Drug And Alcohol Dependence[JOURNAL]
Sun
200 papers
Oral nicotine pouch use motives and dependence among individuals who use both cigarettes and e-cigarettes.
Pokhrel P, Phillips KT, Kawamoto CT … +2 more , Lee DN, Herzog TA
Drug Alcohol Depend · 2026 Aug · PMID 42172907 · Publisher ↗
BACKGROUND: The motives for oral nicotine pouch (ONP) use among individuals who smoke cigarettes and use e-cigarettes are not well understood beyond cessation-related reasons. This study compared a range of ONP use motiv...
BACKGROUND: The motives for oral nicotine pouch (ONP) use among individuals who smoke cigarettes and use e-cigarettes are not well understood beyond cessation-related reasons. This study compared a range of ONP use motives among adults who concurrently smoke and use e-cigarettes and examined the associations between the motives and ONP dependence. METHODS: Cross-sectional self-report data were collected from 297 adults (mean age = 33.8 years, SD = 5.1; 35% women) who reported past-30-day cigarette smoking, e-cigarette use, and ONP use. RESULTS: Motives such as using ONPs in places or situations where smoking or vaping is not possible, for stimulation, fun, or flavors were endorsed more strongly than motives related to quitting smoking or vaping. After accounting for demographic variables and e-cigarette and cigarette dependence as covariates, cessation-related motives explained 6-8% of the variance in ONP dependence, while use of ONP for stimulation, to get along with friends, and to increase energy for physical activity, each explained 13-15%. The composite motive score was significantly and positively associated with higher ONP dependence. CONCLUSIONS: ONP use among those engaging in dual use of cigarettes and e-cigarettes is driven by motives not limited to cessation, some of which are more strongly associated with ONP dependence.
Psychosocial interventions for alcohol use disorder in China: A systematic review and meta-analysis.
Kong X, Liu Y, Liu H … +4 more , Watkins LE, Liu J, Hao W, Tang YL
Drug Alcohol Depend · 2026 Aug · PMID 42172906 · Publisher ↗
AIMS: Alcohol use disorder (AUD) is a public health concern in China. Psychosocial interventions are a key component of comprehensive treatment. We conducted the first systematic review and meta-analysis of Chinese studi...
AIMS: Alcohol use disorder (AUD) is a public health concern in China. Psychosocial interventions are a key component of comprehensive treatment. We conducted the first systematic review and meta-analysis of Chinese studies evaluating the effectiveness of psychosocial interventions on AUD, and depressive and anxiety symptoms. METHODS: A systematic search was conducted across both English and Chinese databases, covering records from inception to June 10, 2025. The primary outcome was relapse rate; secondary outcomes included anxiety and depressive symptoms, assessed using HAMA and HAMD, respectively. Quality assessment was performed using the Cochrane Risk of Bias tool. Meta-analyses were conducted using RevMan 5.3. Forty-eight studies were included (44 in Chinese and 4 in English), involving 4592 patients (2317 in the intervention and 2275 in the control groups). OUTCOMES: Psychosocial interventions significantly reduced relapse compared to control groups [40 studies, n = 3819, OR = 0.28, 95% CI (0.24, 0.32), P < 0.001]. Psychosocial treatments also improved anxiety [13 studies，n = 1249, SMD = -1.85, 95% CI (-2.46, -1.23), P < 0.001] and depression [16 studies, n = 1694; SMD = -1.62, 95% CI (-2.13, -1.11), P < 0.001]. Funnel plots suggested a high risk of publication bias. CONCLUSIONS: Evidence from studies in Chinese patients indicates that structured or standardized psychosocial interventions are more effective than routine care alone in reducing relapse and improving mood symptoms in patients with AUD. The findings support their broader integration into treatment in China, though publication bias must be considered.
Associations of endocannabinoid serum concentrations with behavioral impulsivity and substance use in late childhood to early adolescence.
Shankula CA, Sullivan RM, Stinson EA … +7 more , Baacke KA, Kaiver CM, Wallace AL, Bernal ES, Paltzer ZR, Hillard CJ, Lisdahl KM
Drug Alcohol Depend · 2026 Aug · PMID 42161038 · Publisher ↗
OBJECTIVE: Adolescence is characterized by rapid neurobehavioral development. The endocannabinoid (eCB) system modulates several co-developing neurotransmitter systems and is well-implicated in preclinical substance use...
OBJECTIVE: Adolescence is characterized by rapid neurobehavioral development. The endocannabinoid (eCB) system modulates several co-developing neurotransmitter systems and is well-implicated in preclinical substance use (SU) models. Few studies, however, have investigated associations between the eCB system and SU in adolescence. The present study evaluated associations between circulating eCB lipids and SU, impulsivity, and behavioral approach endophenotypes. METHODS: Concentrations of eCBs [2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine (AEA)] and related small bioactive lipids were quantified in serum samples from a substudy of youth (n = 432) enrolled in the Adolescent Brain Cognitive Development Study using liquid chromatography-mass spectrometry. Youth completed the UPPS-P Impulsive Behavior and Behavioral Inhibition/Behavioral Approach System Scales, a SU interview, and questionnaire on factors that impact circulating eCBs. Generalized additive models assessed for associations and sex interactions between eCB concentrations and behaviors. RESULTS: 2-AG and 2-oleoylglycerol were broadly associated with behavioral approach and urgency, while AEA and other N-acylethanolamines were associated with higher-order functions like perseverance and planning, with several sex interactions observed. 2-AG and AEA were negatively associated with low-level substance use and full-unit substance use, respectively. CONCLUSIONS: Although relationships between serum eCBs and concentrations in brain are not known, the associations observed between peripheral eCB concentrations and substance use behaviors could reflect differences in eCB homeostasis in the brain. Observed sex differences may suggest hormonal or sex-specific eCB influences on brain development. Further work using direct measures of eCB concentrations in the brain are needed to validate these speculations. Future studies should investigate these mechanisms longitudinally.
Sex-based effectiveness in buprenorphine/naloxone and methadone treatment for opioid use disorder: Findings from the OPTIMA trial.
McAnulty C, Bastien G, Pek C … +7 more , Pelletier McCrea T, Bouthillier A, Stewart SH, Socias ME, Le Foll B, Jutras-Aswad D, OPTIMA Research Group within the Canadian Research Initiative in Substance Misuse
Drug Alcohol Depend · 2026 Aug · PMID 42161037 · Publisher ↗
INTRODUCTION: Opioid use disorder (OUD) is a public health challenge globally. Few studies examine sex differences in opioid agonist therapy outcomes, especially in contexts of high potency opioid consumption. Clarifying...
INTRODUCTION: Opioid use disorder (OUD) is a public health challenge globally. Few studies examine sex differences in opioid agonist therapy outcomes, especially in contexts of high potency opioid consumption. Clarifying these could inform personalized treatment strategies. METHODS: We conducted exploratory sex-stratified analyses using data from a 24-week, multicentric, pragmatic, open-label randomized controlled trial. Participants with OUD (n male=179, n female=93) were randomized to flexible take-home dosing of buprenorphine/naloxone (n male=95, n female=43) or standard methadone (n male=84, n female=50) models of care. Retention was defined as having both an active prescription and a positive urine drug screen for the assigned treatment at week 24. Opioid use was assessed as the proportion of opioid-positive urine samples. Craving was measured using the Brief Substance Craving Scale and withdrawal using the Clinical Opiate Withdrawal Scale. Substance-use-related problems were evaluated via the Addiction Severity Index (ASI). RESULTS: In sex-stratified analyses, retention appeared overall lower for females (buprenorphine/naloxone=11.6%, methadone=26.0%) than males (buprenorphine/naloxone =28.4%, methadone=38.1%). Females showed higher opioid use overall; there was no treatment group effect on opioid use in either sex (p > 0.05). Both sexes improved in drug and psychiatric ASI domains (p < 0.05), while family-related problems improved only in males (p = 0.036). Craving decreased in both sexes, with females reporting lower craving on buprenorphine/naloxone than on methadone (p < 0.001). Withdrawal scores were higher with buprenorphine/naloxone versus methadone in males only (p = 0.026). CONCLUSIONS: We found potential sex differences in treatment outcomes, suggesting that these may benefit from sex-based adaptations. Future research into this possibility is warranted.
Impact of schedule V controlled substance classification of gabapentin on adult gabapentin-involved overdose rates, West Virginia, 2016-2019: A controlled time series analysis.
Gora Combs K, Hincapie-Castillo JM, Dasgupta N … +4 more , Vickers-Smith R, Kinlaw A, Smith GS, Marshall SW
Drug Alcohol Depend · 2026 Aug · PMID 42155429 · Full text
OBJECTIVE: Assess the association between West Virginia's classification of gabapentin as a schedule V controlled substance and fatal overdoses involving gabapentin, relative to a control state. METHODS: Using a controll...
OBJECTIVE: Assess the association between West Virginia's classification of gabapentin as a schedule V controlled substance and fatal overdoses involving gabapentin, relative to a control state. METHODS: Using a controlled interrupted time series design, we modeled a segmented linear regression using Newey-West standard errors to estimate the immediate and trend changes in gabapentin-involved fatal overdoses among adults in West Virginia associated with gabapentin's scheduling in June 2018. Data from North Carolina (no gabapentin scheduling) was used as a control to account for potential secular changes. Quarterly rates were computed from 2016 to 2019. RESULTS: The introduction of West Virginia's policy was associated with an immediate decrease in the rate of gabapentin-involved fatal overdoses (drop of 0.39 overdoses per 100,000 adults) in West Virginia relative to North Carolina (95% CI: -0.75, -0.03). There was no evidence to suggest a change in trend relative to North Carolina (0.02 overdoses per 100,000 adults per quarter; 95% CI: -0.06, 0.10). CONCLUSIONS: Classifying gabapentin as a schedule V controlled substance was associated with an immediate decrease in the rate of gabapentin-involved fatal overdoses in West Virginia, relative to North Carolina. POLICY IMPLICATIONS: Combined with broader efforts to address overdose deaths, scheduling gabapentin is a potential supply-side intervention that may contribute to reductions in gabapentin involvement in fatal overdoses.
Cigarette smoking, history of major depression and PTSD diagnosis are associated with metabolite levels in the left dorsolateral prefrontal cortex in those in treatment for alcohol use disorder.
Durazzo TC, Carolan RE, Beauregard LH … +2 more , Gu M, Padula CB
Drug Alcohol Depend · 2026 Aug · PMID 42150346 · Publisher ↗
BACKGROUND: Despite the known systemic health risks associated with cigarette smoking, research investigating the neurobiological consequences of smoking in those with alcohol use disorder (AUD) is minimal. This study co...
BACKGROUND: Despite the known systemic health risks associated with cigarette smoking, research investigating the neurobiological consequences of smoking in those with alcohol use disorder (AUD) is minimal. This study compared metabolite levels in the left dorsolateral prefrontal cortex (DLPFC) in non-cigarette smoking individuals, former cigarette smoking individuals and active cigarette smoking individuals who were Veterans in residential treatment for AUD. METHODS: Water scaled concentrations were obtained for N-acetylaspartate (NAA), choline-containing compounds (Cho) creatine-containing compounds (Cr), gamma-aminobutyric acid (GABA) and glutamate (Glu). Actively smoking AUD (AsAUD, n = 46) used cigarettes daily; former smoking AUD (FsAUD, n = 41) were predominately daily cigarette consumers prior to study, with variable lengths of cessation; non-smoking AUD (NsAUD, n = 32) never used cigarettes or seldomly smoked during lifetime. Given the high prevalence of major depressive disorder (MDD) and post-traumatic stress disorder (PTSD) in Veterans with AUD, these conditions served as factors in all analyses. RESULTS: AsAUD had lower NAA, Cho and Cr than NsAUD and lower Cr than FsAUD; there were no metabolite level differences between FsAUD and NsAUD. Individuals with no history of MDD showed lower NAA and Cho levels than those with current MDD and past MDD; current MDD and past MDD were not different on any metabolite concentration. Individuals with a current PTSD diagnosis demonstrated lower Cr level than those with no PTSD diagnosis. CONCLUSIONS: Results suggest that smoking, MDD and PTSD history are associated with left DLPFC brain metabolite concentrations during early AUD recovery. These novel findings also support the clinical practice of offering smoking cessation resources concurrent with AUD treatment.
Dose and age matter: Xylazine prevents age-dependent fentanyl lethality in rats.
Zuarth-Gonzalez JD, Zolali E, Mehta Y … +2 more , McMahon LR, Obeng S
Drug Alcohol Depend · 2026 Aug · PMID 42143952 · Publisher ↗
BACKGROUND: Xylazine, a veterinary sedative not approved for human use, has emerged as a common adulterant in North America's illicit opioid supply, e.g., detected in over 90% of Philadelphia's street samples. Preclinica...
BACKGROUND: Xylazine, a veterinary sedative not approved for human use, has emerged as a common adulterant in North America's illicit opioid supply, e.g., detected in over 90% of Philadelphia's street samples. Preclinical studies of fentanyl-xylazine interactions have employed widely varying dose ratios, making it difficult to draw conclusions relevant to real-world exposures. METHODS: Using an epidemiologically-relevant ratio derived from Philadelphia's drug supply (~1:3 fentanyl:xylazine), we administered fentanyl alone (0.56mg/kg, i.p.) or fentanyl-xylazine combination (0.56mg/kg + 1.78mg/kg) to drug-naive Sprague-Dawley rats at two ages: young adults (9 weeks, n = 8/group) and adults (16 weeks, n = 8/group). Plasma fentanyl concentrations were measured at 15- and 60- min post-administration. RESULTS: In 9-week-old rats, fentanyl alone produced 75% mortality (100% males, 50% females), whereas the fentanyl-xylazine combination resulted in zero mortality (p = 0.0023). Xylazine alone produced no adverse effects. In 16-week-old rats, neither treatment caused mortality, revealing age-dependent vulnerability. Pharmacokinetic analysis showed xylazine co-administration reduced plasma fentanyl concentrations 8-fold at 15min, with apparent pattern reversal by 60min, consistent with delayed absorption. CONCLUSIONS: At an epidemiologically-relevant 1:3 ratio, xylazine completely prevented fentanyl mortality in young animals. These data, along with emerging clinical evidence, suggest fentanyl-xylazine interactions are more complex than current models predict. While xylazine contamination remains a serious public health concern, understanding actual toxicological interactions at real-world ratios is essential for evidence-based harm reduction and policy responses.
Associations between daily pain severity and concurrent alcohol craving among women in early recovery following alcohol treatment.
Ferguson E, Min J, Battle CL … +2 more , Stein MD, Abrantes AM
Drug Alcohol Depend · 2026 Aug · PMID 42143951 · Publisher ↗
BACKGROUND: Rates of alcohol use disorder (AUD) for women are rising, and women remain more likely to experience serious alcohol-related harms and consequences compared to men. Pain may complicate AUD, as it often co-occ...
BACKGROUND: Rates of alcohol use disorder (AUD) for women are rising, and women remain more likely to experience serious alcohol-related harms and consequences compared to men. Pain may complicate AUD, as it often co-occurs with alcohol use. However, relations between pain and alcohol craving, an important predictor of return to alcohol use, are underexplored, particularly among women with AUD. PURPOSE: The present study investigated the relationship between daily pain severity and concurrent alcohol craving among women with AUD who were engaged in alcohol treatment and reported co-occurring depressive symptoms (N = 72, M=44.1, 90.3% White). Additionally, we sought to understand any differences in pain-alcohol craving associations by type of pain (joint/muscle vs. headache pain). METHODS: Data were drawn from a randomized controlled trial testing the efficacy of a lifestyle physical activity intervention for improving alcohol abstinence. Participants completed three, 10-day periods of ecological momentary assessment (EMA) during the first 90 days post-treatment to report pain severity (headache and joint/muscle pain) and alcohol craving. RESULTS: Results indicated that greater average headache pain (γ=.21, p = .013) and joint/muscle pain (γ=.27, p < .001) were associated with greater alcohol craving. On days with higher headache pain than their average, participants also reported increased alcohol craving (γ=.03, p = .036). CONCLUSIONS: Findings highlight pain as a relevant factor in AUD recovery for women and suggest that pain management may be an important consideration for AUD treatment programs.
Factors associated with the development of systemic versus local infections in people who inject drugs.
Sabra R, Donnadieu H, Eiden C … +3 more , Le Moing V, Peyrière H, French Addictovigilance Network (FAN)
Drug Alcohol Depend · 2026 Aug · PMID 42142487 · Publisher ↗
OBJECTIVES: To describe bacterial infections among people who inject drugs (PWID) in France, identify factors associated with systemic infection and define patient groups based on demographic and consumption profiles. ME...
OBJECTIVES: To describe bacterial infections among people who inject drugs (PWID) in France, identify factors associated with systemic infection and define patient groups based on demographic and consumption profiles. METHODS: National, cross-sectional, multicenter study using spontaneous reports collected by the French Addictovigilance Network from January 2019 to December 2024. Local and systemic infections were compared to identify associated sociodemographic and injection-related factors. These variables were used to build patient profiles through hierarchical clustering approach. RESULTS: A total of 727 bacterial infections were analyzed (56% local and 44% systemic) in mainly men (79%), with a median age of 39 years. The most common infections were soft skin and tissue infections (65%), abscesses (51%), endocarditis (20%) and sepsis (15%). Cocaine (46.5%), heroin (16.5%) and buprenorphine (16.6%) were the main injected substances. Injecting stimulants only was associated with lower odds of systemic infection when compared to injecting a stimulants/opioids combination (OR 0.61 [95%CI: 0.40-0.93]) while older age (OR 1.02 [95%CI: 1.01-1.04]) and HIV-negative individuals not engaging in slam (OR 3.62 [95%CI: 1.46-8.98]) were associated with systemic infection compared to HIV-negative individuals engaging in slam. Five clusters were identified: I- Male, single substance injectors, opioids or stimulant, II- Female, single substance injectors, opioids or stimulant, III- Both opioids and stimulants injectors, IV- Young PWID, injectors of single substances outside opioids/stimulants presenting local infections, V- HIV-positive men, engaging in slam, having local infections. CONCLUSION: Our findings illustrate how the type of psychoactive substances and the sociodemographic profile are related to the infection type among PWID.
Feasibility of continuous sleep and environmental monitoring in residential substance use recovery: Associations with mental health outcomes.
Rossa KR, Edmed SL, Mann DL … +6 more , Stokes HA, Pattinson CL, Allan AC, Lorimer N, Salom C, Smith SS
Drug Alcohol Depend · 2026 Jul · PMID 42119197 · Publisher ↗
INTRODUCTION: Quality sleep is important for substance use recovery. Supporting and monitoring sleep during residential treatment poses challenges, but unobtrusive technologies like actigraphy or environmental sensors of...
INTRODUCTION: Quality sleep is important for substance use recovery. Supporting and monitoring sleep during residential treatment poses challenges, but unobtrusive technologies like actigraphy or environmental sensors offer objective low burden measurement. We examined the feasibility and acceptability of these technologies, and associations between sleep and mental health outcomes. METHODS: This pilot and feasibility study employed a naturalistic design. Fifty-two adults in residential treatment for diverse substance-related issues wore actigraphs and completed daily sleep diaries over a period of up to 4 weeks during live-in treatment. Subjective assessments of pre-sleep arousal and sleep quality were collected alongside routine clinical measures at study entry and exit. Environmental sensors continuously recorded sleep environment (temperature, light) data. RESULTS: Of the 52 participants, thirty-three participants wore actigraphs for > 14 days; 23 completed exit questionnaires, and 11 interviews. Significant positive associations were found between subjective pre-sleep arousal and symptoms of depression, anxiety, and post-traumatic stress. Objective sleep regularity was negatively associated with post-traumatic stress, anxiety, and pre-sleep somatic arousal. Later sleep midpoint was linked to greater subjective sleep disturbance and anxiety. Objective sleep duration was not associated with any mental health variables. DISCUSSION: Continuous, unobtrusive monitoring of sleep and bedroom environments is feasible in residential settings for many residents, though feasibility varied across longer-term actigraphy monitoring and questionnaire completion. This approach may offer a first step in identifying targets for future interventions to improve sleep and support recovery.
Time-varying mediated effects of the nicotine patch on smoking before and after a quit attempt when it is added to varenicline and counseling.
Kim N, Baker TB, Coffman DL … +3 more , Piper ME, Stein JH, McCarthy DE
Drug Alcohol Depend · 2026 Jul · PMID 42107144 · Publisher ↗
BACKGROUND: Even with evidence-based treatment, most people who try to quit smoking return to regular smoking within weeks. Mediation analyses simultaneously test hypotheses about how treatments affect possible smoking d...
BACKGROUND: Even with evidence-based treatment, most people who try to quit smoking return to regular smoking within weeks. Mediation analyses simultaneously test hypotheses about how treatments affect possible smoking determinants and how these determinants may influence smoking risk. Such evidence may inform treatment enhancement. OBJECTIVES: Conduct secondary analyses that assess the extent to which: a) active vs. placebo nicotine patch used in conjunction with varenicline and counseling affect candidate mediators in the peri-cession period, b) candidate mediators predict next-day smoking, and c) treatment effects on next-day smoking are mediated via candidate mediators. METHODS: Time-varying mediation models (TVMM) were fit to ecological momentary assessment data collected nightly from 1202 adults motivated to quit smoking in the 2 weeks preceding and 2 weeks following the target date to quit smoking in a placebo-controlled, double-blinded randomized controlled trial of adjuvant nicotine patch therapy used with varenicline and individual counseling. RESULTS: Analyses confirmed the predictive value of hypothesized mediators (cravings to smoke, nicotine withdrawal symptoms, reduced positive affect, and low quitting confidence) on next-day smoking risk, but also found that only positive affect mediated active (vs. placebo) patch effects on next-day abstinence 3-9 days after a target quit day. DISCUSSION: Adding nicotine patches to varenicline and counseling improves positive affect in ways that predict lower next-day smoking risk in the first days of attempts to quit smoking but does not significantly improve withdrawal management or sustain confidence in quitting.
Measurement challenges in binge drinking research: Addressing sex and gender diversity in national surveys.
Azagba S
Drug Alcohol Depend · 2026 Jul · PMID 42107143 · Publisher ↗
BACKGROUND: Accurate measurement of binge drinking is essential for understanding population-level health disparities. However, national surveys commonly rely on binary sex-based thresholds, which may introduce classific...
BACKGROUND: Accurate measurement of binge drinking is essential for understanding population-level health disparities. However, national surveys commonly rely on binary sex-based thresholds, which may introduce classification challenges when applied across diverse sex and gender classifications. METHODS: Data from the 2019-2023 Behavioral Risk Factor Surveillance System were used to examine binge drinking patterns among adults reporting transgender identity. Binge drinking was defined using standard sex-based thresholds (≥5 drinks for men, ≥4 drinks for women on a single occasion). Multivariable logistic regression was used to estimate associations between sex assigned at birth, gender identity, and binge drinking, adjusting for demographic characteristics and using cisgender men and women as reference groups. RESULTS: Estimated odds of binge drinking varied by gender identity and reference group, indicating sensitivity to sex-based thresholds. Compared to cisgender women, individuals assigned female at birth who reported transgender identity had higher odds of binge drinking (e.g., transmasculine: OR = 1.55, 95% CI = 1.08-2.22), although these differences were not consistently observed when compared to cisgender men. Additionally, 26% of individuals identifying as transmasculine reported a sex assigned at birth of male, and 13% of those identifying as transfeminine reported a sex assigned at birth of female, suggesting reporting differences that may reflect variation in how survey questions are interpreted. CONCLUSIONS: Differences in how sex and gender are defined in national surveys may introduce measurement uncertainty in the application of standard sex-based binge drinking thresholds. A clearer distinction between sex assigned at birth and gender identity may improve the interpretability of surveillance estimates.
Opioid and α-adrenoceptors interaction on the lethality, antinociception, antinociceptive tolerance, and precipitated withdrawal in mice treated with fentanyl and xylazine.
Albores-García D, Cruz SL
Drug Alcohol Depend · 2026 Jul · PMID 42107142 · Publisher ↗
BACKGROUND: Xylazine, an α-adrenoceptor agonist approved for veterinary use, has increasingly been identified as an adulterant in illicit fentanyl supplies and is associated with increased overdose mortality. We previous...
BACKGROUND: Xylazine, an α-adrenoceptor agonist approved for veterinary use, has increasingly been identified as an adulterant in illicit fentanyl supplies and is associated with increased overdose mortality. We previously showed that xylazine potentiates fentanyl-induced lethality in mice and that 30mg/kg naloxone prevents mortality, whereas α-adrenoceptor antagonism does not. This study examines whether opioid and adrenergic antagonists modulate the lethality, antinociceptive tolerance, and physical dependence produced by fentanyl and xylazine administered in combination. METHODS: Male Swiss Webster mice received fentanyl and xylazine either at high doses to assess lethality (10 and 56mg/kg, respectively) or at lower, analgesic doses (0.3 and 5.6mg/kg) to evaluate antinociception, tolerance, and withdrawal. The selective kappa opioid receptor antagonist GNTI and the highly selective α-adrenoceptor antagonist atipamezole were administered alone or in combination with naloxone, depending on the endpoint assessed. Antinociception over two hours was measured using the tail-flick test, and withdrawal was precipitated with different antagonists. RESULTS: A non-lethal dose of xylazine markedly increased fentanyl-induced lethality, an effect significantly reduced by naloxone combined with GNTI but not with atipamezole. At analgesic doses, xylazine produced mild antinociception and did not enhance fentanyl's peak effect. Full reversal of fentanyl/xylazine antinociception required naloxone plus atipamezole. Repeated xylazine attenuated fentanyl-induced antinociceptive tolerance. Mice receiving fentanyl/xylazine displayed significantly milder naloxone-precipitated withdrawal than fentanyl alone, whereas naloxone combined with GNTI exacerbated withdrawal signs. CONCLUSIONS: Fentanyl-xylazine interactions are dose- and endpoint-dependent and involve distinct opioid and α-adrenergic mechanisms affecting lethality, analgesia, tolerance and withdrawal.
Fentanyl, xylazine, and bromazolam: Urine toxicology trends in a San Francisco safety net opioid treatment patient cohort 2023-2025.
Halifax JC, Lim L, Ahern J … +3 more , Steiger S, Shapiro BJ, Lynch KL
Drug Alcohol Depend · 2026 Jul · PMID 42096994 · Publisher ↗
OBJECTIVES: To gain insights on the illicit drug supply in San Francisco using urine toxicology of opioid use disorder intake patients to assess temporal trends and co-occurrence patterns and detect emerging compounds of...
OBJECTIVES: To gain insights on the illicit drug supply in San Francisco using urine toxicology of opioid use disorder intake patients to assess temporal trends and co-occurrence patterns and detect emerging compounds of concern. To inform local overdose prevention and opioid use disorder treatment efforts. METHODS: We analyzed 1763 opioid treatment intake patient urine samples at a safety net clinic over 2.5 years from March 2023-August 2025. We assessed urine toxicology by untargeted liquid chromatography high resolution mass spectrometry (LC-HRMS) using an in-house library containing > 500 small molecules, including fentanyl analogs, nitazene compounds, non-FDA approved benzodiazepines, medetomidine, and xylazine. We calculated auto and cross correlations between pairs of drug classes to assess contemporaneous and lagged weekly associations between drug classes over the study period. RESULTS: Xylazine was widely detected over the study period, with multiple spikes in prevalence. No nitazene compounds were ever detected. Fentanyl, methamphetamine, and cocaine were the most prevalent drug classes and fentanyl was correlated with both stimulants contemporaneously. Norcarfentanil was detected once, medetomidine was detected twice, and bromazolam was detected 23 times. Xylazine had an auto-correlation lag pattern suggestive of surges in prevalence lasting two weeks. CONCLUSIONS: Urine toxicology of a relevant patient population establishes the presence of xylazine in the San Francisco drug supply. Multiple other compounds of concern for overdose risk were also intermittently detected. The highly dynamic prevalences of substances of concern for fatal overdose suggests the value of ongoing monitoring.
Alcohol and pregnancy: Benefits and harms of pregnancy-specific alcohol policies among maternal-infant dyads covered by Medicaid.
Roberts SCM, Dennis E, Subbaraman M … +1 more , Liu G
Drug Alcohol Depend · 2026 Jul · PMID 42096993 · Publisher ↗
BACKGROUND: Previous research finds pregnancy-specific alcohol policies are associated with adverse infant/maternal outcomes among people covered by commercial insurance. Here, we examine whether findings generalize to p...
BACKGROUND: Previous research finds pregnancy-specific alcohol policies are associated with adverse infant/maternal outcomes among people covered by commercial insurance. Here, we examine whether findings generalize to people covered by Medicaid. METHODS: In this retrospective cohort study, we combined outcome data on births from 2000 to 2019 from Medicaid Analytic eXtract and Transformed Medicaid Statistical Information System Analytic Files databases with pregnancy-specific alcohol policy data. Outcomes included infant morbidities related to maternal alcohol consumption, infant injuries consistent with maltreatment at 50% and 75% positive predictive value (PPV), severe maternal morbidities (SMM), and infant healthcare utilization. Adjusted analyses used logistic regression with individual- and state-level controls, state- and year-fixed effects, state-specific time trends, and standard errors clustered by state. We replicated analyses with models stratified by race/ethnicity. RESULTS: The cohort included 10,329,565 maternal-infant dyads. 2.4% had an infant morbidity; 3.0% and 0.3% had injuries with 50% and 75% PPV respectively; 4.2% experienced a SMM. Only one policy - Reporting Requirements for Assessment/Treatment - was robustly associated with improvements in all outcomes (ranging from aOR 0.86 95% CI 0.82, 0.89 for SMM to 0.95 95% CI 0.92, 0.99 for infant injuries 50% PPV). One policy - Reporting Requirements for Child Protective Services - was robustly associated with detriments in infant outcomes (aORs of 1.14 95% CI 1.08, 1.19 for infant morbidities and 1.19 95% CI 1.06, 1.35 for infant injuries 75% PPV) but not SMM (aOR 0.92 95% CI 0.88, 0.96). For other policies, improvements in one outcome were offset by detriments in another or among a racial/ethnic subgroup. CONCLUSIONS: While some individual pregnancy-specific alcohol policies were associated with benefits among births covered by Medicaid, benefits were often offset by adverse effects. Policymakers should not assume pregnancy-specific alcohol policies improve infant/maternal health.
Cannabis use disorder risk among midlife adults reporting medical and nonmedical cannabis use, 2019-2024.
Terry-McElrath YM, Patrick ME
Drug Alcohol Depend · 2026 Jul · PMID 42096992 · Publisher ↗
BACKGROUND: High-frequency cannabis use is a key cannabis use disorder (CUD) risk factor that also is associated with medical (vs. nonmedical) use. This analysis examined overall and sex- and age-stratified associations...
BACKGROUND: High-frequency cannabis use is a key cannabis use disorder (CUD) risk factor that also is associated with medical (vs. nonmedical) use. This analysis examined overall and sex- and age-stratified associations between medical cannabis use, use frequency, and CUD outcomes among midlife adults. METHODS: Monitoring the Future Longitudinal Panel study data from 5454 US adults ages 40-60 reporting past 12-month use surveyed in 2019-2024 were used. Logistic regression models examined overall and sex- and age-stratified associations between medical cannabis use and self-reported CUD symptom prevalence, severity, and criteria before and after controlling for use frequency. RESULTS: Among adults using cannabis, prevalence of any and moderate/severe CUD symptoms was 23.9% and 9.4%, respectively; among those using near-daily (20 + occasions in past 30 days), 49.7% had CUD symptoms. Medical (vs. nonmedical) use was associated with any CUD symptoms (33.8% vs. 22.5%; p < .001), moderate/severe symptoms (15.1% vs. 8.7%; p < .001), and 10 of the 11 individual CUD criteria (p = 0.037 to <.001). Controlling for use frequency explained all overall medical (vs. nonmedical) use and CUD associations. Stratification models showed medical use remained associated with tolerance among females but not males (p = 0.017 vs. 0.981), and range of CUD outcomes among those ages 55-60 (but not 40-50), including tolerance (p = 0.007 vs. 0.826) and moderate/severe CUD symptoms (p = 0.012 vs. 0.118). DISCUSSION: Overall, high-frequency cannabis use-medical or nonmedical-is associated with CUD risk. Even after controlling for use frequency, medical use is associated with tolerance among females and older adults, and moderate/severe CUD symptoms among older adults.
Adolescents view cannabis as less harmful than cigarettes, nicotine vapes, and alcohol: Findings from two California school surveys.
Agarwal D, Wang J, Li S … +2 more , Anderson CM, Zhu SH
Drug Alcohol Depend · 2026 Jul · PMID 42091353 · Publisher ↗
BACKGROUND: Perceptions that substances are harmful help protect against their use. The purpose of this study was to investigate adolescent perceptions of the harmfulness of everyday and occasional use of cannabis compar...
BACKGROUND: Perceptions that substances are harmful help protect against their use. The purpose of this study was to investigate adolescent perceptions of the harmfulness of everyday and occasional use of cannabis compared to those for cigarettes, nicotine vapes, and alcohol, and how those perceptions varied with age. METHODS: Participants were 160,222 adolescents who took the 2019-2020 California Student Tobacco Survey and 14,922 adolescents who took the 2024 California Youth Tobacco Survey. Descriptive statistics were used to examine harm perceptions by substance use history, use frequency, the proportion of friends using a substance, and grade level. RESULTS: In the 2019-2020 survey, everyday use of cannabis was perceived as harmful by the smallest proportion of adolescents (66.8%), followed by alcohol (77.7%), vapes (85.3%), and cigarettes (92.6%; all p's < 0.0001). Harm perceptions for each substance were lower for occasional use than for everyday use, and lower among those who had ever used the substance than among those who had never used it. Harm perceptions remained unchanged or increased with grade for cigarettes, vapes, and alcohol but decreased for cannabis. For each substance, harm perceptions declined as the proportion of participants' friends who used the substance increased. Data from the 2024 survey followed similar patterns. CONCLUSIONS: Adolescents perceived cannabis as less harmful than cigarettes, nicotine vapes, and alcohol. As adolescents aged, they were less likely to perceive cannabis as harmful, unlike other substances. Increased education and prevention messaging may be needed to raise awareness of the risks of using cannabis during adolescence.
Perceived harmfulness of e-cigarettes and heated tobacco products compared to cigarettes: Findings from the 2020 ITC Malaysia survey.
Noh MAM, Hairi FM, Nordin ASA … +11 more , Yee A, Tajuddin NAA, Hasan SI, Danaee M, Kamaludin IS, Subramaniyan M, Pravinassh R, Driezen P, Yan M, Quah ACK, Fong GT
Drug Alcohol Depend · 2026 Jul · PMID 42090843 · Publisher ↗
INTRODUCTION: Misperceptions about nicotine product harms may influence product use and switching behaviors. METHODS: Data were from the 2020 International Tobacco Control (ITC) Malaysia Survey, a nationally representati...
INTRODUCTION: Misperceptions about nicotine product harms may influence product use and switching behaviors. METHODS: Data were from the 2020 International Tobacco Control (ITC) Malaysia Survey, a nationally representative survey of 1047 adults aged ≥ 18 who smoked cigarettes at least monthly and had smoked ≥ 100 cigarettes (n = 1047). Respondents reported awareness of HTPs and ECs and perceived harmfulness relative to cigarettes. For regression analyses, perceived harmfulness vs cigarettes were categorized as less harmful, equally/more harmful, or don't know; for HTP-EC comparisons, categories were HTP more harmful, equally/EC more harmful, or don't know. RESULTS: Overall, 53.4% respondents had heard of HTPs, with lower awareness among women, ethnic minorities, and those with lower educational attainment. Among those aware of HTPs, 39.7% perceived HTPs as less harmful and 38.9% as equally harmful as cigarettes. Ethnic minority respondents were more likely to perceive HTPs as equally/more harmful than cigarettes or to report don't know, while those with secondary or lower education had lower odds of reporting don't know. Among adults aware of ECs, 46.4% perceived ECs as less harmful than cigarettes, while 29.7% and 14.1% perceived them as equally or more harmful. Respondent aged ≥ 40 had higher odds of perceiving ECs as equally/more harmful than cigarettes or reporting don't know. When comparing HTPs and ECs directly, 49.5% perceived them as equally harmful and 25.3% perceived HTPs as more harmful than ECs, while respondents aged ≥ 40 were more likely to report don't know. CONCLUSION: Perceptions of harm varied across products and sociodemographic groups, indicating gaps in understanding nicotine product harms.
The effects of acute and repeated M1 agonist VU0364572 administration on cocaine-vs-food choice in male and female Sprague-Dawley rats.
Marsh SA, Banks ML
Drug Alcohol Depend · 2026 Jul · PMID 42090842 · Full text
Cocaine use disorder (CUD) represents a public health crisis for which there are currently no pharmacotherapies. Repeated administration of the muscarinic agonist xanomeline significantly decreased cocaine self-administr...
Cocaine use disorder (CUD) represents a public health crisis for which there are currently no pharmacotherapies. Repeated administration of the muscarinic agonist xanomeline significantly decreased cocaine self-administration. However, the pharmacological mechanisms mediating xanomeline effects on cocaine reinforcement remain to be determined. The present aim was to determine whether selective M1 receptor activation with the M1 agonist VU0364572 was sufficient to attenuate cocaine-vs-food choice in male and female rats. Rats were trained to respond under a concurrent fixed-ratio (FR)5:FR5 schedule of intravenous cocaine infusions and liquid food during daily 2h sessions. VU0364572 (0.32-10mg/kg, IP) or vehicle was administered acutely before the cocaine choice session and VU034572 effects were observed for two-to-four weeks. Additionally, VU0364572 was administered using a 5-day dosing regimen to model clinical aspects of substance use disorder medication dosing regimens. During saline administration, cocaine maintained a dose-dependent increase in percent cocaine choice. Neither acute nor repeated VU0364572 administration up to 10mg/kg significantly altered cocaine choice in male and female rats. These results do not support VU0364572 as a candidate CUD pharmacotherapy and further suggest that xanomeline effectiveness to attenuate cocaine choice is not exclusively mediated by M1 receptors.
Frequent police contact and nonfatal overdose among people who use drugs in rural Appalachia.
Cepeda JA, Loeb T, Salazar ZR … +7 more , Williams B, Hiltz B, Del Pozo B, Pitpitan EV, Beletsky L, Young AM, Havens JR
Drug Alcohol Depend · 2026 Jul · PMID 42090841 · Full text
INTRODUCTION: Police contact shapes subsequent health practices and outcomes among people who use drugs (PWUD). However, the relationship between police encounters with overdose remains under-researched. We evaluated how...
INTRODUCTION: Police contact shapes subsequent health practices and outcomes among people who use drugs (PWUD). However, the relationship between police encounters with overdose remains under-researched. We evaluated how police stop-and-search was associated with nonfatal overdose and identified correlates of frequent police contact among PWUD in rural Kentucky. METHODS: From May 2023 - April 2024, 774 PWUD were enrolled in the Social Networks of Appalachian People and KyOSK studies. The exposure of interest was self-reported police stop-and-search in the past 6 months (0, 1-3, ≥4 times). The primary outcome was self-reported nonfatal overdose in the past 6 months. We evaluated the association between police stops and nonfatal overdose using multivariable logistic regression, adjusting for sociodemographic, housing, polysubstance use, and mental health covariates. RESULTS: Nearly all participants were non-Hispanic White (99%), 52% were female, and 45% used both opioids and methamphetamine in the past 6 months. Thirty-seven percent reported being stopped and searched; 17% experienced a nonfatal overdose. PWUD who were stopped and searched by police ≥ 4 times in the past six months had more than double the odds of nonfatal overdose (adjusted odds ratio: 3.19, 95% CI: 1.60, 6.32) compared to PWUD with no police contact, controlling for other factors. PWUD reporting frequent police contact were significantly more likely to be unstably housed and less likely to be on medications for opioid use disorder. CONCLUSION: Police stop-and-search was associated with elevated subsequent overdose risk among PWUD. Efforts to improve PWUD health should recast police encounters as opportunities for harm reduction.
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