Early Abstinence Research Articles

Dopamine transmission at D1 and D2 receptors in the nucleus accumbens contributes to the expression of incubation of cocaine craving.

Relapse represents a consistent clinical problem for individuals with substance use disorder. In the incubation of craving model of persistent craving and relapse, cue-induced drug seeking progressively intensifies or "incubates" during the first weeks of abstinence from drug self-administration and then remains high for months. Previously, we and others have demonstrated that expression of incubated cocaine craving requires strengthening of excitatory synaptic transmission in the nucleus accumbens core (NAcc). However, despite the importance of dopaminergic signaling in the NAcc for motivated behavior, little is known about the role that dopamine (DA) plays in the incubation of cocaine craving. Here we used fiber photometry to measure DA transients in the NAcc of male and female rats during cue-induced seeking tests conducted in early abstinence from cocaine self-administration, prior to incubation, and late abstinence, after incubation of craving has plateaued. We observed DA transients time-locked to cue-induced responding but their magnitude did not differ significantly when measured during early versus late abstinence seeking tests. Next, we tested for a functional role of these DA transients by injecting DA receptor antagonists into the NAcc just before the cue-induced seeking test. Blockade of either D1 or D2 DA receptors reduced cue-induced cocaine seeking after but not before incubation. We found no main effect of sex or significant interaction of sex with other factors in our experiments. These results suggest that DA contributes to incubated cocaine seeking but the emergence of this role reflects changes in postsynaptic responsiveness to DA rather than presynaptic alterations.

Bed nucleus of the stria terminalis network responses to unpredictable threat in early alcohol abstinence.

Anxiety during early alcohol abstinence, likely resulting from neural changes caused by chronic alcohol use, contributes to high relapse rates. Studies in rodents show heightened activation during early abstinence in the bed nucleus of the stria terminalis (BNST)-a neural hub for anxiety-and its extended anxiety-related corticolimbic network. Despite the clinical importance of early abstinence, few studies investigate the underlying neural mechanisms. To address this gap, we investigated brain function in early alcohol abstinence (EA = 20, 9 women) relative to controls (HC = 20, 11 women) using an unpredictable threat task shown to engage the BNST and corticolimbic brain regions involved in anxiety and alcohol use disorder (AUD). Group, anxiety, and sex were predictors used to determine whole-brain activation and BNST functional connectivity. We found widespread interactions of group × anxiety and group × anxiety × sex for both activation and BNST connectivity during unpredictable threat. In the EA group, higher anxiety was correlated with activation in the BNST, rostral anterior cingulate cortex (ACC), insula (men only), and dorsal ACC (men only). In the HC group, higher anxiety was negatively correlated with activation in the BNST, nucleus accumbens, thalamus, and insula (men only). For connectivity, anxiety was positively correlated in EA and negatively correlated in HC, between the BNST and the amygdala, ventromedial prefrontal cortex (PFC), and dorsomedial PFC; EA men showed stronger BNST-vmPFC connectivity than HC men. These novel findings provide preliminary evidence for alterations in the BNST and anxiety-related corticolimbic brain regions in early alcohol abstinence, adding to growing literature in humans supporting the BNST's role in anxiety and sex-dependent effects of chronic alcohol use.

Buprenorphine treatment and clinical outcomes under the opioid use disorder cascade of care

BackgroundChallenges to engagement and retention on buprenorphine undermine treatment of individuals with opioid use disorder (OUD). Under the OUD Cascade of Care framework, we sought to identify patient characteristics and treatment response associated with superior clinical outcomes. MethodsA retrospective cohort study of specialty buprenorphine treatment patients entering treatment (n=19,487) based on EHR records from a large multi-state buprenorphine treatment network (2011–2019). Person-level care episodes were evaluated across treatment intake, engagement (i.e. 2+ visits in the month following intake), and retention at 6, 12, and 24 months. Time to achieving 90 days of continuous opioid abstinence was assessed using Cox proportional hazards regressions models and also assessed as a predictor of long-term retention. ResultsMost patients engaged (82.4 %), but retention steadily declined over 6-month (38.7 %), 12-month (26.2 %), and 24-month (17.1 %) timepoints. Opioid-positive baseline tests were associated with lower hazards of achieving continuous abstinence for both buprenorphine-positive (aHR=0.33, p<.001) and buprenorphine-negative (aHR=0.49,p<.001) intakes. Opioid abstinence was associated with buprenorphine-positive baseline testing (aHR=1.59,p<.001), especially for those testing opioid-negative (aHR=1.82,p<.001). Patients who achieved and sustained abstinence at 6 months in care were 4.1 and 5.5 times as likely to achieve 12-month and 24-month retention, respectively, compared to patients with intermittent opioid use. ConclusionTreatment discontinuation was concentrated early in care and buprenorphine and opioid status at intake were prognostic of achieving and sustaining abstinence. Early abstinence was associated with higher likelihood of subsequent stage progression. Implementing interventions to support early clinical stability for high-risk patients is critical to improve clinical outcomes.

Brain mGlu5 Is Linked to Cognition and Cigarette Smoking but Does Not Differ From Control in Early Abstinence From Chronic Methamphetamine Use.

The group-I metabotropic glutamate receptor subtype 5 (mGlu5) has been implicated in methamphetamine exposure in animals and in human cognition. Because people with methamphetamine use disorder (MUD) exhibit cognitive deficits, we evaluated mGlu5 in people with MUD and controls and tested its association with cognitive performance. Positron emission tomography was performed to measure the total VT of [18F]FPEB, a radiotracer for mGlu5, in brains of participants with MUD (abstinent from methamphetamine for at least 2 weeks, N = 14) and a control group (N = 14). Drug use history questionnaires and tests of verbal learning, spatial working memory, and executive function were administered. Associations of VT with methamphetamine use, tobacco use, and cognitive performance were tested. MUD participants did not differ from controls in global or regional VT, and measures of methamphetamine use were not correlated with VT. VT was significantly higher globally in nonsmoking vs smoking participants (main effect, P = .0041). MUD participants showed nonsignificant weakness on the Rey Auditory Verbal Learning Task and the Stroop test vs controls (P = .08 and P = .13, respectively) with moderate to large effect sizes, and significantly underperformed controls on the Spatial Capacity Delayed Response Test (P = .015). Across groups, Rey Auditory Verbal Learning Task performance correlated with VT in the dorsolateral prefrontal cortex and superior frontal gyrus. Abstinent MUD patients show no evidence of mGlu5 downregulation in brain, but association of VT in dorsolateral prefrontal cortex with verbal learning suggests that medications that target mGlu5 may improve cognitive performance.

The Role of Repetitive Transcranial Magnetic Stimulation in Reduction of Opioid Craving; A Single Blinded Randomized Sham Controlled Clinical Trial

Abstract Background Opioid use disorder (OUD) poses a great concern due to problems associated with their abuse as well as fatal and non fatal overdose consequences. Craving has a complex relationship with opioid use and relapse. Developing new, effective treatments for substance use disorders (SUDs), including opioid use disorders is crucial. This study aimed to assess the effect of 18 sessions of high frequency (HF) repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) on opioid craving in early abstinence using brief substance craving scale (BSCS) for Tramadol and morphine and Heroin craving questionnaire (HCQ) for Heroin craving. Results There was a statistically significant reduction in craving scores in the group of OUD patients receiving real rTMS compared to those receiving sham rTMS for both BSCS( p value = 0.044) and HCQ (p value = 0.002). A statistically significant positive correlation was revealed between the number of hospital admissions and the mean scores of post rTMS HCQ scores (r = 0.05, p value = 0.040). Conclusion High frequency 10 Hz rTMS over the left DLPFC for 18 treatment sessions reduced craving OUD patients during early abstinence. These preliminary results suggest that 10 Hz rTMS of the left DLPFC may be used in treatment of OUD; so our study recommends that use of rTMS in reduction of opioid craving in early abstinence.

Dopamine transmission at D1 and D2 receptors in the nucleus accumbens contributes to the expression of incubation of cocaine craving.

Relapse represents a consistent clinical problem for individuals with substance use disorder. In the incubation of craving model of persistent craving and relapse, cue-induced drug seeking progressively intensifies or 'incubates' during the first weeks of abstinence from drug self-administration and then remains high for months. Previously, we and others have demonstrated that expression of incubated cocaine craving requires strengthening of excitatory synaptic transmission in the nucleus accumbens core (NAcc). However, despite the importance of dopaminergic signaling in the NAcc for motivated behavior, little is known about the role that dopamine (DA) plays in the incubation of cocaine craving. Here we used fiber photometry to measure DA transients in the NAcc of male and female rats during cue-induced seeking tests conducted in early abstinence from cocaine self-administration, prior to incubation, and late abstinence, after incubation of craving has plateaued. We observed DA transients time-locked to cue-induced responding but their magnitude did not differ significantly when measured during early versus late abstinence seeking tests. Next, we tested for a functional role of these DA transients by injecting DA receptor antagonists into the NAcc just before the cue-induced seeking test. Blockade of either D1 or D2 DA receptors reduced cue-induced cocaine seeking after but not before incubation. We found no main effect of sex in our experiments. These results suggest that DA contributes to incubated cocaine seeking but the emergence of this role reflects changes in postsynaptic responsiveness to DA rather than presynaptic alterations.

Altered Physiological, Affective, and Functional Connectivity Responses to Acute Stress in Patients With Alcohol Use Disorder

BackgroundThere is evidence that the processing of acute stress is altered in alcohol use disorder (AUD), but little is known about how this is manifested simultaneously across different stress parameters and which neural processes are involved. The current study examined physiological and affective responses to stress and functional connectivity in AUD. MethodsSalivary cortisol samples, pulse rate, and affect ratings were collected on 2 days from 34 individuals with moderate or severe AUD during early abstinence and 34 control participants. On one of the days, stress was induced, and on the other day, a nonstressful control task was performed. Following the intervention, participants underwent functional magnetic resonance imaging to assess functional connectivity, with a focus on cortical and subcortical seed regions previously reported to be involved in AUD and/or stress. ResultsFor pulse rate and cortisol, stress responses were blunted in AUD, whereas the affective response was stronger. Neuroimaging analyses revealed stress-related group differences in functional connectivity, involving the connectivity of striatal seeds with the posterior default mode network, cerebellum, and midcingulate cortex and of the posterior default mode network seed with the striatum and thalamus. ConclusionsThe results suggest a dissociation between subjectively experienced distress and the physiological stress response in AUD as well as stress-related alterations in functional connectivity. These findings highlight the complex interplay between chronic alcohol use and acute stress regulation, offering valuable considerations for the development of therapeutic strategies.

Neuropsychological Functioning in Patients with Opioids Dependence during Early Abstinence: A Comparative Study

Neuropsychological Functioning in Patients with Opioids Dependence during Early Abstinence: A Comparative Study

Changes in processing speed during early abstinence from alcohol dependence.

Processing speed is a task-independent construct underpinning more complex goal-related abilities. Processing speed is impaired in alcohol dependence (AD) and is linked to relapse, as are the functions it underpins. Reliable measurement of processing speed may allow tracking of AD recovery trajectories and identify patients requiring additional support. To assess changes in reaction time (RT) from baseline (at the start of a detoxification programme) across early abstinence. Vibrotactile RT was assessed in early recovery between days 3 and 7 of treatment in 66 individuals with AD (25 females; aged 19-74, 44.60 ± 10.60 years) and against 35 controls tested on one occasion (19 females; 41.00 ± 13.60), using two multivariate multiple regressions. A mixed multivariate analysis of covariance (MANCOVA) of available AD data (n = 45) assessed change in RT between timepoints and between treatment settings (outpatient vs inpatient). The group (AD vs control) significantly predicted choice RT at baseline and follow-up but did not significantly predict simple RT or RT variability, which is inconsistent with previous findings. At follow-up, mental fatigue was also predicted by the group, and MANCOVA indicated that this had worsened in inpatients but improved in outpatients. Recovery of RT measures so early in the treatment journey was not in line with previous research which indicates persisting deficits. The interaction between setting and timepoint indicates that despite being typically less medically complex, outpatients require ongoing support and monitoring during their recovery.

Characterizing reward and relief/habit drinking profiles in a study of naltrexone, varenicline, and placebo.

This study aims to clarify differences in mood, craving, and treatment response between reward and relief/habit individuals in a study of naltrexone, varenicline, and placebo. We hypothesized that relief/habit individuals would have a poorer mood during early abstinence and higher levels of alcohol craving than reward individuals. We hypothesized that reward individuals would demonstrate better drinking outcomes on naltrexone versus placebo. Data were culled from a randomized, double-blind, placebo-controlled human trial of 53 individuals (18F/16M) with alcohol use disorder randomized to varenicline (n = 19), naltrexone (n = 15), or matched placebo (n = 19). In this 6-day practice quit trial, participants attempted to abstain from drinking and completed daily diaries. Participants were classified into reward or relief/habit subgroups based on self-reported motivation for drinking. Multilinear models tested differences in mood and alcohol craving between reward and relief/habit individuals. General linear models tested differences between reward and relief/habit individuals' drinking outcomes on each medication versus placebo. Relief/habit individuals showed decreases in positive mood and increases in negative mood over the quit attempt across medications, compared to reward individuals (P's < .05). Reward individuals' tension decreased on naltrexone, while relief/habit individuals' tension remained stable (F = 3.64, P = .03). Reward individuals in the placebo group had higher percent days abstinent than relief individuals in the placebo group (P < .001). This study suggests relief/habit individuals' mood worsens during early abstinence. Our finding that reward individuals' tension decreased on naltrexone and increased on placebo may suggest a clinical response to the medication.

The Insular Cortex→Bed Nucleus of the Stria Terminalis Pathway during Early Abstinence from Chronic Alcohol Use: A Promising Target for Mitigating Negative Emotions and Relapse Risk.

The Insular Cortex→Bed Nucleus of the Stria Terminalis Pathway during Early Abstinence from Chronic Alcohol Use: A Promising Target for Mitigating Negative Emotions and Relapse Risk.

Altered individual gray matter structural covariance networks in early abstinence patients with alcohol dependence.

While alterations in cortical thickness have been widely observed in individuals with alcohol dependence, knowledge about cortical thickness-based structural covariance networks is limited. This study aimed to explore the topological disorganization of structural covariance networks based on cortical thickness at the single-subject level among patients with alcohol dependence. Structural imaging data were obtained from 61 patients with alcohol dependence during early abstinence and 59 healthy controls. The single-subject structural covariance networks were constructed based on cortical thickness data from 68 brain regions and were analyzed using graph theory. The relationships between network architecture and clinical characteristics were further investigated using partial correlation analysis. In the structural covariance networks, both patients with alcohol dependence and healthy controls displayed small-world topology. However, compared to controls, alcohol-dependent individuals exhibited significantly altered global network properties characterized by greater normalized shortest path length, greater shortest path length, and lower global efficiency. Patients exhibited lower degree centrality and nodal efficiency, primarily in the right precuneus. Additionally, scores on the Alcohol Use Disorder Identification Test were negatively correlated with the degree centrality and nodal efficiency of the left middle temporal gyrus. The results of this correlation analysis did not survive after multiple comparisons in the exploratory analysis. Our findings may reveal alterations in the topological organization of gray matter networks in alcoholism patients, which may contribute to understanding the mechanisms of alcohol addiction from a network perspective.

Predicting alcohol relapse post-detoxification: The role of cognitive impairments in alcohol use disorder patients.

Studies on early abstinence suggest that cognitive function is significantly reduced in the first year of abstinence, which raises the question of whether it is relevant to early relapse in patients with substance use disorders. This study investigates the extent to which impairments in executive function and memory predict alcohol relapse in patients with alcohol use disorder (AUD). Understanding these relationships is crucial for improving therapeutic approaches to prevent relapse in patients with AUD. We selected 116 adult patients (79 male and 37 female) diagnosed with AUD based on DSM-5 criteria, all of whom were undergoing alcohol detoxification treatment. A comprehensive array of neuropsychological tests was administered to assess global cognition, memory, and executive functions. Patients' alcohol use was monitored monthly during a 6-month follow-up period. Logistic regression and Cox regression were used to explore the relationship between cognitive function and the likelihood of alcohol relapse. Impairments in global cognition, semantic and phonemic fluency, cognitive flexibility, and learning ability during detoxification were significant predictors of relapse in AUD patients, showing similar predictive values at both 3 and 6 months post-treatment. An abnormal Montreal Cognitive Assessment (MoCA) score increased the risk of relapse by 123% (HR: 2.227), and impairments in both semantic and phonemic fluency each increased the risk by 142% (HR: 2.423). Additionally, abnormal performance on the MoCA, Trail Making Test Part B (TMT-B), and California Verbal Learning Test (CVLT) was associated with a higher number of drinking days at 3 months (IRR: 3.764; IRR: 2.237; IRR: 2.738, respectively) and abnormal MoCA and TMT-B scores at 6 months (IRR: 2.451; IRR: 1.859, respectively). The MoCA test is a valuable tool for predicting relapse risk in AUD patients undergoing detoxification treatment, with similar predictive value for relapse at 3 or 6 months. Learning ability needs to be assessed and their impairments considered in the treatment of AUD patients.Future research should explore strategies for managing patients with impairments in memory and learning ability to enhance treatment effectiveness and prevent relapse.

Interactions between overweight/obesity and alcohol dependence impact human brain white matter microstructure: evidence from DTI.

There is inconsistent evidence for an association of obesity with white matter microstructural alterations. Such inconsistent findings may be related to the cumulative effects of obesity and alcohol dependence. This study aimed to investigate the possible interactions between alcohol dependence and overweight/obesity on white matter microstructure in the human brain. A total of 60 inpatients with alcohol dependence during early abstinence (44 normal weight and 16 overweight/obese) and 65 controls (42 normal weight and 23 overweight/obese) were included. The diffusion tensor imaging (DTI) measures [fractional anisotropy (FA) and radial diffusivity (RD)] of the white matter microstructure were compared between groups. We observed significant interactive effects between alcohol dependence and overweight/obesity on DTI measures in several tracts. The DTI measures were not significantly different between the overweight/obese and normal-weight groups (although widespread trends of increased FA and decreased RD were observed) among controls. However, among the alcohol-dependent patients, the overweight/obese group had widespread reductions in FA and widespread increases in RD, most of which significantly differed from the normal-weight group; among those with overweight/obesity, the alcohol-dependent group had widespread reductions in FA and widespread increases in RD, most of which were significantly different from the control group. This study found significant interactive effects between overweight/obesity and alcohol dependence on white matter microstructure, indicating that these two controllable factors may synergistically impact white matter microstructure and disrupt structural connectivity in the human brain.

Structural indices of brain aging in methamphetamine use disorder

BackgroundMethamphetamine use is surging globally. It has been linked to premature stroke, Parkinsonism, and dementia, suggesting that it may accelerate brain aging. MethodsWe performed a retrospective study to determine if structural indices of brain aging were more prevalent prior to old age (26 – 54 years) in individuals with Methamphetamine Use Disorder (MUD), who were in early abstinence (M ± SD = 22.1 ± 25.6 days) than in healthy control (HC) participants. We compared T1-weighted MRI brain scans in age- and sex-matched groups (n = 89/group) on three structural features of brain aging: the brain volume/cerebrospinal fluid (BV/CSF) index, volume of white matter hypointensities/lesions, and choroid plexus volume. ResultsThe MUD group had a lower mean BV/CSF index and larger volumes of white matter hypointensities and choroid plexus (p-values < 0.01). Regression analyses showed significant age-by-group effects, indicating different age trajectories of the BV/CSF index and choroid plexus volume, consistent with abnormal global brain atrophy and choroid plexus pathology in the MUD group. Significant age and group main effects reflected a larger volume of white matter hypointensities for older participants across groups and for the MUD group irrespective of age. None of the three measures of brain aging correlated significantly with recent use or duration of recent abstinence from methamphetamine. ConclusionsPremature brain pathology, which may reflect cerebrovascular damage and dysfunction of the choroid plexus, occurs in people with MUD. Such pathology may affect cognition and thereby efficacy of behavioral treatments for MUD.

The anterior insula and its projection to amygdala nuclei modulate the abstinence-exacerbated expression of conditioned place preference

RationaleRelapse into substance use is often triggered by exposure to drug-related environmental cues. The magnitude of drug seeking depends on the duration of abstinence, a phenomenon known as the incubation of drug craving. Clinical and preclinical research shows that the insular cortex is involved in substance use disorders and cue-induced drug seeking. However, the role of the insula on memory retrieval and motivational integration for cue-elicited drug seeking remains to be determined.ObjectivesWe investigated the role of the anterior insular cortex (aIC) and its glutamatergic projection to amygdala nuclei (aIC-AMY) on the expression of conditioned place preference (CPP) during early and late abstinence.MethodsMale adult C57BL/6J mice underwent amphetamine-induced CPP, and their preference was tested following 1 or 14 days of abstinence. aIC and aIC-AMY functional role in CPP expression was assessed at both abstinence periods by employing optogenetic silencing and behavioral pharmacology.ResultsCompared to a single day, an exacerbated preference for the amphetamine-paired context was observed after 14 days of abstinence. Photoinhibition of either aIC or aIC-AMY projection reduced CPP expression following late but not early abstinence. Similarly, the antagonism of aIC NMDA receptors reduced CPP expression after 14 days of abstinence but not 1 day.ConclusionsThese results suggest that aIC and its glutamatergic output to amygdala nuclei constitute critical neurobiological substrates mediating enhanced motivational cue reactivity during the incubation of amphetamine craving rather than contextual memory recall. Moreover, cortical NMDA receptor signaling may become sensitized during abstinence, ultimately modulating disproportioned drug seeking.

Forced Abstinence from Volitional Ethanol Intake Drives a Vulnerable Period of Hyperexcitability in BNST-Projecting Insular Cortex Neurons.

The insular cortex (IC) integrates sensory and interoceptive cues to inform downstream circuitry executing adaptive behavioral responses. The IC communicates with areas involved canonically in stress and motivation. IC projections govern stress and ethanol recruitment of bed nucleus of the stria terminalis (BNST) activity necessary for the emergence of negative affective behaviors during alcohol abstinence. Here, we assess the impact of the chronic drinking forced abstinence (CDFA) volitional home cage ethanol intake paradigm on synaptic and excitable properties of IC neurons that project to the BNST (IC→BNST). Using whole-cell patch-clamp electrophysiology, we investigated IC→BNST circuitry 24 h or 2 weeks following forced abstinence (FA) in female C57BL6/J mice. We find that IC→BNST cells are transiently more excitable following acute ethanol withdrawal. In contrast, in vivo ethanol exposure via intraperitoneal injection, ex vivo via ethanol wash, and acute FA from a natural reward (sucrose) all failed to alter excitability. In situ hybridization studies revealed that at 24 h post FA BK channel mRNA expression is reduced in IC. Further, pharmacological inhibition of BK channels mimicked the 24 h FA phenotype, while BK activation was able to decrease AP firing in control and 24 h FA subjects. All together these data suggest a novel mechanism of homeostatic plasticity that occurs in the IC→BNST circuitry following chronic drinking.

A Comparative Assessment of Comprehensive Trail Making Test and Wisconsin Card Sorting Test Among Alcohol Dependence Patients

Introduction: Alcohol, when used frequently, accelerates the ageing process, causes brain damage, and results in a reduced volume of grey and white matter, leading to frontal lobe abnormalities. The neurotoxicity resulting from alcohol overuse affects the higher functions of the brain. This study aimed to evaluate the effect of alcohol dependence on the executive functioning of the brain. Methods: This study was carried out as a case-control study among 60 patients with alcohol dependence and 60 controls. Assessment of executive function was carried out using the Comprehensive trail-making test (CTMT) and the Wisconsin card sorting test (WCST). Comparison between the alcohol dependence group and normal healthy controls were calculated using the Mann-Whitney U test as data followed a non-parametric distribution. Results: The mean age of the participants among the cases and controls was 38.3±5.5 years and 37.8±5.4 years, respectively. The results showed a significant difference in both WCST and CTMT between cases and controls (p&lt;0.05). Conclusion: This study concludes that there was an impaired performance in executive functions in alcohol- dependence patients in early abstinence compared to normal controls showing frontal lobe impairment in alcohol-dependence patients.

Multivariate classification based on large-scale brain networks during early abstinence predicted lapse among male detoxified alcohol-dependent patients.

Identifying biomarkers to predict lapse of alcohol-dependence (AD) is essential for treatment and prevention strategies, but remains remarkably challenging. With an aim to identify neuroimaging features for predicting AD lapse, 66 male AD patients during early-abstinence (baseline) after hospitalized detoxification underwent resting-state functional magnetic resonance imaging and were then followed-up for 6 months. The relevance-vector-machine (RVM) analysis on baseline large-scale brain networks yielded an elegant model for differentiating relapsing patients (n = 38) from abstainers, with the area under the curve of 0.912 and the accuracy by leave-one-out cross-validation of 0.833. This model captured key information about neuro-connectome biomarkers for predicting AD lapse.

Telehealth-Based Contingency Management Targeting Stimulant Abstinence: A Case Series From the COVID-19 Pandemic.

Contingency management (CM) is the gold standard treatment for stimulant use disorder but typically requires twice- to thrice-weekly in-person treatment visits to objectively verify abstinence and deliver therapeutic incentives. There has been growing interest in telehealth-based delivery of CM to support broad access to this essential intervention--a need that has been emphatically underscored by the COVID-19 pandemic. Herein, we present observations from initial efforts to develop and test a protocol for telehealth-based delivery of prize-based CM treatment incentivizing stimulant abstinence. Four participants engaged in hybrid courses of CM, including one or more telehealth-based treatment sessions, involving self-administered oral fluid testing to confirm abstinence. Observations from initial participants informed iterative improvements to telehealth procedures, and a 12-week course of telehealth-based CM was subsequently offered to two additional participants to further evaluate preliminary feasibility and acceptability. In most cases, participants were able to successfully join telehealth treatment sessions, self-administer oral fluid testing, and share oral fluid test results to verify stimulant abstinence. However, further improvements in telehealth-based toxicology testing may be necessary to interpret test results accurately and reliably, especially when colorimetric immunoassay results reflect substance concentrations near the cutoff for point-of-care testing devices. Preliminary findings suggest that telehealth-based CM is sufficiently feasible and acceptable to support future development, in particular through improved methods for remote interpretation and verification of test results. This is especially important in CM, wherein accurate and reliable detection of both early and sustained abstinence is crucial for appropriate delivery of therapeutic incentives.