Adverse childhood experiences and early initiation of substance use: A survival analysis.

OBJECTIVE: Early adversity, such as adverse childhood experiences (ACEs), is a risk factor for the development of substance use disorder (SUD). ACEs are associated with earlier initiation of substance use. This study examined the relationship between ACEs and age of initiation of substance use using survival analysis. It is hypothesized that individuals with higher ACEs will have an earlier age of initiation. METHOD: Participants were recruited from the University of Kentucky's Laboratory for Human Behavioral Pharmacology. Participants were 18 years or older, English speaking, and actively engaged in substance use. Participants were not in substance abuse treatment nor were they seeking treatment. ACE scores were calculated, and age of substance use initiation was recorded. A Cox proportional hazard model was used to examine the effect of ACE score on age of substance use initiation. RESULTS: A total of 107 participants completed the study. An average number of 2.3 ACEs (SD = 2.2) were endorsed with 24% of participants reporting 4 or more ACEs. Higher ACE scores were associated with cigarette smoking and non-medical prescription opioid use onset ( hazard ratio (HR) = 1.14, 95% CI=1.02-1.28, p = 0.02, and HR=1.19, 95% CI = 1.04-1.37, p = 0.01, respectively. CONCLUSIONS: A significant association was found between higher ACE scores and earlier initiation of cigarette and non-medical prescription opioid use, consistent with prior research. Primary prevention of ACEs, screening for ACEs during childhood, and interventions for ACEs if detected, may help to reduce the risk of substance use/SUD in adulthood.

Use of drug purchase tasks in medications development research: orexin system regulation of cocaine and drug demand.

Commodity purchase tasks provide a useful method for evaluating behavioral economic demand in the human laboratory. Recent research has shown how responding to purchase tasks for blinded drug administration can be used to study abuse liability. This analysis uses data from a human laboratory study to highlight how similar procedures may be particularly useful for understanding momentary changes in drug valuation when screening novel interventions. Eight nontreatment-seeking participants with cocaine use disorder (one with partial data) were enrolled in a cross-over, double-blind, randomized inpatient study. Participants were maintained on the Food and Drug Administration-approved insomnia medication suvorexant (oral; 0, 5, 10, 20 mg/day) in randomized order with experimental sessions completed after at least 3 days of maintenance on each suvorexant dose. Experimental sessions included administration of a sample dose of 0, 10 and 30 mg/70 kg intravenous cocaine. Analyses focused on purchase tasks for the blinded sample dose as well as alcohol, cigarettes and chocolate completed 15 min after the sample dose. As expected based on abuse liability, near zero demand was observed for placebo with dose-related increases in cocaine demand. Suvorexant maintenance increased cocaine demand in a dose-related manner with the greatest increase observed for the 10 mg/kg cocaine dose. Increased demand under suvorexant maintenance was also observed for alcohol. No effect of cocaine administration was observed for alcohol, cigarette, or chocolate demand. These data support the validity of demand procedures for measuring blinded drug demand. Findings also parallel self-administration data from this study by showing increases in cocaine use motivation under suvorexant maintenance.

Differential impacts of economic and demographic variables on substance use patterns during the COVID-19 pandemic.

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 (ß = -1.12) and tobacco (ß = 1.59) use. Additionally, certain predictor variables (e.g., participants' age [ß = 1.22], race [ß = -4.43], psychiatric disorders including ADHD [ß = -2.73] and anxiety [ß = 1.53], and concomitant substance use [ß = 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.

Comparing Changes in Controlled Substance Prescribing Trends by Provider Type.

BACKGROUND AND OBJECTIVES: Forty-nine out of 50 states have implemented Prescription Drug Monitoring Programs (PDMPs) to monitor controlled substance (CS) prescribing. PDMPs change health care provider behavior, but few studies have examined changes in CS prescription by health care provider type. METHODS: Aggregated yearly data, including number of CS prescriptions, doses, and doses per prescription by health care provider type (physician, advanced practice registered nurse [APRN], and dentist) for each year from 2011 to 2017 was provided by the state PDMP, Kentucky All Schedule Prescription Electronic Reporting System (KASPER). In aggregate, this data set included 64,578,307 total prescriptions and 3,982,130,994 total doses of Schedule II-V medications. RESULTS: Physicians and dentists showed a trend of decreasing prescriptions and doses for Schedule II opioids from 2012 to 2017 (27-32% reduction in 2017 compared to 2011). APRNs showed a substantive increase in the number of doses and prescriptions (121-204% increase in 2017 compared to 2011), with increases remaining when controlling for number of providers. Physicians increased doses and prescriptions of Schedule II stimulants (37% increase for both doses and prescriptions), but by a smaller magnitude than APRN increases in stimulants (334-360% increase). Dentists showed decreases in Schedule II stimulants prescribed (69-80% reduction). Similar trends, but more modest in magnitude, were observed for Schedule III-IV. DISCUSSION AND CONCLUSIONS: Although monitoring and continuing education requirements are similar across all providers in Kentucky, differences in prescription trends for Schedule II opioids and stimulants were noted for physicians, APRNs, and dentists. SCIENTIFIC SIGNIFICANCE: Changes in prescribing following introduction of mandatory use of KASPER markedly differed based on provider type, with increases observed for APRNs compared with physicians and dentists. These findings advance prior research by providing a detailed examination of prescribing trends by provider type subsequent to a PDMPs mandatory use law. (Am J Addict 2019;00:00-00).

Feasibility, Acceptability, and Initial Efficacy of Delivering Alcohol Use Cognitive Interventions via Crowdsourcing.

BACKGROUND: Inhibitory control training and working memory training are 2 cognitive interventions that have been considered for alcohol use disorder (AUD). Existing studies have typically relied on small samples that preclude the evaluation of small effects. Crowdsourcing is a sampling method that can address these limitations by effectively and efficiently recruiting large samples with varying health histories. This study tested the feasibility and acceptability of delivering cognitive training interventions via crowdsourcing. METHODS: Participants with AUD were recruited from the crowdsourcing website Amazon Mechanical Turk (mTurk) (ClinicalTrials.gov; NCT03438539). Following completion of a baseline survey, participants were randomized to an inhibitory control, working memory, or control training condition. Participants were asked to complete training tasks daily over a 2-week period. Follow-up assessments evaluating acceptability measures and alcohol and soda consumption were completed immediately following and 2 weeks after training. RESULTS: Response rates were satisfactory over the 2-week intervention period (65% of training tasks completed), and performance on training tasks was consistent with expected effects. A majority of participants indicated that they were satisfied with the study procedures (94.6%), would participate again (97.4%), and would consider incorporating the training task in their daily life (81.1%). Modest reductions in alcohol consumption were observed (e.g., 0.5 drinking day/wk), primarily in the inhibitory control group, and these effects were selective to alcohol use and did not extend to soda consumption. CONCLUSIONS: These findings demonstrate the feasibility and acceptability of utilizing crowdsourcing methods for interventions development. Such a demonstration helps establish the crowdsourcing setting for future large sample studies testing novel interventions for AUD and other substance use disorders.

Adverse Childhood Experiences, Tobacco Use, and Obesity: A Crowdsourcing Study.

Background: Exposure to adverse childhood experiences (ACEs) increases health risk behavior in adulthood and is a risk for premature mortality. For example, ACEs are associated with both tobacco smoking and obesity, which remain significant health challenges for many adults, despite widespread knowledge about the risks. Objective: The present investigation used a novel online crowdsourcing platform (Amazon.com mechanical turk) to study the relationship between ACEs and later tobacco smoking and obesity. Methods: Participants were recruited based on smoking (n = 74 smokers; n = 75 nonsmokers) and stratified based on obesity (n = 52 BMI ≥ 30; n = 97 BMI < 30). Participants had no recent history of other substance use, except alcohol. The relationship between ACE score and smoking and obesity categories was analyzed using logistic regression. Results: The average age of the sample was 38.6-years old and was mostly female (66.4%), employed (82.6%) and college educated (63.1%). Those with 4+ ACEs had a significantly greater odds of cigarette use. Any ACEs exposure was associated with a significantly greater odds of obesity. Conclusions/Importance: Findings are concordant with previous studies and suggest crowdsourcing is a viable platform for studying ACEs and health behavior. Access to large samples and specific populations provided by crowdsourcing could help examine theoretical models about how exposure to ACEs could be connected to later adoption of high-risk behaviors such as tobacco cigarette smoking and obesity.

Evaluation of the "Pipeline" for Development of Medications for Cocaine Use Disorder: A Review of Translational Preclinical, Human Laboratory, and Clinical Trial Research.

Cocaine use disorder is a persistent public health problem for which no widely effective medications exist. Self-administration procedures, which have shown good predictive validity in estimating the abuse potential of drugs, have been used in rodent, nonhuman primate, and human laboratory studies to screen putative medications. This review assessed the effectiveness of the medications development process regarding pharmacotherapies for cocaine use disorder. The primary objective was to determine whether data from animal and human laboratory self-administration studies predicted the results of clinical trials. In addition, the concordance between laboratory studies in animals and humans was assessed. More than 100 blinded, randomized, fully placebo-controlled studies of putative medications for cocaine use disorder were identified. Of the 64 drugs tested in these trials, only 10 had been examined in both human and well-controlled animal laboratory studies. Within all three stages, few studies had been conducted for each drug and when multiple studies had been conducted conclusions were sometimes contradictory. Overall, however, there was good concordance between animal and human laboratory results when the former assessed chronic drug treatment. Although only seven of the ten reviewed drugs showed fully concordant results across all three types of studies reviewed, the analysis revealed several subject-related, procedural, and environmental factors that differ between the laboratory and clinical trial settings that help explain the disagreement for other drugs. The review closes with several recommendations to enhance translation and communication across stages of the medications development process that will ultimately speed the progress toward effective pharmacotherapeutic strategies for cocaine use disorder.

Influence of Cocaine-Related Images and Alcohol Administration on Inhibitory Control in Cocaine Users.

BACKGROUND: Alcohol use and impulsivity, including decreased inhibitory control, predict poor treatment outcomes for individuals with cocaine use disorders. This study sought to determine the effects of alcohol administration on inhibitory control following cocaine-related and neutral cues on the Attentional Bias-Behavioral Activation (ABBA) task in cocaine users. We hypothesized that the proportion of inhibitory failures would increase following cocaine, compared to neutral, cues. We further hypothesized that there would be an interaction between alcohol administration and task version, such that alcohol would impair inhibitory control following cocaine, but not neutral cues. METHODS: Fifty current cocaine users completed this mixed-model, double-blind, placebo-controlled, crossover study over 2 experimental sessions. The ABBA task was completed following alcohol administration (0.0 and 0.65 g/kg). Subject-rated drug effect and physiological measures were collected prior to and after alcohol administration. RESULTS: Proportion of inhibitory failures was increased following cocaine-related cues compared to neutral cues independent of alcohol dose. Alcohol administration also produced prototypical subject-rated drug effects. CONCLUSIONS: A better understanding of the relationship between alcohol consumption and inhibitory control in cocaine users could direct the development of interventions to decrease the risk of relapse in individuals who drink and display impaired inhibitory control.

Effects of acute buspirone administration on inhibitory control and sexual discounting in cocaine users.

OBJECTIVE: Cocaine users display deficits in inhibitory control and make impulsive choices that may increase risky behavior. Buspirone is an anxiolytic that activates dopaminergic and serotonergic systems and improves impulsive choice (i.e., reduces sexual risk-taking intent) in cocaine users when administered chronically. We evaluated the effects of acutely administered buspirone on inhibitory control and impulsive choice. METHODS: Eleven subjects with a recent history of cocaine use completed this within-subject, placebo-controlled study. Subjects performed two cued go/no-go and a sexual risk delay-discounting task following oral administration of buspirone (10 and 30 mg), triazolam (0.375 mg; positive control), and placebo (negative control). Physiological and psychomotor performance and subject-rated data were also collected. RESULTS: Buspirone failed to change inhibitory control or impulsive choice; however, slower reaction times were observed at the highest dose tested. Buspirone did not produce subject-rated drug effects but dose-dependently decreased diastolic blood pressure. Triazolam impaired psychomotor performance and increased ratings of positive subject-rated effects (e.g., Like Drug). CONCLUSIONS: These findings indicate that acutely administered buspirone has little impact on behavioral measures of inhibitory control and impulsive sexual decision-making. Considering previous findings with chronic dosing, these findings highlight that the behavioral effects of buspirone differ as a function of dosing conditions.

Separate and Combined Effects of Naltrexone and Extended-Release Alprazolam on the Reinforcing, Subject-Rated, and Cardiovascular Effects of Methamphetamine.

Opioid antagonists (eg, naltrexone) and positive modulators of γ-aminobutyric acid type A receptors (eg, alprazolam) each modestly attenuate the abuse-related effects of stimulants. A previous study demonstrated that acute pretreatment with the combination of naltrexone and alprazolam attenuated a greater number of the subject-rated effects of D-amphetamine than the constituent drugs alone. This study tested the hypothesis that maintenance on the combination of naltrexone and alprazolam XR would attenuate the reinforcing and "positive" subject-rated effects of methamphetamine to a greater extent than the constituent drugs alone.Eight non-treatment-seeking, stimulant-using individuals completed a placebo-controlled, crossover, double-blind inpatient protocol. Participants were maintained on naltrexone (0 and 50 mg), alprazolam XR (0 and 1 mg), and the combination of naltrexone and alprazolam XR (50 mg and 1 mg, respectively) for 6 to 7 days. Under each maintenance condition, participants sampled intranasal doses of methamphetamine (0, 10, and 30 mg), and were then offered the opportunity to work for the sampled dose on a modified progressive-ratio procedure. Subject-rated drug effect questionnaires, psychomotor, and physiology assessments were collected.Intranasal methamphetamine functioned as a reinforcer and produced prototypical stimulant-like "positive" subject-rated and physiological effects. Maintenance on naltrexone significantly decreased the reinforcing, but not subject-rated drug effects of 10-mg methamphetamine. Alprazolam XR and the combination of naltrexone and alprazolam XR did not impact methamphetamine self-administration or subject-rated drug effects. The results support the continued evaluation of naltrexone for methamphetamine dependence, as well as the identification of other drugs that enhance its ability to reduce drug-taking behavior.

Cigarette Cue Attentional Bias in Cocaine-Smoking and Non-Cocaine-Using Cigarette Smokers.

INTRODUCTION: Cigarette smoking in cocaine users is nearly four times higher than the national prevalence and cocaine use increases cigarette smoking. The mechanisms underlying cigarette smoking in cocaine-using individuals need to be identified to promote cigarette and cocaine abstinence. Previous studies have examined the salience of cigarette and cocaine cues separately. The present aim was to determine whether cigarette attentional bias (AB) is higher in cigarettes smokers who smoke cocaine relative to individuals who only smoke cigarettes. METHODS: Twenty cigarette smokers who smoke cocaine and 20 non-cocaine-using cigarette smokers completed a visual probe task with eye-tracking technology. During this task, the magnitude of cigarette and cocaine AB was assessed through orienting bias, fixation time, and response time. RESULTS: Cocaine users displayed an orienting bias towards cigarette cues. Cocaine users also endorsed a more urgent desire to smoke to relieve negative affect associated with cigarette craving than non-cocaine users (g = 0.6). Neither group displayed a cigarette AB, as measured by fixation time. Cocaine users, but not non-cocaine users, displayed a cocaine AB as measured by orienting bias (g = 2.0) and fixation time (g = 1.2). There were no significant effects for response time data. CONCLUSIONS: Cocaine-smoking cigarettes smokers display an initial orienting bias toward cigarette cues, but not sustained cigarette AB. The incentive motivation underlying cigarette smoking also differs. Cocaine smokers report more urgent desire to smoke to relieve negative affect. Identifying differences in motivation to smoke cigarettes may provide new treatment targets for cigarette and cocaine use disorders. IMPLICATIONS: These results suggest that cocaine-smoking cigarette smokers display an initial orienting bias towards cigarette cues, but not sustained attention towards cigarette cues, relative to non-cocaine-using smokers. Smoked cocaine users also report a more urgent desire to smoke to relieve negative affect than non-cocaine users. Identifying differences in motivation to smoke cigarettes may provide new treatment targets for both cigarette and cocaine use disorders.

Alcohol Administration Increases Cocaine Craving But Not Cocaine Cue Attentional Bias.

BACKGROUND: Alcohol consumption is a known antecedent to cocaine relapse. Through associative conditioning, it is hypothesized that alcohol increases incentive motivation for cocaine and thus the salience of cocaine-related cues, which are important in maintaining drug-taking behavior. Cocaine-using individuals display a robust cocaine cue attentional bias as measured by fixation time during the visual probe task. The purpose of this study was to evaluate the influence of alcohol administration on cocaine cue attentional bias using eye-tracking technology to directly measure attentional allocation. METHODS: Twenty current cocaine users completed a double-blind, placebo-controlled, within-subjects study that tested the effect of 3 doses of alcohol (0.00, 0.325, and 0.65 g/kg) on cocaine cue attentional bias using the visual probe task with eye-tracking technology. The participant-rated and physiological effects of alcohol were also assessed. RESULTS: Participants displayed a robust cocaine cue attentional bias following both placebo and alcohol administration as measured by fixation time, but not response time. Alcohol administration did not influence cocaine cue attentional bias, but increased craving for cocaine in a dose-dependent manner. Alcohol produced prototypic psychomotor and participant-rated effects. CONCLUSIONS: Alcohol administration increases cocaine craving but not cocaine cue attentional bias. Alcohol-induced cocaine craving suggests that alcohol increases incentive motivation for cocaine but not the salience of cocaine-related cues.

Profile of internet access in active cocaine users.

BACKGROUND AND OBJECTIVES: Web-based interventions have received attention for substance abuse treatment. Few studies have examined Internet use among substance users. METHODS: Internet-use data were examined for 66 participants screened to participate in behavioral pharmacology studies. RESULTS: A majority of active cocaine users reported regular Internet use. Demographic profiles generally did not impact Internet use, but Internet users were more likely to be younger and report other drug use. DISCUSSION AND CONCLUSIONS: Active cocaine users have similar rates of Internet access as the general population. SCIENTIFIC SIGNIFICANCE: Our findings contribute to the limited data on Internet use in active drug users by demonstrating Internet access in cocaine-using populations, supporting the use of this medium to conduct research and clinical interventions.

Methamphetamine self-administration in humans during D-amphetamine maintenance.

Agonist replacement may be a viable treatment approach for managing stimulant use disorders. This study sought to determine the effects of D-amphetamine maintenance on methamphetamine self-administration in stimulant using human participants. We predicted that D-amphetamine maintenance would reduce methamphetamine self-administration. Eight participants completed the protocol, which tested 2 D-amphetamine maintenance conditions in counterbalanced order (0 and 40 mg/d). Participants completed 4 experimental sessions under each maintenance condition in which they first sampled 1 of 4 doses of intranasal methamphetamine (0, 10, 20, or 30 mg). Participants then had the opportunity to respond on a computerized progressive-ratio task to earn portions of the sampled methamphetamine dose. Subject-rated drug effect and physiological measures were completed at regular intervals prior to and after sampling methamphetamine. Methamphetamine was self-administered as an orderly function of dose regardless of the maintenance condition. Methamphetamine produced prototypical subject-rated effects on 12 items of the drug-effects questionnaires, 8 of which were attenuated by D-amphetamine maintenance (eg, increased ratings were attenuated on items such as Any Effect, Like Drug, and Willing to Take Again on the Drug Effect Questionnaire). Methamphetamine produced significant increases in systolic blood pressure, which were attenuated by D-amphetamine maintenance compared to placebo maintenance. Methamphetamine was well tolerated during D-amphetamine maintenance and no adverse events occurred. Although D-amphetamine attenuated some subject-rated effects of methamphetamine, the self-administration results are concordant with those of clinical trials showing that D-amphetamine did not reduce methamphetamine use. Unique pharmacological approaches may be needed for treating amphetamine use disorders.

Relationship between intranasal cocaine self-administration and subject-rated effects: predictors of cocaine taking on progressive-ratio schedules.

OBJECTIVE: Subject-rated measures and drug self-administration represent two of the most commonly used methods of assessing abuse potential of drugs, as well as screening intervention efficacy in the human laboratory. Although the results from these methods are often consistent, dissociations between subject-rated and self-administration data have been observed. The purpose of the present retrospective analysis was to examine the relationship between subject-rated effects and intranasal cocaine self-administration to help guide future research design and intervention assessment. METHODS: Data were combined from two previous studies in which drug and an alternative reinforcer (i.e., money) were available on concurrent progressive-ratio schedules of reinforcement. Pearson correlation coefficients and regression model selection utilizing corrected Akaike information criterion were used to determine which subject-rated measures were associated with and best predicted cocaine self-administration. RESULTS: Eleven subject-rated effects were positively associated with cocaine-maintained breakpoints. A combination of three of these subject ratings (i.e., Like Drug, Performance Improved, and Rush) best predicted cocaine taking. CONCLUSIONS: The present findings suggest that, at least under certain conditions with intranasal cocaine, some, but not all, positive subject-rated effects may predict drug self-administration. These findings will be useful in guiding future examinations of putative interventions for cocaine-use disorders.

Optimally combining transcranial magnetic stimulation with antidepressants in major depressive disorder: A systematic review and Meta-analysis.

There is a critical knowledge gap in optimally combining transcranial magnetic stimulation (TMS) and antidepressants to treat patients with major depressive disorder (MDD). TMS is effective in treating MDD in patients who have failed at least one antidepressant trial, with accelerated protocols showing faster remission in treatment-resistant depression (TRD). Although clinicians routinely augment antidepressants with TMS, there is a knowledge gap in stopping versus continuing antidepressants or the dosing strategies when starting or tapering TMS. These considerations are important when considering maintenance TMS (delivered alone or in combination with suitable antidepressants) to maintain remission in MDD after the index course of TMS. As the first step towards filling this knowledge gap, we reviewed randomized controlled trials (RCTs) and open-label trials from 2 databases (PubMed/Medline and EMBASE) that compared active TMS combined with a pre-specified antidepressant dosed in the same manner for adults with MDD versus sham TMS combined with the same antidepressant as in the active arm. All studies were published between January 1, 2000, and December 31, 2023. We excluded case reports, case series, and clinical studies that augmented TMS with antidepressants and vice versa. We found 10 RCTs (n = 654 participants) and performed a meta-analysis. This showed active TMS combined with pre-specified antidepressants had greater efficacy for MDD treatment than sham TMS combined with the same antidepressants as in the active arm (Hedge's g = 1; 95 % CI [0.27, 1.73]). The review and meta-analysis indicate greater short-term efficacy in combining antidepressants with TMS from the get-go in MDD. Given the increasing role of accelerated TMS protocols in expediting remission in MDD and the results of our meta-analysis, we advocate for RCTs examining the short-term and long-term effects of various antidepressant classes on these TMS protocols in MDD. This can also optimize and individualize maintenance TMS protocols to prevent relapse in MDD.

Intermittent theta burst stimulation and functional connectivity in people living with HIV/AIDS who smoke tobacco cigarettes: a preliminary pilot study.

Background: People living with HIV (PLWHA) smoke at three times the rate of the general population and respond poorly to cessation strategies. Previous studies examined repetitive transcranial magnetic stimulation (rTMS) over left dorsolateral prefrontal cortex (L. dlPFC) to reduce craving, but no studies have explored rTMS among PLWHA who smoke. The current pilot study compared the effects of active and sham intermittent theta-burst stimulation (iTBS) on resting state functional connectivity (rsFC), cigarette cue attentional bias, and cigarette craving in PLWHA who smoke. Methods: Eight PLWHA were recruited (single-blind, within-subject design) to receive one session of iTBS (n=8) over the L. dlPFC using neuronavigation and, four weeks later, sham iTBS (n=5). Cigarette craving and attentional bias assessments were completed before and after both iTBS and sham iTBS. rsFC was assessed before iTBS (baseline) and after iTBS and sham iTBS. Results: Compared to sham iTBS, iTBS enhanced rsFC between the L. dlPFC and bilateral medial prefrontal cortex and pons. iTBS also enhanced rsFC between the right insula and right occipital cortex compared to sham iTBS. iTBS also decreased cigarette craving and cigarette cue attentional bias. Conclusion: iTBS could potentially offer a therapeutic option for smoking cessation in PLWHA.

Relationship between drug discrimination and ratings of subjective effects: implications for assessing and understanding the abuse potential of D-amphetamine in humans.

The discriminative and subjective effects of drugs in humans are related, but the full extent of this relationship remains to be determined. To further explore this relationship, a retrospective analysis was conducted on data from six studies completed in our laboratory that used identical procedures. The relationship between the discriminative and subjective effects of a range of doses of D-amphetamine (i.e. 2.5-15 mg) was examined using correlational analyses. Significant correlations with discrimination performance were observed on 15 of 20 items from the Drug-Effect Questionnaire across a range of qualities [e.g. Pay For (a positive effect indicative of abuse potential) and Active (a stimulant-like effect)], but the magnitude of these relationships was modest (r<0.52). The current findings demonstrate that diverse subjective effects contribute to the discriminative effects of D-amphetamine and indicate that the former are a more practical means to assess the abuse potential of drugs. Although these procedures are fundamentally related in that they rely on the presence of an interoceptive drug state, they differ in the dimension(s) of the interoceptive effects that participants must quantify. The simultaneous use of drug discrimination and subjective effects may, therefore, reveal complimentary aspects of drug effects that underlie their potential for abuse.

Relationship between oral D-amphetamine self-administration and ratings of subjective effects: do subjective-effects ratings correspond with a progressive-ratio measure of drug-taking behavior?

The abuse potential of drugs has traditionally been determined in humans using subjective ratings of drug effects. However, drug self-administration procedures also provide valuable information about the reinforcing effects of drugs that may contribute to their potential for abuse. Although ratings of subjective effects and drug self-administration data are generally concordant, some divergent findings have been reported. Therefore, the aim of the present analysis was to directly investigate the relationship between the subjective-effects profile and self-administration of oral D-amphetamine in healthy volunteers with a history of stimulant use or abuse, using Pearson's correlational analyses. The results indicated that positive subjective and reinforcing effects significantly increased as a function of D-amphetamine dose. Further, significant, but modest, correlations were observed between ratings of six of 17 total items (Any Effect, High, Like Drug, Good Effects, Willing to Pay For, and Willing to Take Again) and D-amphetamine self-administration under a progressive-ratio schedule of reinforcement. The current findings suggest that, at least under the current set of conditions with oral D-amphetamine, subjective-effects measures and drug self-administration data likely provide different but complimentary information about abuse potential. The most informative findings will thus be obtained from studies that use ratings of subjective effects and drug self-administration methods.