The scientific study of human consciousness has greatly benefited from the development of non-invasive brain imaging methods. The quest to identify the neural correlates of consciousness combined psychophysical experimentation with neuroimaging tools such as functional magnetic resonance imaging (fMRI) to map the changes in neural activity associated with conscious vs. unconscious percepts. Different neuroimaging methods have also been applied to characterize spontaneous brain activity fluctuations during altered states of consciousness, and to develop quantitative metrics for the level of consciousness. Most of these studies, however, have not explored the dynamic nature of the whole-brain imaging data provided by fMRI. A series of empirical and computational studies strongly suggests that the temporal fluctuations observed in this data present a non-trivial structure, and that this structure is compatible with the exploration of a discrete repertoire of states. In this review we focus on how dynamic neuroimaging can be used to address theoretical accounts of consciousness based on the hypothesis of a dynamic core, i.e. a constantly evolving and transiently stable set of coordinated neurons that constitute an integrated and differentiated physical substrate for each conscious experience. We review work exploring the possibility that metastability in brain dynamics leads to a repertoire of dynamic core states, and discuss how it might be modified during altered states of consciousness. This discussion prompts us to review neuroimaging studies aimed to map the dynamic exploration of the repertoire of states as a function of consciousness. Complementary studies of the dynamic core hypothesis using perturbative methods are also discussed. Finally, we propose that a link between metastability in brain dynamics and the level of consciousness could pave the way towards a mechanistic understanding of altered states of consciousness using tools from dynamical systems theory and statistical physics.

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.

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.

N,N-Dimethyltryptamine (DMT) is a short acting psychedelic tryptamine found naturally in many plants and animals. When combined with a monoamine oxidase inhibitor, such as in the Amazonian brew known as ayahuasca, DMT becomes orally active and its effects are extended. Few studies to date addressed the neural and psychological effects of DMT alone, either administered intravenously or inhaled in freebase form, and none conducted in natural settings. We combined state-of-the-art wireless electroencephalography (EEG) with psychometric questionnaires to study the acute effects of inhaled DMT in 35 participants in natural settings, focusing on questions tuned to the advantages of conducting field research, including the effects of contextual factors (known as set and setting), the possibility of studying a comparatively large number of subjects, and the relaxed mental state of participants consuming DMT in familiar and comfortable settings. We observed that DMT 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. The pharmacokinetics of inhaled DMT was similar to intravenous administration, but we observed a faster return to baseline for power in the alpha band. Gamma power increases correlated with subjective reports indicative of mystical-type experiences. DMT also increased/decreased global synchrony and metastability in the gamma/alpha band, and resulted in widespread increases in signal complexity measured using the Lempel-Ziv algorithm. These results are consistent with previous studies of psychedelic action in the human brain, while at the same time suggesting potential EEG markers of mystical-type experiences in natural settings. In summary, we conducted one of the first field studies on the neural and psychological effects of a serotonergic psychedelic, yielding new insights and advancing our understanding of the translation between laboratory findings and those obtained in the contexts where these compounds are most frequently consumed.

N,N-Dimethyltryptamine (DMT) is a classic psychedelic capable of inducing short-lasting but profound changes in consciousness. As with other psychedelics, the experience induced by DMT strongly depends upon contextual factors, yet the neurobiological determinants of this variability remain unknown. The present study investigated changes in neural oscillations elicited by inhaled DMT, and whether baseline electroencephalography (EEG) recordings could predict the subjective effects reported by the participants. Healthy volunteers (N = 35) were measured with EEG before and during the acute effects of DMT consumed in a natural setting. Source-localized neural oscillations were correlated with the results of multiple questionnaires employed to assess the subjective effects of the drug. DMT resulted in a marked reduction of alpha and beta oscillations, and increased posterior spectral power in the delta, theta and gamma bands. The power of fronto-temporal theta oscillations was inversely correlated with scales indexing feelings of unity and transcendence, which are an integral part of the phenomenology of mystical-type experiences. The robustness of these results was supported using a machine learning model for regression trained and tested following a cross-validation procedure. These results are consistent with the observation that the state of mind prior to consuming a psychedelic drug influences the ensuing subjective experience of the user. They also suggest that baseline EEG screenings before administration of a serotonergic psychedelic could be useful to estimate the likelihood of inducing mystical-type experiences, previously linked to sustained positive effects in well-being and improved outcome of therapeutic interventions.

Background and aimsThe COVID-19 pandemic and its consequences represent a major challenge to the mental health and well-being of the general population. Building on previous work on the potential long-term benefits of psychedelics, we hypothesized that lifetime use of these drugs could be linked to better mental health indicators in the context of the ongoing pandemic.MethodsTwo anonymous online surveys were conducted between April and June 2020, including questions about lifetime experience with psychedelics and other psychoactive drugs, and psychometric scales designed to measure personality traits, anxiety, negative, and positive affect, well-being, and resilience. Principal component analysis was applied to divide the sample into groups of subjects based on their drug use reports.ResultsFive thousand six hundred eighteen participants (29.15 0.12 years, 71.97% female) completed both surveys and met the inclusion criteria, with 32.43% of the sample reporting at least one use of a psychedelic drug. Preliminary analyses showed that certain psychedelics were linked to improved mental health indicators, while other psychoactive drugs exhibited the opposite behavior. Lifetime psychedelic use was linked to increased openness and decreased conscientiousness, and to higher scores of positive affect. The reported number of past psychedelic experiences predicted higher scores of the secondary personality trait beta factor, which has been interpreted as a measure of plasticity. No significant associations between lifetime use of psychedelics and indicators of impaired mental health were observed.ConclusionWe did not find evidence of an association between lifetime use of psychedelics and poor mental health indicators. Conversely, experience with psychedelic drugs was linked to increased positive affect and to personality traits that favor resilience and stability in the light of the ongoing crisis.

N,N-Dimethyltryptamine (DMT) is a classic psychedelic capable of inducing short-lasting but profound changes in consciousness. As with other psychedelics, the experience induced by DMT strongly depends upon contextual factors, yet the neurobiological determinants of this variability remain unknown. We combined wireless electroencephalography and source imaging to map changes in neural oscillations elicited by inhaled DMT. Furthermore, we found that the power of frontal and temporal theta oscillations was inversely correlated with scales indexing feelings of unity and transcendence, which are an integral part of the phenomenology of mystical-type experiences. Finally, we established the robustness of these results using a machine learning model for regression trained and tested following a cross-validation procedure. Our results are consistent with the observation that the state of mind prior to consuming a psychedelic drug influences the ensuing subjective experience of the user. We also suggest that priming subjects to reduce their theta power before administration of a serotonergic psychedelic could enhance the likelihood of inducing mystical-type experiences, leading to sustained positive effects in well-being and improving the outcome of therapeutic interventions.

The use of low sub-hallucinogenic 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 limits our knowledge of microdosing and its effects. Moreover, research conducted in laboratory settings might fail to capture the motivation of individuals engaged in microdosing protocols. We recruited 34 individuals planning to microdose with psilocybin mushrooms (Psilocybe cubensis), one of the materials most frequently used for this purpose. Following a double-blind placebo-controlled design, we investigated the effects of 0.5 g dried mushrooms on subjective experience, behavior, creativity, perception, cognition, and brain activity. The reported acute effects were significantly more intense for the active dose compared to the placebo, which could be explained by unblinding. For the other measurements, we observed either null effects or a trend towards cognitive impairment and, in the case of EEG, towards reduced theta band spectral power. Our findings support the possibility that expectation effects underlie at least some of the anecdotal benefits attributed to microdosing with psilocybin mushrooms.