American Journal of Drug and Alcohol Abuse最新文献

Background: The immune system and inflammation have emerged as critical components in alcohol use disorder (AUD). The inflammatory molecule lipocalin-2 (LCN2) has been investigated in alcohol-associated liver disease, and assessment of LCN2 concentrations may aid in prevention and treatment of AUD. However, it is unknown how LCN2 concentrations fluctuate in response to acute and chronic alcohol exposure.Objectives: We examined plasma LCN2 concentrations in rats made alcohol-dependent via chronic, intermittent alcohol vapor exposure, and in people with AUD after acute alcohol administration. We hypothesized that chronic and/or acute alcohol exposure would alter LCN2 concentrations.Methods: Plasma LCN2 concentrations were measured in alcohol-dependent (n = 9) and nondependent (n = 8) male rats. LCN2 concentrations were also examined in two human laboratory studies with cue-reactivity and oral/intravenous alcohol administration in 15 (80% males) and 16 (68.8% males) participants with AUD, respectively.Results: A significant effect of Timepoint (morning versus afternoon; p = .001) but not of chronic alcohol exposure on LCN2 concentrations were found in rats. No significant effects were found after acute alcohol administration in humans.Conclusions: Chronic alcohol exposure in rats or acute alcohol administration in people with AUD had no impact on LCN2 concentrations. In rats, LCN2 concentrations were lower in the morning than in the afternoon, indicating time-related variations in LCN2 concentrations. Together, these findings suggest that LCN2 might play a role in the circadian rhythm, which is often disrupted in people with AUD. However, prospective studies are needed to further examine LCN2's potential clinical relevance in AUD.Clinical Trials Numbers: NCT01751386, NCT01779024.

Background: In animal models, third-trimester-equivalent acute alcohol exposure (TTAAE) leads to cell death in the subiculum, a hippocampal region critical for long-term memory. Proximal and distal regions of the dorsal subiculum have projections that contribute to different aspects of cognitive processing. GABAergic interneurons regulate excitatory pyramidal neurons in the subiculum, but the long-term effects of TTAAE on these interneurons remain unclear.Objective: To test the hypothesis that TTAAE triggers apoptotic pathways in dorsal subiculum interneurons, leading to a persistent reduction in their numbers and alterations in their functional properties during adolescence.Methods: Postnatal day (P) 7 vesicular GABA transporter (VGAT)-Venus mice were injected (2 × 2.5 mg/kg; subcutaneously, 2 hr apart). Cleaved caspase-3 expression was quantified 8 hr after the last injection. Adolescent neuronal and interneuronal densities were quantified using an anti-NeuN marker and Venus fluorescence. Whole-cell patch-clamp recordings were performed from interneurons and pyramidal neurons.Results: TTAAE activated apoptotic pathways in dorsal subicular interneurons in both regions (proximal, p = .005, g = -1.1; distal, p = .003, g = -1.1). Adolescent neuronal density was significantly decreased in exposed males' distal dorsal subiculum (p < .0001, g = -0.8). Ethanol exposure decreased instantaneous frequency evoked by 250-400 pA current injection in fast-spiking GABAergic interneurons only in female mice (250: p = .019, g = -1.08; 300-450: p = .038, g = -1.06 to- 1.18) but did not significantly affect spontaneous inhibitory postsynaptic currents (sIPSCs) evoked by interneuronal GABA release onto pyramidal neurons.Conclusion: TTAAE activates apoptotic pathways in subicular interneurons, leading to long-term, sex-specific changes, reducing male neuron density and altering female interneuron function. These effects may underlie memory deficits demonstrated in mice with TTAAE.

The minimum legal age (MLA) for non-medical cannabis use remains a contentious issue. While current regulations range from 18 to 21 years across jurisdictions, some advocates propose raising the threshold to 25, arguing that brain maturation continues until that age. They postulate that even individuals 22 through 25 exhibit increased neurodevelopmental vulnerability to cannabis. This Perspective examines this assertion, discussing the neuroscientific evidence on brain development and its implications for setting legal age limits for cannabis use. While most major macrostructural and microstructural brain development occurs early in life, processes such as synaptic pruning, gene expression, and prefrontal cortical changes persist through adolescence, with more subtle changes extending into the third decade. Nonetheless, there is no empirically defined neurodevelopmental endpoint at age 25. Brain maturation is a nonlinear process, region-specific, influenced by sex and specific physiological processes. Importantly, existing evidence does not demonstrate greater long-term cognitive or neurophysiological harm attributable to cannabis use in individuals aged 18-25 years compared to those older than 25. This Perspective concludes that an MLA between 18-21 years is a scientifically supportable and socially coherent threshold for non-medical cannabis use. Policy decisions should be informed not only by neurobiological evidence but also by legal, justice, sociocultural, psychological, and historical considerations.

Background: People with opioid use and opioid use-related problems are highly stigmatized groups. Negative attitudes and perceptions held by healthcare providers and the stigma that results are key barriers to treatment entry and treatment provision. A contemporary measure for assessing the attitudes and perceptions of healthcare providers toward this population is needed.Objective: The current study aims to examine the psychometric properties of an adapted person-centered opioid and opioid problems perception questionnaire (PC-OOPPQ).Methods: The adapted PC-OOPPQ psychometric properties were assessed using a nationwide online sample of practicing nurses (N = 493, 460 were female nurses). The sample was randomly divided to perform exploratory (EFA; n = 247) and confirmatory (CFA; n = 246) factor analyses.Results: Using the principal axis factoring (PAF) with orthogonal (Varimax) rotation, the EFA indicated a 19-item four-factor structure (without item # 16), which explained 70.2% of the total variance. Meanwhile, the CFA recommended an 18-item five-factor structure (without items # 14 and 16) that had the best model fit (Comparative Fit Index (CFI) = .938, the Tucker-Lewis Index (TLI) = .924, Standardized Root Mean Square Residual (SRMR) = .055, and Root Mean Square Approximation (RMSEA) = .088)).Conclusions: Apart from one item (item # 16), the proposed five-factor structure is consistent with the person-centered drug and drug problems perception questionnaire factor structure. The current study aims to address stigma associated with opioid use among healthcare professionals using language.

Background: Opioid use disorder (OUD) is a chronic relapsing condition with a high mortality rate. While medications such as methadone are valuable first-line therapies, retention is poor, with the highest dropout rates early in a treatment attempt. Poor outcomes are due in part to the very high rates of co-morbid depression in people with OUD, as depression can drive opioid use. Therefore, administering a rapid-acting antidepressant such as ketamine early in a treatment attempt may be an effective strategy to improve outcomes.Objectives: Here, we describe a case series of three patients (two males, one female) diagnosed with OUD initiating methadone treatment and endorsing symptoms of depression, who met criteria for a single-arm open-label feasibility trial (NCT05051449) at an opioid treatment program in Baltimore, Maryland.Methods: Participants underwent a 2-week ketamine regimen (0.5 mg/kg infusion over 40 min, three times per week for 2 weeks).Results: Ketamine was safe and generally well-tolerated. At 10-day follow-up post-ketamine infusions, participant acceptability ratings were mostly favorable. All three patients remained in treatment through the 3-month timepoint with strong treatment adherence. With treatment, self-reported depression symptoms decreased from severe to mild/moderate in two patients, and from moderate to remission in the third.Conclusions: Randomized controlled trials are warranted to test whether ketamine may be a feasible and safe adjunctive treatment for OUD in patients initiating methadone treatment.

Background: Simultaneous Alcohol and Cannabis (SAC) use is associated with greater negative consequences than individual use. Motives to use are robust predictors of alcohol and cannabis consumption, both separately and simultaneously. Despite the recent development of both a SAC motives measure and its short form, no Spanish adaptation is currently available.Objectives: To provide a Spanish adaptation of the full-length and short-form versions of the simultaneous alcohol and cannabis motives measure and to examine its psychometric properties in a sample of young adult SAC users.Methods: A targeted sampling procedure was used to recruit 612 young cannabis users, of whom 479 reported SAC use (18-25 years old [M = 21.01, SD = 2.14]; 36% female). Following adaptation and translation, participants completed the scale, along with measures of frequency of alcohol, cannabis, and simultaneous use, cannabis motives, and alcohol- and cannabis-related negative consequences.Results: Confirmatory factor analyses showed a four-factor structure (conformity, positive effects, calm/coping, and social). Moreover, the results indicated acceptable internal consistency (.70-.88), providing evidence of convergent, discriminant, and predictive validity for most dimensions.Conclusions: The results suggest that both versions of the scale are valuable tools for assessing motives for SAC consumption among young adults. These scales could aid in investigating motives for SAC use and informing interventions to mitigate associated harms.

Background: Drug checking is a harm reduction intervention that uses chemical analytical methods to provide information on the composition of illicit drug mixtures. It is necessary to expand the reach of drug checks to fully meet the needs of populations who use drugs who are at risk of overdose. Technical barriers to drug checking, such as software that is challenging to use without extensive training and practice, hinder the expansion of these services.Objectives: This study describes the development, architecture, and deployment of a custom FTIR-based software framework. Components of this framework are useful across several models of drug checking.Methods: A kiosk application controls a spectrometer and uploads the spectral and survey data to a centralized database. An analysis suite facilitates spectral interpretation using libraries, a repository of previous data, and analysis tools. Individual drug checking results are accessible online. Aggregated data are viewed internally via a dashboard. Public-facing reports are tailored to different communities.Results: The software was successfully deployed with a total of 6 remote service sites operating by 2024. Between May 2022 and December 2024, 2673 drug samples were checked for 1926 clients, including hundreds accessing drug checking for the first time. Weekly and monthly reports of aggregate drug data were created.Conclusions: By lowering technical barriers and supporting real-time reporting, our software framework expanded service access and provided actionable data to both communities and public health stakeholders. This method represents a meaningful advancement in the technological infrastructure necessary to sustain and expand drug checking efforts.

Background: Gabapentin may help manage opioid withdrawal symptoms, but its effectiveness during buprenorphine taper and transition to naltrexone is uncertain.Objectives: To assess gabapentin's efficacy in improving outcomes for lifetime prescription opioid use disorder (POUD) during outpatient buprenorphine taper and transition to extended-release naltrexone.Methods: This 12-week randomized, double-blind, placebo-controlled trial enrolled 117 (55% male) POUD participants. Weeks 1-3, participants attended clinic 5 days/week for medication, therapy, and assessments, including weekly craving and thrice-weekly opioid withdrawal and supervised urine screens. Participants were inducted onto buprenorphine (12 mg), randomized to receive either placebo or gabapentin (800 mg BID), and underwent a 10-day buprenorphine taper. In week 4, participants transitioned from oral to extended-release naltrexone. Chi-square and generalized estimating equation models assessed outcomes. A subset with baseline fentanyl tests was also examined for fentanyl's impact on outcomes.Results: Of 117 participants, 75 (64.1%) completed the buprenorphine taper (41 gabapentin, 34 placebo), and 24 (20.5%) transitioned to naltrexone (12 gabapentin, 12 placebo). No significant group differences were observed in taper completion, naltrexone transition, craving, withdrawal, or opioid use. Fentanyl-positive participants had lower taper completion (47.8% vs. 75.8%, OR = 0.286, p = .033) and more opioid-positive urines (z = -4.24, p < .0001). Fentanyl-positive participants on gabapentin had higher COWS (z = 3.70, p = .001) and SOWS (z = 3.73, p = .001) scores, while fentanyl-negative participants on gabapentin had lower SOWS scores than those on placebo (z = -3.52, p = .002).Conclusions: Fentanyl exposure impairs buprenorphine taper success and worsens withdrawal in the presence of gabapentin, underscoring the need to tailor OUD treatment in fentanyl-exposed patients. (Clinicialtrials.gov ID NCT02543944).

Background: Healthcare readmissions are often perceived as negative outcomes. However, in the context of substance use disorder (SUD) treatment, they may reflect both systemic gaps and sustained engagement. Despite their frequency, the determinants of SUD readmission remain underexplored, particularly in Latin America, where non-injected drug use is highly prevalent.Objective: To identify factors associated with SUD treatment readmission and examine contextual influences shaping readmission risk in Chile.Method: We employed a mixed-methods parallel convergent design. Quantitative analyses included 107,559 treatment episodes (84,978 males; 22581 females) recorded from 2010 to 2019. We estimated Average Hazard Ratios (AHR) using a PWP-GT model. Qualitative data from 14 in-depth interviews explored social, familial, and environmental contributors to readmission.Results: Compared to those who did not complete, completing ambulatory treatment was associated with a lower risk of readmission (AHR = 0.83, 95% CI: 0.78-0.88), while no significant effect was found in residential programs. Women had a higher risk of readmission than men in both ambulatory (AHR = 1.36, 95% CI: 1.31-1.42) and residential settings (AHR = 1.42, 95% CI: 1.33-1.51). Qualitative findings revealed reintegration difficulties post-discharge, especially in high-risk environments. Gender roles pressured women to seek treatment, particularly when they were primary caregivers.Conclusion: Support for caregiving responsibilities may enhance treatment retention and reduce readmissions among women. Clinicians and policymakers should consider implementing structured post-discharge follow-up and community-based support systems, especially after residential treatment, to mitigate environmental risks and sustain recovery.