RESUMEN
There is emerging evidence that the endocannabinoid system (ECS) plays a significant role in the pathophysiology of many psychiatric disorders, including attention deficit hyperactivity disorder (ADHD). Increasing evidence suggests that a number of neurobiological correlates between endogenous cannabinoid function and cognitive dysfunction are seen in ADHD, making the ECS a possible target for therapeutic interventions. Cannabis use and cannabis use disorder are more prevalent in individuals with ADHD, compared to the general population, and there is growing popular perception that cannabis is therapeutic for ADHD. However, the relationship between cannabis use and ADHD symptomology is poorly understood. Further understanding of the role of the ECS in ADHD pathophysiology and the molecular alterations that may be a target for treatment is needed. To further the science on this emerging area of research, this scoping review describes the preclinical and clinical evidence seeking to understand the relationship between the ECS and ADHD.
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Trastorno por Déficit de Atención con Hiperactividad , Endocannabinoides , Trastorno por Déficit de Atención con Hiperactividad/fisiopatología , Trastorno por Déficit de Atención con Hiperactividad/metabolismo , Humanos , Endocannabinoides/metabolismo , Animales , Abuso de Marihuana/fisiopatología , Abuso de Marihuana/metabolismo , Uso de la Marihuana/metabolismoRESUMEN
BACKGROUND: Human immunodeficiency virus 1 (HIV-1) tissue reservoirs remain the main obstacle against an HIV cure. Limited information exists regarding cannabis's effects on HIV-1 infections in vivo, and the impact of cannabis use on HIV-1 parenchymal tissue reservoirs is unexplored. METHODS: To investigate whether cannabis use alters HIV-1 tissue reservoirs, we systematically collected 21 postmortem brain and peripheral tissues from 20 men with subtype C HIV-1 and with suppressed viral load enrolled in Zambia, 10 of whom tested positive for cannabis use. The tissue distribution and copies of subtype C HIV-1 LTR, gag, env DNA and RNA, and the relative mRNA levels of cytokines IL-1ß, IL-6, IL-10, and TGF-ß1 were quantified using PCR-based approaches. Utilizing generalized linear mixed models we compared persons with HIV-1 and suppressed viral load, with and without cannabis use. RESULTS: The odds of tissues harboring HIV-1 DNA and the viral DNA copies in those tissues were significantly lower in persons using cannabis. Moreover, the transcription levels of proinflammatory cytokines IL-1ß and IL-6 in lymphoid tissues of persons using cannabis were also significantly lower. CONCLUSIONS: Our findings suggested that cannabis use is associated with reduced sizes and inflammatory cytokine expression of subtype C HIV-1 reservoirs in men with suppressed viral load.
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Citocinas , Infecciones por VIH , VIH-1 , Carga Viral , Humanos , Masculino , VIH-1/genética , VIH-1/efectos de los fármacos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Adulto , Citocinas/metabolismo , Citocinas/genética , Provirus/genética , Persona de Mediana Edad , Zambia , ADN Viral , Antirretrovirales/uso terapéutico , Encéfalo/virología , Encéfalo/metabolismo , Adulto Joven , Uso de la Marihuana/metabolismoAsunto(s)
Biomarcadores/metabolismo , Líquido del Lavado Bronquioalveolar/inmunología , Cannabis/efectos adversos , Regulación de la Expresión Génica/efectos de los fármacos , Uso de la Marihuana/patología , Líquido del Lavado Bronquioalveolar/química , Estudios de Casos y Controles , Humanos , Uso de la Marihuana/genética , Uso de la Marihuana/inmunología , Uso de la Marihuana/metabolismo , RNA-SeqRESUMEN
Cannabis consumption has been increasing worldwide among pregnant women. Due to the negative effects of prenatal cannabis exposure, it is necessary to develop an objective, sensitive, and specific method to determine cannabinoids use during pregnancy. In this study, we compared four different biological samples, maternal hair, meconium, umbilical cord, and placenta, for the detection of in utero cannabis exposure. The biological samples were collected from 627 mother-newborn dyads. All hair and meconium samples were analyzed, and umbilical cord and placenta if hair and/or meconium were positive for cannabinoids. Meconium and hair showed to complement each other, with an agreement between hair and meconium results of 96.7% but only 34.3% if just positive results were considered. Umbilical cord and placenta results showed a better agreement with meconium (91.3% and 92.6%, respectively) than with hair (39.1% and 34.6%, respectively). The predominant metabolites in meconium were 11-nor-carboxy-THC (THCCOOH) and 8,11-dihydroxy-THC (diOHTHC), and in umbilical cord and placenta was THCCOOH-glucuronide. Cannabidiol (CBD) and cannabinol (CBN) were detected in meconium but not in any umbilical cord or placenta. For the first time, prenatal marijuana exposure was analyzed and compared in paired hair, meconium, umbilical cord, and placental samples. Hair and meconium positivity rate was similar, but a more sensitive and specific analytical method for the hair may resolve discrepancies between the matrices. Umbilical cord and placenta may be considered suitable alternative matrices to meconium through the determination of THCCOOH-glucuronide as a biomarker of cannabis exposure.
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Cannabinoides/análisis , Uso de la Marihuana/metabolismo , Detección de Abuso de Sustancias/métodos , Cannabinoides/administración & dosificación , Cannabinoides/farmacocinética , Femenino , Cabello/química , Humanos , Recién Nacido , Meconio/química , Placenta/química , Embarazo , Sensibilidad y Especificidad , Distribución Tisular , Cordón Umbilical/químicaRESUMEN
Impulse control deficits are often found to co-occur with substance use disorders (SUDs). On the one hand, it is well known that chronic intake of drugs of abuse remodels the brain with significant consequences for a range of cognitive behaviors. On the other hand, individual variation in impulse control may contribute to differences in susceptibility to SUDs. Both of these relationships have been described, thus leading to a "chicken or the egg" debate which remains to be fully resolved. Does impulsivity precede drug use or does it manifest as a function of problematic drug usage? The link between impulsivity and SUDs has been most strongly established for cocaine and alcohol use disorders using both preclinical models and clinical data. Much less is known about the potential link between impulsivity and cannabis use disorder (CUD) or the directionality of this relationship. The initiation of cannabis use occurs most often during adolescence prior to the brain's maturation, which is recognized as a critical period of development. The long-term effects of chronic cannabis use on the brain and behavior have started to be explored. In this review we will summarize these observations, especially as they pertain to the relationship between impulsivity and CUD, from both a psychological and biological perspective. We will discuss impulsivity as a multi-dimensional construct and attempt to reconcile the results obtained across modalities. Finally, we will discuss possible avenues for future research with emerging longitudinal data.
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Encéfalo/metabolismo , Conducta Impulsiva/efectos de los fármacos , Abuso de Marihuana/metabolismo , Abuso de Marihuana/psicología , Autocontrol/psicología , Animales , Encéfalo/diagnóstico por imagen , Encéfalo/efectos de los fármacos , Cannabis , Humanos , Conducta Impulsiva/fisiología , Abuso de Marihuana/diagnóstico por imagen , Uso de la Marihuana/metabolismo , Uso de la Marihuana/psicología , Tomografía de Emisión de Positrones/métodos , Tomografía de Emisión de Positrones/tendenciasRESUMEN
We have recently shown that levels of fatty acid amide hydrolase (FAAH), the enzyme that metabolizes the endocannabinoid anandamide, are lower in the brains of adult cannabis users (CUs) (34 ± 11 years of age), tested during early abstinence. Here, we examine replication of the lower FAAH levels in a separate, younger cohort (23 ± 5 years of age). Eighteen healthy volunteers (HVs) and fourteen CUs underwent a positron emission tomography scan using the FAAH radioligand [11 C]CURB. Regional [11 C]CURB binding was calculated using an irreversible two-tissue compartment model with a metabolite-corrected arterial plasma input function. The FAAH C385A genetic polymorphism (rs324420) was included as a covariate. All CUs underwent a urine screen to confirm recent cannabis use and had serum cannabinoids measured. One CU screened negative for cannabinoids via serum and was removed from analysis. All HVs reported less than five lifetime cannabis exposures more than a month prior to study initiation. There was a significant effect of group (F1,26 = 4.31; P = .048) when two A/A (rs324420) HVs were removed from analysis to match the genotype of the CU group (n = 16 HVs, n = 13 CUs). Overall, [11 C]CURB λk3 was 12% lower in CU compared with HV. Exploratory correlations showed that lower brain [11 C]CURB binding was related to greater use of cannabis throughout the past year. We confirmed our previous report and extended these findings by detecting lower [11 C]CURB binding in a younger cohort with less cumulative cannabis exposure.
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Amidohidrolasas/metabolismo , Uso de la Marihuana/metabolismo , Adolescente , Adulto , Encéfalo/metabolismo , Cannabis , Femenino , Humanos , Masculino , Ontario , Tomografía de Emisión de Positrones , Adulto JovenRESUMEN
HIV infection and drug use intersect epidemiologically, and their combination can result in complex effects on brain and behavior. The extent to which drugs affect the health of persons with HIV (PWH) depends on many factors including drug characteristics, use patterns, stage of HIV disease and its treatment, comorbid factors, and age. To consider the range of drug effects, we have selected two that are in common use by PWH: methamphetamine and cannabis. We compare the effects of methamphetamine with those of cannabis, to illustrate how substances may potentiate, worsen, or even buffer the effects of HIV on the CNS. Data from human, animal, and ex vivo studies provide insights into how these drugs have differing effects on the persistent inflammatory state that characterizes HIV infection, including effects on viral replication, immune activation, mitochondrial function, gut permeability, blood brain barrier integrity, glia and neuronal signaling. Moving forward, we consider how these mechanistic insights may inform interventions to improve brain outcomes in PWH. This review summarizes literature from clinical and preclinical studies demonstrating the adverse effects of METH, as well as the potentially beneficial effects of cannabis, on the interacting systemic (e.g., gut barrier leakage/microbial translocation, immune activation, inflammation) and CNS-specific (e.g., glial activation/neuroinflammation, neural injury, mitochondrial toxicity/oxidative stress) mechanisms underlying HIV-associated neurocognitive disorders.
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Barrera Hematoencefálica/efectos de los fármacos , Encéfalo/efectos de los fármacos , Infecciones por VIH/tratamiento farmacológico , Uso de la Marihuana , Metanfetamina/efectos adversos , Trastornos Relacionados con Anfetaminas/epidemiología , Trastornos Relacionados con Anfetaminas/metabolismo , Animales , Barrera Hematoencefálica/metabolismo , Encéfalo/metabolismo , Cannabis , Infecciones por VIH/epidemiología , Infecciones por VIH/metabolismo , Humanos , Uso de la Marihuana/epidemiología , Uso de la Marihuana/metabolismo , Trastornos Neurocognitivos/tratamiento farmacológico , Trastornos Neurocognitivos/metabolismoRESUMEN
RATIONALE: The amygdala is a key brain structure to study in relation to cannabis use as reflected by its high-density of cannabinoid receptors and functional reactivity to processes relevant to drug use. Previously, we identified a correlation between cannabis use in early adolescence and amygdala hyper-reactivity to angry faces (Spechler et al. 2015). OBJECTIVES: Here, we leveraged the longitudinal aspect of the same dataset (the IMAGEN study) to determine (1) if amygdala hyper-reactivity predicts future cannabis use and (2) if amygdala reactivity is affected by prolonged cannabis exposure during adolescence. METHODS: First, linear regressions predicted the level of cannabis use by age 19 using amygdala reactivity to angry faces measured at age 14 prior to cannabis exposure in a sample of 1119 participants. Next, we evaluated the time course of amygdala functional development from age 14 to 19 for angry face processing and how it might be associated with protracted cannabis use throughout this developmental window. We compared the sample from Spechler et al. 2015, the majority of whom escalated their use over the 5-year interval, to a matched sample of non-users. RESULTS: Right amygdala reactivity to angry faces significantly predicted cannabis use 5 years later in a dose-response fashion. Cannabis-naïve adolescents demonstrated the lowest levels of amygdala reactivity. No such predictive relationship was identified for alcohol or cigarette use. Next, follow-up analyses indicated a significant group-by-time interaction for the right amygdala. CONCLUSIONS: (1) Right amygdala hyper-reactivity is predictive of future cannabis use, and (2) protracted cannabis exposure during adolescence may alter the rate of neurotypical functional development.
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Conducta del Adolescente/psicología , Amígdala del Cerebelo/diagnóstico por imagen , Amígdala del Cerebelo/metabolismo , Uso de la Marihuana/metabolismo , Uso de la Marihuana/psicología , Adolescente , Conducta del Adolescente/fisiología , Amígdala del Cerebelo/efectos de los fármacos , Reconocimiento Facial/fisiología , Femenino , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética/métodos , Masculino , Uso de la Marihuana/tendencias , Adulto JovenRESUMEN
RATIONALE: Previous studies have suggested that chronic cannabis use has been associated with increased blood oxygen level-dependent (BOLD) response during a response inhibition task; however, these studies primarily included males. OBJECTIVES: We investigated whether gender moderated the effects of cannabis use on BOLD response and behavioral performance during a Go-NoGo task in adolescents and young adults following 2 weeks of monitored abstinence. METHODS: Participants included 77 16-26-year olds (MJ = 36, controls = 41). An emotion-based Go-NoGo task required participants to inhibit their response during a calm face. A whole-brain analysis looked at differences between cannabis group, gender, and their interaction. RESULTS: Significant greater BOLD responses were observed in cannabis users compared with that in controls in the left frontal cortex, left cingulate cortex, and the left thalamus during correct response inhibitions; gender did not moderate these effects. CONCLUSION: Supporting previous research, cannabis users showed greater BOLD responses in core areas associated with response inhibition during a Go-NoGo task, even after a minimum of 2 weeks of abstinence.
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Encéfalo/metabolismo , Inhibición Psicológica , Imagen por Resonancia Magnética/tendencias , Uso de la Marihuana/metabolismo , Uso de la Marihuana/psicología , Consumo de Oxígeno/fisiología , Adolescente , Adulto , Encéfalo/diagnóstico por imagen , Emociones/fisiología , Femenino , Humanos , Masculino , Factores de Tiempo , Adulto JovenRESUMEN
Globally, cannabis is the most commonly used illicit drug, with disproportionately high use among persons with HIV. Despite advances in HIV care, nearly half of persons living with HIV continue to experience neurocognitive deficits or impairments that may have negative impacts on their daily function. Chronic cannabis use may play a role in the development or exacerbation of these impairments. Here we present a review summarizing existing research detailing the effect of cannabis use associated with the neuropathogenesis of HIV. We examine evidence for possible additive or synergistic effects of HIV infection and cannabis use on neuroHIV in both the preclinical and adult human literatures, including in vitro studies, animal models, clinical neuroimaging research, and studies examining the cognitive effects of cannabis. We discuss the limitations of existing research, including methodological challenges involved with clinical research with human subjects. We identify gaps in the field and propose critical research questions to advance our understanding of how cannabis use affects neuroHIV. Graphical Abstract.
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Encéfalo/efectos de los fármacos , Cannabinoides/administración & dosificación , Cognición/efectos de los fármacos , Infecciones por VIH/tratamiento farmacológico , Uso de la Marihuana , Animales , Encéfalo/metabolismo , Cannabinoides/metabolismo , Cognición/fisiología , Infecciones por VIH/epidemiología , Infecciones por VIH/metabolismo , Humanos , Uso de la Marihuana/epidemiología , Uso de la Marihuana/metabolismoRESUMEN
BACKGROUND: The aim of the current study is to estimate cannabis use prevalence among individuals with diabetes participating in the United States (US) National Survey on Drug Use and Health (NSDUH), 2005-2018. Plausible biological mechanisms link cannabis use and metabolic regulation. Cannabis use can also alter perception and adherence to treatment especially among patients with insulin-dependent diabetes. METHODS: The NSDUH is designed to select and recruit, annually, a representative sample of the non-institutionalized US population (12+ years). Computer-assisted self-interviews gathered information on cannabis use. The current study sample included 30,915 participants who self-reported a physician diagnosis of diabetes. RESULTS: Prevalence of past 30-day cannabis use increased 340% among individuals with diabetes, from 1.7% (95% confidence interval [CI] = 1.1, 2.6) in 2005 to 5.8% (95% CI = 4.7, 7.1) in 2018. Results from the logistic regression model indicated that this increase was robust (odds ratio of cannabis use per NSDUH year = 1.13; 95% CI = 1.10, 1.15). The increase was observed among different sociodemographic subgroups and in states with or without medical cannabis laws. CONCLUSIONS: As cannabis use prevalence increases, screening for use among diabetes patients is needed to optimize outcomes and reduce potential adverse effects.
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Diabetes Mellitus/epidemiología , Encuestas Epidemiológicas/tendencias , Uso de la Marihuana/epidemiología , Uso de la Marihuana/tendencias , Adolescente , Adulto , Anciano , Niño , Diabetes Mellitus/metabolismo , Femenino , Encuestas Epidemiológicas/métodos , Humanos , Masculino , Uso de la Marihuana/metabolismo , Persona de Mediana Edad , Prevalencia , Autoinforme , Trastornos Relacionados con Sustancias/epidemiología , Estados Unidos/epidemiología , Adulto JovenRESUMEN
Activating type 1 cannabinoid (CB1) receptor decreases the particle size of high-density lipoprotein (HDL) and inhibits reverse cholesterol transport (RCT). This study examined whether marijuana (MJ) use is associated with changes of RCT, and how the latter is associated with mitochondrial function and fluid cognition. We recruited 19 chronic MJ users and 20 nonusers with matched age, BMI, sex, ethnicity, and education. We measured their fluid cognition, mitochondrial function (basal and max respiration, ATP production) in peripheral blood mononuclear cells, cholesterol content in serum lipoprotein fractions, enterolactone/creatinine ratio in urine as a marker for dietary polyphenol intake, and lipase activity in serum. We found that higher percentage of large HDL cholesterol (HDL-C) correlated positively, while that of small HDL-C correlated inversely, with mitochondrial function among MJ users, but correlations of the opposite directions were found among nonusers. The concentrations of large and intermediate HDL-C correlated positively with mitochondrial function and fluid cognition among MJ users, but not among nonusers. Both percentage and concentration of large HDL-C correlated positively, while those of small HDL-C correlated inversely, with amounts of daily and lifetime MJ use. In all participants, higher urinary enterolactone/creatinine ratio and lower serum lipase activity were associated with higher large HDL-C/small HDL-C ratio, implying greater RCT. This study suggests that high MJ use may compromise RCT, which is strongly associated with mitochondrial function and fluid cognition among MJ users.
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Colesterol/sangre , Leucocitos Mononucleares/química , Uso de la Marihuana/psicología , Mitocondrias/metabolismo , Adulto , Estudios de Casos y Controles , Cognición , Femenino , Humanos , Lipasa/sangre , Masculino , Uso de la Marihuana/sangre , Uso de la Marihuana/metabolismo , Proyectos Piloto , Adulto JovenRESUMEN
Acute exposure to cannabis comes with neurocognitive impairment, leading to increased risk of human error and injury. Evidence however indicates that such acute effects are less prominent in chronic users, suggesting cannabis tolerance. Models of cannabis tolerance stress the importance of neurobiological or behavioral adaptations following repeated cannabis exposure. The pharmacodynamic model relates neuroadaptive changes in the brain to a blunted response to cannabis. Downregulation of CB1 receptors in chronic cannabis users has been associated with a normalization of dopaminergic output from the ventral tegmental area to the mesolimbic circuit, and a reduction of impairment during acute cannabis exposure. Such neuroadaptions are absent in occasional users, who show strong increments of dopamine and glutamate levels in the striatum, a loss of functional connectivity within the mesolimbic circuit and neurocognitive impairments when exposed to cannabis. Evidence for a behavioral model of cannabis tolerance that poses that users can have volitional control to overcome functional impairment during cannabis intoxication is relatively weak, and at best shows limited control over a limited number of behavioral functions. Cannabis tolerance is most likely to occur in users that consume high doses of cannabis continuously, at a high pace, for a prolonged period of time. Knowledge on frequency, dose and duration of cannabis use that is needed to achieve, maintain or lessen tolerance however is very limited, but will be of importance in the context of cannabis therapeutics and in legal settings when evaluating the impact of cannabis exposure on human function.
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Adaptación Fisiológica/fisiología , Dronabinol/metabolismo , Tolerancia a Medicamentos/fisiología , Alucinógenos/metabolismo , Uso de la Marihuana/metabolismo , Receptores de Cannabinoides/metabolismo , Adaptación Fisiológica/efectos de los fármacos , Animales , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Dronabinol/farmacología , Alucinógenos/farmacología , Humanos , Uso de la Marihuana/psicología , Uso de la Marihuana/tendenciasRESUMEN
Stress and cannabis use are risk factors for the development of psychosis. We have previously shown that subjects at clinical high risk for psychosis (CHR) exhibit a higher striatal dopamine response to stress compared with healthy volunteers (HV), with chronic cannabis use blunting this response. However, it is unknown if this abnormal dopamine response extends to the prefrontal cortex (PFC). Here, we investigated dorsolateral PFC (dlPFC) and medial PFC (mPFC) dopamine release using [11 C]FLB457 positron emission tomography (PET) and a validated stress task. Thirty-three participants completed two PET scans (14 CHR without cannabis use, eight CHR regular cannabis users [CHR-CUs] and 11 HV) while performing a Sensory Motor Control Task (control scan) and the Montreal Imaging Stress Task (stress scan). Stress-induced dopamine release (ΔBPND ) was defined as percent change in D2/3 receptor binding potential between both scans using a novel correction for injected mass of [11 C]FLB457. ΔBPND was significantly different between groups in mPFC (F(2,30) = 5.40, .010), with CHR-CUs exhibiting lower ΔBPND compared with CHR (.008). Similarly, salivary cortisol response (ΔAUCI ) was significantly lower in CHR-CU compared with CHR (F(2,29) = 5.08, .013; post hoc .018) and positively associated with ΔBPND . Furthermore, CHR-CUs had higher attenuated psychotic symptoms than CHR following the stress task, which were negatively associated with ΔBPND . Length of cannabis use was negatively associated with ΔBPND in mPFC when controlling for current cannabis use. Given the global trend to legalize cannabis, this study is important as it highlights the effects of regular cannabis use on cortical dopamine function in high-risk youth.
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Dopamina/metabolismo , Abuso de Marihuana/diagnóstico por imagen , Corteza Prefrontal/diagnóstico por imagen , Trastornos Psicóticos/diagnóstico por imagen , Estrés Psicológico/diagnóstico por imagen , Adulto , Radioisótopos de Carbono , Estudios de Casos y Controles , Femenino , Humanos , Hidrocortisona/metabolismo , Masculino , Abuso de Marihuana/metabolismo , Abuso de Marihuana/psicología , Uso de la Marihuana/metabolismo , Uso de la Marihuana/psicología , Tomografía de Emisión de Positrones , Corteza Prefrontal/metabolismo , Síntomas Prodrómicos , Trastornos Psicóticos/metabolismo , Trastornos Psicóticos/psicología , Pirrolidinas , Radiofármacos , Riesgo , Salicilamidas , Saliva/química , Estrés Psicológico/metabolismo , Estrés Psicológico/psicología , Adulto JovenRESUMEN
AIMS: To explore the association of marijuana use with mean plasma fasting insulin levels and homeostasis model assessment of insulin resistance (HOMA-IR) score in obese adults with different HOMA-IR. METHODS: The National Health and Nutrition Examination Survey (NHANES) is a survey research program designed to assess the health and nutrition status of individuals in the United States and to track changes over time. We abstracted data from NHANES 2009-2016. We estimated the minimal lifetime marijuana use (MLU) using the duration of regular exposure and the frequency of use. We assessed the association of MLU and both plasma fasting insulin and HOMA-IR score using log-linear regression models. RESULTS: A total of 65,209 obese individuals aged 18 to 59 years were included. In obese individuals who never used marijuana (reference), the mean value (± standard deviation) was 19.0 (± 12.8) µU/mL for plasma fasting insulin and 4.78 (± 3.49) for HOMA-IR. In individuals with HOMA-IR < 2.13 or ≥ 5.72, we found no association of marijuana use with HOMA-IR. In those with HOMA-IR < 5.72, the highest tertile of MLU (i.e., ≥ 1799 times) was associated with 12% decrease (95% confidence intervals, 4-19%) in the fasting insulin and 10% decrease in HOMA-IR (95% CI 1-19%), as compared with their counterparts who never used marijuana. In those with HOMA-IR ≥ 2.13, we found a marked impact of marijuana use only in adults who used marijuana ≥ 1799 times, with 13% decrease (95% CI 5-19%) in fasting insulin and 10% decrease (95% CI 3-18%) in HOMA-IR score. CONCLUSIONS: Marijuana use is associated with reduced fasting insulin levels and HOMA-IR score in US obese adults with HOMA-IR ≥ 2.13, but not in those with HOMA-IR < 2.13 or ≥ 5.72. The impact of marijuana use is the greatest after long-term exposure and is independent of BMI.
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Resistencia a la Insulina , Uso de la Marihuana/metabolismo , Obesidad/metabolismo , Adolescente , Adulto , Ayuno/sangre , Femenino , Homeostasis/efectos de los fármacos , Humanos , Insulina/sangre , Masculino , Persona de Mediana Edad , Obesidad/fisiopatología , Adulto JovenRESUMEN
Given the aging Baby Boomer generation, changes in cannabis legislation, and the growing acknowledgment of cannabis for its therapeutic potential, it is predicted that cannabis use in the older population will escalate. It is, therefore, important to determine the interaction between the effects of cannabis and aging. The aim of this report is to describe the link between cannabis use and the aging brain. Our review of the literature found few and inconsistent empirical studies that directly address the impact of cannabis use on the aging brain. However, research focused on long-term cannabis use points toward cumulative effects on multimodal systems in the brain that are similarly affected during aging. Specifically, the effects of cannabis and aging converge on overlapping networks in the endocannabinoid, opioid, and dopamine systems that may affect functional decline particularly in the hippocampus and prefrontal cortex, which are critical areas for memory and executive functioning. To conclude, despite the limited current knowledge on the potential interactive effects between cannabis and aging, evidence from the literature suggests that cannabis and aging effects are concurrently present across several neurotransmitter systems. There is a great need for future research to directly test the interactions between cannabis and aging.
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Envejecimiento/efectos de los fármacos , Envejecimiento/metabolismo , Moduladores de Receptores de Cannabinoides/farmacología , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/metabolismo , Uso de la Marihuana/metabolismo , Animales , HumanosRESUMEN
Objective: The objective of this study was to use electroencephalogram (EEG) biomarkers derived from a short, easily administered neurocognitive testbed to determine acute cannabis intoxication and its effect on driving performance in a driving simulator.Methods: The data analyzed were from a study examining the relationship between psychomotor task performance, EEG data, and driving performance in a simulator. EEG data were collected using a STAT® X-24 EEG Wireless Sensor Headset, which was worn during the psychomotor and driving tasks. Driving data were collected for segments of consistent driving environments, including urban driving, urban curves, interstate, interstate curves, dark rural, and rural straightaways. Dependent measures included measures of lateral and longitudinal vehicle control.Results: There was a significant relationship between impaired driving performance as indicated by increased standard deviation of lane position and EEG power in slow theta band (3-5 Hz) in parietal and occipital areas.Conclusions: These results, combined with our prior reported results, suggest that EEG and electrocardiogram (ECG) acquired concurrent with neuropsychological tests hold potential to provide a highly sensitive, specific, and dose-dependent profile of cannabis intoxication and level of impairment.
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Conducir bajo la Influencia/estadística & datos numéricos , Electroencefalografía/estadística & datos numéricos , Uso de la Marihuana/metabolismo , Desempeño Psicomotor , Adulto , Biomarcadores/análisis , Femenino , Humanos , Masculino , Adulto JovenRESUMEN
BACKGROUND: We examined marijuana and alcohol use trends among drivers aged ≥16 years evaluated at Level I trauma centers before and after Arizona legalized medical marijuana in April 2011. METHODS: We conducted interrupted time series (ITS) analysis of urine drug screens for marijuana metabolites and blood alcohol concentration (BAC) data from the 2008-2014 Arizona State Trauma Registry. RESULTS: Among 30,083 injured drivers, 14,710 had marijuana test results, and 2590 were positive for marijuana; of these, 1087 (42%) also tested positive for alcohol. Among 23,186 drivers with BAC results, 5266 exceeded the legal limit for their age. Compared with prelaw trends (models if law had not been enacted), postlaw models showed small but significant annual increases in the proportions of drivers testing positive for either substance. By the end of 2014, the proportion of drivers testing positive for marijuana was 9.6% versus a projected 5.6% if the law had not been enacted, and the proportion of drivers with illegal BACs was 15.7% versus a projected 8.2%. When ITS was restricted to only substance-tested drivers, no significant differences were detected. CONCLUSIONS: Despite the small annual postlaw increases in the proportion of marijuana-positive drivers compared with the prelaw trend, alcohol-impaired driving remains a more prevalent threat to road safety in Arizona.
Asunto(s)
Accidentes de Tránsito/tendencias , Consumo de Bebidas Alcohólicas/epidemiología , Conducción de Automóvil , Análisis de Series de Tiempo Interrumpido/métodos , Uso de la Marihuana/epidemiología , Centros Traumatológicos/tendencias , Accidentes de Tránsito/legislación & jurisprudencia , Adolescente , Adulto , Anciano , Consumo de Bebidas Alcohólicas/metabolismo , Consumo de Bebidas Alcohólicas/terapia , Arizona/epidemiología , Conducción de Automóvil/legislación & jurisprudencia , Nivel de Alcohol en Sangre , Etanol/sangre , Etanol/orina , Femenino , Humanos , Masculino , Uso de la Marihuana/metabolismo , Uso de la Marihuana/terapia , Marihuana Medicinal/sangre , Marihuana Medicinal/orina , Persona de Mediana Edad , Adulto JovenRESUMEN
The pregnenolone-progesterone-allopregnanolone pathway is receiving increasing attention in research on the role of neurosteroids in pathophysiology, particularly in stress-related and drug use disorders. These disorders involve an allostatic change that may result from deficiencies in allostasis or adaptive responses, and may be downregulated by adjustments in neurotransmission by neurosteroids. The following is an overview of findings that assess how pregnenolone and/or allopregnanolone concentrations are altered in animal models of stress and after consumption of alcohol or cannabis-type drugs, as well as in patients with depression, anxiety, post-traumatic stress disorder or psychosis and/or in those diagnosed with alcohol or cannabis use disorders. Preclinical and clinical evidence shows that pregnenolone and allopregnanolone, operating according to a different or common pharmacological profile involving GABAergic and/or endocannabinoid system, may be relevant biomarkers of psychiatric disorders for therapeutic purposes. Hence, ongoing clinical trials implicate synthetic analogs of pregnenolone or allopregnanolone, and also modulators of neurosteroidogenesis.
Asunto(s)
Alcoholismo/metabolismo , Uso de la Marihuana/metabolismo , Neuroesteroides/metabolismo , Pregnanolona/metabolismo , Pregnenolona/metabolismo , Progesterona/metabolismo , Transducción de Señal/fisiología , Estrés Psicológico/metabolismo , Alcoholismo/tratamiento farmacológico , Animales , Uso de la Marihuana/tratamiento farmacológicoRESUMEN
Importance: Cannabis is the most commonly used illicit drug in the world. Cannabinoids have been shown to modulate immune responses; however, the association of cannabis with neuroimmune function has never been investigated in vivo in the human brain. Objective: To investigate neuroimmune activation or 18-kDa translocator protein (TSPO) levels in long-term cannabis users, and to evaluate the association of brain TSPO levels with behavioral measures and inflammatory blood biomarkers. Design, Setting, and Participants: This cross-sectional study based in Toronto, Ontario, recruited individuals from January 1, 2015, to October 30, 2018. Participants included long-term cannabis users (n = 24) and non-cannabis-using controls (n = 27). Cannabis users were included if they had a positive urine drug screen for only cannabis and if they used cannabis at least 4 times per week for the past 12 months and/or met the criteria for cannabis use disorder. All participants underwent a positron emission tomography scan with [18F]FEPPA, or fluorine F 18-labeled N-(2-(2-fluoroethoxy)benzyl)-N-(4-phenoxypyridin-3-yl)acetamide. Main Outcomes and Measures: Total distribution volume was quantified across regions of interest. Stress and anxiety as well as peripheral measures of inflammatory cytokines and C-reactive protein levels were also measured. Results: In total, 24 long-term cannabis users (mean [SD] age, 23.1 [3.8] years; 15 men [63%]) and 27 non-cannabis-using controls (mean [SD] age, 23.6 [4.2] years; 18 women [67%]) were included and completed all study procedures. Compared with the controls, cannabis users had higher [18F]FEPPA total distribution volume (main group effect: F1,48 = 6.5 [P = .01]; ROI effect: F1,200 = 28.4 [P < .001]; Cohen d = 0.6; 23.3% higher), with a more prominent implication for the cannabis use disorder subgroup (n = 15; main group effect: F1,39 = 8.5 [P = .006]; ROI effect: F1,164 = 19.3 [P < .001]; Cohen d = 0.8; 31.5% higher). Greater TSPO levels in the brain were associated with stress and anxiety and with higher circulating C-reactive protein levels in cannabis users. Conclusions and Relevance: The results of this study suggest that TSPO levels in cannabis users, particularly in those with cannabis use disorder, are higher than those in non-cannabis-using controls. The findings emphasize the need for more complementary preclinical systems for a better understanding of the role of cannabinoids and TSPO in neuroimmune signaling.