Effects Of Acute Intoxication Research Articles

Validity of the brief executive-function assessment tool in an outpatient substance use disorder setting

The Brief Executive-function Assessment Tool (BEAT) was developed and validated for use in residential substance use disorder treatment settings, where participants are mostly abstinent. It is therefore unclear whether the BEAT is valid for use in outpatient settings, where participants may be actively using substances. The effects of acute intoxication and withdrawal have the potential to alter the results of the BEAT. The current study sought to establish construct and criterion validity of the BEAT in an outpatient substance use disorder sample and to detect its sensitivity to substance use over the previous 24 hours and also over the past month. A total of 74 clients of a New South Wales-based outpatient substance use disorder service participated in the current study. Construct validity was demonstrated by significant correlations between the BEAT and three performance-based tests of executive functioning. Criterion validity was established in that the BEAT discriminated between those deemed impaired or not on a criterion composite measure of executive functioning. Test operating characteristics (88% sensitivity, 69% specificity, 44% PPV, and 95% NPV) were also established relative to this composite measure as a reference standard. The BEAT was insensitive to use/abstinence over the previous 24 hours and the past month.

Intoxication due to Δ9-tetrahydrocannabinol is characterized by disrupted prefrontal cortex activity

Neural states of impairment from intoxicating substances, including cannabis, are poorly understood. Cannabinoid 1 receptors, the main target of Δ9-tetrahydrocannabinol (THC), the primary intoxicating cannabinoid in cannabis, are densely localized within prefrontal cortex; therefore, prefrontal brain regions are key locations to examine brain changes that characterize acute intoxication. We conducted a double-blind, randomized, cross-over study in adults, aged 18–55 years, who use cannabis regularly, to determine the effects of acute intoxication on prefrontal cortex resting-state measures, assessed with portable functional near-infrared spectroscopy. Participants received oral THC (10–80 mg, individually dosed to overcome tolerance and achieve acute intoxication) and identical placebo, randomized for order; 185 adults were randomized and 128 completed both study days and had usable data. THC was associated with expected increases in subjective intoxication ratings (ES = 35.30, p < 0.001) and heart rate (ES = 11.15, p = 0.001). THC was associated with decreased correlations and anticorrelations in static resting-state functional connectivity within the prefrontal cortex relative to placebo, with weakest correlations and anticorrelations among those who reported greater severity of intoxication (RSFC between medial PFC-ventromedial PFC and DEQ scores, r = 0.32, p < 0.001; RSFC between bilateral mPFC and DEQ scores, r = –0.28, p = 0.001). Relative to placebo, THC was associated with increased variability (or reduced stability) in dynamic resting-state functional connectivity of the prefrontal cortex at p = 0.001, consistent across a range of window sizes. Finally, using frequency power spectrum analyses, we observed that relative to placebo, THC was associated with widespread reduced spectral power within the prefrontal cortex across the 0.073–0.1 Hz frequency range at p < 0.039. These neural features suggest a disruptive influence of THC on the neural dynamics of the prefrontal cortex and may underlie cognitive impairing effects of THC that are detectable with portable imaging. This study is registered in Clinicaltrials.gov (NCT03655717).

Effect of acute alcohol consumption on blunt bowel mesenteric injury: a retrospective analysis

BackgroundThe effect of alcohol consumption on trauma remains controversial. The effects of alcohol on hemorrhage and peritonitis after blunt abdominal trauma have rarely been discussed. This study aimed to explore the effects of acute alcohol intoxication on the clinical characteristics, injury patterns, and outcomes in a surgical blunt bowel mesenteric injury (BBMI) cohort.MethodsA retrospective data analysis was performed using trauma cases of patients who had been tested for alcohol and had surgically proven BBMI from a Trauma Registry System from 2009 to 2021. Patients were grouped according to their positive blood alcohol concentration (BAC; >0.5% vs. no BAC; less than 0.5% no BAC) upon arrival at the emergency department (ED). The injury characteristics, physiological parameters, and outcomes with respect to post-injury complications and mortality were assessed.ResultsIn total, 142 patients with surgical BBMI were included. Of these, 116 and 26 patients were assigned to the BAC-negative and BAC-positive groups, respectively. The overall injury severity, injury pattern, and age were comparable between the groups. The patients in the BAC-positive group had a significantly lower systolic blood pressure (99 mmHg vs. 119 mmHg; p = 0.046), worse shock index (0.96 vs. 0.82; p = 0.048), and lower percentage and number of packed red blood cells transfused (34.6% vs. 57.8%; p = 0.032 and 0 U vs. 2 U; p = 0.031) than those in the BAC-negative group. Additionally, although not statistically significant, patients in the BAC-positive group had lower leukocyte counts (9,700 cells/mm3 vs. 11,600 cells/mm3; p = 0.165 ) at the ED. However, significantly reduced percentages of leukocytes ≥ 12,000 cells/mm3 (26.9% vs. 48.3%; p = 0.048) and ≥ 12,000 or ≤ 4,000 cells/mm3 (26.9% vs. 50.9%; p = 0.027) were observed in the BAC-positive group at the ED. Furthermore, the 30-day mortality rate did not show statistically significant differences, and there was a higher incidence of bowel-related mortality in the BAC-positive group (11.5% vs. 1.7%, p = 0.043).ConclusionsFor patients with BBMI arriving alive to the hospital, acute alcohol consumption was associated with significantly worse hemodynamic parameters, interfered inflammation status, and higher bowel related mortality rate.

Neuroprotectant Activity of Novel Water-Soluble Synthetic Neurosteroids on Organophosphate Intoxication and Status Epilepticus-Induced Long-Term Neurological Dysfunction, Neurodegeneration, and Neuroinflammation.

Organophosphates (OPs) and nerve agents are potent neurotoxic compounds that cause seizures, status epilepticus (SE), brain injury, or death. There are persistent long-term neurologic and neurodegenerative effects that manifest months to years after the initial exposure. Current antidotes are ineffective in preventing these long-term neurobehavioral and neuropathological changes. Additionally, there are few effective neuroprotectants for mitigating the long-term effects of acute OP intoxication. We have pioneered neurosteroids as novel anticonvulsants and neuroprotectants for OP intoxication and seizures. In this study, we evaluated the efficacy of two novel synthetic, water-soluble neurosteroids, valaxanolone (VX) and lysaxanolone (LX), in combating the long-term behavioral and neuropathological impairments caused by acute OP intoxication and SE. Animals were exposed to the OP nerve agent surrogate diisopropylfluorophosphate (DFP) and were treated with VX or LX in addition to midazolam at 40 minutes postexposure. The extent of neurodegeneration, along with various behavioral and memory deficits, were assessed at 3 months postexposure. VX significantly reduced deficits of aggressive behavior, anxiety, memory, and depressive-like traits in control (DFP-exposed, midazolam-treated) animals; VX also significantly prevented the DFP-induced chronic loss of NeuN(+) principal neurons and PV(+) inhibitory neurons in the hippocampus and other regions. Additionally, VX-treated animals exhibited a reduced inflammatory response with decreased GFAP(+) astrogliosis and IBA1(+) microgliosis in the hippocampus, amygdala, and other regions. Similarly, LX showed significant improvement in behavioral and memory deficits, and reduced neurodegeneration and cellular neuroinflammation. Together, these results demonstrate the neuroprotectant effects of the novel synthetic neurosteroids in mitigating the long-term neurologic dysfunction and neurodegeneration associated with OP exposure. SIGNIFICANCE STATEMENT: Survivors of nerve agents and organophosphate (OP) exposures suffer from long-term neurological deficits. Currently, there is no specific drug therapy for mitigating the impact of OP exposure. However, novel synthetic neurosteroids that activate tonic inhibition provide a viable option for treating OP intoxication. The data from this study indicates the neuroprotective effects of synthetic, water-soluble neurosteroids for attenuation of long-term neurological deficits after OP intoxication. These findings establish valaxanolone and lysaxanolone as potent and efficacious neuroprotectants suitable for injectable dosing.

Baseline affective symptomatology moderates acute subjective effects of high potency THC and CBD cannabis concentrates.

Highly potent cannabis concentrates are widely available and associated with affective disturbance and cannabis use disorder. Little is known about the effects of concentrated Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) and their relationship to long-term affect. We explored how baseline affective symptoms (anxiety and depression) relate to acute (i.e., immediate or short-term) subjective mood and intoxication effects during naturalistic use of cannabis concentrates. Fifty-four cannabis users (48% female; Mage = 29.87) were assigned to ad libitum use of either a THC-dominant (84.99% THC and THCa, < 1% CBD) or CBD-dominant (74.7% CBD, 4.1% CBDa, 4.5% THC and THCa) concentrate. Individuals were assessed at baseline and before, immediately after, and 1 hr after naturalistic use of their assigned product. Models regressed each outcome on time, product condition, baseline affective symptoms, and their interactions. An interaction emerged between condition and baseline depression symptoms on positive mood (F = 9.47, p < .005); higher depression symptom level was associated with higher positive mood with THC-dominant product use. There was an interaction between condition, baseline depression symptoms, and time on negative mood (F = 5.55, p < .01); negative mood decreased with CBD-dominant product use for all depression symptom levels but increased with THC-dominant product use at high levels. Finally, there was an interaction between condition and time on intoxication (F = 3.72, p = .03); the THC-dominant condition was more intoxicated postuse than the CBD-dominant condition. This novel exploratory study suggests that baseline affect moderates the acute effects of ad libitum use of THC and CBD concentrates such that preexisting affective symptoms modulate the intensity of subjective drug experiences. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Binge drinking episode causes acute, specific alterations in systemic and hepatic inflammation-related markers.

Frequent binge drinking is a known contributor to alcohol-related harm, but its impact on systemic and hepatic inflammation is not fully understood. We hypothesize that changes in immune markers play a central role in adverse effects of acute alcohol intake, especially in patients with early liver disease. To investigate the effects of acute alcohol intoxication on inflammation-related markers in hepatic and systemic venous plasma in people with alcohol-related liver disease (ArLD), non-alcoholic fatty liver disease (NAFLD) and healthy controls. Thirty-eight participants (13 with ArLD, 15 with NAFLD and 10 healthy controls) received 2.5 mL of 40% ethanol per kg body weight via a nasogastric tube. Seventy-two inflammation-related markers were quantified in plasma from hepatic and systemic venous blood, at baseline, 60 and 180 min after intervention. Alcohol intervention altered the levels of 31 of 72 and 14 of 72 markers in the systemic and hepatic circulation. All changes observed in the hepatic circulation were also identified in the systemic circulation after 180 min. Only FGF21 and IL6 were increased after alcohol intervention, while the remaining 29 markers decreased. Differences in response to acute alcohol between the groups were observed for 8 markers, and FGF21 response was blunted in individuals with steatosis. Acute alcohol intoxication induced changes in multiple inflammation-related markers, implicated in alcohol metabolism and hepatocellular damage. Differences identified between marker response to binge drinking in ArLD, NAFLD and healthy controls may provide important clues to disease mechanisms and potential targets for treatment. NCT03018990.

Experimental evaluation of the influence of electromagnetic radiation and acute alcohol intoxication on the indicators of mineral metabolism and antioxidant protection in erythrocytes and blood plasma of rats

The aim of the research was a comparative analysis of the effect of electromagnetic radiation and acute alcohol intoxication on the parameters of mineral metabolism and antioxidant protection in erythrocytes and blood plasma of rats. Materials and methods. The research was performed on 128 white non-linear rats. The study was conducted on five experimental models: acute ethanol poisoning, acute ethanol poisoning against the background of preliminary alcoholization, exposure to electromagnetic radiation for 1, 2 and 3 months. Spectrophotometrically determined the content of iron, copper, transferrin, ceruloplasmin and the activity of gamma-glutamyl transpeptidase in the blood plasma of rats, the content of glutathione in blood erythrocytes. Results and discussion. A unidirectional nature of changes in the indicators of antioxidant protection and mineral metabolism in acute alcohol intoxication and electromagnetic irradiation was established, which consists in a decrease in the content of iron, transferrin, an increase in the content of ceruloplasmin, glutathione, and gamma-glutamyl transpeptidase activity. At the same time, a decrease in the iron content and a change in the parameters of antioxidant protection in the blood plasma are more pronounced in acute ethanol poisoning than in electromagnetic irradiation. Conclusions. Ceruloplasmin, transferrin, glutathione and gamma-glutamyl transpeptidase are targets for the action of electromagnetic radiation and ethanol. Determination of the activity of gamma-glutamyl transpeptidase in blood plasma has a prognostic value for determining the degree of liver damage not only with alcohol intoxication, but also with electromagnetic irradiation of the decimeter range.

Effects of Acute Ethanol Intoxication on Spinal Cord Injury Outcomes in Female Mice.

Abstract Approximately one in three traumatic spinal cord injuries (SCIs) occurs during or shortly after the consumption of alcohol. A small number of retrospective clinical studies report variable effects of alcohol intoxication on mortality, neurological recovery, and complications after SCI. Some of these studies demonstrate a protective effect of alcohol intoxication on SCI outcomes, whereas others show an increased complication risk. Pre-clinical studies in rat, ferret, and feline SCI models report a detrimental effect of ethanol intoxication on hemorrhage, motor recovery, and biochemical markers of tissue injury. However, no studies to date have investigated the neuropathological consequences of ethanol intoxication at the time of SCI or the reciprocal effect of SCI on ethanol metabolism. Therefore, we combined a pre-clinical mouse model of acute ethanol intoxication and experimental vertebral level T9 contusion SCI to investigate their interactive effects in female mice. We first investigated the effect of SCI on ethanol metabolism and found that T9 SCI does not alter ethanol metabolism. However, we did find that isoflurane anesthesia significantly slowed ethanol metabolism independent of SCI. We also determined how acute ethanol intoxication at the time of SCI alters locomotor recovery and lesion pathology. Using the Basso Mouse Scale (BMS) and CatWalk XT Gait Analysis System, we assessed locomotor recovery for 6 weeks after injury and observed that acute ethanol intoxication at the time of injury did not alter locomotor recovery. We also found no effect of ethanol intoxication on heat hyperalgesia development. There was, however, a detrimental effect of ethanol on tissue sparing after SCI. Therefore, we conclude that acute alcohol intoxication at the time of injury may contribute to the neuropathological consequences of SCI.

Nerve Growth Factor in Psychiatric Disorders: A Scoping Review.

Neurotrophins have been implicated in multiple psychiatric disorders. Nerve Growth Factor (NGF) is one of the major neurotrophins that has attracted much research interest. Therefore, we undertook, to the best of our knowledge, the first scoping review encompassing all major psychiatric disorders and their relation to NGF. This review aimed to identify the current position of NGF in psychiatric research and to outline present gaps in knowledge, which can be answered with a more detailed systematic review in the future. Suitable studies were identified using PubMed. A total of 20 studies were included in the review: two on bipolar affective disorder (BPAD), three on schizophrenia, seven on depression, and eight on alcohol use disorder. NGF levels are definitively reduced in BPAD and depression, while NGF levels in schizophrenia decreased further after treatment than in the drug-naïve state. The effect of treatment on NGF levels in depression varied based on treatment modalities and severity of depression. In patients with depression, raised NGF was a predictor of conversion to bipolar disorder (BD). NGF levels were raised in acute alcohol intoxication and withdrawal but normalized slowly as abstinence was maintained. NGF may play a protective role in preventing the toxic ill effect of acute alcohol intoxication on the central nervous system. Based on current knowledge, NGF levels may be a useful biomarker of a chronic mental stress condition. However, further research is needed before it can be used to identify a specific psychiatric illness or predict treatment response.

Acute alcohol intoxication and alcohol expectancy effects on women's memory for consensual and non-consensual sexual activity.

To test whether acute alcohol intoxication and alcohol expectancy affects how accurately women remember consensual and non-consensual sexual activity that occurred during an interactive hypothetical dating scenario. A balanced placebo randomized study that varied alcohol dose (mean Breath Alcohol Content; BrAC = 0.06%) and alcohol expectancy prior to participants encoding a hypothetical interactive rape scenario was implemented. Participants could elect to consent to sexual activity with a male partner in the hypothetical scenario. If they stopped consenting, non-consensual sexual intercourse (i.e., rape) was described. Seven days later, participants' memory for consensual and non-consensual sexual activity in the scenario was tested. Memory accuracy, confidence, and feelings of intoxication. A total of 90 females (M age = 20.5, SD = 2.2) were tested regarding their memory accuracy for the consensual and non-consensual sexual activities in the scenario. A multi-level logistic regression predicting memory accuracy for the perpetrator's behaviors during the rape indicated no effect of alcohol intoxication. However, a main effect of alcohol expectancy was found, whereby participants who expected to consume alcohol, compared to those who did not, recalled the perpetrator's behaviors during the rape more accurately. A second regression predicting memory accuracy for consensual sexual activity found no main effects for alcohol intoxication or alcohol expectancy. Participants recalled consensual sexual activity with a high degree of accuracy. Calibration analyses indicated that accuracy increased with confidence level, regardless of intoxication level or alcohol expectancy condition, but that women tended to be overconfident in general. This study provides an important test of how accurately women remember consensual and non-consensual sexual activities. The accuracy of this information is important for forensic medical examinations and police investigations following an allegation of sexual assault. Increased memory accuracy was found for offence details when participants expected to consume alcohol, suggesting there may be important differences in attentional processes (e.g., hypervigilance) depending on whether threat is present. Further research is necessary to investigate memory for sexual violence in real-world settings and to test methods for ascertaining the most complete and reliable accounts.

Elevated creatinine kinase levels amongst Dutch adolescents with acute alcohol intoxication

This study aims to explore the prevalence of creatinine kinase elevation amongst a sample of Dutch adolescents admitted for acute alcohol intoxication. The data on all admitted adolescents < 18 years old with acute alcohol intoxication between 2008 and 2021 were collected from a Dutch major district general hospital, Reinier de Graaf Gasthuis, in Delft. Overall, 495 adolescents who were treated for symptoms of acute alcohol intoxication during this period were included in the study. When evaluating the blood samples of the included patients, elevated creatinine kinase levels were found in 60% of the cases, with a mean of 254 U/I (normal value ≤ 145 U/I). A confirmed diagnosis of rhabdomyolysis (increase in CK > fivefold the upper limit of normal) was present in 4.4% of cases. Moreover, using a linear regression this study found that a higher blood alcohol concentration was associated with higher creatinine kinase levels, when adjusted for positive drug screenings amongst the adolescents with acute alcohol intoxication (p = 0.027; β = 66.88; 95% CI 7.68 − 126.08). Conclusions: This is the first study focusing on how acute alcohol intoxication affects adolescents’ muscle tissue. The results could potentially help to prevent alcohol use within the sports world. It could also aid understanding of how acute alcohol intoxication influences the breakdown of adolescents’ muscle tissue.What is Known:• Alcohol, alongside pharmaceutical agents and illicit drugs, is a significant cause of rhabdomyolysis (increase in creatinine kinase > fivefold the upper limit of normal).• Creatinine kinase elevation in alcohol intoxicated patients may be as a result of direct “muscular” toxicity” (myotoxicity) or from prolonged immobilization and ischemic compression induced by coma.What is New:• Our retrospective cohort study is a pioneer in addressing the effect of acute alcohol intoxication amongst adolescents (< 18 years) upon muscle tissue (creatinine kinase level) within a large population. When evaluating the blood samples of the included population, elevated creatinine kinase levels were found in 60% of the cases, with a mean of 254 U/I (normal value ≤ 145 U/I).• There is an association between alcohol intoxication and elevated creatinine kinase levels amongst adolescents. Future research is needed to further understand the pathophysiology and causality of this interaction.

Predictive impact of different acute cannabis intoxication effects with regard to abstinence motivation and cessation of use

Cannabis use is a common risk factor for psychoses. But although prevalence of consumption as well as potency of cannabis increased, the incidence of schizophrenia remained stable. The discontinuation hypothesis suggests that a potential increase of psychoses incidence may be relativized by more frequent cessation of consumption due to higher rates of adverse psychosis-like intoxication effects (PLE), caused by stronger cannabis. A mixed methods online survey was administered to 441 current and past users to analyze the predictive impact of different acute intoxication effects regarding abstinence motivation/cessation of use. Our hypothesis was that PLE would be experienced as the most aversive intoxication effect and therefore have the highest predictive significance. Possible confounds were included (craving, patterns of consumption and sociodemographics). Further analyzes compared past versus current users regarding the quality of intoxication effects, suggesting that past users retrospectively experienced more unpleasant experiences than current users. Free-text data explored subjective reasons for abstinence. We found that paranoid/dysphoric intoxication effects were most predictive for abstinence motivation. Less predictive were psychosis-like intoxication effects such as hallucinations. Group comparisons revealed significant more unpleasurable and less positive intoxication effects in past users compared with current users. Current users with the intention to stop consumption showed significantly more paranoia/dysphoria intoxication compared to users with no intention to stop use. As a conclusion, different intoxication experiences have different effects on abstinence motivation and substance use behavior. They therefore provide a focus that should be increasingly integrated into treatment concepts.

The effect of acute alcohol intoxication on alcohol cue salience: An event-related brain potential study.

Alcohol cue salience is considered core to the broader understanding of drinking behaviors. In the present research, we sought to build the knowledge of alcohol cue salience by exploring P3 responses to alcohol images among social drinkers within a large-scale alcohol-administration study. Participants (N = 246) were randomly assigned to receive either a moderate dose of alcohol (target BAC = .08%) or a nonalcoholic control beverage. Following beverage administration, participants engaged in image-viewing tasks while EEG was recorded. We examined the impact of alcohol on the amplitude of P3 responses to pictures of alcoholic versus nonalcoholic beverages, exploring both beverage-manipulation and individual-difference moderators of these effects. Results revealed a significant effect of acute alcohol intoxication on P3 responses across stimulus types, with the overall amplitude of P3 being significantly smaller among participants consuming alcohol versus a nonalcoholic beverage. In addition, results revealed a significant main effect of image type, such that P3 amplitude was larger for alcohol images compared to nonalcohol images. No interactions emerged between stimulus type and beverage condition or stimulus type and AUD risk level. With the aim of better understanding the potential influence of the broader context on responses to individual cues, the present study examined the perceived salience of alcohol cues within a drinking setting. Findings provide evidence for alcohol cue salience that is both robust and also widespread across drinkers. More generally, the present study's findings may offer new directions for understanding neurocognitive processes of alcohol cue salience across contexts. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Intoxicating effects of alcohol depend on acid-sensing ion channels.

Persons at risk for developing alcohol use disorder (AUD) differ in their sensitivity to acute alcohol intoxication. Alcohol effects are complex and thought to depend on multiple mechanisms. Here, we explored whether acid-sensing ion channels (ASICs) might play a role. We tested ASIC function in transfected CHO cells and amygdala principal neurons, and found alcohol potentiated currents mediated by ASIC1A homomeric channels, but not ASIC1A/2 A heteromeric channels. Supporting a role for ASIC1A in the intoxicating effects of alcohol in vivo, we observed marked alcohol-induced changes on local field potentials in basolateral amygdala, which differed significantly in Asic1a-/- mice, particularly in the gamma, delta, and theta frequency ranges. Altered electrophysiological responses to alcohol in mice lacking ASIC1A, were accompanied by changes in multiple behavioral measures. Alcohol administration during amygdala-dependent fear conditioning dramatically diminished context and cue-evoked memory on subsequent days after the alcohol had cleared. There was a significant alcohol by genotype interaction. Context- and cue-evoked memory were notably worse in Asic1a-/- mice. We further examined acute stimulating and sedating effects of alcohol on locomotor activity, loss of righting reflex, and in an acute intoxication severity scale. We found loss of ASIC1A increased the stimulating effects of alcohol and reduced the sedating effects compared to wild-type mice, despite similar blood alcohol levels. Together these observations suggest a novel role for ASIC1A in the acute intoxicating effects of alcohol in mice. They further suggest that ASICs might contribute to intoxicating effects of alcohol and AUD in humans.

Development and initial validation of a reliable German self-report measure to assess acute cannabis intoxication-effects (CanTox-17).

ObjectivesBoth positive and negative including psychotic‐like cannabis intoxication effects are well‐established. Yet, consequences for consumption patterns, addictive behavior or psychotic developments are poorly researched in general, in Germany not at all. Thus, objective was to develop the first German‐language questionnaire operationalizing acute cannabis intoxication effects, based on the original “Cannabis Experience Questionnaire” (CEQ).MethodsAfter expert translation of the CEQ, items related to acute intoxication effects were presented to a sample of 537 cannabis users. Four‐ and five‐factorial solutions of explorative factor analysis with a randomly split sub‐sample 1 were cross‐validated by confirmatory factor analysis on sub‐sample 2.ResultsAfter content review of factors and analysis of external validity, a 17 item four‐factorial model was approved. Factors are (1) “paranoia/dysphoria”, (2) “confusion/disorientation”, (3) “euphoria/creativity”, (4) “psychosis‐like/loss of reality”. Model fit is satisfactory (RMSEA = 0.058, SRMR = 0.065, CFI = 0.929, TLI = 0.914). Correlations with corresponding external measures support construct validity.ConclusionsThe present questionnaire is a time‐efficient, valid and reliable instrument. Thus, predictors of different cannabis intoxication effects can be analysed for the first time in German‐speaking area, as well as their significance for substance use or psychosis risk.

Diisopropylfluorophosphate (DFP) volatizes and cross-contaminates wells in a common 96-well plate format used in zebrafish larvae toxicology studies

Diisopropylfluorophosphate (DFP) is an organophosphate (OP) that is commonly used as a surrogate of OP nerve agents to study the neurotoxic effects of acute OP intoxication. In preliminary studies, we discovered abnormally high incidence of deaths in DMSO control zebrafish larvae housed in the same 96-well plate as DFP-exposed larvae and hypothesized that DFP volatilizes and cross-contaminates wells when using static waterborne exposures. Survivability and acetylcholinesterase activity assays were indicative of the presence of DFP in the tissues of zebrafish ostensibly exposed to DMSO only. These findings are consistent with DFP cross-contamination, which raises concerns for the experimental design of studies evaluating the toxicity of volatile and semi-volatile substances in zebrafish using medium-to-high throughput approaches.

Assessing driving-relevant attentional impairment after a multiday drinking session: A two-phase pilot study.

BackgroundThe possibility of residual impairment of cognitive performance after multiday drinking sessions is particularly important given the potential for the deleterious effects of fatigue and hangover. This pilot study aimed to devise a methodology to compare sober performance on driving‐relevant attentional tasks at the end of a 4‐day music festival with performance at varying levels of the breath–alcohol curve.MethodsFifty‐two participants completed selective and sustained attention tasks at a breath alcohol concentration (BrAC) of 0.00%, 0.05%, and 0.08% following acute dosing in a controlled laboratory setting. A subset of participants (n = 13) were then tested at the conclusion of a 4‐day music festival at 0.00% BrAC, with task performance compared with laboratory results.ResultsDuring the laboratory phase, sustained attention was poorer at the 0.05% ascending timepoint only (compared to 0.00% BrAC). During the festival phase, participants made a greater number of errors on the selective attention task predeparture than at 0.00% and 0.05% BrAC in the laboratory. Sustained attention performance was poorer while intoxicated in the laboratory.ConclusionsOur findings suggest that the absence of blood alcohol acutely may not be indicative of unimpaired cognitive performance and that other factors related to multiday drinking may produce driving‐related attentional deficits. The findings reinforce the need to measure attentional performance in real‐world drinking contexts despite the methodological complexities of doing so. A larger study is warranted to replicate the findings and should include attentional measures that either are more sensitive to the effects of acute alcohol intoxication than those in our study or are based on a driving simulator.

Nephrotoxic Effects of Paraoxon in Three Rat Models of Acute Intoxication.

The delayed effects of acute intoxication by organophosphates (OPs) are poorly understood, and the various experimental animal models often do not take into account species characteristics. The principal biochemical feature of rodents is the presence of carboxylesterase in blood plasma, which is a target for OPs and can greatly distort their specific effects. The present study was designed to investigate the nephrotoxic effects of paraoxon (O,O-diethyl O-(4-nitrophenyl) phosphate, POX) using three models of acute poisoning in outbred Wistar rats. In the first model (M1, POX2x group), POX was administered twice at doses 110 µg/kg and 130 µg/kg subcutaneously, with an interval of 1 h. In the second model (M2, CBPOX group), 1 h prior to POX poisoning at a dose of 130 µg/kg subcutaneously, carboxylesterase activity was pre-inhibited by administration of specific inhibitor cresylbenzodioxaphosphorin oxide (CBDP, 3.3 mg/kg intraperitoneally). In the third model (M3), POX was administered subcutaneously just once at doses of LD16 (241 µg/kg), LD50 (250 µg/kg), and LD84 (259 µg/kg). Animal observation and sampling were performed 1, 3, and 7 days after the exposure. Endogenous creatinine clearance (ECC) decreased in 24 h in the POX2x group (p = 0.011). Glucosuria was observed in rats 24 h after exposure to POX in both M1 and M2 models. After 3 days, an increase in urinary excretion of chondroitin sulfate (CS, p = 0.024) and calbindin (p = 0.006) was observed in rats of the CBPOX group. Morphometric analysis revealed a number of differences most significant for rats in the CBPOX group. Furthermore, there was an increase in the area of the renal corpuscles (p = 0.0006), an increase in the diameter of the lumen of the proximal convoluted tubules (PCT, p = 0.0006), and narrowing of the diameter of the distal tubules (p = 0.001). After 7 days, the diameter of the PCT lumen was still increased in the nephrons of the CBPOX group (p = 0.0009). In the M3 model, histopathological and ultrastructural changes in the kidneys were revealed after the exposure to POX at doses of LD50 and LD84. Over a period from 24 h to 3 days, a significant (p = 0.018) expansion of Bowman’s capsule was observed in the kidneys of rats of both the LD50 and LD84 groups. In the epithelium of the proximal tubules, stretching of the basal labyrinth, pycnotic nuclei, and desquamation of microvilli on the apical surface were revealed. In the epithelium of the distal tubules, partial swelling and destruction of mitochondria and pycnotic nuclei was observed, and nuclei were displaced towards the apical surface of cells. After 7 days of the exposure to POX, an increase in the thickness of the glomerular basement membrane (GBM) was observed in the LD50 and LD84 groups (p = 0.019 and 0.026, respectively). Moreover, signs of damage to tubular epithelial cells persisted with blockage of the tubule lumen by cellular detritus and local destruction of the surface of apical cells. Comparison of results from the three models demonstrates that the nephrotoxic effects of POX, evaluated at 1 and 3 days, appear regardless of prior inhibition of carboxylesterase activity.

A laboratory study of the effects of men's acute alcohol intoxication, perceptions of women's intoxication, and masculine gender role stress on the perpetration of sexual aggression.

Although research has established an association between alcohol use and sexual assault, few studies have examined how characteristics of the perpetrator may influence sexual aggression depending upon whether alcohol is consumed by the perpetrator and/or the victim. This laboratory-based investigation was designed to disentangle the effects of individual differences in masculine gender role stress (MGRS) and the perpetration of sexual aggression as a function of (1) men's acute alcohol intoxication and (2) whether a woman was consuming alcohol or not. A community sample of 156 men participated in two laboratory sessions, during which they completed a self-report measure of MGRS (Session 1) and a modified version of the sexual imposition paradigm after consuming an alcoholic or non-alcoholic beverage (Session 2). In this paradigm, participants and a male friend were told that an ostensible female participant had consumed or not consumed alcohol. They were also told that she did not wish to view sexual content. Participants were then provided the opportunity to make the female confederate view a sexually or non-sexually explicit film. Sexual aggression was operationalized by selection of the sexually explicit film. A hierarchical logistic regression showed that men higher in MGRS who were intoxicated were (1) more likely than sober men to select the sexually explicit film when the woman was intoxicated and (2) less likely than sober men to select the sexually explicit film when the woman was sober. These findings suggest that the perpetration of sexual aggression is most likely among men with higher MGRS when there is concordance in drinking (i.e., when either the man and woman are both drinking or are both not drinking).

Acute objective and subjective intoxication effects of legal-market high potency THC-dominant versus CBD-dominant cannabis concentrates.

As the market for cannabis concentrate products grows, the lack of research regarding the effects of concentrated THC and CBD becomes more glaring. The present study analyzes cannabinoid blood levels and subjective outcomes of physical sensation and affective state after ad libitum use of legal-market concentrate products. Recreational cannabis users were randomly assigned to THC- or CBD-dominant concentrate products, completing a baseline session, and an experimental mobile laboratory session consisting of timepoints before, immediately after, and one-hour after concentrate use. THC-dominant concentrates induced higher intoxication, and higher ratings of drug effect and drug liking than the CBD-dominant concentrate. Both products induced immediate feelings of elation, diminishing over the subsequent hour. Subjective outcomes in the CBD-dominant group revealed immediate decreases in tension and anxiety relative to pre-use, while the THC-dominant group only saw significant decreases in anxiety after one hour. Paranoia spiked immediately post-use in THC-dominant concentrate users, returning to baseline within an hour. Overall, the CBD-dominant concentrate invoked positive mood effects, lower intoxication and an absence of undesirable effects experienced with the THC-dominant concentrate, potentially mitigating negative effects when combined. Results support the need for further investigation into harm-reduction potential of concentrated CBD when used alone and with THC.