The impact of socio-environmental factors on doxycycline post-exposure prophylaxis awareness in the US: a cross-sectional study.

Background We investigated awareness and use of doxycycline post-exposure prophylaxis (doxyPEP) in the US. DoxyPEP has preventative benefits for bacterial STIs among people assigned male at birth. We considered how individual, interpersonal and social determinants of health, such as state-level LGBTQ equality, impact doxyPEP awareness. Methods We conducted an online snapshot cross-sectional survey in June 2023. Survey questions included demographics, sexual and substance use behaviours, and socio-environmental factors, and provided a short explanation of doxyPEP, with questions regarding prior awareness and use. Results Among a racially diverse sample of 196 participants (median age 33 years), 94% identified as cisgender men, 26% were aware of doxyPEP, whereas only 14 (7%) had ever used it. Factors significantly associated with awareness included being college educated (OR 2.50, 95% CI 1.09-5.74), a past year bacterial STI (OR 4.20, 95% CI 1.97-8.89), having discussed HIV pre-exposure prophylaxis with a health care provider (OR 3.88, 95% CI 1.99-7.57) and having taken HIV pre-exposure prophylaxis (OR 2.29, 95% CI 1.11-4.70). Socio-environmental factors associated with doxyPEP awareness included living in a large urban city (OR 2.14, 95% CI 1.12-4.10) and living in a state with higher levels of LGBTQ policy equality (OR 2.18, 95% CI 1.07-4.44). Conclusions Considering the disproportionate impact of bacterial STIs on men who have sex with men, especially those living in lower LGBTQ equality regions, such as the Southern US, our study emphasises how socio-environmental factors may limit awareness and uptake of novel biomedical approaches that have the potential to prevent morbidity and enhance sexual health.

Young Adult Nightclub Participants Who Attend Adult Entertainment Clubs: Sexual Risk and Substance Use Behaviors.

This secondary analysis of cross-sectional baseline data from an intervention trial study examines demographics, sexually transmitted infection (STI) history, substance use and sexual risk behaviors among young adult nightclub participants who do (n = 79) and do not (n = 419) frequent "strip" or adult entertainment clubs (AECs) in Miami, Florida. AEC patrons were older, and more likely to identify as Black race and report STI history. Compared to those who do not, AEC patrons also reported greater recent (past 90-day) frequencies of alcohol and ecstasy use, higher numbers of recent sex partners and were more likely to report recently being high during sex a majority of the time. Increased HIV/STI prevention efforts among young adult AEC patrons appear warranted.

Polysubstance use trends and variability among individuals with opioid use disorder in rural versus urban settings.

Rural areas of the United States have been disproportionately impacted by the opioid epidemic, exacerbated by COVID-19-related economic upheavals. While polysubstance use is an important determinant of overdose risk, variability in polysubstance use as a result of numerous factors (e.g., access, preference) has yet to be described, particularly among rural persons with opioid use disorder (PWOUD). Survey data on past-month use of prescription and illicit opioids and 12 non-opioid psychoactive drug classes were analyzed from a national sample of rural (n = 3872) and urban (n = 8153) residents entering treatment for OUD from 2012 to 2019. Trend analyses for opioid and stimulant use were compared between rural and urban PWOUD. Latent class analyses assessed substance use trends through identified typologies of rural/urban PWOUD, which then underwent comparative analyses. By 2019, prescription opioid use remained greater in rural versus urban PWOUD, and methamphetamine use showed greater growth in rural, compared to urban areas. Latent class analyses identified variability in polysubstance use, with five identical subgroups in rural/urban PWOD: high polysubstance, polyprescription, prescription opioid-focused, prescription opioid-focused with polysubstance use, and illicit opioid-focused. Polyprescription was highest in rural areas, with illicit opioid-focused use highest in urban areas. Demographic characteristics, co-morbid conditions and healthcare coverage were all associated with between-group differences. There is significant variability in polysubstance use that may identify specific prevention and treatment needs for subpopulations of OUD patients: interventions focused on reducing opioid prescriptions, early engagement with mental health resources, wider distribution of naloxone, and screening/treatment plans that take into account the use of multiple substances.

Polysubstance Use: A Broader Understanding of Substance Use During the Opioid Crisis.

Objectives. To understand important changes in co-occurring opioid and nonopioid drug use (i.e., polysubstance use) within the opioid epidemic in the United States.Methods. We analyzed survey data on the past month co-use of prescription and illicit opioids and 12 nonopioid psychoactive drug classes from a national sample of 15 741 persons entering treatment of opioid use disorder.Results. Past-month illicit opioid use increased from 44.8% in 2011 to 70.1% in 2018, while the use of prescription opioids alone dropped from 55.2% to 29.9%, yet overall remained high (94.5% to 85.2%). Past-month use of at least 1 nonopioid drug occurred in nearly all participants (> 90%), with significant increases in methamphetamine (+85%) and decreases across nonopioid prescription drug classes (range: -40% to -68%).Conclusions. Viewing opioid trends in a "silo" ignores the fact not only that polysubstance use is ubiquitous among those with opioid use disorder but also that significant changes in polysubstance use should be monitored alongside opioid trends.Public Health Implications. Treatment, prevention, and policymaking must address not only the supply and demand of a singular drug class but also the global nature of substance use overall.

Understanding multi-pill ingestion of prescription opioids: Prevalence, characteristics, and motivation.

PURPOSE: Oral use is the primary route of administration among non-medical prescription opioid users. While progression to non-oral routes and shifts to stronger opioids have been previously studied as ways to cope with tolerance, the prevalence and patterns of those who cope by increasing the number of pills/tablets ingested at one time (ie, multi-pill use) has not been assessed. METHODS: A subset (N = 231) of treatment-seeking opioid users from a national opioid surveillance system, participating in the Researchers and Participants Interacting Directly (RAPID) Program, completed an online survey centered on multi-pill use. RESULTS: Over two-thirds of non-medical prescription opioid users had a history of multi-pill use (67.7%), defined as ingesting four or more of the same pill, intact and at the same time. Among these (n = 154), the median maximum number of pills taken at one time was eight, with over 20% ingesting 11 or more pills in a single instance. Nearly half engaged in multi-pill ingestion more than once a day in the past month (43.8%), with accessibility to lower dose pills being the primary motivator (85.4%). Hydrocodone immediate-release (IR) compounds were by far the most frequently endorsed (90.3%), followed by oxycodone IR tablets with acetaminophen (76.0%) and oxycodone IR tablets containing no acetaminophen/ibuprofen (56.5%). CONCLUSIONS: These results indicate that the ingestion of multiple opioid pills/tablets is extremely common among treatment-seeking opioid users. This, and other forms of non-medical oral use of prescription opioids, should be taken under consideration when developing prevention and intervention efforts targeting the opioid epidemic.

Relative preferences in the abuse of immediate-release versus extended-release opioids in a sample of treatment-seeking opioid abusers.

PURPOSE: Although differences in the pharmacological properties of immediate-release (IR) and extended-release (ER) opioid formulations have been reported, there are few studies comparing the real world abuse and relative preferences for these formulations. METHODS: To examine drug preferences, we used a structured survey of 8304 individuals entering treatment (2011-2014) for opioid use disorder followed by a more focused online survey (2014-2015) with a subset of these patients (N = 301). RESULTS: Our results demonstrated that both ER and IR opioids were frequently abused by those with an opioid use disorder in terms of lifetime (91.0% vs. 98.7%, respectively) or past month (46.1% vs. 67.4%, respectively) abuse, but given the choice, only 4% of the sample selected ER compounds as their preferred formulation. The remainder had no preference (29.9%) or a distinct preference for IR formulations (66.1%), regardless of route of administration-oral or non-oral (smoking/snorting or injecting). This preference for IR formulations seems to be related to: (i) the perceived immediacy and quality of the high (73.0%) from IR products; and (ii) they were easier to use, particularly when manipulated for non-oral abuse, than ER products (31.2%). CONCLUSIONS: Based on these results, while most abusers have experience with both formulations, there is a greater preference for IR formulations, compared to ER, regardless of route of administration. As a result, it may not be unreasonable to suggest that supply-side initiatives to restrict the diversion and abuse of prescription opioids may be just as important for both IR and ER opioids. Copyright © 2016 John Wiley & Sons, Ltd.

Understanding motivations and use typologies of gabapentin with opioid agonist medications.

BACKGROUND: Prior research suggests a potential relationship between the nonmedical use of gabapentin and use of opioid agonist medications (OAMs), buprenorphine and methadone. However, this research has been limited in scope and understanding despite increases in gabapentin prescribing in opioid use disorder (OUD) treatment settings and increased detection in opioid overdose fatalities. METHODS: Data were analyzed for 346 participants of a follow-up program to an ongoing national opioid surveillance program of new entrants to treatment for opioid use disorder. Data were sourced from a cross-sectional online survey distributed in July/August 2021. RESULTS: Lifetime exposure to gabapentin was reported by 60.0 % of the sample, while lifetime history of nonmedical use was reported by 43.2 %. Of those nonmedically using gabapentin, 50.0 % did so while also on a dosage of either buprenorphine or methadone, with 28.4 % engaged in concurrent nonmedical use of both gabapentin and OATs. Motivations for concurrent nonmedical use included high-seeking (38.6 %), self-management of pain/physical symptoms (33.3 %), and self-management of OUD (22.2 %). CONCLUSIONS: Gabapentin exposure in treatment-seeking persons with OUD appears to be quite common, and use, both medically and nonmedically, frequently occurs alongside OAMs. Motivations for concurrent nonmedical use of gabapentin and OATs mirrors motivations for off-label prescribing by healthcare providers, but may also serve as a form of self-management of OUD when OAM regimens are interrupted, insufficiently prescribed or prescribed at insufficient dosages. Further research should seek to understand the risks versus benefits of gabapentin in OAM treatment settings.

Differences in Self-identification of Opioid Overdose Risk and Naloxone Perceptions Between Therapeutic and Nontherapeutic Opioid Populations.

OBJECTIVES: Efforts to improve low naloxone uptake to mitigate the current opioid crisis have included coprescribing naloxone with opioid medications and, more recently, expansion through over-the-counter availability, the latter of which necessitates self-identification of overdose risk by consumers. This study sought to understand perceptions of opioid overdose risk and naloxone among distinct opioid populations at elevated risk for overdose. METHODS: A cross-sectional, online survey was provided to 2 opioid populations in June 2020. First, chronic pain opioid managed (CPOM; n = 190) individuals currently treated with an opioid prescription (either >50 daily morphine milligram equivalents [73.2%] or benzodiazepine co-use [52.6%]), restricted by confounders. Second, individuals with a history of opioid use disorder (OUD; n = 152) previously participating in a national opioid surveillance study of new entrants to substance use treatment centers. RESULTS: Risk perceptions significantly differed, with 60.0% (CPOM) versus 28.9% (OUD) reporting that they were "not at all concerned about overdosing," and 62.1% (CPOM) versus 19.1% (OUD) perceiving themselves as having "no risk" of overdose. Perceived need for naloxone was lower among CPOM versus OUD patients (48.3% and 71.8%, respectively), whereas 22.6% and 35.0%, respectively, indicated any likelihood of obtaining naloxone in the future. CONCLUSIONS: Results suggest that a significant proportion of both samples lacked the ability to self-identify their risk of overdose and self-select themselves as needing naloxone, with gaps being more prominent in the CPOM sample. A multi-intervention framework that addresses distinct pathways of behavioral change between unique opioid populations should be considered in conversations surrounding potential transitions to over-the-counter naloxone.

Associations Between Kratom-Related State Policy Environments and Kratom Use in a Nationally Representative Population in the United States.

Limited research has resulted in conflicting views on the risks versus benefits associated with kratom use. Despite no federal policy in the United States, individual states have implemented diverging policies through kratom bans, and legalization and regulation through Kratom Consumer Protection Acts (KCPAs). The Survey of Non-Medical Use of Prescription Drugs (NMURx) Program employs nationally-representative, repeated cross-sectional surveys on drug use. In 2021, weighted prevalence of past-12 month kratom use was compared across three state legal frameworks: no overarching state policy, KCPAs, and state bans. There was lower estimated prevalence of kratom use in banned states (prevalence: 0.75% (0.44, 1.06) relative to states with a KCPA (1.20% (0.89, 1.51)), and relative to states with no policies (1.04% (0.94, 1.13), though odds of use were not significantly associated with policy type. Kratom use was significantly associated with medicated treatment for opioid use disorder. While there were observed differences in the prevalence of past-12 month kratom use by state policy type, low uptake mitigated meaningful distinctions by limiting statistical precision, and potentially confounding effects, such as accessibility online. Future kratom-related policy decisions should be informed through evidence-based research.

Associations of Transactional Sex and Sexually Transmitted Infections Among Treatment-Seeking Individuals With Opioid Use Disorder.

INTRODUCTION: Coinciding with the rise in opioid use across the U.S., the rates of sexually transmitted infections have reached historically high levels, underscoring the need to understand multiple pathways of disease spread. Although prevention is often focused on injection-related behaviors, this study sought to identify the prevalence and associations of a little understood pathway, transactional sex, among individuals with opioid use disorder, including associations of transactional sex with the prevalence of sexually transmitted infection diagnoses. METHODS: Data were sourced from a nationwide opioid surveillance program of treatment-seeking individuals with opioid use disorder utilizing a serial, cross-sectional survey of 4,366 new entrants to 1 of 99 substance use treatment programs for opioid use disorder in 37 states from October 2018 to June 2021. RESULTS: A quarter of the sample (24.9%) self-reported a lifetime history of transactional sex for drugs, with rates highest for sexual (56.6%) and gender (53.8%) minority, female (33.4%), Latinx (30.4%), and Black (29.6%) subgroupings. Lifetime diagnoses of all specific sexually transmitted infections analyzed were significantly higher (p<0.001) among those reporting transactional sex, particularly syphilis (14.3% vs 4.4%) and HIV (4.0 vs 0.9%). Financial hardship, trauma, and psychiatric disorder were significantly associated with transactional sex engagement. CONCLUSIONS: Transactional sex is relatively common among patients with opioid use disorder, particularly among sexual/gender minorities, which was associated with a greater lifetime prevalence of all sexually transmitted infections assessed. Sexually transmitted infection testing remains at low levels within substance use treatment programs, occurring in just 26.3% of programs; sexual health screenings and sexually transmitted infection prevention/testing need to be prioritized and integrated into opioid use disorder patient care.

Gabapentin Use Among Individuals Initiating Buprenorphine Treatment for Opioid Use Disorder.

Importance: Gabapentin prescriptions have drastically increased in the US due to off-label prescribing in settings such as opioid use disorder (OUD) treatment to manage a range of comorbid conditions and withdrawal symptoms, despite a lack of evidence. Objective: To assess the purpose and associated risks of off-label gabapentin use in OUD treatment. Design, Setting, and Participants: This retrospective recurrent-event case-control study with a crossover design used administrative claims data from MarketScan Commercial and Multi-State Medicaid databases from January 1, 2006, to December 31, 2016. Individuals aged 12 to 64 years with an OUD diagnosis and filling buprenorphine prescriptions were included in the primary analysis conducted from July 1, 2022, through June 1, 2023. Unit of observation was the person-day. Exposures: Days covered by filled gabapentin prescriptions. Main Outcomes and Measures: Primary outcomes were receipt of gabapentin in the 90 days after initiation of buprenorphine treatment and drug-related poisoning. Drug-related poisonings were defined using codes from International Classification of Diseases, Ninth Revision, and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision. Results: A total of 109 407 patients were included in the analysis (mean [SD] age, 34.0 [11.2] years; 60 112 [54.9%] male). Among the 29 967 patients with Medicaid coverage, 299 (1.0%) were Hispanic, 1330 (4.4%) were non-Hispanic Black, 23 112 (77.1%) were non-Hispanic White, and 3399 (11.3%) were other. Gabapentin was significantly less likely to be prescribed to Black or Hispanic patients, and more likely to be prescribed to female patients, those with co-occurring substance use or mood disorders, and those with comorbid physical conditions such as neuropathic pain. Nearly one-third of persons who received gabapentin (4336 [31.1%]) had at least 1 drug-related poisoning after initiating buprenorphine treatment, compared with 13 856 (14.5%) among persons who did not receive gabapentin. Adjusted analyses showed that days of gabapentin use were not associated with hospitalization for drug-related poisoning (odds ratio, 0.98 [95% CI, 0.85-1.13]). Drug-related poisoning risks did not vary based on dosage. Conclusions and Relevance: Gabapentin is prescribed in the context of a myriad of comorbid conditions. Even though persons receiving gabapentin are more likely to have admissions for drug-related poisoning, these data suggest that gabapentin is not associated with an increased risk of drug-related poisoning alongside buprenorphine in adjusted analyses. More data on the safety profile of gabapentin in OUD settings are needed.

Abuse of tapentadol compared to other atypical opioids among individuals entering treatment for opioid use disorders.

OBJECTIVE: Tapentadol is an atypical opioid analgesic thought to have dual mechanisms of action: µ-receptor agonism and inhibition of norepinephrine reuptake. Unlike other atypical opioids, tapentadol is a schedule II-controlled substance. We compared the prevalence of abuse (use to get high) of tapentadol to other atypical opioids used to treat pain (buprenor-phine and tramadol). DESIGN: An observational, serial cross-sectional study. SETTING: Individuals enrolling in treatment programs for opioid use disorder in 2019. Each completed a self-administered, paper questionnaire assessing prescription drug abuse and illegal drug use within 1 week of enrollment. MAIN OUTCOME MEASURES: Indication of past month abuse of tapentadol or comparator drugs on a self-administered ques-tionnaire. RESULTS: There were 6,987 respondents. Unadjusted and utilization-adjusted logistic regression models were used to compare odds of endorsement of tapentadol to tramadol and buprenorphine products indicated for the management of pain. Unadjusted abuse prevalence was 0.20 percent for total tapentadol (0.03 percent for NUCYNTA® and 0.06 percent for NUCYNTA ER). Relative to total tapentadol, the odds of abuse of buprenorphine for pain was 2.9 times greater (95 percent CI: 1.6 to 5.3, p < 0.001), and for tramadol, 43.1 times greater (95 percent CI: 25.3 to 73.3, p < 0.001). Adjusting for prescriptions dispensed, differences in odds of abuse were not statistically significant (odds ratio (OR) = 1.6, 95 per-cent CI: 0.9 to 3.0, p = 0.108 for buprenorphine for pain and OR = 0.7, 95 percent CI: 0.4 to 1.2, p = 0.209 for tramadol). CONCLUSIONS: Tapentadol use to get high is less frequent than other atypical opioids. Findings suggest tapentadol is rarely the primary drug abused by an individual.

Nonmedical use of gabapentin and opioid agonist medications in treatment-seeking individuals with opioid use disorder.

BACKGROUND: As prescriptions for gabapentin have increased in recent years, nonmedical use and risk of adverse outcomes (e.g., hospitalizations and overdose) have been identified, particularly in association with opioids, including opioid agonist medications (OAMs) buprenorphine and methadone. However, there is a lack of systematic, nationwide data assessing the relationship between the nonmedical use of gabapentin and OAMs. METHODS: Data were sourced from two nationwide opioid surveillance programs of treatment-seeking individuals with opioid use disorder (OUD). Both programs utilized an identical serial, cross sectional survey of 12,792 new entrants to one of 163 substance use treatment programs for OUD in 46 states and the District of Columbia from January 2019 to December 2020. RESULTS: Past month nonmedical use of gabapentin was endorsed by 9.3% of the sample. Of those using gabapentin nonmedically, 64.1% also endorsed nonmedical use of an OAM, including concomitant use of methadone (35.3%), and buprenorphine (49.0%). Concomitant nonmedical use of gabapentin and OAMs was more prevalent (versus nonmedical use of gabapentin alone) in the Southern region, among those living in a street dwelling, those with chronic pain and healthcare professionals. CONCLUSIONS: Nonmedical use of gabapentin in people with OUD appears to frequently coincide with nonmedical use of OAMs. As prescriptions and off-label use of gabapentin increase, provider education should include the risks of concomitant gabapentin and OAM use, particularly amongst buprenorphine prescribers. Future research should investigate motivations (e.g., OUD self-management) for nonmedical use of gabapentin and OAMs within the context of OUD treatment access and retention.

Association between recent overdose and chronic pain among individuals in treatment for opioid use disorder.

Chronic pain increases risk for opioid overdose among individuals with opioid use disorder. The purpose of this study is to evaluate the relationship between recent overdose and whether or not chronic pain is active. 3,577 individuals in treatment for opioid use disorder in 2017 or 2018 were surveyed regarding recent overdoses and chronic pain. Demographics from the 2017 Treatment Episode Data Set, which includes all U.S. facilities licensed or certified to provide substance use care, were used to evaluate the generalizability of the sample. χ2 tests and logistic regression models were used to compare associations between recent overdoses and chronic pain. Specifically, active chronic pain was associated with opioid overdose among people in treatment for opioid use disorder. Individuals with active chronic pain were more likely to have had a past month opioid overdose than those with no history chronic pain (adjusted OR = 1.55, 95% CI 1.16-2.08, p = 0.0003). In contrast, individuals with prior chronic pain, but no symptoms in the past 30 days, had a risk of past month opioid overdose similar to those with no history of chronic pain (adjusted OR = 0.88, 95% CI 0.66-1.17, p = 0.38). This suggests that the incorporation of treatment for chronic pain into treatment for opioid use disorder may reduce opioid overdoses.

Role of key informants and direct patient interviews in epidemiological studies of substance abuse.

PURPOSE: The present study was undertaken to assess the degree to which key informants' perceptions of relative abuse liability of opioids in their communities correspond to actual drug use in their patients. METHODS: Key informants (n = 49) and their patients (n = 738) were asked to complete anonymous, independent paper surveys about perceived or actual abuse of nine targeted opioid drugs: buprenorphine, fentanyl, heroin, hydrocodone, hydromorphone, methadone, morphine, oxycodone and tramadol. RESULTS: There was a strong correspondence (R = 0.98) between KI rankings of relative abuse of opioids in their patient population and the actual rank order calculated from their patients' selection of a primary euphorigenic opioid. The patient surveys not only validated the KI's conclusions, but also provided a great deal of important information about the nature of the abuse patterns. Notably, significant co-morbidity was found in the patient population: 55% had a history of psychiatric problems; chronic pain of moderate intensity was common; 67% were nicotine dependent; and 43% were diagnosed alcoholics. DISCUSSION: Our results demonstrate that KI's perceived rank order of drugs of choice correlated almost perfectly with their patients' choice of a primary drug. These data suggest that key informants, as they have for decades in epidemiological research, provide a reliable, high-level view of substance abuse in their catchment area. As such, KIs provide valid and reliable information on scope and patterns of abuse, but if more detail is required about the characteristics of abuse, such as that required for FDA-mandated Risk Evaluation and Mitigation Strategies, then direct interviews with the abusers themselves seem more appropriate.

Multiple Determinants of Specific Modes of Prescription Opioid Diversion.

Numerous national surveys and surveillance programs have shown a substantial rise in the abuse of prescription opioids over the past 15 years. Accessibility of these drugs to non-patients is the result of their unlawful channeling from legal sources to the illicit marketplace (diversion). Empirical data on diversion remain absent from the literature. This paper examines abusers' sources of diverted drugs from two large studies: 1) a national sample of opioid treatment clients (N=1983), and 2) a South Florida study targeting diverse populations of opioid abusers (N=782). The most common sources of diverted medications were dealers, sharing/trading, legitimate medical practice (e.g., unknowing medical providers), illegitimate medical practice (e.g., pill mills), and theft, in that order. Sources varied by users' age, gender, ethnicity, risk-aversiveness, primary opioid of abuse, injection drug use, physical health, drug dependence, and either access to health insurance or relative financial wealth. Implications for prescription drug control policy are discussed.

Shifting Pathways of Stimulant Use Among Individuals With Opioid Use Disorder: A Retrospective Analysis of the Last Thirty Years.

Background: Stimulant use among individuals with opioid use disorder has recently increased, driven by changes in drug distribution channels. However, our understanding of polysubstance use is often limited by a need to provide targeted treatment to a primary drug of addiction. Yet there is a crucial need to better understand pathways to addiction, and how the use of multiple substances may differ between populations, as well as time periods. Methods: Using a national opioid surveillance system, we analyzed survey data from new entrants to 124 opioid use disorder treatment centers from 2017 to 2020. Age of first use was collected for prescription opioids, illicit opioids, prescription stimulants, crack/cocaine, and methamphetamines. Year of initial use of an opioid or stimulant was calculated and grouped by 5 year blocs, inclusive of initial use starting from 1991 and ending in 2020 (n = 6,048). Results: Lifetime exposure to stimulants was 82.5% among individuals with opioid use disorder. Mean age of initiation increased for all drugs in 2016-2020, in particular prescription opioids (22.3 to 31.8). Stimulants were initiating drugs for a substantial proportion of individuals with opioid use throughout the analyzed time period. Those initiating opioid/stimulant use from 1991 to 1995 had a mean average of 6.8 years between first and second drug exposure, which steadily decreased to 1.5 years between exposures in 2016-2020. Sankey plots depict significantly more drug transitions in those initiating use from 1991 to 2000 (65.1% had at least two drug transitions) compared to 2010-2020 (16.0%). Opioid-stimulant use increased over time among racial/ethnic minorities, sexual minorities, and those with an educational attainment of high school or less. Conclusion: These data highlight not only the substantial prevalence of stimulant use among individuals who develop opioid use disorder, but also the variability through which pathways of use occur. Prevention and intervention efforts need to take into account increasing ages of initial drug exposures, demographic shifts in stimulant-using populations, and more rapid drug transitions between opioid and stimulants. But at a broader level, prevention, harm reduction ideology, and addiction medicine needs to take into account the ubiquity of polysubstance use among individuals with substance use disorders.