ABSTRACT
Learing Objectives (1) Define nonmedical use of prescription opioids and the routes of administration used, including oral intact, oral manipulation, and non-oral routes. (2) Describe differences in patient characteristics and behaviors of those who report nonmedical use of prescription opioids via oral intact versus oral manipulation versus nonoral routes of administration. (3) Describe the reasons why nonmedical use of prescription opioids via oral manipulation should be considered high risk behavior in your patient population. Purpose While overdose deaths involving prescription opioid medications are decreasing, the latest data regarding overall substance abuse in the United States are daunting, exacerbated by the collision of the opioid epidemic and the COVID-19 pandemic. Recent studies have focused on closing the knowledge gap regarding the substance use pathways and behavioral profiles contributing to this ongoing public health crisis. The increased risk of prescription opioid abuse via non-oral routes of administration has been studied, suggesting the relative risk of an exposure resulting in a life-threatening event or death was 2.43 (95% CI 1.97, 2.99) if non-oral routes were reported compared to exposures involving oral route only. The increased risk associated with non-oral routes of administration of a prescription opioid is important, however, the majority of prescription opioid use occurs via the oral route of administration. Oral route of administration includes ingesting an intact tablet or capsule ('oral intact'), as well as manipulation of prescription opioid products prior to ingestion (chewing, crushing or dissolving) for the purpose of changing the user experience, for example, to increase the speed and intensity of a psychotropic effect ('oral manipulation'). Regardless of intent, oral manipulation is considered nonmedical use (NMU), meaning that the prescription medication is being used in a different way or for a different purpose than intended, whether it be for therapeutic reasons (misuse) or for psychotropic effect such as to get high (abuse). It is unknown whether those who engage in prescription opioid oral manipulation are at an increased risk of also using illicit drugs or engaging in even higher risk non-oral routes of administration. The purpose of this study was to utilize data from a general population study in the United States (US) to compare biopsychosocial and behavioral characteristics among those reporting prescription opioid NMU via oral intact route only, oral manipulation, and non-oral routes of administration. Methods This was an observational study conducted with a nationally representative sample of the general adult US population. Participants were recruited via e-mail through YouGov, a survey panel company that has an established participant registry as well as a validated sampling methodology to ensure representativeness of the research. The study used a self-administered online survey drawn from the opt-in panelists using samplematching methods to represent a target population of US adults ages 18-49 years. Inclusion criteria was a history of prescription opioid NMU. Four mutually exclusive groups were studied: (1) those who only reported prescription opioid NMU via oral intact route of administration, (2) those who reported oral manipulation but no non-oral routes of administration, (3) those who reported non-oral route of administration but no oral manipulation, and (4) those who reported both oral manipulation and non-oral routes of administration. Prescription opioid NMU via oral intact route of administration may have also been reported in groups 2, 3, and 4. Data were collected on demographics (age, sex, race, ethnicity, education, college enrollment, employment, etc.), select co-morbidities (diagnosis of anxiety, depression, alcohol use disorder, substance use disorder, etc.), routes of administration, sources of drug procurement, primary reason for use, factors influencing use of non-oral routes of administration, and concomitant use of other substances wi h prescription opioid NMU. Prescription opioid product names, active ingredients, and photos were used to aid in selection of substances used. Prescription opioid NMU included ANY of the following: (1) use for any reason, even once, without your own prescription, (2) use in ways other than prescribed (such as taking more than prescribed, more often than prescribed, or for any other reason or way than prescribed), and (3) use for the feeling or experience the medication caused (such as a feeling of being high, enhancement of other drugs, prevention or treatment of withdrawal symptoms, or other feelings). The route referenced as oral manipulation was defined as physical alteration of a prescription medication, such as chewing, crushing, cutting, or dissolving, prior to ingestion. Results Of the 24,000 study participants, 4,590 reported a history of prescription opioid NMU and met inclusion criteria for analysis: 3,477 (75.8%) reported prescription opioid NMU via oral intact only;438 (9.5%) reported oral manipulation but no non-oral routes of administration;390 (8.5%) reported non-oral routes of administration but no oral manipulation;and 285 (6.2%) reported both oral manipulation and nonoral route of administration. Compared to oral intact only users, those who reported oral manipulation and/or nonoral routes were more likely to be male, younger in age, and cover healthcare costs through Medicare and/or Medicaid. They were also more likely to have been arrested compared to oral intact only users. Those who reported oral manipulation (with or without non-oral routes) were more likely to be currently enrolled in a college or university than those who reported prescription opioid NMU via oral intact route only. The prevalence of lifetime diagnosis of select behavioral and mental health comorbidities was significantly higher among all oral manipulation and non-oral route study groups compared to the oral intact only group. The prevalence of anxiety, ADHD, bipolar, and alcohol use disorder was similar between those who reported prescription opioid NMU via oral manipulation and those who reported non-oral routes. The prevalence of substance use disorder significantly increased from the oral manipulation group to the non-oral route group to the oral manipulation plus non-oral route group. The age of initiation for most substances was younger among those in the oral manipulation and non-oral route groups compared to the oral intact only group. In relation to polysubstance use, the prevalence of concomitant use of tobacco, alcohol, marijuana, cocaine, sedatives, methamphetamine, prescription stimulants, heroin, and street fentanyl was significantly higher for those reporting prescription opioid NMU via oral manipulation and those reporting any non-oral route of administration compared to the oral intact only group. The prevalence of use to treat or prevent opioid-related withdrawal was similar between those who reported prescription opioid NMU via oral manipulation only (11.9) and non-oral routes only (13.6), yet over 3 times that (42.5) for those who reported both oral manipulation and non-oral routes of administration. Interestingly, those who reported oral manipulation were significantly more likely to do so to treat pain, for energy/stimulation, or to enhance the effect of other drugs than those who reported prescription opioid NMU via non-oral routes. Conclusion This study illustrates that biopsychosocial characteristics and behaviors of individuals that engage in prescription opioid NMU via oral manipulation are more similar to those that engage in non-oral routes of administration than with those that engage in oral intact route only. Hence, oral manipulation cannot be presumed as benign or insignificant. While this study did not allow for determination of causation, the data suggest a greater likelihood of high-risk behaviors in those who engage in prescription opioid NMU via oral manipulation than oral intact. These conclusions may be surprising to clinicians who view non-oral (intranasal or intravenous) use as the firs sign of concerning behavior. Overall, these findings have significant implications for clinicians and the greater research community as they highlight why oral manipulation (chewing, crushing, dissolving prior to ingestion) of a prescription opioid medication is not to be ignored and should be as concerning as non-oral use: both oral manipulated and non-oral routes suggest a significant potential for prescription opioid misuse, abuse and diversion, and related consequences such as overdose and death.