Dose–response relationships of psilocybin-induced subjective experiences in humans

Background: Psilocybin is the psychoactive component in Psilocybe mushrooms (‘magic mushrooms’). Whether and how the quality of the psilocybin-induced experience might mediate beneficial health outcomes is currently under investigation, for example, in therapeutic applications. However, to date, no meta-analysis has investigated the dose-dependency of subjective experiences across available studies. Aim: Establishing dose–response relationships of the subjective experiences induced by psilocybin in healthy study participants and a comparison of patient groups. Method: We applied a linear meta-regression approach, based on the robust variance estimation framework, to obtain linear dose–response relationship estimates on questionnaire ratings after oral psilocybin administration. Data were obtained from the Altered States Database, which contains data extracted from MEDLINE-listed journal articles that used standardized and validated questionnaires: the Altered States of Consciousness Rating Scale, the Mystical Experience Questionnaire and the Hallucinogen Rating Scale. Results: Psilocybin dose positively correlated with ratings on most factors and scales, mainly those referring to perceptual alterations and positively experienced ego dissolution. Measures referring to challenging experiences exhibited small effects and were barely modulated by dose. Conclusion: Psilocybin intensified almost all characteristics of altered states of consciousness assessed with the given questionnaires. Because subjective experiences are not only determined by dose, but also by individual and environmental factors, the results may only apply to controlled laboratory experiments and not to recreational use. This paper may serve as a general literature citation for the use of psilocybin in experimental and clinical research, to compare expected and observed subjective experiences

Dose-response relationships of LSD-induced subjective experiences in humans

Lysergic acid diethylamide (LSD) is a potent classic serotonergic psychedelic, which facilitates a variety of altered states of consciousness. Here we present the first meta-analysis establishing dose-response relationship estimates of the altered states of consciousness induced by LSD. Data extracted from articles identified by a systematic literature review following PRISMA guidelines were obtained from the Altered States Database. The psychometric data comprised ratings of subjective effects from standardized and validated questionnaires: the Altered States of Consciousness Rating Scale (5D-ASC, 11-ASC) and the Mystical Experience Questionnaire (MEQ30). We performed meta-regression analyses using restricted cubic splines for data from studies with LSD doses of up to 200 μg base. Most scales revealed a sigmoid-like increase of effects, with a plateauing at around 100 μg. The most strongly modulated factors referred to changes in perception and illusory imagination, followed by positively experienced ego-dissolution, while only small effects were found for Anxiety and Dread of Ego Dissolution. The considerable variability observed in most factors and scales points to the role of non-pharmacological factors in shaping subjective experiences. The established dose-response relationships may be used as general references for future experimental and clinical research on LSD to compare observed with expected subjective effects and to elucidate phenomenological differences between psychedelics

Comparative phyloinformatics of virus genes at micro and macro levels in a distributed computing environment

<p>Abstract</p> <p>Background</p> <p>Preparedness for a possible global pandemic caused by viruses such as the highly pathogenic influenza A subtype H5N1 has become a global priority. In particular, it is critical to monitor the appearance of any new emerging subtypes. Comparative phyloinformatics can be used to monitor, analyze, and possibly predict the evolution of viruses. However, in order to utilize the full functionality of available analysis packages for large-scale phyloinformatics studies, a team of computer scientists, biostatisticians and virologists is needed – a requirement which cannot be fulfilled in many cases. Furthermore, the time complexities of many algorithms involved leads to prohibitive runtimes on sequential computer platforms. This has so far hindered the use of comparative phyloinformatics as a commonly applied tool in this area.</p> <p>Results</p> <p>In this paper the graphical-oriented workflow design system called <it>Quascade </it>and its efficient usage for comparative phyloinformatics are presented. In particular, we focus on how this task can be effectively performed in a distributed computing environment. As a proof of concept, the designed workflows are used for the phylogenetic analysis of neuraminidase of H5N1 isolates (micro level) and influenza viruses (macro level). The results of this paper are hence twofold. Firstly, this paper demonstrates the usefulness of a graphical user interface system to design and execute complex distributed workflows for large-scale phyloinformatics studies of virus genes. Secondly, the analysis of neuraminidase on different levels of complexity provides valuable insights of this virus's tendency for geographical based clustering in the phylogenetic tree and also shows the importance of glycan sites in its molecular evolution.</p> <p>Conclusion</p> <p>The current study demonstrates the efficiency and utility of workflow systems providing a biologist friendly approach to complex biological dataset analysis using high performance computing. In particular, the utility of the platform Quascade for deploying distributed and parallelized versions of a variety of computationally intensive phylogenetic algorithms has been shown. Secondly, the analysis of the utilized H5N1 neuraminidase datasets at macro and micro levels has clearly indicated a pattern of spatial clustering of the H5N1 viral isolates based on geographical distribution rather than temporal or host range based clustering.</p

Connected to the spirit of the frog: An Internet-based survey on Kambô, the secretion of the Amazonian Giant Maki Frog (Phyllomedusa bicolor): Motivations for use, settings and subjective experiences

Background/aim: Kambô is a name for the secretion of the Giant Maki Frog (Phyllomedusa bicolor), which has been used by indigenous cultures from the Amazonas basin and has recently become popular in alternative healing circles in Western countries, with a certain overlap with psychedelic self-exploration. Methods: We carried out an online-based survey in English (54.92%) and German investigating motivations for using Kambô, settings in which rituals take place, and subjective experiences during and after the application. Results: Participants (n = 386, mean age: 38.08 years, (standard deviation = 9.95)) were well-educated individuals with an increased lifetime prevalence of the use of ayahuasca (67.88%). A plethora of motivations for using Kambô was reported, including general healing, detoxification and spiritual growth. Acute effects included severe physical reactions and mild psychoactive effects, most surprisingly, the feeling of being connected to the frog’s spirit (41.97%), whereas predominantly positive persisting psychological effects were reported. Few participants reported long-lasting physical (2.85%) or mental (1.81%) health problems which they attributed to Kambô. Of the participants, 87.31% reported an increase in personal well-being or life satisfaction, and 64.26% considered Kambô to have been at least of ‘very much’ spiritual significance for their lives. Conclusions: The majority of users claimed beneficial effects including more health-orientated behaviors, whereas only very few participants complained about new health problems which they ascribed to Kambô. In retrospect, Kambô was given a high personal and spiritual significance by many participants. Additional research is needed to determine in how far reported effects are modulated by setting and subjective expectations

The Altered States Database: Psychometric data from a systematic literature review

In this paper, we present the development of the Altered States Database (ASDB), an open-science project based on a systematic literature review. The ASDB contains psychometric questionnaire data on subjective experiences of altered states of consciousness (ASC) induced by pharmacological and non-pharmacological methods. The systematic review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Scientific journal articles were identified through PubMed and Web of Science. We included studies that examined ASC using the following validated questionnaires: Altered States of Consciousness Rating Scale (APZ, 5D-ASC, 11-ASC), Phenomenology of Consciousness Inventory (PCI), Hallucinogen Rating Scale (HRS), or Mystical Experience Questionnaire (MEQ30). The systematic review resulted in the inclusion of a total of 165 journal articles, whereof questionnaire data was extracted and is now available on the Open Science Framework (OSF) website (https://osf.io/8mbru) and on the ASDB website (http://alteredstatesdb.org), where questionnaire data can be easily retrieved and visualized. This data allows the calculation of comparable psychometric values of ASC experiences and of dose-response relationships of substances inducing ASC

Content Representation of Tactile Mental Imagery in Primary Somatosensory Cortex

The imagination of tactile stimulation has been shown to activate primary somatosensory cortex (S1) with a somatotopic specificity akin to that seen during the perception of tactile stimuli. Using fMRI and multivariate pattern analysis, we investigate whether this recruitment of sensory regions also reflects content-specific activation (i.e., whether the activation in S1 is specific to the mental content participants imagined). To this end, healthy volunteers (n = 21) either perceived or imagined three types of vibrotactile stimuli (mental content) while fMRI data were acquired. Independent of the content, during tactile mental imagery we found activation of frontoparietal regions, supplemented with activation in the contralateral BA2 subregion of S1, replicating previous reports. While the imagery of the three different stimuli did not reveal univariate activation differences, using multivariate pattern classification, we were able to decode the imagined stimulus type from BA2. Moreover, cross-classification revealed that tactile imagery elicits activation patterns similar to those evoked by the perception of the respective stimuli. These findings promote the idea that mental tactile imagery involves the recruitment of content-specific activation patterns in sensory cortices, namely in S1

Content Representation of Tactile Mental Imagery in Primary Somatosensory Cortex

The imagination of tactile stimulation has been shown to activate primary somatosensory cortex (S1) with a somatotopic specificity akin to that seen during the perception of tactile stimuli. Using fMRI and multivariate pattern analysis, we investigate whether this recruitment of sensory regions also reflects content-specific activation (i.e., whether the activation in S1 is specific to the mental content participants imagined). To this end, healthy volunteers (n = 21) either perceived or imagined three types of vibrotactile stimuli (mental content) while fMRI data were acquired. Independent of the content, during tactile mental imagery we found activation of frontoparietal regions, supplemented with activation in the contralateral BA2 subregion of S1, replicating previous reports. While the imagery of the three different stimuli did not reveal univariate activation differences, using multivariate pattern classification, we were able to decode the imagined stimulus type from BA2. Moreover, cross-classification revealed that tactile imagery elicits activation patterns similar to those evoked by the perception of the respective stimuli. These findings promote the idea that mental tactile imagery involves the recruitment of content-specific activation patterns in sensory cortices, namely in S1

Self-reported life-space mobility in the first year after ischemic stroke: longitudinal findings from the MOBITEC-Stroke project

Background Life-space mobility is defined as the size of the area in which a person moves about within a specified period of time. Our study aimed to characterize life-space mobility, identify factors associated with its course, and detect typical trajectories in the first year after ischemic stroke. Methods MOBITEC-Stroke (ISRCTN85999967; 13/08/2020) was a cohort study with assessments performed 3, 6, 9 and 12 months after stroke onset. We applied linear mixed effects models (LMMs) with life-space mobility (Life-Space Assessment; LSA) as outcome and time point, sex, age, pre-stroke mobility limitation, stroke severity (National Institutes of Health Stroke Scale; NIHSS), modified Rankin Scale, comorbidities, neighborhood characteristics, availability of a car, Falls Efficacy Scale-International (FES-I), and lower extremity physical function (log-transformed timed up-and-go; TUG) as independent variables. We elucidated typical trajectories of LSA by latent class growth analysis (LCGA) and performed univariate tests for differences between classes. Results In 59 participants (mean age 71.6, SD 10.0 years; 33.9% women), mean LSA at 3 months was 69.3 (SD 27.3). LMMs revealed evidence (p ≤ 0.05) that pre-stroke mobility limitation, NIHSS, comorbidities, and FES-I were independently associated with the course of LSA; there was no evidence for a significant effect of time point. LCGA revealed three classes: “low stable”, “average stable”, and “high increasing”. Classes differed with regard to LSA starting value, pre-stroke mobility limitation, FES-I, and log-transformed TUG time. Conclusion Routinely assessing LSA starting value, pre-stroke mobility limitation, and FES-I may help clinicians identify patients at increased risk of failure to improve LSA

Short-term physical exercise impacts on the human holobiont obtained by a randomised intervention study

Background Human well-being has been linked to the composition and functional capacity of the intestinal microbiota. As regular exercise is known to improve human health, it is not surprising that exercise was previously described to positively modulate the gut microbiota, too. However, most previous studies mainly focused on either elite athletes or animal models. Thus, we conducted a randomised intervention study that focused on the effects of different types of training (endurance and strength) in previously physically inactive, healthy adults in comparison to controls that did not perform regular exercise. Overall study duration was ten weeks including six weeks of intervention period. In addition to 16S rRNA gene amplicon sequencing of longitudinally sampled faecal material of participants (six time points), detailed body composition measurements and analysis of blood samples (at baseline and after the intervention) were performed to obtain overall physiological changes within the intervention period. Activity tracker devices (wrist-band wearables) provided activity status and sleeping patterns of participants as well as exercise intensity and heart measurements. Conclusions We could show that different types of exercise have distinct but moderate effects on the overall physiology of humans and very distinct microbial changes in the gut. The observed overall changes during the intervention highlight the importance of physical activity on well-being. Future studies should investigate the effect of exercise on a longer timescale, investigate different training intensities and consider high-resolution shotgun metagenomics technology. Trial registration DRKS, DRKS00015873 . Registered 12 December 2018; Retrospectively registered