Evaluation of the Abuse Potential of Extended Release Hydromorphone Versus Immediate Release Hydromorphone

Abstract

Immediate release (IR) hydromorphone has experienced significant misuse and abuse. An extended release (ER) hydromorphone formulation has been developed to provide sustained pain relief and may reduce the likelihood for abuse by delaying absorption. In this double-blind, placebo-controlled, randomized, 2-part crossover study, the abuse potential of single oral doses of hydromorphone ER (intact: 16-, 32-, and 64-mg; milled: 8-mg) was compared with 8-mg hydromorphone IR and placebo. After drug administration, subjects with a history of recreational opioid use completed a series of assessments, including subjective effects visual analog scales (eg, drug liking) and Addiction Research Center Inventory With Cole Modification, at several timepoints up to 48 hours postdose. Independent of formulation, maximum at-the-moment drug liking was higher for hydromorphone versus placebo. Maximum drug liking occurred earlier and was higher for 8-mg IR versus 16-mg ER but similar to 32- and 64-mg ER. Most positive effects were lower after 16-mg ER compared with other doses, including 8-mg IR. Bad drug effects were higher for hydromorphone ER, particularly the 64-mg dose. Milled 8-mg ER produced similar subjective effects to 8-mg IR. Comparison of scores after administration of 8-mg IR on 2 separate occasions showed that most assessments exhibited good test-retest reliability, although some scores declined marginally between test and retest. Delayed onset of good drug effects and prominent bad drug effects of hydromorphone ER suggest that, when administered intact, this formulation may have lower abuse potential than hydromorphone IR.

Core outcome measures for opioid abuse liability laboratory assessment studies in humans: IMMPACT recommendations

“…However, individuals who do and do not abuse drugs may differ in important ways (e.g., [11]; [17]; [64]; [70]), and further research is warranted on the impact of these differences on ALA. Finally, a number of prescription opioid AL studies include prescreening procedures, initially determining that participants enrolled in the study can distinguish an abused opioid from placebo, and that they report positive subjective effects from the opioid ([6]; [17]; [38]; [57]; [61]). Failure to identify participants who can distinguish an opioid from placebo and report positive subjective effects prior to administering the test drug could result in a study that underestimates the abuse liability of the test drug.…”

Impact of Intravenous Naltrexone on Intravenous Morphine-Induced High, Drug Liking, and Euphoric Effects in Experienced, Nondependent Male Opioid Users

“…The total score is calculated by adding the individual scores (maximum possible total score = 45). [23,28] Since the drug-liking VAS has been used in other studies as a measure of drug attractiveness, [21] data from DEQ question #4, ''Do you like the drug?'' are reported here.…”

“…Ability to distinguish morphine from placebo was assessed by the investigator based on subject responses to a Drug Effects Questionnaire (DEQ; a nine-item questionnaire with a 100 mm visual analog scale [VAS]; 0 = none, 100 = extreme) [27] and the Cole/ARCI Stimulation-Euphoria modified scale, description following in the Study Endpoints section, at designated time points following each dose. [23,28] At the conclusion of the drug discrimination phase, the blind was broken. The investigator determined the subjects who were able to discriminate between morphine and placebo and, further, to report a more positive overall response to morphine versus placebo, using the response to the aforementioned study endpoint measures, along with clinical judgment.…”

Human abuse potential of immediate-release/extended-release versus immediate-release hydrocodone bitartrate/acetaminophen: a randomized controlled trial in recreational users of prescription opioids

“…Human abuse potential (HAP) studies assess an opioid analgesic on physiologic, subjective, and observational measures in volunteer participants under controlled, laboratory conditions to predict the likelihood that the medication will be abused after it is marketed [10]. HAP studies have been used to assess the abuse potential of many drugs, not only those with an abuse-deterrent design [11][12][13][14][15][16][17][18].…”