Objective To evaluate the pharmacokinetics of a purified oral cannabidiol (CBD) capsule administered with and without food in adults with refractory epilepsy. Methods Adult patients who were prescribed CBD for seizures, had localization‐related intractable epilepsy with ≥4 seizures per month, and qualified for Minnesota cannabis were enrolled. A single dose of 99% pure CBD capsules was taken under both fasting (no breakfast) and fed (high fat 840‐860 calorie) conditions. Blood sampling for CBD plasma concentrations was performed under each condition between 0 and 72 hours post‐dose and measured by a validated liquid chormatography‐mass spectometry assay. CBD pharmacokinetic profiles including maximum concentration (Cmax), area‐under‐the‐curve from zero to infinity (AUC0‐∞), and time‐to‐maximum concentration (Tmax) were calculated. The confidence intervals (CIs) for log‐transformed Cmax and AUC0‐∞ ratios between fed and fasting states were calculated. Seizure and adverse events information was collected. Results Eight patients completed the study. On average Cmax was 14 times and AUC0‐∞ 4 times higher in the fed state. The 90% CI for the ratio of fed versus fast conditions for Cmax and AUC0‐∞ were 7.47‐31.86 and 3.42‐7.82, respectively. No sequence or period effect for Cmax and AUC0‐∞ was observed. No adverse events were reported. Significance Administering CBD as a capsule rather than a liquid allows for more precise determination of pharmacokinetics parameters and is more representative of CBD swallowed products. The fat content of a meal can lead to significant increases in Cmax and AUC0‐∞ and can account for variability in bioavailability and overall drug exposure within patients with oral products.
Background: Tone languages such as Thai and Mandarin Chinese use differences in fundamental frequency (F 0 , pitch) to distinguish lexical meaning. Previous behavioral studies have shown that native speakers of a non-tone language have difficulty discriminating among tone contrasts and are sensitive to different F 0 dimensions than speakers of a tone language. The aim of the present ERP study was to investigate the effect of language background and training on the non-attentive processing of lexical tones. EEG was recorded from 12 adult native speakers of Mandarin Chinese, 12 native speakers of American English, and 11 Thai speakers while they were watching a movie and were presented with multiple tokens of low-falling, mid-level and high-rising Thai lexical tones. High-rising or low-falling tokens were presented as deviants among mid-level standard tokens, and vice versa. EEG data and data from a behavioral discrimination task were collected before and after a two-day perceptual categorization training task.
During reading or listening, language comprehenders construct a mental representation of the objects and events mentioned. This model is augmented and modified incrementally as the discourse unfolds. In this paper we focus on the interpretation of bare quantifiers, that is, expressions such as 'two', to investigate the processes underlying the construction and modification of the discourse model. Bare quantifiers are temporarily ambiguous when sentences are processed incrementally. For instance, in 'Three ships were in the port. Two…', 'two' can either refer to a subset of the set just mentioned (e.g.,'two of the three ships'), a different set of the entities mentioned (e.g., 'two other ships'), or a set of different entities (e.g., 'two people'). Data from previous studies, and a current completion study, suggest that the subset interpretation is preferred over the establishment of a different set. The current study aimed to investigate ERP correlates of quantifier interpretation and their timing. Quantifiers that unambiguously signaled the establishment of a new referent elicited a late positive component (900-1500 ms), which we interpret as a Late Positive Complex, related to the difficulty involved in context updating. An additional 500-700ms positivity was elicited only in a subset of readers, suggesting that there are individual differences in quantifier interpretation and the timing thereof.
Working memory capacity (WMC) measures the amount of information that can be maintained online in the face of distraction. Past work has shown that the efficiency with which the frontostriatal circuit filters out task-irrelevant distracting information is positively correlated with WMC. Recent work has demonstrated a role of posterior alpha oscillations (8–13 Hz) in providing a sensory gating mechanism. We investigated the relationship between memory load modulation of alpha power and WMC in two verbal working memory experiments. In both experiments, we found that posterior alpha power increased with memory load during memory, in agreement with previous reports. Across individuals, the degree of alpha power modulation by memory load was negatively associated with WMC, namely, the higher the WMC, the less alpha power was modulated by memory load. After the administration of topiramate, a drug known to affect alpha oscillations and have a negative impact on working memory function, the negative correlation between memory load modulation of alpha power and WMC was no longer statistically significant but still somewhat detectable. These results suggest that (1) individuals with low WMC demonstrate stronger alpha power modulation by memory load, reflecting possibly an increased reliance on sensory gating to suppress task-irrelevant information in these individuals, in contrast to their high WMC counterparts who rely more on frontal areas to perform this function and (2) this negative association between memory load modulation of alpha oscillations and WMC is vulnerable to drug-related cognitive disruption.
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