Positive effects of psychedelics on depression and wellbeing scores in individuals reporting an eating disorder.

PURPOSE: Psychedelic therapy is showing promise for a broad range of mental health conditions, indicative of a transdiagnostic action. While the efficacy of symptom-focused treatments for eating disorders (EDs) is limited, improved mental health and psychological wellbeing are thought to contribute to greater treatment outcomes. This study provides the first quantitative exploration of the psychological effects of psychedelics in those reporting an ED diagnosis. METHODS: Prospective, online data were collected from individuals planning to take a psychedelic drug. Twenty-eight participants reporting a lifetime ED diagnosis completed measures of depressive symptomology (Quick Inventory of Depressive Symptomology; QIDS-SR16) and psychological wellbeing (Warwick-Edinburgh Mental Wellbeing Scale; WEMWBS) 1-2 weeks before, and 2 weeks after a psychedelic experience. Twenty-seven of these participants also completed a measure of emotional breakthrough [Emotional Breakthrough Inventory (EBI)] in relation to the acute psychedelic experience. RESULTS: Bayesian t tests demonstrated overwhelming evidence for improvements in depression and wellbeing scores following the psychedelic experience. Marginal evidence was also found for a correlation between emotional breakthrough and the relevant mental health improvements. CONCLUSION: These findings provide supportive evidence for positive psychological aftereffects of a psychedelic experience that are relevant to the treatment of EDs. It is hoped that this will encourage further research and will bolster initiatives to directly examine the safety and efficacy of psychedelic assisted therapy as a treatment of EDs in future clinical trials. LEVEL OF EVIDENCE: Level III, cohort study.

Canalization and plasticity in psychopathology.

This theoretical article revives a classical bridging construct, canalization, to describe a new model of a general factor of psychopathology. To achieve this, we have distinguished between two types of plasticity, an early one that we call 'TEMP' for 'Temperature or Entropy Mediated Plasticity', and another, we call 'canalization', which is close to Hebbian plasticity. These two forms of plasticity can be most easily distinguished by their relationship to 'precision' or inverse variance; TEMP relates to increased model variance or decreased precision, whereas the opposite is true for canalization. TEMP also subsumes increased learning rate, (Ising) temperature and entropy. Dictionary definitions of 'plasticity' describe it as the property of being easily shaped or molded; TEMP is the better match for this. Importantly, we propose that 'pathological' phenotypes develop via mechanisms of canalization or increased model precision, as a defensive response to adversity and associated distress or dysphoria. Our model states that canalization entrenches in psychopathology, narrowing the phenotypic state-space as the agent develops expertise in their pathology. We suggest that TEMP - combined with gently guiding psychological support - can counter canalization. We address questions of whether and when canalization is adaptive versus maladaptive, furnish our model with references to basic and human neuroscience, and offer concrete experiments and measures to test its main hypotheses and implications. This article is part of the Special Issue on "National Institutes of Health Psilocybin Research Speaker Series".

Psychedelic Communitas: Intersubjective Experience During Psychedelic Group Sessions Predicts Enduring Changes in Psychological Wellbeing and Social Connectedness.

Background: Recent years have seen a resurgence of research on the potential of psychedelic substances to treat addictive and mood disorders. Historically and contemporarily, psychedelic studies have emphasized the importance of contextual elements ('set and setting') in modulating acute drug effects, and ultimately, influencing long-term outcomes. Nevertheless, current small-scale clinical and laboratory studies have tended to bypass a ubiquitous contextual feature of naturalistic psychedelic use: its social dimension. This study introduces and psychometrically validates an adapted Communitas Scale, assessing acute relational experiences of perceived togetherness and shared humanity, in order to investigate psychosocial mechanisms pertinent to psychedelic ceremonies and retreats. Methods: In this observational, web-based survey study, participants (N = 886) were measured across five successive time-points: 2 weeks before, hours before, and the day after a psychedelic ceremony; as well as the day after, and 4 weeks after leaving the ceremony location. Demographics, psychological traits and state variables were assessed pre-ceremony, in addition to changes in psychological wellbeing and social connectedness from before to after the retreat, as primary outcomes. Using correlational and multiple regression (path) analyses, predictive relationships between psychosocial 'set and setting' variables, communitas, and long-term outcomes were explored. Results: The adapted Communitas Scale demonstrated substantial internal consistency (Cronbach's alpha = 0.92) and construct validity in comparison with validated measures of intra-subjective (visual, mystical, challenging experiences questionnaires) and inter-subjective (perceived emotional synchrony, identity fusion) experiences. Furthermore, communitas during ceremony was significantly correlated with increases in psychological wellbeing (r = 0.22), social connectedness (r = 0.25), and other salient mental health outcomes. Path analyses revealed that the effect of ceremony-communitas on long-term outcomes was fully mediated by communitas experienced in reference to the retreat overall, and that the extent of personal sharing or 'self-disclosure' contributed to this process. A positive relationship between participants and facilitators, and the perceived impact of emotional support, facilitated the emergence of communitas. Conclusion: Highlighting the importance of intersubjective experience, rapport, and emotional support for long-term outcomes of psychedelic use, this first quantitative examination of psychosocial factors in guided psychedelic settings is a significant step toward evidence-based benefit-maximization guidelines for collective psychedelic use.

Positive expectations predict improved mental-health outcomes linked to psychedelic microdosing.

Psychedelic microdosing describes the ingestion of near-threshold perceptible doses of classic psychedelic substances. Anecdotal reports and observational studies suggest that microdosing may promote positive mood and well-being, but recent placebo-controlled studies failed to find compelling evidence for this. The present study collected web-based mental health and related data using a prospective (before, during and after) design. Individuals planning a weekly microdosing regimen completed surveys at strategic timepoints, spanning a core four-week test period. Eighty-one participants completed the primary study endpoint. Results revealed increased self-reported psychological well-being, emotional stability and reductions in state anxiety and depressive symptoms at the four-week primary endpoint, plus increases in psychological resilience, social connectedness, agreeableness, nature relatedness and aspects of psychological flexibility. However, positive expectancy scores at baseline predicted subsequent improvements in well-being, suggestive of a significant placebo response. This study highlights a role for positive expectancy in predicting positive outcomes following psychedelic microdosing and cautions against zealous inferences on its putative therapeutic value.

[Reduced preoperative fasting periods. Current status after a survey of patients and colleagues]. / Verkürzte präoperative Nüchternheit. Erhebung eines Istzustands nach Analyse von Patienten- und Mitarbeiteraussagen.

BACKGROUND: Since October 2004 German Anaesthesiology Societies have officially recommended a decreased fasting period of 2 h for clear fluids and 6 h for solid food before elective surgery. A survey of patients and health care workers was carried out in our university clinic to assess the implementation of the new fasting recommendations. METHODS: Surgical patients (n=865) as well as physicians and nurses specialized in anaesthesia and surgery (n=2,355) were invited to complete a written questionnaire. The survey inquired about prescribed and practiced duration of fasting, attitudes towards reduced preoperative fasting and knowledge of the new guidelines. RESULTS: Data from 784 patients (91%) and 557 health care workers (24%) were analysed. Patients reported mean fasting times of 10+/-5 h for fluids and 15+/-4 h for solid food. Of the patients 52% and 16% would have preferred to drink and eat before surgery, respectively and 10% were informed about the new recommendations of shorter preoperative fluid and solid fasting. Such patients reported significantly reduced fasting times for fluids compared with those who were recommended to fast for the traditional longer periods (8+/-6 versus 12+/-4 h, p<0.001). Preoperative fasting advice remembered by the patients significantly differed from the prescribed recommendations (2 h fluid fasting, 22 versus 53%, p<0.001). Anaesthesiologists were significantly more knowledgeable of the new guidelines (90 versus 32-42%, p<0.001) and significantly more willing to recommend the new short preoperative fasting times (75 versus 15-19%, p<0.001) than other health care workers. Of all health care workers 82% and 32% reported patients' frequent desire to drink and eat before surgery, respectively, 92% considered reduced preoperative fasting to be positive, 76% feared increased risks for patients and 42% expected a decreased flexibility in their daily work. CONCLUSION: The current guidelines for preoperative fasting have not been widely implemented. Besides a knowledge discrepancy, remarkable concerns remain regarding higher risk for patients which may be important barriers to implementation. Nevertheless, health care workers are aware of patients' desire for shorter preoperative fasting. If the new guidelines are recommended patients will make use of them. Further training of staff and adequate implementation tools are needed.

Supportive use of megestrol acetate in patients with head and neck cancer during radio(chemo)therapy.

To study the supportive effect of megestrol acetate during intensive combined modality treatment, a randomised, double-blind, placebo-controlled study was performed in patients with head and neck cancer. The patients received either 160 mg of megestrol acetate daily or placebo during radio(chemo)therapy and for up to 6 weeks thereafter. The nutritional status as measured by anthropometric and biochemical parameters and the subjective quality of life were assessed prior to therapy, at weeks 1, 4 and 6 of radiotherapy and 12 and 18 weeks from the start of therapy. 61 of 64 patients were evaluable. In the control group (n = 30), the nutritional parameters deteriorated during therapy and were fully restored during follow-up. By contrast, the patients treated with megestrol acetate (n = 31) could maintain their baseline values. The difference between the groups was most pronounced in patients taking food per mouth (weight loss during treatment: control group: 4.1 kg; megestrol acetate group: 0.8 kg, P = 0.0004), but was not significant in patients fed via percutaneous endoscopically guided gastrostomy (PEG). Subjective quality of life remained constant in the megestrol acetate group while it decreased in the control group. However, differences were not statistically significant. Megestrol acetate prevents further deterioration of nutritional status during radio(chemo)therapy and may have an impact on subjective quality of life.

Paclitaxel and simultaneous radiation in the treatment of stage IIIA/B non-small cell lung cancer.

In a clinical phase II trial, escalating doses of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) were given with concurrent radiation to patients with stage IIIA/B non-small cell lung cancer. Radiotherapy was given in daily doses of 2 Gy, 5 days a week, in weeks 1 through 3 and 6 through 8. Paclitaxel was given on day 1 of weeks 1 through 3 and 6 through 8, at a starting dose level of 50 mg/m2. Subsequent paclitaxel dose levels were 60, 72, 86, and 103 mg/m2. Three to six patients were included at each dose level until intolerable toxicity (World Health Organization grade 3 or 4 leukopenia) occurred in three of six patients. To date, 27 patients have entered the protocol. Hematologic toxicity was mild with no severe myelosuppression up to the 86-mg/m2 dose level. At paclitaxel 103 mg/m2, four of six patients developed grade 3 or 4 leukopenia, and dose escalation was stopped. The maximum tolerated dose was thus determined to be 86 mg/m2. The main clinical toxicity was the occurrence of pulmonary infections (seven patients), one of whom had Pneumocystis carinii infection; the six others had interstitial infections with no pathogen isolated. Mild to moderate esophagitis was seen in five patients. Thus far, of 24 patients evaluable for response, 18 showed decreased tumor size. Four patients achieved major responses (near-complete disappearance of radiologic tumor signs), 11 patients achieved partial remission, and three patients had a minor response. The overall response rate was 75%. In summary, the maximum tolerated dose of paclitaxel in this study has been determined to be 86 mg/m2 weekly. Pulmonary infections represent the major clinical toxicity, and the high response rate merits further clinical evaluation of this regimen.

[Supportive treatment with megestrol acetate during radio(chemo)therapy in patients with tumors in the head-neck area. A randomized study]. / Supportive Behandlung mit Megestrolacetat während der Radio-(Chemo-)Therapie bei Patienten mit Tumoren im Kopf-Hals-Bereich. Eine randomisierte Studie.

BACKGROUND: The value of megestrol acetate in treating tumor anorexia and cachexia of terminal patients is well known. However, the supportive effect of megestrol acetate during intensive radio-(chemo-)therapy was not investigated up to now. Therefore a randomized trial was performed including patients with advanced tumors in the head and neck region. PATIENTS AND METHODS: From June 1991 to December 1993 a total of 64 patients were admitted to a randomized, double-blind placebo-controlled study. During and up to 6 weeks following radiotherapy patients received 160 mg/d megestrol acetate or placebo. The nutritional status (anthropometric and laboratory parameters) and the quality-of-life index according to Padilla et al. [24] were determined prior to therapy, 1, 4, 6 weeks later during radiotherapy and 12, 18 weeks after completion. RESULTS: Sixty-one out of 64 patients were evaluable (control group: n = 30; megestrol acetate patients: n = 31). One patient refused further participation after randomization. One patient in each arm was excluded due to side effects (impotence, diarrhoea). Further side effects were not observed. In the control group the nutritional parameters (body weight, triceps skinfold) and the subjective feeling of the patients deteriorated during radiotherapy and did not restore following radiotherapy. By contrast, the patients of the megestrol acetate group were able to stabilize these parameters. This difference was most prominent in the orally nourished patients (weight loss during therapy: control group: -4.1 kg; megestrol acetate group: -0.8 kg; p = 0.004); but not in the patients fed by percutaneous endoscopically guided gastrostomy (weight loss control group: -2.4 kg; megestrol acetate group: -0.8 kg; p = 0.14). CONCLUSION: In patients on radiochemotherapy megestrol acetate prevents patients from further deterioration of the nutritional status and quality of life.

Dose-response of simvastatin in primary hypercholesterolemia.

In an 8-week, placebo-controlled multicenter study, the efficacy of dose levels of simvastatin 2.5, 5, 10, 20, and 40 mg was evaluated in 166 patients with hypercholesterolemia, of whom 163 completed the trial. The entry criteria were serum total cholesterol (TCHOL) between 6.2 and 7.8 mM and low-density lipoprotein (LDL) cholesterol between 4.3 and 50 mM on a standard diet and after the 2-week run-in period of placebo treatment. Mean percentage changes in serum lipids in each simvastatin-treated group from baseline were statistically significant. Of treated patients, 0% (placebo), 11% (2.5 mg), 7% (5 mg), 33% (10 mg), 42% (20 mg) and 55% (40 mg) had at least 40% reduction from baseline LDL cholesterol value. After 8 weeks of treatment, 0% (placebo), 11% (2.5 mg), 25% (5 mg), 26% (10 mg), 31% (20 mg), and 55% (40 mg) of patients treated reached a TCHOL level of < or = 5.2 mM. There was a significant linear dose response with regard to the decrease in LDL cholesterol, TCHOL, and triglycerides (TG) and the increase in high-density lipoprotein (HDL) cholesterol after 8 weeks of therapy. No serious clinical or laboratory adverse events related to simvastatin were observed even at higher doses. At each dose level, simvastatin reduced TCHOL and LDL cholesterol. Doses of simvastatin > or = 5 mg moderately increased HDL cholesterol and reduced serum TG. Simvastatin therapy resulted in major improvement in serum lipoprotein profile, particularly at higher doses.