Neural and subjective effects of inhaled N,N-dimethyltryptamine in natural settings

Abstract

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.

Baseline Power of Theta Oscillations Predicts Mystical-Type Experiences Induced by DMT in a Natural Setting

“…Our results at the source level are consistent with a previous analysis of this data (71) and with an independent report of EEG changes elicited by intravenous DMT administration (47). The most salient results obtained from the contrast of DMT vs. eyes closed comprise increased delta power and decreased alpha power, in both cases localized to posterior brain regions, replicating previous analyses.…”

“…The data included in this manuscript was used in a previous publication, which can be referenced for further methodological details (71).…”

“…We first compared the EEG source estimates for all frequency bands between the eyes closed and DMT conditions, with the purpose of estimating the validity of the source imaging procedure by comparing the results with analyses previously conducted at the scalp level (71). The results of this analysis are shown in Figure 1.…”

“…Considerable variability exists in the percentage of subjects whose report qualifies as a complete mystical-type experience, according to the criteria put forward by Griffiths and colleagues. These percentages range from 60% for multiple studies using psilocybin (16,17) to 10% for LSD (22), and between 37 and 73% for intravenous or inhaled DMT (23,71). This variability is likely related to contextual factors known as set and setting, i.e., the state of mind of the participant prior to the experience and the environment where the experience takes place, respectively (24).…”

Recreational Psychedelic Users Frequently Encounter Complete Mystical Experiences: Trip Content and Implications for Wellbeing

“…These findings are unsurprising considering the clinical evidence which document the unique reliability of psychedelics for eliciting mystical states. Use of LSD, DMT, and MDMA are each uniquely associated with higher odds of occasioning mystical type experience which corroborates existing clinical evidence for all three substances (Holze et al, 2020;Liechti et al, 2017;Pallavicini et al, 2021;Schmid et al, 2021;Timmermann et al, 2018). Our models reveal an interesting point, that recreational mystical experiences aren't limited to a single psychedelic drug, rather different substances can bring the user to a similar qualitative state.…”