N-acetylcysteine for smoking cessation among dual users of tobacco and cannabis: Protocol and rationale for a randomized controlled trial.

BACKGROUND: Tobacco and cannabis co-use is a growing public health problem. The synergistic effects of cannabis and nicotine on neurobiological systems that mediate reward and shared environmental cues reinforcing use may make tobacco smoking cessation more difficult. N-acetylcysteine (NAC), an FDA-approved medication and over-the-counter supplement, has shown promise in animal studies and randomized controlled trials (RCTs) in reducing tobacco and cannabis craving and use. NAC's potential efficacy in treating addiction may be attributable to its central nervous system effects in reducing excessive glutamatergic activity, oxidative stress, and inflammation. To date, no RCT has examined NAC for smoking cessation among dual users of tobacco and cannabis. METHOD: In a double-blind, placebo-controlled RCT, we will examine NAC for smoking cessation among dual users of tobacco and cannabis. Sixty adult cigarette-cannabis co-users are randomized to receive NAC 3600 mg per day or placebo over 8 weeks. Participants in both groups receive 8 weekly cognitive behavioral therapy sessions addressing smoking cessation and cannabis reduction. Outcomes are assessed at Weeks 0, 4, 8, and 12. Primary aims are to determine NAC's efficacy in decreasing cigarette craving, nicotine dependence, and use; and cannabis craving and use. Exploratory aims include examination of changes in neurocognition with NAC and their potential mediational effects on cigarette and cannabis use outcomes. CONCLUSION: Results will inform smoking cessation treatment among dual users of tobacco and cannabis. CLINICALTRIALS: gov Identifier: NCT04627922.

Development of a mobile mindfulness smartphone app for post-traumatic stress disorder and alcohol use problems for veterans: Beta test results and study protocol for a pilot randomized controlled trial.

BACKGROUND: Post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD) are highly prevalent, and co-occurring among post-9/11 veterans. Mobile health (mHealth) applications, specifically those focused on mindfulness-based techniques, may be an effective avenue to intervene with veterans who cannot or will not seek care at traditional in-person settings. Thus, to address areas of improvement in mHealth for veterans, we developed Mind Guide and prepared it for testing in a pilot randomized controlled trial (RCT) with veterans. METHODS: We have completed phase 1 (treatment development) and Phase 2 (beta test) of our mobile mHealth app, Mind Guide. In this paper we describe the methods for Phase 1 as well as results for our beta test (n = 16; inclusion criteria included screen for PTSD, AUD, a post-9/11 veteran, and not currently receiving treatment) for Mind Guide as well as outline procedures for our pilot RCT of Mind Guide (Phase 3). The PTSD Checklist, self-reported alcohol use, the Perceived Stress Scale, Penn Alcohol Craving Scale, and the Emotion Regulation Questionnaire were used. RESULTS: Results of our beta test of Mind Guide show promising past 30 day effects on PTSD (d = -1.12), frequency of alcohol use (d = -0.54), and alcohol problems (d = -0.44), and related mechanisms of craving (d = -0.53), perceived stress (d = -0.88), and emotion regulation (d = -1.22). CONCLUSION: Our initial beta-test of Mind Guide shows promise for reducing PTSD and alcohol related problems among veterans. Recruitment is ongoing for our pilot RCT in which 200 veterans will be recruited and followed up for 3 months. CLINICALTRIALS: gov Identifier: NCT04769986.

Rationale and design of a multisite randomized clinical trial examining an integrated behavioral treatment for veterans with co-occurring chronic pain and opioid use disorder: The pain and opioids integrated treatment in veterans (POSITIVE) trial.

BACKGROUND: Chronic pain and opioid use disorder (OUD) individually represent a risk to health and well-being. Concerningly, there is evidence that they are frequently co-morbid. While few treatments exist that simultaneously target both conditions, preliminary work has supported the feasibility of an integrated behavioral treatment targeting pain interference and opioid misuse. This treatment combined Acceptance and Commitment Therapy (ACT) and Mindfulness-Based Relapse Prevention (ACT+MBRP). This paper describes the protocol for the adequately powered efficacy study of this integrated treatment. METHODS: A multisite randomized controlled trial will examine the efficacy of ACT+MBRP in comparison to a parallel education control condition, focusing on opioid safety and pain education. Participants include veterans (n = 160; 21-75 years old) recruited from three Veterans Administration (VA) Healthcare Systems with chronic pain who are on a stable dose of buprenorphine. Both conditions include twelve weekly 90 min group sessions delivered via telehealth. Primary outcomes include pain interference (Patient Reported Outcome Measurement Information System - Pain Interference) and hazardous opioid use (Current Opioid Misuse Measure), which will be examined at the end of the active treatment phase and through 12 months post-intervention. Secondary analyses will evaluate outcomes including pain intensity, depression, pain-related fear, and substance use, as well as treatment mechanisms. CONCLUSION: This study will determine the efficacy of an integrated behavioral treatment program for pain interference and hazardous opioid use among veterans with chronic pain and OUD who are prescribed buprenorphine, addressing a critical need for more integrated treatments for chronic pain and OUD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04648228.

Telephone veteran peer coaching for mental health treatment engagement among rural veterans: The importance of secondary outcomes and qualitative data in a randomized controlled trial.

PURPOSE: To determine the effectiveness of telephone motivational coaching delivered by veteran peers to improve mental health (MH) treatment engagement among veterans. METHODS: Veterans receiving primary care from primarily rural VA community-based outpatient clinics were enrolled. Veterans not engaged in MH treatment screening positive for ≥1 MH problem(s) were randomized to receive veteran peer-delivered feedback on MH screen results and referrals plus 4 sessions of telephone motivational coaching (intervention) versus veteran peer-delivered MH results and referrals without motivational coaching (control). Blinded telephone assessments were conducted at baseline, 8, 16, and 32 weeks. Cox proportional hazard models compared MH clinician-directed treatment initiation between groups; descriptive analyses compared MH treatment retention, changes in MH symptoms, quality of life, and self-care. FINDINGS: Among 272 veterans screening positive for ≥1 MH problem(s), 45% who received veteran peer telephone motivational coaching versus 46% of control participants initiated MH treatment (primary outcome) (hazard ratio: 1.09, 95% CI: 0.76-1.57), representing no between-group differences. In contrast, veterans receiving veteran peer motivational coaching achieved significantly greater improvements in depression, posttraumatic stress disorder and cannabis use scores, quality of life domains, and adoption of some self-care strategies than controls (secondary outcomes). Qualitative data revealed that veterans who received veteran peer motivational coaching may no longer have perceived a need for MH treatment. CONCLUSIONS: Among veterans with MH problems using predominantly rural VA community clinics, telephone peer motivational coaching did not enhance MH treatment engagement, but instead had positive effects on MH symptoms, quality of life indicators, and use of self-care strategies.

A pilot trial of collaborative care with motivational interviewing to reduce opioid risk and improve chronic pain management.

BACKGROUND AND AIMS: Opioid use and chronic pain are prevalent in the veteran population. Collaborative care enhances coordination between patients and their care teams, and motivational interviewing (MI) is a communication style designed to facilitate behavior change. This study evaluated the use of collaborative care with MI (CCMI) with patients with chronic pain and high-risk prescription opioid use. DESIGN: Small pilot study of a randomized controlled trial. SETTING: An urban Veterans Affairs (VA) Medical Center in the United States. PARTICIPANTS: One hundred adult veterans with chronic pain currently enrolled into primary care and receiving long-term opioid therapy. INTERVENTION AND COMPARATOR: During an initial 1-hour visit with a study primary-care physician (PCP), all veterans (n = 100) developed a personalized pain care plan, after which they were randomized to receive four sessions (at 4, 6, 8 and 12 weeks) of either CCMI (n = 51) or attention control psychoeducation (ACP; n = 49). Subsequently, participants had 30-minute follow-up visits with study PCPs and post-treatment assessment at 12 weeks. MEASUREMENTS: Co-primary outcomes measures assessed opioid risk and pain interference; secondary measures assessed pain severity, PCP rating of opioid risk and pain management goals. FINDINGS: At 12 weeks, intent-to-treat (ITT) analyses using multivariate mixed-effects linear regression were inconclusive regarding the between-group differences in primary and secondary outcomes at post-intervention (12 weeks). Bayes factors for opioid risk, pain interference, pain severity and PCP ratings were 1.96, 1.36, 0.45 and 0.82, respectively. Veterans in the CCMI group reported implementing more complementary integrative health (CIH) goals (e.g. yoga) than did those in the ACP group (d = 0.54). CONCLUSIONS: US veterans with chronic pain who received collaborative care with motivational interviewing reduced their high-risk opioid use and showed improved pain interference and severity after an intake with a primary-care provider involving shared decision-making and the creation of a personalized pain care plan.

Whole Health Options and Pain Education (wHOPE): A Pragmatic Trial Comparing Whole Health Team vs Primary Care Group Education to Promote Nonpharmacological Strategies to Improve Pain, Functioning, and Quality of Life in Veterans-Rationale, Methods, and Implementation.

BACKGROUND: The Whole Health model of the U.S. Department of Veterans Affairs (VA) emphasizes holistic self-care and multimodal approaches to improve pain, functioning, and quality of life. wHOPE (Whole Health Options and Pain Education) seeks to be the first multisite pragmatic trial to establish evidence for the VA Whole Health model for chronic pain care. DESIGN: wHOPE is a pragmatic randomized controlled trial comparing a Whole Health Team (WHT) approach to Primary Care Group Education (PC-GE); both will be compared to Usual VA Primary Care (UPC). The WHT consists of a medical provider, a complementary and integrative health (CIH) provider, and a Whole Health coach, who collaborate with VA patients to create a Personalized Health Plan emphasizing CIH approaches to chronic pain management. The active comparator, PC-GE, is adapted group cognitive behavioral therapy for chronic pain. The first aim is to test whether the WHT approach is superior to PC-GE and whether both are superior to UPC in decreasing pain interference in functioning in 750 veterans with moderate to severe chronic pain (primary outcome). Secondary outcomes include changes in pain severity, quality of life, mental health symptoms, and use of nonpharmacological and pharmacological therapies for pain. Outcomes will be collected from the VA electronic health record and patient-reported data over 12 months of follow-up. Aim 2 consists of an implementation-focused process evaluation and budget impact analysis. SUMMARY: This trial is part of the Pain Management Collaboratory, which seeks to create national-level infrastructure to support evidence-based nonpharmacological pain management approaches for veterans and military service personnel.

Oxytocin-enhanced group therapy for methamphetamine use disorder: Randomized controlled trial.

BACKGROUND: Methamphetamine (METH) use is a public health crisis that disproportionately affects men who have sex with men (MSM). There are currently no FDA-approved pharmacological interventions to treat methamphetamine use disorder (MUD). MUD is associated with social impairments and extremely high treatment attrition rates. Administration of oxytocin, a neuropeptide involved in social attachment, may be a novel approach to addressing these issues. Moreover, oxytocin administration has shown promise for reducing METH-related addictive behavior in animal models, but has not yet been investigated in clinical trials for MUD. Last, oxytocin is known to modulate stress responsivity via regulation of the autonomic nervous system, which is dysregulated in METH users. We hypothesize that oxytocin, in combination with group psychotherapy, will increase treatment engagement, reduce addiction behavior, and mitigate stress hyperreactivity. METHODS: This is a randomized, double blind trial of oxytocin 40-IU (n = 24) or placebo (n = 24) administered intranasally prior to each of six weekly motivational interviewing group therapy (MIGT) sessions for MUD in MSM. PRIMARY OUTCOME: (a) session attendance. SECONDARY OUTCOMES: (b) group cohesion, (c) anxiety, (d) METH craving, (e) METH use, and (f) in-session cardiac physiology. RESULTS: Participants receiving oxytocin had significantly higher group therapy attendance than those receiving placebo, OR 3.26, 95% CI [1.27-8.41], p = .014. There was a small effect of oxytocin on group cohension, but not anxiety or craving. METH use did not change over the six-week MIGT course in either treatment arm. Participants receiving oxytocin had lower average heart rates during MIGT sessions and higher heart rate variability. There were positive main effects of MIGT over Time regardless of study drug. CONCLUSIONS: This evidence, and the lack of any serious adverse events, suggests that oxytocin may safely increase treatment attendance. One possible mechanism by which it may do so is its modulation of the autonomic nervous system. Further investigation is warranted.

A randomized clinical trial evaluating the efficacy of a brief alcohol intervention supplemented with a substance-free activity session or relaxation training.

OBJECTIVE: Behavioral economic theory suggests that a reduction in alcohol use is most likely when there is an increase in rewarding substance-free activities. Anxiety has also been linked to heavy drinking, and strategies to reduce anxiety may enhance alcohol interventions. The goal of this 2-site randomized controlled clinical trial was to evaluate the efficacy of a brief alcohol intervention that was supplemented with either a behavioral economic substance-free activity session (SFAS) or a relaxation training (Relaxation training [RT]) session. METHOD: Participants were 393 college students (61% female, mean age = 18.77 years) who reported 2 or more past-month heavy drinking episodes. Participants were randomized to 1 of 3 conditions: (a) assessment; (b) alcohol brief motivational intervention (BMI) plus SFAS; or (c) BMI plus RT. Both treatment conditions included 2 in-person sessions plus a phone booster session. Outcomes were evaluated 1-, 6-, 12-, and 16-months postintervention. RESULTS: Generalized linear mixed models indicated that the combination of a BMI plus either the SFAS or RT was associated with significant reductions in alcohol use and problems across the 16-month follow-up compared with assessment only. There were no significant differences between the two active treatment conditions. Changes in proportional reinforcement from substance-related activities, and protective behavioral strategies mediated treatment effects. CONCLUSION: Two-session (plus booster) interventions that combine BMI and either substance-free activity enhancement or RT can result in enduring reductions in alcohol misuse among college drinkers. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Oxytocin-enhanced motivational interviewing group therapy for methamphetamine use disorder in men who have sex with men: study protocol for a randomized controlled trial.

BACKGROUND: The prevalence of methamphetamine use disorder (MUD) in the United States has risen dramatically in the past four decades and is concentrated in populations such as men who have sex with men (MSM). Despite the public health consequences of MUD, there are no FDA-approved psychopharmacological treatments. Psychosocial treatment alone has been shown to reduce methamphetamine use, but high attrition rates limit treatment efficacy. Promising findings from animal models of MUD using exogenous oxytocin, a social neuropeptide, have set the stage for translational work. Along with unique anti-addiction effects, oxytocin holds a primary role in enhancing social salience and modulating stress. In humans, oxytocin administration, combined with evidence-based psychosocial interventions, may act synergistically to improve addiction treatment outcomes and improve retention rates in current MUD treatment. METHODS/DESIGN: We are conducting a randomized, double-blind, placebo-controlled trial of oxytocin-enhanced motivational interviewing group therapy (MIGT). Oxytocin or placebo 40 IU is administered intranasally in conjunction with six, weekly MIGT sessions. We will recruit 50 MSM, initiating treatment for MUD from specialized community health programs in San Francisco, CA, USA. Individuals will be randomized (1:1) to receive six, weekly sessions of MIGT with or without oxytocin. Our primary outcome is session attendance. Other outcomes of interest include: measures of group cohesion, anxiety, psychophysiology, and stimulant craving and use. DISCUSSION: This will be the first study of oxytocin's effects in humans with MUD. Findings from this novel protocol will attempt to bridge existing animal data with the need for innovative clinical treatments for MUD, inform the growing field of pharmacologically-enhanced psychotherapy, and help to elucidate mechanisms behind oxytocin's potential anti-addiction effects. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02881177 . Registered on 26 August 2016.

Hostility in mandated students: exploratory analysis and implications for treatment.

College students mandated to receive an intervention following an alcohol-related campus violation are a high-risk group of students experiencing the negative effects of alcohol. Understanding the psychological properties associated with mandated students' alcohol use may provide useful clinical information. Hostility is a trait that has shown association with heavy drinking in adults but has gone unstudied in mandated students. We examined the relationship between hostility and a variety of drinking-related variables in mandated students (N = 466). Results indicated that individuals reporting higher levels of hostility reported riskier drinking and alcohol-related problems, yet exhibited ambivalence regarding their alcohol use. Findings are discussed in the context of treating mandated students exhibiting high hostility and risky drinking, a particularly challenging population.