RESUMEN
Cannabis use history as predictor of neurocognitive response to cannabis intoxication remains subject to scientific and policy debates. The present study assessed the influence of cannabis on neurocognition in cannabis users whose cannabis use history ranged from infrequent to daily use. Drug users (N = 122) received acute doses of cannabis (300 µg/kg THC), cocaine HCl (300 mg) and placebo. Cocaine served as active control for demonstrating neurocognitive test sensitivity. Executive function, impulse control, attention, psychomotor function and subjective intoxication were significantly worse after cannabis administration relative to placebo. Cocaine improved psychomotor function and attention, impaired impulse control and increased feelings of intoxication. Acute effects of cannabis and cocaine on neurocognitive performance were similar across cannabis users irrespective of their cannabis use history. Absence of tolerance implies that that frequent cannabis use and intoxication can be expected to interfere with neurocognitive performance in many daily environments such as school, work or traffic.
Asunto(s)
Cognición/efectos de los fármacos , Dronabinol/efectos adversos , Consumidores de Drogas/psicología , Desempeño Psicomotor/efectos de los fármacos , Enfermedad Aguda , Adolescente , Adulto , Atención/efectos de los fármacos , Cocaína/administración & dosificación , Cocaína/efectos adversos , Cocaína/farmacología , Trastornos Relacionados con Cocaína/psicología , Estudios Cruzados , Método Doble Ciego , Dronabinol/farmacocinética , Tolerancia a Medicamentos , Función Ejecutiva/efectos de los fármacos , Femenino , Hábitos , Humanos , Conducta Impulsiva/efectos de los fármacos , Masculino , Abuso de Marihuana/psicología , Pruebas de Estado Mental y Demencia , Países Bajos , Adulto JovenRESUMEN
The dopamine ß-hydroxylase (DßH) enzyme transforms dopamine into noradrenaline. We hypothesized that individuals with low activity DBH genotypes (rs1611115 CT/TT) are more sensitive to the influence of cannabis and cocaine on cognitive impulse control and functional connectivity in the limbic 'reward' circuit because they experience a drug induced hyperdopaminergic state compared to individuals with high activity DBH genotypes (rs1611115 CC). Regular drug users (N = 122) received acute doses of cannabis (450 µg/kg THC), cocaine HCl 300 mg and placebo. Cognitive impulse control was assessed by means of the Matching Familiar Figures Test (MFFT). Resting state fMRI was measured in a subset of participants to determine functional connectivity between the nucleus accumbens (NAc) and (sub)cortical areas. The influence of cannabis and cocaine on impulsivity and functional connectivity significantly interacted with DBH genotype. Both drugs increased cognitive impulsivity in participants with CT/TT genotypes but not in CC participants. Both drugs also reduced functional connectivity between the NAc and the limbic lobe, prefrontal cortex, striatum and thalamus and primarily in individuals with CT/TT genotypes. Correlational analysis indicated a significant negative association between cognitive impulsivity and functional connectivity in subcortical areas of the brain. It is concluded that interference of cannabis and cocaine with cognitive impulse control and functional corticostriatal connectivity depends on DBH genotype. The present data provide a neural substrate and behavioral mechanism by which drug users can progress to drug seeking and may also offer a rationale for targeted pharmacotherapy in chronic drug users with high risk DBH genotypes.
Asunto(s)
Encéfalo/efectos de los fármacos , Cocaína/efectos adversos , Dopamina beta-Hidroxilasa/genética , Dronabinol/efectos adversos , Conducta Impulsiva , Psicotrópicos/efectos adversos , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Mapeo Encefálico , Cannabis , Cocaína/administración & dosificación , Cocaína/sangre , Cocaína/farmacocinética , Trastornos Relacionados con Cocaína/diagnóstico por imagen , Trastornos Relacionados con Cocaína/genética , Trastornos Relacionados con Cocaína/fisiopatología , Trastornos Relacionados con Cocaína/psicología , Cognición/efectos de los fármacos , Cognición/fisiología , Estudios Cruzados , Método Doble Ciego , Dronabinol/administración & dosificación , Dronabinol/sangre , Dronabinol/farmacocinética , Función Ejecutiva/efectos de los fármacos , Función Ejecutiva/fisiología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Abuso de Marihuana/diagnóstico por imagen , Abuso de Marihuana/genética , Abuso de Marihuana/fisiopatología , Abuso de Marihuana/psicología , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/efectos de los fármacos , Vías Nerviosas/fisiopatología , Pruebas Neuropsicológicas , Psicotrópicos/administración & dosificación , Psicotrópicos/sangre , Psicotrópicos/farmacocinética , Descanso , Adulto JovenRESUMEN
Trait impulsivity has been linked to addiction in humans. It has been suggested that drug users with high trait impulsivity levels are more sensitive to subjective drug intoxication. This study assessed whether subjective response to drugs differs between drug users with normal or high levels of trait impulsivity. Regular drug users (N = 122) received doses of cocaine HCl, cannabis, and placebo in a three-way crossover study. Their mood, dissociative state, and psychedelic symptoms were measured with subjective rating scales (CADDS, Bowdle, POMS). Trait impulsivity was assessed with the Barratt Impulsiveness Scale. Cannabis increased dissociation and psychedelic state, as well as fatigue, confusion, depression and anxiety, and decreased arousal, positive mood, vigor, friendliness, and elation. Cocaine increased dissociation, psychedelic state, vigor, friendliness, elation, positive mood, anxiety and arousal, while decreasing fatigue. Only a few subjective items revealed a drug × trait impulsivity interaction, suggesting that psychedelic symptoms were most intense in high impulsivity subjects. Trait impulsiveness ratings were negatively correlated with ratings of vigor (r = -.197) and positively correlated with ratings of loss of thought control (r = .237) during cannabis intoxication. It is concluded that a broad association between trait impulsivity and psychedelic subjective drug experience appears to be absent.
Asunto(s)
Cocaína/farmacología , Dronabinol/farmacología , Alucinógenos/farmacología , Conducta Impulsiva/efectos de los fármacos , Adulto , Afecto/efectos de los fármacos , Cannabis/química , Estudios Cruzados , Método Doble Ciego , Femenino , Humanos , Masculino , Adulto JovenRESUMEN
RATIONALE: Knowing how commonly used drugs affect performance monitoring is of great importance, because drug use is often associated with compromised behavioral control. Two of the most commonly used recreational drugs in the western world, 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") and ethanol (alcohol), are also often used in combination. The error-related negativity (ERN), correct-related negativity (CRN), and N2 are electrophysiological indices of performance monitoring. OBJECTIVES: The present study aimed to investigate how ethanol, MDMA, and their co-administration affect performance monitoring as indexed by the electrophysiological correlates. METHODS: Behavioral and EEG data were obtained from 14 healthy volunteers during execution of a speeded choice-reaction-time task after administration of ethanol, MDMA, and combined ethanol and MDMA, in a double-blind, placebo-controlled, randomized crossover design. RESULTS: Ethanol significantly reduced ERN amplitudes, while administration of MDMA did not affect the ERN. Co-administration of MDMA and ethanol did not further impair nor ameliorate the effect of ethanol alone. No drug effects on CRN nor N2 were observed. DISCUSSION: A decreased ERN following ethanol administration is in line with previous work and offers further support for the impairing effects of alcohol intoxication on performance monitoring. This impairment may underlie maladaptive behavior in people who are under influence. Moreover, these data demonstrate for the first time that MDMA does not affect performance monitoring nor does it interact with ethanol in this process. These findings corroborate the notion that MDMA leaves central executive functions relatively unaffected.
Asunto(s)
Etanol/efectos adversos , Alucinógenos/efectos adversos , N-Metil-3,4-metilenodioxianfetamina/efectos adversos , Desempeño Psicomotor/efectos de los fármacos , Adolescente , Adulto , Conducta de Elección/efectos de los fármacos , Estudios Cruzados , Método Doble Ciego , Interacciones Farmacológicas , Fenómenos Electrofisiológicos , Etanol/administración & dosificación , Femenino , Alucinógenos/administración & dosificación , Humanos , Masculino , N-Metil-3,4-metilenodioxianfetamina/administración & dosificación , Tiempo de Reacción/efectos de los fármacos , Adulto JovenRESUMEN
BACKGROUND AND PURPOSE: Cannabis is the most popular drug used in the European Union, closely followed by cocaine. Whereas cannabis impairs neurocognitive function in occasional cannabis users, such impairments appear less prominent in heavy users, possibly as a result of tolerance. The present study was designed to assess whether the impairing effects of Δ(9) -tetrahydrocannabinol (THC) in heavy cannabis users would present in a wide range of neuropsychological functions or selectively affect specific performance domains. We also assessed the acute effects of cocaine on neurocognitive functions of heavy cannabis users. EXPERIMENTAL APPROACH: Heavy cannabis users, who had a history of cocaine use (n = 61), participated in a double-blind, placebo-controlled, three-way crossover study. Subjects received single doses of cocaine HCl (300 mg), cannabis (THC µg·kg(-1) ) and placebo, and completed a number of tests measuring impulse control and psychomotor function. KEY RESULTS: Single doses of cannabis impaired psychomotor function and increased response errors during impulsivity tasks. Single doses of cocaine improved psychomotor function and decreased response time in impulsivity tasks, but increased errors. CONCLUSIONS AND IMPLICATIONS: Heavy cannabis users display impairments in a broad range of neuropsychological domains during THC intoxication. Impairments observed in psychomotor tasks, but not in impulsivity tasks, appeared smaller in magnitude as compared with those previously reported in occasional cannabis users. Heavy cannabis users were sensitive to the stimulating and inhibitory effects of cocaine on psychomotor function and impulsivity respectively. The reduction in proficiency in impulse control may put drug users at increased risk of repeated drug use and addiction.
Asunto(s)
Estimulantes del Sistema Nervioso Central/administración & dosificación , Trastornos Relacionados con Cocaína/psicología , Cocaína/administración & dosificación , Dronabinol/administración & dosificación , Alucinógenos/administración & dosificación , Conducta Impulsiva/psicología , Abuso de Marihuana/psicología , Fumar Marihuana/psicología , Administración por Inhalación , Administración Oral , Adulto , Estimulantes del Sistema Nervioso Central/farmacocinética , Cocaína/farmacocinética , Cognición/efectos de los fármacos , Estudios Cruzados , Método Doble Ciego , Dronabinol/farmacocinética , Femenino , Alucinógenos/farmacocinética , Humanos , Masculino , Pruebas Neuropsicológicas , Desempeño Psicomotor/efectos de los fármacos , Tiempo de Reacción/efectos de los fármacos , Factores de Tiempo , Adulto JovenRESUMEN
OBJECTIVE: The amplitude and latency of the P300 may be associated by variations in dopaminergic genes. The current study was conducted to determine whether functional variants of the catechol-O-methyltransferase (COMT) and dopamine beta-hydroxylase (DBH) gene were associated with P300 amplitude and latency in an auditory oddball task. METHODS: The P300 ERP was assessed by a two-tone auditory oddball paradigm in a large sample of 320 healthy volunteers. The Val108/158Met polymorphism (rs4680) of the COMT gene and the -1021C>T polymorphism (rs1611115) of the DBH gene were genotyped. P300 amplitude and latency were compared across genotype groups using analysis of variance. RESULTS: There were no differences in demographic characteristics in subjects for genotypic subgroups. No genotype associations were observed for the P300 amplitude and latency on frontal, central and parietal electrode positions. CONCLUSIONS: COMT Val108/158Met and DBH -1021C>T polymorphisms do not show evidence of association with characteristics of the P300 ERP in an auditory oddball paradigm in healthy volunteers. SIGNIFICANCE: We failed to find evidence for the association between dopaminergic enzymatic polymorphisms and the P300 ERP in healthy volunteers, in the largest study undertaken to date.
Asunto(s)
Catecol O-Metiltransferasa/genética , Dopamina beta-Hidroxilasa/genética , Potenciales Relacionados con Evento P300/genética , Potenciales Evocados Auditivos/genética , Polimorfismo de Nucleótido Simple , Adolescente , Adulto , Anciano , Femenino , Genotipo , Humanos , Masculino , Metionina/genética , Persona de Mediana Edad , Pruebas Neuropsicológicas , Valina/genética , Adulto JovenRESUMEN
PURPOSE: In conventional Digital Breast Tomosynthesis (DBT) systems a single x-ray source moves over a limited angle arc. This leads to motion blurring in the projection images associated with x-ray source motion and total scan times. We have developed a stationary DBT (s-DBT) system which forgoes a rotating source for an array of carbon nanotube (CNT) based x-ray sources. Here we report the results of evaluating the performance and the optimization of image acquisition parameters of the s-DBT system. METHODS: The s-DBT system consists of a linear source array with 31 x-ray generating focal spots distributed over a 30 degree angular span. The source array has been retrofitted onto a Hologic Selenia Dimensions DBT system. An American College of Radiology accreditation phantom was imaged to assess the quality of the reconstruction images in different configurations. A line wire phantom is used to measure the modulation transfer function (MTF). RESULTS: For the standard imaging protocol, the system resolution along the scanning direction is increased from 3.0 cycles/mm in DBT to 4.2 cycles/mm in s-DBT at a magnification factor of 1.08. The MTF did not have a noticeable change between different configurations, whereas in DBT the MTF can be degraded for larger angular spans due to faster x-ray source motion. The overall image quality factor is found to be best for the configuration with a large angular span and intermittent number of projection views. CONCLUSIONS: We demonstrated successful construction and operation of the s-DBT system integrating a CNT x-ray source array with a Hologic DBT system. The spatial resolution of the s-DBT system is demonstrated to be substantially increased over the corresponding DBT system. It was found that a configuration with a large angular span, an intermittent number of projection views, and an even dose distribution resulted in the best overall image quality. Hologic INC has provided the Hologic Selenia Dimensions used in the research. The project is supported by the National Cancer Institute under grant number U54CA119343 and R01CA134598 and the UNC University Cancer Research Fund. Dr. Xin Qian is supported by a fellowship from the Department of Defense under grant number BC087505.
RESUMEN
Studies have shown that digital breast tomosynthesis (DBT) can improve breast cancer diagnosis by reconstructing 3D images. However, DBT scanners based on rotation gantry prolong the imaging time and reduce spatial resolution due to motion comparing with the regular two-view mammography. To obtain three dimension reconstruction images and maintain the high image quality of conventional mammography, we proposed a prototype stationary digital breast tomosynthesis system (s-DBT). The proposed s-DBT system acquires projection images without mechanical movement. The core component of the s-DBT system is a specially designed spatially distributed multi-beam x-ray tube based on the carbon nanotube field emission x-ray technology. The multi-beam x-ray source array enables collection of all projection images from different viewing angles without mechanical motion. Preliminary results show the s-DBT system can achieve a scan time comparable to the regular two-view mammography, and improve the spatial resolution comparing with rotating gantry DBT.
RESUMEN
Tomosynthesis requires projection images from different viewing angles. Using a distributed x-ray source this can be achieved without mechanical motion of the source with the potential for faster image acquisition speed. A distributed x-ray tube has been designed and manufactured specifically for breast tomosynthesis. The x-ray tube consists of 31 field emission x-ray sources with an angular range of 30°. The total dose is up to 100mAs with an energy range between 27 and 45 kVp. We discuss the source geometry and results from the characterization of the first prototype. The x-ray tube uses field emission cathodes based on carbon nanotubes (CNT) as electron source. Prior to the manufacturing of the sealed x-ray tube extensive testing on the field emission cathodes has been performed to verify the requirements for commercial tomosynthesis systems in terms of emission current, focal spot size and tube lifetime.
RESUMEN
The aim of this study was to investigate if biomarkers in QEEG, genetic and neuropsychological measures are suitable for the prediction of antidepressant treatment outcome in depression. Twenty-five patients diagnosed with major depressive disorder were assessed twice, pretreatment and at 8-wk follow-up, on a variety of QEEG and neuropsychological tasks. Additionally, cheek swab samples were collected to assess genetic predictors of treatment outcome. The primary outcome measure was the absolute decrease on the HAM-D rating scale. Regression models were built in order to investigate which markers contribute most to the decrease in absolute HAM-D scores. Patients who had a better clinical outcome were characterized by a decrease in the amplitude of the Auditory Oddball N1 at baseline. The 'Met/Met' variant of the COMT gene was the best genetic predictor of treatment outcome. Impaired verbal memory performance was the best cognitive predictor. Raised frontal Theta power was the best EEG predictor of change in HAM-D scores. A tentative integrative model showed that a combination of N1 amplitude at Pz and verbal memory performance accounted for the largest part of the explained variance. These markers may serve as new biomarkers suitable for the prediction of antidepressant treatment outcome.
Asunto(s)
Antidepresivos/uso terapéutico , Catecol O-Metiltransferasa/genética , Trastorno Depresivo Mayor/tratamiento farmacológico , Potenciales Evocados Auditivos , Lóbulo Frontal/fisiopatología , Memoria , Ritmo Teta , Aprendizaje Verbal , Adulto , Percepción Auditiva , Biomarcadores , Factor Neurotrófico Derivado del Encéfalo/genética , Cognición , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/genética , Trastorno Depresivo Mayor/fisiopatología , Trastorno Depresivo Mayor/psicología , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Electroencefalografía , Femenino , Estudios de Seguimiento , Humanos , Modelos Lineales , Masculino , Metionina , Persona de Mediana Edad , Pruebas Neuropsicológicas , Proyectos Piloto , Polimorfismo de Nucleótido Simple , Valor Predictivo de las Pruebas , Resultado del TratamientoRESUMEN
Tomosynthesis imaging requires projection images from different viewing angles. Conventional systems use a moving xray source to acquire the individual projections. Using a stationary distributed x-ray source with a number of sources that equals the number of required projections, this can be achieved without any mechanical motion. Advantages are a potentially faster image acquisition speed, higher spatial and temporal resolution and simple system design. We present distributed x-ray sources based on carbon nanotube (CNT) field emission cathodes. The field emission cathodes deliver the electrons required for x-ray production. CNT emitters feature a stable emission at high current density, a cold emission, excellent temporal control of the emitted electrons and good configurability. We discuss the use of stationary sources for two applications: (i) a linear tube for stationary digital breast tomosynthesis (sDBT), and (ii) a square tube for on-board tomosynthesis image-guided radiation therapy (IGRT). Results from high energy distributed sources up to 160kVp are also presented.