Opioid Risk Tool, in-hospital opioid exposure, and opioid demand predict pain outcomes following traumatic injury.

Prescribed opioids are a mainstay pain treatment after traumatic injury, but a subgroup of patients may be at risk for continued opioid use. We evaluated the predictive utility of a traditional screening tool, the Opioid Risk Tool (ORT), and two other measures: average in-hospital milligram morphine equivalents (MME) per day and an assessment of opioid demand in predicting pain outcomes. Assessments of pain-related outcomes (pain intensity, interference, injury-related stress, and need for additional pain treatment) were administered at 2 weeks and 12 months post-discharge in a sample of 34 patients hospitalized for traumatic injury. Bayesian linear models were used to evaluate changes in responses over time as a function of predictors. High-risk ORT, higher MME per day, and greater opioid demand predicted less change in outcomes over time. This report provides first evidence that malleable factors of opioid and opioid demand have utility in predicting pain outcomes following traumatic injury.

Contingency management plus acceptance and commitment therapy for initial cocaine abstinence: Results of a sequential multiple assignment randomized trial (SMART).

BACKGROUND: This study tested an adaptive intervention for optimizing abstinence outcomes over phases of treatment for cocaine use disorder using a SMART design. Phase 1 assessed whether 4 weeks of contingency management (CM) improved response with the addition of Acceptance and Commitment Therapy (ACT). Phase 2 assessed pharmacological augmentation with modafinil (MOD) vs. placebo (PLA) for individuals not achieving abstinence during Phase 1. METHOD: For Phase 1 of treatment, participants (N=118) were randomly allocated to ACT+CM or Drug Counseling (DC+CM), the comparison condition. At week 4, treatment response was defined as the submission of six consecutive cocaine-negative urine drug screens (UDS). Phase 1 non-responders were re-randomized to MOD or PLA as adjunct to their initial treatment. Phase 1 responders continued receiving their initial treatment. Primary outcomes included response rate and proportion of cocaine-negative UDS for Phase 1 and 2. Analyses used Bayesian inference with 80% pre-specified as the posterior probability (PP) threshold constituting moderate evidence that an effect exists. RESULTS: Phase 1 response was higher in the ACT+CM group (24.5%) compared to the DC+CM group (17.5%; PP = 84.5%). In Phase 2, the proportion of cocaine-negative UDS among Phase 1 responders did not differ by initial treatment (PP = 61.8%) but remained higher overall compared to Phase 1 non-responders (PPs > 99%). No evidence of an effect favoring augmentation with MOD was observed. DISCUSSION: Adding ACT to CM increased abstinence initiation. Initial responders were more likely to remain abstinent compared to initial non-responders, for whom modafinil was not an effective pharmacotherapy augmentation strategy.

A meta-analysis of electrophysiological biomarkers of reward and error monitoring in substance misuse.

Substance use disorders are characterized by marked changes in reward and error processing. The primary objective of this meta-analysis was to estimate effect sizes for the reward positivity (RewP) and error-related negativity (ERN), two event-related potential indicators of outcome monitoring, in substance users compared to controls. The secondary objective was to test for moderation by demographic, substance type, and EEG experiment parameters. Final PubMed searches were performed in August 2023. Inclusion criteria were substance use disorder/dependence or validated self-report of substance misuse, RewP/ERN means available, healthy control comparison group, non-acute drug study, peer-reviewed journal, English language, and human participants. Selection bias was tested through modified Egger's regression and exploratory 3-parameter selection model tests. The RewP results (19 studies, 1641 participants) did not support an overall effect (Hedges' g = 0.07, 95% CI [-0.44, 0.58], p = .777) and nor effect of any moderators. The ERN results (20 studies, 1022 participants) indicated no significant overall effect (g = 0.41, 95%CI [-0.05, 0.88]). Subgroup analyses indicated that cocaine users had a blunted ERN compared to controls (g = 1.12, 95%CI [0.77, 1.47]). There was limited evidence for publication/small study bias. Although the results indicate a potential dissociation between substance types, this meta-analysis revealed the need for additional research on the RewP/ERN in substance using populations and for better designed experiments that adequately address research questions.

An opioid-minimizing multimodal pain regimen reduces opioid exposure and pain in trauma-injured patients at high risk for opioid misuse: Secondary analysis from the mast trial.

BACKGROUND: Screening to identify patients at risk for opioid misuse after trauma is recommended but not commonly used to guide perioperative opioid management interventions. The Multimodal Analgesic Strategies for Trauma trial demonstrated that an opioid-minimizing multimodal pain regimen reduced opioid exposure in a heterogeneous trauma patient population. Here, we assess the efficacy of the Multimodal Analgesic Strategies for Trauma multimodal pain regimen in a critical patient subgroup who screened at high risk for opioid misuse. METHODS: The Multimodal Analgesic Strategies for Trauma trial compared an opioid-minimizing multimodal pain regimen (oral acetaminophen, naproxen, gabapentin, lidocaine patch, as-needed opioid) against an original multimodal pain regimen (intravenous followed by oral acetaminophen, 48-hour celecoxib and pregabalin, followed by naproxen and gabapentin, scheduled tramadol, as-needed opioid), in a randomized trial conducted from April 2018 to March 2019. A total of 631 enrolled patients were classified either as low- or high-risk via the Opioid Risk Tool. Bayesian analyses evaluated the moderating influence of Opioid Risk Tool risk (high/low) on the effect of Multimodal Analgesic Strategies for Trauma multimodal pain regimen (versus original) on opioid exposure (morphine milligram equivalents/day), opioids prescribed at discharge, and pain scores. RESULTS: Multimodal Analgesic Strategies for Trauma multimodal pain regimen effectively reduced morphine milligram equivalents/day in low- and high-Opioid Risk Tool risk groups. Moderation was observed for opioids at discharge and pain scores; Multimodal Analgesic Strategies for Trauma multimodal pain regimen was effective in the high-risk group only (opioids at discharge: 63% vs 77%, relative risk = 0.86, 95% Bayesian credible interval [0.66-1.08], posterior probability (relative risk <1) = 90%; pain scores: b = 3.8, 95% Bayesian credible interval [3.2-4.4] vs b = 4.0, 95% Bayesian credible interval [3.4-4.6], posterior probability (b <0) = 87%). CONCLUSION: This study is the first to show the moderating influence of opioid misuse risk on the effectiveness of an opioid-minimizing multimodal pain regimen. The Opioid Risk Tool was useful in identifying high-risk patients for whom the Multimodal Analgesic Strategies for Trauma multimodal pain regimen is recommended for perioperative pain management.

Exenatide as an adjunct to nicotine patch for smoking cessation and prevention of postcessation weight gain among treatment-seeking smokers with pre-diabetes and/or overweight: study protocol for a randomised, placebo-controlled clinical trial.

INTRODUCTION: Obesity and smoking are the two leading causes of preventable death in the USA. Unfortunately, most smokers gain weight after quitting. Postcessation weight gain (PCWG) is frequently cited as one of the primary barriers to a quit attempt and a common cause of relapse. Further, excessive PCWG may contribute to the onset or progression of metabolic conditions, such as hyperglycaemia and obesity. The efficacy of the current treatments for smoking cessation is modest, and these treatments have no clinically meaningful impact on mitigating PCWG. Here, we outline a novel approach using glucagon-like peptide 1 receptor agonists (GLP-1RA), which have demonstrated efficacy in reducing both food and nicotine intake. This report describes the design of a double-blind, placebo-controlled, randomised clinical trial that evaluates the effects of the GLP-1RA exenatide as an adjunct to nicotine patches on smoking abstinence and PCWG. METHODS AND ANALYSIS: The study will be conducted at two university-affiliated research sites in Houston, Texas, the UTHealth Center for Neurobehavioral Research on Addiction and Baylor College of Medicine Michael E. DeBakey VA Medical Centre. The sample will consist of 216 treatment-seeking smokers with pre-diabetes (haemoglobin A1c of 5.7%-6.4%) and/or overweight (body mass index of 25 kg/m2 or above). Participants will be randomised (1:1) to receive subcutaneous injections of placebo or 2 mg exenatide, once weekly for 14 weeks. All participants will receive transdermal nicotine replacement therapy and brief smoking cessation counselling for 14 weeks. The primary outcomes are 4-week continuous abstinence and changes in body weight at the end of treatment. The secondary outcomes are (1) abstinence and changes in body weight at 12 weeks post end of treatment and (2) changes in neuroaffective responses to cigarette-related and food-related cues as measured by electroencephalogram. ETHICS AND DISSEMINATION: The study has been approved by the UTHealth Committee for the Protection of Human Subjects (HSC-MS-21-0639) and Baylor College of Medicine Institutional Review Board (H-50543). All participants will sign informed consent. The study results will be disseminated via peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT05610800.

Assessing cocaine motivational value: Comparison of brain reactivity bias toward cocaine cues and cocaine demand.

The behavioral economic measure drug demand and the neural measure late positive potential (LPP) are two measures of motivational value that have been associated with drug relapse risk and treatment outcomes. Despite having overlapping themes, no studies have directly compared drug demand and LPP. Participants (N = 59) included treatment-seeking individuals with cocaine use disorder that had completed both a baseline cocaine demand task and an electroencephalogram (EEG) picture-viewing task of drug-related and pleasant picture cues. Associations between the LPP difference score amplitude (drug-pleasant) and five demand indices (Q0, essential value [EV], Omax, Pmax, and breakpoint [BP]) were evaluated via Bayesian generalized linear modeling. Positive associations (posterior probabilities ≥ 75%) were found between LPP amplitude and four demand indices (Q0, EV, Omax, BP). These results suggest that individuals who attach greater relevance to cocaine cues also exhibit greater valuation of cocaine reward. Implications for incorporating methodology from behavioral science and brain imaging are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Late positive potential as a candidate biomarker of motivational relevance in substance use: Evidence from a meta-analysis.

The objective of the current meta-analysis was to assess the effect size of the Late Positive Potential (LPP) to drug and emotional cues in substance users compared to controls. The secondary objective was to test for moderation by: age, gender, years of use, use status, and substance type. Search was performed in August 2021 using PubMed. Inclusion criteria were: substance use disorder/dependence or validated self-report, LPP means, healthy control comparison, non-acute drug study, data available, peer-reviewed journal, English, and human participants. Selection bias was tested through modified Egger's regression and exploratory 3-parameter selection model tests. Results (k = 11) indicated LPP to drug cues was larger in substance use compared to control group, with a large effect size (Hedges' g=1.66, 95%CI [0.64,2.67], p = 0.005). There were no overall differences for emotional cues. Though threats of selection bias were not severe, inclusion of more studies with larger sample sizes in future meta-analyses will allow more robust tests of publication bias and more accurate measures of effect size.

Early pain, stress, and opioid use following traumatic injury.

OBJECTIVE: Prescription opioids are an effective pain treatment strategy but can lead to long-term opioid misuse. Identifying at risk patients during hospitalization can inform the development of prevention interventions post-discharge. Using the Opioid Risk Tool (ORT) as a screening measure, this study predicted factors associated with pain and opioid use at 2 weeks post-discharge in trauma patients. DESIGN: A quality improvement prospective study design was used. SETTING: Participant recruitment took place at an inpatient Level 1 trauma center in Houston, Texas. PARTICIPANTS: Participants (n = 103) were patients admitted to the adult trauma service. Patients completed the ORT in the hospital and a survey at 2 weeks post-discharge. MAIN OUTCOME MEASURE: The survey assessed pain intensity and interference, injury-related stress, medication use, and need for additional pain treatment. Wilcoxon-Mann-Whitney U test, the Spearman rank-order correlation, and chisquare test of independence tested the ORT as a predictor of follow-up outcomes. Post hoc analyses relied on logistic and quantile regression. RESULTS: The ORT identified 15.5 percent of patients at high risk for opioid-related aberrant behavior. Survey results indicated high percentages of patients reporting moderate to severe pain (79.6 percent), pain interference (77.9 percent), taking pain pills (59.6 percent), experiencing stress (76.9 percent), and needing pain treatment (52.4 percent). The ORT predicted injury-related stress with the high-risk category having higher stress levels than low risk (Z = 2.518, p = 0.012). CONCLUSION: Risk of opioid misuse assessed in hospitalized trauma patients was associated with injury-related stress reported post-discharge. This highlights the importance of including stress assessments in follow-up appointments.

Delta-9-tetrahydrocannabinol reduces willingness to exert effort in women.

BACKGROUND: The use of cannabis has been clinically associated with decreased motivation to engage in normally rewarding activities. However, evidence from previous controlled studies is mixed. METHOD: In this study, we examined the effects of acute delta-9-tetrahydrocannabinol (THC) versus placebo on a task measuring willingness to exert effort for rewards. This is a secondary analysis of a larger study examining interactions between ovarian hormones and THC. In this within-subjects study, oral THC and placebo were administered under double-blind conditions in counterbalanced order to healthy young adult (M age = 24 years) women with previous cannabis experience who were not regular users. Forty subjects completed three 4-h sessions with PL, 7.5 and 15 mg THC, while an additional 18 completed only PL and 15 mg THC sessions (design abridged due to pandemic). At each session, they completed a task consisting of making repeated choices between a hard and an easy task, which were worth varying amounts of money at varying probabilities. RESULTS: THC dose-dependently decreased hard task choices (drug effect, b = - 0.79, SE = 0.29, z = - 2.67, p < 0.01), especially at moderate to high expected values of reward (drug × probability × amount interaction, b = 0.77, SE = 0.38, z = 1.99, p = 0.04). THC also slowed task performance (drug effect, b = 0.01, SE = 0.005, t(5.24) = 2.11, p = 0.04), but the effect of THC on choice was still significant after controlling for this psychomotor slowing. CONCLUSIONS: These findings support the idea that cannabis acutely reduces motivation to earn non-drug rewards. Still to be determined are the neurochemical mechanisms underlying this effect.

Distress tolerance: prospective associations with cognitive-behavioral therapy outcomes in adults with posttraumatic stress and substance use disorders.

74Distress tolerance (DT; perceived or actual ability to tolerate aversive physical or emotional states) is related to both posttraumatic stress disorder (PTSD) symptoms and substance use disorders (SUD). This investigation evaluates self-report and behavioral measures of DT as potential predictors of PTSD and SUD cognitive-behavioral therapy outcomes. Participants included 41 treatment-seeking adults (53.7% women; 73.2% African American; Mage = 44.90, SD = 9.68) who met at least four symptoms of DSM-5 PTSD and DSM-IV substance dependence, assessed via structured interviews. At baseline (pre-treatment), participants completed the Distress Tolerance Scale (DTS), Mirror-Tracing Persistence Task (MTPT), Breath Holding task, and Paced Auditory Serial Addition Task. The Clinician-Administered PTSD Scale for DSM-5 severity scores and percent days of primary substance use, measured via Timeline Follow-back, were used as indicators of PTSD symptoms and substance use, respectively. Covariates included treatment condition, baseline PTSD symptom severity, and baseline substance use. Lower perceived DT at baseline (DTS total score) was associated with higher PTSD symptom severity at end-of-treatment. Lower behavioral DT at baseline (MTPT duration) was associated with higher substance use at the conclusion of treatment (i.e. proportion of number of use days to total number of days between two final treatment sessions).

Nonjudgmental acceptance: Associations with substance-related cue reactivity in adults with substance use disorders and posttraumatic stress.

The present investigation examined the predictive utility of nonjudgmental acceptance, a facet of mindfulness defined as the ability to remain aware and nonevaluative about internal experience, in terms of substance-related cue reactivity among adults with substance use disorders (SUD) and posttraumatic stress (PTS) symptomatology. We hypothesized that higher nonjudgmental acceptance, indexed via self-report, would predict higher levels of self-reported control over oneself and safety 'in the moment', broadly, and lower levels of substance-related craving in response to substance script cues. Effects were expected after subtracting reactivity to neutral script cues from each outcome rating. PTS severity was included as a covariate. The sample was comprised of 53 adults (48.1% women; 75.9% African American; 74.1% with past-month PTSD) with substance dependence per DSM-IV and at least four symptoms of PTSD per DSM-5. Higher baseline nonjudgmental acceptance predicted greater safety and control in response to substance cues; no effects were found for craving. These experimental laboratory results elucidate the potential clinical utility of mindfulness-based interventions in bolstering recovery from addiction among adults with SUD/PTS by fostering safety and control in response to substance cues.

Electrophysiological responses to emotional and cocaine cues reveal individual neuroaffective profiles in cocaine users.

Smokers with stronger neuroaffective responses to drug-related cues compared to nondrug-related pleasant images (C > P) are more vulnerable to compulsive smoking than individuals with the opposite brain reactivity profile (P > C). However, it is unknown if these neurobehavioral profiles exist in individuals abusing other drugs. We tested whether individuals with cocaine use disorder (CUD) show similar neuroaffective profiles to smokers. We also monitored eye movements to assess attentional bias toward cues and we further performed exploratory analyses on demographics, personality, and drug use between profiles. Participants with CUD (n = 43) viewed pleasant, unpleasant, cocaine, and neutral images while we recorded electroencephalogram. For each picture category, we computed the amplitude of the late positive potential (LPP), an event-related potential component that reflects motivational relevance. k-means clustering classified participants based on their LPP responses. In line with what has been observed in smokers, clustering participants using LPP responses revealed the presence of two groups: one with larger LPPs to pleasant images compared to cocaine images (P > C) and one group with larger LPPs to cocaine images compared to pleasant images (C > P). Individuals with the C > P reactivity profile also had higher attentional bias toward drug cues. The two groups did not differ on demographic and drug use characteristics, however individuals with the C > P profile reported lower distress tolerance, higher anhedonia, and higher posttraumatic stress symptoms compared to the P > C group. This is the first study to report the presence of these neuroaffective profiles in individuals with CUD, indicating that this pattern may cut across addiction populations. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Posttraumatic stress symptom clusters differentially predict late positive potential to cocaine imagery cues in trauma-exposed adults with cocaine use disorder.

BACKGROUND: While studies have investigated the effects of posttraumatic stress disorder (PTSD) symptoms on substance use, information on these associations in the context of drug cue reactivity is lacking, which can provide meaningful information about risk for relapse. The current study assessed the associations between PTSD symptom clusters and reactivity to cues in trauma-exposed adults with cocaine use disorder. METHODS: We recorded electroencephalogram on 52 trauma-exposed participants (Mage = 51.3; SD = 7.0; 15.4 % women) diagnosed with cocaine use disorder while they viewed pleasant (i.e., erotic, romantic, sweet foods), unpleasant (i.e., mutilations, violence, accidents), neutral, and cocaine-related images. Reactivity was measured with the late positive potential (LPP), an indicator of motivational relevance. It was hypothesized that individuals with greater PTSD avoidance and negative alterations in cognition and mood (NACM) symptoms, as determined by the PTSD Checklist for DSM-5 (PCL-5), would have higher LPPs to cocaine-related images, indicating greater cue reactivity. RESULTS: Linear mixed modeling indicated that higher NACM symptomatology was associated with higher LPPs to cocaine cues and higher arousal/reactivity was associated with lower LPPs to cocaine cues. CONCLUSIONS: These results highlight the potential clinical utility of the LPP in assessing drug cue reactivity in trauma-exposed adults with substance use disorder.

Acute drug effects differentially predict desire to take dextroamphetamine again for work and recreation.

RATIONALE: Misuse of dextroamphetamine occurs in work and recreational contexts. While acute drug effects broadly predict abuse liability, few studies have considered the relationship between acute effects and context. OBJECTIVES: This study examined how individual differences in acute effects of dextroamphetamine relate to desire to take dextroamphetamine again in different contexts. METHODS: This secondary analysis used data from healthy adults with no history of moderate-to-severe substance use disorder, who received oral doses of placebo and dextroamphetamine (10 and 20 mg) over 3 sessions under double-blind, randomized conditions. Subjects rated subjective effects and completed reward-related behavioral tasks. Subjects rated their desire to take dextroamphetamine again in hypothetical work and recreational contexts. Multilevel models examined within-subjects change scores (10 mg-placebo; 20 mg-placebo) to determine how subjective effects and behavioral outcomes predicted desire to take dextroamphetamine again for work versus recreation. RESULTS: Subjects reported more desire to take 20 mg dextroamphetamine again for work than for recreation. At 20 mg, there was an interaction between context and liking/wanting, such that liking/wanting predicted desire to use dextroamphetamine for work only. There was also an interaction at 20 mg between context and psychomotor speed, such that psychomotor speed predicted interest in using dextroamphetamine for recreation only. CONCLUSIONS: We found that positive subjective effects predicted desire to use dextroamphetamine again for work, while increased motor effects predicted desire to use dextroamphetamine recreationally. Hedonic effects may be perceived as advantageous when working, while increased physical energy may be preferred during recreation, suggesting that context of intended use is important when examining abuse liability.

The effects of combination levodopa-ropinirole on cognitive improvement and treatment outcome in individuals with cocaine use disorder: A bayesian mediation analysis.

BACKGROUND: Chronic cocaine users show impairments in cognitive processes associated with dopamine (DA) circuitry. Medications aimed at bolstering cognitive functions via DA modulation might enhance treatment outcome. METHODS: The trial used a double-blind, double-dummy, parallel-group design with four treatment arms comparing placebo (PLC) to levodopa/carbidopa 800 mg/200 mg alone (LR0), levodopa plus extended release (XR) ropinirole 2 mg (LR2) or XR ropinirole 4 mg (LR4). Adults (n = 110) with cocaine use disorder attended thrice weekly clinic visits for 10 weeks. Potential cognitive mediators assessed at week 5 consisted of measures of decision-making (Iowa Gambling Task, Risky Decision-Making Task), attention/impulsivity (Immediate Memory Task), motivation (Progressive Ratio task), and cognitive control (Cocaine Stoop task). The primary outcome measure was the treatment effectiveness score (TES) calculated as the number of cocaine-negative urines collected from weeks 6-10. RESULTS: Bayesian mediation examined indirect and total effects of the relationships between each active treatment (compared to PLC) and TES. Total (direct) effects were supported for LR0 and LR2, but not for LR4. Indirect effects were tested for each mediator. Notably, 22.3 % and 35.4 % of the total effects of LR0 and LR2 on TES were mediated by changes in attention/impulsivity. CONCLUSIONS: The hypothesized mediation effect was strongest for levodopa plus 2 mg ropinirole, indicating that this DA medication combination predicted change (improvement) in attention/impulsivity, which in turn predicted change (reduction) in cocaine use. This finding provides modest support for cognitive enhancement as a target for medications to treat cocaine use disorder.

Cocaine-specific speed-accuracy trade-off during anti-saccade testing differentiates patients with cocaine use disorder who achieve initial abstinence during treatment.

BACKGROUND: The response time speed-accuracy trade-off (SATO) is an established index of information processing ability, but rarely examined as a variable in association with treatment of substance use disorder (SUD). AIM: The purpose of this study was to test baseline information-processing ability differences between individuals who respond to treatment for cocaine use disorder v. those who do not. METHODS: Eighty patients enrolled in a clinical trial for cocaine use disorder completed a baseline drug-specific eye-tracking (anti-saccade) assessment prior to treatment, which included trials with both cocaine-related and neutral stimuli. SATO functions were computed for treatment responders v. non-responders. RESULTS: Unexpectedly, responders demonstrated statistically different SATO functions, showing poorer accuracy when executing faster response times. This difference was present on trials that presented cocaine stimuli only. CONCLUSIONS: SATO during performance of an eye-movement task may be useful for predicting differential response to substance use disorder treatment. However, in the present study, results were specific to cocaine cues rather than an overall SATO performance decrement.

Using pharmacological manipulations to study the role of dopamine in human reward functioning: A review of studies in healthy adults.

Dopamine (DA) plays a key role in reward processing and is implicated in psychological disorders such as depression, substance use, and schizophrenia. The role of DA in reward processing is an area of highly active research. One approach to this question is drug challenge studies with drugs known to alter DA function. These studies provide good experimental control and can be performed in parallel in laboratory animals and humans. This review aimed to summarize results of studies using pharmacological manipulations of DA in healthy adults. 'Reward' is a complex process, so we separated 'phases' of reward, including anticipation, evaluation of cost and benefits of upcoming reward, execution of actions to obtain reward, pleasure in response to receiving a reward, and reward learning. Results indicated that i) DAergic drugs have different effects on different phases of reward; ii) the relationship between DA and reward functioning appears unlikely to be linear; iii) our ability to detect the effects of DAergic drugs varies depending on whether subjective, behavioral, imaging measures are used.