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.