•Pharmacodynamics were assessed for oral/vaporized CBD and CBD-dominant cannabis.•100 mg vaporized pure cannabidiol (CBD) produced discriminable subjective effects.•The subjective effects following ...pure CBD exposure were not “THC like”.•Neither CBD nor CBD dominant cannabis acutely impaired cognitive functioning.•Women reported stronger subjective effects than men after CBD/cannabis inhalation.
The use and availability of oral and inhalable products containing cannabidiol (CBD) as the principal constituent has increased with expanded cannabis/hemp legalization. However, few controlled clinical laboratory studies have evaluated the pharmacodynamic effects of oral or vaporized CBD or CBD-dominant cannabis.
Eighteen healthy adults (9 men; 9 women) completed four, double-blind, double-dummy, drug administration sessions. Sessions were separated by ≥1 week and included self-administration of 100 mg oral CBD, 100 mg vaporized CBD, vaporized CBD-dominant cannabis (100 mg CBD; 3.7 mg THC), and placebo. Study outcomes included: subjective drug effects, vital signs, cognitive/psychomotor performance, and whole blood THC and CBD concentrations.
Vaporized CBD and CBD-dominant cannabis increased ratings on several subjective items (e.g., Like Drug Effect) relative to placebo. Subjective effects did not differ between oral CBD and placebo and were generally higher for CBD-dominant cannabis compared to vaporized CBD. CBD did not increase ratings for several items typically associated with acute cannabis/THC exposure (e.g., Paranoid). Women reported qualitatively higher ratings for Pleasant Drug Effect than men after vaporized CBD and CBD-dominant cannabis use. CBD-dominant cannabis increased heart rate compared to placebo. Cognitive/psychomotor impairment was not observed in any drug condition.
Vaporized CBD and CBD-dominant cannabis produced discriminable subjective drug effects, which were sometimes stronger in women, but did not produce cognitive/psychomotor impairment. Subjective effects of oral CBD did not differ from placebo. Future research should further elucidate the subjective effects of various types of CBD products (e.g., inhaled, oral, topical), which appear to be distinct from THC-dominant products.
Abstract
Introduction
Sleep deprivation has often been associated with decreased cognitive control, including deficits in the ability to sustain attention. Psychomotor vigilance speed slows following ...a period of fatigue, and can lead to disastrous results in daily life. In order to determine the brain areas correlated with reduced psychomotor vigilance speed, as a result of diminished sleep, a voxel-based morphometry analysis was performed prior to a period of monitored sleep deprivation. The mean speed of response time during the final 17 hours of a 29-hour sleep deprivation was then measured with the Psychomotor Vigilance Test (PVT), a reaction-timed task that measures the speed participants respond to a visual stimulus.
Methods
45 healthy individuals (male=23 female=22) between the ages of 20-43 years (M=25.4 SD=5.6) participated in the study. Structural neuroimaging data were collected using a T3 magnetic resonance imaging scanner following a typical night’s sleep. Mean PVT speed was monitored with an hourly 10-minute PVT assessment during a monitored overnight sleep deprivation session. Speed was defined as the reciprocal of reaction time (1/RT).
Results
PVT speed was negatively correlated with grey matter volume (P<.05 FWE-corrected) in the prefrontal cortex, specifically the right posterior inferior frontal gyrus (p=.030; MNI coordinates = 36, 12, 26).
Conclusion
Our findings indicate that gray matter within the right posterior inferior frontal gyrus is greater in individuals who are more vulnerable to slowing of PVT responses during an overnight period of sleep deprivation. These findings suggest that inter-individual differences in the ability to sustain psychomotor vigilance during sleep loss may be related to increased gray matter in the right lateral prefrontal cortex and could have implications for understanding the neurobiological substrates of vulnerability and resilience to sleep loss.
Support
Abstract
Introduction
Sleep deprivation and circadian misalignment impairs human sensorimotor performance and reduces vigilant attention, which increases the potential for errors in occupations that ...require 24-hour operations. The psychomotor vigilance task (PVT) is the gold-standard measure for evaluating the impact of sleepiness on performance, however, it is not practical to administer in many operational environments, because it only provides a snapshot of performance and requires an individual to focus on the task for several minutes, multiple times over a work shift. As a result, passive, continuous monitoring of sleepiness is desirable for operational environments. The goal of the present study was to determine if complex oculomotor behavioral metrics track PVT performance during sleep deprivation.
Methods
Twelve healthy adults (mean age 24.8 ± 5.4 years; 6F) maintained a fixed schedule with 8.5 hours in bed for two weeks, during which they abstained from caffeine, alcohol, and other medications, followed by a ~24 hours constant routine laboratory stay. Participants completed the PVT and a radial step-ramp ocular tracking task hourly throughout the study. Twelve oculometrics were derived from smooth pursuit and saccadic eye movements collected through video-oculography and were compared to the PVT and Karolinska Sleepiness Scale (KSS) using linear regression and receiver operating characteristic curves.
Results
Nine oculometrics spanning pursuit, saccade, and directional motion processing performance correlated with the PVT and KSS (p < 0.05), including: (a) pursuit latency; (b) open-loop pursuit acceleration; (c) proportion smooth; (d) steady-state pursuit gain; (e) saccadic amplitude; (f) saccadic dispersion; (g) saccadic rate; (h) direction asymmetry; and (i) direction noise.
Conclusion
The oculometrics that we examined exhibited a distinct pattern that tracked PVT performance. Future studies should examine whether these metrics can be extracted through passive monitoring techniques.
Support
None
Abstract
Introduction
Sustained attention is important for optimal neurobehavioral performance, but many biological and environment factors (e.g., circadian rhythm, distraction) may cause sustained ...attention deficits. Mastication (chewing) has been suggested to provide a countermeasure to sustained attention deficits. To investigate this, we conducted a randomized, within-subjects, cross-over study of sustained attention with a mastication condition and a control condition.
Methods
N=58 adults (ages 18–45; 38 females) completed a 5h in-laboratory study. Subjects entered the laboratory at 09:00. Following training on performance tasks, they had a 1h break before beginning the first of two test bouts at 11:00. Each test bout was 40min long and included subjective rating scales, the Sustained Attention to Response Task, and the Psychomotor Vigilance Test (PVT). Here we focus on PVT lapses of attention (RT > 500 ms), false starts, and mean reaction time (RT) as measures of sustained attention. In between test bouts, subjects had a 1h break inside the laboratory. During one of the two test bouts, subjects were instructed to chew a piece of gum at a steady, comfortable rate. Mastication activity was verified via electromyography (EMG). Half of the sample was assigned to the mastication condition during the first test bout, the other half during the second test bout.
Results
Controlling for order of conditions, there were no significant differences between conditions for PVT lapses (F1,56=0.40, P=0.54) or false starts (F1,56=0.10, P=0.80). Mean RT was higher in the mastication condition by 8.9±2.5ms (F1,56 =12.68, P<0.001).
Conclusion
Using this test paradigm, we were unable to detect any significant improvement in PVT performance, although mastication resulted in a very small increase in mean RT. However, subjects were not sleep-deprived, distracted, or otherwise perturbed. A follow-up study under conditions of sleep deprivation and/or with longer task duration may provide further insight into the countermeasure potential of mastication.
Support
Mars Wrigley Confectionery, U.S., LLC
Scientific literature and documents pertaining to the effects of inhalation exposure to carbon dioxide (CO2) on human health and psychomotor performance were reviewed. Linear physiological changes in ...circulatory, cardiovascular, and autonomic systems on exposure to CO2 at concentrations ranging from 500 to 5000 ppm were evident. Human experimental studies have suggested that short-term CO2 exposure beginning at 1000 ppm affects cognitive performances including decision making and problem resolution. Changes in autonomic systems due to low-level exposure to CO2 may involve these effects. Further research on the long-term effects of low-level CO2 exposure on the autonomic system is required. Numerous epidemiological studies indicate an association between low-level exposure to CO2 beginning at 700 ppm and building-related symptoms. Respiratory symptoms have been indicated in children exposed to indoor CO2 concentrations higher than 1000 ppm. However, other indoor comorbid pollutants are possibly involved in such effects. In the context of significant linear increase of globally ambient CO2 concentration caused by anthropogenic activities and sources, reducing indoor CO2 levels by ventilation with ambient air represents an increase in energy consumption in an air-conditioned building. For the efficient energy control of CO2 intruding a building from ambient air, the rise of atmospheric CO2 concentration needs to be urgently suppressed.
•Direct effects of low-level CO2 exposure on human health should be focused.•Physiological changes occur at CO2 exposures levels between 500 and 5000 ppm.•Effects on cognitive performance begin at 1000 ppm during short-term exposure.•Comorbid indoor pollutants may be involved in building-related symptoms.•The rise of atmospheric CO2 concentration needs to be urgently suppressed.
Introduction Current tools to evaluate daytime sleepiness lack sensitivity and specificity. Additions to the multiple sleep latency test (MSLT) have been proposed, including the psychomotor vigilance ...test (PVT). The PVT has been extensively examined in controls to characterize effects of sleep loss, but its use as a tool to diagnose and classify individual patients remains incompletely characterized. We assessed whether sleep clinicians/researchers could differentiate PVT performance between patients with hypersomnolence and non-sleepy controls tasked with either performing their best or simulating sleepiness. Methods Twenty-eight patients (EDS group, mean age 35.2 (SD 15.8), 64.3% women) with excessive daytime sleepiness confirmed with clinical interview, Epworth>10, and MSLT mean sleep latency ≤8 minutes underwent 10-minute PVT, typically before MSLT nap 2. Thirty-seven age- and gender-matched, non-patient controls, all with Epworth≤10, also performed 10-minute PVT. Controls were instructed to perform their best (CON group) or to make their performance look as though they were sleepy, without specific instructions about how to do so (simulated sleepiness, CON-SS). Four sleep clinician-scientists (2 ABPN board-certified in Sleep Medicine, 1 ABSM board-certified, and 1 nurse practitioner) and two sleep researchers classified each participant’s detailed PVT output, blinded to group allocation. Kappa was calculated using SAS MAGREE macro. Results Individual raters performed similarly, with four reviewers correctly classifying 55% of cases, one 57%, and one 65%. Classification was significantly better than chance, with moderate agreement between raters (kappa 0.54, p < 0.0001). Considering each group separately, agreement remained higher than chance. Agreement was only fair for EDS (kappa 0.40), but was substantial for CON and CON-SS (kappa 0.62 for both). When EDS were misclassified, they were typically classified as CON (87.4% of misclassifications). When CON were misclassified, they were typically classified as EDS (89.2%). When CON-SS were misclassified, they were typically classified as EDS (74.3%). Conclusion The PVT can provide supplemental information as part of hypersomnolence evaluation. However, used in isolation, it would result in substantial misclassification of hypersomnolent patients. Patients with pathologic sleepiness cannot always be distinguished from non-sleepy controls attempting to appear sleepy. Support (If Any) K23NS083748
Abstract
Introduction
V117957 is an investigational nociceptin/orphanin-FQ peptide (NOP) receptor partial agonist designed to treat insomnia by promoting sleep onset and maintenance with minimal ...residual next-day somnolence or psychomotor impairment. The satisfactory safety/tolerability profile of V117957 has been previously established in ~200 healthy subjects with maximum doses at 30mg following a single oral administration and 10mg once daily for 2 weeks. The present study was conducted to assess the safety/tolerability and pharmacokinetics (PK) of V117957 with co-administered alcohol.
Methods
A randomized, double-blind, double-dummy, placebo-controlled, balanced six-period crossover design was employed. Single doses (2mg, 6mg) of V117957 and placebo were administered orally to healthy subjects in the morning with and without alcohol (0.7g/kg). Pharmacodynamic (PD) effects of V117957 were assessed, and safety/tolerability and PK interactions were also characterized. The primary PD endpoints (body sway, Digit Vigilance Test, and numeric working memory) were measured through 12 hours postdosing.
Results
Forty-eight subjects were enrolled and randomized; 46 completed. Compared with placebo, alcohol alone showed an impairment on psychomotor/cognitive performances through 2 hours postdose. V117957 alone showed a dose-dependent impairment. Compared with V117957 alone and alcohol alone, co-administration of alcohol and V117957 showed greater impairment until 8 hours postdose. No subject discontinued due to an adverse event (AE). No clinically meaningful treatment-emergent (TE) changes in clinical laboratory values, vital signs, SpO2 measurements, or 12-lead ECG results were observed. The most common TEAE was somnolence. All plasma and urine PK parameters for V117957 and alcohol were comparable when V117957 or alcohol was administered alone or in combination.
Conclusion
Single oral doses of V117957, 2mg or 6mg, administered alone or in combination with alcohol in healthy subjects resulted in no notable PK interaction between V117957 and alcohol. A dose-effect relationship in the magnitude and duration of impairment was observed for most psychomotor/cognitive performance parameters. Greater effects of V117957 with alcohol were observed for most psychomotor/cognitive performance parameters up to 8 hours post-dose.
Support
Funded by Imbrium Therapeutics, a subsidiary of Purdue Pharma L.P.
Abstract
This study intends to generate a valid, practical and effective guided inquiry model of Physics learning instruments to increase the results of senior high school students. The learning ...material was developed based on Kemp with steps: 1) topic and goal, 2) student characteristics, 3) study goals, 4) content, 5) preliminary research, 6) source of learning activities, 7) support service, 8) evaluation. The instrument was tested to eleven grades eleven in the second semester with a pre-experimental one-group pretest-posttest design. Study data was collected through observation, tests and questionnaires. The study revealed that revised learning instruments were valid. Practicability level of learning instrument based on lesson plan practicability were in good category and fulfill the guided inquiry model syntax. Instrument effectiveness could be seen from an Increase in student ability in concept understanding, as shown by N-gain with a high category in 0.81 value; Positive students respond to learning instrument and learning activity, in which 96% responded positively, and 4% responded negatively. Based on the study finding, it was concluded that student learning results shown by student concept comprehension, psychomotor skill, and character that consist of discipline and responsibility increased upon the implementation of learning instrument developed by the guided inquiry model on dynamic fluid learning material. This research implies that the development of physics learning tools will have a positive impact on increasing students' abilities in learning physics on dynamic fluid topics.
Brain dopamine (DA) has long been implicated in cognitive control processes, including working memory. However, the precise role of DA in cognition is not well-understood, partly because there is ...large variability in the response to dopaminergic drugs both across different behaviors and across different individuals. We review evidence from a series of studies with experimental animals, healthy humans, and patients with Parkinson's disease, which highlight two important factors that contribute to this large variability. First, the existence of an optimum DA level for cognitive function implicates the need to take into account baseline levels of DA when isolating the effects of DA. Second, cognitive control is a multifactorial phenomenon, requiring a dynamic balance between cognitive stability and cognitive flexibility. These distinct components might implicate the prefrontal cortex and the striatum, respectively. Manipulating DA will thus have paradoxical consequences for distinct cognitive control processes, depending on distinct basal or optimal levels of DA in different brain regions.
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