Ibudilast, a nonselective phosphodiesterase inhibitor, is used clinically in Asia for the treatment of asthma and poststroke dizziness. Recent preclinical studies have suggested that it also inhibits glial cell activation in rodents, and may alter opioid-mediated effects, including analgesia and withdrawal symptoms. The effects of ibudilast on the abuse potential of opioids in humans are largely unknown. The present study was designed to examine the influence of ibudilast on subjective (including drug craving), reinforcing, and analgesic effects of oxycodone in human volunteers diagnosed with opioid dependence (equivalent to moderate-severe opioid use disorder). Non-treatment-seeking opioid-dependent male volunteers (n=11) underwent an in-patient detoxification with morphine, followed by maintenance on placebo (0 mg b.i.d.) and active ibudilast (50 mg b.i.d.). Under each maintenance dose, six experimental sample and choice sessions were completed involving oral oxycodone administration (0, 15, and 30 mg/70 kg, p.o.). Subjective effects of oxycodone and drug craving were measured with visual analog scales (VAS) and a Drug Effects Questionnaire. The cold pressor test was used to produce pain, and a modified progressive-ratio choice procedure was used to measure the reinforcing effects of oxycodone. Under the active ibudilast condition compared with the placebo condition, ratings of drug liking following 15 mg of oxycodone were decreased significantly. The mean drug breakpoint value was also significantly lower in the active vs the placebo ibudilast condition under the 15 mg oxycodone condition, but not significantly lower under the 30 mg oxycodone condition. Heroin craving was significantly reduced under active ibudilast vs placebo, and similar effects were observed for tobacco and cocaine craving. Furthermore, mean subjective ratings of pain were lower in the active ibudilast condition. Our data suggest that ibudilast may be useful for treating opioid use disorders and it may enhance the analgesic effects of oxycodone.

Possibly through its effects on glia, the peroxisome proliferator-activated gamma receptor (PPARγ) agonist pioglitazone (PIO) has been shown to alter the effects of heroin in preclinical models. Until now, these results have not been assessed in humans. Heroin-dependent participants were randomized to either active (45 mg, n = 14) or placebo (0 mg, n = 16) PIO maintenance for the duration of the three-week study. After stabilization on buprenorphine (8 mg), participants began a two-week testing period. On the first to fourth test days, participants could self-administer drug or money by making verbal choices for either option. On the fifth day, active heroin and money were administered and participants could work to receive heroin or money using a progressive ratio choice procedure. Test days 6-10 were identical to test days 1-5 with the exception that, during one of the test weeks, placebo was available on the first four days, and during the other week heroin was available. PIO failed to alter the reinforcing or positive subjective effects of heroin, but it did reduce heroin craving and overall anxiety. Although we were unable to replicate the robust effects found in preclinical models, these data provide an indication of drug effects that deserves further exploration.

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Background Deceptive methods of falsifying urine samples are of concern for anyone who relies on accurate urine toxicology results. A novel method to combat these efforts utilizes polyethylene glycol (PEG) markers administered orally prior to providing a urine sample. By using various PEG combinations to create a tracer capsule of unique composition, each urine sample can be matched to that individual. The goal of this study was to determine the effectiveness of using the PEG marker system among active heroin users screening for research studies. Methods Upon each screening visit, participants (N=55) were randomized to provide an unobserved urine sample, or the PEG tracer procedure was used. LCMS analysis was used to distinguish the PEG combinations, and allowed us to provide a unique qualitative analysis of patterns of drug use (N=168, total urine specimens). Results The unique composition of the tracer capsules was accurately detected in 83.5% of the urine specimens. Analyses of inconsistencies implicated a number of possible attempts at fraudulence (11.4%) and investigator/lab error (5.1%). Among this sample, the concurrent use of multiple classes of psychoactive drugs was more common than not, though concomitant drug use was often underreported. Conclusion Urine drug testing should be the minimum standard for obtaining information about drug use as self-report was unreliable even in a situation where there were no perceived adverse consequences for full disclosure. In cases where there are significant pressures for individuals to falsify these data, more protective collection methods such as the PEG marker system should be considered.

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