Examining NSDUH's Assessment of Fentanyl Use: A Comparison of Trends in Fentanyl Use and Fentanyl Overdose Deaths from 2015-2020.

OBJECTIVE: The National Survey on Drug Use and Health (NSDUH), as the primary source of epidemiological substance use data in the US, could illuminate trends in fentanyl use behaviors contributing to the opioid overdose crisis. We hypothesized that the trend in NSDUH prevalence of lifetime fentanyl injection would match the direction and magnitude of the trend in synthetic opioid overdose deaths. METHOD: Using logistic regression, we modeled the 2015-2020 trend in synthetic opioid overdose deaths as a proportion of all deaths. We modeled contemporary trends from cross-sectional NSDUH data for (1) lifetime fentanyl injection, (2) past year prescription fentanyl (PF) misuse, (3) prescription tramadol misuse (the other synthetic opioid counted alongside fentanyl in the overdose deaths category), and (4) combined prescription fentanyl or tramadol misuse. Average annual NSDUH weighted sample size was 272,519,038 (51.5% female, 48.5% male). RESULTS: Synthetic opioid overdose deaths increased from 2015-2020 (OR 3.39, meaning the odds of a death being from synthetic opioid overdose in 2020 were 3.39 times the odds of death from that cause in 2015, 95% CI: 3.34, 3.44). None of the substance use trends significantly increased. CONCLUSION: Per NSDUH data, the prevalence of fentanyl misuse did not significantly increase in tandem with synthetic opioid overdose deaths from 2015 to 2020. Scrutiny of NSDUH's approach to assessing fentanyl misuse casts doubt on the utility of NSDUH fentanyl data collection. We acknowledge recent changes to the survey and recommend two further changes to optimize a vital source of data on behaviors related to the opioid overdose crisis.

Establishing a research agenda for the study and assessment of opioid withdrawal.

The opioid crisis is an international public health concern. Treatments for opioid use disorder centre largely on the management of opioid withdrawal, an aversive collection of signs and symptoms that contribute to opioid use disorder. Whereas in the past 50 years more than 90 medications have been developed for depression, only five medications have been developed for opioid use disorder during this period. We posit that underinvestment has occurred in part due to an underdeveloped understanding of opioid withdrawal syndrome. This Personal View summarises substantial gaps in our understanding of opioid withdrawal that are likely to continue to limit major advancements in its treatment. There is no firm consensus in the field as to how withdrawal should be precisely defined; 10-550 symptoms of withdrawal can be measured on 18 scales. The imprecise understanding of withdrawal is likely to result in overestimating or underestimating the severity of an individual's withdrawal syndrome or potential therapeutic effects of different candidate medications. The severity of the opioid crisis is not remitting, and an international research agenda for the study and assessment of opioid withdrawal is necessary to support transformational changes in withdrawal management and treatment of opioid use disorder. Nine actionable targets are delineated here: develop a consensus definition of opioid withdrawal; understand withdrawal symptomatology after exposure to different opioids (particularly fentanyl); understand precipitated opioid withdrawal; understand how co-exposure of other drugs (eg, xylazine and stimulants) influences withdrawal expression; examine individual variation in withdrawal phenotypes; precisely characterise the protracted withdrawal syndrome; identify biomarkers of opioid withdrawal severity; identify predictors of opioid withdrawal severity; and understand which symptoms are most closely associated with treatment attrition or relapse. The US Food and Drug Administration recently established a formal indication for opioid withdrawal that has invigorated interest in drug development for opioid withdrawal management. Action is now needed to support these interests and help industry identify new classes of medications so that real change can be achieved for people with opioid use disorder.

Virtual focus groups among individuals with use disorders: assessing feasibility and acceptability in an underserved clinical population.

Objective: There are substantial barriers to conducting research among individuals with stigmatized and complicated health conditions like substance use disorders. These barriers slow progress when developing, refining, and assessing interventions to better treat underserved populations. Virtual focus groups are an innovative method for collecting data from individuals via a discreet and accessible platform which can inform novel as well as existing treatment approaches. This article reports on the feasibility and acceptability of virtual focus groups as a mechanism to recruit and engage geographically and demographically diverse samples of participants with substance use disorders that are otherwise logistically difficult to assess. Method: Participants were assessed for eligibility for a virtual focus group study based on demographic features, drug use history, and psychiatric history via a remote, interview-based screening. Focus groups were completed anonymously without video or name-sharing. Discussion contributions, quantified with number of times speaking and total number of words spoken, were compared across gender, and treatment status. Participants provided quantitative and qualitative feedback on the focus group experience in a follow-up survey. Results: Focus groups (N=26) based in geographical areas throughout the United States were conducted with 88 individuals with opioid use disorder or stimulant use disorder. Discussion contributions were comparable between genders and among individuals in treatment versus those seeking treatment. A follow-up survey (n=50, 57% of focus group participants) reflected high levels of enjoyment, comfort, and honesty during focus group discussions. Discussion: Findings suggest virtual focus groups can be an effective and efficient tool for substance use research.

Suvorexant alters dynamics of the sleep-electroencephalography-power spectrum and depressive-symptom trajectories during inpatient opioid withdrawal.

STUDY OBJECTIVES: Opioid withdrawal is an aversive experience that often exacerbates depressive symptoms and poor sleep. The aims of the present study were to examine the effects of suvorexant on oscillatory sleep-electroencephalography (EEG) band power during medically managed opioid withdrawal, and to examine their association with withdrawal severity and depressive symptoms. METHODS: Participants with opioid use disorder (N = 38: age-range:21-63, 87% male, 45% white) underwent an 11-day buprenorphine taper, in which they were randomly assigned to suvorexant (20 mg [n = 14] or 40 mg [n = 12]), or placebo [n = 12], while ambulatory sleep-EEG data was collected. Linear mixed-effect models were used to explore: (1) main and interactive effects of drug group, and time on sleep-EEG band power, and (2) associations between sleep-EEG band power change, depressive symptoms, and withdrawal severity. RESULTS: Oscillatory spectral power tended to be greater in the suvorexant groups. Over the course of the study, decreases in delta power were observed in all study groups (ß = -189.082, d = -0.522, p = <0.005), increases in beta power (20 mg: ß = 2.579, d = 0.413, p = 0.009 | 40 mg ß = 5.265, d = 0.847, p < 0.001) alpha power (20 mg: ß = 158.304, d = 0.397, p = 0.009 | 40 mg: ß = 250.212, d = 0.601, p = 0.001) and sigma power (20 mg: ß = 48.97, d = 0.410, p < 0.001 | 40 mg: ß = 71.54, d = 0.568, p < 0.001) were observed in the two suvorexant groups. During the four-night taper, decreases in delta power were associated with decreases in depressive symptoms (20 mg: ß = 190.90, d = 0.308, p = 0.99 | 40 mg: ß = 433.33, d = 0.889 p = <0.001), and withdrawal severity (20 mg: ß = 215.55, d = 0.034, p = 0.006 | 40 mg: ß = 192.64, d = -0.854, p = <0.001), in both suvorexant groups and increases in sigma power were associated with decreases in withdrawal severity (20 mg: ß = -357.84, d = -0.659, p = 0.004 | 40 mg: ß = -906.35, d = -1.053, p = <0.001). Post-taper decreases in delta (20 mg: ß = 740.58, d = 0.964 p = <0.001 | 40 mg: ß = 662.23, d = 0.882, p = <0.001) and sigma power (20 mg only: ß = 335.54, d = 0.560, p = 0.023) were associated with reduced depressive symptoms in the placebo group. CONCLUSIONS: Results highlight a complex and nuanced relationship between sleep-EEG power and symptoms of depression and withdrawal. Changes in delta power may represent a mechanism influencing depressive symptoms and withdrawal.

Polymorphisms in the A118G SNP of the OPRM1 gene produce different experiences of opioids: A human laboratory phenotype-genotype assessment.

Allelic variations in the A118G SNP of the OPRM1 gene change opioid signaling; however, evaluations of how allelic differences may influence opioid effects are lacking. This human laboratory paradigm examined whether the AA versus AG/GG genotypes determined opioid response profiles. Individuals with limited opioid exposure (N = 100) completed a five-day within-subject, double-blind, placebo-controlled, residential study. Participants were admitted (Day 1), received 4 mg hydromorphone (Day 2) and 0 mg, 2 mg and 8 mg hydromorphone in randomized order (Days 3-5) and completed self-reported visual analog scale (VAS) ratings and Likert scales, observed VAS, and physiological responses at baseline and for 6.5 h post-dose. Outcomes were analysed as peak/nadir effects over time as a function of genotype (available for N = 96 individuals; AG/GG = 13.5%, AA = 86.4%). Participants with AG/GG rated low and moderate doses of hydromorphone as significantly more positive (e.g., Good Effects VAS, coasting, drive, friendly, talkative, stimulation) with fewer negative effects (e.g., itchy skin, nausea, sleepiness), and were also observed as being more talkative and energetic relative to persons with AA. Persons with AG/GG were less physiologically reactive as determined by diastolic blood pressure and heart rate, but had more changes in core temperature compared with those with AA. Persons with AA also demonstrated more prototypic agonist effects across doses; persons with AG/GG showed limited response to 2 mg and 4 mg. Data suggest persons with AG/GG genotype experienced more pleasant and fewer unpleasant responses to hydromorphone relative to persons with AA. Future studies should replicate these laboratory findings in clinical populations to support a precision medicine approach to opioid prescribing.

Increases in primary opioid use disorder diagnoses co-occurring with anxiety or depressive disorder diagnoses in mental health treatment in the United States, 2015-2019.

BACKGROUND: Opioid use disorders (OUDs) often co-occur with anxiety and depressive disorders. While the proportion of mental health (MH) treatment facilities providing substance use treatment has increased, the proportion of these facilities able to simultaneously treat MH and substance use decreased. This warrants investigation into the integrated treatment needs of persons with a primary OUD diagnosis treated in MH treatment facilities. METHODS: Using the Mental Health Client Level Data, we examined a sample of N = 83,975 adults with OUD as their primary diagnosis who received treatment from a MH treatment facility in the United States from 2015 to 2019. Joinpoint regression was used to examine annual trends of the number of individuals with co-occurring anxiety or depression diagnoses. RESULTS: Most of the sample were men (53.7%) and received treatment in a community-based program (93.3%). Approximately 17% of the sample had either an anxiety or depressive disorder diagnosis. Approximately 9% of our sample had an anxiety disorder diagnosis, and 10% had a depressive disorder diagnosis. An increase in the number of individuals with a co-occurring anxiety disorder diagnosis from 2015 to 2019 was identified (annual percent change (APC) = 61.4; 95% confidence interval (CI) = [10.0, 136.9]; p =.029). An increase in the number of individuals with a co-occurring depressive disorder diagnosis from 2015 to 2019 was identified (APC = 39.0; 95% CI = [7.4; 79.9]; p =.027). CONCLUSIONS: This study highlights increases in adults receiving MH treatment for OUD having co-occurring anxiety or depression diagnoses, furthering the importance of integrated dual disorder treatment.

Functional imaging studies of acute administration of classic psychedelics, ketamine, and MDMA: Methodological limitations and convergent results.

Functional magnetic resonance imaging (fMRI) is increasingly used to non-invasively study the acute impact of psychedelics on the human brain. While fMRI is a promising tool for measuring brain function in response to psychedelics, it also has known methodological challenges. We conducted a systematic review of fMRI studies examining acute responses to experimentally administered psychedelics in order to identify convergent findings and characterize heterogeneity in the literature. We reviewed 91 full-text papers; these studies were notable for substantial heterogeneity in design, task, dosage, drug timing, and statistical approach. Data recycling was common, with 51 unique samples across 91 studies. Fifty-seven studies (54%) did not meet contemporary standards for Type I error correction or control of motion artifact. Psilocybin and LSD were consistently reported to moderate the connectivity architecture of the sensorimotor-association cortical axis. Studies also consistently reported that ketamine administration increased activation in the dorsomedial prefrontal cortex. Moving forward, use of best practices such as pre-registration, standardized image processing and statistical testing, and data sharing will be important in this rapidly developing field.

Control Conditions in Randomized Trials of Psychedelics: An ACTTION Systematic Review.

Objective: To systematically review control conditions of all available randomized psychedelic trials.Data Sources: We searched PubMed, PsycINFO, and EMBASE for randomized trials of psychedelics in humans from 1940 through May 2020 with no language restrictions. PRISMA guidelines were followed. (PROSPERO registration number: PROSPERO-CRD42020205341.).Study Selection: All randomized trials of psychedelics in humans from 1940 through May 2020 were included.Data Extraction: Two independent reviewers performed extraction. Extracted data included study design, demographics, blinding type, whether and how blind integrity was assessed, psychedelic used and dose, drug control condition and dose, type of non-drug control condition, number of dosing sessions, and recruitment source. Outcome data were not collected.Results: In total, 126 articles were included, encompassing 86 unique studies. Of studies with a drug control condition (80), 49 (61.2%) used an inert placebo control, 16 (20.0%) used active comparators, 12 (15.0%) used both, and 3 (3.8%) used only different active psychedelic doses as a control. Only 3 of 21 therapeutic trials compared the use of psychological support to a minimally supportive condition. The majority (81/86; 94%) of studies were blinded, though only 14 (17.3%) included blind assessment; only 8 of these 14 studies assessed participants' blinding. Blinding success, assessed in highly varied ways, was generally poor.Conclusions: Randomized psychedelic trials underutilize elements that would improve quality or provide important information: blind assessment, active drug controls, and testing psychological support against minimal-support conditions. Several queried categories, including blind integrity assessment and details of non-drug control conditions, were insufficiently reported by many reviewed studies. Recommendations are provided to improve trial methods.

Operational definition of precipitated opioid withdrawal.

Background: Opioid withdrawal can be expressed as both a spontaneous and precipitated syndrome. Although spontaneous withdrawal is well-characterized, there is no operational definition of precipitated opioid withdrawal. Methods: People (N = 106) with opioid use disorder maintained on morphine received 0.4 mg intramuscular naloxone and completed self-report (Subjective Opiate Withdrawal Scale, SOWS), visual analog scale (VAS), Bad Effects and Sick, and observer ratings (Clinical Opiate Withdrawal Scale, COWS). Time to peak severity and minimal clinically important difference (MCID) in withdrawal severity were calculated. Principal component analysis (PCA) during peak severity were conducted and analyzed with repeated measures analyses of variance (ANOVA). Results: Within 60 min, 89% of people reported peak SOWS ratings and 90% of people had peak COWS scores as made by raters. Self-reported signs of eyes tearing, yawning, nose running, perspiring, hot flashes, and observed changes in pupil diameter and rhinorrhea/lacrimation were uniquely associated with precipitated withdrawal. VAS ratings of Bad Effect and Sick served as statistically significant severity categories (0, 1-40, 41-80, and 81-100) for MCID evaluations and revealed participants' identification with an increase of 10 [SOWS; 15% maximum percent effect (MPE)] and 6 (COWS; 12% MPE) points as meaningful shifts in withdrawal severity indicative of precipitated withdrawal. Conclusion: Data suggested that a change of 10 (15% MPE) and 6 (12% MPE) points on the SOWS and COWS, respectively, that occurred within 60 min of antagonist administration was identified by participants as a clinically meaningful increase in symptom severity. These data provide a method to begin examining precipitated opioid withdrawal.

Clinical Trial Design Challenges and Opportunities for Emerging Treatments for Opioid Use Disorder: A Review.

Importance: Novel treatments for opioid use disorder (OUD) are needed to address both the ongoing opioid epidemic and long-standing barriers to existing OUD treatments that target the endogenous µ-opioid receptor (MOR) system. The goal of this review is to highlight unique clinical trial design considerations for the study of emerging treatments for OUD that address targets beyond the MOR system. In November 2019, the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership with the US Food and Drug Administration sponsored a meeting to discuss the current evidence regarding potential treatments for OUD, including cannabinoids, psychedelics, sedative-hypnotics, and immunotherapeutics, such as vaccines. Observations: Consensus recommendations are presented regarding the most critical elements of trial design for the evaluation of novel OUD treatments, such as: (1) stage of treatment that will be targeted (eg, seeking treatment, early abstinence/detoxification, long-term recovery); (2) role of treatment (adjunctive with or independent of existing OUD treatments); (3) primary outcomes informed by patient preferences that assess opioid use (including changes in patterns of use), treatment retention, and/or global functioning and quality of life; and (4) adverse events, including the potential for opioid-related relapse or overdose, especially if the patient is not simultaneously taking maintenance MOR agonist or antagonist medications. Conclusions and Relevance: Applying the recommendations provided here as well as considering input from people with lived experience in the design phase will accelerate the development, translation, and uptake of effective and safe therapeutics for individuals struggling with OUD.

Objective sleep outcomes in randomized-controlled trials in persons with substance use disorders: A systematic review.

BACKGROUND: Improving sleep health is an important target for substance use disorder (SUD) research. However, there is little guidance for SUD researchers regarding the use of technologies to objectively assess sleep outcomes in randomized-controlled trials (RCTs). This systematic review aimed to describe the use of technologies to objectively measure sleep outcomes in RCTs conducted in persons with SUDs, in order to inform future sleep intervention studies in SUD populations. METHODS: This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) on May 7th, 2020 (CRD42020182004). RCTs were reviewed here if they were peer-reviewed manuscripts that included objective measures of sleep in RCTs that sought to improve sleep in persons with SUDs. RESULTS: The initial search yielded 13,403 potential articles, with 27 meeting a priori criteria to be included in this review. The most common SUD was alcohol use disorder (59%). The most common technology used to assess sleep was polysomnography (41%), followed by actigraphy (37%), ambulatory polysomnography or components of polysomnography (e.g., electroencephalography; 19%), and at-home sleep apnea testing (7%). The most common sleep outcome reported was total sleep time (96%). CONCLUSIONS: There are a range of options to assess objective sleep outcomes. Polysomnography or ambulatory devices that directly measure brain activity are critical to advance medications through the regulatory process for the indication of improving sleep duration, continuity, and/or sleep onset latency outcomes. Actigraphy is also useful in preliminary investigations and in detecting the relationship between diurnal and SUD-related behaviors.

Patient-reported sleep outcomes in randomized-controlled trials in persons with substance use disorders: A systematic review.

BACKGROUND: Sleep disturbances and disorders are a common and sometimes recalcitrant problem in persons recovering from substance use disorders (SUDs). As such, several randomized-controlled trials (RCTs) have been conducted to address sleep disturbances in a variety of SUD subpopulations and clinical scenarios. The goal of this systematic review was to collate patient-reported sleep outcomes used in past SUD-related RCTs to provide guidance for future sleep research in persons with SUDs. METHODS: This systematic review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) on May 7th, 2020 (CRD42020182004). Studies were included if they were peer-reviewed manuscripts describing RCTs in an SUD population. RESULTS: The initial search yielded 13,403 candidate articles, and 76 met a priori criteria and were included in this review. Thirty-five (46.1%) assessed sleep as a primary outcome (i.e., sleep improvement was the primary goal of the research) and 41 (53.9%) assessed sleep as a secondary outcome (i.e., sleep improvement was an important outcome, but not the primary outcome). The most commonly used measures included the Pittsburgh Sleep Quality Index, the Insomnia Severity Index, and sleep diaries. However, multiple additional sleep assessments were also used, including visual analogue and Likert scales. CONCLUSIONS: The field of addiction medicine would benefit from a streamlined approach in assessing patient-reported sleep in RCTs, including commonly used and validated assessments of sleep quality, inserting daily or repeated measures into RCTs, and including questionnaires that assess clinically relevant insomnia or other sleep disorders.

If the Doors of Perception Were Cleansed, Would Chronic Pain be Relieved? Evaluating the Benefits and Risks of Psychedelics.

Psychedelic substances have played important roles in diverse cultures, and ingesting various plant preparations to evoke altered states of consciousness has been described throughout recorded history. Accounts of the subjective effects of psychedelics typically focus on spiritual and mystical-type experiences, including feelings of unity, sacredness, and transcendence. Over the past 2 decades, there has been increasing interest in psychedelics as treatments for various medical disorders, including chronic pain. Although concerns about adverse medical and psychological effects contributed to their controlled status, contemporary knowledge of psychedelics suggests that risks are relatively rare when patients are carefully screened, prepared, and supervised. Clinical trial results have provided support for the effectiveness of psychedelics in different psychiatric conditions. However, there are only a small number of generally uncontrolled studies of psychedelics in patients with chronic pain (eg, cancer pain, phantom limb pain, migraine, and cluster headache). Challenges in evaluating psychedelics as treatments for chronic pain include identifying neurobiologic and psychosocial mechanisms of action and determining which pain conditions to investigate. Truly informative proof-of-concept and confirmatory randomized clinical trials will require careful selection of control groups, efforts to minimize bias from unblinding, and attention to the roles of patient mental set and treatment setting. PERSPECTIVE: There is considerable promise for the use of psychedelic therapy for pain, but evidence-based recommendations for the design of future studies are needed to ensure that the results of this research are truly informative.

Suvorexant ameliorated sleep disturbance, opioid withdrawal, and craving during a buprenorphine taper.

Increased orexin/hypocretin signaling is implicated in opioid withdrawal, sleep disturbances, and drug-seeking behaviors. This study examined whether a dual-orexin receptor antagonist would improve sleep and withdrawal outcomes when compared with placebo during a buprenorphine/naloxone taper. Thirty-eight participants with opioid use disorder were recruited to a clinical research unit and maintained on 8/2 to 16/4 mg of buprenorphine/naloxone treatment for 3 days before being randomized to 20 mg of suvorexant (n = 14), 40 mg of suvorexant (n = 12), or placebo (n = 12); 26 individuals completed the study. After randomization, participants underwent a 4-day buprenorphine/naloxone taper and 4-day post-taper observation period. Total sleep time (TST) was collected nightly with a wireless electroencephalography device and wrist-worn actigraphy; opioid withdrawal symptoms were assessed via the Subjective Opiate Withdrawal Scale (SOWS); and abuse potential was assessed on a 0- to 100-point visual analog scale of "High" every morning. A priori outcomes included two-group (collapsing suvorexant doses versus placebo) and three-group comparisons of area-under-the-curve (AUC) scores for TST, SOWS, and High. In two-group comparisons, participants receiving suvorexant displayed increased TST during the buprenorphine/naloxone taper and decreased SOWS during the post-taper period. In three-group comparisons, participants receiving 20 mg of suvorexant versus placebo displayed increased AUC for TST during the buprenorphine/naloxone taper, but there was no difference in SOWS among groups. There was no evidence of abuse potential in two- or three-group analyses. The results suggest that suvorexant might be a promising treatment for sleep and opioid withdrawal in individuals undergoing a buprenorphine/naloxone taper.

Gender parity and homophily in the Drug and Alcohol Dependence editorial process.

BACKGROUND: Despite efforts towards gender parity and some improvement over time, gender bias in peer review remains a pervasive issue. We examined gender representation and homophily in the peer review process for Drug and Alcohol Dependence (DAD). METHODS: We extracted data for papers submitted to DAD between 2004 and 2019, inclusive. Inferred gender was assigned to handling editors and reviewers using the NamSor gender inference Application Programming Interface (API). RESULTS: Men and women handling editors were approximately equally likely to invite women reviewers over time, with only a few exceptions. Over time, 47.1% of editors were women, and 42.6% of review invitations were sent to women. Men were largely consistent over time in their likelihood of accepting a review invitation, while the likelihood of women accepting a review invitation was more variable over time. Gender differences in rates of accepting a review invitation were minimal; however, as women approached half of all invited reviewers in recent years, there has been a greater trend for women, relative to men, to decline review invitations. Evidence of homophily on the part of reviewers accepting invitations was minimal, but in certain years, a tendency to accept review invitations at higher rates from editors of the same gender was observed. DISCUSSION: Given the benefits of diversity in scientific advancement, these results underline the importance of continuing efforts to increase gender diversity among editors and in reviewer pools, and the need for reviewers to be mindful of their own reviewing practices.

A comparison of registered and published primary outcomes in clinical trials of opioid use disorder: ACTTION review and recommendations.

BACKGROUND AND AIMS: Prospective trial registration can increase research integrity. This Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) review was designed to compare the primary outcomes (PO) reported in registries with associated publications for opioid use disorder (OUD) clinical trials. DESIGN: The World Health Organization's International Clinical Trials Registry Platform (ICTRP) was searched for completed trials (2010 through 2019). Associated publications were identified and paired with trial registry data based on the publication date. MEASUREMENTS: Reviewers independently rated the occurrence of discrepancies between the POs in the registry compared to the publication. An analysis of prospective versus retrospective registration was also completed. FINDINGS: One-hundred and forty trials were identified in the search, and 43 registry-publication pairs evaluated. Only 34 of the 43 pairs could be examined for discrepancies because nine did not report a PO in registry and publication. Of the 34 pairs, only four met rigorous criteria for prospective trial registration and had an exact match of POs. In contrast, the majority of the 34 trials, or 80%, had inconsistent POs (e.g., registered secondary outcomes published as primary; the timing of PO not specified) and/or were retrospectively registered. CONCLUSIONS: Many clinical trials focused on OUD have not met the standards of trial registration, such as consistent reporting of POs and prospective registration. Failure to properly register trial characteristics undermines the validity of research findings and can delay the development of life-saving treatments. Recommendations for improving prospective trial reporting practices are provided.

Characterization of basal ganglia volume changes in the context of HIV and polysubstance use.

HIV and psychoactive substances can impact the integrity of the basal ganglia (BG), a neural substrate of cognition, motor control, and reward-seeking behaviors. This study assessed BG gray matter (GM) volume as a function of polysubstance (stimulant and opioid) use and HIV status. We hypothesized that comorbid polysubstance use and HIV seropositivity would alter BG GM volume differently than would polysubstance use or HIV status alone. We collected structural MRI scans, substance use history, and HIV diagnoses. Participants who had HIV (HIV +), a history of polysubstance dependence (POLY +), both, or neither completed assessments for cognition, motor function, and risk-taking behaviors (N = 93). All three clinical groups showed a left-lateralized pattern of GM reduction in the BG relative to controls. However, in the HIV + /POLY + group, stimulant use was associated with increased GM volume within the globus pallidus and putamen. This surpassed the effects from opioid use, as indicated by decreased GM volume throughout the BG in the HIV-/POLY + group. Motor learning was impaired in all three clinical groups, and in the HIV + /POLY + group, motor learning was associated with increased caudate and putamen GM volume. We also observed associations between BG GM volume and risk-taking behaviors in the HIV + /POLY- and HIV-/POLY + groups. The effects of substance use on the BG differed as a function of substance type used, HIV seropositivity, and BG subregion. Although BG volume decreased in association with HIV and opioid use, stimulants can, inversely, lead to BG volume increases within the context of HIV.