Fatal Suicidal Intoxication with Pentoxifylline Complicated by Cardiovascular Disorders.

Pentoxifylline is a xanthine derivative used in vascular disorders that is recognized as a safe drug for patients. The paper describes a rare case of fatal and suicidal pentoxifylline poisoning in an 82-year-old man with multiple preexisting diseases (arterial hypertension, coronary artery disease, type 2 diabetes, and intermittent claudication). The patient was admitted to the clinical toxicology unit approximately 2 h after the overdose and died 36 h after the admission despite intensive care. Multiple arterial blood gas analyses and other laboratory tests were performed during the hospitalization and are reported in the paper. Postmortem examination of the biological material was carried out with the use of histopathological techniques. The toxicological studies using chromatographic techniques coupled with mass spectrometry showed that postmortem blood levels of pentoxifylline have been found in the range which is described in the available literature to be toxic and lethal. The analysis of test results and clinical data showed that the patient died as a result of increasing circulatory and respiratory failure, complicated by disorders of the acid-base and electrolyte balance (respiratory alkalosis, concomitant lactic acidosis, and hypokalemia), hyperglycemia, and coagulation disorders.

No party, no drugs? Use of stimulants, dissociative drugs, and GHB/GBL during the early COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic is presumably having an impact on the consumption of psychoactive substances. Social distancing and lockdown measures may particularly affect the use of "party drugs" (e.g., stimulants, dissociatives, and GHB/GBL) through the absence of typical use settings. We aimed to analyse the use patterns of those substances and underlying motivations before and during the pandemic. METHODS: A subsample of 1,231 users of stimulants (amphetamine, methamphetamine, MDMA/ecstasy, cocaine), dissociative drugs (ketamine, dextromethorphan, PCP), and GHB/GBL was assessed from 30th April to 4th August 2020 as part of the Corona Drug Survey, a cross-sectional international online survey in five languages that included a total of 5,049 participants. The reported use of distinct substances and the underlying motivations were ascertained before (retrospectively) and during the pandemic. Furthermore, associations between drug use as a coping mechanism, pandemic-related stressors, and substance use were examined. RESULTS: Regarding the reported frequency of use during the pandemic, 48.0-64.8% of the sample ceased or decreased, 11.9-25.5% maintained, and 23.6-29.1% increased their consumption. MDMA/ecstasy showed the strongest decrease and GHB/GBL and dissociatives the highest increase. Participants reported that price, quality, and supply were mostly unaffected by the pandemic. The most common motivations before and during the pandemic were mood-related factors, such as a desire to feel exhilarated, euphoric, high, or buzzed. The relevance of social purposes and mood-related motivators declined during the pandemic, whereas dealing with boredom increased. Overall, 16.4-35.6% perceived drug use as helpful for dealing with pandemic-related stressors, which were associated with an increased consumption frequency. CONCLUSION: The early stage of the COVID-19 pandemic was associated with major changes in the use of "party drugs". Those who increased their level of drug use and perceived it as a coping strategy in particular might be targeted with adaptive preventive and therapeutic measures.

Cannabis use during the early COVID-19 pandemic: Use patterns, predictors, and subjective experiences.

Background: Even in the early stages, global crises such as the COVID-19 pandemic lead to serious dislocations of social life, secondary adjustment reactions to external restrictions and individual concerns. Coping mechanisms may also include dysfunctional strategies like an increase of drug use. Considering the wide-spread use of cannabis, the aim of this study was to elucidate the interplay of social restrictions, psychopathology, concerns related to the pandemic in addition to the users' experiences, motivations and consumption quantities during the early COVID-19 pandemic. It was presumed that cannabis intake would increase during the early phase of the crisis and that consumption quantities would be related to corona-related restrictions, concerns as well as subjective substance effects and psychopathology. Materials and methods: As part of an international, cross-sectional, internet-based survey (N = 5,049) available in five languages, consumption quantities and patterns of cannabis use in the early phase of the pandemic from April to August 2020 were examined. Participants retrospectively rated restrictions and concerns related to the pandemic, motives of cannabis use prior to and during 1 month the pandemic, and subjective consumption effects. Results: Cannabis use behavior showed no significant differences when consumption quantities prior and during 1 month after the COVID-19 outbreak were compared. Higher quantities of cannabis intake prior and during 1 month of the pandemic as well as more corona-related concern were associated with an increased perception of positive effects of cannabis during the pandemic. Predictors of its use during 1 month of pandemic were higher pre-pandemic consumption quantity, older age, quarantinization, a lesser degree of being affected by negative effects of the pandemic and a stronger subjective experience of corona-related positive effects of cannabis. Comparisons of the motives for cannabis intake in the pre-pandemic versus the pandemic period showed that all rationales for consumption were reported less frequently, except boredom. Conclusion: Frequencies of cannabis intake remained relatively stable in the early pandemic phase. Risk factors for increased use seem related to habitual consumption patterns that become more prominent under quarantinization. The use of cannabis as a dysfunctional coping strategy might not be amenable via self-report and should therefore receive special attention in clinical contexts.

Psychedelic Experiences During the Early COVID-19 Pandemic: Findings From an International Online Survey.

Introduction: The current corona virus disease (COVID-19) pandemic has caused a serious global health crisis that has affected large parts of the public and private life worldwide, including the use of psychoactive substances. In this study, we investigated the effect of the COVID-19 pandemic on the use of serotonergic psychedelics, i.e., the settings in which people use psychedelics, the motives of usage, and the subjective quality of psychedelic experiences. Methods: The study was part of an international, cross-sectional, internet-based survey (N = 5,049) available in five languages (English, German, Spanish, Italian, and Korean) carried out during the early phase of the pandemic from April to August 2020. Participants were asked to retrospectively rate settings and motives of psychedelic substance use before the pandemic and in the last 4 weeks during the pandemic, as well as changes in psychedelic experiences. Results: Of n = 1,375 participants that reported the use psychedelics in 2019 or 2020, n = 642 (46.6%) also took psychedelics during the pandemic. During the pandemic, participants used psychedelics significantly less often in settings that were outside their home. Top motives to use psychedelics were comparable before and during the pandemic, but participants consumed less out of curiosity, to celebrate, or because friends took it, and more out of boredom. An increase in positively connoted, often pro-social experiences was observed. Two thirds of participants who used psychedelics during the pandemic claimed that psychedelics had helped them to deal better with the corona pandemic at least slightly. Discussion: Changes in setting and motives were mostly in line with restrictions caused by control measures to contain the spread of the virus. The unexpected increase in positively connoted experiences possibly reflects a favorable interaction of environmental macro- and individual micro-contexts during the pandemic (e.g., by reducing the use in more uncontrolled recreational settings or by encouraging a strong self-selection of substance users due to the expectation of "bad trips"). Increased pro-social feelings under psychedelics might reflect a desire for social interactions in times of social distancing and pandemic-related stress and anxiety.

Predictors of Alcohol Consumption Among Younger Adults During the First Phase of the COVID-19 Pandemic.

Background: The COVID-19 pandemic may lead to negative mental health effects but the effect on alcohol consumption among younger adults is unclear. We assess predictors of change in alcohol consumption during the first phase of the COVID-19 pandemic among younger adults. Methods: This cross-sectional internet-based survey was part of an overarching project, the Corona Drug Survey, which was conducted from April 30 to August 4, 2020. Participants of any sex and ≥18 years old were included. The primary outcome measure was change in alcohol consumption during the early COVID-19 pandemic. We implemented an ordinal logistic regression to assess the effect (odds ratio [OR] and 95% confidence interval [CI]) of the following predictors: quarantine restrictions on leaving the residence, number of individuals in the household, problematic alcohol consumption before the pandemic (CAGE [cutting down, annoyance by criticism, guilty feeling, and eye-opener] score), personal concern regarding the pandemic, age, and sex. Results: 3,321 participants with a mean age of 32 (SD: 13) years were included in this study. 70.4% of participants reported less or unchanged alcohol consumption in the recent 4 weeks of the pandemic compared to before the pandemic. A higher number of individuals in the household was associated with a reduced alcohol consumption (OR = 0.869; 95% CI = 0.815-0.927). No quarantine restrictions on leaving the residence (OR = 1.593; 95% CI = 1.397-1.817), a higher age (1.006; 1.001-1.011), and female sex (compared to males: 1.206; 1.062-1.371) were associated with an increase in alcohol consumption. The CAGE score before the pandemic (OR = 0.983; 95% CI = 0.931-1.037) and the pandemic concern (0.927; 0.857-1.003) were not associated with a significant change in alcohol consumption. Celebrations were no longer frequent drinking occasions during the pandemic compared to before the pandemic. The majority of participants (60.9%) did not use alcohol drinking as a coping mechanism to mitigate negative effects of the pandemic. Interpretation: In this cohort of younger adults with fewer celebratory drinking occasions, restrictions on leaving the residence and the number of persons in the household were the strongest predictors of reduced alcohol consumption during the early phase of the pandemic.

Th2 cells lacking T-bet suppress naive and memory T cell responses via IL-10.

Exacerbated immune responses and loss of self-tolerance lead to the development of autoimmunity and immunopathology. Novel therapies to target autoreactive T cells are still needed. Here, we report that Th2-polarized T cells lacking the transcription factor T-bet harbor strong immunomodulatory potential and suppress antigen-specific CD8+ T cells via IL-10. Tbx21-/- Th2 cells protected mice against virus-induced type 1 diabetes development and suppressed not only naive but also memory CD8+ T cell responses. IL-10-producing, but not IL-10-deficient Tbx21-/- Th2 cells down-regulated costimulatory molecules on dendritic cells and reduced their IL-12 production after lymphocytic choriomeningitis virus infection. Impaired dendritic cell activation hindered effector and cytotoxic CD8+ T cell development after infection. These findings indicate that Tbx21-/- Th2 cells strongly suppress proinflammatory responses of naive and memory T cells via IL-10. Thus, in vivo IL-10-secreting Th2 cells could harbor a therapeutic potential for the treatment of T cell-mediated inflammatory disorders.

IL-33 in T Cell Differentiation, Function, and Immune Homeostasis.

Recent studies have highlighted a role for the alarmin interleukin (IL)-33 in CD4(+) and CD8(+) T cell activation and function, and have also revealed important distinctions. The IL-33 receptor ST2 is constitutively and abundantly expressed on T-helper-2 (Th2) and GATA-3(+) regulatory T cells in a GATA-3- and STAT5-dependent manner. Upon activation, Th1 and cytotoxic T cells express ST2 transiently, driven by T-bet and/or STAT4. We review these findings here, and critically examine evidence indicating that IL-33 enhances the differentiation and functionality of various T cell subsets through positive feedback loops involving lineage-specifying transcription factors. In this context, we discuss how quantitative and qualitative differences in ST2 expression between effector and GATA-3(+) regulatory T cells may contribute to immune homeostasis, and outline important areas of future inquiry.