Binge Alcohol Research Articles

Problematic familial alcohol use and adolescent outcomes: Do associations differ by parental education?

Aim: To investigate the associations between problematic familial alcohol use and adolescent subjective health, binge drinking, relationships with parents, school performance, and future orientation, and to study whether these associations differ in relation to parental education. Methods: Cross-sectional data from the Stockholm School Survey (SSS) collected among students in the 9th and 11th grades in 2018 and in 2020 were used (n = 19,415). Subjective health, parent-youth relationships, and school performance were coded as continuous variables; binge drinking and future orientation were coded as binary variables. Familial drinking included three categories: problematic; don't know/missing; and not problematic. Parental university education distinguished between adolescents with two, one, or no university-educated parent(s). Control variables included gender, grade, family structure, migration background, parental unemployment, and survey year. Linear and binary logistic regression analyses were performed. Results: Problematic familial alcohol use was associated with worsened subjective health, a higher likelihood of engaging in binge drinking, worse relationships with parents, and a higher likelihood of having a pessimistic future orientation, even when adjusting for all control variables. Having less than two university-educated parents was associated with a higher likelihood of reporting problematic familial alcohol use. Parental university education moderated the association between problematic familial alcohol use and binge drinking as this relationship was stronger for adolescents with no and one university-educated parent(s). Conclusions: Adolescents with problematic familial alcohol use fared worse with regards to all studied outcomes, except for school performance. Parental university education only moderated the association between problematic familial alcohol use and binge drinking. However, since problematic familial alcohol use was more common among adolescents with less than two university-educated parents, we argue that at the group level, this category may be more negatively affected by alcohol abuse in the family. Policy interventions could benefit from having a socioeconomic perspective on how children are affected by alcohol's harms to others.

Therapeutic role of mesenchymal stem cell-derived extracellular vesicles in neuroinflammation and cognitive dysfunctions induced by binge-like ethanol treatment in adolescent mice.

Extracellular vesicles (EVs) are heterogeneous membrane vesicles secreted by cells in extracellular spaces that play an important role in intercellular communication under both normal and pathological conditions. Mesenchymal stem cells (MSC) are anti-inflammatory and immunoregulatory cells capable of secreting EVs, which are considered promising molecules for treating immune, inflammatory, and degenerative diseases. Our previous studies demonstrate that, by activating innate immune receptors TLR4 (Toll-like receptor 4), binge-like ethanol exposure in adolescence causes neuroinflammation and neural damage. To evaluate whether the intravenous administration of MSC-derived EVs is capable of reducing neuroinflammation, myelin and synaptic alterations, and the cognitive dysfunction induced by binge-like ethanol treatment in adolescent mice. MSC-derived EVs obtained from adipose tissue were administered in the tail vein (50 microg/dose, one weekly dose) to female WT adolescent mice treated intermittently with ethanol (3.0 g/kg) during two weeks. MSC-derived EVs from adipose tissue ameliorate ethanol-induced up-regulation of inflammatory genes (e.g., COX-2, iNOS, MIP-1α, NF-κB, CX3CL1, and MCP-1) in the prefrontal cortex of adolescent mice. Notably, MSC-derived EVs also restore the myelin and synaptic derangements, and the memory and learning impairments, induced by ethanol treatment. Using cortical astroglial cells in culture, our results further confirm that MSC-derived EVs decrease inflammatory genes in ethanol-treated astroglial cells. This, in turn, confirms in vivo findings. Taken together, these results provide the first evidence for the therapeutic potential of the MSC-derived EVs in the neuroimmune response and cognitive dysfunction induced by binge alcohol drinking in adolescence.

P-007 A Four Arm Prospective Randomized Control Trial to Investigate the Role of Advance Sperm Selection Techniques for Raised Sperm DNA Fragmentation Index

Abstract Study question Role of Testicular Sperm Aspiration (TESA), Magnetic Activated Cell Sorting (MACS), Microfluidics & Daily ejaculation, to reduce raised Sperm DNA Fragmentation Index (SDF) & evaluate impact on outcomes? Summary answer Amongst the advance sperm selection methods, Microfluidic sperm sorting seems to significantly reduce the SDF and offer the best reproductive outcomes What is known already Raised SDF is known to affect the reproductive outcomes of a couple. There are various sperm processing methods/interventions shown to reduce the sperm DNA fragmentation, but their effectiveness to optimize reproductive outcomes is still debatabl. Study design, size, duration RCT approved by the Institutional Ethical Committee. IEC No.:1312/Inst/TG/2019. Couples undergoing IVF with raised SDF were randomized into four arms by computer generated randomized numbers from October 2019 to May 2022 (n = 466). Of those 373 patients recruited to, TESA (n = 129), MACS (n = 92), Microfluidics (n = 116) Daily ejaculation (n = 36) . Males with SDF > 25% & Age 25-40 yrs were included. Women>37 yrs, BMI >30 and men with Smoking, Binge alcohol, varicocele excluded. Couples with one failed IVF were offered SDF. SDF>25%was considered raised and were included in study. Participants/materials, setting, methods After Oocyte Pick Up (OPU), sample processed for ICSI and was sent for post intervention SDF. TESA done as per SOP of clinic. MACS & Microfluidics done as per instruction from manufacturer. Daily ejaculate group, patient ejaculated daily for 1week prior to OPU and at OPU, fresh ejaculate processed through density gradient. Men with high SDF, after randomization were subjected to OPU, ICSI, Blastocyst Culture, Freeze all policy and Frozen Embryo Transfer with 2blastocysts Main results and the role of chance Primary outcome-magnitude of reduction in SDF post intervention Secondary outcomes – Blastocyst Rate (BR), Implantation rates (IR), Live birth (LBR)Mean of SDF on Raw Semen Sample Vs Post Intervention Sample: TESA – 44% Vs 25.75% Microfluidics - 34.4% Vs 9.8% (p < 0.05; Significant) MACS – 32.2% Vs 27.95% Daily Ejaculation 39.37% Vs 19.66% Microfluidics seem to be beneficial intervention in significantly reducing the SDF. MACS seemed to have offered the least reduction of SDF. BR: This was comparable between all groups with no statistical significance Reproductive Outcomes for TESA, Microfluidics, MACS & Daily ejaculation: IR – 39.3% Vs 57.27% Vs 46.4% Vs 61% (p = 0.1) LBR – 60% VS 65% Vs 64% Vs 61% (p = 0.41) Miscarriage Rates and Multiple Pregnancy rates were comparable between the groups and statistically not significant. We observe that microfluidics was the best sperm processing method as it significantly reduced the DFI and had the best reproductive outcomes. It is noninvasive and can be done easily. Even though there was no statistical significance, Daily ejaculation yielded equivocal outcomes than the other 3 groups. Considering the ease, cost effectiveness and optimal reproductive outcomes Daily Ejaculation can also be offered to patients with raised SDF. Though TESA had acceptable outcomes, considering its invasiveness adequate counselling is warranted. Outcomes for MACS were guarded and be suggested with caution. Limitations, reasons for caution The sample size is small in the daily ejaculate arm as there were many dropouts. The unequal size of the arms would affect the results. So, we are continuing the randomization and intend to look into the results with equal size of the arms in the future Wider implications of the findings Published literature has shown raised SDF to be detrimental to reproductive outcomes. There is an urgent need for an efficient intervention which is safe, economical, easy to use and offers the best reproductive outcomes. Daily ejaculation, a traditional concept which is cost effective needs due consideration over other techniques. Trial registration number CTRI. Trial No.: REF/2021/05/043439

Cohort effects of women's mid-life binge drinking and alcohol use disorder symptoms in the United States: Impacts of changes in timing of parenthood.

Alcohol use is increasing among women in mid-life concurrently with societal changes in timing of parenthood and changing cultural norms, which may influence alcohol use. The aim of this study was to determine if age of first parenting was associated with excessive drinking [i.e. past 2-week binge drinking and past 5-year alcohol use disorder (AUD) symptoms] among women during mid-life in the United States and to determine if there were pronounced cohort effects influencing these relationships. This was a retrospective cohort, longitudinal study. Data were drawn from the Monitoring the Future survey, an annual ongoing survey of high school students' substance use behaviors in the United States. Participants were women who completed the age 35 survey between 1993 and 2019, corresponding to high school senior years 1976-2002 (n = 9988). Past 2-week binge drinking and past 5-year AUD symptoms were self-reported. Age of first parenting was self-reported. Binge drinking and AUD symptoms were higher among women in recent than in older cohorts. Women from the 2018-19 cohort had increased odds of binge drinking [odds ratio (OR) = 1.73, 95% confidence interval (CI) = 1.41-2.12] and AUD symptoms (OR = 1.51, CI = 1.27-1.80) relative to women from the 1993-97 cohort. Throughout cohorts, there was an inverse association between transition to parenthood and excessive drinking outcomes (e.g. range for ORs for binge drinking among those without children compared with those who had had children between the ages of 18 and 24: 1.22-1.55). Simultaneously, there was a population shift towards delaying parenting in recent cohorts (i.e. 54% of women in the 1993-97 cohort had children before age 30 compared with 39% in the two recent cohorts), increasing the size of the group at highest risk for excessive drinking. In the United States, subgroups of women at highest risk of excessive drinking appear to be expanding, probably supported in part by a trend towards delayed parenting.

Cannabis and Alcohol Use by U.S. Young Adults, 2008–2019: Changes in Prevalence After Recreational Cannabis Legalization

Young adults' cannabis and alcohol use patterns have changed after state recreational cannabis legalization according to studies based on college samples but not nationally representative samples. Associations between recreational cannabis legalization and changes in cannabis and alcohol use outcomes among young adults were examined, including differences by college enrollment and minor status (ages 18-20 vs 21-23 years). Repeated cross-sectional data (2008-2019) were collected from college-eligible participants aged 18-23 years in the National Survey on Drug Use and Health. Self-reported past-month cannabis use and frequent use (≥20 days) and a proxy for past-year DSM-5 cannabis use disorder were primary outcomes; past-month frequent alcohol use and binge drinking were secondary outcomes. Multilevel logistic regression models quantified changes in outcome prevalence from the study years before to after recreational cannabis legalization, adjusting for secular trends. Analyses were conducted on March 22, 2022. Prevalence increased from before to after recreational cannabis legalization for past-month cannabis use (from 21% to 25%) and past-year proxy cannabis use disorder (from 11% to 13%); the increases were statistically significant [adjusted odds ratio (95% CI) = 1.20 (1.08-1.32) and 1.14 (1.003-1.30), respectively]. Increases were detected for young adults who were not in college and who were aged 21-23 years. Recreational cannabis legalization impacts were not detected for secondary outcomes. Some young adults appear sensitive to state recreational cannabis legalization, including in terms of cannabis use disorder risk. Additional prevention efforts should be directed to young adults who are not in college and timed to occur before age 21 years.

Binge alcohol consumption dampens somatostatin peptide release and signaling in cortical microcircuits in mice

Binge alcohol consumption dampens somatostatin peptide release and signaling in cortical microcircuits in mice

Can bacterial products reach the brain after alcohol binge drinking?

Can bacterial products reach the brain after alcohol binge drinking?

Role of an Insula-Amygdala Circuit on Alcohol Binge Drinking in Mice

Role of an Insula-Amygdala Circuit on Alcohol Binge Drinking in Mice

Alcohol Misuse, Binge Drinking, and their Associations with Psychosocial Factors during COVID-19 among Harlem Residents in New York City.

This study examined alcohol misuse and binge drinking prevalence among Harlem residents, in New York City, and their associations with psycho-social factors such as substance use, depression symptom severity, and perception of community policing during COVID-19. An online cross-sectional study was conducted among 398 adult residents between April and September 2021. Participants with a score of at least 3 for females or at least 4 for males out of 12 on the Alcohol Use Disorders Identification Test were considered to have alcohol misuse. Binge drinking was defined as self-reporting having six or more drinks on one occasion. Modified Poisson regression models were used to examine associations. Results showed that 42.7% used alcohol before COVID-19, 69.1% used it during COVID-19, with 39% initiating or increasing alcohol use during COVID-19. Alcohol misuse and binge drinking prevalence during COVID-19 were 52.3% and 57.0%, respectively. Higher severity of depression symptomatology, history of drug use and smoking cigarettes, and experiencing housing insecurity were positively associated with both alcohol misuse and binge drinking. Lower satisfaction with community policing was only associated with alcohol misuse, while no significant associations were found between employment insecurity and food insecurity with alcohol misuse or binge drinking. The findings suggest that Harlem residents may have resorted to alcohol use as a coping mechanism to deal with the impacts of depression and social stressors during COVID-19. To mitigate alcohol misuse, improving access to mental health and substance use disorder services, and addressing public safety through improving relations with police could be beneficial.

Maternal alcohol consumption and the risk of miscarriage in the first and second trimesters: a systematic review and dose-response meta-analysis.

According to a precautionary principle, it is recommended that pregnant women and women trying to conceive abstain from alcohol consumption. In this dose-response meta-analysis, we aimed to examine the association between alcohol consumption and binge drinking and the risk of miscarriage in the first and second trimesters. The literature search was conducted in MEDLINE, Embase and the Cochrane Library in May 2022, without any language, geographic or time limitations. Cohort or case-control studies reporting dose-specific effects adjusting for maternal age and using separate risk assessments for first- and second-trimester miscarriages were included. Study quality was assessed using the Newcastle-Ottawa Scale. This study is registered with PROSPERO, registration number CRD42020221070. A total of 2124 articles were identified. Five articles met the inclusion criteria. Adjusted data from 153 619 women were included in the first-trimester analysis and data from 458 154 women in the second-trimester analysis. In the first and second trimesters, the risk of miscarriage increased by 7% (odds ratio [OR] 1.07, 95% confidence interval [CI] 0.96-1.20) and 3% (OR 1.03, 95% CI 0.99-1.08) for each additional drink per week, respectively, but not to a statistically significant degree. One article regarding binge drinking and the risk of miscarriage was found, which revealed no association between the variables in either the first or second trimester (OR 0.84 [95% CI 0.62-1.14] and OR 1.04 [95% CI 0.78-1.38]). This meta-analysis revealed no dose-dependent association between miscarriage risk and alcohol consumption, but further focused research is recommended. The research gap regarding miscarriage and binge drinking needs further investigation.

High-mobility group box 1 (HMGB1) crosses the BBB bidirectionally

High-mobility group box 1 (HMGB1) is a ubiquitous protein that regulates transcription in the nucleus, and is an endogenous damage-associated molecular pattern molecule that activates the innate immune system. HMGB1 activates the TLR4 and RAGE recepto, inducing downstream signals reminiscent of cytokines that have been found to cross the blood–brain barrier (BBB). Blood HMGB1 increases in stroke, sepsis, senescence, alcohol binge drinking and other conditions. Here, we examined the ability of HMGB1 radioactively labeled with iodine (I-HMGB1) to cross the BBB. We found that I-HMGB1 readily entered into mouse brain from the circulation with a unidirectional influx rate of 0.654 μl/g-min. All brain regions tested took up I-HMGB1; uptake was greatest by the olfactory bulb and least in the striatum. Transport was not reliably inhibited by unlabeled HMGB1 nor by inhibitors of TLR4, TLR2, RAGE, or CXCR4. Uptake was enhanced by co-injection of wheatgerm agglutinin, suggestive of involvement of absorptive transcytosis as a mechanism of transport. Induction of inflammation/neuroinflammation with lipopolysaccharide is known to increase blood HMGB1; we report here that brain transport is also increased by LPS-induced inflammation. Finally, we found that I-HMGB1 was also transported in the brain-to-blood direction, with both unlabeled HMGB1 or lipopolysaccharide increasing the transport rate. These results show that HMGB1 can bidirectionally cross the BBB and that those transport rates are enhanced by inflammation. Such transport provides a mechanism by which HMGB1 levels would impact neuroimmune signaling in both the brain and periphery.

Chronic binge alcohol-induced hippocampal plasticity in SIV-infected female rhesus macaques

Human immunodeficiency virus (HIV) infection is detrimental to central nervous system (CNS) function and may result in HIV-associated neurocognitive disorder (HAND) over time. HIV-associated cognitive deficits are further exacerbated by chronic alcohol use. With the rising prevalence of alcohol use disorder (AUD) in females and people living with HIV (PLWH), understanding the neurobiological impact of chronic alcohol exposure in these populations is increasingly important. As the hippocampus plays a prominent role in cognition, examining neuroadaptations in this brain region in the context of comorbid HIV infection and alcohol exposure is critical for understanding the mechanisms of neurocognitive impairment. We hypothesized that simian immunodeficiency virus (SIV)-infected female rhesus macaques with a history of chronic binge alcohol (CBA) administration (n=7-8 per group) would exhibit increased phosphorylation of mitogen-activated protein kinase (MAPK) family members, indicative of increased hippocampal activity and potential hyperexcitability. We also measured cognitive performance in macaques via the novel object recognition (NOR) task and further hypothesized a manifestation of cognitive deficits in the CBA-treated group. Finally, we incorporated additional groups of ovariectomized (OVX) females in the design as we hypothesized that the loss of ovarian hormones would reduce cognitive performance. Data were analyzed via two-way ANOVA with CBA treatment and OVX as factors. Western blot analyses demonstrated that CBA significantly increased phosphorylation of MAPK-family members extracellular signal-regulated kinase (ERK; F=8.278, p=0.0093) and p38 mitogen-activated protein kinase (p38 MAPK; F=4.414, p=0.0485). Furthermore, CBA significantly increased both phosphorylated and total levels of Jun N-terminal kinase (JNK; F=5.989, p=0.0233; F=7.158, p=0.0145). While analysis of the NOR task revealed a significant reduction in latency to approach the novel versus familiar object on test day across all groups (F = 11.97, p=0.0013), no significant difference was seen between CBA and control groups. Interestingly, no main effects of OVX or interactive CBA/OVX effects were observed for either molecular or behavioral outcomes. We are currently considering alternative cognitive tasks that may better reveal CBA-associated cognitive deficits, as well as neuroadaptations in nuclear signaling downstream of MAPK activity. Together, these data suggest that chronic alcohol use results in profound changes in hippocampal plasticity, potentially facilitating cognitive decline and other CNS symptoms observed in PLWH. This research was supported by grant # T32AA007577 and #P60AA009803 from the NIAAA at the National Institutes of Health. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Differential expression of adipocyte and myotube extracellular vesicle miRNA cargo in chronic binge alcohol-administered SIV-infected male macaques.

Our studies in chronic binge alcohol (CBA) -treated simian immunodeficiency virus (SIV)-infected macaques and in people living with HIV (PLWH) show significant alterations in metabolic homeostasis. CBA promotes a profibrotic phenotype in adipose tissue and skeletal muscle (SKM) and decreases adipose-derived stem cell and myoblast differentiation, making adipose and SKM potential drivers in metabolic dysregulation. Furthermore, we have shown that the differential expression of microRNAs (miRs) in SKM contributes to impaired myoblast differentiation potential. Beyond modulation of intracellular responses, miRs can be transported in extracellular vesicles (EVs) to mediate numerous cellular responses through intercellular and interorgan communication. This study tested the hypothesis that CBA alters concentration and miR cargo of EVs derived from adipocytes and myotubes isolated from SIV-infected male macaques. Fourteen male rhesus macaques received either CBA (2.5g/kg/day) or sucrose (VEH) for 14.5 months. Three months following the initiation of CBA/VEH, all animals were infected with SIVmac251 and 2.5 months later were initiated on antiretroviral therapy. SKM and adipose tissue samples were collected at the study endpoint (blood alcohol concentration=0mM). EVs were isolated by ultracentrifugation of myotube and adipocyte cell culture supernatant. Nanoparticle tracking revealed no differences in concentration or size of particles between VEH and CBA groups. Adipocyte-derived EVs from CBA animals showed decreased miR-let-7a expression (p=0.03). Myotube-derived EVs from CBA animals had decreased miR-16 (p=0.04) and increased miR-133a and miR-133b (both p=0.04) expression. These results indicate that CBA administration differentially regulates EV miR content but does not alter the number of EVs from adipocytes or myotubes. Future studies are warranted to determine the functional relevance of CBA-altered EV miR cargo and their role in intercellular and interorgan communication and metabolic dysregulation.

Chronic binge alcohol alters hepatic expression of metabolic genes in SIV-infected female rhesus macaques

Background: Alcohol-related liver injury includes steatosis, fibrosis, and inflammation, which can culminate in alcoholic hepatitis and cirrhosis. The pre-clinical alterations in gene expression underlying these pathophysiological changes are ill-defined. Chronic binge alcohol (CBA) consumption produces marked alterations in metabolic processes and our studies show this is accentuated in chronic infection such as in HIV. This study tested the hypothesis that CBA disrupts expression of hepatic genes involved in glycolytic, gluconeogenic, and lipid turnover pathways in rhesus macaques infected with simian immunodeficiency virus (SIV). Methods: Female rhesus macaques were administered CBA (13-14g ethanol/kg/week, n=7) or vehicle (VEH, n=8) starting 3 months prior to SIV infection. All animals were treated with anti-retroviral therapy starting at 2.5 months post-SIV infection and sacrificed at 14.5 months and liver samples obtained for histological analysis, determination of gene expression by qPCR, triglyceride content by colorimetric assay, and pyruvate kinase activity by a colorimetric enzymatic assay. Results: Expression of lipid handling genes including perilipin 1, peroxisome proliferator-activated receptor γ (PPARγ), carbohydrate responsive binding protein (CHREBP), and acetyl-CoA carboxylase B were higher in CBA-treated compared to VEH-treated macaques. Expression of glycolytic (phosphofructokinase) and gluconeogenic (pyruvate carboxylase) enzymes including aldolase A was increased in the CBA group compared to VEH. No changes were observed in expression of the β-oxidation regulatory protein PPARα. Triglyceride content and pyruvate kinase activity were not significantly different between the groups. Conclusions: These results show significant CBA-mediated alteration of mRNA expression of lipid handling genes that could reflect increased lipid turnover despite lack of alterations in hepatic triglyceride content. Future studies will confirm the findings with protein expression of the differentially regulated genes and levels of non-esterified fatty acid in the liver. Supported by T32AA007577 & P60AA009803. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

MicroRNA-206 improves alcohol-mediated decreased myoblast differentiation

Background: With recent advances in antiretroviral therapy (ART), people living with HIV (PLWH) have a near-normal life expectancy but have higher risk for aging-related comorbidities, such as metabolic disorders and frailty earlier in life than the general population. At-risk alcohol use is twice as likely in PLWH compared to the general population and alcohol-related myopathy occurs in 40- 60% of people with alcohol use disorder. Previous studies demonstrated that in vivo chronic binge alcohol (CBA) administration in simian immunodeficiency virus (SIV)-infected male rhesus macaques decreased myoblast differentiation and downregulated microRNA-206 (miR-206) expression in skeletal muscle. We hypothesized that increasing miR-206 expression would increase differentiation in CBA-derived primary macaque myoblasts. Methods: Eight SIV-infected female rhesus macaques received either water (VEH) or CBA (13- 14 g/kg/week) for 14.5 months. Three months into either VEH or CBA administration, animals were vaginally infected with SIVmac251, and ART was started 2.5 months later. Animals were sacrificed after 9 months, and primary myoblasts isolated from vastus lateralis muscle 24 hours after the last dose of alcohol (blood alcohol=0 mM). Myoblasts at passage 4 (VEH & CBA) were proliferated for three days. Cells were then transfected with either miR-206 mimic or control (miR scramble). Four experimental groups were studied at day 5 of differentiation: VEH+scramble, CBA+scramble, VEH+miR-206, and CBA+miR-206. Expression of miR-206 was determined by qPCR. Myoblast differentiation was determined by myotube density, calculated as the average number of myotubes per frame, and fusion index calculated as the percentage of myonuclei that fused into myotubes. Results: In non-transfected CBA-derived cells, myotube density and miR-206 expression was lower compared to VEH-derived myotubes (p<0.001 and p<0.05, respectively). miR-206 transfection resulted in over 150-fold higher miR-206 expression compared to VEH-scramble (p<0.05) in CBA- and VEH-derived cells. miR-206 overexpression significantly increased myotube fusion index (p<0.05) compared to myoblasts transfected with miR scramble in CBA-derived cells. Conclusions: Data show significant improvement of alcohol-mediated decreased myoblast differentiation with miR-206 overexpression. These findings suggest that increasing muscle miR-206 can potentially be used as a therapeutic strategy to improve regenerative capacity in response to muscle injury or atrophy. (Supported by: T35AA021097, F30AA029358, P60AA009803, K01AA024494) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Cannabis use among cancer survivors before and during the COVID-19 pandemic, 2019-2021

We estimated the prevalence of past 30-day cannabis use, evaluated reasons for use, and identified individual-level factors associated with cannabis use among cancer survivors before (2019) and during (2020 and 2021) the COVID-19 pandemic. Cancer survivors, aged 18 years and older, were identified from the 2019 (n = 8185), 2020 (n = 11 084), and 2021 (n = 12 248) Behavioral Risk Factor Surveillance System. Prevalence of past 30-day cannabis use among survivors held steady through the pandemic (8.7%, 7.4%, and 8.4% in 2019, 2020 and 2021, respectively). Of those who used cannabis, 48.7% used it for medical reasons in 2019, 54.5% in 2020, and 43.5% in 2021. Survivors were more likely to report past 30-day cannabis use if they were younger, male, current or former tobacco smokers, and binge alcohol consumers and if they experienced poor mental health in the past 30-days. Our study identified subpopulations of cancer survivors that need to be targeted for evidence-informed discussions about cannabis use.

Alcohol Use Among Treatment-Seeking Individuals With Opioid Use Disorder.

Individuals in the United States with opioid use disorder (OUD) have high rates of co-occurring alcohol use disorder. However, there is limited research on co-use patterns among opioid and alcohol use. The present study examined the relationship between alcohol and opioid use in treatment-seeking individuals with an OUD. The study used baseline assessment data from a multisite, comparative effectiveness trial. Participants with an OUD who had used nonprescribed opioids in the last 30 days (n = 567) reported on their alcohol and opioid use during the past 30 days using the Timeline Followback. Two mixed-effects logistic regression models were used to assess the effect of alcohol use and binge alcohol use (≥4 drinks/day for women and ≥5 drinks/day for men) on opioid use. The likelihood of same-day opioid use was significantly lower on days in which participants drank any alcohol (p < .001) as well as on days in which participants reported binge drinking (p = .01), controlling for age, gender, ethnicity, and years of education. These findings suggest that alcohol or binge alcohol use is associated with significantly lower odds of opioid use on a given day, which was not related to gender or age. The prevalence of opioid use remained high on both alcohol use and non-alcohol use days. In line with a substitution model of alcohol and opioid co-use, alcohol may be used to treat symptoms of opioid withdrawal and possibly play a secondary and substitutive role in individuals with OUD substance use patterns.

Hepatic progesterone receptor membrane component 1 attenuates ethanol-induced liver injury by reducing acetaldehyde production and oxidative stress.

Alcohol-associated liver disease (ALD) is caused by excessive abuse of alcohol. One of the most representative causes of ALD is the action of acetaldehyde. Acetaldehyde is a toxic material produced when alcohol is metabolized through some enzymes, and it causes endoplasmic reticulum (ER) stress, mitochondrial dysfunction, and tissue injury. In this study, we assessed the relationship between Progesterone receptor membrane component 1 (PGRMC1) and ALD because PGRMC1 is expressed in the ER and mitochondria in the liver. Using the chronic and binge alcohol feeding models, we assessed acetaldehyde level, liver damage, alcohol-degrading enzymes, and ER stress. Compared with wild-type (WT) mice ethanol-fed Pgrmc1 knockout (KO) mice had higher levels of alanine aminotransferase (ALT) and alcohol-degrading enzymes, and Pgrmc1 KO mice had high serum acetaldehyde and ER stress levels compared with WT mice with control and ethanol feeding. Loss of Pgrmc1 increased acetaldehyde production through increased expression of alcohol dehydrogenase and catalase, which led to increased ER stress and suggested that cell death was promoted. In conclusion, it has been proposed that the loss of PGRMC1 could promote ALD and cause liver damage in alcohol-abusing humans.NEW & NOTEWORTHY Loss of Pgrmc1 increased acetaldehyde production, and excess acetaldehyde consequently increased ER stress, which activates apoptosis. Since low expression of PGRMC1 is vulnerable to alcoholic liver damage, the loss of PGRMC1 expression may increase susceptibility to ALD.

Weight Discrimination and Health Risk Behavior in Racial, Ethnic, and Sexual Minority Adults.

People with obesity face significant discrimination due to their weight. Exposure to such discrimination is associated with poor health outcomes. Little is known about pathways that explain that association, and even less is known about those pathways in racial, ethnic, and sexual minorities. Health risk behaviors may serve as one such pathway. We examined associations between weight discrimination and health risk behaviors and assessed whether associations are moderated by gender, race, ethnicity, or sexual orientation. Quota sampling was used to oversample Black (36%), Latino (36%), and sexual minority (29%) adults (n = 2,632) who completed an online survey. Using regression analysis, health risk behaviors (maladaptive eating behaviors, physical inactivity, sitting, smoking, alcohol use, and sleep disturbance) were predicted from previous experience with weight discrimination while controlling for demographic characteristics, BMI, and depressive symptoms. Additional analyses tested for interactions between weight discrimination and key demographic variables (i.e., gender, race, ethnicity, and sexual minority status). Weight discrimination was associated with greater emotional eating, binge eating, unhealthy weight control behaviors, cigarette smoking, problematic alcohol use, and sleep disturbance. Gender moderated the association between weight discrimination and binge eating, alcohol use, and physical activity, with stronger effects observed in men than women. Exploratory analyses provided limited evidence for differential effects of weight discrimination across specific combinations of intersecting identities. Weight discrimination was associated with engagement in unhealthy behaviors and relationships were largely similar across diverse demographic groups. Health risk behaviors may represent a key pathway through which weight discrimination harms health.

Negative and positive allosteric modulators of the α7 nicotinic acetylcholine receptor regulates the ability of adolescent binge alcohol exposure to enhance adult alcohol consumption.

Rationale and Objectives: Ethanol acts directly on the α7 Nicotinic acetylcholine receptor (α7). Adolescent-binge alcohol exposure (ABAE) produces deleterious consequences during adulthood, and data indicate that the α7 receptor regulates these damaging events. Administration of an α7 Negative Allosteric Modulator (NAM) or the cholinesterase inhibitor galantamine can prophylactically prevent adult consequences of ABAE. The goals of the experiments were to determine the effects of co-administration of ethanol and a α7 agonist in the mesolimbic dopamine system and to determine if administration of an α7 NAM or positive allosteric modulator (PAM) modulates the enhancement of adult alcohol drinking produced by ABAE. Methods: In adult rats, ethanol and the α7 agonist AR-R17779 (AR) were microinjected into the posterior ventral tegmental area (VTA), and dopamine levels were measured in the nucleus accumbens shell (AcbSh). In adolescence, rats were treated with the α7 NAM SB-277011-A (SB) or PNU-120596 (PAM) 2 h before administration of EtOH (ABAE). Ethanol consumption (acquisition, maintenance, and relapse) during adulthood was characterized. Results: Ethanol and AR co-administered into the posterior VTA stimulated dopamine release in the AcbSh in a synergistic manner. The increase in alcohol consumption during the acquisition and relapse drinking during adulthood following ABAE was prevented by administration of SB, or enhanced by administration of PNU, prior to EtOH exposure during adolescence. Discussion: Ethanol acts on the α7 receptor, and the α7 receptor regulates the critical effects of ethanol in the brain. The data replicate the findings that cholinergic agents (α7 NAMs) can act prophylactically to reduce the alterations in adult alcohol consumption following ABAE.