HIV-Risk Behavior Among Adults with Opioid Use Disorder During 12 Months Following Pre-trial Detention: Results from a Randomized Trial of Methadone Treatment.

This was a three group randomized clinical trial of interim methadone and patient navigation involving 225 pre-trial detainees with opioid use disorder in Baltimore. The HIV Risk Assessment Battery (RAB) was administered at baseline (in jail), and at 6 and 12 months post-release. Generalized linear mixed model analyses indicated the condition × time interaction effect failed to reach significance (ps > .05) for both the drug risk and sex risk subscale scores. Therefore, findings suggest that there were no intervention effects on drug or sex risk behaviors. However, increased use of cocaine at baseline was associated with increases in drug- (b = .04, SE = .02) and sex-risk (b = .01, SE = .003) behaviors. These results suggest that interventions targeting cocaine use among pre-trial detainees may serve as a means of reducing HIV risk associated with drug- and sex-risk behaviors.Clinical Trials Registration: Clinicaltrials.gov NCT02334215.

Methadone treatment of arrestees: A randomized clinical trial.

BACKGROUND: Opioid use disorder is common among detainees in US jails, yet methadone treatment is rarely initiated. METHODS: This is a three-group randomized controlled trial in which 225 detainees in Baltimore treated for opioid withdrawal were assigned to: (1) interim methadone (IM) with patient navigation (IM + PN); (2) IM; or (3) enhanced treatment-as-usual (ETAU). Participants in both IM groups were able to enter standard methadone treatment upon release, while ETAU participants received an assessment/referral number. Follow-up assessments at 1, 3, 6, and 12 months post-release determined treatment enrollment, urine drug testing results, self-reported days of drug use, criminal activity, and overdose events. Generalized linear mixed modelling examined two planned contrasts: (1) IM groups combined vs. ETAU; and (2) IM + PN vs. IM. RESULTS: On an intention-to-treat basis, compared to ETAU, significantly more participants in the combined IM groups were in treatment 30 days post-release, while the IM + PN vs. IM groups did not significantly differ. By month 12, there were no significant differences in the estimated marginal means of enrollment in any kind of drug treatment (0.40 and 0.27 for IM + PN and IM groups, respectively, compared to 0.29 for ETAU). There were no significant differences for either contrast in opioid-positive tests, although all groups reported a sharp decrease in heroin use from baseline to follow-up. There were five fatal overdoses, but none occurred during methadone treatment. CONCLUSION: Initiating methadone treatment in jail was effective in promoting entry into community-based drug abuse treatment but subsequent treatment discontinuation attenuated any potential impact of such treatment.

Assessment of nalmefene glucuronide as a selective gut opioid antagonist.

Opioid use often causes troublesome constipation as a side-effect. Selective antagonism of the intestinal actions of opioids might be useful in the treatment of opioid-induced constipation. We tested the inactive metabolite of nalmefene, nalmefene glucuronide, which showed promise of gut selectivity in rodent models, by administering ascending doses in single-blind, placebo-controlled fashion to five methadone-maintained, opioid-dependent male volunteers. Assessment of whether systemic or gut-selective opioid antagonist effects occurred was measured by vital signs, pupillary diameter, opioid withdrawal symptom scales, and bowel function. Oral nalmefene glucuronide precipitated symptoms and signs consistent with the opioid abstinence syndrome in all five subjects a mean of 9.0 h after dosing. We conclude that nalmefene glucuronide does not appear to exert sufficient gut selectivity to be useful in antagonizing constipation due to exogenous opioid administration without antagonizing systemic opioid effects.

Reinforcing effects of triazolam in sedative abusers: correlation of drug liking and self-administration measures.

Six male subjects with histories of sedative abuse were allowed to orally self-administer a maximum of 18 color-coded triazolam and placebo capsules during daily 3-h sessions. The schedule of reinforcement was a signaled fixed-interval 10-min schedule in which triazolam and placebo were concurrently available as mutually exclusive choices. Triazolam was shown to be a reinforcer in four of the six subjects. The two subjects who did not self-administer triazolam in preference to placebo also had lesser histories of drug dependence. Self-administration of triazolam (0.125 or 0.25 mg per capsule) was generally stable over 7-10 days. Manipulations of triazolam dose (0.0312-0.25 mg) per capsule in two subjects showed that the number of capsules self-administered was inversely related to capsule dose. Subject ratings of drug liking obtained from experimenter-administered doses of triazolam were correlated with self-administration behavior occurring 1-7 days later. Of the subject ratings, next day ratings obtained on the day after dosing resulted in significant correlations whereas same day ratings obtained while subjects were under the influence of triazolam did not. These results have important implications for abuse liability prediction and suggest that next day ratings have greater predictive validity than measures collected while subjects are under the influence of benzodiazepines.

Drug users' self-reports of behaviors and affective states under the influence of alcohol.

This study tested a modified version of the Alcohol-Related Behavior Questionnaire (ARBQ) to investigate the influence of alcohol on negative mood states. The ARBQ asked subjects (substance users and those not misusing drugs or alcohol) to recall various moods and behaviors under three drug conditions: sober, drinking, and drunk. Tests of the ARBQ subscales provided support for its reliability and validity. Scale scores measuring negative affect increased as levels of recalled alcohol intake increased, suggesting that larger amounts of alcohol produced more negative and aggressive feelings. Alcohol-dependent subjects reported more anger and aggression with increasing levels of alcohol intake than nonproblem drinkers. These data further indicated that, among those with alcohol dependence, a history of childhood aggression is an important predictor of negative behaviors and feelings associated with alcohol intake. Among other groups of drug users, a diagnosis of antisocial personality was relatively more important.

Housing conditions influence acquisition of sufentanil aerosol self-administration in rats.

At weaning, rats were housed either individually or in pairs and as adults were trained to poke their nose in and out of a port that dispensed a 2-s exposure of sufentanil aerosol (50-micrograms/ml solution). During the acquisition phase, which consisted of five nightly sessions lasting 14-16 h, individually caged rats responded for more sufentanil aerosol than did pair-caged animals when the fixed ratio (FR) requirement was gradually increased from FR 1 to FR 5 over the five sessions. During the maintenance phase, which consisted of daytime 2-h sessions at an FR 5 schedule of reinforcement, there were no differences between individually and pair-caged animals responding for sufentanil or for water vapor. Both groups responded significantly more for sufentanil than for water vapor. Based upon present evidence, it is suggested that environmental and biologic determinants may change psychomotor behavior in a way that could influence the rate by which animals acquire drug-seeking behavior.

A controlled trial of buprenorphine treatment for opioid dependence.

OBJECTIVE: To assess the efficacy of buprenorphine for short-term maintenance/detoxification. DESIGN: A randomized, double-blind, parallel group study comparing buprenorphine, 8 mg/d, methadone, 60 mg/d, and methadone, 20 mg/d, in a 17-week maintenance phase followed by an 8-week detoxification phase. SETTING: Outpatient facilities at the Addiction Research Center, Baltimore, Md. PATIENTS: One hundred sixty-two volunteers seeking treatment for opioid dependence. INTERVENTION: In addition to the medication, counseling using a relapse prevention model was offered but not required. PRIMARY OUTCOME MEASURES: Retention time in treatment, urine samples negative for opioids, and failure to maintain abstinence. RESULTS: Throughout the maintenance phase, retention rates were significantly greater for buprenorphine (42%) than for methadone, 20 mg/d (20%, P less than .04); the percentage of urine samples negative for opioids was significantly greater for buprenorphine (53%, P less than .001) and methadone, 60 mg/d (44%, P less than .04), than for methadone, 20 mg/d (29%). Failure to maintain abstinence during the maintenance phase was significantly greater for methadone, 20 mg/d, than for buprenorphine (P less than .03). During the detoxification phase, no differences were observed between groups with respect to urine samples negative for opioids. For the entire 25 weeks, retention rates for buprenorphine (30%, P less than .01) and methadone, 60 mg/d (20%, P less than .05), were significantly greater than for methadone, 20 mg/d (6%). All treatments were well tolerated, with similar profiles of self-reported adverse effects. The percentages of patients who received counseling did not differ between groups. CONCLUSIONS: Buprenorphine was as effective as methadone, 60 mg/d, and both were superior to methadone, 20 mg/d, in reducing illicit opioid use and maintaining patients in treatment for 25 weeks.

Supersensitivity to naloxone following acute morphine pretreatment in humans: behavioral, hormonal and physiological effects.

The effects of naloxone (10 mg/70 kg) given 6 h following acute exposure to morphine (4, 8, 16 mg/70 kg) were assessed in 5 opiate-abusing volunteers who were not physically dependent upon entering the study. Naloxone increased cortisol plasma levels more following morphine than placebo pretreatment. Naloxone reversed the effects of morphine on pupil diameter and oral temperature and decreased skin temperature as a function of morphine pretreatment. Subjects' ability to detect the effects of naloxone, their scores on an opiate-withdrawal questionnaire, and their visual-analog ratings of 'bad effects', 'chills', 'confused' and 'restlessness' increased when naloxone followed pretreatment with 8 and 16 mg, but not 4 mg, of morphine. Performance on the Digit Symbol Substitution Test was not discernibly affected under any of the dose conditions. Overall, results from the present study provide further evidence in humans that the administration of naloxone shortly following acute morphine pretreatment increases naloxone sensitivity, produces signs and symptoms typical of opiate withdrawal and that these effects are dependent on the dose of morphine administered.

Treatment of cocaine dependence in methadone maintenance clients: a pilot study comparing the efficacy of desipramine and amantadine.

We conducted a pilot study (N = 22) comparing the efficacy of desipramine and amantadine for treatment of cocaine dependence in methadone maintenance clients. The study which lasted 12 weeks, was double-blind, randomly assigned, and placebo-controlled. Subjects met DSM-III-R criteria for active cocaine dependence. All three groups' cocaine use, craving, and depressive symptoms declined significantly, but intergroup differences were not significant. Clients receiving desipramine were significantly more likely to remain in treatment and to be cocaine free at study completion. The results emphasize the importance of delivering comprehensive services to the cocaine user in methadone treatment. Further evaluations of these two medications as adjuncts in the treatment of cocaine dependence are needed.

Neuroendocrine responses to a glucose challenge in substance users with high and low levels of aggression, impulsivity, and antisocial personality.

Plasma glucose concentrations, and plasma prolactin and cortisol responses to a 5-hour oral glucose tolerance test (OGTT) in 37 substance abusers, were examined to assess the relationship between varying degrees of antisocial personality, impulsivity, and aggressiveness and measures of endocrine function. Childhood and presenting aggression, impulsivity and antisocial personality features were evaluated by several self-report questionnaires. Those with high scores for psychopathic deviance (MMPI) differed in glucose levels following OGTT from those with low scores. Lower cortisol nadir levels were associated with higher scores on measures of antisocial personality and aggressiveness. Also, prolactin response to glucose was attenuated relative to baseline levels in the more antisocial and aggressive subjects. The results indicate that substance abusers with high levels of self-reported antisocial personality and aggressive behavior have altered neuroendocrine responses to glucose challenge, although there was no evidence of hypoglycemia. No one personality or behavioral trait, as measured by our test battery, more strongly predicted neuroendocrine responses to glucose administration. Thus, our data partially support other reports of altered neuroendocrine responses to stressful challenges in aggressive/antisocial individuals.

Carbamazepine produces nonspecific effects on cocaine self-administration in rats.

Anecdotal evidence in humans suggest that carbamazepine suppresses cocaine-induced rush and craving. Such claims are unsupported in controlled trials using a placebo control. In the present study, rats were trained to self-administer i.v. cocaine in daily 2-hr sessions in which every tenth lever press delivered 1 mg/kg cocaine. After responding was stable, they were injected before each session with the vehicle for 2 days followed by carbamazepine for 2 days. At a 7 mg/kg dose, carbamazepine was without effect, whereas 15 mg/kg suppressed responding for cocaine only on the second (day 4) day of carbamazepine treatment. With 4 consecutive days of treatment, carbamazepine (15 mg/kg) reduced cocaine-maintained responding slightly, but significantly. In another group of animals trained to lever-press for food reinforcement, carbamazepine (15 mg/kg) also significantly decreased the rate of responding, suggesting that the suppression of responding was not specific to cocaine-reinforced behavior.