Tripping into the unknown: Exploring the experiences of first-time LSD users through global drug survey insights.

BACKGROUND: The recreational use of LSD, a synthetic psychedelic drug, has surged in recent years, coinciding with a renewed research focus on its potential psychotherapeutic properties. AIM: This study aims to describe the experiences and perceptions of individuals engaging in LSD use for the first time, derived from a large international sample. METHODS: This study utilised 2018 Global Drug Survey data collected from 6 November 2017 to 10 January 2018. Participants who initiated LSD use in the preceding 12 months answered questions on their experiences, social settings, harm-reduction behaviours, and demographics. Descriptive statistics were employed, and characteristics of those seeking emergency medical treatment (EMT) and those not planning further LSD use were compared with other respondents. RESULTS: Among 3340 respondents who used LSD in the past year, their first-time experiences generally exceeded expectations, with 97.7% expressing excitement. Adverse and unwanted side effects were rarely reported, and only 17 individuals needed EMT. Feelings of fear were reported by most (64.1%), but only very mildly and not enough to put them off from wanting to use LSD again. DISCUSSION: Although the occurrence of unwanted side effects seems low and the LSD experience is generally pleasurable, vigilance amid the rising illicit use of LSD through harm-reduction education is still important in preventing possible risks.

Sweating for Sobriety: Exploring the Relationship Between Exercise Engagement and Substance Use Disorders.

Despite various interventions available for substance use disorders, relapse rates remain substantial and, therefore, alternative strategies for attenuating dependence are needed. This study examined the associations between exercise frequency, illicit substance use, and dependence severity among a large sample of people who use drugs. The study utilized data from the Global Drug Survey 2018 (N = 57,110) to investigate the relationship between exercise frequency, illicit substance use, and substance dependence severity. Binomial regressions were employed to examine the relationship between exercise and SDS scores for 9 drugs. Greater exercise frequency correlated with reduced severity of substance dependence for specific drugs: cannabis (χ2 = 14.75, p < .001), MDMA (χ2 = 4.73, p = .029), cocaine (χ2 = 8.37, p = .015), amphetamine powder (χ2 = 6.39, p = .041), and methamphetamine (χ2 = 15.17, p < .001). These findings suggest a potential link between exercise and reduced substance use dependency. Further research is needed to understand the complex dynamics between exercise and substance use, considering potential bidirectional relationships and concurrent factors.

Drinking and mental health in middle adulthood: exploring the impact of wellbeing, mental health literacy, and drinking motives on risk of alcohol dependence.

OBJECTIVES: Risky drinking is a concern among UK-based middle-aged adults. We aimed to explore the relationship between risky drinking, drinking motives, wellbeing, and mental health literacy (MHL). METHOD: Cross-sectional analysis of online survey data completed by 193 UK-based adults aged 40-65 who drank alcohol, incorporating the Alcohol Use Disorders Identification Test (AUDIT); Drinking Motives Questionnaire-Revised (DMQ-R); Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS); Mental Health Literacy Scale (MHLS) and demographic questions. RESULTS: Coping, enhancement and conformity motives and gender significantly predicted higher AUDIT scores (measuring risky drinking). Enhancement motives were found to mediate the relationship between the self-help component of MHL and AUDIT scores, while coping motives mediated the association between wellbeing and AUDIT scores. CONCLUSION: Findings support research emphasising the influence of drinking motives on risky drinking and highlights how low wellbeing may interact with coping motives to explain risky drinking among middle-aged adults, particularly men. Interventions supporting individuals to understand the relationship between drinking motives and risky drinking, develop adaptive coping strategies, and address the causes of low wellbeing, may be beneficial. However, as the sample was 84% ethnically White, 64% women, 85% educated to at least undergraduate level, and reported a relatively high mean socioeconomic status (6.98 out of 10), the results may not generalise beyond these groups. Future research should use stratified sampling to increase generalisability, as well as exploring whether alcohol-specific, component-specific, or disorder-specific MHL is associated with risky drinking and wellbeing.

Regrets, I've Had a Few: Exploring Factors Associated with Getting Drunk and Regret in an International Study of People Who Drink Alcohol.

BACKGROUND: Excessive alcohol consumption is often followed by feelings of regret. This study aimed to explore country differences in experiences of drunkenness and regrets and predictors of experiencing a greater number of regrettable drinking occasions. METHODS: This study draws on a sample of 82,821 respondents from 31 countries who completed the 2020 Global Drug Survey. Respondents were asked to report how many times in the last year they had been drunk, how many of those times they felt regret afterwards and to complete a range of sociodemographic measures. RESULTS: In the last 12 months, the median times drunk was 6 and the median number of regretted occasions was 2. There was an inverse relationship between times drunk and regret. Respondents who got drunk more often regretted it a smaller percentage of the time than those who got drunk less often. Respondents from Argentina and Colombia regretted being drunk the most and Denmark the least. Being younger, in higher AUDIT categories were associated with more times drunk. Being a woman, having mental health conditions were associated with more regretted occasions.Discussion and conclusions: Country variations may reflect relative acceptability of being drunk. Those who drink more, per occasion, may become accustomed to the consequences and feel fewer regrets. Interventions promoting reduced alcohol consumption may benefit from encouraging people to consider their future regret following a drinking occasion but should account for lower levels of regret in those who get drunk more often.

Discrimination, gender dysphoria, drinking to cope, and alcohol harms in the UK trans and non-binary community.

Transgender (trans) and non-binary people may be at increased risk of alcohol harms, but little is known about motives for drinking in this community. This study explored the relationship between risk of alcohol dependence, experience of alcohol harms, drinking motives, dysphoria, and discrimination within a United Kingdom sample of trans and non-binary people with a lifetime history of alcohol use. A cross-sectional survey was co-produced with community stakeholders and administered to a purposive sample of trans and non-binary people from 1 February until 31 March 2022. A total of 462 respondents were included-159 identified as non-binary and/or genderqueer (identities outside the man/woman binary), 135 solely as women, 63 solely as men, 15 as another gender identity, 90 selected multiple identities. Higher levels of reported discrimination were associated with higher risk of dependence and more reported harms from drinking. Coping motives, enhancement motives, and drinking to manage dysphoria were associated with higher Alcohol Use Disorders Identification Test scores. Social, coping, and enhancement motives alongside discrimination and drinking to have sex were associated with harms. The relationship between discrimination and risk of dependence was mediated by coping motives and drinking to manage dysphoria. Further to these associations, we suggest that reducing discrimination against trans and non-binary communities might reduce alcohol harms in this population. Interventions should target enhancement motives, coping motives and gender dysphoria. Social and enhancement functions of alcohol could be replaced by alcohol free supportive social spaces.

Resurrection of 2'-5'-oligoadenylate synthetase 1 (OAS1) from the ancestor of modern horseshoe bats blocks SARS-CoV-2 replication.

The prenylated form of the human 2'-5'-oligoadenylate synthetase 1 (OAS1) protein has been shown to potently inhibit the replication of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus responsible for the Coronavirus Disease 2019 (COVID-19) pandemic. However, the OAS1 orthologue in the horseshoe bats (superfamily Rhinolophoidea), the reservoir host of SARS-related coronaviruses (SARSr-CoVs), has lost the prenylation signal required for this antiviral activity. Herein, we used an ancestral state reconstruction approach to predict and reconstitute in vitro, the most likely OAS1 protein sequence expressed by the Rhinolophoidea common ancestor prior to its prenylation loss (RhinoCA OAS1). We exogenously expressed the ancient bat protein in vitro to show that, unlike its non-prenylated horseshoe bat descendants, RhinoCA OAS1 successfully blocks SARS-CoV-2 replication. Using protein structure predictions in combination with evolutionary hypothesis testing methods, we highlight sites under unique diversifying selection specific to OAS1's evolution in the Rhinolophoidea. These sites are located near the RNA-binding region and the C-terminal end of the protein where the prenylation signal would have been. Our results confirm that OAS1 prenylation loss at the base of the Rhinolophoidea clade ablated the ability of OAS1 to restrict SARSr-CoV replication and that subsequent evolution of the gene in these bats likely favoured an alternative function. These findings can advance our understanding of the tightly linked association between SARSr-CoVs and horseshoe bats.

Shouldn't We Know This Already? UK Women's Views About Communicating the Link Between Alcohol Consumption and Risk of Breast Cancer.

Alcohol is a causal factor in about 10% of breast cancer (BCa) cases, but awareness of this link is low. This study explored how to raise awareness and inform the development of an intervention using the COM-B model (capability, opportunity, motivation, behavior) framework. Eight online focus groups were conducted with 36 participants (6 expert stakeholders,and 30 women aged 40-65). Participants reflected on a package of information about alcohol and BCa and discussed how to impart this information and encourage women to reduce drinking. Thematic analysis of focus group transcripts was undertaken. Three themes were identified: understanding ineffective messaging; transitions and challenges; and message acceptability. Current health information about alcohol was perceived as judgmental and BCa was put down to chance. Mid-life consisted of many challenges that could lead to increased consumption, but menopause transition may be a key moment for alcohol reduction. Barriers and enablers to communicating risk information and encouraging alcohol reduction were mapped onto the COM-B model. Psychological capability (relating to knowledge), social opportunity (in the form of social pressure) and automatic motivation (relating to drinking to cope) were barriers to behavior change.  These will be targeted in an alcohol reduction intervention. It is important to tailor information to women's experiences, taking into account the social benefits of drinking, and encourage the development of healthy coping strategies. Acceptable intervention messages may include personal stories, clear statistics, and suggest healthy alternatives to drinking. It is vital that messaging does not appear judgmental or patronizing.

Calling time on responsible drinking: A qualitative study of perceptions of information on alcohol product labels.

OBJECTIVES: This study aimed to explore (a) how people interpret responsible drinking messages on alcohol product labels, and (b) the acceptability of including health information on labels. DESIGN: Qualitative interviews. METHODS: Face-to-face semi-structured interviews were conducted with 20 people aged 21-63; 18 were classified risky drinkers using AUDIT-C. They were shown three sets of alcohol product labels: one including three responsible drinking messages (drink responsibly), one with three positively worded health messages (drinking less reduces risks) and one with three negatively worded health messages (drinking more increases risks). Health messages included information about cancer, liver and heart disease. RESULTS: Thematic analysis identified three themes: ambiguity about alcohol labelling; identifying oneself as responsible; and acceptability of enhanced product labelling. Participants were critical of responsible drinking messages and wary of conflicting health information in the media. They positioned themselves as responsible, knowledgeable drinkers and distanced themselves from problem drinkers. They did not appear to support the inclusion of health information on labels; however, novel information was considered more impactful. CONCLUSIONS: Responsible drinking messages were seen by our sample as an alcohol industry ploy. Although health messages about cancer were seen as potentially impactful, the ability of consumers to position themselves as unproblematic drinkers means that they may not see the information on the label as relevant to themselves. Understanding factors that increase the personal relevance of messages is needed, alongside an exploration of a wider range of methods for alcohol health communication.

Connecting Through Dance: Understanding Conscious Clubbing Event Experiences.

Individuals abstaining from alcohol consumption frequently find themselves in contexts encouraging consumption, with limited alternative social interaction opportunities. Conscious clubbing events exclude alcohol and drugs, possibly providing valuable social connections, but little is known about event benefits. Twelve conscious clubbing event attendees and facilitators aged 25-55 from across Europe participated in semi-structured photo-elicitation interviews, which were analysed using thematic analysis. Findings suggested that conscious clubbing appears to enhance health, healing and growth, aiding recovery from substance dependency and trauma. Positioned as a modern ritual, symbolic and ritualistic preparations and experiences promoted storytelling and self-discovery. Connecting through synchronised but unchoreographed movement, participants engaged in powerful journeys and transformative experiences detached from life constraints. Inclusive digital and face-to-face conscious clubbing communities provided a sense of meaning and belonging away from substance use pressures and harms, particularly for those marginalised within society. Findings provide important and in-depth insights, including novel harm prevention implications. Future work should consider participatory barriers, event sustainability and misconceptions to increase event availability and participation.

Global comparisons of responses to alcohol health information labels: A cross sectional study of people who drink alcohol from 29 countries.

AIMS: The aim of this paper was to explore responses to alcohol health information labels from a cross sectional survey of people who drink alcohol from 29 countries. DESIGN: This paper draws on findings from the Global Drug Survey (GDS) - an annual cross sectional online survey. PARTICIPANTS: 75,969 (64.3% male) respondents from 29 countries were included in the study. MEASURES: Respondents were shown seven health information labels (topics were heart disease, liver, cancer, calories, violence, taking two days off and myth of benefits of moderate drinking). They were asked if the information was new, believable, personally relevant, and if it would change their drinking. A multivariate multilevel Bayesian logistic regression model was used to estimate predicted probabilities for newness, believability, relevance and if messages would change drinking behaviour by country and information label. FINDINGS: Predicted probabilities showed substantial variability in responses across countries. Respondents from Colombia, Brazil and Mexico were more likely to consider drinking less as well as have lower levels of previous awareness. Those from Denmark and Switzerland were not as likely to say the labels would make them consider drinking less. The cancer message was consistently the newest and most likely to make people consider drinking less across countries. CONCLUSIONS: Country differences in responses to messages can be used to create targeted harm reduction measures as well as inform what should be on labels. The provision of such health information on alcohol product labels may play a role in raising awareness of the risk of drinking. Global comparisons of responses to alcohol health information labels: a cross sectional study of people who drink alcohol from 29 countries.

Testing socioeconomic status and family socialization hypotheses of alcohol use in young people: A causal mediation analysis.

INTRODUCTION: The effect of socioeconomic status on adolescent substance abuse may be mediated by family socialization practices. However, traditional mediation analysis using a product or difference method is susceptible to bias when assumptions are not addressed. We aimed to use a potential outcomes framework to assess assumptions of exposure-mediator interaction and of no confounding of the results. METHOD: We revisited a traditional mediation analysis with a multiple mediator causal mediation approach using data from 17,761 Norwegian young people (13-18 years), 51% female. Data were collected through a print questionnaire. Socioeconomic status was operationalized as parental education and employment status (employed or receiving welfare); drinking behavior as the frequency of alcohol consumption and frequency of intoxication in the past year; and socialization practices as general parenting measures, alcohol-related parental permissiveness, and parent drinking behavior. RESULTS: There was no consistent evidence of exposure-mediator interaction. Formal sensitivity analysis of mediator-outcome confounding was not possible in the multiple mediator model, and this analysis supported the hypothesis that socioeconomic status effects on adolescent substance abuse are fully mediated by family socialization practices, with apparently stronger effects in younger age groups observed in plots. CONCLUSION: We found that the effect of socioeconomic status on adolescent substance abuse was fully mediated by family socialization practices. While our analysis provides more rigorous support for causal inferences than past work, we could not completely rule out the possibility of unmeasured confounding.

Taking Action in Student Harassment Situations: Application of the Behaviour Change Wheel to Bystander Intervention.

This study applied the Behaviour Change Wheel (BCW) to understand barriers and facilitators to bystander behaviors in UK students. The BCW includes detailed examination of the capabilities, opportunities, and motivations involved in behaviors. Two surveys (n = 515; n = 201) and a focus group study (n = 12) were undertaken. Capability to intervene may be influenced by confidence and beliefs about physical ability and safety. Students appeared to have the physical opportunity to intervene, but social opportunity might be influenced by cultural norms. Motivations might be influenced by beliefs as well as inherent stereotypes about perpetrators and victims. Behavior change techniques (BCTs) such as instruction on how to perform the behavior, reattribution and creating a valued self-identity should be applied to overcome these barriers. A logic model to theorize the change processes underlying bystander behaviors in this population offers a new perspective on what needs to be addressed in interventions.

Impacts of changes in alcohol consumption patterns during the first 2020 COVID-19 restrictions for people with and without mental health and neurodevelopmental conditions: A cross sectional study in 13 countries.

BACKGROUND: The initial period of COVID-19-related restrictions affected substance use in some population groups. We explored how changes in alcohol use at the beginning of the pandemic impacted the health and wellbeing of people with and without mental health and neurodevelopmental conditions (MHDCs). METHODS: Data came from the Global Drug Survey Special Edition on COVID-19 conducted in May-June 2020. Measured were; changes in drinking compared to February 2020 (pre-COVID-19 restrictions), reasons for changes, and impact on physical health, mental health, relationships, finances, work/study, and enjoyment. This study included 38,141 respondents (median age = 32 IQR 25-45; 51.9% cis man; 47.8% cis woman; 1.2% trans/non-binary; 30.2% with MHDCs e.g. depression 20.0%, anxiety 16.3%, ADHD 3.8%, PTSD 3.3%). RESULTS: A third (35.3%) of respondents with MHDCs and 17.8% without MHDCs indicated that increased drinking affected their mental health negatively (p<.001); 44.2% of respondents with MHDCS compared to 32.6% without MHDCs said it affected their physical health negatively (p<.001). Reduced drinking was associated with better mental health among a fifth (21.1%) of respondents with MHDCS and 14.4% without MHDCs (p<.001). Age, relationship status, living arrangements, employment, coping and distress were significant predictors of increases in drinking. CONCLUSION: Among people with MHDCS, reduced alcohol consumption was associated with better mental health, while the negative effects of increased drinking were more pronounced when compared to people without MHDCS. When supporting people in reducing alcohol consumption during uncertain times, people with MHDCS may need additional support, alongside those experiencing greater levels of distress.

HCMV carriage in the elderly diminishes anti-viral functionality of the adaptive immune response resulting in virus replication at peripheral sites.

Human cytomegalovirus (HCMV) infection and periodic reactivation is, generally, well controlled by adaptative immune responses in the healthy. In older people, overt HCMV disease is rarely seen despite the association of HCMV with increased risk of mortality; evidence from studies of unwell aged populations suggest that HCMV seropositivity is an important co-morbidity factor. HCMV genomes have been detected in urine from older donors, suggesting that the immune response prevents systemic disease but possibly immunomodulation due to lifelong viral carriage may alter its efficacy at peripheral tissue sites. Previously we have demonstrated that there were no age-related expansions of T cell responses to HCMV or increase in latent viral carriage with age and these T cells produced anti-viral cytokines and viremia was very rarely detected. To investigate the efficacy of anti-HCMV responses with increasing age, we used an in vitro Viral Dissemination Assay (VDA) using autologous dermal fibroblasts to determine the anti-viral effector capacity of total PBMC, as well as important subsets (T cells, NK cells). In parallel we assessed components of the humoral response (antibody neutralization) and combined this with qPCR detection of HCMV in blood, saliva and urine in a cohort of young and old donors. Consistent with previous studies, we again show HCMV specific cIL-10, IFNγ and TNFα T cell responses to peptides did not show an age-related defect. However, assessment of direct anti-viral cellular and antibody-mediated adaptive immune responses using the VDA shows that older donors are significantly less able to control viral dissemination in an in vitro assay compared to young donors. Corroborating this observation, we detected viral genomes in saliva samples only from older donors, these donors had a defect in cellular control of viral spread in our in vitro assay. Phenotyping of fibroblasts used in this study shows expression of a number of checkpoint inhibitor ligands which may contribute to the defects observed. The potential to therapeutically intervene in checkpoint inhibitor pathways to prevent HCMV reactivation in the unwell aged is an exciting avenue to explore.

A prenylated dsRNA sensor protects against severe COVID-19.

Inherited genetic factors can influence the severity of COVID-19, but the molecular explanation underpinning a genetic association is often unclear. Intracellular antiviral defenses can inhibit the replication of viruses and reduce disease severity. To better understand the antiviral defenses relevant to COVID-19, we used interferon-stimulated gene (ISG) expression screening to reveal that 2'-5'-oligoadenylate synthetase 1 (OAS1), through ribonuclease L, potently inhibits severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We show that a common splice-acceptor single-nucleotide polymorphism (Rs10774671) governs whether patients express prenylated OAS1 isoforms that are membrane-associated and sense-specific regions of SARS-CoV-2 RNAs or if they only express cytosolic, nonprenylated OAS1 that does not efficiently detect SARS-CoV-2. In hospitalized patients, expression of prenylated OAS1 was associated with protection from severe COVID-19, suggesting that this antiviral defense is a major component of a protective antiviral response.

Where and What You Drink Is Linked to How Much You Drink: An Exploratory Survey of Alcohol Use in 17 Countries.

BACKGROUND: This paper aimed to explore the differences in subjective experiences of intoxication depending on drinking location and drink type. Methods: Data came from 32,194 respondents to The Global Drug Survey (GDS) 2015, an annual, cross-sectional, online survey. Respondents selected their usual drinking location (home alone: home with partner/family: house parties: pubs/bars or clubs) and usual drink (wine; beer/cider/lager; spirits or alcopops/coolers). They indicated how many drinks they required to reach three stages of intoxication (feeling the effects; an ideal stage of intoxication; and the tipping point) and how frequently they reached each stage. Results: Drink type affected grams of alcohol reported to reach the tipping point: 109 gm wine, 127 gm alcopops, 133 gm of beer, and 134 gm of spirts. Respondents who drank at home alone, or in clubs reached their tipping point more frequently compared to other locations. Conclusions: Where people drink, and the type of alcohol they drink, affected the amount of alcohol reported to reach different stages of intoxication. Understanding why different drinking locations, and drink types lead to a need for greater consumption to reach an ideal state of drunkenness, such as social cues from other people who drink, may enable people to reduce their drinking.

The effect of alcohol strength on alcohol consumption: findings from a randomised controlled cross-over pilot trial.

BACKGROUND: Reducing the alcohol content of drinks has the potential to reduce alcohol consumption. The aims of this study are to (1) test the feasibility of a randomised controlled trial (RCT) to assess the effect of alcohol strength on alcohol consumption within licensed premises in the United Kingdom (UK), and to (2) provide data to estimate key parameters for a RCT. METHODS: This study is a double-blind randomised controlled cross-over pilot trial based within four licensed premises in the UK. Participants (n = 36) purchased and consumed ad libitum a 3.5% lager and a 4.8% lager during two separate study sessions. Descriptive statistics reported the efficacy and efficiency of the study processes, and the rates of licensed premises recruitment, and participant recruitment and attrition. Mean and the 95% confidence interval (CI) compared alcohol consumption between conditions. The mean, standard deviation (SD) and CI of UK units of alcohol consumed were used to calculate a sample size for a RCT. Responses to participant questionnaires and duration of participation in study sessions between conditions were analysed. RESULTS: Components of the study protocol were effective and efficient. The venue recruitment rate was less than anticipated. The participant recruitment rate was greater than anticipated. The rate of attrition was 23% and varied by less than 1% according to the arm of the trial. There was a reduction of alcohol consumed under the intervention conditions. Estimated mean difference, and 95% CI (UK units): - 3.76 (- 5.01 to - 2.52). The sample size required for a RCT is 53. Participants did not find one lager more pleasant in taste: (on a scale of one to 10) - 0.95 (- 2.11 to 0.21). Participants found the reduced-strength lager less enjoyable: (on a scale of one to 10) - 1.44 (- 2.64 to - 0.24) and they perceived themselves to be less intoxicated after consuming it: (on a scale of one to 10) - 1.00 (- 1.61 to - 0.40). CONCLUSION: A RCT is feasible with minor alterations to the study protocol and scoping work to establish different brands of alcohol that are more alike and more enjoyable than the products used in the pilot trial. TRIAL REGISTRATION: Registered in the American Economic Association (AEA) Randomised Controlled Trial (RCT) Registry as of 16 June 2017. Unique identifying number: AEARCTR-0002266 .

Perceptions of cannabis health information labels among people who use cannabis in the U.S. and Canada.

BACKGROUND: The emergence of legal cannabis industries poses a new public health challenge. Health information labels are part of the public health strategy for tobacco and alcohol, but there is limited research on cannabis-related messaging. This study explored perceptions of cannabis health information labels among people who used cannabis in the last 12 months residing in the U.S. and Canada. METHODS: The Global Drug Survey (GDS) is a large anonymous cross-sectional web-survey. In GDS2019, respondents were presented with six labels with cannabis-related health information (dependence; driving stoned; harms of smoking; harms to developing brain; lack of motivation; effects on memory), and asked if information was new, believed, would it change behavior, and about acceptability of having health labels on legal products. This paper includes 1,275 respondents from Canada and 2,224 from U.S. states where cannabis was legal at the time of the survey, and 5,230 from other U.S. states. RESULTS: Few respondents said that the information was new (6.6-24.6%). Most said the information was believable (63.5-72.0%) other than for the dependence message (28.1% new, 56.8% believed), which was perceived to be the least likely to change behavior (10.2%). Driving stoned was the message perceived to be the most likely to change behavior (58.5%). Respondents living in Canada were less likely to say information was new and rated most messages more believable than those in the U.S. Respondents from legal U.S. states were less likely to say information was new compared to other states. Respondents who used cannabis daily rated acceptability of labels lower (27.8%) than those using 1-48 days (40.6%). CONCLUSIONS: Novel, believable information may be more effective at changing behavior. Regular consumers may be less susceptible to messages. Information focusing on safer use strategies and benefits of reducing use may be more acceptable and should be assessed in future research.

Inhaling alcohol vapour or mist: An international study of use, effects and harms.

OBJECTIVES: To determine the prevalence, patterns of use and consequences of inhaling alcohol vapour or mist. DESIGN: Cross-sectional survey recruiting an international non-probability sample of people who use alcohol and other drugs as part of the annual Global Drug Survey (GDS). SETTING: Online questionnaire translated into 19 languages. PARTICIPANTS: 110,557 people took part in GDS2020 and 88,124 completed a question about inhaling alcohol in the last 12 months. The focus of this study is GDS2020 respondents who reported inhaling alcohol mist/vapour from a balloon in the last 12 months. MAIN OUTCOMES: Last 12-month use of alcohol vapour, onset duration, intensity of effects, value for money compared with alcohol, and incidence of falls/injuries. RESULTS: A total of 803 people reported the use of alcohol vapour in the last 12 months, with 51% of the sample coming from 3 countries: Australia, Denmark and England. Two-thirds were male, and they were more likely to be under 25. 45.7% reported that they were a bit/very drunk before they inhaled alcohol. 51.3% reported that the effects lasted for less than 5 mins. Both the intensity of effect and perceived value for money showed a normal distribution on a 10-point scale. 12.7% of respondents reported falling/injuring themselves. CONCLUSION: Inhaling alcohol vapour appears to be more common amongst younger, higher-risk drinkers. The rapid onset of action and inability to titrate consumption to effect is a risk for acute injury. We consider that alcohol is harmful enough through oral consumption without adding to the risk of injury by offering such a potentially risky additional administration method.

Assessing Anti-HCMV Cell Mediated Immune Responses in Transplant Recipients and Healthy Controls Using a Novel Functional Assay.

HCMV infection, reinfection or reactivation occurs in 60% of untreated solid organ transplant (SOT) recipients. Current clinical approaches to HCMV management include pre-emptive and prophylactic antiviral treatment strategies. The introduction of immune monitoring to better stratify patients at risk of viraemia and HCMV mediated disease could improve clinical management. Current approaches quantify T cell IFNγ responses specific for predominantly IE and pp65 proteins ex vivo, as a proxy for functional control of HCMV in vivo. However, these approaches have only a limited predictive ability. We measured the IFNγ T cell responses to an expanded panel of overlapping peptide pools specific for immunodominant HCMV proteins IE1/2, pp65, pp71, gB, UL144, and US3 in a cohort of D+R- kidney transplant recipients in a longitudinal analysis. Even with this increased antigen diversity, the results show that while all patients had detectable T cell responses, this did not correlate with control of HCMV replication in some. We wished to develop an assay that could directly measure anti-HCMV cell-mediated immunity. We evaluated three approaches, stimulation of PBMC with (i) whole HCMV lysate or (ii) a defined panel of immunodominant HCMV peptides, or (iii) fully autologous infected cells co-cultured with PBMC or isolated CD8+ T cells or NK cells. Stimulation with HCMV lysate often generated non-specific antiviral responses while stimulation with immunodominant HCMV peptide pools produced responses which were not necessarily antiviral despite strong IFNγ production. We demonstrated that IFNγ was only a minor component of secreted antiviral activity. Finally, we used an antiviral assay system to measure the effect of whole PBMC, and isolated CD8+ T cells and NK cells to control HCMV in infected autologous dermal fibroblasts. The results show that both PBMC and especially CD8+ T cells from HCMV seropositive donors have highly specific antiviral activity against HCMV. In addition, we were able to show that NK cells were also antiviral, but the level of this control was highly variable between donors and not dependant on HCMV seropositivity. Using this approach, we show that non-viraemic D+R+ SOT recipients had significant and specific antiviral activity against HCMV.