Faculty Bibliography

Borderline personality disorder is a complex psychiatric disorder with limited treatment options that are associated with large heterogeneity in treatment response and high rates of dropout. New or complementary treatments for borderline personality disorder are needed that may be able to bolster treatment outcomes. In this review, the authors comment on the plausibility for research on 3,4-methylenedioxymethamphetamine (MDMA) used in conjunction with psychotherapy for borderline personality disorder (i.e., MDMA-assisted psychotherapy [MDMA-AP]). On the basis of the promise of MDMA-AP in treating disorders overlapping with borderline personality disorder (e.g., posttraumatic stress disorder), the authors speculate on initial treatment targets and hypothesized mechanisms of change that are grounded in prior literature and theory. Initial considerations for designing MDMA-AP clinical trials to investigate the safety, feasibility, and preliminary effects of MDMA-AP for borderline personality disorder are also presented.

BACKGROUND:Overdose education and naloxone distribution (OEND) trains people who use opioids (PWUO) in how to intervene in cases of opioid overdose but best practices have not been assessed empirically. METHODS:PWUO along with a significant other (SO) were randomized to one of three training conditions. In the Treatment-as-Usual (TAU) condition, participants were randomized to receive minimal overdose-related education. In the extended training (ET) condition, PWUO received an extended training, while their SO received no overdose training. In the final condition, both the participant and SO received the extended overdose training (ETwSO). Outcome measures were naloxone use and overdose knowledge and competency assessed immediately before and after training, and at 1-, 3-, 6-, and 12-month timepoints following training. RESULTS:Three hundred and twenty-one PWUO (w/ a SO) were randomized. All intensities of OD training were associated with sustained increases in OD knowledge/ competency (versus pre-training baseline p's < 0.01). PWUO intervened in 166 ODs. The 12-month incidence of naloxone use did not significantly differ between groups. Extended training (ET + ETwSO) compared to TAU resulted in significantly greater naloxone utilization by: 30 days (10.1% vs 4.1%, p = 0.041), 60 days (16.4% vs 5.2%, p<0.001) and 90 days (17.9% vs 9.5%, p = 0.039). CONCLUSIONS:All intensities of OD training were associated with sustained increases in OD knowledge and competency, and equivalent rates of successful naloxone use. More extensive training increased naloxone utilization during the first 3 months. However, the benefits of more comprehensive training should be balanced against feasibility.

People with advanced cancer are at heightened risk of desire for hastened death (DHD), suicidal ideation (SI), and completed suicide. Loss of Meaning (LoM), a component of demoralization, can be elevated by a cancer diagnosis and predicts DHD and SI in this population. We completed a randomized controlled trial in which psilocybin-assisted psychotherapy (PAP) produced rapid and sustained improvements in depression, demoralization, and hopelessness in people with cancer. Converging epidemiologic and clinical trial findings suggests a potential antisuicidal effect of this treatment. To probe our hypothesis that PAP relieves SI through its beneficial impacts on depression and demoralization (LoM in particular), we performed secondary analyses assessing within- and between-group differences with regard to LoM and an SI composite score. Among participants with elevated SI at baseline, PAP was associated with within-group reductions in SI that were apparent as early as 8 h and persisted for 6.5 months postdosing. PAP also produced large reductions in LoM from baseline that were apparent 2 weeks after treatment and remained significant and robust at the 6.5 month and 3.2 and 4.5 year follow-ups. Exploratory analyses support our hypothesis and suggest that PAP may be an effective antisuicidal intervention following a cancer diagnosis due to its positive impact on hopelessness and demoralization and its effects on meaning-making in particular. These preliminary results implicate psilocybin treatment as a potentially effective alternative to existing antidepressant medications in patients with cancer that are also suicidal, and warrant further investigation in participants with elevated levels of depression and suicidality.

Importance/UNASSIGNED:Opioid addiction is a major public health problem. Despite availability of evidence-based treatments, relapse and dropout are common outcomes. Efforts aimed at identifying reuse risk and gaining more precise understanding of the mechanisms conferring reuse vulnerability are needed. Objective/UNASSIGNED:To use tools from computational psychiatry and decision neuroscience to identify changes in decision-making processes preceding opioid reuse. Design, Setting, and Participants/UNASSIGNED:A cohort of individuals with opioid use disorder were studied longitudinally at a community-based treatment setting for up to 7 months (1-15 sessions per person). At each session, patients completed a risky decision-making task amenable to computational modeling and standard clinical assessments. Time-lagged mixed-effects logistic regression analyses were used to assess the likelihood of opioid use between sessions (t to t + 1; within the subsequent 1-4 weeks) from data acquired at the current session (t). A cohort of control participants completed similar procedures (1-5 sessions per person), serving both as a baseline comparison group and an independent sample in which to assess measurement test-retest reliability. Data were analyzed between January 1, 2018, and September 5, 2019. Main Outcomes and Measures/UNASSIGNED:Two individual model-based behavioral markers were derived from the task completed at each session, capturing a participant's current tolerance of known risks and ambiguity (partially unknown risks). Current anxiety, craving, withdrawal, and nonadherence were assessed via interview and clinic records. Opioid use was ascertained from random urine toxicology tests and self-reports. Results/UNASSIGNED:Seventy patients (mean [SE] age, 44.7 [1.3] years; 12 women and 58 men [82.9% male]) and 55 control participants (mean [SE] age, 42.4 [1.5] years; 13 women and 42 men [76.4% male]) were included. Of the 552 sessions completed with patients (mean [SE], 7.89 [0.59] sessions per person), 252 (45.7%) directly preceded opioid use events (mean [SE], 3.60 [0.44] sessions per person). From the task parameters, only ambiguity tolerance was significantly associated with increased odds of prospective opioid use (adjusted odds ratio, 1.37 [95% CI, 1.07-1.76]), indicating patients were more tolerant specifically of ambiguous risks prior to these use events. The association of ambiguity tolerance with prospective use was independent of established clinical factors (adjusted odds ratio, 1.29 [95% CI, 1.01-1.65]; P = .04), such that a model combining these factors explained more variance in reuse risk. No significant differences in ambiguity tolerance were observed between patients and control participants, who completed 197 sessions (mean [SE], 3.58 [0.21] sessions per person); however, patients were more tolerant of known risks (B = 0.56 [95% CI, 0.05-1.07]). Conclusions and Relevance/UNASSIGNED:Computational approaches can provide mechanistic insights about the cognitive factors underlying opioid reuse vulnerability and may hold promise for clinical use.

BACKGROUND/UNASSIGNED:A recently published randomized controlled trial compared single-dose psilocybin with single-dose niacin in conjunction with psychotherapy in participants with cancer-related psychiatric distress. Results suggested that psilocybin-assisted psychotherapy facilitated improvements in psychiatric and existential distress, quality of life, and spiritual well-being up to seven weeks prior to the crossover. At the 6.5-month follow-up, after the crossover, 60-80% of participants continued to meet criteria for clinically significant antidepressant or anxiolytic responses. METHODS/UNASSIGNED:The present study is a long-term within-subjects follow-up analysis of self-reported symptomatology involving a subset of participants that completed the parent trial. All 16 participants who were still alive were contacted, and 15 participants agreed to participate at an average of 3.2 and 4.5 years following psilocybin administration. RESULTS/UNASSIGNED:Reductions in anxiety, depression, hopelessness, demoralization, and death anxiety were sustained at the first and second follow-ups. Within-group effect sizes were large. At the second (4.5 year) follow-up approximately 60-80% of participants met criteria for clinically significant antidepressant or anxiolytic responses. Participants overwhelmingly (71-100%) attributed positive life changes to the psilocybin-assisted therapy experience and rated it among the most personally meaningful and spiritually significant experiences of their lives. CONCLUSION/UNASSIGNED:These findings suggest that psilocybin-assisted psychotherapy holds promise in promoting long-term relief from cancer-related psychiatric distress. Limited conclusions, however, can be drawn regarding the efficacy of this therapy due to the crossover design of the parent study. Nonetheless, the present study adds to the emerging literature base suggesting that psilocybin-facilitated therapy may enhance the psychological, emotional, and spiritual well-being of patients with life-threatening cancer.

Cancer is highly prevalent and one of the leading causes of global morbidity and mortality. Psychological and existential suffering is common in cancer patients, associated with poor psychiatric and medical outcomes. Promising early-phase clinical research (1960s to early 1970s) suggested a therapeutic signal for serotoninergic psychedelics (e.g. psilocybin, LSD) in treating cancer-related psychiatric distress. After several decades of quiescence, research on psychedelic-assisted therapy to treat psychiatric disorders in cancer patients has resumed within the last 2 decades in the US and Europe. This review article is based on a systematic search of clinical trials from 1960-2018 researching the therapeutic use of psychedelic treatment in patients with serious or terminal illnesses and related psychiatric illness. The search found 10 eligible clinical trials, with a total of 445 participants, with the vast majority of the patients having advanced or terminal cancer diagnoses. Six open label trials, published between 1964 and 1980 (n = 341), suggested that psychedelic therapy (mostly with LSD) may improve cancer-related depression, anxiety, and fear of death. Four RCTs trials were published between 2011 and 2016 (n = 104), mostly with psilocybin treatment (n = 92), and demonstrated that psychedelic-assisted treatment can produce rapid, robust, and sustained improvements in cancer-related psychological and existential distress.