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Background: Psilocybin is being studied for depression, but little is known about how it interacts with common antidepressants. Limited data suggest that psilocybin's effects may be diminished by serotonergic antidepressants acutely and even after a medication washout period. Aims: To learn the extent to which antidepressants may diminish the effects of psilocybin-containing mushrooms both concurrently and after discontinuation of antidepressants. Methods: Online retrospective survey of individuals with use of psilocybin mushrooms (1) with an antidepressant and/or (2) within 2 years of discontinuing an antidepressant. Participants who took mushrooms with an antidepressant and either took the same dose pre-antidepressant or took the same dose with other people not on antidepressant reported the strength of drug effects relative to their expectation. Participants who took mushrooms following discontinuation of an antidepressant also reported the presence of weakened effects. Results: In reports (n = 611) of taking mushrooms with an antidepressant, probabilities [95% CI] of weaker than expected drug effects were 0.47 [0.41–0.54] (selective serotonergic reuptake inhibitors, SSRIs), 0.55 [0.44–0.67] (serotonin norepinephrine reuptake inhibitors, SNRIs) and 0.29 [0.2–0.39] (bupropion). Following SSRI/SNRI discontinuation (n = 1,542 reports), the probability of reduced drug effects was not significantly different from the earliest post-discontinuation timepoint (within 1 week) until 3–6 months, probability = 0.3 [0.20–0.46], p = 0.001. A sensitivity analysis found that removing responses involving fluoxetine, which has an especially long half-life, did not significantly alter this result. Conclusions: SSRI/SNRIs appear to weaken psilocybin drug effects relative to a non-serotonergic antidepressant. This dampening effect may last as long as 3 months following antidepressant discontinuation. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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; M age=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. [ABSTRACT FROM AUTHOR]