Predictors of Psychedelic Experience: A Thematic Analysis.

Research on the therapeutic potential of psychedelic substances is expanding. A limitation within this field is the unpredictability of individual responses to psychedelics. Better understanding of factors predicting psychedelic experience is essential to clinical progress and wider harm reduction frameworks. Ketamine, MDMA, LSD and psilocybin were selected for comparison due to their promising therapeutic effects and different mechanisms of action. This study aimed to (a) identify factors that produce positive and adverse psychedelic experience, and (b) compare these potential predictors across four psychedelic substances. A thematic analysis was conducted on twenty-two first-person reports of psychedelic use (six per substance), sourced from the Erowid database. This revealed three external predictors (nature, music, and preparation) and three internal predictors (understanding, mind-set, and motivation). Each factor identified contained two sub-themes that further elucidated meaning and impact. Nature and music emerged as potential tools for de-escalating adverse reactions to psychedelics. Substance-specific perceptual and sensorial effects were also examined. Finally, the importance of, and interrelationship between, preparation, mind-set, understanding, and motivation was examined as common themes that emerged. The broader clinical and sociological implications are discussed, with reference to developing harm reduction frameworks. These findings constitute an early step in developing a more nuanced understanding of factors shaping psychedelic experience.

Learned uncertainty: The free energy principle in anxiety.

Generalized anxiety disorder is among the world's most prevalent psychiatric disorders and often manifests as persistent and difficult to control apprehension. Despite its prevalence, there is no integrative, formal model of how anxiety and anxiety disorders arise. Here, we offer a perspective derived from the free energy principle; one that shares similarities with established constructs such as learned helplessness. Our account is simple: anxiety can be formalized as learned uncertainty. A biological system, having had persistent uncertainty in its past, will expect uncertainty in its future, irrespective of whether uncertainty truly persists. Despite our account's intuitive simplicity-which can be illustrated with the mere flip of a coin-it is grounded within the free energy principle and hence situates the formation of anxiety within a broader explanatory framework of biological self-organization and self-evidencing. We conclude that, through conceptualizing anxiety within a framework of working generative models, our perspective might afford novel approaches in the clinical treatment of anxiety and its key symptoms.

Do psychedelics change beliefs?

Renewed interest in psychedelics has reignited the debate about whether and how they change human beliefs. In both the clinical and social-cognitive domains, psychedelic consumption may be accompanied by profound, and sometimes lasting, belief changes. We review these changes and their possible underlying mechanisms. Rather than inducing de novo beliefs, we argue psychedelics may instead change the impact of affect and of others' suggestions on how beliefs are imputed. Critically, we find that baseline beliefs (in the possible effects of psychedelics, for example) might color the acute effects of psychedelics as well as longer-term changes. If we are to harness the apparent potential of psychedelics in the clinic and for human flourishing more generally, these possibilities must be addressed empirically.

Rapid epinephrine administration improves early outcomes in out-of-hospital cardiac arrest.

INTRODUCTION: Early administration of epinephrine (Epi) improves outcomes in animal models of cardiac arrest, but there is limited time-dependent clinical data regarding its benefit. OBJECTIVE: Our objective was to assess whether timing of Epi administration was associated with improved outcomes after out of hospital cardiac arrest (OHCA). METHODS: We performed a retrospective analysis of a cardiac arrest database from a suburban EMS system from November 2005 to April 2011. Data was abstracted from EMS run sheets, including drug treatment, route and timing of drug administration, and other Utstein variables. Our primary outcome was return of spontaneous circulation (ROSC). Secondary outcomes measured were survival to hospital admission and discharge. For analysis, data were dichotomized according to timing of Epi administration: early Epi group (defined as 911 call to Epi administration of ≤10 min) and late Epi group (>10 min). Further, exploratory analyses were conducted looking at subgroups sorted by initial rhythm and whether the arrest was witnessed. Wilcoxon rank sum tests, chi-square tests, 95% confidence intervals, and multi-variable regression were used for statistical analysis. RESULTS: We reviewed 809 patients from study communities: 123 patients were excluded, leaving a sample size of 686 for study analysis. The mean time from 911-Epi was 14.3±5.5 min, with 155 (22.6%) receiving early Epi. Key arrest and treatment characteristics were similar between groups. Patients who received early Epi were more likely to have ROSC (32.9% vs. 23.4%, OR 1.59 (1.07, 2.38)), however, no significant increase in survival to admission or discharge was observed. Patients with an initial rhythm of PEA had an increased rate of ROSC (48.6% vs. 21.5%, OR 3.45 (1.56, 7.62)) but not survival to discharge (5.9% vs. 2.6%), OR 2.35 (0.38, 14.7) with early Epi. In a multivariable analysis of bystander witnessed arrests, early Epi was associated with a higher rate of ROSC (OR 3.20 (1.75, 5.88) but not survival to discharge (OR 1.48 (0.50, 4.36)). No improvement in ROSC or secondary outcomes was noted in patients with other arrest rhythms or un-witnessed arrest with Early Epi. CONCLUSIONS: Within the limitations of our study, this data suggests improved rates of ROSC with early Epi administration during OHCA resuscitation, but this study lacks adequate sample size to demonstrate impact on survival to discharge. Large prospective trials are needed to further delineate the benefit of early Epi administration in OHCA.

Use of a phosphotyrosine-antibody pair as a general detection method in homogeneous time-resolved fluorescence: application to human immunodeficiency viral protease.

A homogeneous time-resolved fluorescence (HTRF) assay has been developed for human immunodeficiency viral (HIV) protease. The assay utilizes a peptide substrate, differentially labeled on either side of the scissile bond, to bring two detection components, streptavidin-cross-linked XL665 (SA/XL665) and a europium cryptate (Eu(K))-labeled antiphosphotyrosine antibody, into proximity allowing fluorescence resonance energy transfer (FRET) to occur. Cleavage of the doubly labeled substrate by HIV protease precludes complex formation, thereby decreasing FRET, and allowing enzyme activity to be measured. Potential substrates were evaluated by HTRF with the best results being obtained using (LCB)K4AVSQNbeta-NapPIVpYA(NH2) and Eu(K)-pY20 where the peptide titrated with an EC50 of 7.7 +/- 0.3 nM under optimized detection conditions. Using these HTRF detection conditions, HIV protease cleaved the substrate in 50 mM NaOAc, 150 mM KF, 0.05% Tween 20, pH 5.5, with apparent first-order kinetics with a Km of 37.8 +/- 8.7 microM and a kcat of 0.95 +/- 0.07 s-1. Examination of the first-order rate constant versus enzyme concentration suggested a Kd of 9.4 +/- 2.7 nM for the HIV protease monomer-dimer equilibrium. The HTRF assay was also utilized to measure the inhibition of the enzyme by two known inhibitors.

Controlled substances registration for nonlicensed physicians.

Changes in drug laws and the addition of many formerly uncontrolled drugs to the controlled substances list has caused some concern about the registration of nonlicensed physicians. The question is, how does the recent medical school graduate obtain authorization to use the controlled substances he may need in the course of his postgraduate training at the hospital? The University of Alabama Hospitals, Birmingham, have answered the question with an effective system for hospital registration of nonlicensed physicians.