Studying transitions in and out of the altered state of consciousness caused by intravenous (IV) N,N-Dimethyltryptamine (DMT - a fast-acting tryptamine psychedelic) offers a safe and powerful means of advancing knowledge on the neurobiology of conscious states. Here we sought to investigate the effects of IV DMT on the power spectrum and signal diversity of human brain activity (6 female, 7 male) recorded via multivariate EEG, and plot relationships between subjective experience, brain activity and drug plasma concentrations across time. Compared with placebo, DMT markedly reduced oscillatory power in the alpha and beta bands and robustly increased spontaneous signal diversity. Time-referenced and neurophenomenological analyses revealed close relationships between changes in various aspects of subjective experience and changes in brain activity. Importantly, the emergence of oscillatory activity within the delta and theta frequency bands was found to correlate with the peak of the experience - particularly its eyes-closed visual component. These findings highlight marked changes in oscillatory activity and signal diversity with DMT that parallel broad and specific components of the subjective experience, thus advancing our understanding of the neurobiological underpinnings of immersive states of consciousness.
The imidazoline binding site (IBS) is thought to be expressed in glia and implicated in the regulation of glial fibrillary acidic protein. A PET ligand for this target would be important for the investigation of neurodegenerative and neuroinflammatory diseases. C-BU99008 has previously been identified as a putative PET radioligand. Here, we present the first in vivo characterization of this PET radioligand in humans and assess its test-retest reproducibility. Fourteen healthy male volunteers underwent dynamic PET imaging with C-BU99008 and arterial sampling. Six subjects were used in a test-retest assessment, and 8 were used in a pharmacologic evaluation, undergoing a second or third heterologous competition scan with the mixed IBS/α-adrenoceptor drug idazoxan ( = 8; 20, 40, 60, and 80 mg) and the mixed irreversible monoamine oxidase type A/B inhibitor isocarboxazid ( = 4; 50 mg). Regional time-activity data were generated from arterial plasma input functions corrected for metabolites using the most appropriate model to derive the outcome measure (regional distribution volume). All image processing and kinetic analyses were performed in MIAKAT. Brain uptake of C-BU99008 was good, with reversible kinetics and a heterogeneous distribution consistent with known IBS expression. Model selection criteria indicated that the 2-tissue-compartment model was preferred. estimates were high in the striatum (105 ± 21 mL⋅cm), medium in the cingulate cortex (62 ± 10 mL⋅cm), and low in the cerebellum (41 ± 7 mL⋅cm). Test-retest reliability was reasonable. The uptake was dose-dependently reduced throughout the brain by pretreatment with idazoxan, with an average block across all regions of about 60% ( , ∼30 mL⋅cm) at the highest dose (80 mg). The median effective dose for idazoxan was 28 mg. Uptake was not blocked by pretreatment with the monoamine oxidase inhibitor isocarboxazid. C-BU99008 in human PET studies demonstrates good brain delivery, reversible kinetics, heterogeneous distribution, specific binding signal consistent with IBS distribution, and good test-retest reliability.
Background: This report documents the phenomenology of the subjective experiences of 15 healthy psychedelic experienced volunteers who were involved in a functional magnetic resonance imaging (fMRI) study that was designed to image the brain effects of intravenous psilocybin. Methods: The participants underwent a semi-structured interview exploring the effects of psilocybin in the MRI scanner. These interviews were analysed by Interpretative Phenomenological Analysis. The resultant data is ordered in a detailed matrix, and presented in this paper. Results: Nine broad categories of phenomenology were identified in the phenomenological analysis of the experience; perceptual changes including visual, auditory and somatosensory distortions, cognitive changes, changes in mood, effects of memory, spiritual or mystical type experiences, aspects relating to the scanner and research environment, comparisons with other experiences, the intensity and onset of effects, and individual interpretation of the experience. Discussion: This article documents the phenomenology of psilocybin when given in a novel manner (intravenous injection) and setting (an MRI scanner). The findings of the analysis are consistent with previous published work regarding the subjective effects of psilocybin. There is much scope for further research investigating the phenomena identified in this paper.
Taylor et al. (2000) proposed that female behavioral responses to stress are characterized better as "tend and befriend" than "fight or flight." Q methodology was adopted to investigate different responses to stress. A Q set of 61 statements was sorted by 40 participants (18 male, 22 female) using principal components factor analysis. Four factors were extracted, accounting for 53.5% of the total variance. The 4 factors corresponded with fight, flight, tend, and befriend stress responses. Females were more likely to portray a tend-and-befriend response to stress. The implications of these findings are discussed in relation to past research that has been conducted with participants, predominantly of a single gender and for future stress research studies.
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