Behavioral economic analysis of opioid consumption in heroin-dependent individuals: Effects of alternative reinforcer magnitude and post-session drug supply

Abstract

This study investigated the extent to which hydromorphone (HYD) choice and behavioral economic demand were influenced by HYD unit price (UP), alternative money reinforcement magnitude and post-session HYD supply. Heroin dependent research volunteers (n=13) stabilized on buprenorphine 8 mg/day first sampled two HYD doses (12 and 24 mg IM, labeled Drug A [session 1] and Drug B [session 2]). In each of the final six sessions, volunteers were given access to a 12-trial choice progressive ratio (PR) task and could earn a HYD unit dose (2 mg, fixed) or money ($2 or $4, varied across sessions), administered immediately after the work session. Before the PR task, volunteers were told which HYD supplemental dose (none, Drug A or B) would be available 3 hr after receiving the PR-contingent dose. PR-contingent HYD choice significantly decreased when $4 relative to $2 was concurrently available. Information about the post-session HYD supplement moderated this effect: when subjects were told a supplemental dose was available, HYD-seeking behavior decreased when the money alternative was smaller ($2), but this information did not further attenuate HYD choice, which was already low, when the money alternative was higher ($4). HYD demand elasticity was only increased by the $4 relative to $2 alternative without the HYD supplement. In summary, opioid-seeking behavior is influenced by the availability of concurrent non-drug and drug alternatives. These findings show that drug availability and non-drug alternatives interact to modulate drug-seeking behavior.

Sustained-Release Buprenorphine (RBP-6000) Blocks the Effects of Opioid Challenge With Hydromorphone in Subjects With Opioid Use Disorder

“…19 This dose, therefore, has substantial clinical relevance to concerns about possibly overriding the opioid blockade effect by using large opioid agonist doses. 19 Furthermore, Greenwald et al 7,10, 11 previously found that repeated administration of 24 mg bolus doses of hydromorphone in addition to daily buprenorphine doses to be safe. The 6 mg hydromorphone parenteral dose is approximately equivalent in analgesic potency to 45 mg of parenterally administered morphine, a dose in the range commonly used in opioid abuse liability assessment studies.…”

“…If the normality assumption was violated, the analyses were carried out on the log (base 10) transformed hydromorphone breakpoint value, as previously described. 11 …”

Predictors of buprenorphine initial outpatient maintenance and dose taper response among non-treatment-seeking heroin dependent volunteers

“…Advertisements and word-of-mouth referrals were used to recruit volunteers for three source studies (Greenwald and Steinmiller, 2009; Greenwald, 2010; Greenwald et al, 2013). …”

“…Inpatient experimental procedures varied slightly across the three programmatically-related source studies, but each involved two hydromorphone fixed-dose sampling sessions followed by six sessions during which participants could work on a behavioral choice task to earn units of money and/or hydromorphone (Greenwald and Steinmiller, 2009; Greenwald, 2010; Greenwald et al, 2013). The total amount of hydromorphone administered varied across studies due to differences in experimental design (see Table 1) and variability in participants’ choice responding.…”

Motivational assessment of non-treatment buprenorphine research participation in heroin dependent individuals

“…Data were collected during the screening phase for three similar laboratory-based opioid pharmacology research studies, which were registered as NIH clinical trials NCT00218309 (Greenwald and Hursh, 2006), NCT00218361 (Greenwald and Steinmiller, 2009), and NCT00608504 (Greenwald, 2010). For each study, candidates were told during the initial telephone interview and again during in-person screening that the study involved a minimum 10-day outpatient induction onto buprenorphine, two further weeks of buprenorphine maintenance during a continuous inpatient stay, and a standardized three-week outpatient buprenorphine dose taper (Greenwald, 2008).…”