High frequency cocaine use is associated with poor psychological and health outcomes. However, we know little about the computational processes that contribute to high frequency use, especially among individuals with cocaine use disorder. Here, we demonstrate a role for efficiency of evidence accumulation (EEA) in these use patterns. Treatment-seeking adults (N = 127) with cocaine use disorder completed cognitive tasks and self-report measures at baseline, as part of a larger trial. Using hierarchical drift diffusion modeling, we estimated subject-level, condition-specific drift rates – the speed of evidence accumulation for goal-relevant stimuli – for two neurocognitive tasks (n-Back, Cued Go/No Go). Confirmatory factor analysis supported the existence of a task-general EEA factor that drives performance across cognitive tasks. Lower EEA statistically mediated the effect of trait impulsivity on high frequency cocaine use. These findings support the view that EEA constitutes a proximal neurocomputational mechanism of high frequency cocaine use.

OBJECTIVE:Objectively verified reductions in cocaine use may be a more viable treatment target compared to complete abstinence. However, few studies have examined the associated health benefits of this change. This study assessed how quality-of-life outcomes (psychological functioning, social functioning, sleep) change with reductions in cocaine-positive urine drug screens. METHOD:Participants (n = 107) with cocaine use disorder enrolled in a 12-week contingency management trial and were randomly assigned to high-value, low-value, or noncontingent control groups. Quality of life was measured at predetermined intervals over the course of the trial. Linear mixed models disaggregated the proportion of cocaine-negative urine screens into between-subject (i.e., a participant's average use across the trial) and within-subject (i.e., a participant's deviation from their average) components to separately estimate their associations with quality-of-life outcomes. RESULTS:Overall, higher proportions of cocaine-negative urine test results were associated with statistically significant, although modest, between- and within-subject changes in several quality-of-life measures, including psychosocial functioning, mental health, and sleep. Participants who reached at least 75% cocaine-negative urine test results during treatment demonstrated improvements in all Short Inventory of Problems-Cocaine outcomes, excluding Total Score. CONCLUSIONS:These findings indicate that reducing cocaine use improves quality-of-life outcomes in people with cocaine use disorder. These results also extend prior research on more robust health improvements that emerge when participants attain 75% negative urine test results over a trial. Future research should explore the extent to which these beneficial outcomes apply to other cocaine use disorder samples, including those with more severe comorbid psychosocial challenges at baseline. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

Introduction Limited prospective research has evaluated the health benefits associated with changing levels of drug use, aside from complete abstinence. This study determined whether lower levels of cocaine use impacted physiological indices (e.g., mean arterial pressure) and biomarkers (e.g., stromal cell derived factor-1a [SDF-1a], soluble intercellular adhesion molecule-1 [ICAM-1], neutrophil activating peptide-2 [CXCL7]) of cardiovascular health. Methods Treatment seeking participants enrolled in a 12-week single-blind, randomized, controlled cocaine contingency management trial. Participants were randomly assigned to High Value Reinforcers for cocaine abstinence (n = 41), Low Value Reinforcers for cocaine abstinence (n = 33) or a non-contingent Control group (n = 33). Physiological indices were collected at each clinic visit and averaged over each week of treatment. Biomarkers were assayed at 6-week intervals. Percent benzoylecgonine negative urines matching measurement timeframes were used to predict changes in outcomes using generalized linear models. Results Reductions in mean arterial pressure were observed in the High Value group, particularly during follow-up (χ(1,107)2= 6.6, p < .05). Regardless of group, less cocaine use was associated with decreased SDF-1a and increased ICAM-1 and CXCL7 levels (all χ(1,107)2> 4.7; p values < 0.05). Conclusions Improved blood pressure was observed in the High Value treatment group, who provided the greatest percent of cocaine negative urine samples but did not achieve total abstinence. Less cocaine use was also associated with changes in cardiac biomarkers that may indicate tissue repair. These results indicate that less cocaine use, even without complete abstinence, can improve blood pressure, and potentially heal cardiovascular insult, in individuals with Cocaine Use Disorder.

OBJECTIVES/GOALS: Contingency management (CM) procedures yield measurable reductions in cocaine use. This poster describes a trial aimed at using CM as a vehicle to show the biopsychosocial health benefits of reduced use, rather than total abstinence, the currently accepted metric for treatment efficacy. METHODS/STUDY POPULATION: In this 12-week, randomized controlled trial, CM was used to reduce cocaine use and evaluate associated improvements in cardiovascular, immune, and psychosocial well-being. Adults aged 18 and older who sought treatment for cocaine use (N=127) were randomized into three groups in a 1:1:1 ratio: High Value ($55) or Low Value ($13) CM incentives for cocaine-negative urine samples or a non-contingent control group. They completed outpatient sessions three days per week across the 12-week intervention period, totaling 36 clinic visits and four post-treatment follow-up visits. During each visit, participants provided observed urine samples and completed several assays of biopsychosocial health. RESULTS/ANTICIPATED RESULTS: Preliminary findings from generalized linear mixed effect modeling demonstrate the feasibility of the CM platform. Abstinence rates from cocaine use were significantly greater in the High Value group (47% negative; OR = 2.80; p = 0.01) relative to the Low Value (23% negative) and Control groups (24% negative;). In the planned primary analysis, the level of cocaine use reduction based on cocaine-negative urine samples will serve as the primary predictor of cardiovascular (e.g., endothelin-1 levels), immune (e.g., IL-10 levels) and psychosocial (e.g., Addiction Severity Index) outcomes using results from the fitted models. DISCUSSION/SIGNIFICANCE: This research will advance the field by prospectively and comprehensively demonstrating the beneficial effects of reduced cocaine use. These outcomes can, in turn, support the adoption of reduced cocaine use as a viable alternative endpoint in cocaine treatment trials.

This study determined the effects of reduced cocaine use on immune function. Treatment seeking participants with Cocaine Use Disorder enrolled in a 12-week contingency management trial to reduce cocaine use. Participants were randomly assigned 1:1:1 to High Value Reinforcers (i.e., $55/negative urine sample) for cocaine abstinence (n = 41), Low Value Reinforcers (i.e., $13/negative urine sample) for cocaine abstinence (n = 33) or Non-Contingent Control (n = 33). Immune measures were collected at 6-week intervals. The High Value group had greatest use reductions, increased erythema and IL-6 and decreased IL-10 and CCL5, suggesting an activated immune response. Cocaine use reduction may promote changes in immune health.

Background: Contingency Management (CM) is being piloted as a treatment for stimulant use disorder in several US states, highlighting the need for treatment optimization. One important goal of optimization is decreasing drug use during the early stages of treatment, which has predicted success in other interventions. However, this "critical period" has not been reported in CM trials. The purpose of this analysis was to determine if, after accounting for baseline abstinence and incentive condition, abstinence in a CM trial for people with Cocaine Use Disorder (CUD) could be predicted by cocaine use during a first-week critical period. Methods: Eighty-seven participants with CUD were randomized to receive contingent high or low value incentives for cocaine abstinence or were in a non-contingent control group. Generalized estimating equations (GEE) were used to analyze urine test results over 36 timepoints during the 12-week intervention. To assess for a critical period, the first three visits were included in the GEE as a covariate for remaining urine test results. Results: Participants who provided more negative samples during the critical period were significantly more likely to produce a negative urine sample during the remainder of the trial, though some effects of group remained after controlling for the critical period. Conclusions: These results indicate that a critical period exists for CM trials, and it can explain a substantial amount of future performance. Early contact with an abstinence-contingent high magnitude alternative reinforcer may explain additional performance beyond the critical period, further justifying the use of high magnitude alternative reinforcers.

Objectives Highly effective treatments for cannabis use disorder (CUD) are lacking, and patient preferences have not been considered during treatment development. We therefore conducted an exploratory crowdsourced survey of individuals reporting current cannabis use and a willingness to cut down or quit their cannabis use, to determine their interest in various treatment aspects. Methods Subjects (n = 63) were queried about their willingness to take medications as a function of type, route, and regimen and to participate in adherence monitoring. Subjects were also asked about their willingness to engage in behavioral/psychosocial interventions as a function of type, setting, and duration. Measures theorized to be associated with treatment preferences were also collected, including cannabis use variables, readiness to change, reduction or cessation goal, perceived cessation barriers, and medication use beliefs and behaviors. Results Survey responses indicated that efforts to develop CUD medications should focus on nonsynthetic compounds administered orally or by mouth spray no more than once per day to maximize patient acceptance. Remote adherence monitoring and one-on-one outpatient behavioral treatment approaches, especially contingency management, are also anticipated to enhance participation. Most subjects indicated a preference to reduce their cannabis use rather than quit. Conclusions These data provide guidance for the development of CUD interventions based on the preferences of individuals interested in treatment for their cannabis use. Additional research is needed to confirm these results in a larger sample and determine if matching CUD patients with their preferred treatments improves success rates.

ABSTRACT Background: The COVID-19 pandemic and subsequent economic crisis has provided a unique opportunity to investigate the effects of economic shifts on substance use. Existing literature on this relationship is limited and conflicting, warranting further exploration. Objective: This study aimed to identify relationships between socioeconomic status (SES), demographic variables, and substance use patterns before and after government-mandated business closures due to COVID-19. Methods: Participants were recruited based on self-reported substance use through Amazon’s Mechanical Turk (MTurk). Qualifying participants (N = 315, 43% female, mean age = 35.35) reported their substance use and SES for two-week periods before and after pandemic-related business closures. Regression models analyzed relationships between substance use and study variables. Results: Regression models found that, during COVID-19 closures, greater financial strain predicted decreased benzodiazepine (β = −1.12) and tobacco (β = 1.59) use. Additionally, certain predictor variables (e.g., participants’ age [β = 1.22], race [β = −4.43], psychiatric disorders including ADHD [β = −2.73] and anxiety [β = 1.53], and concomitant substance use [β = 3.38]) predicted changes in substance use patterns; however, the directionality of these associations varied across substances. Conclusion: Specific substance use patterns were significantly and differentially impacted by economic strain, psychiatric diagnoses, and concomitant substance use. These results can help direct harm reduction efforts toward populations at greatest risk of harmful substance use following the pandemic.

Spinal cord injury (SCI) can have profound effects on the autonomic and cardiovascular systems, notably with injuries above high-thoracic levels that result in the development of autonomic dysreflexia (AD) characterized by volatile hypertension in response to exaggerated sympathetic reflexes triggered by afferent stimulation below the injury level. Pathophysiological changes associated with the development of AD include sprouting of both nociceptive afferents and ascending propriospinal 'relay' neurons below the injury, as well as dynamic changes in synaptic inputs onto sympathetic preganglionic neurons. However, it remains uncertain whether synapse formation between sprouted c-fibers and propriospinal neurons contributes to the development of exaggerated sympathetic reflexes produced during AD. We previously reported that once daily treatment with the anti-epileptic and neuropathic pain medication, gabapentin (GBP), at low dosage (50 mg/kg) mitigates experimentally induced AD soon after injections, likely by impeding glutamatergic signaling. Since much higher doses of GBP are reported to block the formation of excitatory synapses, we hypothesized that continuous, high dosage GBP treatment after SCI might prevent the formation of aforementioned aberrant synapses and, accordingly, reduce the incidence and severity of AD. Adult female rats implanted with aortic telemetry probes for hemodynamic monitoring underwent T4-transection SCI and immediately received 100 mg/kg (i.p.) of GBP and then every six hours (400 mg/kg/day) for 4-weeks after injury. We assessed daily body weight, mean arterial pressure, heart rate, frequency of spontaneous AD, and hemodynamic changes during colorectal distension (CRD) to establish whether high dose GBP treatment prophylactically mitigates both AD and associated aberrant synaptic plasticity. This regimen significantly reduced both the absolute blood pressure reached during experimentally induced AD and the time required to return to baseline afterwards. Conversely, GBP prevented return to pre-injury body weights and paradoxically increased the frequency of spontaneously occurring AD. While there were significant decreases in the densities of excitatory and inhibitory pre-synaptic markers in the lumbosacral dorsal horn following injury alone, they were unaltered by continuous GBP treatment. This indicates distinct mechanisms of action for acute GBP to mitigate induced AD whereas chronic GBP increases non-induced AD frequencies. While high dose prophylactic GBP is not recommended to treat AD, acute low dose GBP may hold therapeutic value to mitigate evoked AD, notably during iatrogenic procedures under controlled clinical conditions.

Our previous studies reported that pharmacological maintenance of mitochondrial bioenergetics after experimental spinal cord injury (SCI) provided functional neuroprotection. Recent evidence indicates that endogenous mitochondrial transfer is neuroprotective as well, and, therefore, we extended these studies with a novel approach to transplanting exogenous mitochondria into the injured rat spinal cord. Using a rat model of L1/L2 contusion SCI, we herein report that transplantation of exogenous mitochondria derived from either cell culture or syngeneic leg muscle maintained acute bioenergetics of the injured spinal cord in a concentration-dependent manner. Moreover, transplanting transgenically labeled turbo green fluorescent (tGFP) PC12-derived mitochondria allowed for visualization of their incorporation in both a time-dependent and cell-specific manner at 24h, 48h, and 7 days post-injection. tGFP mitochondria co-localized with multiple resident cell types, although they were absent in neurons. Despite their contribution to the maintenance of normal bioenergetics, mitochondrial transplantation did not yield long-term functional neuroprotection as assessed by overall tissue sparing or recovery of motor and sensory functions. These experiments are the first to investigate mitochondrial transplantation as a therapeutic approach to treating spinal cord injury. Our initial bioenergetic results are encouraging, and although they did not translate into improved long-term outcome measures, caveats and technical hurdles are discussed that can be addressed in future studies to potentially increase long-term efficacy of transplantation strategies.

Autonomic dysreflexia (AD) is a potentially life-threatening syndrome in individuals with spinal cord injury (SCI) above the T6 spinal level that is characterized by episodic hypertension in response to noxious stimuli below the lesion. Maladaptive intraspinal plasticity is thought to contribute to the temporal development of AD, and experimental approaches that reduce such plasticity mitigate the severity of AD. The mammalian target of rapamycin (mTOR) has gained interest as a mediator of plasticity, regeneration, and nociceptor hypersensitivity in the injured spinal cord. Based on our preliminary data that prolonged rapamycin (RAP) treatment markedly reduces mTOR activity in the cord weeks after high-thoracic (T4) spinal transection, we sought to determine whether RAP could modulate AD development by impeding intraspinal plasticity. Naïve and injured rats were administered RAP or vehicle every other day, beginning immediately after injury for four weeks, and hemodynamic monitoring was conducted to analyze the frequency of spontaneously occurring AD, as well as the severity of colorectal distention (CRD) induced AD. Results showed that after SCI, RAP significantly exacerbated sustained body weight loss and caused a marked elevation in resting blood pressure, with average daily blood pressure rising above even normal naïve levels within one week after injury. Moreover, RAP significantly increased the frequency of daily spontaneous AD and increased the absolute blood pressure induced by CRD at three weeks post-injury. These dynamic cardiovascular effects were not, however, correlated with changes in the density of nociceptive c-fibers or c-Fos+ neurons throughout the spinal cord, indicating that intraspinal plasticity associated with AD was not altered by treatment. These findings caution against the use of RAP as a therapeutic intervention for SCI because it evokes toxic weight loss and exacerbates cardiovascular dysfunction perhaps mediated by increased peripheral nociceptor sensitivity and/or vascular resistance.

Pioglitazone is an FDA-approved PPAR-γ agonist drug used to treat diabetes, and it has demonstrated neuroprotective effects in multiple models of central nervous system (CNS) injury. Acute treatment after spinal cord injury (SCI) in rats is reported to suppress neuroinflammation, rescue injured tissues, and improve locomotor recovery. In the current study, we additionally assessed the protective efficacy of pioglitazone treatment on acute mitochondrial respiration, as well as functional and anatomical recovery after contusion SCI in adult male C57BL/6 mice. Mice received either vehicle or pioglitazone (10mg/kg) at either 15min or 3h after injury (75kdyn at T9) followed by a booster at 24h post-injury. At 25h, mitochondria were isolated from spinal cord segments centered on the injury epicenters and assessed for their respiratory capacity. Results showed significantly compromised mitochondrial respiration 25h following SCI, but pioglitazone treatment that was initiated either at 15min or 3h post-injury significantly maintained mitochondrial respiration rates near sham levels. A second cohort of injured mice received pioglitazone at 15min post injury, then once a day for 5days post-injury to assess locomotor recovery and tissue sparing over 4weeks. Compared to vehicle, pioglitazone treatment resulted in significantly greater recovery of hind-limb function over time, as determined by serial locomotor BMS assessments and both terminal BMS subscores and gridwalk performance. Such improvements correlated with significantly increased grey and white matter tissue sparing, although pioglitazone treatment did not abrogate long-term injury-induced inflammatory microglia/macrophage responses. In sum, pioglitazone significantly increased functional neuroprotection that was associated with remarkable maintenance of acute mitochondrial bioenergetics after traumatic SCI. This sets the stage for dose-response and delayed administration studies to maximize pioglitazone's efficacy for SCI while elucidating the precise role that mitochondria play in governing its neuroprotection; the ultimate goal to develop novel therapeutics that specifically target mitochondrial dysfunction.

The current study demonstrates the feasibility of using serial magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) in vivo to quantify temporally spinal cord injury (SCI) pathology in adult female Sprague-Dawley rats that were scanned prior to a moderate or severe upper lumbar contusion SCI. Injured rats were behaviorally tested for hind limb locomotion (Basso, Beattie, Bresnahan [BBB] scores) weekly for 4 weeks and scanned immediately after each session, ending with terminal gait analyses prior to euthanasia. As a measure of tissue integrity, fractional anisotropy (FA) values were significantly lower throughout the spinal cord in both injury cohorts at all time-points examined versus pre-injury. Moreover, FA values were significantly lower following severe versus moderate SCI at all time-points, and FA values at the injury epicenters at all time-points were significantly correlated with both spared white and gray matter volumes, as well as lesion volumes. Critically, quantified FA values at subacute (24 h) and all subsequent time-points were highly predictive of terminal behavior, reflected in significant correlations with both weekly BBB scores and terminal gait parameters. Critically, the finding that clinically relevant subacute (24 h) FA values accurately predict long-term functional recovery may obviate long-term studies to assess the efficacy of therapeutics tested experimentally or clinically. In summary, this study demonstrates a reproducible serial MRI procedure to predict the long-term impact of contusion SCI on both behavior and histopathology using subacute DTI metrics obtained in vivo to accurately predict multiple terminal outcome measures, which can be particularly valuable when comparing experimental interventions.

While a number of early studies demonstrated that hippocampal damage attenuates the expression of recent, but not remotely trained tasks, an emerging body of evidence has shown that damage to, or inactivation of, the hippocampus often impairs recall across a wide range of training–testing intervals. Collectively, these data suggest that the time course of hippocampal involvement in the storage or recall of previously-acquired memories may differ according to hippocampal subregion and the particular learning task under consideration. The present study examined the contributions of dorsal (DH) and ventral (VH) hippocampus to the expression of previously-acquired trace fear conditioning, a form of Pavlovian conditioning in which the offset of an initially neutral cue or cues and the onset of an aversive stimulus is separated by a temporal (trace) interval. Specifically, either saline or the GABA-A agonist muscimol was infused into DH or VH prior to testing either 1, 7, 28, or 42days after trace fear conditioning. The results revealed a marked dissociation: pre-testing inactivation of DH failed to impair performance at any time-point, while pre-testing inactivation of VH impaired performance at all time-points. Importantly, pre-testing inactivation of VH had no effect on the performance of previously-acquired delay conditioning, suggesting that the deficits observed in trace conditioning cannot be attributed to a deficit in performance of the freezing response. Collectively, these data suggest that VH, but not DH, remains a neuroanatomical locus critical to the recall or expression of trace fear conditioning over an extended period of time.