Faculty Bibliography

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.

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.

BACKGROUND AND AIMS/OBJECTIVE:The opioid crisis continues to exert a tremendous toll in North America, with existing interventions often falling short of addressing ongoing needs. Psychedelics are emerging as a possible alternative therapy for mental health and substance use disorders. This study aimed to gather insights on how people use or are considering using psychedelics to manage opioid use disorder (OUD), how these experiences are perceived to impact opioid use and what these lessons imply for future research and practice. METHODS:We conducted a qualitative study using the Reddit online community platform. We extracted posts that contained key psychedelic terms from the two most subscribed-to subreddits dedicated to discussions of OUD treatment (r/OpiatesRecovery and r/Methadone) from 2018 to 2021. We thematically analyzed content from 151 relevant posts and their respective comments. RESULTS:Two prominent themes identified in discussions were perspectives on the effectiveness of psychedelics in treating OUD, and mechanisms through which psychedelics were thought to impact use and desire to use opioids. For many, psychedelics were deemed to have a strong impact on opioid use via multiple mechanisms, including alleviating physical symptoms of dependence, shifting motivations around desire to use opioids and addressing underlying mental health problems and reasons for use. Others saw the potential promise around psychedelics as exaggerated, acknowledging many people eventually return to use, or even considered psychedelics dangerous. CONCLUSIONS:There appear to be diverse perspectives on the effects of using psychedelics to treat opioid use disorder and an urgent need for controlled studies to better understand the impact of different psychedelics on opioid use, how they may be used in the context of existing treatments and what strategies they must be combined with to ensure safety and effectiveness. Integrating the experiences of people who use drugs will help guide psychedelics research toward effective person-centered interventions to enhance health and wellness.

OBJECTIVE/UNASSIGNED:Evidence suggests that psilocybin-assisted therapy (PAT) leads to durable shifts in personality structure. However, such changes have yet to be characterized in disorders of addiction. In this secondary analysis from a randomized controlled trial, the authors examined the effect of PAT on personality dimensions in patients with alcohol use disorder (AUD), hypothesizing that PAT would attenuate personality abnormalities in AUD and that reductions in trait impulsiveness would be associated with lower drinking. METHODS/UNASSIGNED:Eighty-four adults with AUD were randomized to two medication sessions of either psilocybin (N=44) or active placebo (diphenhydramine; N=40), received 12 weekly psychotherapy sessions, and completed follow-up for an additional 24 weeks. Changes in personality traits (week 36 vs. baseline) were assessed with the revised NEO Personality Inventory; daily alcohol consumption was quantified using the timeline followback. RESULTS/UNASSIGNED:Relative to the placebo group, the psilocybin group showed significant reductions in neuroticism and increases in extraversion and openness. Secondary analyses showed that reductions in neuroticism were driven by decreases in the facets depression, impulsiveness, and vulnerability; increases in openness were driven by increases in the facets openness toward feelings and fantasy. Across all participants, decreases in impulsiveness were associated with lower posttreatment alcohol consumption, and an exploratory analysis revealed that these associations were strongest among psilocybin-treated participants who continued moderate- or high-risk drinking prior to the first medication session. CONCLUSIONS/UNASSIGNED:PAT elicited durable shifts in personality, suggesting normalization of abnormal personality trait expression in AUD. Further study is needed to clarify whether PAT exerts its beneficial effects by reducing impulsiveness or whether impulsive individuals inherently respond better to PAT.

Existential distress is commonly experienced by patients diagnosed with a life-threatening illness. This condition has been shown to adversely impact quality of life and is correlated with increased suicidal ideation and requests for hastened death. While palliative care teams are experienced in treating depression and anxiety, existential distress is a distinct clinical condition for which traditional medications and psychotherapy approaches demonstrate limited efficacy or duration of effect. Psychedelic drugs, including psilocybin and lysergic acid diethylamide (LSD), in conjunction with psychotherapy have been shown to produce rapid and sustained reductions in existential and psychiatric distress and may be a promising treatment for patients facing existential distress in palliative care settings. In this narrative review article, we describe the history of psychedelic medicine including early studies and the modern wave of research over the past 20 years, which includes high quality clinical trial data. This review outlines specific considerations for therapeutic application of psilocybin including pharmacokinetics, patient selection, dosing, protocol designs, and safeguards to reduce potential adverse effects to help guide future psychedelic practitioners. With growing public interest and evolving state level policy reforms allowing access to psychedelic treatments, it is critical for palliative care providers to gain familiarity with the current state of science and the potential of psilocybin assisted psychotherapy in the treatment of existential distress.