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Objective: Prescription stimulant non-medical use (NMU) is a national predicament. While the risks of prescription stimulant NMU have been considered, less is known about non-oral use. To focus on this gap, a sample of adults with non-oral prescription stimulant NMU within the last 5-years was recruited. The purpose of the present study was to characterize the pathways and substance transitions associated with prescription stimulant NMU and non-oral prescription stimulant NMU in this unique sample of adults.Methods: Adults (n = 225) reporting non-oral prescription stimulant NMU within the last 5 years were recruited to complete an online survey by banner ads placed on the Reddit website between February and September 2019. After completion of the survey, a second study consisting of an in-depth telephone interview was conducted with 23 participants: interviews took place between July and September 2019. Data reported here include substance, route of administration and class transitions, as well as qualitative data from the interviews.Results: Approximately 1 in 5 began their substance use trajectory with prescription stimulants (19.1%). Other than marijuana, most exposures to illicit substances occurred after both initial prescription stimulant NMU and initial non-oral prescription stimulant NMU. The most frequently reported route of administration transition was from oral use to snorting (n = 158, 70.2%), however, other route of administration transitions included oral use to injection drug use (n = 14, 6%). In-depth interviews elaborated upon these transitions and indicated that prescription stimulant NMU was consequential to substance use pathways.Conclusions: Oral prescription stimulant NMU was a precursor to non-oral prescription stimulant NMU. Non-oral prescription stimulant NMU was a precursor to illicit substance use, suggesting that prescription stimulant NMU impacts substance use pathways and revealing opportunities for intervention.

Tapentadol, a Schedule II opioid with a combination of µ-opioid activity and norepinephrine reuptake inhibition, is used for the management of moderate to severe acute and chronic pain. Its dual mechanism of action is thought to reduce opioid-related side effects that can complicate pain management. Since approval, tapentadol has been tracked across multiple outcomes suggesting abuse liability, and a pattern of relatively low, although not absent, abuse liability has been found. This retrospective cohort study further details the abuse liability of tapentadol as an active pharmaceutical ingredient (API) when immediate-release as well as extended-release formulations were on the market together (fourth quarter of 2011 to second quarter of 2016). Tapentadol (API) was compared with tramadol, hydrocodone, morphine, oxycodone, hydromorphone, and oxymorphone across Poison Center, Drug Diversion, and Treatment Center Programs Combined data streams from the Researched Abuse, Diversion and Addiction-Related Surveillance system. Findings suggest the public health burden related to tapentadol to date is low, but present. Event rates of abuse per population-level denominators were significantly lower than all other opioids examined. However, when adjusted for drug availability, event rates of abuse were lower than most Schedule II opioids studied, but were not the lowest. Disentangling these 2 sets of findings further by examining various opioid formulations, such as extended-release and the role of abuse-deterrent formulations, is warranted. Perspective This article presents the results from an examination of tapentadol API across the Researched Abuse, Diversion and Addiction-Related Surveillance System: a broad and carefully designed postmarketing mosaic. Data to date from Poison Center, Drug Diversion, and Treatment Centers combined suggest a low, but present public health burden related to tapentadol.

Background and objectives Opioid use disorder (OUD) is a chronic condition with potentially severe health and social consequences. Many who develop moderate to severe OUD will repeatedly seek treatment or interact with medical care via emergency department visits or hospitalizations. Thus, there is an urgent need to develop feasible and effective approaches to help persons with OUD achieve and maintain abstinence from opioids. Treatment that includes one of the three FDA-approved medications is an evidence-based strategy to manage OUD. The purpose of this review is to address practices for managing persons with moderate to severe OUD with a focus on opioid withdrawal and naltrexone-based relapse-prevention treatment. Methods Literature available on PubMed was used to review the evolution of treatment strategies from the 1960s onward to manage opioid withdrawal and initiate treatment with naltrexone. Results Emerging practices for extended-release naltrexone induction include the use of agonist tapers and adjuvant medications. Clinical challenges frequently encountered when initiating this therapy include managing withdrawal and ongoing opioid use during treatment. Clinical factors may inform decisions regarding patient selection and length of naltrexone treatment, such as recent opioid use and patient preferences. Conclusions and scientific significance Treatment strategies to manage opioid withdrawal have evolved, but many patients with OUD do not receive medication for the prevention of relapse. Clinical strategies for induction onto extended-release naltrexone are now available and can be safely and effectively implemented in specialty and select primary care settings. (© 2018 The Authors. The American Journal on Addictions Published by Wiley Periodicals, Inc. on behalf of The American Academy of Addiction Psychiatry (AAAP);27:177-187).

Highlights • Adults reporting past 5-year non-oral prescription stimulant NMU were studied. • Non-oral NMU preferences were snorting (59%) injecting (4%) or smoking (1%). • Polysubstance use was reported by 79.1% of the sample. • Route of administration and motivation for prescription stimulant NMU were related. • Prescription stimulant oral and intranasal NMU was to enhance performance. • Prescription stimulant intravenous and smoking NMU was to get high., Objective Increased prescription stimulant nonmedical use (NMU) is part of a growing polysubstance use landscape. The purpose of the present study was to characterize prescription stimulant NMU among adults reporting past 5-year non-oral prescription stimulant NMU. Methods Adults who reported non-oral prescription stimulant NMU within the last 5 years were recruited by banner ads placed on the Reddit website between February and September 2019. Types of prescription stimulants used, routes of administration, preferred routes of administration, motivations for prescription stimulant NMU, concurrent substances used simultaneously during prescription stimulant NMU, illicit substances used and factors impacting prescription stimulant NMU were queried. Results Respondents (n = 225) were male (86.2%), non-Hispanic (92.4%), white (78.2%), between 18 and 24 (48.0%) or 25–34 (43.1%) years with some amount of college education (81.3%). Most reported lifetime intranasal (93.8%) or oral use (85.2%). Prescription stimulants were diverted: 64.5% reported the prescription stimulants were given to them by a family or a friend and 10.5% reported that they had stolen these medications from a family or friend. Preferred route of administration was oral use (70.2%). Motivations to use were stratified by route of administration: intranasal (55.6%) or oral (63.0%) use was primarily endorsed as an attempt to enhance performance at work or at school; use by injection (57.1%) or smoking (62.5%) was primarily endorsed to get high. Most of the sample reported concurrent drug use (79.1%) including tobacco (57.3%), marijuana (52.0%), caffeine (47.6%) or alcohol (41.8%), among others. When excluding licit substances, 30.7% reported using 1 illicit substance concurrently with prescription stimulants and 25.3% reported using 2 or more illicit substances concurrently with prescription stimulants. Whether participants would undertake prescription stimulant NMU was determined by their work/school schedules or the location of the NMU (48.9%) whereas the route of administration employed was primarily influenced by the desired feeling or effect (56.9%). Conclusions Adults reporting lifetime non-oral prescription stimulant NMU engage in substantial risky behaviors that in addition to alternate routes of administration include polysubstance use, diversion and concurrent substance use.

NMU of prescription stimulant medications (RxStim) intended for treatment of attention deficit/hyperactivity disorder (ADHD) is a growing public health concern, particularly when used via non-oral routes of administration. However, the role of non-oral routes of administration for RxStim NMU in the larger substance abuse pathway is less well studied. The purpose of this study was to characterize RxStim NMU and investigate substance use trajectories among adults who reported non-oral RxStim NMU recruited from Reddit.Eligible participants must have been located in the US, English speaking, age 18 y, and have reported RxStim NMU via a non-oral route (any route other than ingestion) within the past 5 y. Participants were recruited from Feb-Sep 2019 using banner ads on Reddit, the 5th most visited website in the US. Participants completed an online survey which captured demographics, lifetime RxStim NMU and illicit substance use; they were compensated for their time. For purposes of this study, NMU included ANY of the following: (1) use for any reason, even once, without their own prescription, (2) use in ways other than prescribed, and (3) use for the feeling or experience the medication caused.Respondents (n=225) were primarily male (86.2%), 18–24 (48.0%) or 25–34 (43.1%) years of age, and Caucasian (78.2%), Black (7.1%) or Hispanic (5.3%). Lifetime diagnosis of ADHD was reported by 27.6%, with 53.2% diagnosed at age 11–19 and 35.5% at age 20+ years. RxStim NMU via snorting was reported by 99.1%, smoking 3.6% and injecting 6.2% (multiple routes could be reported). Almost all (n=222; 98.7%) also reported lifetime illicit drug use, among whom 182 (82.0%) initiated substance use by using an illicit drug (77.9% marijuana, 1.8% cocaine/crack, 0.9% inhalants, 0.9% hallucinogens, 0.5% methamphetamine/amphetamines) prior to RxStim NMU. Forty (18.0%) respondents initiated with RxStim NMU; 14.4% then initiated marijuana use, 0.9% initiated cocaine/crack use, 0.9% initiated barbiturate use, and 0.5% initiated heroin, inhalant, methamphetamine/amphetamine, and hallucinogen use. Average age of initial RxStim NMU was 18.7 (SD 3.7) years and most often was via swallowing (89.1%) followed by snorting (10.9%). Respondents began using marijuana at age 15.9 (SD 2.5), cocaine or crack at 19.7 (SD 3.3), and heroin at 20.9 (SD 5.5).Engagement in RxStim NMU via a non-oral route of administration is most often preceded by marijuana use. Among this Reddit-recruited population of non-oral RxStim nonmedical users, only 1 in 4 reported an ADHD diagnosis and Funding. Arbor Pharmaceuticals, LLC

Objective: Studies have suggested that the N-methyl-D-aspartate antagonist dextromethorphan may be useful in the treatment of opioid dependence.Design: This double-blinded, placebo-controlled inpatient study evaluated the effects of 0, 30, and 60 mg of dextromethorphan and quinidine (DMQ) on the reinforcing and subjective effects of heroin in recently detoxified heroin abusers.Participants: Nine heroin-dependent participants were admitted and then detoxified from heroin over the course of several days.Interventions: Participants were subsequently stabilized on 0, 30, or 60 mg of DMQ. Each dose of DMQ was administered for two consecutive weeks, and the effects of heroin (0, 12.5, and 50 mg) were studied under each DMQ maintenance dose condition. DMQ and heroin dose were administered in random order both within and between participants.Results: Planned comparisons revealed statistically significant increases in progressive ratio breakpoint values and positive subjective ratings as a function of heroin dose. There were no consistent changes in any of the responses as a function of DMQ maintenance dose, other than a modest reduction in craving.Conclusions: In summary, results from this study suggest that maintenance on dextromethorphan in combination with quinidine has a limited role in the treatment of opioid dependence.

This qualitative study summarizes information that individuals shared online about use of OxyContin following the August 2010 introduction of the abuse deterrent formulation (ADF). Purpose The primary objective was to study online posts that endorsed continued use of OxyContin or a switch from OxyContin to another formulation of oxycodone or another substance altogether following the introduction of the ADF. A secondary objective was to determine whether posts revealed that the ADF led to cessation of OxyContin use. Methods Data were collected with the Researched Abuse, Diversion, and Addiction-Related Surveillance System Web Monitoring Program, an online surveillance system that collects and organizes posts about prescription drugs from social media websites, blogs, and forums from 3Q2009 to 4Q2014 using a commercially available web platform. Results Posts were categorized by whether they conveyed a switch to drugs other than reformulated OxyContin or a continuation of reformulated OxyContin abuse. “Switch posts” primarily discussed switching to immediate-release opioids. “Continue abusing” posts identified tampering strategies for alternate routes of administration, oral use, and continued use although post authors were generally unhappy with the experience. No reference to OxyContin cessation as a function of the introduction of the ADF was found; however, discontinued use was discussed. Conclusions Web Monitoring data are useful for capturing cross sections of Internet conversation reflecting reactions to new drug formulations. These data support the notion that users will gravitate to non-ADFs generally, and to immediate-release non-ADF opioid formulations, specifically, as long as these options remain on the market.

The progression from prescription opioid (RXO) abuse to RXO addiction is not well understood in adolescents, nor is the progression from RXO addiction to heroin abuse. The purpose of this pilot study was to characterize the development of RXO drug abuse, RXO drug addiction, and heroin abuse in a small cohort of adolescents recovering from opioid addiction at Massachusetts Recovery High Schools (RHS). A self-report questionnaire was administered to 31 adolescent, former RXO abusers across two Massachusetts RHS. RXO abuse was primarily initiated due to curiosity; RXOs were initially obtained through illicit and licit methods. Fifty-eight percent (N = 18) of the RXO abusers became addicted to RXOs. Many addicted adolescents initiated RXO abuse under the influence of marijuana, yet believed that they became addicted due to the stress from difficult life situations. A subgroup indicated they abused and became addicted to RXOs that had been obtained from legitimate prescriptions due to their pain. Sixte...

Background The characteristics of patients with co-occurring chronic pain and prescription opioid abuse have not been well described, and even less is known about differences between men and women in this population. Objectives This study evaluated sex differences in the demographic, diagnostic, and behavioral attributes of patients with chronic pain and opioid abuse. Methods Data were collected via self-report and semistructured clinical interviews from 162 patients (120 men and 42 women) who screened for a study investigating the abuse liability of prescription opioids. Results There were no differences between men and women in age, race, education, marital status, or employment status. Participants had used prescription opioids for 5.4 ± 6.7 years. The majority of participants (60%) had low back pain in addition to opioid dependence as defined by the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition. More women reported more arthritic pain than men, but otherwise there were no differences in types of pain. Pain exerted a greater effect in women on mood, walking ability, and social relations. Men reported more of certain aberrant behaviors, including abuse of alcohol or illicit drugs, unauthorized dose increases, contact with street culture, and being arrested by police. Women were more depressed than men. Conclusions The demographic profile of opioid-abusing patients with chronic pain presenting for treatment in a clinical trial was similar between sexes; however, some important differences were observed. Women reported more psychiatric comorbidity and endorsed greater pain-related physical and social impairment. Men reported more aberrant behaviors. These differences suggest that men with chronic pain and opioid abuse/dependence may benefit by closer monitoring of aberrant behaviors whereas women may benefit from closer attention paid to physical and psychological effects of pain.

This double-blind, placebo-controlled study investigated the effects of oral morphine (0, 45, 135 mg/70 kg) and oral oxycodone (0, 15, 45 mg/70 kg) on buprenorphine-maintained opioid addicts. As a 3: 1 morphine : oxycodone oral dose ratio yielded equivalent subjective and physiological effects in nondependent individuals, this ratio was used in the present study. Two self-administration laboratory procedures - that is, a drug versus money and a drug versus drug procedure - were assessed. Study participants (N=12) lived in the hospital and were maintained on 4 mg/day sublingual buprenorphine. When participants chose between drug and money, money was preferred over all drug doses; only high-dose oxycodone was self-administered more than placebo. When participants chose between drug and drug, both drugs were chosen more than placebo, high doses of each drug were chosen over low doses, and high-dose oxycodone was preferred over high-dose morphine. The subjective, performance-impairing, and miotic effects of high-dose oxycodone were generally greater than those of high-dose morphine. The study demonstrated that a 3: 1 oral dose ratio of morphine : oxycodone was not equipotent in buprenorphine-dependent individuals. Both self-administration procedures were effective for assessing the relative reinforcing effects of drugs; preference for one procedure should be driven by the specific research question of interest.

International audience; Few studies have examined abuse of prescription opioids 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. Participants (n=25) were transitioned from their preadmission 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 prescription opioids) or receive money during laboratory sessions. Drug choice (percentage) was the primary dependent variable. Subjective ratings of clinical pain and withdrawal symptoms also were measured. Mann-Whitney tests compared percentage of 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. Pain was significantly reduced while participants were maintained on Bup/Nx compared to preadmission ratings. No differences in percentage 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. 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.

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.

Aims To examine whether tamper-resistant formulations (TRFs) of tapentadol hydrochloride extended-release (ER) 50 mg (TAP50) and tapentadol hydrochloride 250 mg (TAP250) could be converted into forms amenable to intranasal (study 1) or intravenous abuse (study 2). Design Randomized, repeated-measures study designs were employed. A non-TRF of OxyContin® 40 mg (OXY40) served as a positive control. No drug was taken in either study. Setting The studies took place in an out-patient setting in New York, NY. Participants Twenty-five experienced, healthy ER oxycodone abusers participated in each study. Measurements The primary outcome for study 1 was the percentage of participants who indicated that they would snort the tampered tablets, while the primary outcome for study 2 was the percentage yield of active drug in solution. Other descriptive variables, such as time spent manipulating the tablets, were also examined to characterize tampering behaviors more clearly. Findings Tampered TRF tablets were less desirable than the tampered OXY40 tablets. Few individuals were willing to snort the TRF particles (TAP50: 24%, TAP250: 16%; OXY40: 100% P < 0.001). There was less drug extracted from the TAP50 tablet than from the OXY40 tablet (3.52 versus 37.02%,P = 0.008), and no samples from the TAP250 tablets contained analyzable solutions of the drug. It took participants longer to tamper with the TAPs (study 1: TAP50 versus OXY40, P < 0.01; TAP250 versus OXY40, P < 0.01; study 2: TAP250 versus OXY40, P < 0.05). Conclusions Tamper-resistant formulations of tapten- tadol (pain relief) tablets do not appear to be well-liked by individuals who tamper regularly with extended-release oxycodone tablets. Employing tamper-resistant technology may be a promising approach towards reducing the abuse potential of tapentadol extended-release.

Background Few marijuana smokers in treatment achieve sustained abstinence, yet factors contributing to high relapse rates are unknown. Methods Study 1: data from five inpatient laboratory studies assessing marijuana intoxication, withdrawal, and relapse were combined to assess factors predicting the likelihood and severity of relapse. Daily, nontreatment-seeking marijuana smokers ( n = 51; 10 ± 5 marijuana cigarettes/day) were enrolled. Study 2: to isolate the effects of cigarette smoking, marijuana intoxication, withdrawal, and relapse were assessed in daily marijuana and cigarette smokers ( n = 15) under two within-subject, counter-balanced conditions: while smoking tobacco cigarettes as usual (SAU), and after at least 5 days without cigarettes (Quit). Results Study 1: 49% of participants relapsed the first day active marijuana became available. Tobacco cigarette smokers (75%), who were not abstaining from cigarettes, were far more likely to relapse than non-cigarette smokers (odds ratio: 19, p .01). Individuals experiencing more positive subjective effects (i.e., feeling "high") after marijuana administration and those with more negative affect and sleep disruption during marijuana withdrawal were more likely to have severe relapse episodes ( p 87%) relapsed to marijuana whether in the SAU or Quit phase. Tobacco cigarette smoking did not significantly influence relapse, nor did it affect marijuana intoxication or most symptoms of withdrawal relative to tobacco cessation. Conclusions Daily marijuana smokers who also smoke cigarettes have high rates of marijuana relapse, and cigarette smoking versus recent abstinence does not directly influence this association. These data indicate that current cigarette smoking is a clinically important marker for increased risk of marijuana relapse.

Background The extent of 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 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 These data suggest that the oxymorphone DCR formulations may be a promising technology for reducing opioid abuse.

Aims Research on drug dependence often involves the administration of drugs of abuse to experienced drug users under controlled laboratory conditions. The primary objective of this study was to assess whether participation in such research alters the frequency of heroin use by non-treatment-seeking opioid-dependent volunteers after study completion. Design Data were examined from four in-patient studies involving controlled opioid administration. Setting Substance Use Research Center at Columbia University, New York State Psychiatric Institute. Participants Sixty-nine heroin-dependent volunteers. Measurements Participants' self-reported heroin use prior to and 1 month after study participation was compared using a Wilcoxon test. Because a number of participants reported that they had stopped using heroin, a logistic regression was used to identify correlates of heroin cessation 1 month after study completion. Findings One hundred and one participants entered laboratory studies and 69 completed them. Self-reported heroin use significantly decreased 1 month after study participation [1.7 (±2.0) bags per day] compared to baseline [6.8 (±4.2) bags per day], P

Buprenorphine induction poses a barrier for physician adoption of office-based opioid dependence treatment. We conducted a retrospective chart review of the first 41 patients inducted at a newly established outpatient treatment program to examine the induction process and determine strategies associated with greater induction efficiency. Timed withdrawal scales, medication log, and notes enabled reconstruction of the initial day of buprenorphine treatment. To assess change with experience, consecutive patients were divided into three chronological groups for analyses (Phases 1–3). The time required for induction was substantial in Phase 1 (mean 5.5 hours), but temporal efficiency improved to a mean 1.5 hours spent at the program by Phase 3 (p

This pilot study sought to characterize typical nonmedical oxycodone use in the New York Metropolitan area. Accordingly, a clinical interview was administered to 25 intranasal (IN) and 25 intravenous (IV) oxycodone abusers to capture demographics and patterns of use within the region. IN and IV abusers shared a number of similar characteristics including age, proportion of men and women, criminal history, drug use history, and current recreational drug use. However, the two populations also differed in a number of aspects. IV oxycodone users had lower rates of employment, earlier onset of illicit drug use, and more current heroin use. Although IN users reported somewhat more frequent use of oxycodone weekly, IV users were more likely to supplement their oxycodone use with other opioid drugs, most notably heroin. Additional research is needed to confirm these observed differences, yet these data may assist treatment efforts by providing information to guide targeted treatment and population-specific interventions. (Am J Addict 2011; 00:1–6)

Some sources suggest that significant misuse of opioid drugs exists among patients with chronic pain. However, the risk factors and motivation behind their abuse may differ from those of other opioid abusers. This study sought to examine the abuse liability of oxycodone among patients with chronic, non-malignant pain who met the DSM-IV criteria for opioid abuse. Eighteen opioid-dependent patients with chronic pain lived on an in-patient unit of the New York State Psychiatric Institute during the 7-week study. Participants were given oral oxycodone (0, 10, 20, 40, and 60 mg/70 kg) while maintained on various doses of sublingual buprenorphine/naloxone (Bup/Nx; 2/0.5, 8/2, and 16/4 mg/day). Doses of both medications were administered under double-blind conditions. Oxycodone produced an overall positive, but less robust, subjective profile than previously reported in recreational opioid users without pain. Furthermore, unlike our findings in recreational opioid users and more similar to effects in non-drug-abusing individuals, oxycodone failed to serve as a reinforcer. As for the maintenance drug, Bup/Nx produced a dose-related reduction in some of the effects of acutely administered oxycodone. These data suggest that sublingual Bup/Nx has the potential as an analgesic medication and further research should investigate its use in treating patients with chronic pain who abuse opioids.

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).

Sex differences in the analgesic effects of mu-opioid agonists have been documented extensively in rodents and, to a lesser extent, in non-human primates. To date, there have been few experimental studies investigating this effect in humans, and the conclusions have been equivocal. The aims of the present study were to examine potential sex differences in the analgesic, subjective, performance, and physiological effects of morphine in human research volunteers. Using a double-blind outpatient procedure, the present study investigated the effects of intramuscular morphine (0, 5, and 10 mg/70 kg, i.m.) in men (N = 8) and women (N = 10). The primary dependent measure was analgesia, as assessed by the cold pressor and mechanical pressure tests. Secondary dependent measures included subjective, performance, and physiological effects of morphine, as well as plasma levels of morphine. No differences in the analgesic and performance effects of morphine were observed between men and women, but significant differences in morphine’s subjective effects were found. Specifically, men reported greater positive effects, whereas women reported greater negative effects after morphine administration. These data suggest that, in humans, there are sex differences in the subjective mood-altering effects of morphine but, based on this limited sample, there is little evidence for sex differences in its analgesic effects.

OBJECTIVES Many adolescents and young adults report having chronic pain. Urine drug toxicology (UDT) is not routinely used in the pediatric pain management population, despite more routine use in adults with pain, particularly those prescribed opioids. As a first step toward establishing monitoring practices in pediatric and adolescent pain management, the present study evaluated the role of UDT in conjunction with a standard clinical interview in identifying the rate of adherence to an established analgesic regimen. The study also aimed to assess the use of UDT in identifying possible aberrant behaviors in this population. METHODS Data were acquired from a convenience sample of 50 pediatric and adolescent pain management initial consultations, during which a clinical interview and UDT were conducted. Data were analyzed to determine adherence to an established analgesic prescription regimen, and for identification of aberrant behaviors including concurrent use of illicit substances and prescription medication misuse. Other pertinent demographic and clinical factors were examined as factors in adherence. RESULTS Opioid medications were prescribed for 42% of the sample receiving pain medications, and 22% of the sample was nonadherent to their prescription analgesic regimen. Factors associated with a higher likelihood of nonadherence were an older age and having an opioid prescription. The majority (90%) of those nonadherent to their analgesic regimen displayed some form of aberrant behavior. Among the nonadherent patients, 50% were identified by UDT alone, and 50% were identified by self-report during the clinical encounter. CONCLUSIONS These results highlight the challenges of identifying nonadherence to a prescription regimen among adolescents with chronic pain. In addition, this preliminary work suggests that UDT could be used in conjunction with careful clinical interviewing to substantiate patient report and increase the likelihood of detecting analgesic nonadherence and aberrant behaviors.

Objectives Individuals with HIV constitute the largest group using cannabinoids for medicinal reasons; yet, no studies have directly compared the tolerability and efficacy of smoked marijuana and oral dronabinol maintenance in HIV-positive marijuana smokers. This placebo-controlled within-subjects study evaluated marijuana and dronabinol across a range of behaviors: eating topography, mood, cognitive performance, physiologic measures, and sleep. Methods HIV-positive marijuana smokers (n = 10) completed 2 16-day inpatient phases. Each dronabinol (5 and 10 mg) and marijuana (2.0% and 3.9% Delta9-tetrahydrocannabinol [THC]) dose was administered 4 times daily for 4 days, but only 1 drug was active per day, thereby maintaining double-blind dosing. Four days of placebo washout separated each active cannabinoid condition. Results As compared with placebo, marijuana and dronabinol dose dependently increased daily caloric intake and body weight in HIV-positive marijuana smokers. All cannabinoid conditions produced significant intoxication, except for low-dose dronabinol (5 mg); the intoxication was rated positively (eg, "good drug effect") with little evidence of discomfort and no impairment of cognitive performance. Effects of marijuana and dronabinol were comparable, except that only marijuana (3.9% THC) improved ratings of sleep. Conclusions These data suggest that for HIV-positive marijuana smokers, both dronabinol (at doses 8 times current recommendations) and marijuana were well tolerated and produced substantial and comparable increases in food intake.

Previously, we reported that gabapentin, a nonselective gamma-aminobutyric acid agonist, reduced 'positive' subjective effects of cocaine without reducing cocaine self-administration. We speculated that the self-administration procedure used in that study was not sensitive to subtle shifts in the reinforcing effects of cocaine. Thus, this study examined the effects of gabapentin maintenance on cocaine self-administration using a purchase-cocaine choice procedure. During this 48-day inpatient/outpatient study, nontreatment-seeking cocaine abusers (n = 12) were maintained on gabapentin (0, 600, 1200 mg/day); four doses of cocaine (0, 12, 25, 50 mg) were each tested twice under each gabapentin condition. All cocaine testing was conducted while participants were inpatients. Before the start of each session, participants were provided with 25 dollars (five 5 dollar bills, one for each choice opportunity) and smoked the 'sample' cocaine dose once. Subsequently, participants were given five opportunities to purchase the sampled dose of cocaine (at 5 dollars per dose) or to keep 5 dollars for that choice trial. Choice to self-administer cocaine increased significantly with escalating cocaine doses; gabapentin maintenance did not alter choice to self-administer cocaine. These results concur with findings from our previous investigations of gabapentin and with those from a clinical trial examining the effects of larger gabapentin doses on cocaine use by treatment-seeking cocaine-dependent individuals. Together, the data indicate that gabapentin does not show promise as a treatment medication for cocaine dependence.

The aim of this study was to test the hypothesis that desipramine would be an effective treatment in cocaine abusers with current depressive disorders.This was a randomized, 12-week, double-blind, 'placebo-controlled trial of outpatients (N = 111) meeting DSM-III-R criteria for cocaine dependence and major depression or dysthymia (by SCID interview). Participants were treated with desipramine, up to 300 mg per day, or matching placebo. All patients received weekly individual manual-guided relapse prevention therapy. Weekly outcome measures included the Clinical Global Impression Scale, self-reported cocaine use and craving, urine toxicology, and the Hamilton Depression Scale (biweekly). Summary measures of mood and cocaine use outcome were compared between treatment groups with chi2- or t-tests. Dichotomous summary measures of depression response and cocaine response were the primary outcomes. Mixed effect models were also fit to explore the relationship of cocaine use to mood improvement and treatment over weeks in the trial.Desipramine was associated with a higher rate of depression response (51%, 28/55) than placebo (32%, 18/56) (p0.05), but treatment groups did not differ in rate of cocaine response. Depression improvement was associated with improvement in cocaine use. Desipramine was associated with more dropouts due to side effects and medical adverse events, while placebo was associated with more dropouts due to psychiatric worsening.Desipramine was an effective treatment for depression among cocaine-dependent patients. Improvement in mood was associated with improvement in cocaine abuse, but a direct effect of medication on cocaine outcome was not clearly established and rates of sustained abstinence were low. Future research should examine newer antidepressant medications with more benign side effect profiles and combinations of behavioral and pharmacological treatments to maximize effects on cocaine use.

Oral Delta-9-tetrahydrocannabinol (Delta(9)-THC; Marinol) is medically available for the treatment of nausea associated with cancer chemotherapy and for wasting syndromes related to HIV/AIDS. Little is known about its reinforcing effects.This study was conducted to characterize the reinforcing effects of oral Delta(9)-THC in experienced marijuana smokers under controlled laboratory conditions.Ten healthy male marijuana users completed this 17-day residential study. On days 2, 6, 10, and 14, at 0900 h, participants received a "sample" oral dose of Delta(9)-THC (0, 10, 20 mg) and an alternative reinforcer, a 2 US dollars voucher (redeemable for cash at study's end). Over the next 3 days, they had 11 opportunities to self-administer either the sampled dose of Delta(9)-THC or to receive a 2 US dollars voucher.Participants chose active Delta(9)-THC (10 and 20 mg) more often than placebo (two selections vs approximately four selections, respectively). However, they chose active Delta(9)-THC on less than 50% of choice opportunities. Both active Delta(9)-THC doses produced significant increases in "positive" subjective effects, impaired psychomotor performance, and increased heart rate, relative to the placebo conditions.These data indicate that oral Delta(9)-THC may have modest abuse liability in experienced marijuana smokers.

We examined whether drug use behaviors during a 2-week lead-in for a pharmacotherapy trial were predictive of retention in treatment and of the level of cocaine use during the subsequent 12 weeks of treatment. Fifty cocaine dependent patients were grouped based on: (1) principal route of cocaine administration: intranasal versus smoking, and (2) level of cocaine use during the 2-week lead-in: high versus low. Results indicate that level of cocaine use during the 2-week lead-in was a significant predictor of cocaine use during the subsequent 12 weeks of treatment. Patients with reported higher level of use during the lead-in period were more likely to continue using cocaine during the treatment. Patients who used smoking as their primary route of cocaine use were more likely to drop out early in the treatment. Findings of this study suggest that route and level of cocaine use during lead-in be used as a covariate in models testing treatment effect.

There is a noticeable lack of targeted treatment options for marijuana dependence, in particular pharmacologic approaches. This is the first study evaluating a targeted pharmacologic approach for marijuana dependence. The goals of the study were to determine if such patients would seek pharmacologic treatment, whether these patients could be retained in treatment using a design previously developed for cocaine-dependent patients, and especially whether divalproex sodium showed promise as a treatment agent for marijuana dependence. We found that marijuana-dependent patients will seek treatment, and such patients can be adequately maintained in a pharmacologic trial. Regardless of treatment group, patients reported a significant reduction in their frequency and amount of marijuana use as well as a reduction in irritability. Given the lack of proven effective treatments for marijuana dependence, pharmacotherapies should be sought. The design of a preliminary clinical trial should include a psychosocial/behavioral intervention emphasizing motivation and medication compliance and a placebo control group.

This chapter reviews the conduct of the human abuse potential study from the regulatory perspective, as outlined in the Food and Drug Administration (FDA)'s 2010 Guidance for Industry: Assessment of Abuse Potential of Drugs. Using the guidance as an outline, the chapter describes how human abuse potential studies are conceived and conducted, how they are analyzed, how Adverse Events (AEs) are considered, and how abuse liability may continue to be monitored after drug approval. Human abuse potential trials by themselves are not sufficient to bring about drug scheduling; however, they are a critical piece of the abuse liability assessment submitted to the FDA as part of a New Drug Application (NDA). Thus, this chapter summarizes a critical piece of the regulatory package.

Tolerance to the analgesic effects of opioids has been demonstrated in laboratory animals after repeated drug administration; yet, this effect has been studied less frequently under controlled laboratory conditions in humans. This within-subject, double-blind, placebo-controlled study was designed to determine whether tolerance developed to the analgesic, subjective, and physiological effects of the commonly prescribed opioid oxycodone when it was administered daily for 5 days. The effects of oxycodone (0, 5, and 20 mg/70 kg, orally) were compared, using a within-session cumulative dosing procedure, on the first and fifth days of the 'daily' dosing phase to assess for tolerance; active oxycodone was administered on the second and fourth days of the daily dosing phase. Changes in the effects of oxycodone were also compared when the medication was only administered on the first and the fifth day of a 5-day 'intermittent' dosing phase; placebo medication was administered on the second and fourth days of the intermittent dosing phase. A 9-day 'washout' period occurred between phases during which no medication was administered. Healthy volunteers (N=10) with no history of drug dependence or current drug use participated in this outpatient study. Analgesia was assessed using the cold pressor test, pain and drug effects were measured using a variety of questionnaires, and pupil diameter was monitored as an index of physiological effects. When administered daily, no differences were observed in oxycodone-induced analgesia between the first and the fifth days, but tolerance did develop to some of the positive subjective effects of oxycodone. In contrast, oxycodone-induced analgesia and participant ratings of some positive subjective drug effects were greater on the fifth compared with the first day of the intermittent dosing phase. No differences in the miotic effects of oxycodone between the first and the fifth days of either dosing phase were detected. Although obtained under limited experimental conditions, these findings suggest that tolerance may not develop to the analgesic effects of therapeutic doses of oxycodone under short-term daily dosing conditions, even though some of its subjective effects may decrease. These data also suggest that intermittent administration may enhance the analgesic effects of oxycodone, while also increasing some of the drug's positive subjective effects related to abuse liability.

Background: μ-Opiate receptor agonism has been associated with weight gain, whereas μ-antagonists have been associated with weight neutrality, or even weight loss.Aim: This study examined the course of weight changes in opiate-dependent patients over the first 6 months of treatment in methadone (agonist) versus naltrexone (antagonist) maintenance.Design: A retrospective chart review was conducted on 36 opiate-dependent patients maintained on methadone (n = 16) or naltrexone (n = 20). Outcome measures and analyses: The primary outcome measure was change in body weight from baseline to 3 months and 6 months into treatment. Analysis of variance was used to compare mean weights between the methadone- and naltrexone-maintained patients. Secondarily, mean percent weight changes from baseline to 3 months and from baseline to 6 months into treatment were compared using Student’s t-test.Results: There was no difference between weight at baseline, 3 months, or 6 months into treatment between the two treatment groups. Furthermore, there was also no difference between the two groups regarding percent weight change from baseline to 3 months or baseline to 6 months. At 3 months, n = 16 methadone patients had a mean weight increase of 1.86 percent (standard deviation [SD] = 7.22 percent) when compared with n = 20 Behavioral Naltrexone Therapy (BNT) patients with an increase of 4.63 percent (SD = 6.49 percent). At 6 months, n = 16 methadone patients had a mean weight increase relative to baseline of 3.67 percent (SD = 9.52 percent) when compared with n = 20 BNT patients, who demonstrated a mean increase of 6.69 percent (SD = 7.56 percent). No association was found between baseline weight, defined as “low” or “high” relative to group medians, and percent gain within and between treatment groups.Conclusions: This study did not detect a statistically different course of weight gain between methadone and naltrexone maintenance treatment for opiate-dependent patients.

Dronabinol (Δ9tetrahydrocannabinol) is approved for HIV-related anorexia, yet, little is known about its effects in HIV-positive marijuana smokers. HIV-negative marijuana smokers require higher than recommended dronabinol doses to experience expected effects. Employing a within-subjects, double-blind, placebo-controlled design, we assessed the effects of repeated high-dose dronabinol in HIV-positive marijuana smokers taking antiretroviral medication. Participants (N = 7), who smoked marijuana 4.2 ± 2.3 days/week, resided in a residential laboratory for two 16-day stays, receiving dronabinol (10 mg QID) in one stay and placebo in the other. Efficacy was assessed with objectively verified food intake and body weight. Tolerability was measured with sleep, subjective, and cognitive assessments. For analyses, each inpatient stay was divided into two phases, days 1–8 and 9–16; we compared dronabinol’s effects with placebo in each 8-day phase to investigate tolerance. Despite sustained increases in self-reported food cravings, dronabinol only increased caloric intake in the initial 8 days of dosing. Similarly, sleep quality was improved only in the first 8 days of dosing. Dronabinol’s mood-enhancing effects were sustained across the 16-day inpatient stay. Dronabinol was well tolerated, causing few negative subjective or cognitive effects. In HIV-positive marijuana smokers, high dronabinol doses safely and effectively increased caloric intake. However, repeated high-dose dronabinol appeared to result in selective tolerance to these effects. These findings indicate that HIV-positive individuals who smoke marijuana may require higher dronabinol doses than are recommended by the FDA. Future research to establish optimal dosing regimens, and reduce the development of tolerance, is required.

Previous studies have demonstrated that sex differences in pain responsivity can be detected using various models of experimentally induced pain. The present study employed the mechanical pressure test in order to examine potential differences in pain report among men, normally menstruating women (NMW), and women taking monophasic oral contraceptives (OCW). Testing occurred during 5 phases of the menstrual cycle (menstrual, follicular, ovulatory, luteal, and late luteal) and all participants completed 10 sessions (2 sessions per phase). Menstrual-cycle phase was estimated for OCW based on their first day of menses. Men were tested at time points that roughly corresponded to the intervals during which the different phases occurred in NMW. During the mechanical pressure test, 4 different weights were placed on the fingers, one at a time, and ratings of pain were recorded for 30 seconds. The statistical decision-making model and a forced-choice procedure were used to analyze the response data. Two variables, based on signal detection theory, were thus generated: P(A), a measure of sensory pain, and B, a measure of response bias. P(A) is believed to be a measure of pain sensitivity while B measures stoicism. NMW tended to report lower P(A) values, indicating reduced ability to discriminate among different stimulus intensities, during the menstrual and late luteal phases compared to the luteal phase. OCW reported lower B values, indicating less stoicism, during the menstrual compared to the follicular and ovulatory phases. Men tended to have significantly lower B values than OCW, but not NMW. These results demonstrate subtle menstrual-cycle effects in NMW and OCW. Sex differences were few, with more group differences and trends emerging between OCW and men, as opposed to men and NMW. Perspective The lack of consistent differences between men and NMW underscores the subtle impact of sex and hormonal changes in pain report. In addition, the data obtained in NMW support the notion that changes in hormone levels during the menstrual cycle can lead to changes in pain responsivity as NMW had trends for better discrimination in menstrual phases when estradiol levels were highest.

The rate of drug delivery to the central nervous system is believed to be an important predictor of the reinforcing strength of a drug. However, only a few studies have directly examined the relationship between drug-taking behavior and rate of drug administration. The purpose of the present experiment was to determine whether manipulating the infusion rate of a fixed dose of opioid alters its reinforcing effectiveness in humans. Twelve heroin-dependent participants (11 male, one female) completed the 2.5-week inpatient study. During test days, participants received $20 and a dose of drug (0 or 40 mg oxycodone administered intravenously over 2, 15, 30, 60, or 90 minutes) in random order during a morning sample session. Participants then worked for the sampled dose and/or money amount during an afternoon choice session by making finger presses on a computer mouse. Under these conditions, 40 mg oxycodone served as a reinforcer only when it was delivered over 2 and 15 minutes. Subjective ratings of drug liking, good effect, and high were similar to the self-administration results. Peak plasma levels of oxycodone generally occurred at the end of each infusion, eg, 2 minutes for the 2-minute infusion duration. Extended-release opioid medications are commonly prescribed for treating pain. The present results provide empirical support for the development of extended-release opioid medications that are difficult to convert into more rapid-acting forms. Specifically, these “abuse-deterrent formulations” could prevent patients from tampering with their medications to enhance their euphoric and reinforcing effects.

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, 30 mg/70 kg, PO) were examined. One dose was tested per day under double-blind conditions and sessions were separated by at least 48 h. 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 °C) and six sessions involved immersions in warm water (37 °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.

Abuse of prescription opioid medications has increased dramatically in the United States during the past decade, as indicated by a variety of epidemiological sources. However, few studies have systematically examined the relative reinforcing effects of commonly abused opioid medications. The current double-blind, placebo-controlled in-patient study was designed to compare the effects of intravenously delivered fentanyl (0, 0.0625, 0.125, 0.187, and 0.250 mg/70 kg), oxycodone (0, 6.25, 12.5, 25, and 50 mg/70 kg), morphine (0, 6.25, 12.5, 25, and 50 mg/70 kg), buprenorphine (0, 0.125, 0.5, 2, and 8 mg/70 kg), and heroin (0, 3.125, 6.25, 12.5, and 25 mg/70 kg) in morphine-maintained heroin abusers (N=8 completers maintained on 120 mg per day oral morphine in divided doses (30 mg q.i.d.)). All of the participants received all of the drugs tested; drugs and doses were administered in non-systematic order. All of the drugs produced statistically significant, dose-related increases in positive subjective ratings, such as 'I feel a good drug effect' and 'I like the drug.' In general, the order of potency in producing these effects, from most to least potent, was fentanyl>buprenorphine>or=heroin >morphine=oxycodone. In contrast, buprenorphine was the only drug that produced statistically significant increases in ratings of 'I feel a bad drug effect' and it was the only drug that was not self-administered above placebo levels at any dose tested. These data suggest that the abuse liability of buprenorphine in heroin-dependent individuals may be low, despite the fact that it produces increases in positive subjective ratings. The abuse liabilities of fentanyl, morphine, oxycodone, and heroin, however, appear to be similar under these experimental conditions.

Naltrexone is an opioid antagonist that is currently approved as a treatment for opioid and alcohol dependence. Although it is highly effective in completely antagonizing the effects of opioids, medication noncompliance is a difficult obstacle to treatment. Therefore, a sustained-release form of naltrexone may improve treatment outcome. The present study was designed to evaluate the time course, safety, and effectiveness of a depot formulation of naltrexone (Depotrex®). Five heroin-dependent individuals participated in an 8-week inpatient study. After a 1-week detoxification period, the effects of a range of heroin doses (0, 6.25, 12.5, and 25 mg, i.v.) were examined. Participants then received 384 mg naltrexone base. The effects of heroin were again evaluated for the next 6 weeks. One dose of heroin was tested per day and the entire dose range was tested each week. Doses were administered in non-systematic order. During a morning sample session, participants received a dose of heroin and $20 and subjective, performance, and physiological effects were measured both before and after drug administration. During an afternoon choice session, participants were given the opportunity to choose the sampled heroin dose and/or amount of money using a modified progressive ratio procedure. Depot naltrexone antagonized both the reinforcing and subjective effects of heroin for 4–5 weeks. Subjective ratings of withdrawal were reduced after week 2 and throughout the remainder of the study. The effects of heroin on mean trough pupil diameter began to emerge by week 5. There were no clinically significant effects on respiratory or cardiovascular function. The present results extend our previous findings by showing that the reinforcing effects of heroin were reduced for 4–5 weeks after administration of 384 mg depot naltrexone.

s / Drug and Alcohol Dependence 140 (2014) e86–e168 e133 Sex differences among opioid-abusing chronic pain patients in a clinical trial Jeanne M. Manubay1,2, J.W. Davidson1, S.K. Vosburg1,2, Jermaine D. Jones1,2, Ziva D. Cooper1,2, J. Fogel2, Sandra D. Comer1,2, Maria Sullivan1,2 1 Psychiatry, Columbia University, New York, NY, United States 2 Substance Abuse, NYSPI, New York, NY, United

Aims: The incidence of prescription opioid abuse among pain patients is substantial, and the ability of sublingual buprenorphine simultaneously to alleviate pain and reduce opioid abuse has not been investigated adequately. This study examined the utility of buprenorphine/naloxone (bup/nx; Suboxone) for treating patients diagnosed with concurrent chronic pain and opioid abuse. Methods: Participants with chronic, non-malignant pain meeting DSM-IV criteria for opioid abuse enrolled in a 7-week inpatient phase examining the effects of bup/nx on the reinforcing effects of prescription opioids. Those who completed this phase were subsequently enrolled in a 12-week outpatient trial designed to examine the safety, tolerability, and efficacy of bup/nx in relieving clinical pain. Participants attended twice-weekly visits, completed pain ratings, and met with the study physician. The bup/nx dose was titrated to optimal clinical benefit. Primary outcomes were retention in treatment, pain reduction from pre-study baseline, and percentage of opioid-negative urine samples. Results: The majority of patients (31/43; 72.1%) inducted onto bup/nx completed the inpatient phase and were enrolled in the present trial. Further, the majority (18/31; 58.1%) of patients who began the 12-week outpatient phase were retained at study completion. Mean ratings of average pain on the Pain Assessment and Documentation Tool (PADT) decreased significantly from 6.2/11 (±1.2) at prestudy baseline to 3.6 (±2.5; t(17) =4.17, p= .001) at Week12. Themeandaily dose of bup/nx atWk1was 15.8mg (±2.3, range 4–20) and atWk 12was 21.3mg (±7.8, range 4-32). The percentage of urine toxicologies negative for illicit opioids increased from 6.4% at baseline to 88.5% at Wk 1, 90% at Wk 4, and 93.4% at Wk 12. Conclusions: Bup/nx was well tolerated and effective in preventing relapse to prescription opioid abuse while providing adequate analgesic relief. Sublingual bup/nx has potential as an analgesic and may be well suited to treating patients with chronic pain who abuse opioids. Financial support: NIDA RO1 DA20448.