Optimizing buprenorphine training during undergraduate medical education: Medical student feedback and attitudes.

BACKGROUND AND OBJECTIVES: Strong evidence supports efficacy of medications for opioid use disorder (MOUD), but stringent prescribing policies impair access. Many physicians report discomfort prescribing MOUD due to inadequate knowledge. Most medical students believe MOUD training should occur during undergraduate medical education (UME). As legislation surrounding buprenorphine prescribing shifts, it is timely to consider how best to incorporate MOUD training into UME. METHODS: At the start of 3rd year, all students (n = 290) received a survey regarding experiences working with people with OUDs, and beliefs and knowledge regarding harm reduction and treatment. During orientation, students completed an 8-h online MOUD training. Afterwards, students completed another survey, including questions about training perceptions. RESULTS: One-third of students (32.8%) completed MOUD training and both surveys. Before training, 60.0% had not heard of the waiver, but 82.1% endorsed interest in prescribing buprenorphine. Despite mixed feelings about training content and delivery, 79.1% believed future classes should receive it. Most thought it should be integrated longitudinally throughout the curriculum rather than as separate online training. CONCLUSION AND SCIENTIFIC SIGNIFICANCE: Medical students want more MOUD education throughout their training; however, the 8-h online training may be less-than-optimal. As this training is no longer required to prescribe buprenorphine, there is an opportunity to modify the content presented. There is an urgent need for physicians with the knowledge and willingness to treat patients with OUD. Introducing integrated training about MOUD should help future physicians feel confident in their knowledge to treat patients and comfortable applying for the waiver.

Heroin delay discounting and impulsivity: Modulation by DRD1 genetic variation.

BACKGROUND: Dopamine D1 receptors (encoded by DRD1) are implicated in drug addiction and high-risk behaviors. Delay discounting (DD) procedures measure decisional balance between choosing smaller/sooner rewards vs larger/later rewards. Individuals with higher DD (rapid discounting) are prone to maladaptive behaviors that provide immediate reinforcement (eg, substance use). DRD1 variants have been linked with increased DD (in healthy volunteers) and opioid abuse. This study determined whether four dopaminergic functional variants modulated heroin DD and impulsivity. METHODS: Substance use, DD, and genotype data (DRD1 rs686 and rs5326, DRD3 rs6280, COMT rs4680) were obtained from 106 current heroin users. Subjects completed an array of DD choices during two imagined conditions: heroin satiation and withdrawal. Rewards were expressed as $10 heroin bag units, with maximum delayed amount of 30 bags. Delays progressively increased from 3 to 96 hours. RESULTS: DRD1 rs686 (A/A, n = 25; G/A, n = 56; G/G, n = 25) was linearly related to the difference in heroin DD (area under the curve; AUC) between the heroin satiation and withdrawal conditions; specifically, G/G homozygotes had a significantly smaller (satiation minus withdrawal) AUC difference score had higher drug-use impulsivity questionnaire scores, relative to A/A homozygotes, with G/A intermediate. DRD3 and COMT variants were not associated with these DD and impulsivity outcomes. CONCLUSION: DRD1 rs686 modulated the difference in heroin DD score between pharmacological states and was associated with drug-use impulsivity. These data support a role of DRD1 in opioid DD and impulsive behaviors.

A Comparison of Substance Use Patterns Among Lifetime Heroin-Injecting Individuals By Racial Groups.

BACKGROUND: Studies have identified differential substance use patterns by racial groups. One of the most commonly reported differences is a higher rate of injection drug use (IDU) among Non-Hispanic Whites compared to African Americans, but this is complicated by factors related to IDU (e.g., earlier drug-use initiation) that overlap with being White. OBJECTIVE: We explored differential substance use-patterns by racial groups within a sample of injection heroin users. METHODS: Substance-use data were collected from 373 not-in-treatment heroin users who endorsed any lifetime injection use (69.4% male). We examined differences in substance-use patterns (e.g., age of initiation, gateway adherence) by racial groups. Multiple t-tests with Bonferroni correction were conducted to understand which demographic and substance-use characteristics varied by racial groups. RESULTS: Relative to Non-Hispanic Whites, African Americans (45.8% of sample) were more likely to start using heroin earlier in their life, but also more likely to experience a longer delay between starting and regularly using heroin. We also identified differences in the degree of (injection) heroin-use consequences by racial groups. After correcting for multiple comparisons and controlling for age and gender, we observed differences for six substance-use and demographic characteristics by racial group. White participants were younger, started cocaine use earlier, and experienced more heroin-use consequences across two separate domains. CONCLUSIONS: After controlling for injection use, we observed differential substance-use characteristics by racial groups. The findings could be used to develop targeted prevention and harm-reduction strategies.

Relationship between opioid cross-tolerance during buprenorphine stabilization and return to opioid use during buprenorphine dose tapering.

RATIONALE: Opioid injection drug use (IDU) has been linked to a more severe pattern of use (e.g. tolerance, overdose risk) and shorter retention in treatment, which may undermine abstinence attempts. OBJECTIVES: This secondary data analysis of four human laboratory studies investigated whether current opioid IDU modulates subjective abuse liability responses to high-dose hydromorphone during intermediate-dose buprenorphine stabilization (designed to suppress withdrawal but allow surmountable agonist effects), and whether hydromorphone response magnitude predicts latency of return to opioid use during buprenorphine dose-tapering. METHODS: Regular heroin users not currently seeking treatment (n = 54; 29 current injectors, 25 non-injectors) were stabilized on 8-mg/day sublingual buprenorphine and assessed for subjective responses (e.g. 'liking', craving) to hydromorphone 24-mg intramuscular challenge (administered 16-hr post-buprenorphine) under randomized, double-blinded, controlled conditions. A subgroup (n = 35) subsequently completed a standardized 3-week outpatient buprenorphine dose-taper, paired with opioid-abstinent contingent reinforcement, and were assessed for return to opioid use based on thrice-weekly urinalysis and self-report. RESULTS: During buprenorphine stabilization, IDU reported lower 'liking' of buprenorphine and post-hydromorphone peak 'liking', 'good effect' and 'high' compared to non-IDU. Less hydromorphone peak increase-from-baseline in 'liking' (which correlated with less hydromorphone-induced craving suppression) predicted significantly faster return to opioid use during buprenorphine dose-tapering. CONCLUSIONS: In these buprenorphine-stabilized regular heroin users, IDU is associated with attenuated 'liking' response (more cross-tolerance) to buprenorphine and to high-dose hydromorphone challenge and, in turn, this cross-tolerance (but not IDU) predicts faster return to opioid use. Further research should examine mechanisms that link cross-tolerance to treatment response.

Attention-deficit/hyperactivity disorder combined subtype exacerbates opioid use disorder consequences: Mediation by impulsive phenotypes.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is highly prevalent and associated with opioid use disorder (OUD). Yet, little is known about the mechanisms by which ADHD (which is a heterogeneous construct/diagnosis) might alter the trajectory of OUD outcomes in persons who use heroin. AIM: We examined whether ADHD subtypes are related to heroin-use consequences and the extent to which the effects of ADHD on lifetime heroin-use consequences are mediated by two impulsivity factors that may be partly independent of ADHD: foreshortened time perspective and drug-use impulsivity. METHODS: Individuals who reported regular heroin use (N=250) were screened using the Assessment of Hyperactivity and Attention (AHA), Impulsive Relapse Questionnaire (IRQ), Stanford Time Perception Inventory (STPI), and a comprehensive assessment of lifetime and current substance use and substance-related consequences. This secondary analysis examined whether ADHD or intermediate phenotypes predicted heroin-use consequences. RESULTS: Relative to participants whose AHA scores indicated lifetime absence of ADHD (n=88), those with scores indicating persistent ADHD (childhood and adult, n=62) endorsed significantly more total lifetime heroin-use consequences despite comparable heroin-use severity. Likewise, there was a significant indirect effect of the combined ADHD subtype in childhood on lifetime heroin-use consequences. This effect was mediated by STPI scores indicating less future (and more hedonism in the present) temporal orientation and by IRQ scores indicating less capacity for delaying drug use. CONCLUSION: The combined ADHD subtype is significantly associated with lifetime heroin-use consequences, and this effect is mediated through higher drug-use impulsivity (less capacity for delay) and lower future temporal orientation.

Effects of neuromodulation on cognitive and emotional responses to psychosocial stressors in healthy humans.

Physiological and psychological stressors can exert wide-ranging effects on the human brain and behavior. Research has improved understanding of how the sympatho-adreno-medullary (SAM) and hypothalamic-pituitary-adrenocortical (HPA) axes respond to stressors and the differential responses that occur depending on stressor type. Although the physiological function of SAM and HPA responses is to promote survival and safety, exaggerated psychobiological reactivity can occur in psychiatric disorders. Exaggerated reactivity may occur more for certain types of stressors, specifically, psychosocial stressors. Understanding stressor effects and how the body regulates these responses can provide insight into ways that psychobiological reactivity can be modulated. Non-invasive neuromodulation is one way that responding to stressors may be altered; research into these interventions may provide further insights into the brain circuits that modulate stress reactivity. This review focuses on the effects of acute psychosocial stressors and how neuromodulation might be effective in altering stress reactivity. Although considerable research into stress interventions focuses on treating pathology, it is imperative to first understand these mechanisms in non-clinical populations; therefore, this review will emphasize populations with no known pathology and consider how these results may translate to those with psychiatric pathologies.

Anhedonia modulates benzodiazepine and opioid demand among persons in treatment for opioid use disorder.

Background: Benzodiazepine (BZD) misuse is a significant public health problem, particularly in conjunction with opioid use, due to increased risks of overdose and death. One putative mechanism underlying BZD misuse is affective dysregulation, via exaggerated negative affect (e.g., anxiety, depression, stress-reactivity) and/or impaired positive affect (anhedonia). Similar to other misused substances, BZD consumption is sensitive to price and individual differences. Although purchase tasks and demand curve analysis can shed light on determinants of substance use, few studies have examined BZD demand, nor factors related to demand. Methods: This ongoing study is examining simulated economic demand for alprazolam (among BZD lifetime misusers based on self-report and DSM-5 diagnosis; n = 23 total; 14 male, 9 female) and each participant's preferred-opioid/route using hypothetical purchase tasks among patients with opioid use disorder (n = 59 total; 38 male, 21 female) who are not clinically stable, i.e., defined as being early in treatment or in treatment longer but with recent substance use. Aims are to determine whether: (1) BZD misusers differ from never-misusers on preferred-opioid economic demand, affective dysregulation (using questionnaire and performance measures), insomnia/behavioral alertness, psychiatric diagnoses or medications, or urinalysis results; and (2) alprazolam demand among BZD misusers is related to affective dysregulation or other measures. Results: Lifetime BZD misuse is significantly (p < 0.05) related to current major depressive disorder diagnosis, opioid-negative and methadone-negative urinalysis, higher trait anxiety, greater self-reported affective dysregulation, and younger age, but not preferred-opioid demand or insomnia/behavioral alertness. Alprazolam and opioid demand are each significantly positively related to higher anhedonia and, to a lesser extent, depression symptoms but no other measures of negative-affective dysregulation, psychiatric conditions or medications (including opioid agonist therapy or inpatient/outpatient treatment modality), or sleep-related problems. Conclusion: Anhedonia (positive-affective deficit) robustly predicted increased BZD and opioid demand; these factors could modulate treatment response. Routine assessment and effective treatment of anhedonia in populations with concurrent opioid and sedative use disorder may improve treatment outcomes. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT03696017, identifier NCT03696017.

Building a strong foundation from the ground up: the impact of a medical student substance use disorder organization on curriculum and community.

Due to the increasing rates of substance use disorders (SUDs), accidental overdoses, and associated high mortality rates, there is an urgent need for well-trained physicians who can grasp these complex issues and help struggling patients. Preparing these physicians occurs through targeted education and clinical exposure in conjunction with medical school curricula in the field of addiction medicine. Medical students can often feel overwhelmed by the medical school curriculum and changes to the curriculum take time, money, and administrative commitment to ratify. Implementing a student organization dedicated to SUD education can be a solution to provide clinical exposure, education and student autonomy in their medical school experience. At Wayne State University School of Medicine, Detroit vs. Addiction (DvA) is a student-run organization that is filling the gap in SUD education for medical students whilst providing assistance to the community. DvA not only extends clinical education for physicians in training, but it also provides the medical school with an opportunity to allow students to create a blueprint for education initiatives that can be incorporated as a mainstay in the school's technical trainings. Herein, we describe the evolution of this organization and its activities.

How Should Clinicians Determine a Traumatized Patient's Readiness to Return to Work?

A clinician's standard primary role is to treat and monitor their patients' health and to be their ally. Clinicians with obligations to patients and to organizations, however, must also assess patients for nontherapeutic purposes (eg, readiness to resume work). These 2 obligations can conflict, and, when they do, clinicians must balance their duties to patients and to society. We propose criteria clinicians should consider when determining a patient's readiness to return to work and offer recommendations for interpreting factors that influence this decision.

La función principal de un médico es tratar y controlar la salud de sus pacientes, además de ser su aliado. Sin embargo, los médicos que tienen obligaciones con los pacientes y con las organizaciones también deben evaluar a los pacientes con fines no terapéuticos (p. ej., su disposición a reincorporarse al trabajo). Estas dos obligaciones pueden entrar en conflicto y, cuando lo hacen, los médicos deben equilibrar sus deberes con los pacientes y con la sociedad. Proponemos los criterios que los médicos deberían tener en cuenta al determinar si un paciente está preparado para volver al trabajo y ofrecemos recomendaciones para interpretar los factores que influyen en esta decisión.

Long-term effects of opioid overdose prevention and response training on medical student knowledge and attitudes toward opioid overdose: A pilot study.

BACKGROUND: Medical settings provide ideal opportunities to identify patients with substance use disorders and provide harm reduction and treatment resources. Medical students often volunteer in the community and can spend substantial time with patients, serving as touchpoints. Accordingly, medical schools have begun training in harm reduction. Initial studies show such training acutely improves knowledge, but sustained effects remain unclear. This pilot study explored longer-term impacts of Opioid Overdose Prevention and Response Training (OOPRT) on medical student knowledge about opioids, overdose, and naloxone. METHODS: Students completed a survey about knowledge of opioid use disorder, overdoses, and attitudes towards patients. This included Opioid Overdose Knowledge (OOKS) and Opioid Overdose Attitudes (OOAS) scales. A subset of students was invited to attend OOPRT and complete a post-training survey. All who completed the baseline survey were invited to complete a 6-month follow-up. We analyzed long-term training effects on OOKS and OOAS scores. RESULTS: 89 students completed baseline and 6-month follow-up surveys; of these, 22 received training. OOPRT yielded significant improvements in knowledge of signs of opioid overdose (F(2,38) = 18.04, P < .001), actions to take during overdose (F(2,38) = 8.32, P = .001), and naloxone use (F(2,38) = 35.46, P < .001), along with attitudes regarding overdose competencies (F(2,38) = 99.40, P < .001) and concerns (F(2,38) = 8.86, P < .001). When comparing over time, students who attended OOPRT retained significantly higher competency scores than those who did not attend F(1,87) = 40.82, P < .001). No other significant differences were observed. CONCLUSIONS: This study demonstrates immediate efficacy of OOPRT in improving opioid overdose knowledge and attitudes and sustained changes at 6 months, compared to standard undergraduate medical curricula alone. Future research with larger sample sizes is underway to validate these preliminary findings and examine the difference in attitudes and knowledge retention over time. Given that students report interest in receiving OOPRT and consider it worthwhile, systematic study is warranted.

At the intersection of sleep deficiency and opioid use: mechanisms and therapeutic opportunities.

Due to the ongoing opioid epidemic, innovative scientific perspectives and approaches are urgently needed to reduce the unprecedented personal and societal burdens of nonmedical and recreational opioid use. One promising opportunity is to focus on the relationship between sleep deficiency and opioid use. In this review, we examine empirical evidence: (1) at the interface of sleep deficiency and opioid use, including hypothesized bidirectional associations between sleep efficiency and opioid abstinence; (2) as to whether normalization of sleep deficiency might directly or indirectly improve opioid abstinence (and vice versa); and (3) regarding mechanisms that could link improvements in sleep to opioid abstinence. Based on available data, we identify candidate sleep-restorative therapeutic approaches that should be examined in rigorous clinical trials.

Training medical students in opioid overdose prevention and response: Comparison of In-Person versus online formats.

Medical education has increasingly shifted towards replacing large lectures with a combination of online and smaller in-person group sessions. This study compares the efficacy of a virtual Opioid Overdose Prevention and Response Training (OOPRT) for first-year medical students with an identical in-person training. During their first unit of medical school, students in the class of 2023 (cohort 1) received OOPRT in-person and students in the class of 2024 (cohort 2) received training via Zoom. Aside from the delivery format, trainings were identical. Both cohorts completed identical surveys at medical school entry and post-training to evaluate knowledge and experiences using the Opioid Overdose Knowledge Scale, Opioid Overdose Attitudes Scale, Medical Conditions Regard Scale, and Naloxone Related Risk Compensation Beliefs. Of 430 students, 84.2% (362: 124 in cohort 1; 238 in cohort 2) completed baseline and post-training surveys. Students reported significantly improved opioid overdose knowledge and attitudes in all 4 knowledge and 3 attitudes subscales after training. Only one outcome differed by training type: knowledge of opioid overdose signs. Cohorts did not differ in opinions of training; 97.2% enjoyed it and 99.4% believed future classes should receive it. Medical students' attitudes and knowledge significantly improved after OOPRT; only one of 13 outcomes showed a cohort difference. There were no differences in enjoyment, indicating that switching to virtual learning does not undermine the learning experience. Further studies are needed to confirm that these results can be extended to other medical school topics where small group interactive discussion is preferred.

History of regular nonmedical sedative and/or alcohol use differentiates substance-use patterns and consequences among chronic heroin users.

BACKGROUND: Concurrent use of sedating substances (e.g. alcohol or benzodiazepines) with opioids is associated with increased negative consequences of opioid use; however, few studies have attempted to differentiate effects of using sedating substances on heroin-use outcomes. This study examines differences between heroin users who use alcohol or misuse sedatives regularly and those who do not. METHODS: Substance-use data were collected from 367 non-treatment seeking, chronic heroin-using, 18-to-55 year-old participants. We created 4 groups based on self-reported lifetime history of regular (at least weekly) substance use: heroin only (n = 95), heroin and sedatives (n = 21), heroin and alcohol (n = 151), and heroin, sedative, and alcohol (n = 100). Chi-square analyses and ANOVAs with Bonferroni post hoc tests were used to explore differences between these groups. RESULTS: Heroin users who denied lifetime alcohol or nonmedical sedative use regularly endorsed fewer consequences associated with any substance they had used. Total adverse consequences of heroin use (e.g. health problems) were significantly higher among those who misused sedatives regularly, irrespective of alcohol use history (F(3,361) = 10.21; p < .001). Regular alcohol use did not independently impact heroin consequences but was associated with increased use of other substances. CONCLUSIONS: Although polysubstance use is normative among heroin users, the risks depend on the substances used. Regular sedative use is associated with increased heroin consequences whereas regular alcohol use is not. This study refines the investigation of polysubstance use and highlights subgroup differences depending on types of substances used regularly. This knowledge is critical for understanding substance-use motivations and creating avenues for harm reduction.

Factors associated with sedative use and misuse among heroin users.

BACKGROUND: Rates of both opioid and sedative use and misuse are rising. Comorbid opioid and sedative use is associated with especially severe consequences (e.g., overdose and poor health outcomes). Heroin users report multiple motivations for sedative use, including self-medication. We aimed to understand differences in lifetime substance use characteristics between heroin users with different sedative use histories. METHODS: Substance use data were collected from 385 non-treatment seeking heroin users. Subjects were divided into four lifetime sedative-use groups: no use, medical use only, non-medical use only, and mixed medical and non-medical use. We examined patterns of use of various substances of abuse (tobacco, alcohol, marijuana, cocaine, heroin, and sedatives) and individual characteristics associated with each. RESULTS: Non-medical sedative use (alone or in addition to medical use) was associated with more negative consequences from using all substances. Medical sedative use alone was not related to increased overdose or emergency room visits associated with heroin use. Non-medical sedative use was associated with increases in 15 of the 21 measured heroin consequences and only one of those - health problems - was also associated with medical sedative use. CONCLUSIONS: Concomitant non-medical sedative use and heroin use is associated with significantly greater negative outcomes than those experienced by heroin users who report use of sedatives only as prescribed. Understanding these differences offers insight into risks related to using both substances and may help treatment providers create targeted harm reduction interventions for this population.

Developing a scale of domains of negative consequences of chronic heroin use.

BACKGROUND: Chronic use of heroin typically leads to numerous negative life consequences and serious clinical impairment. Increased negative consequences can result in poor treatment outcomes as well as adverse health effects and impaired social functioning. Certain risk factors, including early substance use initiation, concurrent use of other illicit substances, and injection drug use are associated with an increase in negative consequences. This study examined whether there are unique domains of heroin consequences and, if so, whether these domains are related to specific substance use characteristics. METHODS: Data regarding substance use characteristics were collected from 370 non-treatment seeking, heroin-using, 18 to 55year-old participants from the Detroit metropolitan area. Principal component analysis (PCA) was used to analyze the factor structure of 21 negative heroin consequence items. RESULTS: PCA demonstrated that heroin consequences could be divided into 5 unique domains. These unique domains were related to specific substance use characteristics and heroin consequence domains. Injection heroin use was significantly associated with increased Factor 1 consequences (primarily acute medical problems) but not with consequences in other domains. Certain substance use characteristics, such as injection status and earlier onset of marijuana use, were associated with increased consequences in specific domains. CONCLUSIONS: These findings support the existence of unique domains of negative consequences, and indicate that some risk factors (e.g. injection use) may be specific to these domains. Potential tailored-treatment strategies aimed at improving treatment engagement and reducing harm for heroin use based on person-specific risks and negative consequences are discussed.