Faculty Bibliography

BACKGROUND:Craving alcohol for reward (positive reinforcement) and relief (negative reinforcement) has been proposed as useful phenotypes for precision medicine approaches to alcohol use disorder (AUD) treatment. This study examined reward and relief craving in nonpharmacological treatments, Motivational Enhancement Therapy (MET) versus MET + Community Reinforcement Approach (CRA), among older adults. METHODS:Secondary analyses of data from The Elderly Study (N = 693; mean age 64.0 years; male 59.7%), a single-blinded, multisite, randomized controlled trial of two nonpharmacological treatments in an elderly population (60+ years) diagnosed with DSM-5 AUD. Latent profile analysis (LPA) was used to identify craving profiles based on The Alcohol Abstinence Self-Efficacy Scale (AASE) temptation subscale scores. The classification performance of clinical cutoff scores on the AASE scale was tested against the LPA solution. Associations between cutoff-based craving groups and treatment success (binary variable representing change in alcohol consumption and quality of life across profiles pre-/posttreatment) were analyzed using logistic regression, stratified on MET versus MET + CRA. Differences in alcohol consumption and quality of life scores pre-/posttreatment were analyzed using the Wilcoxon signed-rank test. RESULTS:Four reward-relief craving profiles were identified but were more distinguished by variation in relief craving (low relief, medium-low relief, medium-high relief, and high relief). Compared to the low relief craving group, the medium-high relief craving group had lower odds for treatment success when receiving MET: adjusted Odds Ratio (aOR) 0.42 (95% CI 0.21-0.84), and the high relief craving group had lower odds for treatment success when receiving MET + CRA: aOR 0.38 (95% CI 0.15-0.94). Alcohol consumption was reduced, and psychological quality of life was improved at follow-up across all relief craving groups. CONCLUSION/CONCLUSIONS:This study identified reward and relief drinking craving among older adults with AUD. Results indicate that considering relief craving when offering nonpharmacological treatment to older adults suffering from AUD may be clinically relevant.

BACKGROUND AND AIMS/OBJECTIVE:It is unclear if findings from randomized controlled trials (RCT) of medications for opioid use disorder apply to real-world settings. We estimated the effectiveness of buprenorphine-naloxone (BUP-NX) versus extended-release naltrexone (XR-NTX) on treatment interruption in a RCT and an observational study based on real-world data. DESIGN/METHODS:Target trial emulation to harmonize the protocol and statistical analyses of X:BOT (target trial) and the observational study (observational emulation). Baseline was randomization in the target trial and medically managed opioid withdrawal (MMOW) discharge in the observational emulation. SETTINGS/METHODS:X:BOT trial and Massachusetts Public Health Data Warehouse observational data (United States). PARTICIPANTS/METHODS:The target trial included all X:BOT participants. The observational emulation trial included MMOW discharges from January 2014 to May 2016. MEASUREMENTS/METHODS:Treatment strategies were BUP-NX versus XR-NTX initiation within 28 days of baseline. The outcome was treatment interruption (earliest of treatment discontinuation, incarceration, MMOW readmission, death). We estimated the 24-week risk and risk difference. FINDINGS/RESULTS:In the target trial, 94% (269/287) and 66% (187/283) of participants randomized to BUP-NX or XR-NTX initiated their assigned treatment within 28 days, respectively. In the observational emulation, BUP-NX and XR-NTX were initiated within 28 days in 9% (5209/59 076) and 3% (1813/59 076) of MMOW discharges, respectively. The adjusted 24-week treatment interruption risks (95% confidence interval) for BUP-NX and XR-NTX were 68% (60%,77%) and 72% (60%,83%) in the target trial [risk difference, -4 percentage points (pp; -17 pp,11 pp)] and 82% (81%,83%) and 93% (92%,95%) in the observational emulation [risk difference,-11 pp (-13 pp,-10 pp)]. CONCLUSIONS:Buprenorphine-naloxone might be superior to extended-release naltrexone in real-world settings where the majority of people struggle to remain on medications for opioid use disorder. Buprenorphine-naloxone initiators had a lower risk of treatment interruption than extended-release naltrexone initiators in an observational emulation, but similar risks in a randomized controlled trial, although confidence intervals were wide. Trial participation, study size and residual confounding may explain these differences.

Both psychotherapeutic interventions and pharmacological agents have demonstrated limited efficacy in the treatment of personality disorders (PDs). Emerging evidence suggests that psychedelic therapy, already showing promise in treating various psychiatric conditions commonly comorbid with PDs, may exert therapeutic effects by promoting adaptive changes in personality. Thus, psychedelic therapy could hold potential for addressing core features of PDs through shared mechanisms of personality modulation. Although historical literature and observational studies suggest the potential clinical utility of psychedelics in treating PDs, rigorous research is lacking, and individuals with PDs are often excluded from modern psychedelic therapy trials. In the present review, we first discuss research on the effects of psychedelics in individuals with a PD through the conventional lens of the Diagnostic and Statistical Manual of Mental Disorders (5th ed., text rev.; DSM-5-TR) categorical model. Next, using the dimensional DSM Alternative Model of Personality Disorders (DSM-AMPD) as a framework, we examine how psychedelics may affect self-functioning, interpersonal functioning, and pathological personality traits. We conclude by discussing the clinical relevance of psychedelic therapy as a treatment for personality pathology, including safety considerations, gaps and limitations, and recommendations for approaching psychedelic therapy within these more complex clinical populations.

INTRODUCTION/UNASSIGNED:Serotonergic psychedelics, serotonin 2A receptor agonists such as psilocybin that can result in substantially altered states of consciousness, are used in recreational and research settings. The safety of psychedelic experiences in research settings is supported by controlled physical environments, presence of clinical and medical staff to address emergent issues, screening for personal and family history of potential contraindications, and psychoeducational preparation with psychological support. Research settings typically provide psychoeducation to participants verbally and in writing (e.g., informed consent), and such documents and conversations can provide safety-related information-but may also introduce a wide range of expectancies. Such expectancies might involve the specific character of the acute subjective effects of psychedelics, possible side effects, and anticipated outcomes. METHODS/UNASSIGNED:To better understand the content of this psychoeducation, we gathered study materials from many psilocybin studies conducted in the past two decades in healthy and therapeutic populations. We conducted a reflexive thematic analysis to better understand these documents. RESULTS/UNASSIGNED:While these documents varied substantially between studies, we identified themes intended to lower levels of risk and optimize therapeutic effects from psychedelic treatments. The most frequently coded themes related to (1) biological and physical safety, (2) psychological safety and well-being, (3) aspects of setting, and (4) potential for expectancies. Prioritizing biological and psychological safety was evident in the materials from all sites. Furthermore, we identify potential contributors to expectancy unrelated to safety and suggest that these extrapharmacological elements be studied systematically in future research. CONCLUSIONS/UNASSIGNED:Ideally, future research should strive to maximize safety while attempting to minimize extraneous expectancies.

BACKGROUND/UNASSIGNED:Psilocybin can produce long-term changes in personality, personal values, and behavior. Although psilocybin-assisted therapy (PAT) is being actively studied for various psychiatric conditions, its effects on personal values in patients with alcohol use disorder (AUD) remain unexplored. This study examined the effects of PAT on personal values in patients with AUD and assessed relationships between value changes, acute psilocybin experiences, and drinking outcomes. METHODS/UNASSIGNED:-tests. Pearson correlations examined the relationship between value changes and acute effects, and also value changes and drinking outcomes. RESULTS/UNASSIGNED:= 0.31). None of the value changes were significantly associated with drinking outcomes. CONCLUSION/UNASSIGNED:PAT may alter value structure in patients with AUD patients by increasing Conservation. Although some associations were found between acute psychedelic effects and changes in Conservation, these value changes were not related to drinking outcomes.

BACKGROUND AND AIMS/OBJECTIVE:US regulatory changes allowed for additional methadone take-home doses following COVID-19 onset. How dispensing practices changed and which factors drove variation remains unexplored. We determined daily methadone dispensing trajectories over six months before and after regulatory changes due to COVID-19 using state sequence analysis and explored correlates. DESIGN/METHODS:Retrospective chart review of electronic health records. SETTINGS/METHODS:Nine opioid treatment programs (OTPs) across nine US states. PARTICIPANTS/METHODS:Adults initiating treatment in 2019 (n = 328) vs. initiating 1 month after the COVID-19 regulatory changes of March 2020 (n = 376). MEASUREMENTS/METHODS:Type of daily methadone medication encounter (in-clinic, weekend/holiday take-home, take-home, missed dose, discontinued) based on OTP clinic; cohort (pre vs. post-COVID-19); and patient substance use, clinical and sociodemographic characteristics. FINDINGS/RESULTS:Following COVID-19 regulatory changes, allotted methadone take-home doses increased from 3.5% to 13.8% of total person-days in treatment within the first 6 months in care. Clinic site accounted for the greatest variation in methadone dispensing (6.2% and 9.5% of the variation of discrepancy between sequences pre- and post-COVID-19, respectively). People who co-use methamphetamine had a greater increase in take-homes than people who did not use methamphetamine (from 3.7% pre-pandemic to 21.2% post-pandemic vs. 3.5% to 12.5%) and higher discontinuation (average 3.6 vs. 4.7 months among people who did not use methamphetamine pre-COVID-19; average 3.3 vs. 4.6 months post-COVID-19). In the post-COVID-19 cohort, females had a higher proportion of missed doses (17.2% vs. 11.9%) than males. People experiencing houselessness had a higher proportion of missed doses (19% vs. 12.3%) and shorter stays (average 3.5 vs. 4.5 months) when compared with those with stable housing. CONCLUSION/CONCLUSIONS:Daily methadone dispensing trajectories in the US both before and following COVID-19 regulatory changes appeared to depend more on the opioid treatment programs' practices than individual patient characteristics or response to treatment.

INTRODUCTION AND BACKGROUND/BACKGROUND:The three medications approved to address OUD are effective in decreasing opioid use and morbidity and mortality; however, their utility is limited by high rates of dropout from treatment. The CTN-0100 trial will develop an evidence base for strategies to improve retention on buprenorphine and extended-release naltrexone. RESEARCH DESIGN AND METHODS/METHODS:The National Drug Abuse Treatment Clinical Trials Network (CTN) study CTN-0100, "Optimizing Retention, Duration and Discontinuation Strategies for Opioid Use Disorder Pharmacotherapy" (RDD), is a multicenter, randomized, non-blinded trial enrolling more than a thousand patients from 18 community-based substance use disorder treatment programs. Participants are adult volunteers seeking to initiate medication treatment for OUD (MOUD). Individuals choose between buprenorphine or extended-release injectable naltrexone. The trial randomizes participants choosing buprenorphine, in a 3 × 2 factorial design, to a medication condition (standard-dose sublingual buprenorphine, high-dose sublingual buprenorphine, or extended-release injectable buprenorphine) and to a behavioral condition (Medical Management or Medical Management plus a digital therapeutic (smartphone) app). Individuals choosing extended-release naltrexone are randomized only to a behavioral condition. Participants receive study medication for 74 weeks and are then followed for a further 24 weeks. The primary outcome is successful retention on MOUD at 26 weeks (six months), with 50- and 74-week retention among the secondary outcomes. DISCUSSION/CONCLUSION/CONCLUSIONS:Dropout from treatment is a major barrier to the effectiveness of MOUD. The CTN-0100 study will determine whether strategies such as high dose sublingual or extended-release buprenorphine, or an app-based behavioral intervention improve retention on MOUD. CLINICALTRIALS/RESULTS:gov Identifier: NCT04464980.

AIMS/OBJECTIVE:Cannabis use is highly prevalent in patients seeking treatment for opioid use disorder. Studies have shown mixed results on the association between cannabis use and opioid use as well as the impact of MOUD on cannabis use. The current study aims to investigate the effects of buprenorphine versus naltrexone on cannabis use outcomes in treatment seeking individuals with Opioid Use Disorder (OUD). METHODS:The current study was based on data from the CTN-0051 X:BOT trial, which compared the time to return to significant opioid use survival outcomes of two treatment seeking groups, one receiving Extended-Release Naltrexone (XR-naltrexone) (N = 283) versus another receiving Buprenorphine-Naloxone (N = 287) for OUD. A mixed-effects logistic regression model including treatment assignment (buprenorphine-naloxone vs XR-naltrexone), time, and a time by treatment interaction was run on the sample with the odds of cannabis use as the outcome, as well as two cross-lagged mediation models to explore the prospective mediation of cannabis use on opioid use outcomes (and opioid use on cannabis use outcomes) by treatment assignment during the trial. RESULTS:There was a significant effect of buprenorphine treatment on reduced cannabis use. Participants receiving buprenorphine treatment were 39 % less likely to use cannabis than those receiving naltrexone over all the timepoints (p = .0499). No significant mediation was found between treatment assignment and opioid use on cannabis use outcomes or between treatment assignment and cannabis use on opioid use outcomes in this trial. CONCLUSION/CONCLUSIONS:Participants in this trial receiving buprenorphine treatment for OUD used less cannabis than those receiving naltrexone treatment.