Background: Little is known about the effect of senescence on liver stress response in aging individuals who receive HIV treatment and consume alcohol. Methods: Senescence of HepG2 and AML-12 was induced by hydrogen peroxide (H2O2), and confirmed by examining senescence molecular makers of p16, p21, IGF-1, or SA-b-gal. The liver cells were treated with anti-HIV drugs Ritonavir (RTV), Lopinavir (LPV) and Darunavir (DRV), and ethanol, and were evaluated for cellular stress responses. Results: In non-senescent control cells, ethanol, RTV, LPV and DRV in combinations slightly increased expression of p21 or SA-b-gal. In senescent HepG2 or AML-12, ethanol and the anti-HIV drugs markedly increased p21 or SA-b-gal. There was no significant difference in IGF-1 expression between control and senescent cells. Expression of ER stress markers, GRP78 and CHOP, was suppressed by senescence. GRP78 and CHOP were upregulated by RTV and LPV in both control and senescent HepG2 cells, but the induction of CHOP by the drugs was less dramatic in non-senescent cells. In AML-12 cells, the drugs induced GRP78 only in control cells. Changes of potential senescence-associated factors including IP3R2, GRP75, PCSK9, Rab8, USP10, USP17, and USP20 were also detected. Basal IP3R2 was altered in the senescent cells and was further changed by RTV and LPV. GRP75 was upregulated by the drugs in both control and senescent cells. PCSK9 and USP10 were inhibited whereas Rab8, USP17 and USP20 were increased in the senescent cells by ethanol and the anti-HIV drugs. Conclusion: Senescent hepatocytes appear less sensitive to cellular stress responses. Alcohol and anti-HIV drugs promote cell dysfunction during senescence.

Alcohol use disorder (AUD) often co-occurs with alcohol-associated liver disease (ALD), yet the impact of liver dysfunction on alcohol consumption and cognition remains poorly understood. Given the bidirectional communication between the liver and brain, it is critical to study how liver pathology influences brain and behavior in relation to alcohol exposure. Here, we examined how chronic ethanol pre-exposure, aimed to induce liver pathology, influences subsequent alcohol voluntary intake and cognitive function in female C57BL/6J mice. Voluntary ethanol intake, measured using a 2-week two-bottle choice paradigm (TBC; 10E), and behavioral measures for spatial working memory (spontaneous alternation test) and recognition memory (novel object recognition test) were assessed in mice after pre-exposure to chronic ethanol via a Lieber-DeCarli liquid diet (LDC-E; 5E). Lieber-DeCarli diet with no ethanol was used as control (LDC-C). Experimental groups included: LDC-C followed with water consumption in TBC (LDC-C + Water), LDC-C followed with 10E in TBC (LDC-C + 10E), LDC-E followed with water in TBC (LDC-E + Water), and LDC-E followed with 10E (LDC-E + 10E). Liver steatosis was assessed using H&E and Oil Red O staining. Immunohistochemistry confirmed mild hepatic steatosis in the LDC-E group compared to LDC-C group at the end of the liquid diet exposure, which was reduced/eliminated by the end of the TBC paradigm. Mice administered LDC-E also consumed significantly more ethanol during the first week of TBC in LDC-E+10E group; this effect dissipated by week two. Following TBC, LDC-E+10E mice showed significant impairments in spatial working memory compared to control LDC-C+water, while recognition memory remained unaltered. These findings suggested that liver pathology induced by chronic ethanol exposure may contribute to cognitive deficits. However, the liver pathology was not sustained in the current experimental strategy and therefore did not allow us to fully capture the complexities of ALD-AUD interactions. This highlights the need for a refined approach to better elucidate mechanisms driving alcohol-related behavioral and cognitive changes. Understanding these interactions through the liver-brain axis will help in identification of new targets for ALD and/or AUD treatments.

Background: Greater parent-adolescent communication has shown to be a protective factor against youth substance use susceptibility, but the impact on susceptibility to new or emerging substances (e.g. oral nicotine products) is poorly understood. Methods: We used data from N=1,641 Southern California high school students (9th grade, ages 14-15) who completed the baseline survey (Spring 2024) of an ongoing prospective cohort study. Parent-adolescent communication was assessed via the validated Revised Parent-Child Communication Scale (RPACS), which includes two subscales assessing both the child’s perception of their parents’ communication and their own communication. Participants also reported their susceptibility to using oral nicotine products, nicotine pouches, e-cigarettes, cannabis edibles, cannabis vape products, and alcohol (separately by product). Analyses were restricted to participants who had never used any of the substances at baseline. We compared the risk of susceptibility to each substance across quartiles of each RPACS subscale using chi-square tests. Results: Students who scored in the highest quartile of the RPACS (both subscales) consistently reported lower risk of susceptibility than students in the lowest quartile for all substances. For example, for the parent items, susceptibility to oral nicotine products (ONPs) was 8.1% among students in the highest quartile of parent-adolescent communication, compared to 18.1% among students in the lowest quartile (p<0.001). A similar pattern was observed in the parent items for nicotine pouches (8.14% vs. 13.7%), e-cigarettes (10.1% vs. 15.6%), cannabis edibles (11.7% vs. 23.1%), cannabis vape products (8.8% vs. 13.3%), and alcohol (28.0% vs. 48.3%) (ps<0.001). Associations were similar for the child communication subscale for all substances (ps<0.001). Conclusion: Findings suggest that greater perceived communication between adolescents and their primary caregiver may be a protective factor against substance use across a range of nicotine, alcohol, and cannabis products.

A significant proportion of people experiencing homelessness (PEH) live in/near Skid Row in Los Angeles. Despite being a “resource rich” area, major health disparities among people who access services persist. These include high prevalence of mental and physical comorbidities and substance use disorders. We hypothesize that the risk of negative health outcomes may be higher based on intersectional gendered risks and housing insecurity. We aimed to understand factors associated with difficulty accessing basic needs and health status among people who access services on Skid Row. We surveyed 101 participants in June 2024 at a community site in the Skid Row area in Los Angeles, California (n=101). Inclusion criteria were: 1) receiving services at this site and 2) 18+ age. We conducted an exploratory factor analysis (EFA), using the maximum likelihood (ml) method, to find key themes prevalent in the sample. Variables meeting the loading threshold for a factor were used to construct index scores for these themes. We then regressed these scores on respondent demographic variables (age, sexual orientation, race, education, and violence) and our key variables of interest: gender and housing status, to examine differences in our indices by these key characteristics. We also performed sub-analyses by gender to understand whether other measures, like exposure to violence, contributed significantly to our findings. The final EFA retained 4 factors and had a Tucker-Lewis index of 0.962. 3 factors had at least 4 questions with a loading of 0.35 or more and were used to construct 3 index scores: health status, difficulty accessing basic needs, and substance use. In a multivariate regression, being unhoused and being forced to move by government or sanitation was significantly associated with difficulty accessing basic needs. Having no access to medical care, being discharged before medical needs were fully addressed, and exposure to violence were all significantly associated with poorer health status. Among women, exposure to violence was strongly associated with reporting poorer health status but was not significant in a sub-analysis of men (p<0.001). PEH have poorer access basic needs. For women, exposure to violence was the strongest indicator of poorer health status. Existing basic needs interventions in Skid Row may be improved by improving access to safe, permanent housing and reducing violent victimization among women.

Fentanyl within the illicit drug supply has led to changes in severity, onset, and frequency of opioid withdrawal. Withdrawal symptoms are debilitating physically (severe pain, immobility) and psychologically (dysphoria, psychosis). Withdrawal management is especially critical among community samples of people who use drugs (PWUD) who are socially disadvantaged. In this study we analyzed cannabis co-use for opioid withdrawal management among a community sample of PWUD in two states that have legalized cannabis use for recreational and/or medical purposes. We recruited 472 PWUD from community settings in Los Angeles, California and Denver, Colorado during 2021-22. Inclusion criteria were: ≥ 18 years of age and self-reported injection drug use and opioid use (classified via use of heroin, fentanyl and/or prescription opioids). We collected data on cannabis use frequency and cannabis use intent (i.e. for opioid withdrawal management) in the last three months. We used linear regression and one-way ANOVA analyses to examine associations between cannabis use, opioid use and withdrawal along with subgroup multiple regression analyses to examine the effects of fentanyl and heroin use type (injected, smoked, or mixed use). In the past three months, 355 (77.34%) PWUD used cannabis. 350 (74.15%) reported opioid withdrawal. Higher cannabis use was associated with higher frequency of opioid withdrawal (p=0.035) but not overall opioid use (p=0.0742). Overall opioid use did not significantly differ between PWUD not using cannabis, PWUD using cannabis with intent of managing opioid use and those using cannabis with no such intention (p=0.154). Opioid withdrawal frequency significantly differed between those not using cannabis, those using cannabis not to manage withdrawal and those using cannabis with the intent of withdrawal management (p=0.03377). Among those PWUD using cannabis with the intent to manage withdrawal, pairwise comparisons indicate significantly higher withdrawal frequency compared to those not using cannabis at all (p=0.04355). Higher opioid withdrawal pain was also associated with more frequent cannabis use (p=0.00634). Our findings support existing trends that cannabis co-use varies with opioid withdrawal frequency and pain among PWID, especially when used with the intent of withdrawal management. More longitudinal data is needed understand how cannabis co-use affects withdrawal frequency and pain.

Refugees are forcibly displaced from homelands due to war, conflict, and climate disasters and live in encampment settings due to the large influx of displaced people, lack of alternative housing and immediate assistance. In contrast, the US housing crisis is driven by a widening wealth gap, housing shortage, and systemic inequalities. People experiencing homelessness (PEH) in the US often live in encampments due to the sense of community and safety, however, are routinely displaced due to encampment “sweeps”. This review compared infectious disease status and mortality between refugees and PEH in encampment settings after experiencing a forced displacement event. We searched 3 electronic databases (PubMed, Embase, and Scopus) in February 2025. No time restrictions were placed, and search terms were constructed using key words. Searches within the title, abstract or keywords across all databases included 3 concepts. [1] Forcibly displaced: “refugee”, “encampment sweep”, “encampment abatement”, “encampment removal”, [2] Communicable Disease: “infectious disease” and “communicable disease” and [3] “All-Cause Mortality”. PEH in the US, were majority male (62.12%) compared to female (35.86%) while refugees had nearly equal males (53.3%) and females (46.65%). Ages ranged between 18-60+ years (PEH) and 0-87 years old (n=13) among refugees. Among refugees, crude mortality rate ranged from 0.22 to 89 per 1000 (n=6) compared to US PEH, which did not have data on displacement and mortality. Among US PEH, infectious diseases included HIV/AIDS (n=2), HCV (n=1), and bacterial infections, TB, Flu, or pneumonia (n=1) compared to refugees reported mainly respiratory infections (n=7), diarrheal disease (n=9), fever (n=4), measles (n=3), and cholera (n=3). A notable difference between groups were high rates of substance use (n=4) among US PEH. Both refugees and PEH experienced overcrowded, temporary unsanitary settings with lack of access to health care and potable water. While refugees experienced a singular forced displacement event, PEH in the US experienced repeated sweeps. Sweeps resulted in increased substance use, medication loss, worsening mental health, and disrupted continuity of care, limiting street medicine and social services in their care delivery. Refugees experienced disruptions in vaccination programs and isolation due to limited integration options and language barriers.

Neuroinflammation resulting from excessive ethanol consumption contributes to several CNS pathologies, including neurodegenerative diseases and alcohol-associated brain injury. Microglia play a central role in mediating these inflammatory processes. The purpose of this study is to investigate the therapeutic potential of dihydromyricetin (DHM), a bioactive polyphenolic compound, in modulating microglial polarization and mitigating ethanol-induced neuroinflammatory damage. Using BV2 cells as an in vitro model, we assessed the hypothesis that DHM attenuates ethanol-induced microglial activation by promoting a shift from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype. Specifically, we wanted to see whether DHM would prevent and or reverse microglial polarization, and therefore inflammation. BV2 cells were cultured and treated with ethanol (20 and 50 mM) and lipopolysaccharide (LPS; 200 ng/mL) to induce neuroinflammatory activation. To assess the ability of DHM to prevent microglial M1 polarization, cells were pretreated with DHM (10 and 30μM) for 6 hours prior to 24-hour EtOH and LPS exposure. Conversely, to assess DHM’s ability to reverse EtOH induced inflammation, DHM was applied for 6 hours after 24-hour EtOH and LPS exposure. Treatment conditions were optimized based on cytotoxicity assays, which determined the IC50 of DHM to be 64.84 µM at 6 hours. Microglial polarization was assessed using qRT-PCR to quantify the markers of M1 (iNOS, TNF-alpha, IL-1 beta, IL-6) and M2 (Arg-1, IL-10, CD206) phenotypes. Initial studies suggest a dose-dependent response, with DHM potentially shifting microglia toward an M0 phenotype and reducing M1 polarization, as indicated by decreased proinflammatory gene expression. These early findings highlight DHM’s potential to modulate microglial polarization and mitigate alcohol-induced neuroinflammatory damage. By shifting microglia away from a pro-inflammatory state, DHM may help preserve neuronal function and reduce neurodegeneration, ultimately contributing to improved cognitive and behavioral outcomes in alcohol use disorder patients. Ongoing investigations are focused on further elucidating the role of DHM role in promoting M2 polarization.

Introduction: Individuals with elevated depression symptoms experience lower positive affect, and higher negative affect and cognitive dysfunction. Affective and cognitive effects also occur during cigarette abstinence. This study examines the real-time associations of depression symptom levels with affect and cognitive dysfunction during a cigarette quit attempt. Method: Adult people from California with daily cigarette smoking (n=209, 49.28% female, 50.00% White) completed a baseline assessment, including measures of depression symptoms. Participants completed 28 days of daily diaries and started a quit attempt approximately one week after starting the daily diaries. Every morning participants reported prior day cigarette abstinence, affect (positive and negative), and cognitive dysfunction. Results: Individuals with elevated depression symptom levels reported lower positive affect, higher negative affect, and greater cognitive dysfunction during the quit attempt. There was also a significant interaction of depression symptom levels and prior day cigarette abstinence with negative affect. Prior day cigarette abstinence (vs. prior day cigarette non-abstinence) significantly increased negative affect in individuals with low depression symptom levels, but did not significantly associate with negative affect in individuals with elevated depression symptom levels. Conclusions: Findings highlight the differential impact of cigarette abstinence on affect and cognitive function, emphasizing the need for tailored smoking cessation strategies for individuals with elevated depression symptoms.

Background: Use of new commercial oral nicotine products (ONPs), with diverse flavors, product types, and nicotine strengths, is rising among young adults. However, research on how these factors interact to influence appeal and sensory experience is limited. In this laboratory experiment of young adults who use e-cigarettes, we assessed ONP sensory and appeal characteristics based on ONP type (pouch vs. gum) and nicotine strength (high vs. low), with a focus on fruity and minty flavor varieties. Methods: Twenty-six young adults (21-29 years of age) who use e-cigarettes participated in a within-subject, double-blind study in which they were randomly assigned to sample 4 ONPs and rate sensory (e.g., sweetness, coolness) and appeal (e.g., liking, disliking) attributes across four product categories (2×2 factorial design): gum vs. pouch and low vs. high nicotine strength (2mg vs. 8mg). Participants sampled fruity (e.g., mango) and minty (e.g., wintergreen) flavors and rated each ONP using a 100-point Visual Analogue Scale after sampling each product for 5 minutes. Results: Ratings for “liking” were directionally higher (though not statistically significant) for gums over pouches (61.6 vs. 51.7; F(1,22=1.36, p=.23), and higher for low nicotine strength over high nicotine strength products (62.7 vs. 50.6; F(1,22)=2.06, p=.17), as well as for minty versus fruity flavors (61.0 vs. 52.3; F(1,22)=2.83, p=.11). In repeated measures ANOVA assessing subjective sweetness, greater divergence was observed for fruity versus minty gums (82.6 vs. 54.9) compared to fruity versus minty pouches (42.3 vs. 40.9); interaction: F(1,22)=8.56, p<.01. Similarly, for subjective coolness, ratings diverged more for fruity versus minty gums (20.0 vs. 74.9) than for fruity versus minty pouches (43.2 vs. 56.6); interaction: F(1,22)=14.12, p<.001. Conclusion: This study provides crucial insights into ONP user preferences among young adults. Notably, subjective flavor differentiation may be diminished in pouches compared to gums, perhaps due to intermittent chewing of gums, which may enhance flavor release. As ONP use continues to rise, particularly among young adults, understanding these factors is critical for developing informed regulatory policies to reduce nicotine use among this population.

Background: Oral nicotine products (ONPs) are novel and emerging products among youth. However, youth’s beliefs about these products are unknown. Aim: To examine youth’s beliefs about ONPs and assess whether these beliefs differ by past 30-day (P30D) e-cigarette use, gender identity, and race/ethnicity. Methods: Data were collected in Fall 2023 from 11th and 12th grade students in Southern California participating in a cohort study (N=3299). We examined participants’ thoughts about ONPs (18 items) overall and by P30D e-cigarette use, gender identity (Male, Female, Other gender), and race/ethnicity (Hispanic, NH White, Asian, All other races). Bivariate logistic regression was used to test for differences in each belief in the stratified analysis (i.e., P30D e-cigarette use, gender identity, and race/ethnicity). Results: The most common beliefs about ONPs were that they “can be used without other people knowing” (24.8%), “a lot of people consume ONPs” (24.6%), “are easier to hide or conceal” (24.4%), “are more socially acceptable than smoking or vaping” (20.2%), come in appealing flavors” (20.1%), and “have attractive advertisements” (19.6%). Youth with P30D e-cigarette use (vs. no use) were more likely to agree (vs. not agree) to all 18 ONP beliefs (ps<0.05 with two exceptions). Significant differences (p-value<0.05) were noted for endorsing the following types of beliefs by gender identity (peer influence [15.6% vs. 22.3% vs. 20.2%], concealability [23.2% vs. 24.1% vs. 33.0%], flavorings [15.1% vs. 23.0% vs. 28.0%], social acceptability [19.0% vs. 20.4% vs. 24.9%], and perceived health benefit [6.7% vs.9.0% vs. 14.4%]), and race/ethnicity (peer influence [23.6% vs. 25.6% vs. 11.8% vs. 20.8%], and decreased harm perception [2.4% vs. 8.5% vs. 4.9% vs. 9.2% ]). Conclusion: About 20-25% of youth endorsed beliefs about ONPs (i.e., concealability, peer influence, flavorings, and attractive advertisement). Youth with P30D e-cigarette use were more likely to agree with nearly all ONP beliefs. Beliefs about peer influence, concealability, flavorings, decreased harm perception, social acceptability, and perceived health benefit differed by gender identity or race/ethnicity. Implications: ONP advertisements and flavorings are potential targets for regulation among youth. Peer influence, ONP concealability, advertisements, and flavorings are critical areas for further research and intervention to prevent ONP use.

The legalization of cannabis for recreational sale and possession in the US has raised concerns about products that contain elevated levels of delta-9-tetrahydrocannabinol (THC), or high potency THC products. Frequent use of these products, especially among young adults has been linked to negative outcomes such as increased risk for cannabis use disorder, early onset of psychosis, and adverse psychological effects like anxiety and paranoia. High potency THC products are widely available in recreational cannabis dispensaries, with cannabis flower now averaging over 20% THC, and ultra-concentrated products, like oils and concentrates, reaching up to 99% THC. Additionally, reports of inflated THC levels suggest that cannabis companies list higher THC concentrations as a marketing strategy. Consumer demand for these products continues to rise, as past studies have found that many believe they offer a “better high,” despite the associated risks. While existing literature has explored consumer preferences, none has examined how frontline cannabis dispensary staff (i.e., budtenders) sell high potency THC products or provided detailed insights into consumer motivations for purchasing them. The present mixed methods study explores the purchasing and selling behaviors associated with high potency THC products in a mock cannabis retail dispensary. Twenty budtenders and 60 young adult cannabis users took part in separate semi-structured interviews focused on the general selling and purchasing behaviors of cannabis products in a mock dispensary. Interview and survey data related to high potency THC products were selected for data analysis. Survey data revealed that 62% of young adult participants consider THC percentage important when making purchasing decisions, 41% buy high potency THC products for their value, and 72% are at least somewhat confident in the accuracy of labeled THC concentrations. Thematic analysis of the interview data identified key themes related to budtender views on high potency THC products, their selling methods, and consumer motivations for purchasing these products. The findings provide valuable insights into the discussion surrounding high potency THC products, both from budtenders’ and consumers’ perspectives, as well as how these products are marketed and sold in retail dispensaries. This study could help inform policymakers as they develop strategies to reduce the potential harm associated with high potency THC products.

Background: Election stress is linked to greater distress and substance use in adults, but its impact on high school students is understudied. Methods: Data were collected from 2,150 10th grade students enrolled in a prospective cohort study in Southern California, who completed the survey either before (Sept. 19-Nov. 5, 2024) or after (Nov. 6, 2024-Jan. 2, 2025) the U.S. presidential election. Election stress was defined as the presence of at least one of six stress-related emotions (yes vs. no). Logistic regression models tested the association of demographic characteristics (race/ethnicity, gender identity, and sexual orientation), anxiety and depression symptoms, and past 30-day use of nicotine, cannabis, and alcohol with election stress, adjusting for sociodemographic characteristics. Results: Overall, 31.0% of participants reported any election stress prior to the election, rising to 44.3% after the election. Pre-election stress was more prevalent among white (vs. Asian) participants (39.7% vs. 29.2%; OR=1.82; 95% CI: 1.17, 2.83), among females (36.5%; OR=1.63; 95% CI=1.24, 2.14), and gender minority individuals (65.1%; OR=4.07; 95% CI=1.81, 9.17) vs. male youth (21.7%), and among bisexual (54.9%; OR=2.43; 95% CI=1.60, 3.69), gay/lesbian (55.9%; OR=3.07; 95% CI=1.40, 6.69), and questioning (48.3%; 2.19 OR; 95% CI: 1.005, 4.76) youth (vs. heterosexual; 26.3%). Post-election stress was elevated among individuals for all races/ethnicities with no significant differences observed. Females (55.6%) and gender minority individuals (76.2%) also had greater post-election stress (vs. males; 28.8%) (OR range=2.62-4.30; p<0.05). Similarly, bisexual (76.7%; OR=3.63; 95%CI=1.84, 6.80), gay/lesbian (78.3%; OR=5.69; 95% CI=1.89, 17.13), and questioning (90.0%; OR=10.54; 95% CI=2.31, 48.03) youth had greater post-election stress than heterosexual youth (38.1%), with stronger associations observed post-election. Election stress was more common in participants with (vs. without) clinical/subclinical depression symptoms pre-election (1.49 OR, 95% CI: 1.09-2.04) and post-election (1.68 OR, 95% CI: 1.13-2:50). No association was observed for anxiety and past 30-day substance use. Conclusion: Findings highlight that election-related stress increased after the result of the 2024 U.S. Presidential Election was announced. Stress (especially post-election stress) was disproportionately higher for females, gender minority, and sexual minority youth.

Alcohol use disproportionately impacts individuals with multiple marginalized identities (MMIs), including racial/ethnic and sexual/gender minorities, due to compounded experiences of discrimination. Studies have consistently shown that individuals with intersecting identities are at higher risk of substance use disorders due to the cumulative effects of racial discrimination, social exclusion, and economic instability. Despite the critical role of resilience in mitigating health disparities, its moderating effect on discrimination-related alcohol use remains underexplored. This study examined how resilience and intersecting marginalized identities influence the relationship between discrimination and alcohol use. We hypothesized that (1) individuals with MMIs would experience greater discrimination and alcohol use than those with fewer marginalized identities, and (2) resilient coping would moderate these associations. Participants (N = 506; M age = 33.59, SD = 11.90, range = 18-83) were primarily women (54%), with 20% reporting no or low marginalized identities, 63% reporting a single marginalized identity, and 17% reporting multiple marginalized identities. A one-way ANOVA revealed significant group differences in daily discrimination, major discrimination, and alcohol use based on marginalized identity. Respondents with MMIs reported significantly higher levels of daily discrimination, F(2, 503) = 8.11, p less than .001, and major discrimination, F(2, 503) = 4.37, p = .01, compared to those with either no/low or single marginalized identity. For alcohol use, participants with no/low marginalized identity reported significantly higher alcohol use scores than those with a single marginalized identity, though there was no significant difference between the no/low group and the MMI group, F(2, 503) = 5.14, p = .003. Stratified regression analyses show that experiences of major discrimination are significantly and positively associated with higher levels of alcohol use among individuals with single marginalized identity (b =0.16, p=.03) or MMIs (b =0.28, p=.04), but not among those with no/low marginalized identities -providing support for our hypothesis. Additional analyses will be conducted to examine the potential moderating effect of resilience on the relationship between discrimination and alcohol use.

Background: Acculturation influences substance use behaviors, yet its role in shaping cannabis-related attitudes and behaviors among young adults is understudied. Prior research suggests that first and second-generation immigrant youth report lower substance use rates than later generations; a trend known as the “immigrant paradox”. However, findings specific to cannabis are mixed. This study examines how acculturation relates to cannabis use and perceptions across generational groups. Methods: A cross-sectional survey assessed cannabis behavior, perception, and cultural background of young adults (ages 18-30) in Los Angeles County. Acculturation was measured via nativity, cultural identity, residential status, and language. Outcomes included cannabis use (lifetime, age of initiation, past 3-month use) and perceptions (perceived benefits/risks, and personal vs. family views on cannabis and related policies). Descriptive statistics, t-tests, and one-way ANOVAs examined associations among generational status, cannabis outcomes, and acculturation. Results: Respondents (N=169; Mage = 22.5) were mostly female (60.6%), with the largest racial/ethnic groups being Hispanic/Latino (35.2%) and White (34.8%). Generational status: 18.9% foreign-born, 57.4% first-generation, and 23.7% second-/third-generation. Lifetime cannabis use differed significantly by generation (χ²(2)=13.09, p=.001), with use increasing across groups: 61.9% (foreign-born), 71.3% (first-gen), and 97.4% (second-/third-gen). Generational status predicted self-perception of cannabis (F(2,134)=10.40, p<.001), with second-/third-gen participants reporting more favorable views than foreign-born (p<.001) and first-gen (p=.010). Across groups, participants viewed cannabis more positively for themselves than their families did (t=12.74, p<.001). Acculturation scores varied significantly: second-/third-gen participants reported higher assimilation than foreign-born (p=.005), while foreign-born participants scored higher on separation than both first-gen (p=.040) and second-/third-gen (p=.004). No significant differences were found in integration scores. Further analyses will examine additional relationships among key variables. Conclusion: Acculturation, particularly generational status, is significantly associated with cannabis use and perceptions. Findings emphasize the importance of cultural context in shaping substance-related attitudes and can inform culturally responsive public health strategies.

Background: Adolescents who feel isolated as a result of their identity may be at increased risk for substance use. Methods: Data are from 11th and 12th graders from the Southern California ADVANCE cohort study, collected at baseline (Fall 2023) and follow-up (Spring 2024) across 11 public high schools (N = 2,737). Participants reported frequency (never, rarely/monthly, weekly/daily) of feelings of isolation related to some aspect of their identity (e.g., race/ethnicity, sexual identity, etc.) at baseline, and whether they had used e-cigarettes, cannabis, or alcohol in the past 6 months (yes/no) at baseline and follow-up. Logistic regression models were used to evaluate the association of isolation at baseline with substance use at baseline and follow-up, adjusting for sociodemographic characteristics. Results: Overall, 31.8% of participants reported feeling isolated rarely or monthly, while 7.0% reported experiencing isolation on a weekly or daily basis. In cross-sectional analyses, substance use was generally more prevalent among those who reported greater levels of social isolation. For exaample, past 6-month e-cigarette use was 11.6% among those who felt isolated weekly or daily compared to 5.5% among those who never felt isolated (OR=2.07; 95%CI=1.33, 3.63). Similar patterns were observed for vaping cannabis (13.2% vs. 5.7%; OR=2.21; 95%CI=1.33, 3.63), smoking cannabis (13.2% vs. 5.5%; OR=2.20; 95%CI=1.35, 3.69), consuming cannabis edibles (11.6% vs. 4.7%; OR=2.13; 95%CI=1.25, 3.61), and alcohol use (23.2% vs. 13.7%; OR=1.66; 95%CI=1.13, 2.47). Longitudinal data revealed similar trends, where social isolation at baseline was associated with greater odds of substance use at follow-up. Individuals who reported weekly or daily isolation (compared to no isolation) had about twice the odds of reporting e-cigarette use in the past 6 months at follow-up (9.0% v. 4.5%; OR=2.14; 95% CI=1.19, 3.86), vaping cannabis (10.0% vs. 5.4%; OR=1.96; 95% CI=1.12, 3.44), and smoking cannabis (8.4% vs. 4.7%; OR=2.05; 95% CI=1.13, 3.72). Conclusion: Findings highlight that identity-based isolation may be a critical risk factor for substance use among adolescents.

Introduction: Simultaneous use of Ethanol (Et) and antiretroviral human immunodeficiency virus (HIV) drugs has been on the rise in people living with HIV; this has been linked to endoplasmic reticulum (ER) stress and protein unfolding. The SET protein, a chaperone protein primarily in the rough ER, is involved in the unfolded protein response and may be involved in increased vulnerability to HIV for people living with HIV and using Et and antiretroviral drugs. The aim of this study is to investigate the effect of Et and antiretroviral drugs on SET and X-box binding protein 1(Xbp1) proteins. Methods: Primary human hepatocytes (PHH) and primary human peripheral blood mononuclear cells (PBMC) were treated with Et (50/100 mM) along with Rotinivar (RTV), Lopinavir (LPV), Darunavir (DRV), or Dolutegravir (DTG) at 25 micrograms/mL. Each treatment was repeated 3 times within a trial and repeated 2-3 times. SET protein expression and ER stress (via Xbp1) were assessed by Western blot and reverse transcription-polymerase chain reaction (RT-PCR). HIV infectivity was measured via an HIV-1 pseudovirus with a luciferase reporter. Statistical analysis of results included student’s t-test (2-groups) or ANOVA (over 2 groups); significant results were defined as p < 0.05. Results: Exposure of PHH and PBMC to Et and antiretroviral drugs resulted in greater expression of the Xbp1 protein and SET proteins than independent exposure and control. RT-PCR revealed greater expression of spliced Xbp1, but no significant increase was found in the expression of SET mRNA. Within PBMCs exposed, SET expression increased in the cytosol; however, this was not the case in the nucleus. Greater SET expression was correlated with greater HIV expression. The introduction of metabolic inhibitors diallyl sulfide, aldehyde dehydrogenase 2, Vitamin C&E, and sodium phenylbutyrate showed decreased SET and HIV expression as compared to Et/drug treatment alone, except peptidyl SET inhibitor increased expression. Conclusion: The results suggest that congruent exposure of PHH and PBMC to EtOH and HIV antiretroviral drugs may facilitate HIV infection potential by exacerbating endoplasmic reticulum stress and SET expression in the cytosol.

Significance: Although use of commercial oral nicotine products (ONPs) has been increasing among young adults (YAs), there is limited research on ONP attitudes. This study examines ONP attitudes among YAs prior to and after sampling these products. Methods: YAs (aged 21-25, N=26) who vape (n=18), smoke (n=1), or dual use both products (n=7) self-administered different flavors of ONPs (gums or pouches, with low or high nicotine concentration). Both prior to, and after self-administration of the products, participants completed an ONP attitude questionnaire with 13 positively worded statements about ONPs. An ONP positive attitude composite was scored as the number of agreements minus disagreements. Pre- vs. Post-consumption ONP attitudes were compared by paired t-test. Results: Prior to use of study ONPs, participants expressed somewhat favorable attitudes (M=5.46, SD=4.64). Subsequent to study use we observed a marginally significant increase in positive ONP attitudes (M=6.77, SD=4.35; t(25) = 1.87, p = .07). Conclusion: Results are suggestive that after sampling ONPs, attitudes towards ONPs may become more favorable. As more data become available, we will 1) assess these results in a larger sample, and 2) investigate how the attributes of the product characteristics (nicotine concentration, flavor, product category), as well as participant characteristics moderate the impact that product exposure has on ONP attitudes.

Background: Ketamine, an NMDA antagonist, exerts dose-dependent effects on neural activity. However, little is known about its impact on the brain at non-therapeutic doses. Previously, our group has reported that a supra-anesthetic dose of ketamine can robustly induce polypopulation spikes (PPS), a highly regular and paroxysmal train of synchronized neural activity resembling interictal spikes. This previous study was limited to local field potential (LFP) recordings in the somatosensory and motor cortex. Therefore, the spatial distribution of PPS in other brain regions is unknown. Given the recent surge in the recreational use of ketamine for its dissociative properties, there is a strong need for characterizing this drug at non-therapeutic doses, such as the PPS phenomenon. Electrophysiology provides high temporal resolution but is limited by sparse spatial coverage. FUSI is a recently developed neuroimaging modality whose strengths, such as high spatial resolution and coverage (100 µm and 10x10cm), complement these limitations. As such, integrating these modalities is promising for characterizing the spatiotemporal patterns of PPS across the entire rat brain. Methods: Six female Sprague Dawley rats (10-14 weeks old, 200-300g) were anesthetized with intraperitoneal (i.p.) injection of ketamine (75 mg/kg) and xylazine (10mg/kg). The animals were fixed onto a stereotactic frame. A bipolar electrode was then implanted in the right S1 and the fUSI probe was placed to cover various cortical and subcortical regions. Simultaneous recordings began after the implantation was completed, during which additional doses of ketamine (36 mg/kg) were administered i.p. at the 2- and 12- minute marks. Results: Consistent with previous studies, supra-anesthetic doses of ketamine-induced a prolonged period (> 20 minutes) of frequent PPS episodes. A time-varying impulse response model was used to identify the dynamic mapping of PPS to fUSI. The explained variance map indicates that the PPS is distributed in the thalamocortical network. Furthermore, PPS may initiate in the thalamus and spread to the cortical regions. However, the timing of PPS eventually synchronizes over time across regions. Discussion: Our findings suggest that a non-therapeutic dose of ketamine induces an abnormal state in the corticothalamic network that manifests as PPS. Given the role of this network in consciousness and sensory gating, PPS may be a novel biomarker of dissociation at this dosage level.

Introduction: People who use drugs (PWUD) typically manage several co-morbid medical conditions. PWUD often receive paternalistic and stigmatizing medical care for medical conditions associated with drug use such as abscesses and injection related infections. Medicalized frameworks of addiction, such as the disease model, pathologize some patients and behaviors including injection drug use, illicit opioid use, delaying or self-discharging from treatment as “high-risk”. Examining how PWUD negotiate risk, prioritize, and strategize daily use routines using embodied processes such as self-monitoring and self-tracking provides insight into the complex decision making involved in navigating substance use, illness/injury and structural vulnerability. Methods: We conducted 30 semi-structured 1:1 interviews at 3 community sites in Los Angeles, California, U.S. We analyzed this qualitative data using constructivist grounded theory. Inclusion criteria were injection drug use, opioid and cannabis use, English fluency, and age 21 years+. Results: We characterized self-monitoring as a process of awareness and attunement into one’s symptoms and physical sensations whereas self-tracking is a comparative process that extends over a period of time and relied on self-monitoring. Our findings show that: 1) PWUD used opioids and cannabis to self-medicate symptoms of co-morbid health conditions while navigating complex structural vulnerabilities such as housing insecurity and material hardship 2) Participants tracked symptoms of their injury/illness along with physical and emotional responses to the substances they were using. This included a) self-monitoring and self-tracking symptoms from illness b)sSelf-monitoring and Self-tracking symptoms before and after substance use and 3) PWUD developed self-management routines informed by self-tracking information to meet their health needs. Discussion: Contrary to descriptions of ‘chaotic’ drug use, participants described tracking symptoms and use modification, goal-setting, and routine adherence to manage their comorbid conditions. Our findings challenge dominant narratives of chaotic drug use by illustrating the logics and processes that inform daily drug use routines and the ways in which they are embedded within the social structural contexts.

As of 2024, there were approximately 15,000 dispensaries across the U.S for medicinal and/or recreational cannabis. Recreational cannabis alone amassed 32 billion dollars in sales in 2024, indicating a demand for cannabis from regulated retail outlets. High frequency of use, however, is associated with adverse physical, mental, and interpersonal consequences. Behaviors that may reduce an individual’s experience of cannabis related consequences, or protective behavioral strategies, are harm reduction techniques that are used before, after, or during use. Although consumers often seek and receive advice from cannabis dispensary staff during visits to dispensaries, it is unclear which, or if, staff present customers with harm reduction strategies in these retail cannabis environments. In this mixed methods study, we investigated the harm reduction messages and strategies that retail dispensary staff (i.e., “budtenders”) may present to customers during their interactions. Twenty budtenders and 60 young adult cannabis users participated separately in semi-structured interviews in a mock dispensary environment to discuss their cannabis selling and purchasing behaviors. As in prior literature, most young adults (72%) reported learning about products in dispensaries by asking budtenders about them and/or for recommendations, and 48% found budtender recommendations at least moderately important when deciding to buy a cannabis product. Using thematic analysis and survey data, harm reduction themes relating to sales methodology, advice about use behavior, and establishing budtender-customer relationships emerged among the budtenders. Young adult interviews revealed themes related to their purchase selections. These results can help researchers and policymakers better understand harm reduction messaging within retail cannabis environments. Doing so can help address potential misinformation related to harm reduction and identify content areas that can be enhanced for the creation of future trainings and science-based educational materials to help consumers implement harm reduction strategies that will work best for them when choosing to use cannabis.

Nicotine pouches, containing nicotine salts and flavoring rather than tobacco leaf, entered the U.S. market in 2016 and are among the fastest-growing tobacco product categories nationally and globally. Despite their growing market share and popularity, there is a lack of studies focused on nicotine pouch use among school-aged students including use by geography (e.g., level of rurality). We conducted a cross-sectional survey of middle and high school students in Kentucky (n=3,167) between September 2023 and April 2024 (grades 4-12, mean age: 13.52, SD=1.55). Data were collected as part of a statewide tobacco/vaping prevention program. Students from 66 of the 120 counties in KY were included. We examined lifetime nicotine pouch use, and conducted logistic regression with robust standard errors to examine county level of rurality (quartiles of the index of relative rurality (IRR)), cigarette use, cohabitation with tobacco users, susceptibility to e-cigarette use, and sociodemographic variables as correlates of ever use. Overall, 4.69% of participants (n = 226) had ever used a nicotine pouch. Correlates of lifetime nicotine pouch use included being male vs. female (OR: 1.54, 95% CI: 1.03-2.30), ever using cigarettes (OR: 6.77, 95% CI: 4.17-10.99), ever using e-cigarettes (OR: 3.12, 95% CI: 2.23-4.37), increasing age (OR: 1.17, 95% CI: 1.01-1.36), being AI/AN (OR: 2.65, 95% CI: 1.15-6.12) or other races (e.g., NH Asian, NH multiracial, etc) vs NH White (OR: 2.73, 95S% CI: 1.11-6.72), and whether participants lived with someone who uses tobacco (OR: 2.02, 95% CI: 1.34-3.06). Living in a county that was more rural based on quartiles of the IRR compared with the most urban counties was associated with higher odds of ever using nicotine pouches (Q3 vs. Q1 OR: 1.81, 95% CI: 1.04-3.16; Q4 vs. Q1 OR: 2.33, 95% CI: 1.31-4.13. Several individual risk factors for nicotine pouch use among Kentucky youth suggest patterns that mirror other smokeless tobacco products, including living in a more rural area, being male and older age. Using cigarettes or e-cigarettes was also a risk factor. Increased odds of lifetime use among AI/AN and youth of other races (e.g., Asian, other pacific islander) may contribute to disparities in tobacco use for these groups. The increasing popularity of nicotine pouches among Kentucky youth underscores the need for targeted prevention efforts particularly in rural communities.

Background: The cannabis use rate is increasing among adolescents, raising public health concerns. Adolescents with Generalized Anxiety Disorder (GAD) or Major Depressive Disorder (MDD) tend to use Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) more, yet early cannabis use may impact emotional regulation and contribute to mental health issues. However, little is known about cannabis preferences among adolescents with mental health disorders. Objectives: To examine (1) whether adolescents with GAD or MDD are more likely to use THC (smoking, vapes, edibles/drinks) over CBD products and prefer vapes to smoke and edibles/drinks for faster symptom relief; (2) how sex at birth and race/ethnicity moderate these relationships. Method: This cross-sectional study collected 3049 11th-12th graders from 11 Southern California schools in spring 2024. Questionnaires assessed demographics, cannabis use, and most-used products. GAD and MDD were measured using the Revised Children’s Anxiety and Depression Scale (and Subscales). Result: 249 (16.0%) adolescents report using cannabis products in the past six months. MDD is significantly positively associated with smoking, edibles /drinks, and vaping THC, and CBD (all p < 0.05*). Both MDD and GAD predicted vaping as the most-used product. Compared to White adolescents, Hispanic adolescents with MDD were more likely to use all product types (ORs = 2.5-2.9, all p < .001**), while Asian adolescents were less likely (ORs = 0.28-0.40, all p < .05*). Multiracial adolescents were more likely to use CBD (OR = 3.07, p < .05*). Conclusion: Adolescents with MDD are more likely to use THC and CBD products. Vape THC products are preferred for both MDD and GAD. Race and ethnicity moderate this relationship, with Hispanic adolescents reporting higher use and Asian adolescents reporting lower use. Findings emphasize the importance of the need for vape THC regulation and culturally tailored cannabis prevention strategies.

This study aimed to explore the relationship between adaptogen and psychedelic use, motivations, and lifestyle choices in adults aged 18-65. Participants (n = 330) completed an online survey assessing their frequency of use of adaptogens and psychedelics, as well as their future intentions of use. Additionally, the survey assessed lifestyle choices, such as exercise, dietary habits, and overall wellness practices. Descriptive results suggest correlations between individuals who only used adaptogens demonstrating greater engagement in wellness practices and health-conscious behaviors than non-users and psychedelic users. These findings suggest that adaptogens may be linked to more proactive lifestyle choices, highlighting the potential for integration into health and wellness strategies. Background: In recent years, the use of adaptogens and psychedelics has gained notable attention for their potential impact on mental and physical well-being. Adaptogens are natural substances derived from plants, roots, and mushrooms believed to aid the body in resisting stress and adapting to everyday stressors, often incorporated into routines to improve wellness. Psychedelics, though traditionally known for their hallucinogenic effects, have shown promise in research regarding mental health treatment and mindfulness practices. Despite the growing interest in these substances, limited research has been conducted on the relationship between their use and lifestyle choices associated with health and wellness. Methods: Participants were adults aged 18 to 65 (N = 330), recruited from universities across Southern California (e.g., USC, CSUN, UCLA), fitness studios, grocery stores, and social media platforms. The mean age of participants was 31.47 years (SD = 5.80), with 70.3% identifying as female. A total of 91.8% of participants reported using adaptogens or psychedelics. Exposure variables included self-reported prior use of adaptogens and/or psychedelics. Outcomes included engagement in healthy lifestyle choices, assessed by The Lifestyle Choice Scale (LCS), a self-reported measure of diet, physical activity, mindfulness practices, and overall wellness behaviors. Associations were analyzed using multiple linear regression and bivariate correlation models, adjusting for age, gender, and education. Results: Adaptogen use was not statistically significantly associated with healthy lifestyle choices (B = 0.00, p = 0.587). However, psychedelic-only users (B = -0.45, p = 0.01)

This study explored the relationships between media use, binge-eating symptoms, and body dissatisfaction among adolescents, including the role of sex as a moderator. Understanding these associations is important, as binge eating during adolescence can lead to long-term physical and emotional health issues. Using ecological momentary assessment (EMA) via mobile phones, real-time data were collected from a sample of 75 adolescents aged 12 to 17. Participants reported on their media use (television and social media), binge-eating symptoms, and body dissatisfaction multiple times per day. The goal was to determine whether higher media use was linked to greater binge-eating symptoms and body dissatisfaction, and whether these associations differed by sex. Results showed that television media use was significantly associated with lower binge-eating symptoms, while social media use was not a significant predictor of either outcome. BMI-z was the strongest predictor of body dissatisfaction, with higher scores linked to greater dissatisfaction. Males reported significantly lower body dissatisfaction than females, and age was positively associated with binge-eating symptoms. However, sex at birth did not moderate the relationships between media use and the outcomes. Rather than focusing on daily changes, this study examined patterns across individuals to reveal broader associations. The observed gender differences highlight the need for targeted interventions to support adolescent mental health.