Safety, tolerability, pharmacodynamic and wellbeing effects of SPL026 (dimethyltryptamine fumarate) in healthy participants: a randomized, placebo-controlled phase 1 trial.

Background: Due to their potential impact on mood and wellbeing there has been increasing interest in the potential of serotonergic psychedelics such as N,N-dimethyltryptamine (DMT) in the treatment of major depressive disorder (MDD). Aim: The aim of Part A of this study was to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamic (PD) profile of escalating doses of SPL026 (DMT fumarate) in psychedelic-naïve healthy participants to determine a dose for administration to patients with MDD in the subsequent Phase 2a part of the trial (Part B: not presented in this manuscript). Methods: In the Phase 1, randomized, double-blind, placebo-controlled, parallel-group, single dose-escalation trial, psychedelic-naïve participants were randomized to placebo (n = 8) or four different escalating doses [9, 12, 17 and 21.5 mg intravenously (IV)] of SPL026 (n = 6 for each dose) together with psychological support from 2 therapy team members. PK and acute (immediately following dosing experience) psychometric measures [including mystical experience questionnaire (MEQ), ego dissolution inventory (EDI), and intensity rating visual analogue scale (IRVAS)] were determined. Additional endpoints were measured as longer-term change from baseline to days 8, 15, 30 and 90. These measures included the Warwick and Edinburgh mental wellbeing scale and Spielberger's state-trait anxiety inventory. Results: SPL026 was well tolerated, with an acceptable safety profile, with no serious adverse events. There was some evidence of a correlation between maximum plasma concentration and increased IRVAS, MEQ, and EDI scores. These trends are likely to require confirmation in a larger sample size. Using the analysis of the safety, tolerability, PD, PK results, doses of 21.5 mg SPL026 were the most likely to provide an intense, tolerated experience. Conclusion: Based on the data obtained from this part of the trial, a dose of 21.5 mg SPL026 given as a 2-phase IV infusion over 10 min (6 mg/5 min and 15.5 mg/5 min) was selected as the dose to be taken into patients in Part B (to be presented in a future manuscript).Clinical trial registration:www.clinicaltrials.gov, identifier NCT04673383; https://www.clinicaltrialsregister.eu, identifier 2020-000251-13; https://www.isrctn.com/, identifier ISRCTN63465876.

Fearless Dominance/Boldness Is Not Strongly Related to Externalizing Behaviors: An Item Response-Based Analysis.

There is substantial and ongoing debate regarding the centrality of Fearless Dominance/Boldness (FD/B) to psychopathic personality due, in part, to its generally weak relations with externalizing behaviors. In response to these findings, proponents of FD/B have offered two hypotheses. First, FD/B may have nonlinear associations with externalizing outcomes such that FD/B may lead to resilience at moderate levels, but an overabundance of FD/B will yield maladaptive behavioral outcomes. Second, FD/B may be related to antisocial outcomes when paired with high scores on other psychopathic traits such as self-centered impulsivity, meanness, or disinhibition. The current study tests these two possibilities using two large samples (Study 1: 787 undergraduates; Study 2: 596 Amazon's Mechanical Turk participants). An item response theory scoring approach particularly sensitive to curvilinearity was used to maximize our ability to find a true curvilinear effect, if present. No evidence in favor of the curvilinearity hypothesis was found. Only a single significant interaction predicting substance use was observed between boldness and meanness. These findings contribute to a growing literature raising concerns regarding the relevance of FD/B to psychopathy.

An fMRI investigation of the relations between Extraversion, internalizing psychopathology, and neural activation following reward receipt in the Human Connectome Project sample.

Quantitative models of psychopathology (i.e., HiTOP) propose that personality and psychopathology are intertwined, such that the various processes that characterize personality traits may be useful in describing and predicting manifestations of psychopathology. In the current study, we used data from the Human Connectome Project (N = 1050) to investigate neural activation following receipt of a reward during an fMRI task as one shared mechanism that may be related to the personality trait Extraversion (specifically its sub-component Agentic Extraversion) and internalizing psychopathology. We also conducted exploratory analyses on the links between neural activation following reward receipt and the other Five-Factor Model personality traits, as well as separate analyses by gender. No significant relations (p < .005) were observed between any personality trait or index of psychopathology and neural activation following reward receipt, and most effect sizes were null to very small in nature (i.e., r < |.05|). We conclude by discussing the appropriate interpretation of these null findings, and provide suggestions for future research that spans psychological and neurobiological levels of analysis.

The relation between narcissism and laboratory aggression is not contingent on environmental cues of competition.

Narcissism has been robustly linked to self-report and lab-based measures of aggression. However, less is known about the role that a competitive context may play in the relations found between narcissism and aggression as measured in behavioral paradigms. In circumstances of competition, narcissistic individuals may be particularly attuned to external indicators of status and use aggression as a way of asserting power and a motivation to "win," rather than to do harm. The goal of the present study was to test the role of competition in understanding the relation between narcissism and related traits (i.e., psychopathy) and aggression by manipulating cues of competition. First, participants (N = 220) completed questionnaires to assess levels of trait narcissism and associated variables (e.g., psychopathy, five-factor model traits, and self-esteem). In a separate session, participants were randomly assigned to interact with an ostensible confederate under the guise of either a competitive or noncompetitive interaction, and then were given the opportunity to administer electric shocks to their partner. Results suggest that the antagonistic and grandiose features of narcissism were significantly related to aggression in both conditions, as was the antagonism factor of psychopathy and (low) Agreeableness dimension of the five-factor model. However, tests of moderation found no significant interaction effects between narcissism and condition in the hypothesized direction (and a few in the opposite direction such that narcissism was more strongly related in the noncompetition condition). Findings are discussed in terms of the importance of antagonism in predicting antisocial outcomes such as aggression. (PsycINFO Database Record (c) 2018 APA, all rights reserved).