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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.

Zolpidem attenuates shift-change-related sleep and performance disruptions. It is unknown whether these benefits alter the reinforcing effects of the drug during shift work. This study examined zolpidem-related reinforcing effects during simulated shift work. Eleven volunteers (3F, 8M) completed this 16-day within-participant, residential laboratory study. Each day participants were given an opportunity to self-administer oral zolpidem (10 mg) or receive a $1 voucher immediately following a 9-h work period and immediately before going to bed. Participants worked under two shift conditions: (1) during the night shift, participants completed computerized task batteries from 00:30 to 09:30 h and went to bed at 16:00 h and (2) during the day shift, participants completed task batteries from 08:30 to 17:30 h and went to bed at 24:00 h. Shift conditions alternated three times during the study. Despite the fact that sleep, psychomotor performance, and some ratings of mood were disrupted during night-shift work, there was no significant effect of shift on choice to take zolpidem. Overall, participants selected markedly fewer zolpidem doses than monetary vouchers (17% versus 83%). Thus, zolpidem did not serve as a reinforcer even when sleep was disrupted. These data are consistent with previous reports indicating that sedatives produce limited reinforcing effects in individuals without a history of drug abuse.

The purpose of this double-blind, randomized, outpatient study was to evaluate the reinforcing and subjective effects of modafinil (200, 400, or 600 mg) in cocaine abusers. Twelve participants (2 female, 10 male) completed this study, consisting of 3 blocks of 7 sessions; each block tested a difference dose of modafinil. During the first 2 sessions of each block, participants "sampled" 1 of the doses of modafinil, and placebo. These doses of modafinil and placebo were available for the subsequent five choice sessions of the block. In each choice session, participants had an opportunity to administer active or placebo capsules. Modafinil administration did not differ from placebo administration, and subjective-effects ratings were not systematically altered as a function of modafinil dose. Results suggest that modafinil does not have abuse liability in cocaine abusers.

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.

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.

Psychiatric comorbidity, particularly depressive disorders, is associated with continued substance use and poor social functioning among methadone maintained patients. Evidence suggests similar neurochemical and environmental pathways may link the two disorders and it is reasonable to hypothesize that pharmacological and environmental factors play important roles in the treating comorbid depression and substance use. The present study tested the efficacy of sertraline for treating syndromally defined depressive disorders among non-abstinent methadone maintained opiate dependent patients. The moderating effects of environmental context on treatment outcome were also examined. Ninety-five patients were randomized in a 12-week, double-blind, placebo-controlled trial of sertraline, a serotonin-selective re-uptake inhibitor. There was no main effect of sertraline on either depression or substance use outcomes. However, sertraline demonstrated significant ameliorative effects on depression among patients with a more positive environment or less negative environment. The odds of being abstinent from heroin and cocaine were greater for patients on sertraline in environments with relatively less adversity. The findings support the hypothesis that contextual factors moderate the efficacy of pharmacological treatment for depression among methadone patients. They also suggest future research should examine a pharmacological treatment that is combined with a behavioral intervention targeting the accessibility of reinforcement or reducing the impact of aversive environmental interactions.

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.

The purpose of this double-blind, outpatient study was to evaluate the reinforcing and subjective effects of the uncompetitive N -methyl- d -aspartate (NMDA) antagonist memantine in cocaine-dependent humans. Eight participants (two females, six males) completed this study which consisted of three blocks of seven sessions; each block tested a different dose of memantine. During the first two sessions of each block, participants “sampled” the memantine capsule (10, 20, or 30 mg) and the placebo capsule that were available for the next five sessions. During the five subsequent sessions, participants had an opportunity to self-administer either the active or placebo capsule. Memantine was not reinforcing and subjective-effects ratings were not altered as a function of dose. Results suggest that these doses of memantine do not have abuse liability in cocaine-dependent individuals.

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.