Trajectories of craving during medication-assisted treatment for opioid-use disorder: Subtyping for early identification of higher risk.

AIMS: To examine evidence for subtypes of opioid craving trajectories during medication for opioid use disorder (MOUD), and to (a) test whether these subtypes differed on MOUD-related outcomes, and (b) determine whether nonresponders could be identified before treatment initiation. DESIGN, SETTING, AND PARTICIPANTS: Outpatients (n = 211) being treated with buprenorphine or methadone for up to 16 weeks. Growth mixture modeling was used to identify unobserved craving-trajectory subtypes. Support Vector Machines (SVM) were trained to predict subtype membership from pretreatment data. MEASUREMENTS: Self-reported opioid craving (Ecological Momentary Assessment - EMA - three random moments per day). Participant-initiated EMA reports of drug use or higher-than-usual stress. Addiction Severity Index (ASI) pretreatment. FINDINGS: Four craving trajectories were identified: Low (73%); High and Increasing (HIC) (10.9%); Increasing and Decreasing (8.5%); and Rapidly Declining (7.6%). The HIC subgroup reported the highest use of heroin, any opiate, and cannabis during treatment. The Low Craving subgroup reported the lowest use of heroin or any opiate use, and the lowest levels of stress and drug-cue exposure during treatment. SVM models predicting HIC membership before treatment initiation had a sensitivity of 0.70, specificity of 0.78, and accuracy of 0.77. Including 3 weeks of EMA reports increased sensitivity to 0.78, specificity to 0.84, and accuracy to 0.85. CONCLUSIONS: Subgroups of MOUD patients show distinct patterns of opioid craving during treatment. Subgroups differ on critical outcomes including drug-use lapse, stress, and exposure to drug cues. Data from enrollment and early in treatment may help focus clinical attention.

Effects of Prereactivation Propranolol on Cocaine Craving Elicited by Imagery Script/Cue Sets in Opioid-dependent Polydrug Users: A Randomized Study.

OBJECTIVES: Relapse to drug misuse may follow exposure to drug cues that elicit craving. The learned associations, or "emotional memories," that underlie responses to cues may be attenuated or erased by the ß-adrenergic antagonist propranolol during a "reconsolidation window" shortly after the memories are reactivated by cues. METHODS: We evaluated the effects of propranolol on cue-induced drug cravings in healthy opioid-dependent individuals who used cocaine while receiving methadone maintenance (n = 33). Participants were asked to recall specific cocaine use and neutral events in an interview; these events were used to develop personalized auditory script/cue sets. Approximately 1 week later, propranolol (40 mg) or placebo (random assignment, double blind) was administered orally before presentation of the script/cue sets; the presentation of the script/cue sets were tested 1 week and 5 weeks after the propranolol/placebo session. Ongoing drug use was monitored via urine screens and self-report in twice-weekly visits. RESULTS: Cue reactivity, as assessed by craving scales and physiological responses, was unexpectedly greater in the propranolol group than in the placebo group. This counterhypothesized group difference was present acutely during propranolol administration and seemed to persist (without reaching statistical significance) during the subsequent test sessions. CONCLUSIONS: Our results do not support the use of propranolol for cue-induced cocaine craving in opioid-maintained patients.

Clonidine blocks stress-induced craving in cocaine users.

RATIONALE: Reactivity to stressors and environmental cues, a putative cause of relapse in addiction, may be a useful target for relapse-prevention medication. In rodents, alpha-2 adrenergic agonists such as clonidine block stress-induced reinstatement of drug seeking, but not drug cue-induced reinstatement. OBJECTIVE: The objective of this study is to test the effect of clonidine on stress- and cue-induced craving in human cocaine users. METHODS: Healthy, non-treatment-seeking cocaine users (n = 59) were randomly assigned to three groups receiving clonidine 0, 0.1, or 0.2 mg orally under double-blind conditions. In a single test session, each participant received clonidine or placebo followed 3 h later by exposure to two pairs of standardized auditory-imagery scripts (neutral/stress and neutral/drug). Subjective measures of craving were collected. RESULTS: Subjective responsivity ("crave cocaine" Visual Analog Scale) to stress scripts was significantly attenuated in the 0.1- and 0.2-mg clonidine groups; for drug-cue scripts, this attenuation occurred only in the 0.2-mg group. Other subjective measures of craving showed similar patterns of effects but Dose × Script interactions were not significant. CONCLUSIONS: Clonidine was effective in reducing stress-induced (and, at a higher dose, cue-induced) craving in a pattern consistent with preclinical findings, although this was significant on only one of several measures. Our results, though modest and preliminary, converge with other evidence to suggest that alpha-2 adrenergic agonists may help prevent relapse in drug abusers experiencing stress or situations that remind them of drug use.

A focus-group study on spirituality and substance-user treatment.

Focus groups were conducted in 2005-2006 with 25 urban methadone-maintained outpatients to examine beliefs about the role of spirituality in addiction and its appropriateness in formal treatment. Thematic analyses suggested that spirituality and religious practices suffered in complex ways during active addiction, but went "hand in hand" with recovery. Participants agreed that integration of a voluntary spiritual discussion group into formal treatment would be preferable to currently available alternatives. One limitation was that all participants identified as strongly spiritual. Studies of more diverse samples will help guide the development and evaluation of spiritually based interventions in formal treatment.

Single and multiple doses of rimonabant antagonize acute effects of smoked cannabis in male cannabis users.

RATIONALE: A single 90-mg dose of the cannabinoid CB1 receptor antagonist rimonabant attenuates effects of smoked cannabis in humans. OBJECTIVES: The objective of this study is to evaluate whether repeated daily 40-mg doses of rimonabant can attenuate effects of smoked cannabis to the same extent as a single higher (90 mg) dose. MATERIALS AND METHODS: Forty-two male volunteers received one of three oral drug regimens in a randomized, double blind, parallel group design: (1) 40 mg rimonabant daily for 15 days, (2) placebo for 14 days, then 90 mg rimonabant on day 15, or (3) placebo for 15 days. All participants smoked an active or placebo cannabis cigarette 2 h after medication on days 8 and 15. Subjective effects were measured with visual analog scales and the marijuana-scale of the Addiction Research Center Inventory. RESULTS: Cannabis-induced tachycardia was significantly lower for the 40-mg group on day 8 and for the 40 and 90 mg rimonabant groups on day 15 as compared to placebo. The 40-mg dose significantly decreased peak subjective effects on day 8. Neither the 90-mg nor 40-mg doses significantly decreased peak subjective effects on day 15. Rimonabant treatment did not significantly affect Delta(9)-tetrahydrocannabinnol pharmacokinetics. CONCLUSIONS: Repeated lower daily rimonabant doses (40 mg) attenuated the acute physiological effects of smoked cannabis to a similar degree as a single 90-mg dose; repeated 40-mg doses attenuated subjective effects after 8 but not 15 days.

Spiritual/Religious experiences and in-treatment outcome in an inner-city program for heroin and cocaine dependence.

Although spirituality is an integral component of some of the most popular approaches to substance abuse treatment, there is little empirical evidence for a causal relationship between spirituality and treatment success. In the present study, 169 (121 male) opiate- or cocaine-abusing treatment seekers completed the Index of Spiritual Experience (INSPIRIT), a questionnaire that assesses both spirituality and religiosity. Responses were analyzed in terms of demographic variables and in-treatment outcome, which was determined by treatment retention and drug screens from observed biweekly urine collections. Religious/spiritual beliefs were common in these participants and were associated with in-treatment outcome: total INSPIRIT score was weakly correlated (r = .16, p < .04) with number of subsequent cocaine-negative urines, and participants reporting that they frequently spent time on religious/spiritual activities showed significantly better outcomes in terms of subsequent drug use and treatment retention. Women and African Americans were more likely than men and non-African Americans to report religious and spiritual beliefs or experiences on several individual items, and African Americans had higher INSPIRIT scores than Caucasians. The results suggest that spiritual and religious experience plays a role in substance abuse recovery and that demographic characteristics should be considered in the design of spiritually oriented behavioral interventions for addiction.

Nonreporting of cannabis use: Predictors and relationship to treatment outcome in methadone maintained patients.

Underreporting of drug use is common and influenced by multiple factors. Cannabis (THC) use nonreporting and its relationship to heroin and cocaine use were investigated in 690 patients enrolled in 25- to 29-week clinical trials of contingency management plus methadone maintenance. Urine specimens and self-reports of drug use were collected 3 times/week. Potential predictors of THC use nonreporting were analyzed by multiple logistic regression; relationships between THC use nonreporting and % cocaine- and opiate-positive urines were analyzed by multiple regression. Compared to non-THC users (n=317), patients with THC-positive urines (n=373) were more likely to be male and have more years of THC use, but were not different on other characteristics. Nonreporting to user ratios were: THC 191/373 (51.2%); opiates 17/686 (2.5%); cocaine 21/681 (3.1%). Predictors of THC use nonreporting were low rate of THC-positive urines during treatment, fewer days of THC use in the last 30 before treatment, African-American race, and absence of antisocial personality disorder. Nonreporting of THC use was associated with significantly greater opiate and cocaine use. Contingency management decreased cocaine use in THC nonreporters to the level of reporters. Nonreporting of THC use is a significant predictor of greater cocaine and heroin use. This association can be eliminated with contingency management therapy.