Routes of abuse of prescription opioid analgesics: a review and assessment of the potential impact of abuse-deterrent formulations

Gąsior, Maciej; Bond, Mary; Malamut, Richard

doi:10.1080/00325481.2016.1120642

Cited by 80 publications

(83 citation statements)

References 111 publications

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“…Despite available opioid substitution treatments, individual differences exist with respect to which opioid addicted individuals will relapse (Bickel, Amass, Higgins et al, 1997;Epstein, Willner-Reid, Vahabzadeh et al, 2009;Preston, Kowalczyk, Phillips et al, 2017). Emerging evidence suggests that a primary aspect by which opioid addicted individuals differ is route of administration -oral versus intravenous (Back, Lawson, Singleton et al, 2011;Gasior, Bond & Malamut, 2016;Kirsh, Peppin & Coleman, 2012;Surratt, Kurtz & Cicero, 2011;Young, Havens & Leukefeld, 2010).…”

Section: Introductionmentioning

confidence: 99%

Oral prescription opioid-seeking behavior in male and female mice

Phillips¹,

McGovern²,

Lee³

et al. 2019

Preprint

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A significant portion of prescription opioid users self-administer orally rather than intravenously. Animal models of opioid addiction have demonstrated that intravenous cues are sufficient to cause drug-seeking. However, intravenous models may not model oral users, and the preference to self-administer orally appears to be partially influenced by the user's sex. Our objectives were to determine whether oral opioid-associated cues are sufficient for relapse and whether sex differences exist in relapse susceptibility. Mice orally selfadministered escalating doses of oxycodone under postprandial (prefed) or non-postprandial (no prefeeding) conditions. Both sexes demonstrated robust cue-induced reinstatement. In separate mice we found that oral oxycodone cues were sufficient to reinstate extinguished oral oxycodone-seeking behavior in the absence of postprandial or prior water self-administration training. During self-administration, we found that female mice earned significantly more mg/kg oxycodone than male mice. Follow-up studies indicated sex differences in psychomotor stimulation and plasma oxycodone/oxymorphone following oral oxycodone administration. In addition, gonadal steroid studies were performed in which we found divergent responses where ovariectomy enhanced and orchiectomy suppressed oral self-administration. While the suppressive effects of orchiectomy were identified across doses and postprandial conditions, the enhancing effects of ovariectomy were selective to non-postprandial conditions. These studies establish that 1) oral drug cues are sufficient to cause reinstatement that is independent of prandial conditions and water-seeking behavior, 2) earned oral oxycodone is larger in female mice compared with male mice potentially through differences in psychomotor stimulation and drug metabolism, and 3) gonadectomy produces divergent effects on oral oxycodone self-administration between sexes.

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Section: Introductionmentioning

confidence: 99%

Oral prescription opioid-seeking behavior in male and female mice

Phillips¹,

McGovern²,

Lee³

et al. 2019

Preprint

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“…2 However, users must eventually determine how to cope with the development of tolerance that is inevitable with the persistent use of any opioid. The literature is primarily devoted to two consequences of tolerance: (1) progressing to non-oral routes of administration such as injection and inhalation, which provide a more rapid response with less drug [2][3][4][5][6] or (2) shifting to stronger opioids (prescription or illicit) to replace a weaker one to which tolerance has developed. [7][8][9][10] What is often overlooked and little understood is a seemingly obvious third pathway for coping with tolerance: increasing the number of pills/tablets ingested at one time.…”

Section: Introductionmentioning

confidence: 99%

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

Ellis

Cicero

Dart

et al. 2018

Pharmacoepidemiology and Drug

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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.

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“…There are notable differences in reported ROAs among prescription opioid analgesic formulations. The preferred ROA most likely reflects the level of attractiveness an abuser perceives for a certain drug, which is itself determined by a myriad of pharmacological, behavioral, and social factors . Furthermore, individual abusers often report using several different routes of abuse .…”

Section: Discussionmentioning

confidence: 99%

“…The preferred ROA most likely reflects the level of attractiveness an abuser perceives for a certain drug, which is itself determined by a myriad of pharmacological, behavioral, and social factors. 24,25 Furthermore, individual abusers often report using several different routes of abuse. 26,27 In this study, the ROA pattern among both adults and adolescents who report abuse of hydrocodone IR combination products demonstrate that the predominant ROA for these opioids is the oral route (adults, 90.3%; adolescents, 81.2%) followed by snorting (adults: 23.4%, adolescents:…”

Section: Discussionmentioning

confidence: 99%

Patterns of abuse and routes of administration for immediate‐release hydrocodone combination products

Cassidy

Oyedele

Mickle

et al. 2017

Pharmacoepidemiology and Drug

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PurposePrescriptions for hydrocodone immediate‐release (IR) combination products have recently decreased, yet they represent the majority of opioid prescriptions dispensed and are commonly abused analgesics among both adults and adolescents. Little data exist to understand the contribution of IR products to the problem of prescription opioid abuse. This study aimed to better understand abuse patterns for hydrocodone IR combination products among adult and adolescent substance abusers.MethodsThis cross‐sectional study examines abuse prevalence (including abuse adjusted for prescription volume and morphine milligram equivalents) and abuse characteristics for hydrocodone IR combination products and other prescription opioids among separate samples of adults and adolescents assessed for substance abuse problems or entering treatment from January 2012 through June 2015.ResultsResults indicate higher abuse for hydrocodone IR combination products than other opioid categories per 100 assessments but lower per prescriptions dispensed. Hydrocodone IR combination products had similar abuse prevalence to all extended‐release and long‐acting opioids when considering abuse measured per morphine milligram equivalents dispensed. An upward trend in hydrocodone IR combination product abuse was observed among adult substance abusers comparing the period prior to and after Drug Enforcement Administration rescheduling of these products in October 2014. Most individuals reported oral abuse of hydrocodone IR combination products, but snorting, reported by 23% of hydrocodone IR combination product abusers, also appears to be a route of abuse that may have public health relevance.ConclusionsGiven their high prescription volume, hydrocodone IR combination products, even at a relatively low prevalence of abuse, may contribute substantially to the overall problem of prescription opioid abuse. Additional public health interventions, including development of abuse‐deterrent formulations for these types of opioid products may aid in reducing their abuse.

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Routes of abuse of prescription opioid analgesics: a review and assessment of the potential impact of abuse-deterrent formulations

Cited by 80 publications

References 111 publications

Oral prescription opioid-seeking behavior in male and female mice

Oral prescription opioid-seeking behavior in male and female mice

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

Patterns of abuse and routes of administration for immediate‐release hydrocodone combination products

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