Article

Differential Effects on Cognitive Functioning in 9- to 12-Year Olds Prenatally Exposed to Cigarettes and Marihuana

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Abstract

Cognitive performance was examined in 131 9-12-year-old children for whom prenatal marihuana and cigarette exposure had been ascertained. The subjects, participants in an ongoing longitudinal study, were from a low-risk, predominantly middle class sample. The tasks included the WISC-III and a series of tests assessing aspects of cognition subsumed under the rubric of executive function. Consistent with results obtained at earlier ages, discriminant function analysis revealed a dose-dependent association, which remained after controlling for potential confounds (including secondhand smoke), between prenatal cigarette exposure and lower global intelligence scores with the verbal subtests of the WISC maximally discriminating among levels of in utero exposure. In contrast, prenatal marihuana exposure was not associated with global intelligence or the verbal subtests. Rather, this drug was negatively associated with the executive function tasks that require impulse control and visual analysis/hypothesis testing and with a number of WISC subtests requiring the same abilities. The interpretation of these results is discussed in terms of executive function and is related to earlier observations of this sample and to the extant prefrontal and general marihuana literature.

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... Attention deficits, but J o u r n a l P r e -p r o o f Journal Pre-proof not lower global IQ scores, were reported for 48-month-old children with PCE in a secondary analysis of data of two randomized control trials from (Smid et al., 2022. The OPPS reported mixed findings in their lower risk cohort, with detrimental associations between PCE and memory at 3 to 4 years of age (Fried & Watkinson, 1990), no effects on memory at 5 to 6 years of age (Fried et al., 1992a) or on IQ and memory at 6 to 9 years (O'Connell & Fried, 1991), and detrimental effects of PCE on verbal reasoning and EF at 9 to 12 years (Fried et al., 1998). Symptoms of sleep disturbance were seen in 9-to 11-year-olds with retrospectively measured PCE in one analysis of the ABCD cohort (Winiger & Hewitt, 2020), but these disappeared after adjustment for covariates in another analysis (Paul et al., 2021). ...
... In the OPPS, PCE was also associated with increased omission errors on a laboratory task and increased caregiver-reported hyperactivity at 6 years (Fried et al., 1992b) and with laboratory measures of attention at 13 to 16 years (Fried & Watkinson, 2001). However, these were not seen in the OPPS at 9 to 12 years (Fried et al., 1998). ...
... In addition, these effects were associated with alterations in social behavior. Consistent with the animal models, changes in behavior regulation and cognitive function are reported in children and adolescents with PCE (Fried, 2002a;Fried et al., 1998;Goldschmidt et al., 2000;2008;2016). ...
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With the increased prevalence, potency, and acceptability of cannabis use during pregnancy, it is important to understand the developmental effects of prenatal cannabis exposure (PCE). This review discusses methodological considerations for studies of PCE, including the assessment of exposures, covariates, and outcomes, and reviews findings from prospective, longitudinal studies of PCE. There is some evidence for associations between PCE and restricted growth at birth, but not for long-term effects on growth. PCE appears to have subtle yet enduring effects on memory and achievement in children and adolescents. Despite differences in sample demographics and measurement, there are remarkably consistent effects of PCE on externalizing behaviors, such as delinquency and substance use, which persist into adulthood. Longitudinal analyses demonstrate the importance of early cannabis initiation for pathways between PCE and adult functioning, including substance use and abuse, memory deficits, and psychotic symptoms. Animal studies demonstrate direct effects on the development of the brain via activation of endogenous endocannabinoid systems. Cannabis-induced activation of the endocannabinoid system causes alterations in the release of neurotransmitters and the modulation of brain plasticity in neural pathways that underlie cognition, motivation, and behavior regulation. Future research should consider cannabis use before pregnancy, the timing and route of exposure, polysubstance exposures, and inter-generational effects.
... Evidence of its effect on brain development is mixed, with some studies reporting nonsignificant relations between PTE and cognitive impairment after adjusting for variables such as socioeconomic status (SES), home environment, and mother's intelligence or education (Baghurst et al., 1992;Kafouri et al., 2009). Yet, other works suggest a twofold to fourfold increase in ADHD diagnosis among offspring whose mothers smoked during pregnancy even after appropriate covariates are applied (Fried et al., 1998;Ernst et al., 2001;Cornelius and Day, 2009;Thapar et al., 2009;Ekblad et al., 2015). An inverse relation has also been shown between (a) PTE and (b) offspring WM and executive functioning impairment (Roy, 2002). ...
... Null findings surrounding association between presence of fetal tobacco exposure and offspring WM capacity were replicated across three independent samples. It may well be that environmental factors such as length and timing of exposure, above and beyond mere presence, drive potential teratologic effects of the exposure (Fried et al., 1998;Ernst et al., 2001;Cornelius and Day, 2009;Thapar et al., 2009;Ekblad et al., 2015). For example Fried et al. (1998) found a dose-dependent negative association between cognitive functioning and PTE. ...
... It may well be that environmental factors such as length and timing of exposure, above and beyond mere presence, drive potential teratologic effects of the exposure (Fried et al., 1998;Ernst et al., 2001;Cornelius and Day, 2009;Thapar et al., 2009;Ekblad et al., 2015). For example Fried et al. (1998) found a dose-dependent negative association between cognitive functioning and PTE. Animal studies have suggested that nicotine exposure during late gestation only may increase the risk of ADHD-like symptoms in offspring (Thomas et al., 2000). ...
Article
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Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental condition affecting between 5 and 8% of all children and adolescents, characterized by impairing levels of inattention, hyperactivity, and impulsivity. Existing cognitive models of ADHD have placed working memory (WM) deficits at the core of ADHD and suggest that primary WM deficits may also underlie the additional deficits associated with the condition. Although not all children with ADHD show WM deficits, those with such deficits have been found to have worse functional outcomes when compared to their diagnosed peers with typical WM functioning. Even so, contributors to the variability of impaired WM functioning seen within this population remain unknown. In the present study, we examined the association between two known prenatal and perinatal risk factors for impaired cognitive functioning – gestational smoking and hypertension – in three independent samples of children and adolescents with ADHD (samples varied with respect to sample size and WM measurement procedures). Contrary to hypotheses and existing literature, presence of high blood pressure during pregnancy was unexpectedly found to be a positive predictor of offspring WM capacity in one of three samples (a sample of all girls with ADHD). Implications and considerations for future research are discussed.
... The first of these studies was a longitudinal study from Canada designed to assess the association between socially used drugs consumed during pregnancy and the effects on offspring. 104 Data collection was by interview each trimester regarding drug use while pregnant. This study included 689 women, mostly middle-class and low-risk, of which 140 women reported some use of marijuana, or smoking at least 16 mg of nicotine daily, or drinking greater than 0.85 oz of alcohol daily. ...
... This study included 689 women, mostly middle-class and low-risk, of which 140 women reported some use of marijuana, or smoking at least 16 mg of nicotine daily, or drinking greater than 0.85 oz of alcohol daily. 104 The control group consisted of 50 randomly selected women who did not use any substances in pregnancy. These children were followed during the neonatal period, yearly until 6 years of age, and at specific preidentified time points through adolescence until 18 to 22 years of age. ...
... 29, 105 In the neonatal period, investigators observed decreased visual habituation, increased tremors and startles, and more hand-to-mouth behavior. 104 During early childhood, they found no adverse effects on IQ or on scales assessing mental, motor, behavioral components, poorer abstract/visual reasoning at 3 years of age and decreased performance on verbal and memory subscales at 4 years of age. 104 By age 6 years, children were found to have poorer sustained attention and higher parental ratings for hyperactivity/ impulsivity. ...
Article
Importance: Marijuana is the most commonly used dependent substance in pregnancy. The main active chemical of marijuana (delta-9-tetrahydrocannabinol [THC]) readily crosses the placenta, and cannabinoid receptors have been identified in fetal brain and placenta. As a result, prenatal marijuana use could potentially have detrimental impact on fetal development. Objective: This review aims to summarize the existing literature and current recommendations for marijuana use while pregnant or lactating. Evidence acquisition: A PubMed literature search using the following terms was performed to gather relevant data: "cannabis," "cannabinoids," "marijuana," "fetal outcomes," "perinatal outcomes," "pregnancy," "lactation." Results: Available studies on marijuana exposure in pregnancy were reviewed and support some degree of developmental disruption, including an increased risk of fetal growth restriction and adverse neurodevelopmental consequences. However, much of the existing prenatal marijuana research was performed in the 1980s, when quantities of THC were lower and the frequency of use was less. Additionally, most human studies are also limited and conflicting as most studies have been observational or retrospective, relying primarily on patient self-report and confounded by polysubstance abuse and small sample sizes, precluding determination of a causal effect specific for marijuana. Given the paucity of evidence, it is currently recommended to avoid using marijuana while pregnant or when breastfeeding. Conclusion and relevance: There is a critical need for research on effects in pregnancy using present-day THC doses. Once the adverse perinatal effects of marijuana exposure are identified and well characterized, patient education and antenatal surveillance can be developed to predict and mitigate its impact on maternal and fetal health.
... They are often smoked by pipe or as a joint [35]. Newer liquid formulations have recently emerged which can be vaporized by electronic cigarette [36]. ...
... It is controversial whether heavy periodic consumption can lead to long term cognition impairment [35][36][37]. But irreversible impairment appears to be minimal if it occurs. ...
Article
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Cannabis is a plant rich in various compounds that have a variety of impacts on the physiology of humans and the effects of these metabolites have a significant role in managing a variety of clinical diseases. A substantial increase in the use of SC (synthetic cannabinoids) had seen in the last few years especially infrequent cannabis users. The SCs will generate psychoactive effects that were similar to cannabis. However, the composition and pharmacological characteristics of these drugs make them possibly hazardous. Like all drugs, cannabis’ pharmacokinetics depends on the route of administration. Several studies showed that the bioavailability is less in oral administration when compared to inhalation. The main reason for this decrease in oral bioavailability is that cannabinoids undergo the first-pass metabolism before entering into the systemic circulation whereas in inhalation, it enters the circulation directly through the lungs. Cannabis sativa is a psychoactive plant that contains more than 500 components of which 104 cannabinoids had been identified. Of these, 2 components such as Δ9-THC (Δ9-tetrahydrocannabinol) and CBD (cannabidol) were under the scientific investigation. Δ9-THC is the primary cannabinoid which was responsible for the consequences of psychotrophy. The potency of cannabis is assessed based on the THC concentration of a sample that is the main psychoactive cannabinoid in cannabis. The adverse effects are in direct relation to the concentration of THC in the product after regular cannabis use. It can be assumed that several cannabinoids will find their way into the pharmacies from preclinical research within a century.
... The effects of prenatal cannabis exposure in humans was investigated in three major prospective longitudinal clinical studies with data on the offspring beyond the early neonatal period: (i) the Ottawa Prenatal Prospective Study (OPPS) (68)(69)(70)(71), started in 1978 with the final objective of studying the effects of cannabis used during pregnancy in white middleclass families; (ii) the Maternal Health Practices and Child Development Study (MHPCD) (72)(73)(74), started in 1982 and focused on high-risk pregnant women with low socioeconomic status, representing both white and African American women; and (iii) the Generation R study (75)(76)(77)(78)(79)(80)(81), an ongoing populationbased study from the Netherlands (for more details see Table 1). All these three studies assessed the effects of cannabis exposure during the gestational period on the fetus with variability on behavioral data (82) (Figure 1). ...
... In addition, disturbances in cognitive behavioral aspects regarding executive function domains, such as attention, planning, or working memory, were also described, entailing a significant impact on daily life experiences. In this respect, prenatal cannabis exposure seems to critically affect attention/impulsivity and problemsolving situations that require integration and manipulation of basic visuoperceptual skills (68). Furthermore, MHPCD study provided important information regarding intellectual abilities and school achievement, revealing that cannabis exposure during the first trimester predicted deficits in reading and spelling, as well as lower child performance, whereas cannabis use during the second trimester was associated with impaired reading comprehension (90). ...
Article
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Nowadays, cannabis is the most consumed illicit drug. The global prevalence of the use of cannabis in 2017 was estimated in 188 million of people, 3.8% of worldwide population. Importantly, the legalization of cannabis in different countries, together with the increase in the apparent safety perception, may result in a great variety of health problems. Indeed, an important concern is the increase in cannabis use among pregnant and breastfeeding women, especially since the content of delta9-tetrahidrocannabinol (THC) is currently around 2-fold higher than it was 15–20 years ago. The purpose of this study was to review cannabis use during pregnancy and breastfeeding including epidemiological aspects, therapeutic or preventive strategies, and experimental considerations and results from animal models of perinatal cannabis exposure to analyze the underlying neurobiological mechanisms and to identify new therapeutic approaches. A recent report revealed that among pregnant women aged 15–44, last month cannabis use prevalence was over 4.9%, raising to 8.5% in the 18–25-year-old age range. Pre- and post-natal exposure to cannabis may be associated with critical alterations in the newborn infants that are prolonged throughout childhood and adolescence. Briefly, several reports revealed that perinatal cannabis exposure was associated with low birth weight, reduction in the head circumference, cognitive deficits (attention, learning, and memory), disturbances in emotional response leading to aggressiveness, high impulsivity, or affective disorders, and higher risk to develop a substance use disorder. Furthermore, important neurobiological alterations in different neuromodulatory and neurotransmission systems have been associated with cannabis consumption during pregnancy and lactation. In spite of the evidences pointing out the negative behavioral and neurobiological consequences of cannabis use in pregnant and breastfeeding women, there are still limitations to identify biomarkers that could help to establish preventive or therapeutic approaches. It is difficult to define the direct association specifically with cannabis, avoiding other confusing factors, co-occurrence of other drugs consumption (mainly nicotine and alcohol), lifestyle, or socioeconomic factors. Therefore, it is necessary to progress in the characterization of short- and long-term cannabis exposure-related disturbances.
... The available published studies on marijuana exposure in pregnancy are limited but support some degree of developmental disruption associated with maternal marijuana use. Prenatal marijuana exposure has been associated with stillbirth, intrauterine growth restriction (IUGR), fetal neurodevelopmental consequences [74][75][76][77][78][79][80][81], and impaired offspring cognitive development [77,79,82]. However, most of the prenatal marijuana research that exists, including animal studies, was performed in the 1980s, reflecting marijuana exposure largely through smoking, with few reports studying doses and routes of administration that are comparable or relevant to contemporary use [83][84][85][86][87]. ...
... Currently, there is insufficient evidence to establish a strong association between prenatal marijuana exposure and later offspring outcomes including sudden infant death syndrome, cognition, academic achievement, and later substance abuse [101]. The literature consists largely of three main large, longitudinal cohort studies from 1970 to 2001 when marijuana was largely smoked and the potency of THC was lower [77,82,102,103]. Prior human studies have suggested that prenatal marijuana exposure may affect neurological development in offspring. ...
Purpose of review: Recent widespread legalization changes have promoted the availability of marijuana and its increased potency and perceived safety. The limited evidence on reproductive and perinatal outcomes from marijuana exposure is enough to warrant concern and action. The objective of this review is to provide a current and relevant summary of the recent literature surrounding this topic. Recent findings: The available published studies on the effect of marijuana exposure on reproductive health and pregnancy outcomes are conflicting. Human studies are often observational or retrospective and confounded by self-report and polysubstance use. However, the current, limited evidence suggests that marijuana use adversely affects male and female reproductive health. Additionally, prenatal marijuana exposure has been reported to be associated with an increased risk of preterm birth and small for gestational age infants. Summary: With the increasing prevalence of marijuana use, there is an urgent need for evidence-driven recommendations and guidelines for couples interested in conception, affected by infertility or who are expecting. At this time, no amount of marijuana use during conception or pregnancy is known to be well tolerated and the limited available evidence suggests that the safest choice is to abstain.
... At the time of school entrance, findings on intellectual development as measured by standardized tests lack consistency (Fried, O'Connell, & Watkinson, 1992;Fried, Watkinson, & Gray, 1992;Goldschmidt, Richardson, Willford, & Day, 2008). During middle-childhood and adolescence, higher-dose prenatal exposure has been associated with poorer performance on assessments of memory, visual analysis, attention, inhibitory control and academic achievement (Fried, Watkinson, & Gray, 1998Goldschmidt, Richardson, Cornelius, & Day, 2004;Richardson, Ryan, Willford, Day, & Goldschmidt, 2002). An overall synthesis of the data suggests that while global IQ is preserved in exposed children, certain components of cognition are affected (Fried et al., 1998(Fried et al., , 2003. ...
... During middle-childhood and adolescence, higher-dose prenatal exposure has been associated with poorer performance on assessments of memory, visual analysis, attention, inhibitory control and academic achievement (Fried, Watkinson, & Gray, 1998Goldschmidt, Richardson, Cornelius, & Day, 2004;Richardson, Ryan, Willford, Day, & Goldschmidt, 2002). An overall synthesis of the data suggests that while global IQ is preserved in exposed children, certain components of cognition are affected (Fried et al., 1998(Fried et al., , 2003. Many of the skills most vulnerable to cannabis exposure, for example, attention, working memory and inhibitory control, are part of a domain of cognitive performance known as executive functioning (Fried & Smith, 2001;Smith et al., 2016). ...
Article
There is a strong increase in prevalence trends for cannabis use during pregnancy and lactation as more states legalize use of this drug. Information on the teratogenic risk of cannabis is limited but some important themes can be gleaned. Studies have not found a unique phenotypic signature of prenatal exposure but an increased risk of congenital anomalies, particularly gastroschisis, has been reported. Changes in fetal growth have been described in some epidemiological studies but long‐term patterns of physical growth appear unaffected. Prenatzith reductions in global IQ but specific cognitive skills, especially attention and memory, can be negatively impacted. Long‐term impacts on psychological health include increased rates of depressive symptoms and anxiety as well as delinquency. Relatively little is known about the risk of maternal cannabis use during lactation but data suggest that infant exposure is relatively low compared to maternal exposure. As delta‐9‐tetrahydrocannabinol (THC) levels increase to meet consumer demand and routes of exposure diversify, there is a strong need for prospective birth‐cohort studies that collect biological samples to quantify exposure. Data from such studies will be critical to overcoming the weaknesses of past cannabis research and are essential to establishing reliable information on the risks of maternal use. Until that time, health care providers should be encouraged to talk about the risks and benefits associated with cannabis use during pregnancy and lactation with their patients, emphasizing that fetal and neonatal risks cannot be excluded at this time.
... Clinical research also finds that prenatal cannabis use is associated with long-term adverse effects on brain, cognitive, and behavioral development of the exposed child, although results have been mixed. Newborns exposed to prenatal cannabis may exhibit changes in arousal (Dahl et al. 1995;Scher et al. 1988), and children exposed prenatally to cannabis exhibit poorer academic performance, with deficits in verbal skills, memory, and attention (Fried 1991(Fried , 1996Fried et al. 1998;Huizink 2014;Smith et al. 2016). In addition, prenatal cannabis exposure is associated with reduced impulse control, affective disorders, disrupted sleep (Nashed et al. 2020), as well as increased risk for psychopathology (Paul et al. 2019). ...
... Clinical studies examining the effects of prenatal cannabis exposure on motor development are limited and have similarly yielded mixed results (Grant et al. 2018;Metz and Borgelt 2018). For example, prenatal cannabis exposure may lead to increased startles and tremors in neonates and advancement of motor development in toddlers (Fried et al. 1998); however, some studies have failed to find any alterations in balance or motor coordination (Chandler et al. 1996). Importantly, the prenatal exposure of these subjects occurred decades ago; thus, results will likely not generalize to the cannabis products and consumption patterns of today. ...
Article
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Rationale In the USA, nicotine and cannabis are the most common licit and illicit drugs used among pregnant women. Importantly, nicotine and cannabis are now being combined for consumption via e-cigarettes, an increasingly popular delivery device. Both nicotine and tetrahydrocannabinol (THC), the primary psychoactive component of cannabis, cross the placenta barrier. However, the consequences of prenatal cannabis use are not well understood, and less is known about potential combination effects when consumed with nicotine, especially via e-cigarettes. Objective The present study used a rodent model to examine how prenatal e-cigarette exposure to nicotine, THC, and the combination impacts motor development among offspring. Methods Pregnant Sprague–Dawley rats were exposed to nicotine (36 mg/mL), THC (100 mg/mL), the combination, or vehicle via e-cigarette inhalation from gestational days (GD) 5–20. One sex pair per litter was tested on an early sensorimotor development task (postnatal days [PD] 12–20) and a parallel bar motor coordination task (PD 30–32). Results Combined prenatal exposure to nicotine and THC delayed sensorimotor development, even though neither drug produced impairments on their own. In contrast, prenatal exposure to either nicotine or THC impaired motor coordination, whereas combined exposure exacerbated these effects, particularly among females. Conclusions These data illustrate that prenatal exposure to either nicotine or THC may alter motor development, and that the combination may produce more severe effects. These findings have important implications for pregnant women as we better understand the teratogenic effects of these drugs consumed via e-cigarettes.
... Neurodevelopmental disorders are also associated with PTE [13,14], many of which are related to auditory system function. In particular, children born with PTE have been found to show lower scores on measures of cognitive function and developmental skills [18,22], memory [23,24], verbal subscales of intelligence tests [24][25][26], and reading and phonological processing [27]. Difficulty with tasks involving auditory processing is repeatedly mentioned in children with PTE [18,[28][29][30][31][32]. ...
... Neurodevelopmental disorders are also associated with PTE [13,14], many of which are related to auditory system function. In particular, children born with PTE have been found to show lower scores on measures of cognitive function and developmental skills [18,22], memory [23,24], verbal subscales of intelligence tests [24][25][26], and reading and phonological processing [27]. Difficulty with tasks involving auditory processing is repeatedly mentioned in children with PTE [18,[28][29][30][31][32]. ...
Article
Prenatal exposures to alcohol (PAE) and tobacco (PTE) are known to produce adverse neonatal and childhood outcomes including damage to the developing auditory system. Knowledge of the timing, extent, and combinations of these exposures on effects on the developing system is limited. As part of the physiological measurements from the Safe Passage Study, Auditory Brainstem Responses (ABRs) and Transient Otoacoustic Emissions (TEOAEs) were acquired on infants at birth and one-month of age. Research sites were in South Africa and the Northern Plains of the U.S. Prenatal information on alcohol and tobacco exposure was gathered prospectively on mother/infant dyads. Cluster analysis was used to characterize three levels of PAE and three levels of PTE. Repeated-measures ANOVAs were conducted for newborn and one-month-old infants for ABR peak latencies and amplitudes and TEOAE levels and signal-to-noise ratios. Analyses controlled for hours of life at test, gestational age at birth, sex, site, and other exposure. Significant main effects of PTE included reduced newborn ABR latencies from both ears. PTE also resulted in a significant reduction of ABR peak amplitudes elicited in infants at 1-month of age. PAE led to a reduction of TEOAE amplitude for 1-month-old infants but only in the left ear. Results indicate that PAE and PTE lead to early disruption of peripheral, brainstem, and cortical development and neuronal pathways of the auditory system, including the olivocochlear pathway.
... Human studies have provided invaluable information on the detrimental effects of prenatal cannabis exposure on the offspring from the neonatal period through early adulthood (Crume et al., 2018;El Marroun et al., 2018;Huizink, 2014;Ryan et al., 2018), revealing increased tremors, startles and altered sleep patterns at birth (Calvigioni et al., 2014;Volkow et al., 2017) and significant impairment of higher cognitive functions beyond infancy (Fried, 2002;Fried et al., 1998;Grant et al., 2018;Huizink et al., 2006;Leech et al., 1999;Passey et al., 2014;Smith et al., 2006). However, one weakness of human studies is that they cannot control for environmental and genetic factors. ...
Article
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Background and purpose: Cannabis sativa is the illicit drug most commonly used among pregnant and breastfeeding women. Different studies reported long-term adverse effects induced by in utero exposure to the main component of Cannabis, Δ9 -tetrahydrocannabinol (THC), both in rodents and humans. However, little is known about any potential sex-dependent effects of cannabis consumption during pregnancy on newborns at early developmental ages. Experimental approach: We studied the effects of prenatal exposure to the cannabinoid receptor agonist WIN55,212-2 (WIN; 0.5 mg/kg from GD5 to GD20) on the emotional reactivity and cognitive performance of male and female rat offspring from infancy through adolescence and tested the role of mGlu5 receptor signaling in the observed effects. Key results: Prenatally WIN-exposed male infant pups emitted less isolation-induced ultrasonic vocalizations (USVs) compared with male control pups when separated from the dam and siblings and showed increased locomotor activity, while females were spared. These effects were normalized when male pups were treated with the positive allosteric modulator of mGlu5 receptor CDPPB. When tested at the prepubertal and pubertal periods, WIN-prenatally exposed rats of both sexes did not show any difference in social play behavior, anxiety and temporal order memory. Conclusion and implications: We reveal a previously undisclosed sexual divergence in the consequences of fetal cannabinoids on newborns at early developmental ages, which is dependent on mGlu5 receptor signaling. These results provide new impetus for the urgent need to investigate the functional and behavioral substrates of prenatal cannabinoid exposure in both the male and female offspring.
... Previous OPPS findings have revealed that children prenatally exposed to cannabis appeared to exhibit deficits in executive functioning across various developmental stages postnatally. For instance, a study of 9 to 12-year-old OPPS participants demonstrated that prenatal cannabis exposure was negatively associated with impulse control during executive function tasks (Fried et al. 1998). Additionally, 13 to 16-year-old participants who were prenatally exposed to cannabis displayed significant deficits in sustained attention (Fried and Watkinson 2001). ...
Article
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There is an emerging consensus that regular cannabis use may be detrimental to the developing brain, including potential long-lasting changes in executive functioning. Consequently, the present study examined neural activation and performance on a working memory n-back task using functional magnetic resonance imaging (fMRI) in a sample of young adults (ages 19 to 21) from a longitudinal research sample. Regular cannabis users (n = 10) were compared with non-regular cannabis user controls (n = 14) while completing the letter n-back task during fMRI. While there were no differences across performance indices, imaging parameters showed significant differences in brain activation during task performance. Specifically, there was evidence of increased activation in the left and right temporal lobes and the right superior frontal cortex in cannabis users, including significantly altered functional connectivity between these areas. Functional connectivity analyses also showed differences in expected patterns of connectivity in both working memory and reward circuitries among cannabis users, possibly reflecting compensatory mechanisms as a result of sustained use.
... Infant and early childhood neurodevelopment has primarily been examined by three cohorts, all of which have significant polysubstance use: the Ottawa Prenatal Prospective Study (Fried et al., 1998), the Maternal Health Practices and Child Development (MHPCD) Study (Day and Richardson, 1991), and the Generation R study (Huizink, 2014;Jaddoe et al., 2012). Taken together the results from these three cohort studies, other case-controlled studies, and meta-analyses are highly inconsistent. ...
Chapter
Historically, research has revealed the pervasive effects of prenatal exposure to potential teratogens during pregnancy on risk for poor birth outcomes and other maternal-fetal/child morbidities and mortality. However, recent research has elucidated maternally mediated exposures ranging from health conditions such as gestational diabetes mellitus to prenatal cannabis exposure can result in changes in fetal brain development and downstream effects on postnatal neurodevelopment. In this chapter, we will summarize several potential prenatal maternally mediated exposures, their mechanisms of action, and their effect on brain development from infancy through early childhood.
... Notably, characteristics of infants born to cannabis users disappear by 30 days of age (Fried et al., 1982), pointing at a remarkable plasticity that allows development of compensatory measures in response to cannabisdriven alterations in physiological processes. Later in childhood, however, prenatal cannabis exposure negatively reflects on attention processes (Leech et al., 1999) and cognitive performance within executive function (Fried et al., 1998;Trezza et al., 2012). In utero CB exposure leads to more aggressive behavior and attention problems in 18-month-old girls (El Marroun et al., 2011). ...
Chapter
The endocannabinoid (eCB) system comprises endogenously produced cannabinoids (CBs), enzymes of their production and degradation, and CB-sensing receptors and transporters. The eCB system plays a critical role in virtually all stages of animal development. Studies on eCB system components and their physiological role have gained increasing attention with the rising legalization and medical use of marijuana products. The latter represent exogenous interventions that target the eCB system. This chapter summarizes knowledge in the field of CB contribution to gametogenesis, fertilization, embryo implantation, fetal development, birth, and adolescence-equivalent periods of ontogenesis. The material is complemented by the overview of data from our laboratory documenting the functional presence of the eCB system within cerebral arteries of baboons at different stages of development.
... According to Fried et al. (1998), effects on neurological development due to exposure to cigarette smoke during pregnancy lead to antisocial manifestations early in life that, in turn, are associated with a higher probability of starting and continuing to smoke (Miles & Weden, 2012). Specifically, antisocial behaviour is defined as a heterogeneous concept encompassing physically aggressive behaviours (for example, bullying or fighting), rule breaking and oppositional behaviours (for example, destroying belongings and disobeying parents), and more severe problems associated with lack of empathy and guilt (Bonino, Cattelino, Ciairano, & Jessor, 2007;Donovan, Jessor, & Costa, 1991;Jessor & Jessor, 1977). ...
Article
Offspring whose mother smokes during pregnancy have higher risk of smoking themselves. In this study, epigenetics, antisocial behaviours, and social learning were investigated as potential mechanisms of mother-to-child transmission of smoking among a population sample drawn from the Birth Cohort Study 1970. Findings on daughters showed that the direct epigenetic hypothesis was mediated by social learning mechanisms, suggesting that exposure to maternal smoking across childhood and adolescence strongly explained why the smoking habits of mother and daughter correlate. However, prenatal smoking effects on sons were only partially explained by observational learning of mother smoking habits. Our estimates provided evidence concerning the potential role also played by the child's persistent antisocial behaviours. These results were confirmed after controlling for early life circumstances and current socioeconomic conditions. Policy implications of the results are discussed.
... Furthermore, cannabis use by the mother can impair the mother's attention and judgement while taking care of the baby, leading to unsafe conditions (Jansson et al., 2018). To date, clinical literature on the topic is dominated by data from two large longitudinal studies of prenatal cannabinoid exposure in humans, the Ottawa Prenatal Prospective Study (OPPS) and the Maternal Health Practices and Child Development Project (MHPCDP) (Campolongo et al., 2009;Fried, 2002b;Fried et al., 1998;Fried and Watkinson, 1990;Goldschmidt et al., 2012;Trezza et al., 2008). Additionally, recently published results from another large longitudinal study conducted in the Netherlands add more current insights to this body of literature from a different population (El Marroun et al., 2018). ...
Article
Marijuana is one of the most commonly used illicit drugs worldwide. In addition, use of synthetic cannabinoids is increasing, especially among adolescents and young adults. Although human studies have shown that the use of marijuana during pregnancy leads to adverse behavioral effects, such as deficiencies in attention and executive function in affected offspring, the rate of marijuana use among pregnant women is steadily increasing. Various aspects of human behavior including emotion, learning, and memory are dependent on complex interactions between multiple neurotransmitter systems that are especially vulnerable to alterations during the developmental period. Thus, exploration of neurotransmitter changes in response to prenatal cannabinoid exposure is crucial to develop an understanding of how homeostatic imbalance and various long-term neurobehavioral deficits manifest following the abuse of marijuana or other synthetic cannabinoids during pregnancy. Current literature confirms that vast alterations to neurotransmitter systems are present following prenatal cannabinoid exposure, and many of these alterations within the brain are region specific, time-dependent, and sexually dimorphic. In this review, we aim to provide a summary of observed changes to various neurotransmitter systems following cannabinoid exposure during pregnancy and to draw possible correlations to reported behavioral alterations in affected offspring.
... For fetal harms with cannabis use in pregnancy not addressed by included reviews, one case-control study found no association between sudden infant death syndrome and maternal cannabis exposure at conception (adjusted OR circumference, persisting until 12 years of age, 42 but not seen at 13 to 16 years of age. 39 Infants of heavy cannabis users were also lightest at birth, but no differences in height, weight, ponderal index, or onset of puberty were seen at 13 to 16 years of age. ...
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The growing demand for improved pain treatments together with expanding legalization of, and access to, cannabinoids, cannabis, and cannabis-based medicines has intensified the focus on risk-benefit considerations in pain management. Given limited harms data from analgesic clinical trials, we conducted an overview of systematic reviews focused on all harms possibly relevant to patients receiving cannabinoids for pain management. This PROSPERO-registered, PRISMA-compliant systematic overview identified 79 reviews, encompassing over 2200 individual reports about psychiatric and psychosocial harms, cognitive/behavioral effects, motor vehicle accidents, cardiovascular, respiratory, cancer-related, maternal/fetal, and general harms. Reviews, and their included studies, were of variable quality. Available evidence suggests variable associations between cannabis exposure (ranging from monthly to daily use based largely on self-report) and psychosis, motor vehicle accidents, respiratory problems, and other harms. Most evidence comes from settings other than that of pain management (eg, nonmedicinal and experimental) but does signal a need for caution and more robust harms evaluation in future studies. Given partial overlap between patients receiving cannabinoids for pain management and individuals using cannabinoids for other reasons, lessons from the crisis of oversupply and overuse of opioids in some parts of the world emphasize the need to broadly consider harms evidence from real-world settings. The advancement of research on cannabinoid harms will serve to guide optimal approaches to the use of cannabinoids for pain management. In the meantime, this evidence should be carefully examined when making risk-benefit considerations about the use of cannabinoids, cannabis, and cannabis-based medicine for chronic pain.
... 315,349,358 However, there is some evidence that prenatal marijuana use may lead to subtle impairments in executive functioning, motor skills, attention and memory in childhood and adolescence. [359][360][361] In a mouse model study, synthetic cannabinoids were found to interact synergistically with ethanol to increase the prevalence of ocular defects. ...
... Evidence on the effect of prenatal marijuana exposure on growth outcomes has been inconsistent [68,71,84]. However, marijuana use may lead to subtle impairments in cognitive and motor skills in childhood and adolescence [85][86][87]. In a mouse model study, synthetic cannabinoids were found to interact with ethanol to increase the prevalence of ocular defects [88]. ...
Article
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Foetal alcohol spectrum disorders (FASDs) are a leading cause of developmental disability. Prenatal alcohol use is the sole necessary cause of FASD, but it is not always sufficient. Multiple factors influence a child’s susceptibility to FASD following prenatal alcohol exposure. Much of the FASD risk factor literature has been limited to discussions of association, rather than causation. While knowledge of predictor variables is important for identifying who is most at risk of FASD and for targeting interventions, causal knowledge is important for identifying effective mechanisms for prevention and intervention programmes. We conducted a systematic search and narrative synthesis of the evidence and used this to create a causal diagram (directed acyclic graph; DAG) to describe the causal pathways to FASD. Our results show that the aetiology of FASD is multifaceted and complex. FASD risk is determined by a range of lifestyle, sociodemographic, maternal, social, gestational, and genetic factors. The causal diagram that we present in this review provides a comprehensive summary of causal risk factors for FASD and can be used as a tool to inform data collection and statistical modelling strategies to minimise bias in future studies of FASD.
... Recent evidence from ABCD and other studies suggests that prenatal cannabis exposure is associated with increased risk of behavioral problems during middle childhood after accounting for potential confounds (Corsi et al., 2020;Paul et al., 2019) and that prenatal opioid exposure is associated with differences in brain structure (Hartwell, Croff, Morris, Breslin, & Dunn, 2020). There are few longitudinal studies extending beyond the preschool period that examine the effect of prenatal substance exposures, and in particular prenatal opioid exposure (POE; Jones et al., 2012;Bakhireva et al., 2019) and prenatal cannabis exposure (Fried, Watkinson, & Gray, 1998;Huizink, 2014;Jaddoe et al., 2012). Studies that follow children to middle childhood, as proposed in HBCD, allow an examination of executive function and other cognitive domains that are not fully mature earlier in development and could be integrated with the ABCD Study, and other studies, to collectively extend research across the life course by integrating data across cohorts. ...
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Identifying factors associated with disruptions in early neurodevelopment is imperative for promoting the health and wellbeing of children. We describe a design framework for biospecimen collection for the forthcoming HEALthy Brain and Child Development (HBCD) study, which seeks to establish a large cohort of pregnant women throughout the USA and follow their children into middle childhood. Biospecimens and biological outcomes of interest, together with validated questionnaires and other measures, may help to disentangle the effect of prenatal exposures from social and environment factors that extend across the prenatal and postnatal periods, including early life adversity (ELA). Biospecimen selection is discussed across four domains of interest: (a) substance use exposure, (b) other environmental exposures, (c) genomics and epigenomics, and (d) other biological markers of neurodevelopment and putative moderators and mediators of developmental effects. HBCD biospecimen working group recommendations were based on nine guiding principles including utility as a biomarker to assess neurodevelopment; feasibility of collection during critical periods of exposure with a broad detection window; logistics and cost of specimen collection, storage, and transportation; cultural acceptability; minimal invasiveness; flexibility; high sensitivity and specificity; anticipated expertise and infrastructure at participating sites; and availability of informative alternative non-biological measures. The proposed essential and recommended biospecimens will need to be integrated with the recommendations from other HBCD working groups to ascertain overall burden for the research participants and families, feasibility of multi-modal collection at each study visit, cost, and implications for recruitment and retention, as well as any potential legal repercussions.
... Several developmental effects have also been reported, such as stunted growth and decreased weight at birth (e.g., Linn et al., 1983;Fried et al., 1984Fried et al., , 1999Cornelius et al., 1995). Other reported effects are problems in visual (Fried et al., 1998) and visuospatial working memory (Smith et al., 2006), verbal reasoning (Fried and Watkinson, 1990), and impulsivity and aggression (Leech et al., 1999;Goldschmidt et al., 2000), among others. ...
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Pre and perinatal administration of Tetrahydrocannabinol (THC) in rodents and their offspring has many effects that have been studied using different methods that have not been integrated using quantitative methods. The effect of THC administration on behavior can be better understood by meta-analytic techniques. We examined whether there is an overall effect on the behavior of the offspring when THC is administered to mothers. Eligibility criteria included experiments using an experimental design with a control group without THC, in which THC is administered to mothers during pregnancy and lactation in rodents, and in which at least one type of behavioral (locomotor, emotional or cognitive) measurement in the offspring was implemented. Cohen’s d was obtained for each study, then each individual study was weighted, and moderator analysis was performed. Analysis was performed using fixed and random effect models, and the heterogeneity was assessed by calculating Qb, I2 and the prediction interval. Furthermore, 3 sub-meta-analyses were carried out according to the type of behavior. The general analysis determined a low weighted effect size of THC on the behavior of the offspring, moderated by type of rat strain. The sub-meta-analyses showed a medium effect for cognitive effects of THC in the offspring, and a low effect on locomotor activity and emotional behavior. In addition, publication bias was not detected. More research is needed to contribute to the understanding of the effect of THC exposure on offspring.
... To date, three large prospective longitudinal cohorts have been used to investigate the consequences of prenatal cannabis exposure on neurodevelopment: The Ottawa Prenatal Prospective Study (OPPS) (72)(73)(74)(75)(76), The Maternal Health Practices and Child Development Study (MHPCD) (77,78), and The Generation R Study (GenR) (79,80). These data highlight several cognitive and behavioral domains affected by in utero exposure to cannabis. ...
Article
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Clinical reports of cannabis use prevalence during pregnancy vary widely from 3% to upwards of 35% in North America; this disparity likely owing to underestimates from self-reporting in many cases. The rise in cannabis use is mirrored by increasing global legalization and the overall perceptions of safety, even during pregnancy. These trends are further compounded by a lack of evidence-based policy and guidelines for prenatal cannabis use, which has led to inconsistent messaging by healthcare providers and medically licensed cannabis dispensaries regarding prenatal cannabis use for treatment of symptoms, such as nausea. Additionally, the use of cannabis to self-medicate depression and anxiety during pregnancy is a growing medical concern. This review aims to summarize recent findings of clinical and preclinical data on neonatal outcomes, as well as long-term physiological and neurodevelopmental outcomes of prenatal cannabis exposure. Although many of the outcomes under investigation have produced mixed results, we consider these data in light of the unique challenges facing cannabis research. In particular, the limited longitudinal clinical studies available have not previously accounted for the exponential increase in (-)-Δ9– tetrahydrocannabinol (Δ9–THC; the psychoactive compound in cannabis) concentrations found in cannabis over the past two decades. Polydrug use and the long-term effects of individual cannabis constituents [Δ9–THC vs. cannabidiol (CBD)] are also understudied, along with sex-dependent outcomes. Despite these limitations, prenatal cannabis exposure has been linked to low birth weight, and emerging evidence suggests that prenatal exposure to Δ9–THC, which crosses the placenta and impacts placental development, may have wide-ranging physiological and neurodevelopmental consequences. The long-term effects of these changes require more rigorous investigation, though early reports suggest Δ9–THC increases the risk of cognitive impairment and neuropsychiatric disease, including psychosis, depression, anxiety, and sleep disorders. In light of the current trends in the perception and use of cannabis during pregnancy, we emphasize the social and medical imperative for more rigorous investigation of the long-term effects of prenatal cannabis exposure.
... ''Phytochemical polymorphism'' often occurs in the Cannabis plant, as the production of monoterpenoids with an insect-repellent effect is more pronounced in the flowers, whereas in the leaves, especially the lower leaves, bitter sesquiterpenoids, that function as antifeedants, are more prevalent (Franz and Novak 2010). Monoterpenoids (especially b-myrcene (18), a-pinene (19), and D-limonene (20), Fig. 14) are usually present in greater amounts, but their content decreases significantly during drying and storage, and sesquiterpenoids, especially b-caryophyllene (21), therefore mostly predominate in dry drugs and also in extracts (Ross and ElSohly 1996). ...
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Cannabis spp. are some of the most controversial medicinal plants in the world. They contain great amounts of biologically active secondary metabolites, including the typical phenolic compounds called cannabinoids. Because of their low toxicity and complex biological activities, cannabinoids can be useful in the therapy of various diseases, but adverse psychological effects (of Δ9-THC in particular) raise concerns. This review summarizes the current knowledge of selected active C. indica compounds and their therapeutic potential. We summarize the main compounds contained in cannabis, the mechanisms of their effects, and their potential therapeutic applications. Further, we mention some of the clinical tests used to evaluate the efficacy of cannabinoids in therapy.
Article
Background Exposure to tobacco during pregnancy may disrupt fetal brain development and impact offspring cognitive development. Aims To perform a systematic review and meta-analysis on maternal smoking during pregnancy and intelligence quotient (IQ) in childhood, adolescence, and adulthood. Methods We searched PubMed, Lilacs, PsycINFO, and Web of Science. Original articles evaluating tobacco use/exposure during pregnancy and the offspring’s IQ as the outcome. The review protocol is registered in PROSPERO (number CRD 42019116257). For the meta-analysis, we included studies with information on the regression coefficient and its confidence interval (CI) or standard error. Random effects model was used for pooling the estimates. Results 25 studies were included in the review, and of these 14 met the inclusion criteria for the meta-analysis. The overall pooled estimate showed that subjects who were exposed to maternal smoking during pregnancy presented lower IQ scores, compared to those not exposed to maternal smoking (β -1.30; 95% CI ―1.74, ―0.86; I² = 87.8%); IQ scores were also lower in crude (β -5.46; 95% CI -7.31, -3.60; I²: 79.0%) and adjusted pooled estimates (β =―0.45; 95% CI ―0.76, ―0.13; I² = 80.4%), for the group exposed to maternal smoking. In the stratified analysis, an inverse association was also observed in studies with large sample size (n≥1000 participants) (β=―0.49; 95% CI ―0.96, ―0.02), among those performed with adolescents (β=―1.16; 95% CI ―2.18, ―0.14), and among those adjusted for maternal education (β=―0.57; 95% CI ―1.05, ―0.08). Conclusions Our findings suggest that exposure to tobacco during pregnancy may have negative effects on IQ. However, the findings of this meta-analysis should be interpreted with caution.
Article
Introduction Cannabis is a widely used substance in pregnancy, yet there is a paucity of literature addressing the neuro-behavioural consequences for prenatally exposed children. Our systematic review synthesizes currently available data for the impact of prenatal cannabis use on offspring intelligence and cognitive functioning. Methods MEDLINE, EMBASE, PsychINFO, CINAHL, and Clinicaltrials.gov were searched. Observational studies comparing prenatal cannabis use to controls were included. Offspring neuro-behavioural outcomes were grouped in prespecified domains of (1) intelligence and (2) cognitive functioning. Random-effect models were performed for meta-analyses when at least three studies reported the same outcome. All others were summarized qualitatively. GRADE (Grading of Recommendations, Assessment, Development and Evaluations) framework was used to assess evidence certainty. Results Of the 1982 reviewed studies (n = 523,107 patients), 28 were included. Significant heterogeneity and cohort redundancy limited meta-analysis. Very low-quality evidence from pooled analyses showed no significant associations between prenatal cannabis exposure and attention [standardized mean difference = −0.27 (95% CI = −0.60 to 0.07)], global intelligence quotient [−0.16 (−0.42 to 0.10)], reading [−0.05 (−0.29 to 0.20)], written comprehension [−0.09 (−0.40 to 0.22)], spelling [−0.04 (−0.26 to 0.17)], and mathematics [−0.01 (−0.15 to 0.13)]. No significant associations were found between prenatal cannabis exposure for all other outcomes. Individual studies reported significant differences between the heavy use groups and non-exposed, although this did not prove to be significant when outcomes were pooled. Conclusions The current review did not find a clear association between prenatal cannabis use and offspring neuro-behavioural outcomes. However, evidence was low quality and heterogenous. Further prospective investigation is needed to elucidate any potential association between prenatal cannabis use and long-term neuro-developmental outcomes.
Article
Objective There is an association between recreational marijuana use in pregnancy and legalization. As more states legalize marijuana, its use in pregnancy may increase. The objective of this study was to evaluate pregnant women’s knowledge and opinions about marijuana use, potential risks, and legalization. Methods A cross-sectional survey of pregnant women at a regional perinatal center in New Jersey was performed from January-December 2019. Pregnant subjects were invited to complete a voluntary, anonymous 23-question survey about marijuana use in pregnancy, potential risks, and legalization. Subjects were excluded if they could not read in English or Spanish. Survey questions were based on a 5-point Likert scale (1 = strongly agree, 2 = agree, 3 = neutral, 4 = disagree, and 5 = strongly disagree). Likelihood of agreeing or disagreeing with potential risks, with neutral responses as the reference, were estimated based on the relative risk (RR) (95% confidence interval [CI]). Associations were examined with prior tobacco/marijuana use and education level. Results During the study period, approximately 1133 consecutive patients were approached and 843 completed the study (74.4% response rate). The majority of participants were English-speaking, college educated, and employed. 204 (25.2%) reported prior marijuana use and 36 (4.5%) reported marijuana use during pregnancy. Overall, pregnant women had poor knowledge about potential risks of marijuana use in pregnancy. Although 234 (29.0%) patients were opposed to legalization, more than 90% of pregnant subjects indicated that they would be more likely to use marijuana in pregnancy if it were legalized. Associations of marijuana risks by prior tobacco use showed that nonsmokers had more awareness about risks. Nonsmokers had higher likelihood of agreeing that marijuana use may be harmful to a pregnancy (RR 1.41, 95% CI 1.12–1.76), may hurt the growth of a baby (RR 1.36, 95% CI 1.07–1.74), may cause preterm birth (RR 1.18, 95% CI 1.00–1.40), and may hurt a child’s ability to learn (RR 1.20, 95% CI 0.95–1.51). Similar trends were observed for subjects who reported no prior marijuana use and for subjects with more than high school education. Conclusions The majority of surveyed pregnant women demonstrated poor knowledge about the possible risks of marijuana in pregnancy and indicated that they would be more likely to use marijuana in pregnancy if it were legalized. As the use of marijuana increases, providers should focus on educating their patients about potential risks associated with marijuana use in pregnancy while additional research is needed to clarify associated risks.
Article
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Background: Despite limited data demonstrating pronounced negative effects of prenatal cannabis exposure, popular opinion and public policies still reflect the belief that cannabis is fetotoxic. Methods: This article provides a critical review of results from longitudinal studies examining the impact of prenatal cannabis exposure on multiple domains of cognitive functioning in individuals aged 0 to 22 years. A literature search was conducted through PsycINFO, PubMed, and Google Scholar. Articles were included if they examined the cognitive performance of offspring exposed to cannabis in utero. Results: An examination of the total number of statistical comparisons (n = 1,001) between groups of participants that were exposed to cannabis prenatally and non-exposed controls revealed that those exposed performed differently on a minority of cognitive outcomes (worse on <3.5 percent and better in <1 percent). The clinical significance of these findings appears to be limited because cognitive performance scores of cannabis-exposed groups overwhelmingly fell within the normal range when compared against normative data adjusted for age and education. Conclusions: The current evidence does not suggest that prenatal cannabis exposure alone is associated with clinically significant cognitive functioning impairments.
Article
The use of cannabis during pregnancy is a growing public health concern. As more countries implement legislation permitting recreational cannabis use, there is an urgent need to better understand its impact on fetal neurodevelopment and its long-term effects in exposed offspring. Studies examining effects of prenatal cannabis exposure typically employ injections of synthetic cannabinoids or isolated cannabis constituents that may not accurately model cannabis use in human populations. To address this limitation, we developed a novel e-cigarette technology-based system to deliver vaporized cannabis extracts to pregnant Long Evans rats. We used this model to determine effects of prenatal cannabis exposure on emotional, social, and cognitive endpoints of male and female offspring during early development and into adulthood. Dams were exposed to cannabis vapor (CANTHC: 400 mg/ml), vehicle vapor (VEH), or no vapor (AIR) twice daily during mating and gestation. Offspring exposed to CANTHC and VEH showed reduced weight gain relative to AIR offspring prior to weaning. CANTHC offspring made more isolation-induced ultrasonic vocalizations (USVs) on postnatal day 6 (P6) relative to VEH-exposed offspring, which is indicative of increased emotional reactivity. Male CANTHC offspring engaged in fewer social investigation behaviors than VEH-exposed male offspring during a social play test on P26. In adulthood, CANTHC-exposed offspring spent less time exploring the open arms of the elevated plus maze and exhibited dose-dependent deficits in behavioral flexibility in an attentional set-shifting task relative to AIR controls. These data collectively indicate that prenatal cannabis exposure may cause enduring effects on the behavioral profile of offspring.
Article
Prenatal marijuana exposure (PME) negatively impacts child development and behavior; however, few studies have examined these associations at early ages among children exposed to today's highly potent marijuana. Using a prospective prenatal cohort (Columbus, Ohio, USA), PME was determined from maternal self-report, medical chart abstraction, and urine toxicology from prenatal visits and delivery. At age 3.5 years, 63 offspring children completed tasks assessing executive function (EF), visual spatial ability, emotion regulation, and aggressive behavior. Caregivers reported on children's EF and problem behaviors. Logistic regressions and analyses of covariance controlling for key variables were used to examine associations between PME and child outcomes. Compared to non-exposed children, children with PME had more sleep-related problems, withdrawal symptoms, and externalizing problems, including aggressive behaviors and oppositional defiant behaviors. Children with and without PME did not differ in terms of executive functioning. Findings suggest behavioral problems associated with PME may manifest by age 3.5.
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Executive dysfunction occurs in many clinical conditions and has significant impact on multiple facets of life. This book summarizes executive function and dysfunction for practitioners, researchers and educators, covering lifespan development, assessment, impact and interventions. Drawing together clinical, neurobiological and developmental viewpoints, the authors summarize the latest research findings in practical and applied terms, and review conceptual approaches to assessing and identifying executive function and dysfunction. Several chapters are devoted to practical aspects of executive dysfunction, including research-based treatment strategies, educational implications, forensic cautions and intervention resources. Executive dysfunction in ADHD, LD, MR, autism, mood disorders, epilepsy, cancer and TBI is covered, with test performance, neuroimaging and clinical presentation for these clinical conditions. The book concludes with anticipation of future work in the field. This is a key reference for medical, psychological and educational professionals who work with children, adolescents and young adults in clinical and educational settings.
Chapter
Executive dysfunction occurs in many clinical conditions and has significant impact on multiple facets of life. This book summarizes executive function and dysfunction for practitioners, researchers and educators, covering lifespan development, assessment, impact and interventions. Drawing together clinical, neurobiological and developmental viewpoints, the authors summarize the latest research findings in practical and applied terms, and review conceptual approaches to assessing and identifying executive function and dysfunction. Several chapters are devoted to practical aspects of executive dysfunction, including research-based treatment strategies, educational implications, forensic cautions and intervention resources. Executive dysfunction in ADHD, LD, MR, autism, mood disorders, epilepsy, cancer and TBI is covered, with test performance, neuroimaging and clinical presentation for these clinical conditions. The book concludes with anticipation of future work in the field. This is a key reference for medical, psychological and educational professionals who work with children, adolescents and young adults in clinical and educational settings.
Chapter
Executive dysfunction occurs in many clinical conditions and has significant impact on multiple facets of life. This book summarizes executive function and dysfunction for practitioners, researchers and educators, covering lifespan development, assessment, impact and interventions. Drawing together clinical, neurobiological and developmental viewpoints, the authors summarize the latest research findings in practical and applied terms, and review conceptual approaches to assessing and identifying executive function and dysfunction. Several chapters are devoted to practical aspects of executive dysfunction, including research-based treatment strategies, educational implications, forensic cautions and intervention resources. Executive dysfunction in ADHD, LD, MR, autism, mood disorders, epilepsy, cancer and TBI is covered, with test performance, neuroimaging and clinical presentation for these clinical conditions. The book concludes with anticipation of future work in the field. This is a key reference for medical, psychological and educational professionals who work with children, adolescents and young adults in clinical and educational settings.
Chapter
Executive dysfunction occurs in many clinical conditions and has significant impact on multiple facets of life. This book summarizes executive function and dysfunction for practitioners, researchers and educators, covering lifespan development, assessment, impact and interventions. Drawing together clinical, neurobiological and developmental viewpoints, the authors summarize the latest research findings in practical and applied terms, and review conceptual approaches to assessing and identifying executive function and dysfunction. Several chapters are devoted to practical aspects of executive dysfunction, including research-based treatment strategies, educational implications, forensic cautions and intervention resources. Executive dysfunction in ADHD, LD, MR, autism, mood disorders, epilepsy, cancer and TBI is covered, with test performance, neuroimaging and clinical presentation for these clinical conditions. The book concludes with anticipation of future work in the field. This is a key reference for medical, psychological and educational professionals who work with children, adolescents and young adults in clinical and educational settings.
Chapter
Executive dysfunction occurs in many clinical conditions and has significant impact on multiple facets of life. This book summarizes executive function and dysfunction for practitioners, researchers and educators, covering lifespan development, assessment, impact and interventions. Drawing together clinical, neurobiological and developmental viewpoints, the authors summarize the latest research findings in practical and applied terms, and review conceptual approaches to assessing and identifying executive function and dysfunction. Several chapters are devoted to practical aspects of executive dysfunction, including research-based treatment strategies, educational implications, forensic cautions and intervention resources. Executive dysfunction in ADHD, LD, MR, autism, mood disorders, epilepsy, cancer and TBI is covered, with test performance, neuroimaging and clinical presentation for these clinical conditions. The book concludes with anticipation of future work in the field. This is a key reference for medical, psychological and educational professionals who work with children, adolescents and young adults in clinical and educational settings.
Chapter
Executive dysfunction occurs in many clinical conditions and has significant impact on multiple facets of life. This book summarizes executive function and dysfunction for practitioners, researchers and educators, covering lifespan development, assessment, impact and interventions. Drawing together clinical, neurobiological and developmental viewpoints, the authors summarize the latest research findings in practical and applied terms, and review conceptual approaches to assessing and identifying executive function and dysfunction. Several chapters are devoted to practical aspects of executive dysfunction, including research-based treatment strategies, educational implications, forensic cautions and intervention resources. Executive dysfunction in ADHD, LD, MR, autism, mood disorders, epilepsy, cancer and TBI is covered, with test performance, neuroimaging and clinical presentation for these clinical conditions. The book concludes with anticipation of future work in the field. This is a key reference for medical, psychological and educational professionals who work with children, adolescents and young adults in clinical and educational settings.
Chapter
Executive dysfunction occurs in many clinical conditions and has significant impact on multiple facets of life. This book summarizes executive function and dysfunction for practitioners, researchers and educators, covering lifespan development, assessment, impact and interventions. Drawing together clinical, neurobiological and developmental viewpoints, the authors summarize the latest research findings in practical and applied terms, and review conceptual approaches to assessing and identifying executive function and dysfunction. Several chapters are devoted to practical aspects of executive dysfunction, including research-based treatment strategies, educational implications, forensic cautions and intervention resources. Executive dysfunction in ADHD, LD, MR, autism, mood disorders, epilepsy, cancer and TBI is covered, with test performance, neuroimaging and clinical presentation for these clinical conditions. The book concludes with anticipation of future work in the field. This is a key reference for medical, psychological and educational professionals who work with children, adolescents and young adults in clinical and educational settings.
Chapter
Executive dysfunction occurs in many clinical conditions and has significant impact on multiple facets of life. This book summarizes executive function and dysfunction for practitioners, researchers and educators, covering lifespan development, assessment, impact and interventions. Drawing together clinical, neurobiological and developmental viewpoints, the authors summarize the latest research findings in practical and applied terms, and review conceptual approaches to assessing and identifying executive function and dysfunction. Several chapters are devoted to practical aspects of executive dysfunction, including research-based treatment strategies, educational implications, forensic cautions and intervention resources. Executive dysfunction in ADHD, LD, MR, autism, mood disorders, epilepsy, cancer and TBI is covered, with test performance, neuroimaging and clinical presentation for these clinical conditions. The book concludes with anticipation of future work in the field. This is a key reference for medical, psychological and educational professionals who work with children, adolescents and young adults in clinical and educational settings.
Chapter
Executive dysfunction occurs in many clinical conditions and has significant impact on multiple facets of life. This book summarizes executive function and dysfunction for practitioners, researchers and educators, covering lifespan development, assessment, impact and interventions. Drawing together clinical, neurobiological and developmental viewpoints, the authors summarize the latest research findings in practical and applied terms, and review conceptual approaches to assessing and identifying executive function and dysfunction. Several chapters are devoted to practical aspects of executive dysfunction, including research-based treatment strategies, educational implications, forensic cautions and intervention resources. Executive dysfunction in ADHD, LD, MR, autism, mood disorders, epilepsy, cancer and TBI is covered, with test performance, neuroimaging and clinical presentation for these clinical conditions. The book concludes with anticipation of future work in the field. This is a key reference for medical, psychological and educational professionals who work with children, adolescents and young adults in clinical and educational settings.
Chapter
Executive dysfunction occurs in many clinical conditions and has significant impact on multiple facets of life. This book summarizes executive function and dysfunction for practitioners, researchers and educators, covering lifespan development, assessment, impact and interventions. Drawing together clinical, neurobiological and developmental viewpoints, the authors summarize the latest research findings in practical and applied terms, and review conceptual approaches to assessing and identifying executive function and dysfunction. Several chapters are devoted to practical aspects of executive dysfunction, including research-based treatment strategies, educational implications, forensic cautions and intervention resources. Executive dysfunction in ADHD, LD, MR, autism, mood disorders, epilepsy, cancer and TBI is covered, with test performance, neuroimaging and clinical presentation for these clinical conditions. The book concludes with anticipation of future work in the field. This is a key reference for medical, psychological and educational professionals who work with children, adolescents and young adults in clinical and educational settings.
Chapter
Executive dysfunction occurs in many clinical conditions and has significant impact on multiple facets of life. This book summarizes executive function and dysfunction for practitioners, researchers and educators, covering lifespan development, assessment, impact and interventions. Drawing together clinical, neurobiological and developmental viewpoints, the authors summarize the latest research findings in practical and applied terms, and review conceptual approaches to assessing and identifying executive function and dysfunction. Several chapters are devoted to practical aspects of executive dysfunction, including research-based treatment strategies, educational implications, forensic cautions and intervention resources. Executive dysfunction in ADHD, LD, MR, autism, mood disorders, epilepsy, cancer and TBI is covered, with test performance, neuroimaging and clinical presentation for these clinical conditions. The book concludes with anticipation of future work in the field. This is a key reference for medical, psychological and educational professionals who work with children, adolescents and young adults in clinical and educational settings.
Article
Objective: To study the association between nicotine or cannabis metabolite presence in maternal urine and child neurodevelopmental outcomes. Methods: We conducted a secondary analysis of two parallel multicenter randomized controlled trials of treatment for hypothyroxinemia or subclinical hypothyroidism among pregnant individuals enrolled at 8-20 weeks of gestation. All maternal-child dyads with a maternal urine sample at enrollment and child neurodevelopmental testing were included (N=1,197). Exposure was urine samples positive for nicotine (cotinine) or cannabis 11-nor-9-carboxy-delta-9-tetrahydrocannabinol [THC-COOH]) or both metabolites. Primary outcome was child IQ at 60 months. Secondary outcomes included cognitive, motor and language, attention, behavioral and social competency, and differential skills assessments at 12, 24, 36, and 48 months. Quantile regression analysis was performed with confounder adjustment. Results: Of 1,197 pregnant individuals, 99 (8.3%) had positive cotinine samples and 47 (3.9%) had positive THC-COOH samples; 33 (2.8%) were positive for both. Groups differed in self-reported race and ethnicity, education, marital status, insurance, and thyroid status. Median IQ was similar between cotinine-exposed and -unexposed children (90 vs 95, adjusted difference in medians -2.47, 95% CI -6.22 to 1.29) and THC-COOH-exposed and -unexposed children (89 vs 95, adjusted difference in medians -1.35, 95% CI -7.76 to 5.05). In secondary outcome analysis, children with THC-COOH exposure compared with those unexposed had higher attention scores at 48 months of age (57 vs 49, adjusted difference in medians 6.0, 95% CI 1.11-10.89). Conclusions: Neither prenatal nicotine nor cannabis exposure was associated with a difference in IQ. Cannabis exposure was associated with worse attention scores in early childhood. Longitudinal studies assessing associations between child neurodevelopmental outcomes and prenatal nicotine and cannabis exposure with a focus on timing and quantity of exposure are needed. Clinical trial registration: ClinicalTrials.gov, NCT00388297.
Chapter
Executive dysfunction occurs in many clinical conditions and has significant impact on multiple facets of life. This book summarizes executive function and dysfunction for practitioners, researchers and educators, covering lifespan development, assessment, impact and interventions. Drawing together clinical, neurobiological and developmental viewpoints, the authors summarize the latest research findings in practical and applied terms, and review conceptual approaches to assessing and identifying executive function and dysfunction. Several chapters are devoted to practical aspects of executive dysfunction, including research-based treatment strategies, educational implications, forensic cautions and intervention resources. Executive dysfunction in ADHD, LD, MR, autism, mood disorders, epilepsy, cancer and TBI is covered, with test performance, neuroimaging and clinical presentation for these clinical conditions. The book concludes with anticipation of future work in the field. This is a key reference for medical, psychological and educational professionals who work with children, adolescents and young adults in clinical and educational settings.
Chapter
Executive dysfunction occurs in many clinical conditions and has significant impact on multiple facets of life. This book summarizes executive function and dysfunction for practitioners, researchers and educators, covering lifespan development, assessment, impact and interventions. Drawing together clinical, neurobiological and developmental viewpoints, the authors summarize the latest research findings in practical and applied terms, and review conceptual approaches to assessing and identifying executive function and dysfunction. Several chapters are devoted to practical aspects of executive dysfunction, including research-based treatment strategies, educational implications, forensic cautions and intervention resources. Executive dysfunction in ADHD, LD, MR, autism, mood disorders, epilepsy, cancer and TBI is covered, with test performance, neuroimaging and clinical presentation for these clinical conditions. The book concludes with anticipation of future work in the field. This is a key reference for medical, psychological and educational professionals who work with children, adolescents and young adults in clinical and educational settings.
Chapter
Executive dysfunction occurs in many clinical conditions and has significant impact on multiple facets of life. This book summarizes executive function and dysfunction for practitioners, researchers and educators, covering lifespan development, assessment, impact and interventions. Drawing together clinical, neurobiological and developmental viewpoints, the authors summarize the latest research findings in practical and applied terms, and review conceptual approaches to assessing and identifying executive function and dysfunction. Several chapters are devoted to practical aspects of executive dysfunction, including research-based treatment strategies, educational implications, forensic cautions and intervention resources. Executive dysfunction in ADHD, LD, MR, autism, mood disorders, epilepsy, cancer and TBI is covered, with test performance, neuroimaging and clinical presentation for these clinical conditions. The book concludes with anticipation of future work in the field. This is a key reference for medical, psychological and educational professionals who work with children, adolescents and young adults in clinical and educational settings.
Chapter
Executive dysfunction occurs in many clinical conditions and has significant impact on multiple facets of life. This book summarizes executive function and dysfunction for practitioners, researchers and educators, covering lifespan development, assessment, impact and interventions. Drawing together clinical, neurobiological and developmental viewpoints, the authors summarize the latest research findings in practical and applied terms, and review conceptual approaches to assessing and identifying executive function and dysfunction. Several chapters are devoted to practical aspects of executive dysfunction, including research-based treatment strategies, educational implications, forensic cautions and intervention resources. Executive dysfunction in ADHD, LD, MR, autism, mood disorders, epilepsy, cancer and TBI is covered, with test performance, neuroimaging and clinical presentation for these clinical conditions. The book concludes with anticipation of future work in the field. This is a key reference for medical, psychological and educational professionals who work with children, adolescents and young adults in clinical and educational settings.
Chapter
While it is commonly known that cannabis impacts the developing adolescent brain, it is important for clinicians tp understand the basic science underlying the impact of cannabis on neurodevelopment. A brief basic science review of the endocannabinoid system and how THC interacts with it to alter neuromaturation provides the background necessary for understanding the consequences of fetal and adolescent exposure to cannabis. The prevalence of cannabis use during pregnany is discussed along with its impact on neural migration and axonal growth in the fetus. Data regarding long-term functional consequences of fetal exposure to THC are presented. The second period of rapid neurodevelopment takes place during adolescence and is also altered by too frequent cannabis exposure. Structural and functional impacts that linger beyond the period of acute intoxication are reviewed, including measurable deficits in memory, executive functions, inhibition control/impulsivity, error recognition, risk assessment, motivation, affect, an increased potential for psychosis, and pragmatic life consequences.
Chapter
The cultivation of cannabis for its psychoactive compound Δ⁹-tetrahydrocannabinol (THC), significant in both religious and medicinal use, reaches far into our cultural history. Due to the easing of legislative restrictions, the commercialization of cultivation, and the increasing rise of its acceptance in recreational and medical use, cannabis has gained immense popularity. While the largely reversible effects of THC on the adult brain are well researched, its potential disruptive nature during critical developmental periods, especially during adolescence, are far from understood. This is a pressing need, as the widespread availability of high potency cannabis preparations accessible to teenagers exposes the developing brain to unwanted drug effects. This chapter aims to elucidate the molecular mechanisms of endogenous cannabinoid (“endocannabinoid”) signaling during brain development, by correlating human longitudinal studies and in-depth animal experimentation, and conclude that plant-derived cannabinoids are efficacious to disrupt endocannabinoid functions leading to adverse network modifications and behavioral outcomes in later life.
Article
This research examines maternal smoking during pregnancy and risk for poorer executive function in siblings discordant for exposure. Data ( N = 173 families) were drawn from the Missouri Mothers and Their Children study, a sample, identified using birth records (years 1998–2005), in which mothers changed smoking behavior between two pregnancies (Child 1 [older sibling]: M age = 12.99; Child 2 [younger sibling]: M age = 10.19). A sibling comparison approach was used, providing a robust test for the association between maternal smoking during pregnancy and different aspects of executive function in early-mid adolescence. Results suggested within-family (i.e., potentially causal) associations between maternal smoking during pregnancy and one working memory task (visual working memory) and one response inhibition task (color-word interference), with increased exposure associated with decreased performance. Maternal smoking during pregnancy was not associated with stop-signal reaction time, cognitive flexibility/set-shifting, or auditory working memory. Initial within-family associations between maternal smoking during pregnancy and visual working memory as well as color-word interference were fully attenuated in a model including child and familial covariates. These findings indicate that exposure to maternal smoking during pregnancy may be associated with poorer performance on some, but not all skills assessed; however, familial transmission of risk for low executive function appears more important.
Article
Given increases in cannabis use in pregnancy and animal model research showing effects of in‐utero cannabis exposure, high‐quality information on long‐term consequences of in‐utero cannabis exposure in humans is needed. While reviews have summarized findings from observational studies with humans, reviews have not focused on limitations of these studies and recommendations for future research. Therefore, we critically reviewed observational research on in‐utero cannabis exposure and psychiatric and neurodevelopmental outcomes measured at or after age 3 and provided recommendations for future research. We used Web of Science, Google Scholar, and work cited from relevant identified publications to identify 46 papers to include in our review. Our review includes two main sections. The first section highlights the extensive limitations of the existing research, which include small and nongeneralizable samples, reliance on self‐reported data, lack of detail on timing and amount of exposure, inclusion of older exposure data only, not accounting for important confounders, inclusion of potential mediators as covariates, not including outcome severity measures, and not assessing for offspring sex differences. The second section provides recommendations for future research regarding exposure and outcome measures, sample selection, confounder adjustment, and other methodological considerations. For example, with regard to exposure definition, we recommend that studies quantify the amount of cannabis exposure, evaluate the influence of timing of exposure, and incorporate biological measures (e.g., urine toxicology measures). Given that high‐quality information on long‐term consequences of in‐utero cannabis exposure in humans does not yet exit, it is crucial for future research to address the limitations we have identified.
Article
Objectives We hypothesized that prenatal cannabis exposure (PCE) would be associated with increased attention problems and altered neurocognition in young adolescents. Methods Data were obtained from the Adolescent Brain Cognitive Development (ABCD study®), a cohort of approximately 12,000 children. Presence or absence of PCE after knowledge of pregnancy was measured by caregiver report. All participants with PCE (N = 224) were included and compared to two control groups; those matched on tobacco and alcohol exposure and those without prenatal tobacco or alcohol exposures. Outcomes were measured with the ABCD baseline assessment when participants were 9–10 years old and included attention, internalizing, externalizing and total problems scales on the Child Behavior Checklist (CBCL). Teacher reports were used when available. Mixed effects modeling assessed the association between PCE and outcomes controlling for parental psychopathology, prematurity and socioeconomic status. For participants with available data, patterns of brain activity during three fMRI tasks (the Stop Signal Task measuring response inhibition, the Monetary Incentive Delay (MID) task measuring reward processing and the EN-Back task measuring working memory) were analyzed using Permutation Analyses of the Linear Model. Results Compared to both control groups, participants with PCE had significantly higher attention problems, externalizing, and total problem scores. PCE did not impact cognitive performance or patterns of brain activation during fMRI tasks. Conclusions There are long-term associations between PCE and early adolescent attention and behavioral problems. These are not reflected in cognitive performance or task fMRI measures, a finding that is consistent with reports that fewer than half of children with ADHD have any specific cognitive deficit (Nigg et al., 2005; Willcutt et al., 2005). The young age of the sample may also relate to this finding and future investigation of neurodevelopmental trajectories of youth with PCE is warranted.
Article
Background Normalisation of medicinal and recreational marijuana use has increased the importance of fully understanding effects of marijuana use on individual‐and population‐level health, including prenatal exposure effects on child development. We undertook a systematic review of the literature to examine the long‐term effects of prenatal marijuana exposure on neuropsychological function in children aged 1‐11 years. Methods Primary research publications were searched from Medline, Embase, PsychInfo, CINAHL EbscoHost, Cochrane Library, Global Health and ERIC (1980‐2018). Eligible articles documented neuropsychological outcomes in children 1‐11 years who had been prenatally exposed to marijuana. Studies of exposure to multiple prenatal drugs were included if results for marijuana exposure were reported separately from other substances. Data abstraction was independently performed by two reviewers using a standardised protocol. Results The eligible articles (n = 21) on data from seven independent longitudinal studies had high quality based on the Newcastle‐Ottawa Scale. Some analyses found associations (P < 0.05) between prenatal marijuana exposure and decreased performance on memory, impulse control, problem‐solving, quantitative reasoning, verbal development and visual analysis tests; as well as increased performance on attention and global motion perception tests. Limitations included concurrent use of other substances among study participants, potential under‐reporting and publication biases, non‐generalisable samples and limited published results preventing direct comparison of analyses. Conclusions The specific effects of prenatal marijuana exposure remain unclear and warrant further research. The larger number of neuropsychological domains that exhibit decreased versus increased psychological and behavioural functions suggests that exposure to marijuana may be harmful for brain development and function.
Article
Full-text available
A potent, synthetic cannabinoid was radiolabeled and used to characterize and precisely localize cannabinoid receptors in slide-mounted sections of rat brain and pituitary. Assay conditions for 3H-CP55,940 binding in Tris-HCl buffer with 5% BSA were optimized, association and dissociation rate constants determined, and the equilibrium dissociation constant (Kd) calculated (21 nM by liquid scintillation counting, 5.2 nM by quantitative autoradiography). The results of competition studies, using several synthetic cannabinoids, add to prior data showing enantioselectivity of binding and correlation of in vitro potencies with potencies in biological assays of cannabinoid actions. Inhibition of binding by guanine nucleotides was selective and profound: Nonhydrolyzable analogs of GTP and GDP inhibited binding by greater than 90%, and GMP and the nonhydrolyzable ATP analog showed no inhibition. Autoradiography showed great heterogeneity of binding in patterns of labeling that closely conform to cytoarchitectural and functional domains. Very dense 3H-CP55,940 binding is localized to the basal ganglia (lateral caudate-putamen, globus pallidus, entopeduncular nucleus, substantia nigra pars reticulata), cerebellar molecular layer, innermost layers of the olfactory bulb, and portions of the hippocampal formation (CA3 and dentate gyrus molecular layer). Moderately dense binding is found throughout the remaining forebrain. Sparse binding characterizes the brain stem and spinal cord. Densitometry confirmed the quantitative heterogeneity of cannabinoid receptors (10 nM 3H-CP55,940 binding ranged in density from 6.3 pmol/mg protein in the substantia nigra pars reticulata to 0.15 pmol/mg protein in the anterior lobe of the pituitary). The results suggest that the presently characterized cannabinoid receptor mediates physiological and behavioral effects of natural and synthetic cannabinoids, because it is strongly coupled to guanine nucleotide regulatory proteins and is discretely localized to cortical, basal ganglia, and cerebellar structures involved with cognition and movement.
Article
Full-text available
Investigated developmental changes in performance on cognitive and memory tests purported to reflect frontal lobe functioning in 52 normal children and adolescents, including 17 children aged 7–8 yrs, 17 children aged 9–12 yrs, and 18 adolescents aged 13–15 yrs. The tests included measures of verbal and design fluency, memory, problem solving and concept formation, and response modulation. With the exception of Delayed Alternation (a problem solving task), developmental changes were confirmed on all of the tests. Several measures of cognition and organization of memory showed major gains in adolescents as compared with 9–12 yr olds. A principal components analysis revealed a 3-factor solution, including a semantic association/concept formation factor, a freedom from perseveration factor, and a planning/strategy factor. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Article
Full-text available
A potent, synthetic cannabinoid was radiolabeled and used to characterize and precisely localize cannabinoid receptors in slide-mounted sections of rat brain and pituitary. Assay conditions for 3H-CP55,940 binding in Tris-HCl buffer with 5% BSA were optimized, association and dissociation rate constants determined, and the equilibrium dissociation constant (Kd) calculated (21 nM by liquid scintillation counting, 5.2 nM by quantitative autoradiography). The results of competition studies, using several synthetic cannabinoids, add to prior data showing enantioselectivity of binding and correlation of in vitro potencies with potencies in biological assays of cannabinoid actions. Inhibition of binding by guanine nucleotides was selective and profound: Nonhydrolyzable analogs of GTP and GDP inhibited binding by greater than 90%, and GMP and the nonhydrolyzable ATP analog showed no inhibition. Autoradiography showed great heterogeneity of binding in patterns of labeling that closely conform to cytoarchitectural and functional domains. Very dense 3H-CP55,940 binding is localized to the basal ganglia (lateral caudate-putamen, globus pallidus, entopeduncular nucleus, substantia nigra pars reticulata), cerebellar molecular layer, innermost layers of the olfactory bulb, and portions of the hippocampal formation (CA3 and dentate gyrus molecular layer). Moderately dense binding is found throughout the remaining forebrain. Sparse binding characterizes the brain stem and spinal cord. Densitometry confirmed the quantitative heterogeneity of cannabinoid receptors (10 nM 3H-CP55,940 binding ranged in density from 6.3 pmol/mg protein in the substantia nigra pars reticulata to 0.15 pmol/mg protein in the anterior lobe of the pituitary). The results suggest that the presently characterized cannabinoid receptor mediates physiological and behavioral effects of natural and synthetic cannabinoids, because it is strongly coupled to guanine nucleotide regulatory proteins and is discretely localized to cortical, basal ganglia, and cerebellar structures involved with cognition and movement.
Article
Full-text available
Clinicians report that chronic cannabis users seem to have symptoms, such as mental confusion and memory problems when entering treatment. The present study systematizes observations that were made during treatment of cannabis users during and after cessation of cannabis use. Cognitive symptoms prior to cessation are described in the conceptual framework of cognitive categories in the I.Q. test. Normalization of these cognitive functions during therapy is discussed.
Article
Objective. —To assess whether frequent marijuana use is associated with residual neuropsychological effects.Design. —Single-blind comparison of regular users vs infrequent users of marijuana.Participants. —Two samples of college undergraduates: 65 heavy users, who had smoked marijuana a median of 29 days in the past 30 days (range, 22 to 30 days) and who also displayed cannabinoids in their urine, and 64 light users, who had smoked a median of 1 day in the last 30 days (range, 0 to 9 days) and who displayed no urinary cannabinoids.Intervention. —Subjects arrived at 2 PM on day 1 of their study visit, then remained at our center overnight under supervision. Neuropsychological tests were administered to all subjects starting at 9 AM on day 2. Thus, all subjects were abstinent from marijuana and other drugs for a minimum of 19 hours before testing.Main Outcome Measures. —Subjects received a battery of standard neuropsychological tests to assess general intellectual functioning, abstraction ability, sustained attention, verbal fluency, and ability to learn and recall new verbal and visuospatial information.Results. —Heavy users displayed significantly greater impairment than light users on attentional/executive functions, as evidenced particularly by greater perseverations on card sorting and reduced learning of word lists. These differences remained after controlling for potential confounding variables, such as estimated levels of premorbid cognitive functioning, and for use of alcohol and other substances in the two groups.Conclusions. —Heavy marijuana use is associated with residual neuropsychological effects even after a day of supervised abstinence from the drug. However, the question remains open as to whether this impairment is due to a residue of drug in the brain, a withdrawal effect from the drug, or a frank neurotoxic effect of the drug.(JAMA. 1996;275:521-527)
Article
There has long been speculation as to the development of behaviors attributed to frontal lobe functioning in children. Controversy exists as to when behaviors attributed to frontal lobe functioning become fully developed. This study examined the performance of normal male and female children at four age levels between 6 and 12 years of age. Performance on verbal and nonverbal proactive and retroactive inhibition, verbal and nonverbal conflict, and two perseve‐ration tasks was assessed. The results suggested that in children, the development of behaviors associated with frontal lobe functioning is a multistage process. The greatest period of development appeared to occur at the 6‐ and 8‐year‐old levels. By the age of 10, the ability to inhibit attention to irrelevant stimuli and perseveratory responses was fairly complete, with mastery evident by age 12.
Article
遠隔記憶障害を検出する場合,想起された内容の真実性,再学習の有無,興味や関心の個人差,時間的傾斜の検出の可否が問題となる。社会的なことがらを利用した遠隔記憶検査では興味や関心の個人差が,自伝的なことがらを利用した遠隔記憶検査では想起された内容の真実性が特に問題となる。また,比較的やさしい課題で健常群の天井効果を認める場合,または,比較的難しい課題で健忘群の床効果を認める場合には,時間的傾斜の有無に関して確実なことがいえなくなる。流暢性ベースの遠隔記憶検査は,単位時間内に知人の名前や体験した出来事をできるだけたくさん想起する課題であり,検査の構造上,天井効果が起こりえないために時間的傾斜の問題を考える場合には好都合である。また,内容の異なる遠隔記憶でも流暢性ベースで質問することにより,記憶以外の条件を等しくできる利点もある。コルサコフ症候群において,自伝的記憶流暢性検査の成績は,従来までの自伝的記憶検査の成績と有意な相関を認めており,遠隔記憶検査として有用性が高いと思われた。
Article
Normative‐developmental performance on a battery of executive function tasks was investigated. Executive function was defined as goal‐directed behavior, including planning, organized search, and impulse control. Measures were drawn from clinical neuropsychology (visual search, verbal fluency, motor sequencing, and Wisconsin Card Sorting Task [WCST]) and from developmental psychology (Tower of Hanoi [TOH] and Matching Familiar Figures Test [MFFT]). A discriminant task, recognition memory, was administered, and IQ scores were available on a subset of the sample. One hundred subjects ranging from 3 to 12 years old participated; an adult group was also studied. Three major results were found: (a) adult‐level performance on different subsets of the executive function tasks was achieved at three different ages—6 years old, 10 years old, and adolescence; (b) the measures clustered into three different factors reflecting speeded responding, set maintenance, and planning; and (c) most of the executive function tasks were uncorrelated with IQ. The implications of these results for our understanding of the development of prefrontal lobe functions are discussed.
Article
The electroencephalographic (EEG) changes in a number of cortical and subcortical structures in the rat following intraperitoneal injection of 4 mg/kg THC was found to be characterized, in most animals, by a biphasic alternation between slow and fast frequencies. Using this shift in frequency as a criterion for altering physiological processes, rats were sacrificed following injections of tritiated THC. Autoradiographic techniques and scintillation counts were used to determine the distribution of THC in the nervous system and several non-neural tissues. In addition to the localization of the drug, the degree of bonding between the drug and tissue was determined by varying chasing procedures which displaced the labelled THC differentially as a function of tissue incorporation. The results indicated that approximately 0.80% of the total THC injected produced the EEG changes observed, and only 0.19% became lipophilically bound. In the nervous system, the drug appeared to be localized primarily in grey matter and deposited extensively in the extra-pyramidal motor system and some limbic structures. Non-neural organs which had extensive deposits included the liver, spleen, and kidney.
Article
A heuristic for assessing frontal lobe function in children and adolescents is described. Information presents to an input operator, which is regulated by the operations of orientation, anticipatory set, and interference control. Working memory then represents information as one of three symbol‐level systems that collectively form the knowledge base: mental models (images or more abstract representations of information whose structure corresponds to the structure of the situation they describe), semantic representations (propositions concerned with meaning), and intentional representations (propositions concerned with the knowledge and beliefs that people entertain about themselves and about each other). Knowledge base systems may undergo further elaboration or metarepresentation, becoming integrated with habits or procedures and with declarative forms of knowledge; they are also involved in monitoring the match between internal states and the external world. The heuristic helps assess and explain some observed deficits in the frontal lobe functions of attention regulation, executive control, and the intentional states important for social discourse.
Article
This review presents the potential contribution of developmental psychology to a more complete understanding of the nature of frontal lobe functioning in children. The cognitive construct of “executive function” has been adopted as a possible behavioral marker of prefrontal functioning from infancy through childhood. Instead of focusing exclusively on mature, adult‐level functioning of the frontal lobes, our article reviews evidence for the view that frontally mediated executive functions emerge in the first year of life and continue to develop at least until puberty, if not beyond. A key theme in this review is that measures used to detect executive functions must be developmentally appropriate, and suggestions regarding viable executive function measures are offered. The contribution of the animal models tested by Diamond and Goldman‐Rakic to our understanding of rudimentary executive functions in infancy is discussed. Another behavioral domain, self‐control, is proposed as a possible source of frontal assessment tools for very young children. In addition, several cognitive tasks from developmental psychology are highlighted as potential frontal measures for school‐age children. Critical issues and current problems associated with research in developmental neuropsy‐chology are discussed.
Article
Controversy exists as to when behaviors associated with frontal lobe functioning become fully developed in normal children. This investigation examined the normal development in children of the nonverbal ability to regulate and inhibit motor action and perform on tasks involving temporal ordering. Normal Black and White boys and girls ranging in age from 5 to 12 years were examined on tasks involving go‐no go decisions, auditory‐sequential and visual‐simultaneous conflict tasks, and on a task of temporal ordering. Significant age effects were found on all tasks. Six‐year‐olds clearly performed less well than 8‐, 10‐, or 12‐year‐olds, suggesting that significant development takes place between 6 to 8 years of age on these tasks. However, some behaviors attributed to frontal lobe functioning are still not mastered by age 12.
Article
although it is generally agreed that the term executive function refers to mental control processes, there is variability among users of the term as to the inclusion of attentional processes and, to a lesser extent, of inhibitory processes / center this chapter on the undisputed components of executive function, the proactive elements of interference control, effortful and flexible organization, and strategic planning—that is, anticipatory, goal-oriented "preparedness to act" / executive function is linked to learning disabilities neurological affiliations of executive function / conditions prerequisite to executive function assessment [construct validity, content validity, crystallized and fluid abilities, developmental sensitivity, test–retest reliability] / measures and strategies currently available for use [Wisconsin Card Sort Test; verbal fluency; figural fluency; disk/ring transfer tasks: Tower of Hanoi, Tower of London, Tower of Toronto; multitrial verbal (word list) learning; motor tests] / initiatives and stepwise strategies needed for instrument development / measures, instruments, and strategies most efficacious for assessment of responses to intervention and/or treatment (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Book
A major contribution to the neuropsychology of man. The first half is a review of theory and data, and the second half describes methods, chiefly developed by the author, for studying changes in behavior after brain damage in man. Translated from the Russian. Harvard Book List (edited) 1971 #152 (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Article
When a test of multiple ANOVA is found to be significant, it must be followed by other analyses before a researcher can arrive at an accurate understanding of the data set. Two possibilities for follow-up analyses include univariate ANOVA and discriminant analysis. This article presents the results of a Monte Carlo study ( N = 450) wherein typical, but simple, multivariate data were analyzed by the 2 techniques. Results demonstrate that discriminant analysis is capable of showing the underlying dimensionality of the data as well as determining the contribution of individual variables to the underlying dimensions, whereas ANOVA is limited to specifying the contribution of each variable to group separation. It is argued that when researchers analyze multivariate data, primary goals become interpretation and understanding the data set. It is concluded that discriminant analysis is most suitable for this purpose. (29 ref) (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Article
Facets of reading and language were examined in 131 9- to 12-year-old children for whom prenatal exposure to marijuana and cigarettes had been ascertained. The subjects were from a low-risk, predominantly middle class sample who are participants in an ongoing longitudinal study. Discriminant Function Analysis revealed a dose-dependent association that remained after controlling for potential confounds, between prenatal cigarette exposure and lower language and lower reading scores, particularly on auditory-related aspects of this latter measure. The findings are interpreted as consistent with earlier observations of an association between cigarette smoking during pregnancy and altered auditory functioning in the offspring. Similarities and differences between the reading observations and dyslexia are discussed. Maternal prenatal passive smoke exposure did not appear to contribute to either the language or reading outcomes at this age but postnatal secondhand smoke exposure by the child was associated with poorer language scores. Prenatal marijuana exposure was not significantly related to either the reading or language outcomes.
Article
The purpose of this overview is to provide a background for understanding the relation between the biological maturation of the frontal lobes and the development of the psychological concept of executive functions. In the first section, an interactive hierarchical feedback model is presented as a heuristic way of conceptualizing the relationship of the frontal lobes and executive functions to other brain regions and abilities. The following two sections present a synopsis of research on biological maturation and the psychological development of executive functions.
Article
Attentional behavior was examined in one hundred twenty-six 72-month-old children for whom prenatal exposure to marihuana, cigarettes, and alcohol has previously been ascertained. Discriminant Function Analysis revealed a dose-response association between prenatal cigarette exposure and impulsive behavior as manifest on poorer performance on a response inhibition task and increased errors of commission on a sustained vigilance task. Performance on a series of memory tasks particularly those requiring verbal recall was also negatively associated with maternal cigarette use. Prenatal marihuana habits were associated with increased omission errors in the vigilance task, possibly reflecting a deficit in sustained attention. In addition, Discriminant Function Analysis revealed a dose-response relationship between prenatal marihuana use and a higher rating by the mothers on an impulsive/hyperactive scale. Relatively low levels of maternal alcohol consumption was related to decreased impulsive responding both in the response inhibition task and in terms of the mothers' perception of the child's behavior. The multifaceted approach of examining attentional behavior was essential to reveal the differential associations with the three prenatally used drugs. The implications of the observations and how the findings relate to and extend the existing literature is discussed.
Article
Cognitive and receptive language development were examined in 135 60-month-old and 137 72-month-old children for whom prenatal exposure to marijuana, cigarettes, and alcohol had been ascertained. Discriminant Function analysis revealed an association between prenatal cigarette exposure and lower cognitive and receptive language scores at 60 and 72 months. This paralleled and extended observations made with this sample at annual assessments at 12 to 48 months of age. Unlike observations made at 48 months, prenatal exposure to marijuana was not associated with the cognitive and verbal outcomes. Relatively low levels of maternal alcohol consumption did not have significant relationships with the outcome variables. The importance of assessing subtle components rather than global cognitive and language skills to detect potential behavioral teratogenic effects of the drugs being examined is discussed.
Article
Brain event-related potentials (ERPs) were recorded from nine long-term cannabis users during a complex auditory selective attention task and compared with nine nonuser controls. Stimuli consisted of a random sequence of tones varying in location, pitch and duration. Subjects were instructed to respond to long-duration tones of a particular pitch and location. Cannabis users' task performance was significantly worse than controls. The most striking difference between the ERPs of the two groups was in the greatly enhanced early processing negativity in the user group to short-duration stimuli which matched the target on location only. This is indicative of users engaging in unnecessary pitch processing and thus having difficulty in setting up an accurate focus of attention and in filtering out irrelevant information. The data suggest a dysfunction in the allocation of attentional resources and stimulus evaluation strategies. These results imply that long-term cannabis use may impair the ability to efficiently process information.
Article
Previous research has determined that maternal smoking during pregnancy is associated with negative effects for the child at birth and throughout childhood. Much less is known about the consequences of exposure to secondary smoke during fetal development. The present study investigates and compares the long-term consequences of active and passive smoking during pregnancy. Ninety-one children between the ages of six and nine years were tested using a comprehensive neuropsychological test battery. After considering potential confounds, children of nonsmoking mothers generally were found to perform better than the two smoking groups on tests of speech and language skills, intelligence, visual/spatial abilities and on the mother's rating of behavior. The performance of children of passive smokers was found, in most areas, to be between that of the active smoking and nonsmoking groups. It was concluded that there is a continuum of long-term smoking effects and that, although active maternal smoking is associated with effects of greater breadth and magnitude than passive maternal smoking, children of passive smokers are also at risk for a pattern of negative developmental outcomes.
Article
Aspects of neurobehavioral development were examined in 133 36-month- and 130 48-month-old children for whom prenatal exposure to marijuana, cigarettes, and alcohol had been previously ascertained and who have been assessed since birth. Parallelling earlier observations made with this sample at 12 and 24 months, prenatal exposure to cigarette smoking was significantly associated with poorer language development and lower cognitive scores at both 36 and 48 months after statistically controlling for confounding factors. Relatively low levels of maternal alcohol consumption, which had measurable effects at 24 and 36 months, no longer had significant relationships with outcome variables at 48 months of age. At 48 months, significantly lower scores in verbal and memory domains were associated with maternal marijuana use after adjusting for confounding variables. This negative relationship is the first reported association beyond the neonatal stage, and may represent a long-term effect of the drug upon complex behavior that, at a younger age, had not developed and/or could not be assessed.
Article
Sexton M (Department of Epidemiology and Preventive Medicine, University of Maryland School of Medicine, 655 West Baltimore Street, Baltimore, Maryland 21201, USA), Fox NL and Hebel JR. Prenatal exposure to tobacco: II. Effects on cognitive functioning at age three. Interational Journal of Epidemiology 1990, 19: 72–77. Three-year-old children, born to women who smoked ten or more cigarettes at the beginning of pregnancy and identified at the time of registration for prenatal care, were assessed by the McCarthy Scales of Children's Abilities and the Minnesota Child Development Inventory. Children whose mothers quit smoking during pregnancy relative to children whose mothers persisted in smoking performed at a statistically significant higher level on the General Cognitive Index of the McCarthy and on each of the three subscales from which the General Cognitive Index is derived. The scores on the Minnesota Child Development Inventory were similar in showing a higher performance in the children of quitters. Statistical adjustment for environmental factors, characteristics of the child, and fetal maturity did not account for the observed differences between children of women who quit smoking and those of women who continued to smoke.
Article
Working memory has been proposed as an important component of reading and arithmetic skills. The development of working memory was studied in normally achieving and subtypes of learning disabled children. The performance of reading disabled (RD), arithmetic disabled (ARITHD), and attentional deficit disordered (ADD) children, age 7-13, was compared to normal achievers (NA) on 2 working memory tasks, 1 involving sentences and the other involving counting. There was a significant growth of working memory as a function of age. In addition, the RD children had significantly lower scores on both tasks. The ARITHD children had significantly lower scores only on the Working Memory--Counting task, and the ADD group had scores similar to the normally achieving children except at the youngest age level in the Working Memory--Sentences task. Thus, a reading disability appears to involve a generalized deficit in working memory. Children with an arithmetic disability do not have a generalized language deficit but have a specific working memory deficit in relation to processing numerical information. As children with ADD did not have deficits in these tasks, working memory may not have significant attentional components. An important component of the development of reading and computational arithmetic skills appears to be the growth of working memory for language and numerical information.
Article
EEG studies of marihuana use dating back to 1945 were reviewed. The earlier studies depended upon visual analysis of the tracing, and while some minor frequency and amplitude variations occurred in some subjects, there was no consistent THC induced change noticeable across subjects. Quantitative EEG studies of acute exposure to THC came later and produced reliable findings of a placebo controlled dose dependent THC induced increase in relative power of alpha, combined with decreased alpha frequency and a reduction of beta activity. These findings were reported for data collected from central-occipital derivations only. In our present investigation, we report that chronic heavy THC users have EEGs characterized by (1) increased absolute power of all frequencies over all cortical areas (2) hyperfrontality of elevated relative and absolute power and coherence values of alpha activity, and (3) a decrease in relative power of all non-alpha frequencies. Methodological issues were discussed and some suggestions were made for continuing research in this area.
Article
The motor, mental, and language development plus the home environment was examined in 217 twelve-month and 153 twenty-four-month-old children for whom prenatal exposure to marijuana, alcohol and cigarettes was previously ascertained. With this low-risk sample multiple regression analysis was used to assess the association between outcome measures and prenatal drug exposure while adjusting for potential confounding factors. Prenatal exposure to marijuana was uniquely positively associated with a series of items evaluating the child's attitudes and interests that reflect a cognitive factor. Moderate levels of alcohol were significantly associated with lower mental scores at 24 months of age. Prenatal maternal cigarette smoking was significantly associated with lower mental scores at 12 months of age and altered responses on auditory items at 12 and 24 months. However, at 24 months, the strong relationship of postnatal environmental factors with cognitive outcomes and with prenatal maternal smoking resulted in loss of significant, unique predictive power for maternal smoking. Based on the present work and supplemented by previously reported data pertaining to maternal attitudes during pregnancy and neonatal behaviour, a transactional interpretation is presented.
Article
The neurological status of 9- and 30-day-old infants, as assessed by the Prechtl neurological examination, was significantly and differentially related to prenatal exposure of cigarettes, marijuana, and alcohol. Data on approximately 250 babies, born to healthy, white, predominantly middle-class women, were analyzed using discriminant function analyses controlling for potentially confounding variables. Prenatal cigarette exposure was associated with hypertonicity and increased nervous system excitation, particularly at 30 days, prenatal marijuana exposure was associated with symptoms similar to mild narcotic withdrawal, and prenatal exposure to relatively low levels of alcohol was associated with slightly lowered nervous system arousal at 9 days of age. The results were related to behavioral observations on neonates exposed to drugs prenatally.
Article
Recent functional and anatomical studies in nonhuman primates have elucidated the basic neural circuitry underlying delayed-response function in adult nonhuman primates. Thus circuitry includes connections of the principal sulcus with other areas of parietal association and limbic cortex and projections to the caudate nucleus, superior colliculus, and other premotor centers. Anatomical tracing in primate fetuses and in monkeys at various stages of postnatal development indicates that these various classes of cortical connections begin to form by the second trimester of pregnancy. Electromicroscopic studies of the principal sulcus and other areas of cerebral cortex show that the number and density of synapses in the cortex increase rapidly, reaching and maintaining higher than normal adult values between 2 and 4 months postnatally, before slowly declining over a period of years to stable adult levels. The capacity to perform delayed-response and/or AB at short delays emerges around 4 months of age, coinciding with the end of the period of highest synaptic density in the principal sulcus. These findings suggest that a critical mass of cortical synapses is important for the emergence of this cognitive function, and that fully mature capacity may depend upon the elimination of excess synapses that occurs during adolescence and young adulthood. Knowledge of the neural basis of normal cognitive development may prove useful both to social and educational purposes as well as to understanding developmental disorders of cognition.
Article
Infant neonatal behaviour is significantly and differentially related to maternal marihuana, cigarette and alcohol use during pregnancy. Data on 250 babies born to healthy, predominantly middle-class women were analyzed using canonical analysis and multiple regression adjusting for potentially confounding variables. Prenatal marihuana exposure was associated with increased tremors and startles and poorer habituation to visual stimuli, prenatal cigarette exposure with increased tremors and poorer auditory habituation, whereas a relatively low level of alcohol consumption was marginally related to increased neonatal irritability.
Article
MARIHUANA and hashish have been used for centuries and the literature abounds with references to their effects. Only recently, however, have carefully controlled studies attempted to relate dose level and route of administration of Delta9-tetrahydrocannabinol (Delta9-THC), the principal psychoactive constituent of Cannabis sativa, to subjective and objective physiological, behavioural and mentational effects1-3. Attempts have also been made to compare the effects of Delta9-THC with those of ethanol4.
Article
Summarizes the current state of knowledge of prefrontal lobe functions as derived from studies and observations of adult humans following frontal lobe damage. Following an overview of the neuroanatomy and neuropathology, frontal lobe activities are presented under the following headings: motor functions; sensory, perception, and construction functions; attention; abnormal awareness; flexibility–perseveration; language; memory; cognition; personality; localization; and hemispheric activity. Six specific prefrontal functions are suggested as the principal disorders underlying many if not all of the described manifestations. Thus, prefrontal damage can (1) separate action from knowledge, (2) impair the ability to handle sequential behaviors, (3) impair the ability to establish or change a set, (4) impair the ability to maintain a set, (5) impair the ability to monitor personal behavior, and (6) produce attitudes of apathy. (5½ p ref)
Article
Two hundred and seventeen women were interviewed during various stages of pregnancy to determine the extent and changing patterns of alcohol, nicotine and marihuana use in the year before pregnancy and during each trimester of pregnancy. Nutritional intake did not vary among women in the various drug using categories. Before pregnancy, 18% of the women were heavy social drinkers. During the first trimester this proportion was reduced by two-thirds and, in contrast to the other levels of social drinking, continued to decline during the last two trimesters. Age, income, education and smoking were all positively associated with heavy social drinking. Heavy cigarette smoking was reported by 13% of the women before pregnancy and by 8% during each of the trimesters. Education and income were negatively associated with heavy smoking. Three per cent of the women reported smoking more than five joints of marihuana per week before pregnancy and most continued to smoke marihuana heavily during pregnancy. The heavy marihuana users had a lower family income and less formal education than the overall sample. Marihuana use in general was associated with cigarette smoking and was not reported by women over 32 years of age. Except for heavy social drinking, soft drug habits at all levels of usage remained essentially unchanged after the first trimester. The likelihood of any one particular soft drug being reduced once pregnancy was established did not vary as a function of the concomitant use of other soft drug(s).
Article
To analyze the influence of a comprehensive program of nurse home visitation on the intellectual functioning of children born to women who smoked cigarettes during pregnancy. Randomized clinical trial. Treatment 1: sensory and developmental screening at ages 1 and 2 years; treatment 2: screening plus free transportation for prenatal and well-child care; treatment 3: screening, transportation, plus prenatal home visitation; treatment 4: screening, transportation, prenatal home visitation, plus postnatal home visitation through the children's second birthdays. Semi-rural community in Upstate New York. 400 families in which the mothers registered before the 30th week of pregnancy and had no previous live births. Eighty-five percent of the mothers were either teenagers, unmarried, or poor. Analysis was limited to whites, who constituted 89% of sample. Nurse home visitation during pregnancy (treatments 3 and 4) or during pregnancy and the first 2 years of the child's life (treatment 4). During pregnancy, the nurses helped women improve their health-related behaviors, informal social support, and linkage with needed community services. Children born to women who smoked 10 or more cigarettes per day at registration during pregnancy and who were assigned to treatments 3 and 4 had IQs (averaging across the 3rd and 4th years of life) that were 4.86 (95% CI: 0.47, 9.26) points higher after adjustment for covariates than did children born to women who smoked 10+ cigarettes per day and who were assigned to treatments 1 and 2. The positive influence of the home-visiting program on reducing the harmful effect of smoking appears to be due to prenatal visitation. Comprehensive prenatal home-visitation services can offset the impairment in intellectual functioning associated with substantial maternal smoking during pregnancy.
Article
To evaluate the 3-year behavioral and developmental outcome of children prenatally exposed to maternal substances of abuse. Ninety-three children exposed prenatally to cocaine and other drugs taken by the mother during pregnancy (Group 1), 24 polydrug/noncocaine exposed children (Group 2), and 25 nonexposed children (Group 3) were evaluated at 3 years of age as part of a longitudinal prospective study of the impact of intrauterine substance exposure on long-term outcome. The Stanford-Binet Intelligence Scale: Fourth Edition(SBIS) was administered by examiners blinded to the exposure background of the children, and a pediatrician performed a complete medical evaluation on all the children. The children's primary caregiver completed the Achenbach Child Behavior Checklist. Stepwise multiple regression procedures were used to determine the factors that best predicted 3-year growth, intelligence, and behavior. Groups 1 and 2 differed from Group 3 on head circumference. Group 1 scored lower than Group 3 on SBIS Verbal Reasoning. Group 2 scored Slower than Group 3 on SBIS Abstract/Visual Reasoning. Cocaine exposure predicted poor verbal reasoning. Marijuana exposure predicted poor abstract/visual reasoning. Examiner rating predicted intellectual outcome and caregiver ratings. Caregivers rated exposed children as more aggressive than nonexposed. Contrary to information in the popular media, not all substance-exposed children suffer the same poor prognosis. In fact, generalizations about the fate of drug-exposed children must await additional research into the outcome of the broader population of drug-exposed children, examining the roles of maternal and environmental factors across a variety of geographic locations and socioeconomic levels.
Article
In the OPPS we have been studying the effects of marihuana used during pregnancy since 1978. The subjects are primarily middle-class, low risk women who entered the study early in their pregnancy. Extensive demographic and life-style information was gathered several times during pregnancy and postnatally. The offspring have been assessed repeatedly during the neonatal period, at least annually until the age of 6 and less frequently thereafter. The outcome measures include a variety of age appropriate standardized global measures as well as a large battery of neuropsychological tests attempting to assess discrete functioning within particular domains including language development, memory, visual/perceptual functioning, components of reading and sustained attention. The results suggest that in the neonate, state alterations and altered visual responsiveness may be associated with in utero exposure to marihuana. Global measures, particularly between the ages of 1 and 3 years, did not reveal an association with prenatal marihuana exposure. However, this initial, apparent absence of effect during early childhood should not be interpreted as in utero marihuana exposure having only transient effects for, as the children became older, aspects of neuropsychological functioning did discriminate between marihuana and control children. Domains associated with prenatal marihuana exposure at four years of age and older included increased behavioral problems and decreased performance on visual perceptual tasks, language comprehension, sustained attention and memory. The nature and the timing of the appearance of these deficits is congruent with the notion of prenatal marihuana exposure affecting 'executive functioning'--goal directed behavior that includes planning, organized search, and impulse control. Such an interpretation would be consistent with the extant literature with animals and non-pregnant adult users suggesting that chronic marihuana use may impact upon prefrontal lobe functioning.
Article
Our previous research with long term cannabis users established an impaired ability to focus attention and filter out irrelevant information, which was progressive with the cumulative duration of exposure to cannabis. The current study examined these processes in a group of ex-cannabis users. The results suggested a partial recovery of function but the past duration of cannabis use continued to have an adverse effect on the ability to effectively reject complex irrelevant information. There was no indication of improvement with increasing length of abstinence. Whilst relatively subtle in nature, the consequences of such an enduring deficit associated with cannabis use are worthy of further investigation.