Background: Preliminary data suggest that psilocybin-assisted treatment produces substantial and rapid antidepressant effects in patients with major depressive disorder (MDD), but little is known about long-term outcomes. Aims: This study sought to examine the efficacy and safety of psilocybin through 12 months in participants with moderate to severe MDD who received psilocybin. Methods: This randomized, waiting-list controlled study enrolled 27 patients aged 21–75 with moderate to severe unipolar depression (GRID-Hamilton Depression Rating Scale (GRID-HAMD) ⩾ 17). Participants were randomized to an immediate or delayed (8 weeks) treatment condition in which they received two doses of psilocybin with supportive psychotherapy. Twenty-four participants completed both psilocybin sessions and were followed through 12 months following their second dose. Results: All 24 participants attended all follow-up visits through the 12-month timepoint. Large decreases from baseline in GRID-HAMD scores were observed at 1-, 3-, 6-, and 12-month follow-up (Cohen d = 2.3, 2.0, 2.6, and 2.4, respectively). Treatment response (⩾50% reduction in GRID-HAMD score from baseline) and remission were 75% and 58%, respectively, at 12 months. There were no serious adverse events judged to be related to psilocybin in the long-term follow-up period, and no participants reported psilocybin use outside of the context of the study. Participant ratings of personal meaning, spiritual experience, and mystical experience after sessions predicted increased well-being at 12 months, but did not predict improvement in depression. Conclusions: These findings demonstrate that the substantial antidepressant effects of psilocybin-assisted therapy may be durable at least through 12 months following acute intervention in some patients.

Background: Several measures have been developed to examine acute psychedelic effects (e.g. mystical-type and challenging experiences), but no measure assesses acute psychologically insightful experiences that may occur during psychedelic experiences. Aim: The purpose of this study was to develop and examine the psychometric properties of the Psychological Insight Questionnaire. Method: A cross-sectional survey study among psilocybin and LSD users. Respondents ( n=1661; Mage=22.9, standard deviation=8.5; Caucasian/White=83%; non-Hispanic=91%; men=72%; United States resident=66%) completed an Internet-based survey. Results: The Psychological Insight Questionnaire consists of 23 items with two subscales: (a) Avoidance and Maladaptive Patterns Insights and (b) Goals and Adaptive Patterns Insights. Construct validity of the Psychological Insight Questionnaire was supported by strong correlations of the Psychological Insight Questionnaire (and Avoidance and Maladaptive Patterns Insights and Goals and Adaptive Patterns Insights subscales) scores with the insight subscale of the Session Impacts Scale, and weak-to-moderate correlations with the Mystical Experiences and Challenging Experiences Questionnaires. Furthermore, Psychological Insight Questionnaire (and Avoidance and Maladaptive Patterns Insights and Goals and Adaptive Patterns Insights subscales) scores were moderately-to-strongly correlated with retrospectively reported increases in psychological flexibility, and well-being/life satisfaction that were attributed to a memorable psychedelic experience. Lastly, incremental validity was established showing that the Psychological Insight Questionnaire (and Avoidance and Maladaptive Patterns Insights subscale) scores predict unique variance in changes in psychological flexibility, and Psychological Insight Questionnaire (and Avoidance and Maladaptive Patterns Insights and Goals and Adaptive Patterns Insights subscales) scores predict changes in well-being and life satisfaction, beyond measures of acute mystical-type and challenging effects. Conclusions: The Psychological Insight Questionnaire has the potential to extend the understanding of the acute and enduring effects of psychedelics. Further longitudinal research is necessary to determine the long-term predictive validity of the Psychological Insight Questionnaire and to examine the role of psychological insight in predicting therapeutic outcomes.

Psychedelic-assisted treatment is at first glance markedly different in structure and approach from mainstream forms of psychotherapy in the West. A major criticism of clinical psychedelic research rests on the difficulty of executing placebo-controlled studies and distinguishing drug effects from those of the psychotherapeutic container in which psychedelics are typically presented. Detractors also tend to find fault in spiritual or mystical themes that often arise in the context of psychedelic use. Common factors theory of psychotherapy is a useful and extensively studied framework that can help make sense of these issues, and has much to contribute to our understanding of contextual effects that are often discussed in psychedelic literature as “set and setting.” In this article, we examine four major contextual “common factors” shared by various healing traditions: 1) the therapeutic relationship; 2) the healing setting; 3) the rationale, conceptual scheme, or myth; and 4) the ritual. We explain how these factors show up in psychedelic-assisted treatment and how they may contribute to therapeutic effects. Lastly, we discuss the implications of these factors for the concept of placebo, and for future research.

Background Risk stratification of ambulatory heart failure (HF) patients has relied upon peak VO2 (pVO2) <14 mL/min/kg. We investigated whether additional clinical variables might further specify risk of death, ventricular assist device (VAD) implantation (INTERMACS<4) or heart transplantation (HTx; Status 1A or 1B) within one-year after HTx evaluation. We hypothesized that right ventricular stroke work index (RVSWI), pulmonary capillary wedge pressure (PCWP) and the Model for End-stage Liver Disease-Albumin score (MELD-A) would be additive prognostic predictors. Methods We retrospectively collected data on 151 ambulatory patients undergoing HTx evaluation. Primary outcomes were defined as HTx, LVAD or death within one-year following evaluation. Results Our cohort was 54.9±11.1 year-old, 79.1% male, 37.6% with ischemic etiology (LVEF 21±11% and pVO2 12.6±3.5ml/min/kg). Fifty outcomes (33.1%) occurred (27 HTx, 15 VAD, and 8 deaths). Univariate logistic regression showed significant association of RVSWI (mmHg-L/m2) (OR0.47, p=0.036), PCWP (mmHg) (OR2.65, p=0.007), and MELD-A (OR2.73, p=0.006) with one-year events. Stepwise regression showed independent correlation of RVSWI<5 (OR6.70; p<0.01), PCWP>20 (OR5.48; p<0.01), MELD-A>14 (OR3.72; p<0.01) and pVO2<14 (OR3.36; p=0.024) with one-year events. A scoring system was composed with MELD-A>14 and pVO2<14, 1 point each, and PCWP>20 and RVSWI<5, 2 points each. A cutoff at 4 demonstrated a 54% sensitivity and 88% specificity for one-year events. Conclusions Ambulatory HF patients have significant one-year event rates. Risk stratification based on exercise performance, left-sided congestion, right ventricular dysfunction and liver congestion allows prediction of one-year prognosis. This study endorses early and timely referral for VAD and/or transplant.