Objective The objective of this study is to compare maternal and neonatal outcome of opioid-dependent women maintained on buprenorphine or methadone throughout pregnancy in a randomized double-blind double-dummy clinical trial (CT) with a comparison group undergoing a structured standard protocol (SP) at the Medical University of Vienna, Austria. Methods One hundred and fourteen subjects were included in the analysis, with 77 in SP (n=51 methadone, n=26 buprenorphine), and 37 in CT (n=19 methadone, n=18 buprenorphine), comparing maternal concomitant consumption during third trimester, demographic birth data, duration of treatment for neonatal abstinence syndrome (NAS), morphine dose for NAS treatment and length of hospital stay (LOS). Results Both study groups yielded healthy neonates with no significant demographic differences and equivalently low rates of positive maternal urine toxicologies. However, NAS parameters were significantly better in CT regarding total medication dose administered to neonates (p=0.014) and LOS (p=0.015). Superior results were achieved in buprenorphine compared with methadone-exposed neonates regarding gestational age at birth (p=0.003), birth weight (p=0.011), total morphine dose administered (p=0.008), NAS treatment duration (p=0.008) and LOS (p=0.001). Conclusions Comparably favorable outcome for mothers and infants and efficacy and safety of opioid medications were shown in both treatment approaches. Neonatal care could benefit from transferring successful CT procedures into clinical practice. Copyright © 2011 John Wiley & Sons, Ltd.

Background: Prenatal nicotine exposure is associated with increased neonatal mortality, low birth weight, and smaller head circumference. Opioid-dependent pregnant women show a particularly high prevalence of tobacco smoking and are at greater risk for additional adverse events. However, little is known about the impact of tobacco smoking on opioid-maintained pregnant women and neonatal outcomes. Patients and Methods: This study examined the effect of cigarette smoking on 139 opioid-maintained pregnant women and their neonates. Forty-five percent of the participants were maintained on slow-release oral morphine (SROM), 39% received methadone maintenance, and 16% received buprenorphine. Participants were divided into two groups: (1) women who reported a low cigarette consumption of ≤10 cigarettes/day (56.8%) and (2) those reporting heavy consumption of ≥20 cigarettes/day (43.2%). Neonatal outcome measures were assessed, and a standardized Finnegan score was applied to determine the neonatal abstinence syndrome (NAS). Results: Fifty-two percent of the newborns did not require treatment for NAS (54% of neonates born to methadone-maintained mothers, 30% born to SROM-maintained mothers, and 95% born to buprenorphine-maintained mothers; p < 0.001). Heavy cigarette consumption was associated with significantly lower neonatal birth weight (p < 0.001), smaller birth length (p = 0.017) as well as with the severity of NAS (p = 0.03). With regard to concomitant consumption of opioids (p = 0.54), cocaine (p = 0.25), amphetamines (p = 0.90) or benzodiazepines (p = 0.09), no significant differences between heavy or low nicotine consumption were noted. Conclusion: Heavy tobacco smoking in opioid-maintained pregnant women is associated with adverse medical and developmental consequences for the newborn. Future treatment programs for this target group should focus on an individualized approach to opioid maintenance therapy in addition to offering specially tailored counseling for smoking cessation.

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.

Introduction Some fear that distribution of naloxone to persons at risk of experiencing an opioid overdose may reduce the perceived negative consequences of drug use, leading to riskier patterns of use. This study assessed whether participation in naloxone/overdose training altered drug use frequency, quantity or severity among heroin users in and out of treatment. Methods Clinical interviews were performed assessing patterns of heroin and other drug use prior to, and at multiple timepoints after overdose education and naloxone training. This study compared baseline drug use to that at 1 and 3 months post training. Results Both current heroin users (n=61) and former users in agonist maintenance (n=69) typically showed decreases in heroin and polydrug use at both 1 and 3 months after training. The Addiction Severity Index drug composite score also decreased at follow up. Conclusions This analysis found no evidence of compensatory drug use following naloxone/overdose training among two groups of heroin users. These findings support the acceptance and expansion of naloxone distribution to at-risk populations and may assist in allaying concerns about the potential for unintended negative consequences on drug use.

Background and Aims Providing take-home naloxone (THN) to people who use opioids is an increasingly common strategy for reversing opioid overdose. However, implementation is hindered by doubts regarding the ability of people who use opioids to administer naloxone and respond appropriately to overdoses. We aimed to increase understanding of the competencies required and demonstrated by opioid users who had recently participated in a THN programme and were subsequently confronted with an overdose emergency. Design Qualitative study designed to supplement findings from a randomized controlled trial of overdose education and naloxone distribution. Interviews were audio-recorded, transcribed, systematically coded and analysed via Iterative Categorization. Setting New York City, USA. Participants Thirty-nine people who used opioids (32 men, 7 women; aged 22-58 years). Intervention Trial participants received brief or extended overdose training and injectable or nasal naloxone. Measurements The systematic coding frame comprised deductive codes based on the topic guide and more inductive codes emerging from the data. Findings In 38 of 39 cases the victim was successfully resuscitated; the outcome of one overdose intervention was unknown. Analyses revealed five core overdose response 'tasks': (1) overdose identification; (2) mobilizing support; (3) following basic first aid instructions; (4) naloxone administration; and (5) post-resuscitation management. These tasks comprised actions and decisions that were themselves affected by diverse cognitive, emotional, experiential, interpersonal and social factors over which lay responders often had little control. Despite this, participants demonstrated high levels of competency. They had acquired new skills and knowledge through training and brought critical 'insider' understanding to overdose events and the resuscitation actions which they applied. Conclusions People who use opioids can be trained to respond appropriately to opioid overdoses and thus to save their peers' lives. Overdose response requires both practical competency (e.g. skills and knowledge in administering basic first aid and naloxone) and social competency (e.g. willingness to help others, having the confidence to be authoritative and make decisions, communicating effectively and demonstrating compassion and care to victims post-resuscitation).

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Possibly through their actions upon glia, peroxisome proliferator-activated receptor agonists (PPAR) have been shown to alter the abuse potential of addictive drugs in several preclinical models. The current study extends this research into the human laboratory as the first clinical study into the effects of the PPAR gamma agonist, pioglitazone, on the abuse potential of nicotine. Heavy smokers were recruited for this 3-week study. Upon admission, participants were randomized to either active (45 mg, n = 14) or placebo (0 mg, n = 13) PIO maintenance conditions for the duration of the study. After 5–7 days of stabilization on a 7 mg nicotine patch, participants began laboratory testing. On the 1st–4th test days, participants could self-administer cigarettes or receive money by making verbal choices for either option. On the 5th day, participants were administered 10 puffs of their usual brand of cigarette in the morning and later chose between smoking and money by making finger presses on a computer mouse in a progressive ratio self-administration task. Later on the 5th day participants also underwent a smoking cue exposure session. The 8th–11th test days were identical to the 1st–4th test days with the exception that during one of the test weeks de-nicotinized cigarettes were available, and during the other nicotinized cigarettes were available. Nicotinized cigarettes were always administered on the 5th and 12th days. On some measures PIO increased indicators of abuse potential, though this effect was typically not statistically significant. However, PIO did significantly reduce measures of craving.

Pregnant drug-using women were often of low socioeconomic status, with mental health and substance use patterns suggesting the need for targeted mental health/substance use screening and interventions before and during pregnancy, particularly for opioid-polydrug users.