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BACKGROUND: Cannabidiol (CBD) is a widely available cannabis product with many claims as to potential health benefits including alleviating symptoms related to opioid use disorder (OUD). However, little is known as to how individuals with OUD perceive CBD, to what extent they may already be using CBD, and for what purposes. METHODS: A survey was conducted among individuals receiving treatment for OUD at the Addiction Institute of Mount Sinai in New York City from July 2021 to August 2023. The survey consisted of demographic questions, questions about opioid use, CBD use, and perceptions regarding CBD. Statistical analysis using ordinal logistic regression was employed to compare perceptions between CBD users and non-users while adjusting for age and race. RESULTS: Among 587 respondents, 550 completed the survey. Among all survey completers, 129 (23%) reported a history of using CBD for a variety of reasons including: anxiety (81, 62.8%), pain (65, 50.4%), sleep (63, 48.8%), depression (62, 48.1%), recreational purposes (32, 24.8%), or for other reasons (8, 6.2%). Of note, 22 (17.1%) respondents reported using CBD to control their addiction and 54 (41.9%) reported using CBD to ease opioid withdrawal symptoms. CBD users demonstrated more positive perceptions regarding its legality (ß = 0.673, OR = 1.960, 95% CI [1.211, 3.176], p = .006), social acceptance (ß = 0.718, OR = 2.051, 95% CI [1.257, 3.341], p = .004), and therapeutic potential compared to non-users. CBD users also had a more positive view of its potential future role in managing addiction (ß = 0.613, OR = 1.846, 95% CI [1.181, 2.887], p = .007). CONCLUSIONS: This study highlights a significant association between CBD usage and progressive views regarding CBD among individuals with OUD, suggesting a growing interest in CBD as a potential adjunctive therapy for individuals in substance use treatment. Some patients are already using CBD for anxiety, pain, sleep, depression, or as a harm reduction intervention to control their addiction or for opioid withdrawal symptoms. These findings underscore the importance of integrating patient perspectives into future research and treatment strategies involving CBD in the context of OUD.
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Canabidiol , Transtornos Relacionados ao Uso de Opioides , Humanos , Canabidiol/uso terapêutico , Masculino , Feminino , Adulto , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/psicologia , Pessoa de Meia-Idade , Cidade de Nova Iorque , Adulto Jovem , Inquéritos e Questionários , Conhecimentos, Atitudes e Prática em SaúdeRESUMO
OBJECTIVE: To investigate the association between prenatal cannabis use and perinatal outcomes using longitudinal data from pregnant individuals. STUDY DESIGN: This secondary-data analysis study utilized data collected from 894 pregnant individuals followed in the Stress in Pregnancy longitudinal study, conducted between 2009 and 2013. The status of cannabis use was ascertained through interviews and electronic medical record reviews to evaluate the effect of cannabis use on perinatal outcomes (NICU admission, preterm delivery, low birth weight, fetal death). RESULTS: Among participants analyzed, 13.1% used cannabis, who were generally younger (25.9 vs 27.9 years). There was a sevenfold increased risk of fetal death (OR 7.30) among cannabis users relative to non-users. Elevated risk persisted after adjustments of potential confounders (aOR 6.31). Adjusted models also suggested increased low birth weight risk (aOR 1.67). CONCLUSION: This study highlights an association between prenatal cannabis use and elevated risks for fetal death and low birth weight.
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Morte Fetal , Recém-Nascido de Baixo Peso , Humanos , Feminino , Gravidez , Estudos Longitudinais , Recém-Nascido , Adulto , Morte Fetal/etiologia , Resultado da Gravidez , Nascimento Prematuro , Adulto Jovem , Efeitos Tardios da Exposição Pré-Natal , Uso da Maconha/efeitos adversos , Uso da Maconha/epidemiologia , Fatores de Risco , Modelos Logísticos , Cannabis/efeitos adversosRESUMO
Although cannabis is a naturally occurring plant with a long history of use by humans, the chemicals it contains, called cannabinoids, can act on the human body in many ways. Use of cannabis during important periods of development, such as during pregnancy and adolescence, can have a long-lasting impact on the way the brain forms and develops its systems to control emotions and other functions. This article gives an overview of some of the effects of cannabinoids on the developing brain, before birth and as teenagers, and provides information about how young people can prevent or minimize the negative effects of cannabis on their brains.
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Substance use disorders (SUDs) induce widespread molecular dysregulation in the nucleus accumbens (NAc), a brain region pivotal for coordinating motivation and reward. These molecular changes are thought to support lasting neural and behavioral disturbances that promote drug-seeking in addiction. However, different drug classes exert unique influences on neural circuits, cell types, physiology, and gene expression despite the overlapping symptomatology of SUDs. To better understand common and divergent molecular mechanisms governing SUD pathology, our goal was to survey cell-type-specific restructuring of the NAc transcriptional landscape in after psychostimulant or opioid exposure. We combined fluorescence-activated nuclei sorting and RNA sequencing to profile NAc D1 and D2 medium spiny neurons (MSNs) across cocaine and morphine exposure paradigms, including initial exposure, prolonged withdrawal after repeated exposure, and re-exposure post-withdrawal. Our analyses reveal that D1 MSNs display many convergent transcriptional responses across drug classes during exposure, whereas D2 MSNs manifest mostly divergent responses between cocaine and morphine, with morphine causing more adaptations in this cell type. Utilizing multiscale embedded gene co-expression network analysis (MEGENA), we discerned transcriptional regulatory networks subserving biological functions shared between cocaine and morphine. We observed largely integrative engagement of overlapping gene networks across drug classes in D1 MSNs, but opposite regulation of key D2 networks, highlighting potential therapeutic gene network targets within MSNs. These studies establish a landmark, cell-type-specific atlas of transcriptional regulation induced by cocaine and by morphine that can serve as a foundation for future studies towards mechanistic understanding of SUDs. Our findings, and future work leveraging this dataset, will pave the way for the development of targeted therapeutic interventions, addressing the urgent need for more effective treatments for cocaine use disorder and enhancing the existing strategies for opioid use disorder.
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Background: In this review, we provide an updated assessment of available evidence on the pharmacokinetics (PK) of CBD and explore the impact of different factors on PK outcomes. Materials and Methods: This systematic review and meta-regression analysis was preregistered (PROSPERO: CRD42021269857). We systematically searched Medline, Embase, PsycInfo, and Web of Science Core Collection up to November 19, 2022. Trials of CBD in healthy adults were included if they reported at least one of the PK parameters of interest, including Tmax, Cmax, AUC0-t, AUC0-inf, and T1/2, in serum or plasma. Studies of patient populations or CBD co-administration with other medications were excluded. The National Heart, Lung, and Blood Institute's Quality Assessment Tool for Before-After Studies with no Control Group was used. Random-effects multivariable meta-regression analysis was conducted. Results: A total of 112 trial arms from 39 studies were included; 26 trial arms had a "Good" quality, 70 "Fair," and 16 "Poor." Eight arms used inhalation CBD, 29 oromucosal, 73 oral, and 2 intravenous. CBD formulations could be categorized to nanotech (n=14), oil-based (n=21), alcohol-based (n=10), water-based (n=12), Sativex (n=17), and Epidiolex® (n=22). For single-dose studies, CBD doses ranged between 2 and 100 mg in inhalation, 5-50 mg in oromucosal, and 0.42-6000 mg in oral administration. Sixty-six trial arms had only male participants or a higher number of male than female participants. The duration of the PK session was between 4 and 164 h. A higher CBD dose was associated with higher Cmax, AUC0-t, and AUC0-inf. Compared with oral administration, oromucosal administration was associated with lower Cmax, AUC0-t, and AUC0-inf. Fed status was associated with higher Cmax and AUC0-t when compared with the fasting status. A higher ratio of female participants was associated with lower Tmax in oral administration and higher Cmax. Conclusion: As expected, CBD dose, route of administration, and diet were major determinants of CBD PK with oral routes providing higher bioavailability and nanotechnology formulations a faster onset. Although CBD appeared to have a faster onset and longer duration in women, more studies are required to delineate the role of biological sex. Factors that influence CBD PK have implications for medication development and appropriate dosing in clinical practice.
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We appreciate the comments of Gilman et al. (2023) on our paper and their acknowledgement of its importance in highlighting the significance of this area of research. Further, their acknowledgment that the primary results of our study are in a range that is similar to those from other published studies of children exposed to highly stressful environmental events emphasizes the validity of our findings and the important extension of our results to children experiencing these events in utero. They, however, raised concerns about some of the results regarding specific types of psychiatric disorders and sex-specific results related to the prenatal Superstorm Sandy hurricane exposure. We comment on the various issues related to the paper below but will not respond to comments regarding the press coverage of this article, which we think are beyond the scope of this commentary.
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Opioid use disorder (OUD) is influenced by genetic and environmental factors. While recent research suggests epigenetic disturbances in OUD, this is mostly limited to DNA methylation (5mC). DNA hydroxymethylation (5hmC) has been widely understudied. We conducted a multi-omics profiling of OUD in a male cohort, integrating neuronal-specific 5mC and 5hmC as well as gene expression profiles from human postmortem orbitofrontal cortex (OUD = 12; non-OUD = 26). Single locus methylomic analysis and co-methylation analysis showed a higher number of OUD-associated genes and gene networks for 5hmC compared to 5mC; these were enriched for GPCR, Wnt, neurogenesis, and opioid signaling. 5hmC marks also showed a higher correlation with gene expression patterns and enriched for GWAS of psychiatric traits. Drug interaction analysis revealed interactions with opioid-related drugs, some used as OUD treatments. Our multi-omics findings suggest an important role of 5hmC and reveal loci epigenetically dysregulated in OFC neurons of individuals with OUD.
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Epigenoma , Transtornos Relacionados ao Uso de Opioides , Humanos , Masculino , Analgésicos Opioides , 5-Metilcitosina/metabolismo , Metilação de DNA/genética , Córtex Pré-Frontal/metabolismo , Neurônios/metabolismo , Transtornos Relacionados ao Uso de Opioides/genética , Epigênese GenéticaRESUMO
Opioid use disorder (OUD) looms as one of the most severe medical crises facing society. More effective therapeutics will require a deeper understanding of molecular changes supporting drug-taking and relapse. Here, we develop a brain reward circuit-wide atlas of opioid-induced transcriptional regulation by combining RNA sequencing (RNA-seq) and heroin self-administration in male mice modeling multiple OUD-relevant conditions: acute heroin exposure, chronic heroin intake, context-induced drug-seeking following abstinence, and relapse. Bioinformatics analysis of this rich dataset identified numerous patterns of transcriptional regulation, with both region-specific and pan-circuit biological domains affected by heroin. Integration of RNA-seq data with OUD-relevant behavioral outcomes uncovered region-specific molecular changes and biological processes that predispose to OUD vulnerability. Comparisons with human OUD RNA-seq and genome-wide association study data revealed convergent molecular abnormalities and gene candidates with high therapeutic potential. These studies outline molecular reprogramming underlying OUD and provide a foundational resource for future investigations into mechanisms and treatment strategies.
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Heroína , Transtornos Relacionados ao Uso de Opioides , Humanos , Camundongos , Masculino , Animais , Heroína/efeitos adversos , Estudo de Associação Genômica Ampla , Encéfalo , Recompensa , RecidivaRESUMO
BACKGROUND: Early-life adverse experiences can elevate the magnitude of the risk of developmental psychopathology, but the potential synergistic effects of multiple factors have not been well studied. AIMS: To determine whether prenatal exposures to maternal stress (Superstorm Sandy) and maternal cannabis use synergistically alter the risk of developmental psychopathology. METHOD: The study included 163 children (53.4% girls), longitudinally tracked (ages 2-5 years) in relation to the effects of two early-life adverse exposures (Superstorm Sandy and maternal cannabis use). Offspring were grouped by exposure status (neither, only maternal cannabis use, only Superstorm Sandy or both). DSM-IV disorders for offspring were derived from structured clinical interviews; caregiver-reported ratings of family stress and social support were also assessed. RESULTS: A total of 40.5% had been exposed to Superstorm Sandy and 24.5% to maternal cannabis use. Offspring exposed to both (n = 13, 8.0%), relative to those exposed to neither, had a 31-fold increased risk of disruptive behavioural disorders (DBDs) and a seven-fold increased risk of anxiety disorders. The synergy index demonstrated that offspring with two exposures had synergistic elevation in risk of DBDs (synergy index, 2.06, P = 0.03) and anxiety disorders (synergy index, 2.60, P = 0.004), compared with the sum of single risks. Offspring with two exposures had the highest parenting stress and lowest social support. CONCLUSIONS: Our findings are consistent with the double-hit model suggesting that offspring with multiple early-life adverse exposures (Superstorm Sandy and maternal cannabis use) have synergistically increased risks of mental health problems. Given the increasing frequency of major natural disasters and cannabis use, especially among women under stress, these findings have significant public health implications.
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Background: In this review, we provide an updated assessment of available evidence on the pharmacokinetics (PK) of cannabidiol (CBD) and explore the impact of different factors on PK outcomes. Materials and Methods: This systematic review and meta-regression analysis was pre-registered (PROSPERO: CRD42021269857). We systematically searched Medline, Embase, PsychInfo, and Web of Science Core Collection up to November 19, 2022. Trials of CBD in healthy adults were included if they reported at least one of the PK parameters of interest, including Tmax, Cmax, AUC0-t, AUC0-inf, and T 1/2 , in serum or plasma. Studies of patient populations or CBD co-administration with other medications were excluded. The National Heart, Lung, and Blood Institute's Quality Assessment Tool for Before-After Studies with no Control Group was used. Random-effects multivariable meta-regression analysis was conducted. Results: A total of 112 trial arms from 39 studies were included; 26 trial arms had a "Good" quality, 70 "Fair," and 16 "Poor." Eight arms used inhalation CBD, 29 oromucosal, 73 oral, and 2 intravenous. CBD formulations could be categorized to nanotech (n=14), oil-based (n=21), alcohol-based (n=10), water-based (n=12), Sativex (n=17), and Epidiolex (n=22). For single-dose studies, CBD doses ranged between 2-100mg in inhalation, 5-50mg in oromucosal, and 0.42-6000mg in oral administration. Sixty-six trial arms had only male participants or a higher number of males than females. The duration of the PK session was between 4h-164h. A higher CBD dose was associated with higher Cmax, AUC0-t, and AUC0-inf. Compared to oral administration, oromucosal administration was associated with lower Cmax, AUC0-t, and AUC0-inf. Fed status was associated with higher Cmax and AUC0-t when compared to the fasting status. A higher ratio of female participants was associated with lower Tmax in oral administration and higher Cmax. Conclusion: As expected, CBD dose, route of administration, and diet were major determinants of CBD pharmacokinetics with oral routes providing higher bioavailability and nanotechnology formulations a faster onset. Though CBD appeared to have a faster onset and longer duration in females, more studies are required to delineate the role of biological sex. Factors that influence CBD PK have implications for medication development and appropriate dosing in clinical practice.
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Opioid use disorder (OUD) looms as one of the most severe medical crises currently facing society. More effective therapeutics for OUD requires in-depth understanding of molecular changes supporting drug-taking and relapse. Recent efforts have helped advance these aims, but studies have been limited in number and scope. Here, we develop a brain reward circuit-wide atlas of opioid-induced transcriptional regulation by combining RNA sequencing (RNAseq) and heroin self-administration in male mice modeling multiple OUD-relevant conditions: acute heroin exposure, chronic heroin intake, context-induced drug-seeking following prolonged abstinence, and heroin-primed drug-seeking (i.e., "relapse"). Bioinformatics analysis of this rich dataset identified numerous patterns of molecular changes, transcriptional regulation, brain-region-specific involvement in various aspects of OUD, and both region-specific and pan-circuit biological domains affected by heroin. Integrating RNAseq data with behavioral outcomes using factor analysis to generate an "addiction index" uncovered novel roles for particular brain regions in promoting addiction-relevant behavior, and implicated multi-regional changes in affected genes and biological processes. Comparisons with RNAseq and genome-wide association studies from humans with OUD reveal convergent molecular regulation that are implicated in drug-taking and relapse, and point to novel gene candidates with high therapeutic potential for OUD. These results outline broad molecular reprogramming that may directly promote the development and maintenance of OUD, and provide a foundational resource to the field for future research into OUD mechanisms and treatment strategies.
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BACKGROUND: Cannabis use suppresses the endocannabinoid system in healthy individuals. However, the association between cannabis use with the endocannabinoid system is understudied in individuals with psychosis despite the high rate of cannabis use in these individuals. METHODS: We enrolled 83 individuals who were admitted to an inpatient psychiatric unit with psychotic presentations, and measured their plasma levels of main endocannabinoids, Anandamide (AEA) and 2-Acylglycerol (2-AG), and endocannabinoid related compounds, Palmitoylethanolamine, and N-oleoylethanolamine. Cannabis use was assessed with urine toxicology and frequency of cannabis use was assessed using self-reported questionnaires. The Positive and Negative Syndrome Scale was used to assess the severity of psychotic symptoms. RESULTS: Overall, we had 38 individuals in cannabis positive group (CN+) and 45 individuals in cannabis negative group (CN-). Compared to CN-, CN+ group had lower plasma levels of AEA, which remained significant after controlling for age, gender, race/ethnicity, and use of other drugs. CONCLUSION: Cannabis use is associated with low plasma AEA levels in individuals with psychosis, which is in the same line with reported suppressive effects of cannabis on the endocannabinoid system in healthy individuals. Further studies are needed to investigate the clinical significance of this finding.
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Cannabis , Alucinógenos , Transtornos Psicóticos , Humanos , Endocanabinoides , Agonistas de Receptores de Canabinoides , Alcamidas Poli-Insaturadas , Transtornos Psicóticos/tratamento farmacológicoRESUMO
Importance: Although perceived as relatively harmless and nonaddictive, adolescent cannabis use significantly increases the likelihood of developing cannabis use disorder in adulthood, especially for high-potency cannabis. Risky decision-making is associated with chronic cannabis use, but given confounds of human studies, it remains unclear whether adolescent cannabis exposure and Δ9-tetrahydrocannabinol (THC) potency specifically predicts risky decision-making or influences cognitive response to the drug later in life. Objective: To leverage a human data set of cannabis users and a rat model to evaluate the long-term outcomes of adolescent THC exposure on adult decision-making and impulse control. Design, Setting, and Participants: This translational rat study tested the link between adolescent THC exposure and adulthood decision-making. A reanalysis of a previously published dataset of human chronic cannabis users was conducted to evaluate decision-making phenotypes. Computational modeling assessed the human and animal results in a single framework. Data were collected from 2017 to 2020 and analyzed from 2020 to 2022. Main Outcomes and Measures: Decision-making was measured by the Iowa Gambling Task (IGT) and Rat Gambling Task (rGT). Impulse control was assessed in the rat model. Computational modeling was used to determine reward and punishment learning rates and learning strategy used by cannabis users and THC-exposed rats. Cell-specific molecular measures were conducted in the prefrontal cortex and amygdala. Results: Of 37 participants, 24 (65%) were male, and the mean (SD) age was 33.0 (8.3) years. Chronic cannabis users (n = 22; mean [SE] IGT score, -5.182 [1.262]) showed disadvantageous decision-making compared with controls (n = 15; mean [SE] IGT score, 7.133 [2.687]; Cohen d = 1.436). Risky choice was associated with increased reward learning (mean [SE] IGT score: cannabis user, 0.170 [0.018]; control, 0.046 [0.008]; Cohen d = 1.895) and a strategy favoring exploration vs long-term gains (mean [SE] IGT score: cannabis user, 0.088 [0.012]; control, 0.020 [0.002]; Cohen d = 2.218). Rats exposed to high-dose THC but not low-dose THC during adolescence also showed increased risky decision-making (mean [SE] rGT score: vehicle, 46.17 [7.02]; low-dose THC, 69.45 [6.01]; high-dose THC, 21.97 [11.98]; Cohen d = 0.433) and elevated reward learning rates (mean [SE] rGT score: vehicle, 0.17 [0.01]; low-dose THC, 0.10 [0.01]; high-dose THC, 0.24 [0.06]; Cohen d = 1.541) during task acquisition. These animals were also uniquely susceptible to increased cognitive impairments after reexposure to THC in adulthood, which was correlated with even greater reward learning (r = -0.525; P < .001) and a shift in strategy (r = 0.502; P < .001), similar to results seen in human cannabis users. Molecular studies revealed that adolescent THC dose differentially affected cannabinoid-1 receptor messenger RNA expression in the prelimbic cortex and basolateral amygdala in a layer- and cell-specific manner. Further, astrocyte glial fibrillary acidic protein messenger RNA expression associated with cognitive deficits apparent with adult THC reexposure. Conclusions and Relevance: In this translational study, high-dose adolescent THC exposure was associated with cognitive vulnerability in adulthood, especially with THC re-exposure. These data also suggest a link between astrocytes and cognition that altogether provides important insights regarding the neurobiological genesis of risky cannabis use that may help promote prevention and treatment efforts.
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Cannabis , Jogo de Azar , Alucinógenos , Adulto , Humanos , Ratos , Masculino , Adolescente , Animais , Feminino , Jogo de Azar/psicologia , Agonistas de Receptores de Canabinoides , Cognição , Modelos Animais , Dronabinol , Tomada de Decisões/fisiologiaRESUMO
Despite the belief that cannabis is relatively harmless, exposure during adolescence is associated with increased risk of developing several psychopathologies in adulthood. In addition to the high levels of use amongst teenagers, the potency of ∆-9-tetrahydrocannabinol (THC) has increased more than fourfold compared to even twenty years ago, and it is unclear whether potency influences the presentation of THC-induced behaviors. Expanded knowledge about the impact of adolescent THC exposure, especially high dose, is important to delineating neural networks and molecular mechanisms underlying psychiatric risk. Here, we observed that repeated exposure to low (1.5 mg/kg) and high (5 mg/kg) doses of THC during adolescence in male rats produced divergent effects on behavior in adulthood. Whereas low dose rats showed greater sensitivity to reward devaluation and also self-administered more heroin, high dose animals were significantly more reactive to social isolation stress. RNA sequencing of the basolateral amygdala, a region linked to reward processing and stress, revealed significant perturbations in transcripts and gene networks related to synaptic plasticity and HPA axis that were distinct to THC dose as well as stress. In silico single-cell deconvolution of the RNAseq data revealed a significant reduction of astrocyte-specific genes related to glutamate regulation in stressed high dose animals, a result paired anatomically with greater astrocyte-to-neuron ratios and hypotrophic astrocytes. These findings emphasize the importance of dose and behavioral state on the presentation of THC-related behavioral phenotypes in adulthood and dysregulation of astrocytes as an interface for the protracted effects of high dose THC and subsequent stress sensitivity.
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Complexo Nuclear Basolateral da Amígdala , Dronabinol , Ratos , Animais , Masculino , Dronabinol/efeitos adversos , Sistema Hipotálamo-Hipofisário , Transcriptoma , Sistema Hipófise-Suprarrenal , RecompensaRESUMO
BACKGROUND: Growing evidence shows an association between in utero exposure to natural disasters and child behavioral problems, but we still know little about the development of specific psychopathology in preschool-aged children. METHODS: Preschool children (n = 163, mean age = 3.19, 85.5% racial and ethnic minorities) and their parents (n = 151) were evaluated annually at ages 2-5 to assess the emergence of psychopathology using the Preschool Age Psychopathological Assessment (PAPA), a parent-report structured diagnostic interview developed for preschool-age children. Sixty-six (40.5%) children were exposed to Sandy Storm (SS) in utero and 97 (59.5%) were not. Survival analysis evaluated patterns of onset and estimated cumulative risks of psychopathology among exposed and unexposed children, in total and by sex. Analyses were controlled for the severity of objective and subjective SS-related stress, concurrent family stress, and demographic and psychosocial confounders, such as maternal age, race, SES, maternal substance use, and normative prenatal stress. RESULTS: Exposure to SS in utero was associated with a substantial increase in depressive disorders (Hazard Ratio (HR) = 16.9, p = .030), anxiety disorders (HR = 5.1, p < .0001), and attention-deficit/disruptive behavioral disorders (HR = 3.4, p = .02). Diagnostic rates were elevated for generalized anxiety disorder (GAD; HR = 8.5, p = .004), attention-deficit/hyperactivity disorder (ADHD; HR = 5.5, p = .01), oppositional-defiant disorder (ODD; HR = 3.8, p = .05), and separation-anxiety disorder (SAD; HR = 3.5, p = .001). Males had distinctively elevated risks for attention-deficit/disruptive behavioral disorders (HR = 7.8, p = .02), including ADHD, CD, and ODD, whereas females had elevated risks for anxiety disorders (HR = 10.0, p < .0001), phobia (HR = 2.8, p = .02) and depressive disorders (HR = 30.0, p = .03), including SAD, GAD, and dysthymia. CONCLUSIONS: The findings demonstrate that in utero exposure to a major weather-related disaster (SS) was associated with increased risk for psychopathology in children and provided evidence of distinct psychopathological outcomes as a function of sex. More attention is needed to understand specific parent, child, and environmental factors which account for this increased risk, and to develop mitigation strategies.
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Transtorno do Deficit de Atenção com Hiperatividade , Desastres Naturais , Efeitos Tardios da Exposição Pré-Natal , Masculino , Feminino , Gravidez , Pré-Escolar , Humanos , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Comorbidade , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtornos de Deficit da Atenção e do Comportamento DisruptivoRESUMO
Our authors, who direct the Addiction Institute for the Mount Sinai Health System in New York City, address the substance-abuse avalanche brought on by the Covid-19 pandemic.
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Background: An oral route of administration for tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) eliminates the harmful effects of smoking and has potential for efficacious cannabis delivery for therapeutic and recreational applications. We investigated the pharmacokinetics of CBD, Δ9-THC, 11-OH-THC, and 11-nor-9-carboxy-Δ9-THC (THC-COOH) in a novel oral delivery system, Solutech™, compared to medium-chain triglyceride-diluted cannabis oil (MCT-oil) in a healthy population. Materials and Methods: Thirty-two participants were randomized and divided into two study arms employing a comparator-controlled, parallel-study design. To evaluate the pharmacokinetics of Δ9-THC, CBD, 11-OH-THC, and THC-COOH, blood was collected at pre-dose (t=0) and 10, 20, 30, and 45, min and 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, and 48 h post-dose after a single dose of Solutech (10.0 mg Δ9-THC, 9.76 mg CBD) or MCT (10.0 mg Δ9-THC, 9.92 mg CBD). Heart rate and blood pressure were measured at 0.5, 1, 2, 4, 6, 8, 12, 24, and 48 h. Relationships between cannabis use history, body mass index, sex, and pharmacokinetic parameters were investigated. Safety was assessed before and at 48 h post-acute dose. Results: Acute consumption of Solutech provided a significantly greater maximum concentration (Cmax), larger elimination and absorption rate constants, faster time to Cmax and lag time, and half-life for all analytes compared to MCT-oil (p<0.001). In addition, cannabis use history had a significant influence on the pharmacokinetic parameters of CBD, Δ9-THC, 11-OH-THC, and THC-COOH. On average, participants with later age of first use had higher Δ9-THC, CBD, and THC-COOH Cmax and later time-to-Cmax and half-life for Δ9-THC, CBD, THC-COOH, and 11-OH-THC than those with earlier age of first use (p≤0.032). Those with more years of recreational cannabis use had higher area under the curve for Δ9-THC and CBD, Cmax for CBD, and longer 11-OH-THC half-life than those with less (p≤0.048). Conclusion: This study demonstrated that consumption of Solutech enhanced most pharmacokinetics parameters measured compared to MCT-oil. Participant's cannabis use history, including their age of first use and number of years using cannabis significantly impacted pharmacokinetic parameters investigated. Acute consumption of both products was found to be safe and well tolerated. The results suggest that Solutech may optimize bioavailability from cannabis formulations.
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Canabidiol , Cannabis , Humanos , Dronabinol , Fumar , Projetos de PesquisaRESUMO
Substance use disorders (SUDs) are frequently stigmatized by society. However, overcoming stigmas to effectively treat SUDs requires acknowledging the developmental path of neural vulnerability. These vulnerabilities begin long before adulthood, providing opportunities to change the trajectory before the disorder becomes entrenched. This article raises attention to reversible epigenetic underpinnings of this vulnerability.