Tobacco, nicotine, and cannabis use and exposure in an Australian Indigenous population during pregnancy: A protocol to measure parental and foetal exposure and outcomes.

BACKGROUND: The Australian National Perinatal Data Collection collates all live and stillbirths from States and Territories in Australia. In that database, maternal cigarette smoking is noted twice (smoking <20 weeks gestation; smoking >20 weeks gestation). Cannabis use and other forms of nicotine use, for example vaping and nicotine replacement therapy, are nor reported. The 2021 report shows the rate of smoking for Australian Indigenous mothers was 42% compared with 11% for Australian non-Indigenous mothers. Evidence shows that Indigenous babies exposed to maternal smoking have a higher rate of adverse outcomes compared to non-Indigenous babies exposed to maternal smoking (S1 File). OBJECTIVES: The reasons for the differences in health outcome between Indigenous and non-Indigenous pregnancies exposed to tobacco and nicotine is unknown but will be explored in this project through a number of activities. Firstly, the patterns of parental and household tobacco, nicotine and cannabis use and exposure will be mapped during pregnancy. Secondly, a range of biological samples will be collected to enable the first determination of Australian Indigenous people's nicotine and cannabis metabolism during pregnancy; this assessment will be informed by pharmacogenomic analysis. Thirdly, the pharmacokinetic and pharmacogenomic findings will be considered against maternal, placental, foetal and neonatal outcomes. Lastly, an assessment of population health literacy and risk perception related to tobacco, nicotine and cannabis products peri-pregnancy will be undertaken. METHODS: This is a community-driven, co-designed, prospective, mixed-method observational study with regional Queensland parents expecting an Australian Indigenous baby and their close house-hold contacts during the peri-gestational period. The research utilises a multi-pronged and multi-disciplinary approach to explore interlinked objectives. RESULTS: A sample of 80 mothers expecting an Australian Indigenous baby will be recruited. This sample size will allow estimation of at least 90% sensitivity and specificity for the screening tool which maps the patterns of tobacco and nicotine use and exposure versus urinary cotinine with 95% CI within ±7% of the point estimate. The sample size required for other aspects of the research is less (pharmacokinetic and genomic n = 50, and the placental aspects n = 40), however from all 80 mothers, all samples will be collected. CONCLUSIONS: Results will be reported using the STROBE guidelines for observational studies. FORWARD: We acknowledge the Traditional Custodians, the Butchulla people, of the lands and waters upon which this research is conducted. We acknowledge their continuing connections to country and pay our respects to Elders past, present and emerging. Notation: In this document, the terms Aboriginal and Torres Strait Islander and Indigenous are used interchangeably for Australia's First Nations People. No disrespect is intended, and we acknowledge the rich cultural diversity of the groups of peoples that are the Traditional Custodians of the land with which they identify and with whom they share a connection and ancestry.

Patterns of Marijuana Use and Nicotine Exposure in Patients Seeking Elective Aesthetic Procedures.

BACKGROUND: With the increasing legalization and popularity of marijuana, it is frequently and sometimes unintentionally combined with nicotine-containing products. As a consequence, patients may fail to accurately report usage during preoperative examinations or remain unaware of the inclusion of nicotine. This poses a challenge for clinicians in identifying preoperative nicotine exposure. This study aimed to establish normative data on the use of marijuana and nicotine in plastic surgery patients and correlate it with urine nicotine and cotinine levels. METHODS: All consecutive patients presenting to the authors' clinic seeking elective procedures were identified. Patients were surveyed on marijuana and nicotine use, and provided a urine sample for analysis. The survey responses, urine results, surgical treatments, and clinical outcomes were followed up prospectively. RESULTS: A total of 135 patients completed the survey and were categorized as nonusers (50%), active nicotine users (19%), active marijuana users (7%), active users of both (13%), or past users (11%). Marijuana users who denied nicotine use showed significantly elevated nicotine and cotinine levels compared with nonusers (average nicotine level, 23.1 ± 13.5 ng/mL [P = 0.00007]; average cotinine level, 221.2 ± 141.8 ng/mL [P = 0.0002]). Fewer than a third of active marijuana or nicotine users reported active use of these products during clinical encounters. There was no difference in urine levels, reported use, or other patient characteristics in patients with and without postoperative complications. CONCLUSION: This is the first descriptive study to document elevated urine nicotine levels in self-reported marijuana users in an urban, diverse patient population seeking elective plastic surgery procedures.

Cannabis use and patient-reported outcomes among patients at a comprehensive cancer center.

BACKGROUND: Patients with cancer report increasing rates of cannabis use, often to manage symptoms and toxicities. The efficacy and safety of cannabis, however, for some use cases remains unclear. To better understand characteristics of patients with cancer who report using cannabis, we examined data from a cannabis use survey of among patients with cancer seen at a National Cancer Institute-Designated Cancer Center. METHODS: In late 2021, patients with cancer (N = 1608) treated between July 2017 and December 2019 provided cannabis use data. Additional data were obtained from medical records data and routine patient-reported outcomes collected for clinical purposes. Univariable analyses and multivariable regression analyses were conducted to identify correlates of cannabis use at different stages in the cancer care trajectory. RESULTS: Rates of self-reported cannabis use by patients with cancer were 59% before cancer diagnosis and 47% after diagnosis. Longitudinal rates of cannabis use were 29% for no cannabis use, 23% before diagnosis, 12% after diagnosis, and 35% for both before and after diagnosis. Demographic factors associated with cannabis use included age, sex, race, and educational achievement. Tobacco use and binge drinking were associated with higher odds of cannabis use. Cannabis use was also associated with greater self-reported interference with physical functioning due to pain and interference with social functioning due to health problems. CONCLUSIONS: We found high rates of cannabis use among patients with cancer, both before and after their cancer diagnosis. Future studies should further investigate psychosocial factors associated with cannabis use among patients with cancer as well as psychosocial outcomes among patients with cancer using cannabis.

Amygdala volume and depression symptoms in young adolescents who use cannabis.

INTRODUCTION: Both cannabis use and depressive symptomology increase in prevalence throughout adolescence. Concurrently, the brain is undergoing neurodevelopment in important limbic regions, such as the amygdala. Prior research indicates the amygdala may also be related to cannabis use and depressive symptoms. We aimed to investigate the effects of adolescent cannabis use on amygdala volumes as well as the interaction of cannabis use and amygdala morphometry on depressive symptoms in youth. METHOD: Two-hundred-twenty-four participants (ages 12-15), balanced by sex assigned at birth, were selected from a sub-sample of the Adolescent Brain Cognitive Development (ABCD) Study based on hair toxicology and self-report measures of cannabis use. Participants positive for cannabinoids in hair and/or self-reported cannabis use were demographically matched to youth with no self-reported or confirmed cannabis use. The guardians of these youth reported depression symptoms on the Child Behavioral Checklist. Linear mixed effect models were run investigating cannabis use group on amygdala volumes bilaterally, controlling for whole brain volume and random effects of scanner type. Additional analyses examined cannabis group status and bilateral amygdala volume on depression symptoms. RESULTS: Cannabis use was not significantly associated with amygdala volume but was associated with increased depressive symptoms (p<0.01). Cannabis group interacted with amygdala volume, such that individuals with smaller volumes had increased depressive symptoms within the cannabis group (p's<0.01-0.02). CONCLUSION: Aberrations in amygdala volume based on cannabis use were not found in early adolescence; however, more depressive symptoms were related to cannabis group. Youth who use cannabis and have smaller amygdala volumes were at increased risk for depressive symptomology, suggesting potential neurovulnerabilities to cannabis use.

Prenatal Cannabis Use and Maternal Pregnancy Outcomes.

Importance: Many studies have evaluated whether in utero cannabis exposure is associated with fetal and neonatal outcomes, yet little is known about whether prenatal cannabis use is associated with maternal health outcomes during pregnancy. Objective: To evaluate whether prenatal cannabis use is associated with maternal health outcomes during pregnancy. Design, Setting, and Participants: This population-based retrospective cohort study included pregnancies in Northern California from January 2011 to December 2019 that lasted 20 weeks or longer and were screened for prenatal cannabis use. Exposures: Prenatal cannabis use was defined as any self-reported use during early pregnancy or a positive toxicology test result based on universal screening at entrance to prenatal care (approximately 8-10 weeks' gestation). Self-reported frequency of use (daily, weekly, monthly or less, never, unknown), use defined only by self-report, and use defined only by toxicology test results were examined. Main Outcomes and Measures: Electronic health record data were used to define the following outcomes: gestational hypertension, preeclampsia, eclampsia, gestational diabetes, gestational weight gain greater and less than guidelines, placenta previa, placental abruption, placenta accreta, and severe maternal morbidity. Adjusted risk ratios (aRRs) were calculated using a modified Poisson regression. Results: The sample (n = 316 722 pregnancies; 250 221 unique individuals) included 84 039 (26.5%) Asian/Pacific Islander, 20 053 (6.3%) Black, 83 145 (26.3%) Hispanic, and 118 333 (37.4%) White individuals; the mean (SD) age was 30.6 (5.4) years. Overall, 20 053 (6.3%) screened positive for prenatal cannabis use; 2.9% were positive by self-report, 5.3% by toxicology testing, and 1.8% by both. The frequency of cannabis use was 1930 (0.6%) daily, 2345 (0.7%) weekly, 4892 (1.5%) monthly or less, and 10 886 (3.4%) unknown. Prenatal cannabis use was associated with greater risk of gestational hypertension (aRR, 1.17; 95% CI, 1.13-1.21), preeclampsia (aRR, 1.08; 95% CI, 1.01-1.15), weight gain less than (aRR, 1.05; 95% CI, 1.01-1.08) and greater than (aRR, 1.09; 95% CI, 1.08-1.10) guidelines, and placental abruption (aRR, 1.19; 95% CI, 1.05-1.36). The pattern of results was similar when defining prenatal cannabis use only by self-report or only by toxicology testing, and associations between the frequency of prenatal cannabis use and outcomes varied with outcome. Conclusions and Relevance: The results of this cohort study suggest that prenatal cannabis use was associated with several adverse maternal health outcomes during pregnancy. Continued research is needed to understand whether characteristics of prenatal cannabis use (eg, dose, mode, and timing) moderate these associations.

The longitudinal assessment of prenatal cannabis use on neonatal outcomes.

OBJECTIVE: To investigate the association between prenatal cannabis use and perinatal outcomes using longitudinal data from pregnant individuals. STUDY DESIGN: This secondary-data analysis study utilized data collected from 894 pregnant individuals followed in the Stress in Pregnancy longitudinal study, conducted between 2009 and 2013. The status of cannabis use was ascertained through interviews and electronic medical record reviews to evaluate the effect of cannabis use on perinatal outcomes (NICU admission, preterm delivery, low birth weight, fetal death). RESULTS: Among participants analyzed, 13.1% used cannabis, who were generally younger (25.9 vs 27.9 years). There was a sevenfold increased risk of fetal death (OR 7.30) among cannabis users relative to non-users. Elevated risk persisted after adjustments of potential confounders (aOR 6.31). Adjusted models also suggested increased low birth weight risk (aOR 1.67). CONCLUSION: This study highlights an association between prenatal cannabis use and elevated risks for fetal death and low birth weight.

The Impact of Cannabis Use on Cognition in People with HIV: Evidence of Function-Dependent Effects and Mechanisms from Clinical and Preclinical Studies.

PURPOSE OF REVIEW: Cannabis may have beneficial anti-inflammatory effects in people with HIV (PWH); however, given this population's high burden of persisting neurocognitive impairment (NCI), clinicians are concerned they may be particularly vulnerable to the deleterious effects of cannabis on cognition. Here, we present a systematic scoping review of clinical and preclinical studies evaluating the effects of cannabinoid exposure on cognition in HIV. RECENT FINDINGS: Results revealed little evidence to support a harmful impact of cannabis use on cognition in HIV, with few eligible preclinical data existing. Furthermore, the beneficial/harmful effects of cannabis use observed on cognition were function-dependent and confounded by several factors (e.g., age, frequency of use). Results are discussed alongside potential mechanisms of cannabis effects on cognition in HIV (e.g., anti-inflammatory), and considerations are outlined for screening PWH that may benefit from cannabis interventions. We further highlight the value of accelerating research discoveries in this area by utilizing translatable cross-species tasks to facilitate comparisons across human and animal work.

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.

Reduced Diffusivity along Perivascular Spaces on MR Imaging Associated with Younger Age of First Use and Cognitive Impairment in Recreational Marijuana Users.

BACKGROUND AND PURPOSE: The impairment of the glymphatic system, a perivascular network crucial for brain waste clearance, has been linked to cognitive impairment, potentially attributed to the accumulation of brain waste. Although marijuana use has been associated with poorer cognitive performance, particularly in adolescents, its influence on the glymphatic system remains unexplored. This study evaluated the influence of the age of first marijuana use and the total number of lifetime uses on the glymphatic system, measured using the index of DTI along the perivascular space (DTI-ALPS). Furthermore, we explored the correlation between glymphatic clearance and cognitive performance among marijuana users. MATERIALS AND METHODS: In this study, 125 individuals who reported using marijuana at least once in their lifetime (43 men; mean age, 28.60 [SD, 3.84] years) and 125 individuals with zero lifetime cannabis use (nonusers; 44 men; mean age, 28.82 [SD, 3.56] years) were assessed. ALPS indices of all study participants were calculated using 3T diffusion MR imaging data (b = 1000 s/mm2). RESULTS: After we adjusted for age, sex, education years, Pittsburgh Sleep Quality Index, alcohol use, tobacco use, and intracranial volume, our analysis using a univariate General Linear Model revealed no significant difference in the ALPS index among nonusers and marijuana users with different ages of first use or various frequencies of lifetime usage. However, in marijuana users, multiple linear regression analyses showed associations between a lower ALPS index and earlier age of first marijuana use (standardized ß, -0.20; P = .041), lower accuracy in the working memory 0-back task (standardized ß, 0.20; P = .042), and fewer correct responses in the Fluid Intelligence Test (standardized ß, 0.19; P = .045). CONCLUSIONS: This study shows the potential use of DTI-ALPS as a noninvasive indirect indicator of the glymphatic clearance in young adults. Our findings show novel adverse effects of younger age at first use of marijuana on the glymphatic system function, which is associated with impaired working memory and fluid intelligence. Gaining insight into the alterations in glymphatic function following marijuana use could initiate novel strategies to reduce the risk of cognitive impairment.

Impact of deceased organ donor marijuana use on donor culture positivity and solid organ transplant recipient outcomes.

With the increasing prevalence of marijuana use in the US, many deceased organ donors have a history of marijuana use, raising concerns about infectious risks to transplant recipients. We performed a multicenter retrospective cohort study in which exposed donors were those with recent marijuana use (in the prior 12 months) and unexposed donors were those with no recent marijuana use. Primary outcomes included the following: (1) positive donor cultures for bacteria or fungi, (2) recipient infection due to bacteria or fungi within 3 months posttransplant, and (3) recipient graft failure or death within 12 months posttransplant. Multivariable regression was used to evaluate the relationship between donor marijuana use and each outcome. A total of 658 recipients who received organs from 394 donors were included. Recent marijuana use was not associated with donor culture positivity (aOR: 0.84, 95% CI: 0.39-1.81, P = .65), recipient infection (aHR: 1.02, 95% CI: 0.76-1.38, P = .90), or recipient graft failure or death (aHR: 1.65, 95% CI: 0.90-3.02, P = .11). Our data suggest that organs from donors with a history of recent marijuana use do not pose significant infectious risks in the early posttransplant period.

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.

Prenatal cannabis use and the risk of attention deficit hyperactivity disorder and autism spectrum disorder in offspring: A systematic review and meta-analysis.

BACKGROUND: It is plausible that exposure to cannabis in-utero could be associated with an increased risk of neurodevelopmental disorders such as attention deficit hyperactivity disorder (ADHD) symptoms and autism spectrum disorder (ASD) during childhood and adolescence; however, mixed results have been reported. This study investigated whether there is an association between prenatal cannabis use and ADHD symptoms and ASD in offspring using a systematic review and meta-analysis methodology. METHODS: A systematic literature search was conducted in PubMed/Medline, Scopus, EMBASE, Web of Science, Psych-Info, and Google Scholar to identify relevant studies. The study protocol has been preregistered in the Prospective Register of Systematic Reviews (PROSPERO) (CRD42022345001), and the Newcastle-Ottawa Quality Assessment Scale (NOS) was used to assess the methodological quality of included studies. An inverse variance weighted random effect meta-analysis was conducted to pool the overall effect estimates from the included studies. RESULTS: Fourteen primary studies, consisting of ten on ADHD and four on ASD, with a total of 203,783 participants, were included in this study. Our meta-analysis underscores an increased risk of ADHD symptoms and/or disorder [ß = 0.39: 95 % CI (0.20-0.58), I2 = 66.85 %, P = 0.001)] and ASD [RR = 1.30: 95 % CI (1.03-1.64), I2 = 45.5 %, P = 0.14] associated with in-utero cannabis exposure in offspring compared to their non-exposed counterparts. Additionally, our stratified analysis highlighted an elevated risk of ADHD symptoms [ß = 0.54: 95 % CI (0.26-0.82)] and a marginally significant increase in the risk of diagnostic ADHD among exposed offspring compared to non-exposed counterparts [RR = 1.13, 95 % CI (1.01, 1.26)]. CONCLUSION: This study indicated that maternal prenatal cannabis exposure is associated with a higher risk of ADHD symptoms and ASD in offspring.