Maternal Cannabis Use Research Articles

Maternal Cannabis Use During Pregnancy and Maternal and Neonatal Adverse Outcomes.

Cannabis is a psychoactive substance the availability and use of which, in various forms, has been liberalized in many countries across the world. Cannabis use, including by women of reproductive age, has become increasingly common, with (in some studies) >5% of women using the substance even during pregnancy to self treat nausea, vomiting, stress, anxiety, depression, insomnia, chronic pain, and other conditions. Women who use cannabis during pregnancy are more likely to have a medical or mental health condition; they are commonly unaware that cannabis is associated with pregnancy related risks. These risks arise from effects of cannabis on cannabinoid receptors in the placenta as well as from cannabis constituents that cross the placenta and act on receptors in the developing fetal brain; other mechanisms may also operate. This article examines recent cohort studies and meta-analyses on specific maternal and neonatal adverse outcomes associated with gestational exposure to cannabis. Maternal cannabis use during pregnancy is associated with small to moderately increased risks of gestational hypertension, gestational weight gain less than as well as greater than guidelines, and placental abruption. Maternal cannabis use during pregnancy is also associated with small to moderately increased risks of preterm birth (<36 weeks, <34 weeks, and <32 weeks), small for gestational age, low birth weight, neonatal intensive care unit admission, and fetal death. The risk of some of these adverse outcomes is greater with greater frequency of cannabis use. These adverse outcomes have been identified even in women who do not use other substances during pregnancy. Other adverse outcomes, such as major congenital malformations and neurodevelopmental disorders, are also reported (but are not discussed in this article). For these and other reasons, many professional bodies across the world are already discouraging women from using cannabis during pregnancy. It is important for pregnant women to be educated about cannabis and pregnancy related risks in a shared decision-making process.

Prenatal Cannabis Use and Offspring Attention Deficit Hyperactivity Disorder and Disruptive Behavior Disorders: A Retrospective Cohort Study.

To examine whether maternal cannabis use during early pregnancy is associated with offspring attention deficit hyperactivity disorder (ADHD) and disruptive behavior disorders (DBD). We conducted a population-based retrospective birth cohort study of children (N = 141,570) born between 2011 and 2018 to pregnant individuals (N = 117,130) in Kaiser Permanente Northern California universally screened for any prenatal cannabis use at the entrance to prenatal care (at ∼8-10 wk gestation). Prenatal cannabis use was defined as (1) self-reported use and/or a positive toxicology test, (2) self-reported use, (3) a positive toxicology test, and (4) self-reported use frequency. Cox proportional hazards regression models adjusting for maternal characteristics (sociodemographics, other substance use and substance use disorders, prenatal care initiation, comorbidities) examined associations between prenatal cannabis use and offspring ADHD and DBD diagnosed by age 11 years. The sample of pregnant individuals was 27.2% Asian/Pacific Islander, 5.7% Black, 24.5% Hispanic, and 38.8% non-Hispanic White, with a mean (SD) age of 30.9 (5.2) years; 4.6% screened positive for any cannabis use (0.4% daily, 0.5% weekly, 1.1% monthly or less, 2.7% unknown frequency); 3.92% had a positive toxicology test and 1.8% self-reported use; 7.7% of offspring had ADHD and 6.8% had DBD. Maternal prenatal cannabis use was not associated with ADHD (adjusted hazard ratio [aHR]: 0.84, 95% CI, 0.70-1.01), and there was an inverse association with DBD (aHR: 0.83, 95% CI, 0.71-0.97), which remained when cannabis was defined by toxicology testing but not by self-report. Frequency of use was not associated with outcomes. Maternal prenatal cannabis use was not associated with an increased risk of offspring ADHD or DBD.

Maternal Prenatal Cannabis Use and Child Autism Spectrum Disorder

Despite an increase in maternal prenatal cannabis use and associations with adverse neonatal outcomes, research on child neurodevelopmental outcomes is limited. To evaluate the association between maternal cannabis use in early pregnancy and child autism spectrum disorder (ASD). This population-based retrospective birth cohort study included children born between 2011 and 2019 to pregnant Kaiser Permanente Northern California members screened for prenatal cannabis use during pregnancy. Statistical analysis was conducted February 2023 to March 2024. Maternal prenatal cannabis use was assessed at entrance to prenatal care (approximately 8- to 10-weeks' gestation) via self-report and/or positive urine toxicology test. Use frequency was assessed. Child ASD was defined by International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnosis codes ascertained from the electronic health record. Associations between maternal prenatal cannabis use and child ASD were modeled using Cox proportional hazards regression adjusted for maternal sociodemographic, other substance use and disorders, prenatal care initiation, comorbidities, and clustering among maternal siblings. The study cohort included 178 948 singleton pregnancies among 146 296 unique pregnant individuals, including 48 880 (27.3%) Asian or Pacific Islander, 42 799 (23.9%) Hispanic, 9742 (5.4%) non-Hispanic Black, and 70 733 (39.5%) non-Hispanic White pregnancies. The median (IQR) maternal age at pregnancy onset was 31 (6) years; 8486 (4.7%) screened positive for cannabis use, 7054 (3.9%) via urine toxicology testing and 3662 (2.0%) by self-report. In the total study population, the frequency of self-reported use was monthly or less for 2003 pregnancies (1.1%), weekly for 918 pregnancies (0.5%), daily for 741 pregnancies (0.4%), and unknown for 4824 pregnancies (2.7%). ASD was diagnosed in 3.6% of children. After adjustment for maternal characteristics, maternal prenatal cannabis use was not associated with child ASD (hazard ratio [HR], 1.05; 95% CI, 0.84-1.32). When self-reported frequency of use was assessed, no statistically significant associations were observed after confounder adjustment. No sex-specific associations were documented (males: HR, 1.01; 95% CI, 0.77-1.32; and females: HR, 1.19; 95% CI, 0.77-1.85). In this cohort study, maternal cannabis use assessed in early pregnancy was not associated with child ASD. Additional studies are needed to evaluate different patterns of use throughout pregnancy. Given the known adverse neonatal health effects of maternal prenatal cannabis use, clinicians should follow national guidelines and advise against use.

“I don’t need my kid to be high”: prioritizing harm reduction when using cannabis during pregnancy

BackgroundCannabis is the most common illicit substance used in pregnancy. As use continues to increase, understanding peoples’ behaviors surrounding cannabis use during pregnancy is needed to improve maternal and child health outcomes. The aim of this study was to better understand pregnant individuals' perceptions and knowledge of cannabis use and use patterns as well as the social and environmental factors that may influence their use.MethodsWe conducted interviews with 19 participants between December 2022 and March 2023. Individuals self-identified as BIPOC (Black, Indigenous, People of Color), were over 21 years of age, spoke English or Spanish, resided in California, and had used cannabis during pregnancy in the last 0–2 years. Using qualitative, constructivist grounded theory methods, we analyzed the contexts that contributed to participants’ lived experiences surrounding cannabis use behaviors during pregnancy.ResultsParticipants reported making conscious decisions to responsibly manage their cannabis use during pregnancy to minimize potential harm to the fetus. Participants prioritized making what they perceived to be safer adjustments to their use of cannabis: (1) changing the amount of cannabis used, (2) changing the types of cannabis products used, and (3) changing sources of cannabis procurement.DiscussionOur findings show that pregnant individuals are seeking information about safe cannabis use beyond medical supervision and are open to altering their cannabis consumption patterns. However, they are unable to find trustworthy and evidence-based harm reduction practices which can be implemented to mitigate harm to their unborn children. A harm reduction approach is needed in the field of maternal cannabis use to promote positive maternal and fetal health outcomes.ConclusionsMore data is needed on comprehensive harm reduction approaches to cannabis use during pregnancy. This requires implementation of education on these topics in healthcare settings presented by prenatal care clinicians.

Systematic review: the impact of maternal pre-and postnatal cannabis use on the behavioral and emotional regulation in early childhood.

Prenatal exposure to alcohol and tobacco has been associated with child regulatory abilities and problems, but less is known about the associations with cannabis exposure. This review seeks to address this gap primarily focusing on the effects of maternal cannabis use on the child. Thus, we investigate the association between pre- and postnatal cannabis exposure of the child and regulatory abilities and problems, as well as the underlying neurobiological mechanisms potentially mediating the associations. According to the PRISMA guidelines, a systematic literature review was performed based on a systematic literature search through Medline (PubMed), Web of Science and PsycInfo, including studies assessing children aged 0-6 years with cannabis exposure in the preconception, pre-or postnatal period (preconception, pre- and postnatal cannabis exposure [PCE]) and investigating child regulatory abilities, regulatory problems or neurobiological mechanisms. Of n = 1061 screened articles, n = 33 were finally included. Diminished regulatory abilities are more likely to be found in infants after PCE, while specific regulatory problems tend tobe more frequently found after two years of age. Possible mechanisms are related to changes in methylation and expression of key genes involved in endocannabinoid, dopaminergic and opioid systems, increased cortisol reactivity and altered Secretory Immunoglobulin A levels. Furthermore, PCE has been associated with changes in brain structure and connectivity. Current findings indicate that PCE is associated with both age-dependent alterations in self-regulation and neurobiological changes in young children. However, evidence is limited due to the number of studies, small sample sizes and lack of control for maternal psychopathology. Longitudinal studies including psychometric data from mothers are needed in order to further understand the implications of PCE.Trial registration: The review is registered with PROSPERO (ID: CRD42023425115).

Exposure to maternal cannabis use disorder and risk of autism spectrum disorder in offspring: A data linkage cohort study

This study aimed to investigate the association between pre-pregnancy, prenatal and perinatal exposures to cannabis use disorder (CUD) and the risk of autism spectrum disoder (ASD) in offspring. Data were drawn from the New South Wales (NSW) Perinatal Data Collection (PDC), population-based, linked administrative health data encompassing all-live birth cohort from January 2003 to December 2005. This study involved 222 534 mother-offspring pairs. . The exposure variable (CUD) and the outcome of interest (ASD) were identified using the 10th international disease classification criteria, Australian Modified (ICD-10-AM). We found a three-fold increased risk of ASD in the offspring of mothers with maternal CUD compared to non-exposed offspring. In our sensitivity analyses, male offspring have a higher risk of ASD associated with maternal CUD than their female counterparts. In conclusion, exposure to maternal CUD is linked to a higher risk of ASD in offspring, with a stronger risk in male offspring. Further research is needed to understand these gender-specific effects and the relationship between maternal CUD and ASD risk in children.

Risk of Adverse Neonatal Outcomes After Combined Prenatal Cannabis and Nicotine Exposure

The prevalence of cannabis use in pregnancy is rising and is associated with adverse perinatal outcomes. In parallel, combined prenatal use of cannabis and nicotine is also increasing, but little is known about the combined impact of both substances on pregnancy and offspring outcomes compared with each substance alone. To assess the perinatal outcomes associated with combined cannabis and nicotine exposure compared with each substance alone during pregnancy. This retrospective population-based cohort study included linked hospital discharge data (obtained from the California Department of Health Care Access and Information) and vital statistics (obtained from the California Department of Public Health) from January 1, 2012, through December 31, 2019. Pregnant individuals with singleton gestations and gestational ages of 23 to 42 weeks were included. Data were analyzed from October 14, 2023, to March 4, 2024. Cannabis-related diagnosis and prenatal nicotine product use were captured using codes from International Classification of Diseases, Ninth Revision, Clinical Modification, and International Statistical Classification of Diseases, Tenth Revision, Clinical Modification. The main outcomes were infant and neonatal death, infants small for gestational age, and preterm delivery. Results were analyzed by multivariable Poisson regression models. A total of 3 129 259 pregnant individuals were included (mean [SD] maternal age 29.3 [6.0] years), of whom 23 007 (0.7%) had a cannabis-related diagnosis, 56 811 (1.8%) had a nicotine-use diagnosis, and 10 312 (0.3%) had both in pregnancy. Compared with nonusers, those with cannabis or nicotine use diagnoses alone had increased rates of infant (0.7% for both) and neonatal (0.3% for both) death, small for gestational age (14.3% and 13.7%, respectively), and preterm delivery (<37 weeks) (12.2% and 12.0%, respectively). Moreover, risks in those with both cannabis and nicotine use were higher for infant death (1.2%; adjusted risk ratio [ARR], 2.18 [95% CI, 1.82-2.62]), neonatal death (0.6%; ARR, 1.76 [95% CI, 1.36-2.28]), small for gestational age (18.0%; ARR, 1.94 [95% CI, 1.86-2.02]), and preterm delivery (17.5%; ARR, 1.83 [95% CI, 1.75-1.91]). These findings suggest that co-occurring maternal use of cannabis and nicotine products in pregnancy is associated with an increased risk of infant and neonatal death and maternal and neonatal morbidity compared with use of either substance alone. Given the increasing prevalence of combined cannabis and nicotine use in pregnancy, these findings can help guide health care practitioners with preconception and prenatal counseling, especially regarding the benefits of cessation.

The unseen patient: competing priorities between patients and providers when cannabis is used in pregnancy, a qualitative study.

This study aimed to explore competing priorities when cannabis is used during pregnancy from the perspective of providers and Black and Latina people. Maternal cannabis use is increasingly common, but patients and providers alike struggle to navigate it. This pilot used qualitative, constructivist ground theory methods to conduct semi-structured, remote interviews between 16 November 2021, and 7 February 2022 with 7 Black and Latina people who used cannabis during pregnancy, and 10 providers between 15 March 2022, and 6 April 2022, all of who were in Southern California, U.S. We identified three main findings: (1) Providers reported barriers to caregiving and relationship building with patients due to maternal cannabis use stigma, (2) Providers prioritized the fetus despite patients' current health system challenges that drove cannabis use, and (3) Both patients and providers engaged in personal research beyond the healthcare system to better understand maternal cannabis use. Our findings indicate that challenges exist between people who use cannabis during pregnancy and providers. Both groups need accurate, sociocultural sensitive information about maternal cannabis use via a harm reduction lens.

Cannabis Exposure and Adverse Pregnancy Outcomes Related to Placental Function

Cannabis use is increasing among reproductive-age individuals and the risks associated with cannabis exposure during pregnancy remain uncertain. To evaluate the association between maternal cannabis use and adverse pregnancy outcomes known to be related to placental function. Ancillary analysis of nulliparous individuals treated at 8 US medical centers with stored urine samples and abstracted pregnancy outcome data available. Participants in the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be cohort were recruited from 2010 through 2013; the drug assays and analyses for this ancillary project were completed from June 2020 through April 2023. Cannabis exposure was ascertained by urine immunoassay for 11-nor-9-carboxy-Δ9-tetrahydrocannabinol using frozen stored urine samples from study visits during the pregnancy gestational age windows of 6 weeks and 0 days to 13 weeks and 6 days (visit 1); 16 weeks and 0 days to 21 weeks and 6 days (visit 2); and 22 weeks and 0 days to 29 weeks and 6 days (visit 3). Positive results were confirmed with liquid chromatography tandem mass spectrometry. The timing of cannabis exposure was defined as only during the first trimester or ongoing exposure beyond the first trimester. The dichotomous primary composite outcome included small-for-gestational-age birth, medically indicated preterm birth, stillbirth, or hypertensive disorders of pregnancy ascertained by medical record abstraction by trained perinatal research staff with adjudication of outcomes by site investigators. Of 10 038 participants, 9257 were eligible for this analysis. Of the 610 participants (6.6%) with cannabis use, 32.4% (n = 197) had cannabis exposure only during the first trimester and 67.6% (n = 413) had ongoing exposure beyond the first trimester. Cannabis exposure was associated with the primary composite outcome (25.9% in the cannabis exposure group vs 17.4% in the no exposure group; adjusted relative risk, 1.27 [95% CI, 1.07-1.49]) in the propensity score-weighted analyses after adjustment for sociodemographic characteristics, body mass index, medical comorbidities, and active nicotine use ascertained via urine cotinine assays. In a 3-category cannabis exposure model (no exposure, exposure only during the first trimester, or ongoing exposure), cannabis use during the first trimester only was not associated with the primary composite outcome; however, ongoing cannabis use was associated with the primary composite outcome (adjusted relative risk, 1.32 [95% CI, 1.09-1.60]). In this multicenter cohort, maternal cannabis use ascertained by biological sampling was associated with adverse pregnancy outcomes related to placental dysfunction.

Gestational exposure to cannabidiol leads to glucose intolerance in 3-month-old male offspring.

Reports in North America suggest that up to 20% of young women (18-24 years) use cannabis during pregnancy. This is concerning given clinical studies indicate that maternal cannabis use is associated with fetal growth restriction and dysglycemia in the offspring. Preclinical studies demonstrated that prenatal exposure to Δ9-tetrahydrocannabinol, the main psychoactive component of cannabis, in rat dams led to female-specific deficits in β-cell mass and glucose intolerance/insulin resistance. Yet to date, the contributions of cannabidiol (CBD), the primary nonpsychoactive compound in cannabis, remain elusive. This study aimed to define the effects of in utero cannabidiol (CBD) exposure on postnatal glucose regulation. Pregnant Wistar rat dams received daily intraperitoneal injections of either a vehicle solution or 3 mg/kg of CBD from gestational day (GD) 6 to parturition. CBD exposure did not lead to observable changes in maternal or neonatal outcomes; however, by 3 months of age male CBD-exposed offspring exhibited glucose intolerance despite no changes in pancreatic β/α-cell mass. Transcriptomic analysis on the livers of these CBD-exposed males revealed altered gene expression of circadian rhythm clock machinery, which is linked to systemic glucose intolerance. Furthermore, alterations in hepatic developmental and metabolic processes were also observed, suggesting gestational CBD exposure has a long-lasting detrimental effect on liver health throughout life. Collectively, these results indicate that exposure to CBD alone in pregnancy may be detrimental to the metabolic health of the offspring later in life.

Prenatal THC exposure induces long-term, sex-dependent cognitive dysfunction associated with lipidomic and neuronal pathology in the prefrontal cortex-hippocampal network.

With increasing maternal cannabis use, there is a need to investigate the lasting impact of prenatal exposure to Δ9-tetrahydrocannabinol (THC), the main psychotropic compound in cannabis, on cognitive/memory function. The endocannabinoid system (ECS), which relies on polyunsaturated fatty acids (PUFAs) to function, plays a crucial role in regulating prefrontal cortical (PFC) and hippocampal network-dependent behaviors essential for cognition and memory. Using a rodent model of prenatal cannabis exposure (PCE), we report that male and female offspring display long-term deficits in various cognitive domains. However, these phenotypes were associated with highly divergent, sex-dependent mechanisms. Electrophysiological recordings revealed hyperactive PFC pyramidal neuron activity in both males and females, but hypoactivity in the ventral hippocampus (vHIPP) in males, and hyperactivity in females. Further, cortical oscillatory activity states of theta, alpha, delta, beta, and gamma bandwidths were strongly sex divergent. Moreover, protein expression analyses at postnatal day (PD)21 and PD120 revealed primarily PD120 disturbances in dopamine D1R/D2 receptors, NMDA receptor 2B, synaptophysin, gephyrin, GAD67, and PPARα selectively in the PFC and vHIPP, in both regions in males, but only the vHIPP in females. Lastly, using matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS), we identified region-, age-, and sex-specific deficiencies in specific neural PUFAs, namely docosahexaenoic acid (DHA) and arachidonic acid (ARA), and related metabolites, in the PFC and hippocampus (ventral/dorsal subiculum, and CA1 regions). This study highlights several novel, long-term and sex-specific consequences of PCE on PFC-hippocampal circuit dysfunction and the potential role of specific PUFA signaling abnormalities underlying these pathological outcomes.

Association of maternal exposure to Superstorm Sandy and maternal cannabis use with development of psychopathology among offspring: the Stress in Pregnancy Study.

Early-life adverse experiences can elevate the magnitude of the risk of developmental psychopathology, but the potential synergistic effects of multiple factors have not been well studied. To determine whether prenatal exposures to maternal stress (Superstorm Sandy) and maternal cannabis use synergistically alter the risk of developmental psychopathology. The study included 163 children (53.4% girls), longitudinally tracked (ages 2-5 years) in relation to the effects of two early-life adverse exposures (Superstorm Sandy and maternal cannabis use). Offspring were grouped by exposure status (neither, only maternal cannabis use, only Superstorm Sandy or both). DSM-IV disorders for offspring were derived from structured clinical interviews; caregiver-reported ratings of family stress and social support were also assessed. A total of 40.5% had been exposed to Superstorm Sandy and 24.5% to maternal cannabis use. Offspring exposed to both (n = 13, 8.0%), relative to those exposed to neither, had a 31-fold increased risk of disruptive behavioural disorders (DBDs) and a seven-fold increased risk of anxiety disorders. The synergy index demonstrated that offspring with two exposures had synergistic elevation in risk of DBDs (synergy index, 2.06, P = 0.03) and anxiety disorders (synergy index, 2.60, P = 0.004), compared with the sum of single risks. Offspring with two exposures had the highest parenting stress and lowest social support. Our findings are consistent with the double-hit model suggesting that offspring with multiple early-life adverse exposures (Superstorm Sandy and maternal cannabis use) have synergistically increased risks of mental health problems. Given the increasing frequency of major natural disasters and cannabis use, especially among women under stress, these findings have significant public health implications.

Assessing the clinical utility of toxicology testing in the peripartum period

Toxicology testing is frequently used as a means of gathering objective data about substance use in pregnancy, but little is known about the clinical utility of testing in the peripartum setting. This study aimed to characterize the utility of obtaining maternal-neonatal dyad toxicology testing at the time of delivery. We performed a retrospective chart review of all deliveries in a single healthcare system in Massachusetts between 2016 and 2020, and identified deliveries with either maternal or neonatal toxicology testing at delivery. An unexpected result was defined as a positive test for a nonprescribed substance that was not known on the basis of clinical history, self-report, or previous toxicology testing within a week of delivery, excluding results for cannabis. We evaluated the characteristics of maternal-infant dyads with unexpected positive results, unexpected positive results by rationale for testing, changes in clinical management after an unexpected positive test, and maternal outcomes in the year after delivery using descriptive statistics. Of the 2036 maternal-infant dyads with toxicology tests performed during the study period, there were 80 (3.9%) with an unexpected positive result. Diagnosis of substance use disorder with active use in the last 2 years was the clinical rationale for testing that yielded the greatest number of unexpected positive results (10.7% of total tests ordered for this rationale). Inadequate prenatal care (5.8%), maternal use of medication for opioid use disorder (3.8%), maternal medical indications such as hypertension or placental abruption (2.3%), history of substance use disorder in remission (1.7%), or maternal cannabis use (1.6%) yielded lower rates of unexpected results compared with a recent substance use disorder (within the last 2 years). Solely on the basis of findings from unexpected test results, 42% of dyads were referred to child protective services, 30% of dyads had no documentation of maternal counseling during delivery hospitalization, and 31% did not receive breastfeeding counseling after an unexpected test; 22.8% had monitoring for neonatal opioid withdrawal syndrome. Postpartum, 26 (32.5%) were referred to substance use disorder treatment, 31 (38.8%) attended a postpartum mental health visit, and only 26 (32.5%) attended a postpartum visit. Fifteen individuals (18.8%) were readmitted in the year after delivery, all for substance-related medical complications. Unexpected positive toxicology results at delivery were uncommon, particularly when tests were sent for frequently used clinical rationales for testing, suggesting a need to revisit guidelines surrounding appropriateness of indications for toxicology testing. The poor maternal outcomes in this cohort highlight a missed opportunity for maternal connection to counseling and treatment in the peripartum period.

Emerging Roles of Endocannabinoids as Key Lipid Mediators for a Successful Pregnancy

In recent years, Cannabis use/misuse for treating pregnancy-related symptoms and other chronic conditions has increased among pregnant women, favored by decriminalization and/or legalization of its recreational uses in addition to its easy accessibility. However, there is evidence that prenatal Cannabis exposure might have adverse consequences on pregnancy progression and a deleterious impact on proper neurodevelopmental trajectories in the offspring. Maternal Cannabis use could interfere with the complex and finely controlled role performed by the endocannabinoid system in reproductive physiology, impairing multiple gestational processes from blastocyst implantation to parturition, with long-lasting intergenerational effects. In this review, we discuss current clinical and preclinical evidence regarding the role of endocannabinoids in development, function, and immunity of the maternal-fetal interface, focusing on the impact of Cannabis constituents on each of these gestational processes. We also discuss the intrinsic limitations of the available studies and the future perspectives in this challenging research field.

Determining impacts of prenatal cannabis exposure on cannabis vapor self-administration using a novel response-contingent vapor model in pregnant rat dams

Cannabis use during pregnancy is becoming increasingly common despite a lack of knowledge regarding its long-term effects on developing offspring. Determining effects of prenatal cannabis exposure on cannabis use later in life has been especially difficult given the problems inherent to traditional models of cannabinoid self-administration. Thus, we adopted a model of response-contingent cannabis vapor delivery in pregnant rat dams to investigate impacts of maternal cannabis use on reinforcing properties of ∆9-tetrahydrocannabinol (THC)-rich cannabis vapor in offspring. Rat dams were trained to self-administer a vaporized cannabis extract or vehicle vapor in 1-hr sessions twice daily until 24-48 hr prior to parturition, while a third group received no vapor exposure. Cannabis vapor self-administration was assessed in adult offspring using a 22-day escalating reinforcement schedule that culminated in a 3 hr progressive ratio challenge. Dams reliably self-administered cannabis vapor during the gestational period and showed better discrimination for the vapor-paired nosepoke than vehicle self-administering dams. In accordance with human data, cannabis-exposed offspring displayed lower birthweights than vehicle-exposed offspring. Effects of prenatal cannabis exposure on vapor self-administration in adult offspring differed by sex. Male cannabis-exposed offspring made fewer active responses and earned fewer vapor deliveries than vehicle-exposed offspring, regardless of their assigned vapor condition. Conversely, female offspring showed higher rates of responding for cannabis relative to vehicle, but rates of self-administration were unaffected by prenatal cannabis exposure. Altogether, these data demonstrate feasibility of response-contingent cannabis vapor delivery in pregnant rat dams and indicate paradoxical suppressive effects on vapor self-administration in male offspring.

Psychiatric medication use among pregnant and breastfeeding mothers who used cannabis for mental health concerns: A cross-sectional survey study.

Use of cannabis during pregnancy and breastfeeding is increasing. Mental health concerns are reported as common reasons for maternal cannabis use, but little is known about the use of psychiatric medications in this population. This study aimed to describe psychiatric medication use among pregnant and breastfeeding mothers who used cannabis for mental health concerns. Anonymous, online cross-sectional survey. Data were collected from May 2018 to August 2019 among pregnant and breastfeeding mothers who used cannabis. This study included mothers who reported cannabis use for mental health concerns (n = 1363). The survey assessed the timing of cannabis use (during pregnancy and/or lactation); use of cannabis to address depression, posttraumatic stress disorder, or anxiety; use of psychiatric medications; psychiatric distress (Patient Health Questionnaire-4); and demographic information. Differences between groups were examined using t-test and chi-square test in SPSS. The mean age was 29.7 years; most were married (62%); 74% were White non-Hispanic, 9% Hispanic, and 17% Black, Indigenous or other People of Color. Mental health symptoms prompting cannabis use included anxiety (96%), depression (75%), and posttraumatic stress disorder (36%). Only 24% of respondents (n = 322) reported concomitant use of psychiatric medications, primarily selective serotonin reuptake inhibitors (72%, n = 232) and benzodiazepines (21%, n = 68). The composite Patient Health Questionnaire-4 showed most respondents had no (61%) or mild (27%) psychological distress; 14% screened positive for depression; and 17% screened positive for anxiety. Respondents who used psychiatric medications more often screened positive mental health concerns. Most mothers who used cannabis for mental health concerns were not taking psychiatric medications. This may be due to a mismatch between perceived mental health and screening results, un- or under-treated mental illness, or preference for cannabis over psychiatric medications. Improved management of perinatal mental health and effective patient education about risks of cannabis versus medication use are needed.

Prenatal cannabis use disorder and infant hospitalization and death in the first year of life

ObjectiveTo determine whether maternal cannabis use disorder is associated with infant hospitalization or death in the first year of life. MethodsWe queried an administrative birth cohort derived from the hospital discharge database maintained by the California Office of Statewide Health Planning and Development and linked with vital statistics files. We included singleton, live-birth deliveries between 2011 and 2018. Pregnancies with cannabis use disorder were classified from International Classification of Disease codes. Outcomes included infant emergency department visits and hospital admissions identified from health records, and infant deaths identified from death records. Models were adjusted for sociodemographic variables, psychiatric comorbidities and other substance use disorders. ResultsThere were 34,544 births (1.0 %) with a cannabis use disorder diagnosis in pregnancy, with increasing prevalence over the study period. The incidence of infant death in the first year of life was greater among those with a maternal cannabis use disorder diagnosis than those without (1.0 % vs 0.4 %; adjusted risk ratio 1.4 95 % CI: 1.2–1.6). When examining specific causes of death, the increased risk estimates were attributable to perinatal conditions and sudden unexpected infant death. After adjustment, there was no increased risk of infant hospitalizations or emergency department visits. ConclusionsThese findings warrant further investigation into the underlying mechanisms of maternal prenatal CUD on infant outcomes, and add to a rapidly expanding body of literature supporting the need for effective treatment options for pregnant individuals with cannabis use disorders

Cannabis use during lactation may alter the composition of human breast milk.

Cannabis is often used by women to manage symptoms of morning sickness during pregnancy, and postpartum stress and anxiety. While exclusive breastfeeding has been recommended for the first 6 months of an infant's life, the presence of cannabinoids in the milk of cannabis users complicates this recommendation. The objective of this study was to investigate the effect of maternal cannabis use on changes in the levels of macronutrients and bioactive factors in breast milk. Milk was collected from women who were 6-8 weeks postpartum and were either using cannabis post-delivery, had used cannabis during pregnancy, or were non-users. Levels of cannabinoids, macronutrients, lactose, and SIgA were assessed in the milk of all subjects. THC was detected in the milk of women who reported cannabis use during lactation (n = 13, median: 22 ng/mL). Carboxy-THC, 11-hydroxy-THC, CBD, and CBN were also detected in the milk of women who used cannabis postpartum. Relative to non-users (n = 17), lactose levels were higher and SIgA levels were significantly lower in the milk of subjects who used cannabis during lactation (n = 14). The presence of cannabinoids, along with altered lactose and SIgA levels in the milk of cannabis users, may have implications for infant health. Metabolites of cannabis are found in breast milk and can accumulate in higher concentrations with ongoing consumption, which is concerning for potential exposure among infants born to mothers who consume cannabis. This work reports that lactose levels are increased and SIgA levels are decreased in the breast milk of cannabis users, relative to the milk of non-users. Change in levels of lactose and SIgA in the milk of cannabis users may have significant implications on infant health, which must be investigated in the future to better inform mothers.

Prenatal THC Exposure Induces Sex-Dependent Neuropsychiatric Endophenotypes in Offspring and Long-Term Disruptions in Fatty-Acid Signaling Pathways Directly in the Mesolimbic Circuitry.

Despite increased prevalence of maternal cannabis use, little is understood regarding potential long-term effects of prenatal cannabis exposure (PCE) on neurodevelopmental outcomes. While neurodevelopmental cannabis exposure increases the risk of developing affective/mood disorders in adulthood, the precise neuropathophysiological mechanisms in male and female offspring are largely unknown. Given the interconnectivity of the endocannabinoid (ECb) system and the brain’s fatty acid pathways, we hypothesized that prenatal exposure to Δ9-tetrahydrocannabinol (THC) may dysregulate fetal neurodevelopment through alterations of fatty-acid dependent synaptic and neuronal function in the mesolimbic system. To investigate this, pregnant Wistar rats were exposed to vehicle or THC (3 mg/kg) from gestational day (GD)7 until GD22. Anxiety-like, depressive-like, and reward-seeking behavior, electrophysiology, and molecular assays were performed on adult male/female offspring. Imaging of fatty acids using matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) was performed at prepubescence and adulthood. We report that PCE induces behavioral, neuronal, and molecular alterations in the mesolimbic system in male and female offspring, resembling neuropsychiatric endophenotypes. Additionally, PCE resulted in profound dysregulation of critical fatty acid pathways in the developing brain lipidome. Female progeny exhibited significant alterations to fatty acid levels at prepubescence but recovered from these deficits by early adulthood. In contrast, males exhibited persistent fatty acid deficits into adulthood. Moreover, both sexes maintained enduring abnormalities in glutamatergic/GABAergic function in the nucleus accumbens (NAc). These findings identify several novel long-term risks of maternal cannabis use and demonstrate for the first time, sex-related effects of maternal cannabinoid exposure directly in the developing neural lipidome.

Comparison of Ocular and Brain Abnormalities Among Neonates With In Utero Exposure to Opium or Other Drugs.

BackgroundThere are growing concerns regarding ocular and brain abnormalities in infants who had in utero exposure to various kinds of substances/drugs. We compared the ocular and brain abnormalities among neonates based on the type of drug used by mothers.MethodologyThis prospective cohort study of 305 neonates included all neonates at Mahdieh Hospital, Tehran, Iran, who had their records for ophthalmic screening and brain sonography and were born to mothers with a history of substance use disorder (2014-2017). Demographic data, results for viral antibodies (human immunodeficiency virus, hepatitis C, and hepatitis B), and Apgar scores at one and five minutes were collected. We excluded neonates with Apgar score <8 at one minute, weight <1,800 g, gestational age <35 weeks, asphyxia, or anomalies. The neonates’ eyes were examined using tropicamide 0.5%, phenylephrine 2.5%, and tetracaine.ResultsThe prevalence of substance use disorder among pregnant women was 1.8%. The study included 305 neonates with a mean gestational age of 37.8 ± 1.6 weeks, while the mean age of their mothers with substance use disorder was 29.8 ± 6.4 years. Ophthalmologic examination showed that 37 (12%) neonates had abnormal incomplete retina vascularization, and brain abnormalities were seen in 29 (9.5%) neonates; however, no difference was identified based on the type of drug used by mothers. The birth weight (BW) of the neonates depended on the type of drugs used by the mothers (p = 0.027). Maternal use of cannabis and amphetamine were associated with the lowest and highest BWs (2,800 ± 283 and 3,750 ± 42 g), respectively.ConclusionsThe BW of neonates depended on the type of drugs used by the mothers, where cannabis and amphetamine use were associated with the lowest and highest BWs, respectively. However, our data could not identify if neonates’ ocular and brain abnormalities differed based on the types of drugs. This study highlights the importance of a drug-free pregnancy and the need for addiction-prevention programs provided to women of childbearing age.