Subjective effects

Participants were asked to provide ratings of the subjective intensity of the drug effects at every minute for a total of 20 minutes after DMT and placebo administration. Figure 1A displays the group-averaged intensity plots for each minute for a total of 20 minutes post-injection. Paired T-tests revealed that the subjective intensity of the experience remained significantly higher under DMT vs placebo for 17 minutes post-dosing (False Discovery Rate - FDR corrected) and peak subjective effects occurred 2–3 minutes post-injection.

Figure 1 Subjective effects. (A) Real-time intensity ratings for DMT and placebo (mean ± SEM) (****p < 0.001; ***p < 0.005; **p < 0.01; * p < 0.05, FDR corrected, N = 13). (B) Visual analogue scales depict the phenomenological features of DMT and placebo (mean + SEM) (****p < 0.001; ***p < 0.005; **p < 0.01; *p < 0.05, FDR corrected, N = 13). Full size image

Supplementing these basic intensity ratings, participants were asked to rate different aspects of their experiences using various visual analogue scales (VAS). All items were rated significantly higher in the DMT condition compared with placebo (FDR corrected) (Fig. 1B). Ratings were given retrospectively, at ~30 minutes following administration, i.e. once the acute effects of DMT had sufficiently subsided.

Time-averaged EEG results

Averaged EEG from the first 5 minutes of resting state activity following administration of DMT was contrasted against the same period after placebo, focusing on changes in the power spectrum and spontaneous signal diversity (LZs and LZs N ). One participant was excluded due to excessive movement artifacts following DMT. Supporting one aspect of our primary hypothesis, contrasts revealed spatially-widespread and statistically-marked decreases in the alpha band (max. t(11) = −3.87, cluster p = 5.33e-04) and more modest decreases in the beta band (max. t(11) = −3.30, cluster p = 0.033) under DMT (Fig. 2A).

Figure 2 Time-averaged EEG results. (A) The comparison of DMT versus placebo for changes in spectral activity reveals significant decreases for the alpha and beta bands for conventional spectral power. The decomposed spectra into oscillatory and fractal power, revealed similar results for the former and reductions were seen on all bands < 30 Hz for the latter. Filled circles correspond to clusters p < 0.01 and hollow circles for clusters p < 0.05, N = 12. (B) Grand-average spectral power for DMT and placebo corresponding to spectral, oscillatory and fractal (1/f) components of the signal (N = 12). (C) Increases are seen for both measures of spontaneous signal diversity following DMT administration compared to placebo Filled circles correspond to clusters p < 0.01 and hollow circles for clusters p < 0.05, N = 12 (LZs = Lempel-Ziv complexity, LZs N = normalized LZs). Full size image

Decomposing the EEG spectra into its oscillatory and fractal (1/f) components revealed consistent changes in oscillatory power as reported above (alpha: max. t(11) = −3.87, cluster p = 2.67e-04. Beta: max. t(11) = −3.11, cluster p = 0.04), while the fractal component showed significantly reduced power within all frequency bands < 30 Hz (delta: max. t(11) = −3.91, cluster p = 0.024. Theta: max. t(11) = −4.28, cluster p = 0.007. Alpha: max. t(11) = −3.67, cluster p = 0.014. Beta: max. t(11) = −3.48, cluster p = 0.02) (Fig. 2A and see Fig. S1 for detailed results for DMT and placebo separately).

Signal diversity, as measured by Lempel-Ziv complexity (LZs) and normalized Lempel-Ziv complexity (LZs N ), was significantly increased under DMT relative to placebo (max. t(11) = 8.09, cluster p = 2.67e-04; max. t(11) = 4.26, cluster p = 0.0029), respectively (Fig. 2C) – consistent with our primary hypothesis.

Results also revealed the emergence of prominent theta oscillations under DMT, to the extent that this rhythm replaced alpha as the peak frequency in terms of power (within the 4–45 Hz range: mean = 7.36 Hz, SEM = 0.68). This emergent theta rhythm under DMT was more evident in the oscillatory power spectrum, i.e. once the fractal component had been removed. As expected, an alpha peak was maintained throughout the placebo session (mean = 9.28 Hz, SEM = 0.62) (t(11) = −2.52, p = 0.029) (Fig. 2B).

Time-sensitive EEG results

In addition to consistent alpha and beta reductions, minute-by-minute analyses revealed decreases in delta and theta bands only for the first minute post DMT injection – after which recovery (and increases in theta for the oscillatory component) were identified at minutes 2–3. These results indicate that DMT induces a general decrease in total power across all frequency bands between 1 and 30 Hz; however, there is a transient normalization/increases in theta and delta frequencies at the time of peak subjective intensity, which is especially evident in the oscillatory component of the signal. The spontaneous signal diversity measure, LZs, was found to be consistently increased for the whole of the post-injection period - and increases in LZs N were evident from the time of peak intensity onwards (Fig. S2).

Subjective vs EEG effects across time

In order to assess the relationship between the subjective and EEG changes across time, data was segmented into one-minute blocks. Results revealed a negative correlation between changes in total alpha power under DMT and ratings of subjective intensity that was significant for all recorded channels (max. t(11) = −16.05, cluster p = 2.67e-04; white dots, Fig. 3A). Decreased beta power similarly correlated with higher intensity ratings (max. t(11) = −9.83, cluster p = 0.0043). Analysis performed on just the oscillatory component of the signal showed mostly consistent results (alpha: max. t(11) = −14.85, cluster p = 2.67e-04. Beta: max. t(11) = −11.08, cluster p = 0.004), although additional positive correlations between intensity and delta (max. t(11) = 4.68, cluster p = 0.007) and theta power (max. t(11) = 7.17, cluster p = 0.003) also emerged as statistically significant (black dots, Fig. 3A). Fractal power revealed a negative correlation between (higher) intensity ratings and (reduced) theta (max. t(11) = −3.13, cluster p = 0.04), alpha (max. t(11) = −3.12, cluster p = 0.047) and beta power (max. t(11) = −5.21, cluster p = 0.01). These results reveal the emergence of a functionally relevant rhythmicity within the delta and theta frequency bands under DMT that was not evident in total power, which includes the fractal component of the signal. In fact, within the theta band, the fractal component appears to behave in an opposite way to the oscillatory component under DMT, i.e. there is increased theta power in the oscillatory component but decreased theta in the fractal component.

Figure 3 Subjective vs EEG effects across time. (A) Significant inverse relationships were found between real-time intensity ratings and power in alpha and beta bands for all power measures (including the theta band for fractal power). A positive relationship was found between intensity and power at delta and theta bands in the oscillatory component. Increased signal diversity (LZs and LZs N ) correlated positively with intensity ratings also. Filled circles/dots correspond to clusters p < 0.01 and hollow circles for clusters p < 0.05, N = 12. Positive relationships are shown using black dots and negative relationships are shown using white dots/circles (B) Time frequency plot illustrating the associations between intensity ratings and spectral activity for DMT and placebo (red line marks beginning of injection), N = 12. (C) Temporal development of intensity, and EEG measures of spectral activity and spontaneous signal diversity (mean ± SEM, N = 12). (δ = delta, θ = theta, γ = gamma, α = alpha, β = beta, LZs = Lempel-Ziv complexity, LZs N = normalized LZs). Full size image

Supporting our primary hypothesis, increased signal diversity (LZs) under DMT correlated positively with subjective intensity ratings in posterior and central channels (max. t(11) = 9.96, cluster p = 2.67e-04). After controlling for changes in spectral power (LZs N ), the relationship between signal diversity and intensity remained positive in the posterior channels only (max. t(11) = 5.11, cluster p = 0.009).

Plasma DMT vs EEG effects

Here we assessed the relationship between changes in the EEG data (frequency bands and signal diversity) and plasma concentrations of DMT across time. In a similar manner to the subjective values, higher concentrations of DMT in the blood were associated with greater reductions in alpha (max. t(11) = −23.59, cluster p = 2.67e-04) and beta power (max. t(11) = −12.61, cluster p = 0.04). Similar effects were seen when analyses were performed on the oscillatory component of the signal (alpha: max. t(11) = −28.32, cluster p = 2.67e-04. Beta: max. t(11) = −20.62, cluster p = 0.022), while the fractal component showed negative correlation between (higher) plasma concentrations and (reduced) theta power (max. t(11) = −4.11, cluster p = 0.038). As predicted, a relationship was also evident between plasma DMT and increased signal diversity (LZs: max. t(11) = 25.61, cluster p = 2.67e-04 and LZs normalized: max. t(11) = 7.63, cluster p = 2.67e-04) (Fig. 4).

Figure 4 Plasma DMT vs EEG effects. (A) Significant inverse relationships (white dots/circles) were found between plasma levels of DMT and power in the alpha and beta bands for spectral and oscillatory power, while the relationship was found for plasma DMT and power in the theta band for fractal power. A positive relationship (black dots) was found between plasma levels of DMT and complexity measures (LZs and LZs N ). Filled circles correspond to clusters p < 0.01 and hollow circles for clusters p < 0.05, N = 12. (B) Temporal development of DMT plasma concentrations, and EEG measures of total power and spontaneous signal diversity which were found significant to have a significant effect (mean ± SEM, N = 12). Full size image

Neurophenomenology

Micro-phenomenological interviews (MPIs)26,28,29 were performed post-hoc to discover distinct (core) components of the subjective experience – that could then be used to constrain participant ratings referenced to specific time points, i.e. each passing minute. Three major common dimensions were found across participants, i.e.: (1) visual, (2) bodily and (3) emotional/metacognitive experiences. These dimensions were extracted from each of the participants’ interviews and then rated by a researcher not involved in EEG analysis with reference to each passing minute within the 20-minute recording period (see Methods for details) (Fig. 5A).

Figure 5 Neurophenomenology. (A) Average ratings (mean ± SEM) regarding the intensity for the three dimensions of experience which were found to be commonly altered across all participants following DMT administration. (B) Significant inverse relationships (white dots/circles) were found between the progression of visual effects induced by DMT and power at the alpha and the beta bands, as well as increases (black dots) in complexity (LZs and LZs N ). Decreases of central beta band power showed a significant association the trajectory of bodily effects. Decreases in alpha band power and increases in complexity (LZs and LZs N ) were significantly associated to the dynamics of emotional/metacognitive effects. Mostly consistent results were found with oscillatory power, however an intriguing positive relationship found with power at delta and theta bands for visual effects and reduced theta activity was linked to emotional/metacognitive effects. Filled circles/dots correspond to clusters p < 0.01 and hollow circles for clusters p < 0.05, N = 11. (C) Radar plots displaying the constellation of EEG effects associated to different dimensions of experience (mean values displayed). Full size image

Adopting a data-led approach, we chose to look at components of the EEG that had already shown interesting relationships with intensity ratings, namely: alpha, beta, delta and theta power, plus signal diversity measures (LZs and LZs N ). Results revealed a negative correlation between changes in visual intensity and changes in total alpha (max. t(11) = −14.24, cluster p = 2.67e-04) and beta (max. t(11) = −6.17, cluster p = 0.04) power as well as a positive relationship with changes in delta (max. t(11) = 6.06, cluster p = 0.004) and theta (max. t(11) = 6.59, cluster p = 0.01) power - when just the oscillatory component of the signal was used for analyses. Similar positive relationships between intensity ratings and EEG measures were seen for LZ (i.e. LZs: max. t(11) = 16.74, cluster p = 2.67e-04 and LZs N : max. t(11) = 6.62, cluster p = 0.008). Ratings of bodily effects were negatively correlated with changes in the beta band (max. t(11) = 3.17, cluster p = 0.0496) only. Lastly changes in the emotional/metacognitive dimension were primarily associated with decreases in the alpha band (max. t(11) = −4.56, cluster p = 0.008) and increases in the LZ measures (LZs: max. t(11) = 6.15, cluster p = 0.003 and LZs N : max. t(11) = 5.39, cluster p = 2.67e-04) (Fig. 5B). These results support and extend on our primary hypothesis.

Psychometric correlational analyses

In order to further test the relationship between specific EEG measures and the DMT experience, we performed additional post-hoc ‘subjective rating vs EEG’ correlations using both time-sensitive (minute-by-minute) and time-averaged analyses. Time-sensitive analysis revealed relationships that were broadly consistent with those reported above, i.e. negative correlations were evident between (higher) VAS item scores and (reduced) alpha/beta power and positive correlations were evident between (higher) VAS scores and (increased) LZs/theta/delta - during the period of peak subjective intensity (Fig. 6A and see Fig. S3 for specific correlations when oscillatory and fractal components of the signal were used).

Figure 6 Psychometric correlational analyses. (A) Normalized correlation coefficient values between VAS items and EEG measures for each minute following DMT. Significant correlations between these normalized correlation values and intensity ratings are marked with a cross following Bonferroni-correction for multiple comparisons at p < 0.05 (see Fig. S3 for correlations with oscillatory and fractal power and Fig. S4 for 5-minute averaged data correlations). (B) Bar chart displaying the number of significant correlations between normalized correlation values (EEG metrics vs VAS items) and intensity ratings. Results revealed that alpha correlate most with subjective experience when the total power is assessed, whereas theta correlates most when just the oscillatory power is extracted. Conversely, fractal power displayed a small amount of significant correlations (See Fig. S6 for the specific correlation values for each item for oscillatory and fractal power). Finally LZs was a metric which displayed the same amount of significant correlations as alpha in total and oscillatory power. Full size image

Lastly, as one might expect, when group-averaged intensity ratings were correlated with Fisher’s Z normalized coefficient scores across time (i.e. minute-by-minute correlational coefficients for VAS item scores vs the relevant EEG-based values) – the subsequent relationships closely resembled those highlighted by the neurophenomenological analyses. Specifically, changes in alpha correlated strongly with the subjective experience when total and oscillatory power was used, while theta changes correlated strongly when only the oscillatory component was employed for analysis. Also, after the fractal component was extracted correlations with spectral data were overall reduced, i.e. the fractal component appeared to be less functionally relevant than the oscillatory component. Finally the amount of correlations between LZs and subjective ratings were found to be comparable to the number found when alpha power was used (Fig. 6B) (see Fig. S4 for time-averaged psychometric correlations).