Effects of ibudilast on oxycodone-induced analgesia and subjective effects in opioid-dependent volunteers.

Opioid-induced glial activation is hypothesized to contribute to the development of tolerance to opioid-induced analgesia. This inpatient, double-blind, placebo-controlled, within-subject and between-groups pilot study investigated the dose-dependent effects of ibudilast, a glial cell modulator, on oxycodone-induced analgesia. Opioid-dependent volunteers were maintained on morphine (30mg, PO, QID) for two weeks and received placebo ibudilast (0mg, PO, BID) during the 1st week (days 1-7). On day 8, participants (N=10/group) were randomized to receive ibudilast (20 or 40mg, PO, BID) or placebo for the remainder of the study. On days 4 (week 1) and 11 (week 2), the analgesic, subjective, and physiological effects of oxycodone (0, 25, 50mg/70kg, PO) were determined. Analgesia was measured using the cold pressor test; participants immersed their hand in cold water (4°C) and pain threshold and pain tolerability were recorded. Oxycodone decreased pain threshold and tolerability in all groups during week 1. During week 2, the placebo group exhibited a blunted analgesic response to oxycodone for pain threshold and subjective pain ratings, whereas the 40mg BID ibudilast group exhibited greater analgesia as measured by subjective pain ratings (p≤0.05). Oxycodone also increased subjective drug effect ratings associated with abuse liability in all groups during week 1 (p≤0.05); ibudilast did not consistently affect these ratings. These findings suggest that ibudilast may enhance opioid-induced analgesia. Investigating higher ibudilast doses may establish the utility of pharmacological modulation of glial activity to maximize the clinical use of opioids.

Abuse liability of oxycodone as a function of pain and drug use history.

The relationship between pain and prescription opioid abuse is poorly understood. Determining whether a patient is seeking additional opioid medications in order to alleviate pain or to abuse the drugs can be difficult. The present study was designed to evaluate two variables that may influence the abuse liability of opioids: drug use history and the presence or absence of experimentally induced pain. Eighteen healthy participants completed this outpatient study. One group was abusing prescription opioids (N=9) and one group had used prescription opioids medically but did not abuse them (N=9). All participants completed twelve sessions during which the effects of orally delivered oxycodone (0, 15, 30mg/70kg, PO) were examined. One dose was tested per day under double-blind conditions and sessions were separated by at least 48h. During the first "sample" session each week, participants were given $10 and the dose that was available later that week. During the second "choice" session, participants could self-administer either money or the previously sampled dose. Six sessions involved repeated hand immersions in cold water (4 degrees C) and six sessions involved immersions in warm water (37 degrees C). Most of the positive subjective effects of oxycodone were similar between the groups, but oxycodone self-administration significantly differed between groups. Non-abusers self-administered active doses of oxycodone only when they were in pain while abusers self-administered oxycodone regardless of the pain condition. These data suggest that an assessment of the reinforcing effects of opioids may be a sensitive method for differentiating opioid abusers from non-abusers.