BACKGROUND Sublingual buprenorphine is an effective maintenance treatment for opioid dependence, yet intravenous buprenorphine misuse occurs. A buprenorphine/naloxone formulation was developed to mitigate this misuse risk. This randomized, double-blind, crossover study was conducted to assess the intravenous abuse potential of buprenorphine/naloxone compared with buprenorphine in buprenorphine-maintained injection drug users (IDUs). METHODS Intravenous heroin users (n=12) lived in the hospital for 8–9 weeks and were maintained on each of 3 different sublingual buprenorphine doses (2 mg, 8 mg, 24 mg). Under each maintenance dose, participants completed laboratory sessions during which the reinforcing and subjective effects of intravenous placebo, naloxone, heroin, and low and high doses of buprenorphine and buprenorphine/naloxone were examined. Every participant received each test dose under the 3 buprenorphine maintenance dose conditions. RESULTS Intravenous buprenorphine/naloxone was self-administered less frequently than buprenorphine or heroin (P < 0.0005). Participants were most likely to self-administer drug intravenously when maintained on the lowest sublingual buprenorphine dose. Subjective ratings of “drug liking” and “desire to take the drug again” were lower for buprenorphine/naloxone than for buprenorphine or heroin (P = 0.0001). Participants reported that they would pay significantly less money for buprenorphine/naloxone than for buprenorphine or heroin (P < 0.05). Seven adverse events were reported; most were mild and transient. CONCLUSIONS These data suggest that although the buprenorphine/naloxone combination has intravenous abuse potential, it is lower than for buprenorphine alone, particularly when participants received higher maintenance dosages and lower buprenorphine/naloxone challenge doses. Buprenorphine/naloxone may be a reasonable option for managing the risk for buprenorphine misuse during opioid dependence treatment.

Aim Few studies have examined abuse of prescription opioids (PO) among individuals with chronic pain under buprenorphine/naloxone (Bup/Nx) maintenance. The current 7-week inpatient study assessed oral oxycodone self-administration by patients with chronic pain who had a history of opioid abuse. Methods Participants (N=25) were transitioned from their pre-admission prescribed opioid to Bup/Nx. All of the participants were tested under each of the sublingual Bup/Nx maintenance doses (2/0.5, 8/2 or 16/4 mg) in random order. During each maintenance period, participants could self-administer oxycodone orally (0, 10, 20, 40 or 60 mg, PO) or receive money during laboratory sessions. Drug choice (percent) was the primary dependent variable. Subjective ratings of clinical pain and withdrawal symptoms also were measured. Mann-Whitney tests compared % drug choice for each active oxycodone dose to placebo. Logistic regression analyses identified correlates of oxycodone preference, defined as 60% or greater choice of oxycodone compared to money. Results Pain was significantly reduced while participants were maintained on Bup/Nx compared to pre-admission ratings. No differences in percent drug choice were observed between the active oxycodone doses and placebo under each Bup/Nx maintenance dose. However, factors associated with oxycodone preference were: lower Bup/Nx maintenance dose, more withdrawal symptoms and more pain. Conclusions These data suggest that Bup/Nx was effective in reducing pain and supplemental oxycodone use. Importantly, adequate management of pain and withdrawal symptoms by Bup/Nx may reduce oxycodone preference in this population.

Tobacco use is more prevalent and smoking cessation less likely among persons with attention deficit hyperactivity disorder (ADHD) than the general population. Evidence that tobacco use and nicotine hold divergent relationships with inattention (IN) and hyperactivity/impulsivity (HI), the core symptoms of ADHD, prompted this post hoc investigation of abstinence patterns by type of ADHD symptoms. Subjects were 583 adult smokers treated openly with bupropion and nicotine patch during the initial eight-week phase of a maintenance treatment study. Using the ADHD Current Symptom Scale, clinically significant ADHD symptom subtypes, i.e., predominantly inattention (ADHD-IN) and predominantly hyperactivity/impulsivity with or without inattention (ADHD-HI+/-IN), were identified. The study outcome was abstinence status, verified by expired carbon monoxide <8 parts per million, at five clinic visits from Week 1 through the end of treatment at Week 8. The distribution by ADHD symptom status was: No ADHD=540; ADHD-IN=20; ADHD-HI+/-IN=23. The study groups did not differ on demographic or smoking variables. The frequency of past major depression was highest with ADHD-IN and the frequency of past alcohol dependence was highest with ADHD-HI+/-IN. Compared to smokers with no ADHD, smokers of both ADHD subtypes combined showed lower abstinence rates throughout the study (OR=0.54, 95% CI: 0.32-0.99). Disaggregation by symptom subtype and separate comparisons against smokers with no ADHD showed that lower odds of quitting occurred mainly with ADHD-HI+/-IN (OR=0.40, 95% CI:=0.19-0.82), not with ADHD-IN (OR=0.74, 95% CI=p=0.36-1.51). Combined bupropion and nicotine patch treatment appears to be helpful for smokers with IN but not smokers with HI symptoms. The reasons for this divergent treatment response warrant further investigation.

Glial activation is hypothesized to contribute directly to opioid withdrawal. This study investigated the dose-dependent effects of a glial cell-modulator, ibudilast, on withdrawal symptoms in opioid-dependent volunteers after abrupt discontinuation of morphine administration. Methods Non-treatment seeking heroin-dependent volunteers (N = 31) completed the inpatient, double-blind, placebo-controlled, within-subject and between-group study. Volunteers were maintained on morphine (30 mg, QID) for 14 days and placebo (0 mg, QID) for the last 7 days of the 3-week study. Volunteers also received placebo (0 mg, PO, BID) capsules on Days 1–7. On days 8–21, volunteers were randomized to receive ibudilast (20 or 40 mg, PO, BID) or placebo capsules. Subjective and clinical ratings of withdrawal symptoms were completed daily using daily using the Subjective Opioid Withdrawal Scale (SOWS) and Clinical Opioid Withdrawal Scale (COWS). Medication side effects were also monitored. Results Relative to the first two weeks, all groups exhibited withdrawal during the third week as assessed by the SOWS and COWS (p ≤ 0.0001). Although overall SOWS scores did not differ between groups, exploratory analyses pooling the two ibudilast groups demonstrated that they had lower ratings of withdrawal symptoms on SOWS items (‘Anxious,’ ‘Perspiring,’ ‘Restless,’ ‘Stomach Cramps’) during detoxification relative to the placebo group. Ibudilast was well tolerated; no serious adverse events occurred during the study. Conclusion Pharmacological modulation of glial activity with ibudilast decreased some subjective ratings of opioid withdrawal symptoms. These exploratory findings are the first to demonstrate the potential clinical utility of glial modulators for treating opioid withdrawal in humans.

Despite the prevalent worldwide abuse of stimulants, such as amphetamines and cocaine, no medications are currently approved for treating this serious public health problem. Both preclinical and clinical studies suggest that the opioid antagonist naltrexone (NTX) is effective in reducing the abuse liability of amphetamine, raising the question of whether similar positive findings would be obtained for cocaine. The purpose of this study was to evaluate the ability of oral NTX to alter the cardiovascular and subjective effects of D-amphetamine (D-AMPH) and cocaine (COC). Non-treatment-seeking COC users (N=12) completed this 3-week inpatient, randomized, crossover study. Participants received 0, 12.5, or 50 mg oral NTX 60 min before active or placebo stimulant administration during 10 separate laboratory sessions. Oral AMPH (0, 10, and 20 mg; or all placebo) was administered in ascending order within a laboratory session using a 60-min interdose interval. Smoked COC (0, 12.5, 25, and 50 mg; or all placebo) was administered in ascending order within a laboratory session using a 14-min interdose interval. Active COC and AMPH produced dose-related increases in cardiovascular function that were of comparable magnitude. In contrast, COC, but not AMPH, produced dose-related increases in several subjective measures of positive drug effect (eg, high, liking, and willingness to pay for the drug). NTX did not alter the cardiovascular effects of AMPH or COC. NTX also did not alter positive subjective ratings after COC administration, but it did significantly reduce ratings of craving for COC and tobacco during COC sessions. These results show that (1) oral AMPH produces minimal abuse-related subjective responses in COC smokers, and (2) NTX reduces craving for COC and tobacco during COC sessions. Future studies should continue to evaluate NTX as a potential anti-craving medication for COC dependence.

Rates of pediatric obesity have increased dramatically over the past decade. This trend is particularly alarming as obesity is associated with significant medical and psychosocial consequences. Obesity may contribute to cardiovascular, metabolic, and hepatic complications, as well as psychiatric difficulties. The development of obesity appears to be influenced by a complex array of genetic, metabolic, and neural frameworks, as well as behavior, eating habits, and physical activity. Numerous parallels exist between obesity and addictive behaviors, including genetic predisposition, personality, environmental risk factors, and common neurobiological pathways in the brain. Typical treatments for pediatric obesity include behavioral interventions targeting diet and/or exercise. Treatments focusing on diet and exercise have yielded mixed results, and typically have been examined in specialty clinic populations, limiting their generalizability. There are limited medication options for overweight children and adolescents, and no approved medical intervention in children younger than 16. Bariatric surgery may be an option for some adolescents, but due to the risks of surgery it is often seen as a last resort. The parallels between addiction and obesity aid in the development of novel interventions for pediatric obesity. Motivational enhancement and cognitive-behavioral strategies used in addiction treatment may serve to be beneficial. KeywordsPediatric obesity; medical co-morbidity; addiction; treatment; review Pediatric obesity has reached epidemic proportions, with a 200-400% increase in the past 10 years [1][2][3] . Alarmingly, routine screening for obesity in children is very low (0.5% in a recent review of 600 pediatric cases), treatment is only provided to a fraction of children identified as overweight, and the most frequently used treatment (general advice) is known to be ineffective 4 . The current article will review some of the correlates of obesity, examine parallels with addictive behaviors, and review treatment recommendations.Due to concerns about stigma, the CDC recommends the term "overweight", rather than obese, when referring to youth 5 . Overweight is a condition where one has excess adipose tissue 6 . Body Mass Index (BMI) is the most accepted parameter for measuring total body fat. A BMI of > 85 th percentile indicates mild to moderate overweight, and a BMI > 95 th percentile indicates a need for intervention. Based on these criteria, more than 20% of US Medical and psychosocial consequences of overweight in children and adolescentsBeing overweight during childhood and adolescence is associated with a myriad of concurrent medical and psychosocial consequences, as well as placing children and teens at higher risk for medical comorbidity and mortality as adults. One of the most widely documented health consequences of overweight is a metabolic syndrome that includes insulin resistance, type 2 diabetes mellitus, polycystic ovary syndrome, dyslipidemia, and hypertension 13 . This syndrome has b...

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.

Background The extent of intranasal and intravenous prescription opioid abuse has led to the development of formulations that are difficult to crush. The purpose of the present studies was to examine whether experienced prescription opioid abusers (individuals who were using prescription opioids for non-medical purposes regardless of how they were obtained) were able to prepare a formulation of oxymorphone hydrochloride ER 40 mg designed to be crush-resistant (DCR) for intranasal (Study 1) or intravenous abuse (Study 2), utilizing a non-crush-resistant formulation of oxymorphone (40 mg; OXM) as a positive control. Methods No drug was administered in these studies. Participants were provided with DCR and OXM tablets in random order and asked to prepare them for abuse with tools/solutions that they had previously requested. The primary outcome for Study 1 was particle size distribution, and the primary outcome for Study 2 was percent yield of active drug in the extracts. Other descriptive variables were examined to better understand potential responses to these formulations. Results Fewer DCR than OXM particles were smaller than 1.705 mm (9.8% vs. 97.7%), and thus appropriate for analyses. Percent yield of active drug in extract was low and did not differ between the two formulations (DCR: 1.95%; OXM: 1.29%). Most participants were not willing to snort (92%) or inject (84%) the tampered products. Participants indicated that they found less relative value in the DCR than the OXM formulation across both studies. Conclusions Although there are safety issues associated with formulations that gel, these data suggest that the oxymorphone DCR formulations may be a promising technology for reducing opioid abuse.