Laura Alethia de la Fuente

Serotonergic psychedelics induce altered states of consciousness characterised by profound changes in emotional experience. Although psychedelics modulate autonomic arousal, sympathetic engagement during their affective effects remains poorly characterised. We recorded cardiac, electrodermal, and respiratory activity in 19 participants following inhalation of 20 or 40 mg of freebase N,N-dimethyltryptamine (DMT) under a semi-naturalistic blinded design, alongside time-resolved retrospective phenomenological reports. DMT induced robust increases across all autonomic markers, integrated into a multimodal index that selectively tracked subjective emotional intensity. Dose-dependent divergence followed modality-specific profiles: heart rate and respiratory differences emerged within the first 2 min post-inhalation, whereas electrodermal activity diverged only during the later phase, with higher doses showing prolonged autonomic engagement. DMT thus produces a transient sympathetic activation co-varying with emotional arousal, followed by gradual disengagement accompanied by pleasantness and bliss. By combining time- and cost-effective peripheral physiological measures with time-resolved phenomenological reports, this work contributes to the objective characterisation of psychedelic-induced affective states and provides a methodological basis for future biomarker research in clinical applications.

Background: Cocaine consumption is associated with reduced attentional event-related potentials (ERPs), namely P3a and P3b, indicating bottom-up and top-down deficits respectively. At cognitive level, these impairments are larger for faster routes of administration (e.g., smoked cocaine [SC]) than slower routes (e.g., insufflated cocaine [IC]). Here we assess these ERPs considering the route of cocaine administration. We hypothesized that SC dependent (SCD) would exhibit reduced modulation of the P3a, while both SCD and IC dependent (ICD) would show reduced modulation of the P3b. Methods: We examined 25 SCD, 22 ICD matched by poly-consumption profiles, and 25 controls matched by demographic variables. We combined EEG data from the Global-Local task with behavioral data from attentional cognitive tasks. Results: At the behavioral level, SCD exhibited attentional deficits in both bottom-up and top-down processes, while ICD only showed a tendency for top-down deficits. Modulation of P3a and P3b was lower in consumer groups. We observed subtle route-based differences, with larger differences in the P3a for SCD and in the P3b for ICD. Neurophysiological and behavioral data converged, with the P3a associated to bottom-up performance and P3b to top-down. Conclusions: Different routes of administration lead to distinct modulations of attentional neurocognitive profiles. Specifically, SCD showed greater attentional impairment, mainly at bottom-up/P3a, while ICD showed a trend of top-down/P3b deficits. These findings emphasize the crucial role of considering the route of administration in both clinical and research settings and support the use of attentional ERPs as valid measures for assessing attentional deficits in substance abuse.

The use of low sub-perceptual doses of psychedelics (“microdosing”) has gained popularity in recent years. Although anecdotal reports claim multiple benefits associated with this practice, the lack of placebo-controlled studies severely limits our knowledge of microdosing and its effects. Moreover, research conducted in standard laboratory settings could fail to capture the motivation of individuals engaged or planning to engage in microdosing protocols, thus underestimating the likelihood of positive effects on creativity and cognitive function. We recruited 34 individuals starting to microdose with psilocybin mushrooms (Psilocybe cubensis), one of the materials most frequently used for this purpose. Following a double-blind placebo-controlled experimental design, we investigated the acute and short-term effects of 0.5 g of dried mushrooms on subjective experience, behavior, creativity (divergent and convergent thinking), perception, cognition, and brain activity. The reported acute effects were significantly more intense for the active dose compared to the placebo, but only for participants who correctly identified their experimental condition. These changes were accompanied by reduced EEG power in the theta band, together with preserved levels of Lempel-Ziv broadband signal complexity. For all other measurements there was no effect of microdosing except for few small changes towards cognitive impairment. According to our findings, low doses of psilocybin mushrooms can result in noticeable subjective effects and altered EEG rhythms, but without evidence to support enhanced well-being, creativity and cognitive function. We conclude that expectation underlies at least some of the anecdotal benefits attributed to microdosing with psilocybin mushrooms.

Dissipative systems evolve in the preferred temporal direction indicated by the thermodynamic arrow of time. The fundamental nature of this temporal asymmetry led us to hypothesize its presence in the neural activity evoked by conscious perception of the physical world, and thus its covariance with the level of conscious awareness. We implemented a data-driven deep learning framework to decode the temporal inversion of electrocorticography signals acquired from non-human primates. Brain activity time series recorded during conscious wakefulness could be distinguished from their inverted counterparts with high accuracy, both using frequency and phase information. However, classification accuracy was reduced for data acquired during deep sleep and under ketamine-induced anesthesia; moreover, the predictions obtained from multiple independent neural networks were less consistent for sleep and anesthesia than for conscious wakefulness. Finally, the analysis of feature importance scores highlighted transitions between slow ($\approx$20 Hz) and fast frequencies (>40 Hz) as the main contributors to the temporal asymmetry observed during conscious wakefulness. Our results show that a preferred temporal direction is manifest in the neural activity evoked by conscious mentation and in the phenomenology of the passage of time, establishing common ground to tackle the relationship between brain and subjective experience.

Background: N,N-dimethyltryptamine is a short-acting psychedelic tryptamine found naturally in many plants and animals. Few studies to date have addressed the neural and psychological effects of N,N-dimethyltryptamine alone, either administered intravenously or inhaled in freebase form, and none have been conducted in natural settings. Aims: Our primary aim was to study the acute effects of inhaled N,N-dimethyltryptamine in natural settings, focusing on questions tuned to the advantages of conducting field research, including the effects of contextual factors (i.e. “set“ and “setting“), the possibility of studying a comparatively large number of subjects, and the relaxed mental state of participants consuming N,N-dimethyltryptamine in familiar and comfortable settings. Methods: We combined state-of-the-art wireless electroencephalography with psychometric questionnaires to study the neural and subjective effects of naturalistic N,N-dimethyltryptamine use in 35 healthy and experienced participants. Results: We observed that N,N-dimethyltryptamine significantly decreased the power of alpha (8–12 Hz) oscillations throughout all scalp locations, while simultaneously increasing power of delta (1–4 Hz) and gamma (30–40 Hz) oscillations. Gamma power increases correlated with subjective reports indicative of some features of mystical-type experiences. N,N-dimethyltryptamine also increased global synchrony and metastability in the gamma band while decreasing those measures in the alpha band. Conclusions: Our results are consistent with previous studies of psychedelic action in the human brain, while at the same time the results suggest potential electroencephalography markers of mystical-type experiences in natural settings, thus highlighting the importance of investigating these compounds in the contexts where they are naturally consumed.

In cognitive neurosciences, fundamental principles of mental processes and functional brain organization have been established with highly controlled tasks and testing environments. Recent technical advances allowed the investigation of these functions and their brain mechanisms in naturalistic settings. The diversity in those approaches has been recently (Matusz et al. 2019a) classified via a three-category cycle including controlled laboratory, partially naturalistic laboratory, and naturalistic real-world research. Based on this model, we developed the Multidimensional Assessment of Research in Context (MARC) tool to easily delineate the approach researchers have taken in their study. MARC provides means to describe the degree of ecological validity for each component of a study (e.g. sample, location, stimuli, measures, etc.) and the study’s location on the cycle. The tool comprises seven questions concerning study’s characteristics. It outputs a summary of those and a compass plot, which can be used for presentations, pre-registration, grant proposals, and papers. It aims to improve drawing conclusions across studies, and raise awareness about generalizability of research findings.