled with culturally safe ways of addressing the social, historical, and structural determinants of mental health distress and harmful use of substances.

A semi-naturalistic open-label study examining the effect of prescribed medical cannabis use on simulated driving performance.

BACKGROUND: Despite increasing medical cannabis use, research has yet to establish whether and to what extent products containing delta-9-tetrahydrocannabinol (THC) impact driving performance among patients. Stable doses of prescribed cannabinoid products during long-term treatment may alleviate clinical symptoms affecting cognitive and psychomotor performance. AIM: To examine the effects of open-label prescribed medical cannabis use on simulated driving performance among patients. METHODS: In a semi-naturalistic laboratory study, 40 adults (55% male) aged between 23 and 80 years, consumed their own prescribed medical cannabis product. Driving performance outcomes including standard deviation of lateral position (SDLP), the standard deviation of speed (SDS), mean speed and steering variability were evaluated using the Forum8 driving simulator at baseline (pre-dosing), 2.5 h and 5 -h (post-dosing). Perceived driving effort (PDE) was self-reported after each drive. Oral fluid and whole blood samples were collected at multiple timepoints and analysed for THC via liquid chromatography-mass spectrometry. RESULTS: A significant main effect of time was observed for mean speed (p = 0.014) and PDE (p = 0.020), with patients displaying modest stabilisation of vehicle control, increased adherence to speed limits and reductions in PDE post-dosing, relative to baseline. SDLP (p = 0.015) and PDE (p = 0.043) were elevated for those who consumed oil relative to flower-based products. Detectable THC concentrations were observed in oral fluid at 6-h post-dosing (range = 0-24 ng/mL). CONCLUSIONS: This semi-naturalistic study suggests that the consumption of medical cannabis containing THC (1.13-39.18 mg/dose) has a negligible impact on driving performance when used as prescribed.

Computational simulation of transcranial magnetic stimulation-induced electric fields in the dorsolateral prefrontal cortex of heavy cannabis using individuals.

We aimed to investigate the influence of demographic and clinical modulators on the strength of transcranial magnetic stimulation (TMS)-induced electric fields (EFs) in the left dorsolateral prefrontal cortex (lDLPFC) in heavy cannabis using individuals. Structural T1-weighted magnetic resonance imaging scans of 20 heavy cannabis using individuals and 22 non-cannabis users (the controls) in the age range of 18-25 were retrieved. Computational simulations of TMS-induced EFs in the lDLPFC were performed. No significant difference in the strength of TMS-induced EFs was observed between heavy cannabis using individuals and the controls. A negative correlation between the scalp-to-cortex distance demonstrated and the strength of the induced EFs. The severity of cannabis use related problems did not correlate with the induced EFs in the lDLPFC of heavy cannabis using individuals. However, the severity of alcohol use related problems was negatively correlated with the induced EF in the lDLPFC localized by the 5-cm method in the whole sample. Early adulthood seems related to an increase in the induced EFs in the lDLPFC. In conclusion, the dominant factor influencing TMS-induced EFs was the scalp-to-cortex distance. In early adulthood, the interaction between age and comorbid substance use may influence with the magnitude of TMS-induced EFs, thereby complicating the treatment effect of TMS in young people with substance use disorders.

Early exposure to cannabis and bipolar disorder incidence: Findings from a 22-year birth cohort study in Brazil.

BACKGROUND AND OBJECTIVES: Bipolar disorder is a chronic condition affecting millions of people worldwide. Currently, there is some evidence to suggest that cannabis use during adolescence may be an environmental risk factor for its onset, however inconsistencies have been observed across the literature. Considering this, we aimed to assess whether early lifetime cannabis is associated with subsequent bipolar disorder in young adults between 18 and 22 years of age. METHODS: Using data from the 1993 Pelotas (Brazil) birth cohort (n = 5249), cannabis exposure was examined at age 18 by self-report, and bipolar disorder diagnosis was measured at age 22 using the Mini International Neuropsychiatric Interview (MINI). In order to control the analysis, we considered socioeconomic status index, sex, skin color, physical abuse by parents and lifetime cocaine use. RESULTS: A total of 3781 individuals were evaluated in 2015 aged 22 years, of whom 87 were diagnosed with the bipolar disorder onset after the age of 18. Lifetime cannabis use predicted bipolar disorder onset at 22 years old (OR 1.82, 95% CI [1.10, 2.93]), and the effect remained after adjusting for socioeconomic status, sex, skin color, and physical abuse by parents (OR 2.00, 95% CI [1.20, 3.25]). However, this association was attenuated to statistically non-significant after further adjustment for all available covariates, including lifetime cocaine use (OR 1.79, 95% CI [0.95, 3.19]). We also found similar results for early cocaine use, where the association with bipolar disorder onset did not maintain significance in the multivariate model (OR 1.35, 95% CI [0.62, 2.86]). Otherwise, when we considered cannabis or cocaine lifetime use as a unique feature, our findings showed that the adolescent exposure to cannabis or cocaine increased the odds by 1.95 times of developing bipolar disorder at 22 years age, even when controlling for all other study variables (OR 2.14, 95% CI [1.30, 3.47]). Finally, our models suggest that cocaine use may potentially exert a major influence on the effect of lifetime cannabis use on bipolar disorder onset, and that physical abuse by parents and sex may modify the effect of cannabis use for later bipolar disorder onset. CONCLUSION: Based on our findings, early cannabis exposure predicted bipolar disorder onset in young adults, but this association was confounded by cocaine use. Contrary to schizophrenia, cannabis as a sole exposure was not associated with bipolar disorder onset after adjusting for control variables.

Resting state functional connectivity in dependent cannabis users: The moderating role of cannabis attitudes.

BACKGROUND: The global increase in lenient cannabis policy has been paralleled by reduced harm perception, which has been associated with cannabis use initiation and persistent use. However, it is unclear how cannabis attitudes might affect the brain processes underlying cannabis use. METHODS: Resting state functional connectivity (RSFC) within and between the executive control network (ECN), salience network (SN), and default mode network (DMN) was assessed in 110 near-daily cannabis users with cannabis use disorder (CUD) and 79 controls from The Netherlands and Texas, USA. Participants completed a questionnaire assessing the perceived benefits and harms of cannabis use from their personal, friends-family's, and country-state's perspectives and reported on their cannabis use (gram/week), CUD severity, and cannabis-related problems. RESULTS: RSFC within the dorsal SN was lower in cannabis users than controls, while no group differences in between-network RSFC were observed. Furthermore, heavier cannabis use was associated with lower dorsal SN RSFC in the cannabis group. Perceived benefits and harms of cannabis - from personal, friends-family's, and country-state's perspectives - moderated associations of cannabis use, CUD severity, and cannabis use-related problems with within-network RSFC of the SN, ECN, and DMN. Personal perceived benefits and country-state perceived harms moderated the association between CUD severity and RSFC between the ventral and dorsal DMN. CONCLUSIONS: This study highlights the importance of considering individual differences in the perceived harms and benefits of cannabis use as a factor in the associations between brain functioning and cannabis use, CUD severity, and cannabis use-related problems.

Predictors for cannabis cessation during pregnancy: a 10-year cohort study.

The aim of this study is to determine factors associated with cannabis discontinuation, to assess the impact of mental health and addiction interventions on cannabis discontinuation during pregnancy and to investigate the neonatal impact of cannabis discontinuation. This is a 10-year cohort study in a tertiary hospital in Barcelona, Spain, including women with self-reported cannabis use during pregnancy. Main outcome was cannabis discontinuation based on biological sample testing. Secondary outcomes were neonatal intensive care unit (NICU) admission, preterm birth, birth weight and bottle-feeding. When cannabis use was detected during pregnancy, 32 out of 81 (38.3%) discontinued cannabis during pregnancy vs. four out of 61 (6.6%) when detected at birth (p < .001). Multivariate binary logistic regression showed that null parity (OR: 6.95, p = .011), detection of cannabis use during pregnancy (OR: 5.35, p = .018) and early detection and referral to mental health care for counseling on cannabis cessation and interventions on the first trimester (OR: 25.46, p < .001) increased cannabis discontinuation. Risk for preterm birth <37 weeks (11.4% vs. 30.8%) and NICU admission (25.7% vs. 54.2%) were lower when discontinuation. Early detection of cannabis use during pregnancy, cessation counseling with mental health interventions, and null parity are predictors for cannabis discontinuation during pregnancy.

Recreational Marijuana Legalization and Workplace Injuries Among Younger Workers.

This case-control study uses state-by-year workplace injury data to assess recreational marijuana legalization adoption and workplace injuries among younger workers aged 20 to 34 years.

Cannabis-involvement in emergency department visits for self-harm following medical and non-medical cannabis legalization.

AIMS: Cannabis use may increase the risk of self-harm, but whether legalization of cannabis is associated with changes in self-harm is unknown. We examined changes in cannabis-involvement in emergency department (ED) visits for self-harm after the liberalization of medical and legalization of non-medical cannabis in Canada. METHODS: This repeated cross-sectional study used health administrative data to identify all ED visits for self-harm in individuals aged ten and older between January 2010 and December 2021. We identified self-harm ED visits with a co-diagnosis of cannabis (main exposure) or alcohol (control condition) and examined changes in rates of visits over four distinct policy periods (pre-legalization, medical liberalization, non-medical legalization with restrictions, and non-medical commercialization/COVID-19) using Poisson models. RESULTS: The study included 158,912 individuals with one or more self-harm ED visits, of which 7810 (4.9 %) individuals had a co-diagnosis of cannabis use and 24,761 (15.6 %) had a co-diagnosis of alcohol use. Between 2010 and 2021, the annual rate of ED visits for self-harm injuries involving cannabis per 100,000 individuals increased by 90.1 % (3.6 in 2010 to 6.9 in 2021 per 100,000 individuals), while the annual rate of self-harm injuries involving alcohol decreased by 17.3 % (168.1 in 2010 to 153.1 in 2021 per 100,000 individuals). The entire increase in visits relative to pre-legalization occurred after medical liberalization (seasonally adjusted Risk Ratio [asRR] 1.71 95 % CI 1.09-1.15) with no further increases during the legalization with restrictions (asRR 1.77 95%CI 1.62-1.93) or commercialization/COVID-19 periods (asRR 1.63 95%CI 1.50-176). CONCLUSIONS: Cannabis-involvement in self-harm ED visits almost doubled over 12 years and may have accelerated after medical cannabis liberalization. While the results cannot determine whether cannabis is increasingly causing self-harm ED visits or whether cannabis is increasingly being used by individuals at high risk of self-harm, greater detection for cannabis use in this population and intervention may be indicated.

Cannabis use in liver transplant candidates and recipients.

The increasing legality and acceptance of cannabis sale and consumption across the United States has led to a measurable increase in cannabis use nationwide, including in liver transplant (LT) candidates and recipients. With over 75% of liver transplant recipients transplanted in states with legalized use of medicinal and/or recreational cannabis, liver transplant clinicians must have expertise in the assessment of cannabis use given its potential impact on clinical care. In this review, the authors provide an understanding of nomenclature and tools to assess cannabis use, highlight essential components to guide clinical policy development and implementation, and discuss the potential impacts of cannabis use on patients' transplant course.

Prenatal Exposure to Cannabis: Effects on Childhood Obesity and Cardiometabolic Health.

PURPOSE OF REVIEW: To consolidate information on the obesogenic and cardiometabolic effects of prenatal exposure to cannabis. RECENT FINDINGS: A PubMed search strategy updated from January 1, 2014, through 14 June 2023, produced a total of 47 epidemiologic studies and 12 animal studies. Prenatal exposure to cannabis is consistently associated with small for gestational age and low birth weight. After birth, these offspring gain weight rapidly and have increased adiposity and higher glucose (fat mass percentage) in childhood. More preclinical and prospective studies are needed to deepen our understanding of whether these associations vary by sex, dose, timing, and composition of cannabis (e.g., ratio of delta-Δ9-tetrahydrocannabinol [Δ9-THC] to cannabidiol [CBD]). Addressing these gaps may help to solidify causality and identify intervention strategies. Based on the available data, clinicians and public health officials should continue to caution against cannabis use during pregnancy to limit its potential obesogenic and adverse cardiometabolic effects on the offspring.