Baseline power of theta oscillations predicts mystical-type experiences induced by DMT in a natural setting

This EEG study (n=35) showed that the baseline power of theta oscillations (associated with mind-wandering) negatively correlated with the intensity of mystical-type (MEQ30) experiences after smoking DMT.

Abstract

“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.”

Authors: Enzo Tagliazucchi, Federico Zamberlan, Federico Cavanna, Laura Alethia de la Fuente, Celeste Romero, Yontatan Sanz Perl & Carla Pallavicini

Summary

The experience induced by DMT strongly depends upon contextual factors, yet the neurobiological determinants of this variability remain unknown. Theta power is inversely correlated with scales indexing feelings of unity and transcendence, which are an integral part of the phenomenology of mystical-type experiences.

Serotonergic psychedelics (a subset of 5-HT2A receptor agonists) are capable of inducing remarkable changes in perception, affect, self-awareness and cognition. These effects are long-lasting and can be used to treat depression, substance abuse, and existential anxiety, among other uses.

Psilocybin can induce profoundly meaningful experiences of deep personal significance, with a sustained positive effect in well-being and behavior. These experiences are related to the therapeutic effects of the drug when administered in patients suffering from depression, end of life anxiety and substance abuse disorders.

There is considerable variability in the percentage of subjects whose report qualifies as a complete mystical-type experience, which may be related to contextual factors such as the state of mind of the participant prior to the experience and the environment where the experience takes place.

Facilitating mystical-type experiences with psychedelics is only one among multiple challenges related to the optimization of set and setting. Brain activity recordings may also present predictive power concerning the ensuing psychedelic experience.

We found that baseline theta oscillations originating from frontal and temporal brain regions were linked to self-reported subjective effects in a cohort of 35 subjects who inhaled DMT in freebase form in their preferred context of use.

Thirty-five participants were recruited by word-of-mouth and social media advertising between May and December 2019. They were aged between 21 and 65 years and were excluded if they had experienced past difficult experiences with psychedelics.

DMT administration was performed by inhaling smokes and vapors resulting from the combustion of freebase DMT, recrystallized over non-psychoactive plant leaves. The average load of the pipes was estimated at 40 mg freebase DMT, extracted from the root of Mimosa hostilis.

Before the DMT experience, participants completed the STAI trait, the Big Five personality test, the STAI state, and the Tellegen absorption scale. After the DMT experience, participants completed the MEQ30, the NDE, and the Post-experience questionnaire.

EEG data was acquired with a 24-channel mobile system attached to an elastic electrode cap. The system sent digitized EEG data via Bluetooth to a Notebook held by an experimenter sitting behind the participant.

EEG data was preprocessed using EEGLAB, and artifact-laden channels were first detected using EEGLAB automated methods. Infomax independent component analysis (ICA) was then applied to each individual participant, and used to manually identify and remove artifactual components.

Source imaging analysis was performed using Brainstorm, and a 3-shell sphere model was used to compute the forward solutions. A z-score statistical map was generated using dynamical Statistical Parametric Mapping.

Welch method, spectrum normalization, and averaging across epochs were used to compute band-specific power spectral densities. Regional mean spectral power estimates were assessed using Wilcoxon’s nonparametric signed-rank test, and the predictive power of baseline activity was evaluated using Spearman’s nonparametric rank correlation coefficient.

A machine learning regression model was trained using 1000 estimators and used to estimate the 5DASC Unity, MEQ30 Mystical and MEQ30 Transcendence scores in the remaining 50% of the samples.

We first compared the source estimates for all frequency bands between the eyes closed and DMT conditions. We observed posterior increases in delta power under the acute effects of DMT, with similar changes for the theta band, but of opposite sign.

We computed correlations between regional spectral power estimates and questionnaire subscales and identified three significant correlations for the theta band.

Figure 3 shows that theta power is correlated with 5D-ASC Unity, MEQ30 Mystical and MEQ30 Transcendence in fronto-temporal regions, and in the orbital part of the frontal lobe and the anterior cingulate cortex.

Theta power localized at the 90 AAL regions was used to predict individual questionnaire subscale values. The predicted values presented a medium to large correlation with the actual values.

We computed correlations between 5D-ASC Unity, MEQ30 Mystical and MEQ30 Transcendence subitem scores and baseline psychometric scores. We found significant correlations with trait absorption.

We investigated how source-localized EEG spectral power changed after the acute effects of DMT, and how baseline spectral power fluctuations could predict some of the subjective effects reported by the participants after the DMT experience.

The results of this study are consistent with previous analyses and with an independent report of EEG changes elicited by intravenous DMT administration. DMT increased delta power and decreased alpha power, and increased the power of gamma oscillations in posterior brain regions.

Theta oscillations have been linked to multiple cognitive and perceptual processes, including mind-wandering, and could be detrimental to a state of mind conducive to mystical-type experiences. Anxiety prior to the DMT experience could hinder the likelihood of undergoing a mystical-type experience.

Theta band oscillations are thought to reflect top-down influences related to working memory and memory retrieval, as well as to mental time travel and the level of mental workload. They are also inversely correlated with default mode activity, suggesting episodes of sustained attention. We did not assess the prevalence of mind-wandering episodes prior to the DMT experience, but high absorption is predictive of these experiences and inversely correlated with EEG theta power.

We were unable to predict other aspects of the psychedelic experience, such as perceptual, affective or cognitive alterations. However, we can speculate that other characteristics beyond the resolution of EEG could underlie the variability in other dimensions of the psychedelic experience.

This study is limited by the lack of a placebo condition and limited information concerning the administered dose of DMT. However, a certain degree of contextual heterogeneity might represent an advantage.

We studied the acute effects of psychedelics on baseline neurophysiological recordings and found that certain profiles of subjective effects were associated with the improvement of patients after treatment with psychedelics.