Timmerman 5MeoDMT Meditator Study

Chapter 1

This paper is titled "Neural effects and phenomenology of nondual meditation and five-MeO-DMT in an expert meditation practitioner". It was written by Christopher Timmermann, Tommaso Barba, James Sanders, Stéphane Offort, John Dunne, David Erritzoe, and Antoine Lutz. The authors' affiliations include University College London, the Centre for Psychedelic Research at Imperial College London, and the Institut Euthymia for meditation training in France. They also include the Center for Healthy Minds and the Department of Asian Languages and Cultures at the University of Wisconsin-Madison, and the Lyon Neuroscience Research Centre. Christopher Timmermann is the corresponding author. The paper's keywords are psychedelic, mindfulness, consciousness, minimal phenomenal experience, pure awareness, self, and ego-dissolution.

Two terms from the title deserve a quick explanation before anything else. Five-MeO-DMT, pronounced five, M, E, O, D, M, T, is a psychedelic compound. It occurs naturally in some plants and in the skin secretions of the Sonoran Desert toad, and it can also be made synthetically. Compared with better-known psychedelics such as psilocybin or LSD, its effects begin within minutes and are largely over within an hour or two. At high doses, it is known for producing intense experiences of self-dissolution with relatively little visual imagery. In this study it was given as a synthetic nasal spray. Nondual meditation refers to a family of practices in which the usual split between an observer and what is observed, between subject and object, is allowed to relax or fall away. The particular tradition here is Mahamudra, a body of Tibetan Buddhist meditation teachings in which recognising the nondual nature of the mind is the central goal.

One more thing to hold in mind throughout. This is a case study of a single person. Everything you are about to hear describes one expert meditator, measured very carefully across several sessions, rather than a group of participants.

The Abstract states that meditation and psychedelics have separately been studied as powerful tools for probing consciousness, through their capacity to deconstruct the sense of self. Yet direct empirical comparisons remain scarce, particularly in expert meditators. Here, the authors report for the first time a case study of an advanced meditator and Lama from the Mahamudra meditation tradition. He engaged in a traditional style of nondual meditation, received a placebo, meaning an inactive salt-water nasal spray used for comparison, and received two doses of five-MeO-DMT, five milligrams and twelve milligrams. High-density EEG, psychometric scales, and phenomenological interviews were collected in a controlled environment. Three measurement tools were just named, so here is what each one is. EEG, short for electroencephalography, records the brain's electrical activity through electrodes resting on the scalp. The combined activity of large groups of neurons produces tiny voltage changes at the scalp, and these rise and fall in rhythms of different speeds. High-density EEG simply means many electrodes, two hundred fifty-six in this study, which gives a finer picture of where on the scalp each rhythm is strongest. Psychometric scales are structured questionnaires. Here they were visual analogue scales, on which the practitioner rated how strongly he had experienced each of a list of effects. Phenomenological interviews are careful, structured conversations designed to draw out precisely what an experience was like from the inside, moment by moment.

The Abstract continues. The nondual meditation practice employed and low-dose five-MeO-DMT showed overlapping features, including timelessness, reduced labelling of sensory content, and reductions in the narrative self, meaning the sense of being a continuing person with a life story, and in thoughts. Both states were marked by increased alpha power and decreased gamma power. Alpha and gamma are two of the brain's rhythm speeds, measured in cycles per second, or hertz. Alpha is a slower rhythm, roughly eight to thirteen hertz. It is typically strongest when someone is relaxed but awake, and when parts of the brain are being held in check. Gamma is a fast rhythm, above thirty hertz. It is often linked to active local processing, although at the scalp it is also easily contaminated by muscle activity. Power just means how strong a given rhythm is in the recording. Cross-decoding confirmed a significant neural overlap, driven by gamma reductions at posterior and right frontal electrodes. Cross-decoding is a machine-learning check on whether two brain states really look alike. A computer program is trained to recognise the pattern of one state, here the meditation state, and then tested on whether it can tell the drug state from that state's own baseline, data it has never seen. If it can, the two states share part of their neural signature. Posterior electrodes sit toward the back of the head, roughly over the visual and parietal regions, and right frontal electrodes sit over the right side of the forehead. At the same time, the phenomenological and EEG profiles differed. Nondual meditation uniquely emphasised the recognition of nonduality and clarity of mind, while low-dose five-MeO-DMT was characterised by visual imagery. In contrast, high-dose five-MeO-DMT produced a qualitatively distinct profile of sensory disconnection, seeing a "white light", and broad increases in gamma power.

The Abstract closes with the authors' interpretation. These qualitative findings indicate that while self-dissolution in this style of nondual meditation and under five-MeO-DMT overlap in certain respects, they also diverge along specific dimensions. The EEG findings suggest that self-deconstruction, and approximations to contentless awareness, are associated with at least two distinct routes. Contentless awareness, sometimes called pure awareness or minimal phenomenal experience, means a state in which one is conscious but nothing in particular is being experienced. No thoughts, no images, no sense of a body or a self, just awareness itself. Whether such a state truly exists, and what the brain is doing during it, is a live question in consciousness science. The first is a "saturation" route, characterised by increased neural firing, indexed by elevated gamma activity, and by increased entropy. This route was associated with experiences of spaciousness, white light, and sensory disconnection, and it corresponds to high-dose five-MeO-DMT. Entropy, in this context, is a measure of how varied and unpredictable the brain's electrical signal is over time. A signal that keeps repeating the same pattern has low entropy. A signal that constantly changes has high entropy. Higher brain entropy has repeatedly been linked to psychedelic states. Findings for meditation are more mixed, with some studies reporting increases and others decreases. The second is a "subtractive" route, characterised by reduced neuronal firing and decreased entropy. This route was linked to drastic reductions in conceptual elaboration and to increased equanimity, and it corresponds to nondual meditation and low-dose five-MeO-DMT. In plain terms, the authors are proposing two ways of arriving at something like contentless awareness. One is to flood the system, so that so much is happening that ordinary distinctions dissolve. The other is to quieten the system, so that the mind stops labelling and elaborating, and distinctions are simply not drawn. Keep these two routes in mind, because the rest of the paper builds toward them. The latter convergence points to low-dose psychedelics as a potential complement to meditative training, offering synergies that may expand both scientific understanding of consciousness and clinical applications. A promising avenue for testing this possibility, the authors write, would be for future studies to investigate nondual meditation under low-dose five-MeO-DMT.

The Introduction opens by noting that in the past two decades, scientific interest in meditation and psychedelics has dramatically increased, due to their potential use in clinical research and their contribution to the study of consciousness. Evidence from both fields reveals that the states induced by these two families of practices may acutely alter perception, cognition, and emotion in a significant fashion. This leads to a range of possible non-ordinary states of consciousness, depending on the practice, the dose, the substance, or the context.

Within the variability found across meditation practices and psychedelic compounds, a core feature may underlie the dramatic alteration in consciousness they induce. That feature lies in how the sense of self, itself a core feature of conscious experience, is altered under both conditions, with potential beneficial consequences for mental health. Through mechanisms that include significantly slowing the habitual flow of thoughts and dissolving bodily boundaries, certain meditation practices induce states in which two aspects of the self are significantly disrupted. The first is the "narrative" self, related to a conscious, temporally extended sense of identity. This is the self as a character in a story. It is the sense that you are the same person who woke up this morning, who has a history and plans, and who is thinking these thoughts. The second is the "embodied" self, related to a more immediate sensorimotor processing of bodily awareness. This is the self as a body. It is the wordless sense of being located here, inside this skin, feeling and moving. Similarly, psychedelics are known to induce experiences of "self-dissolution", in which both the embodied and the narrative dimensions of the self are significantly dysregulated, minimized, or potentially eliminated. Self-dissolution, also called ego-dissolution in the psychedelic literature, is the experience of the ordinary sense of being a separate self fading or vanishing altogether. Importantly, previous research in both meditation and psychedelics has emphasized one set of changes in particular. Dysregulated connectivity in the Default Mode Network and the medial temporal lobes, together with changes in alpha power, may play a significant role in dissolution of the narrative self. The Default Mode Network is a set of brain regions, many along the midline of the brain, that is most active when a person is not focused on a task, when the mind wanders, remembers, or thinks about itself. The medial temporal lobes, on the inner side of each temple, include the hippocampus and are central to memory. Connectivity means how strongly the activity of different regions rises and falls together. Dissolution of the embodied self, by contrast, may be driven by altered connectivity in the insula and the supplementary motor area, together with reductions in the power of beta rhythms. The insula is a region folded deep within the side of the brain that tracks the internal state of the body, such as heartbeat, breath, and gut sensations. The supplementary motor area, near the top of the head, helps plan and initiate movement. Beta is a rhythm between alpha and gamma in speed, roughly thirteen to thirty hertz. It is strongest over the brain's movement and body-sensing areas, and is linked to bodily and motor processing.

In recent work, the authors and others have emphasized that the scientific study of consciousness may significantly benefit from investigating specific meditation practices and psychedelic compounds that are particularly efficient at deconstructing the self. Timmermann and colleagues set this out in a twenty twenty-three review in Trends in Cognitive Sciences, and Dahl, Lutz, and Davidson made a related argument in twenty fifteen. By leveraging states of radical self-deconstruction, it becomes possible to develop a minimal model of consciousness, corresponding to a conscious state devoid of contents, or so-called "pure awareness". The philosopher Thomas Metzinger has described this as minimal phenomenal experience. The aim is then to determine its neural foundations. Furthermore, suppose such a state can be reached by different routes, such as a specific meditation practice and a specific psychedelic compound. Then any features the two routes share, whether in the brain or in the experience itself, can serve as key markers for the core mechanisms underpinning consciousness.

In this vein, nondual meditation and the psychedelic five-MeO-DMT are strong candidates for exploring this overlap. The authors' previous work shows that both are particularly effective at significantly reducing, or entirely collapsing, the subject-object duality, at inducing feelings of disembodiment, and at producing experiences of timelessness. Subject-object duality is the ordinary structure of experience in which there is a "me" in here who perceives a world out there. Collapsing it means that split stops being felt. Furthermore, both five-MeO-DMT and nondual meditation have been proposed as candidates for approximating a state of contentless awareness, or a "minimal phenomenal experience", with significant gains for the neuroscientific study of conscious experience. From here on, the paper abbreviates the compound to five-MeO, and so will this reading.

The overlaps, and potential synergies, between meditation and psychedelics have been present in anecdotal reports for the past five decades. Both empirical and theoretical work has begun to tackle whether the neural and phenomenological states achieved by the two families of practices are comparable, and whether they can benefit each other. However, studying this overlap has major challenges. Most meditation practitioners never achieve states of self-dissolution or contentless awareness at all, let alone in a controlled laboratory environment. Furthermore, while some expert practitioners may be able to achieve such states, traditional Buddhist frameworks are generally interpreted as discouraging the use of psychoactive substances.

Considering the challenges of mapping extreme states of self-dissolution or contentless awareness in advanced meditation practitioners, recent work has emphasized the value of case studies, or small samples, of expert practitioners who can achieve such states. Novel findings have emerged from this approach concerning the neural correlates of such experiences. A case study measures one person in great depth rather than many people briefly. It cannot say how common a finding is, but it can reveal things that a group average would wash out, especially when the ability being studied is rare. The paper points to two recent intensive case studies of single advanced meditators, one during deep absorption and one during insight meditation. It also cites a two thousand four small-sample study by Antoine Lutz and colleagues, which found that long-term meditators self-induce high-amplitude gamma synchrony during practice.

In this work, the authors report on a direct examination of the overlap and differences between five-MeO and a style of nondual meditation. They administered placebo and two doses of five-MeO to an expert meditator and Lama from the Mahamudra tradition, with over fifteen years of intensive retreat experience. They explored the overlap using psychometric, phenomenological, neural, and cross-decoding machine learning approaches. With that background in place, the paper turns to its Results.

The Results begin with the study itself. The practitioner has fifteen years of retreat experience in the Karma Kagyu lineage of Tibetan Buddhism. The authors estimate this at

Fifty-four, seven hundred fifty hours, assuming ten hours of practice per day. The Karma Kagyu lineage is a branch of the Kagyu school, one of the four major schools of Tibetan Buddhism. Mahamudra is its central meditative teaching. He underwent three separate study visits. Across these visits he performed nondual meditation sessions and received a low dose of five milligrams and a high dose of twelve milligrams of five-MeO, given as a nasal spray, while the authors recorded his brain activity using high-density EEG. A note the Methods section will confirm. Three meditation sessions were run, one per visit, but only the second was analysed. It was rated highest for reaching the target state, seven out of ten against four for the pilot. Like the drug and placebo sessions, it was also done with eyes open. Control conditions consisted of actively letting the mind wander, counting backwards, and administration of a placebo. Controls are comparison conditions. They let the authors ask whether a brain change is specific to meditation or to the drug, rather than something that happens whenever the practitioner sits quietly with electrodes on. The recordings were followed by visual analogue scales and micro-phenomenological interviews, both described in the Materials and Methods.

Under the heading "Psychological effects and phenomenology", the authors first report the rating scales. A visual analogue scale is a line, usually with "not at all" at one end and "extremely" at the other, on which the person marks how strongly they experienced something. The mark is converted to a number from zero to one hundred percent of the maximum. The practitioner completed one such scale for each of dozens of possible effects after every session. Nondual meditation and at least one of the five-MeO doses induced large reported effects, meaning at least fifty percent of the maximum, for general intensity, timelessness, disembodiment, positive emotions, and a sense of gaining intuitive knowledge. In the Mahamudra traditions, all of these would be characterised as different forms of "nyams". The word is pronounced roughly "nyam". The final s is part of the Tibetan spelling, and the same word serves as singular and plural. Nyams are meditation-induced phenomenological features or events that stand out because they are especially intense or unusual, or both. The authors draw this description from Dakpo Tashi Namgyal's classic Mahamudra text, Clarifying the Natural State. Nyams was scored as the highest item for both high-dose five-MeO and nondual meditation.

Other items showed less overlap, but large scores for either nondual meditation or at least one of the doses of five-MeO. The nondual meditation condition resulted in large scores for items corresponding to nonduality, clarity of the nature of mind, not having a perceptual centre, and "spacious mind". All of these are key targets of nondual meditation. "Nature of mind" is the Mahamudra term for the mind's own basic nature, which the practice aims to recognise directly, without concepts. "No perceptual centre" means there was no felt point from which experience was being observed. The last of these, spacious mind, along with "bliss", was reported at forty percent or higher for both high-dose five-MeO and nondual meditation.

High-dose five-MeO induced large scores on items indicating sensory disconnection and perceiving a "white light". Low-dose five-MeO induced large scores on visual imagery and on negative emotions. The authors then subtracted the placebo scores from the scores of each condition and averaged the differences across items. By this measure, the average difference between nondual meditation and low-dose five-MeO was twenty-five point four percent, whereas the difference between nondual meditation and high-dose five-MeO was thirty-one point four percent. This suggests that the psychological effects of the low dose were closer to nondual meditation.

"Everything and nothing" describes a paradoxical experience of being all-encompassing and completely empty at the same time. The authors' earlier five-MeO-DMT study linked it to high doses, which is why its low score here comes up again in the Discussion. "No self-location" is roughly forty percent for the high dose. "Pure awareness" is roughly ten percent, for meditation only. "Cessation of experience" and "loss of consciousness" are small red bars, roughly fifteen and five percent for the high dose, and zero elsewhere. "Void" and "control" are zero in every condition. "Drowsy" is low everywhere, at roughly fifteen percent or less.

These rating-scale findings were complemented with phenomenological interviews, performed to establish the impact of nondual meditation and five-MeO on fine-grained aspects of phenomenology and the sense of self. The interviews averaged forty-two minutes in length. These were micro-phenomenological interviews, a technique described fully in the Methods. In brief, the interviewer guides the person back into a specific moment of the experience and asks, again and again, what it was like, steering away from interpretation and toward the raw structure of the moment. The authors found that nondual meditation and low-dose five-MeO induced similar reductions in the narrative sense of self, in thoughts and reflections, and in phenomenal distinctions. Phenomenal distinctions are the number of separate things one can tell apart in experience at a given moment, such as this sound versus that colour, or me versus the room. Intriguingly, whereas high-dose five-MeO induced a strong form of disconnection from the environment, the nondual and low-dose five-MeO conditions induced a form of "dereification". In dereification, sensory impressions of the environment and of the self, such as bodily sensations, persisted, but were no longer labelled as specific things, or as "self" or "other". To reify something is to treat it as a solid, separate thing. Dereification is the reverse. The sensation is still there, but the mind stops packaging it as an object with a name and an owner. This absence of naming and labelling of phenomena was described by the practitioner as "equanimity", and was not conceptualised as separate from the subject.

The table has one row per category and one column per active condition: nondual meditation, the five milligram dose, and the twelve milligram dose. Each cell gives a short verdict on how that aspect of experience was affected, and then an illustrative quote from the practitioner. Here is the table, row by row.

Phenomenal distinctions. Under nondual meditation, "reduced". The quote repeats the one for sensory connection, and adds a final line. "Also, the notion of time is not there." Under the low dose, "reduced". Rather than a new quote, the authors summarise this as a reduction in clarity, coherence, naming, and labelling, as in the quotes above. Under the high dose, "very reduced". He said: "The connection with the body, the room, was dissolving, then comes something replacing it. A kind of spaciousness, which brought this white light. The awareness is very subtle. It's not even the notion of 'I am aware', it's just awareness of this experience, of these phenomena."

One small mismatch between text and table. The text described similar reductions in narrative self and thoughts for meditation and the low dose. But the table rates both as absent for meditation, and only as reduced for the low dose. Those are the subjective findings. The paper now turns to the brain recordings.

The heading of this part of the Results is "Effects of nondual meditation and five-MeO on high-density EEG". The authors assessed the effect of every condition on two properties of the EEG signal. One was its spectral activity, meaning how much power there is at each frequency. The other was neural entropy. For each session, they contrasted the condition against that session's own preceding baseline recording. They then corroborated these findings with supplementary contrasts against the placebo session. The baseline was chosen as the primary comparison because it is less confounded by fluctuations in arousal present in the placebo condition. A baseline is a recording made just before the condition starts, in the same session, with the same electrode placement. Comparing against it removes a lot of day-to-day noise. Arousal here means general physiological alertness, which shifts the EEG on its own. The authors do not say why it fluctuated in the placebo session.

A few tools make these results easier to follow. First, frequency. EEG rhythms are described by how many times per second they cycle, in hertz. Slow rhythms are called delta and theta, conventionally below four hertz and from four to eight hertz. The spectral tests here did not use fixed bands, and instead searched every frequency from one to forty-five hertz. For a later classifier analysis, though, the authors set bands around this practitioner's alpha peaks at eight and ten hertz. By those definitions, low alpha runs from six to nine hertz and high alpha from nine to thirteen, so a change at seven to eight hertz counts as alpha. Beta runs from thirteen to thirty hertz, and gamma from thirty to forty-five. Second, significance. With hundreds of electrodes and more than one hundred frequency steps there are thousands of comparisons, so some would look different by chance alone. The authors used a cluster-based permutation test to deal with this. It looks for clumps of neighboring electrodes and frequencies that all change in the same direction. It then shuffles the condition labels thousands of times to see how large a clump chance alone tends to produce. A "cluster-corrected" P-value below zero point zero five means fewer than five in every one hundred shuffles produced a clump as strong as the real one.

Nondual meditation resulted in significant increases in power at seven to eight hertz, and decreases in power at nineteen to twenty-seven hertz and at twenty-eight to forty-five hertz. The low-dose five-MeO condition resulted in similar significant increases in power at seven to twelve hertz, as well as decreases at twelve to nineteen hertz and at twenty-one to forty-five hertz. Additionally, the authors found a significant decrease in power at one to six hertz for low-dose five-MeO. All of these comparisons had cluster-corrected P-values below zero point zero five.

The high-dose five-MeO condition resulted in significant increases in power at five to sixteen hertz, and decreases in power at one to seven hertz, in a way similar to the low-dose condition. The two ranges overlap slightly. That is possible because each cluster spans electrodes as well as frequencies, so an increase and a decrease can sit at different places on the scalp. However, unlike the conditions described so far, the high dose also produced significant increases in power at sixteen to twenty-four hertz and at twenty-five to forty-five hertz. Again, all comparisons had cluster-corrected P-values below zero point zero five.

These spectral results are shown in the top half of Figure two, panel A, which has three rows. From top to bottom they are nondual meditation versus baseline, the five milligram dose versus baseline, and the twelve milligram dose versus baseline. On the left of each row is a line graph. Frequency runs along the bottom, from zero to forty-five hertz. The height of the line is the T-value averaged across all electrodes. A T-value expresses how large a difference is relative to how noisy the data are. Zero means no difference. Values above zero mean more power in the condition than at baseline, and values below zero mean less. Stretches where the difference is significant are shaded, pink for increases and green for decreases.

In the top row, for nondual meditation, the line sits near zero across most of the low frequencies. It rises to a small pink peak at around seven to eight hertz. From about nineteen hertz it drops below zero into a green shaded region, and it keeps sinking through the gamma range, reaching about minus six at forty-five hertz. The middle row, for the low dose, looks similar. It dips slightly into green below six hertz, rises to a pink peak at around eight hertz, and then sinks into green all the way up to forty-five hertz. The bottom row, for the high dose, is different. Its vertical scale is wider because the effects are larger. It dips into green at the lowest frequencies. It then shoots up to a tall pink peak at around seven to eight hertz, with a T-value above ten. After that it stays at or just above zero, rising again through the gamma range, so that most of the spectrum from five to forty-five hertz is shaded pink.

On the right of each row are six circular head maps. A topographic head map shows the scalp as if you were looking down on the top of someone's head, with the nose at the top. Colour shows the T-value at each point, with yellow for increases and dark blue for decreases. Small dots mark the electrodes that belong to a significant cluster. Here, red dots mark increases and white dots mark decreases. The six maps show selected frequency ranges: one to six, seven to eight, ten to twelve, thirteen to eighteen, twenty-one to twenty-five, and thirty to forty-five hertz. These are the ranges where significant effects were broadly found across conditions. For nondual meditation, the seven to eight hertz map is bright yellow and covered in red dots, while the twenty-one to twenty-five and thirty to forty-five hertz maps are blue and covered in white dots. The other maps are mid-green, meaning little change, and unmarked. For the low dose, the pattern is similar but broader. The seven to eight and ten to twelve hertz maps carry red dots. The one to six hertz map and every map from thirteen hertz upward carry white dots, and the thirty to forty-five hertz map is the darkest blue of all. For the high dose, the colour scale is wider, running to fifteen and to ten rather than to four. The one to six hertz map is blue, darkest at the back of the head, with white dots across almost the whole scalp. The seven to eight, ten to twelve, and thirty to forty-five hertz maps are warm and densely dotted red. The thirteen to eighteen and twenty-one to twenty-five hertz maps are more mixed, with red dots in patches. The warm, red-dotted gamma map is the opposite of what meditation and the low dose showed.

Next, the authors turn to entropy. Neural entropy has previously been linked with both psychedelic and meditation states. The work cited includes the entropic brain theory of Robin Carhart-Harris and colleagues, and a brain-imaging study of DMT by Timmermann and colleagues. It also includes a study showing increased brain signal diversity under ketamine, LSD, and psilocybin. The authors therefore computed the entropy rate of the EEG signal, using a measure called Lempel-Ziv complexity. Lempel-Ziv complexity comes from data compression. Imagine turning the brain signal into a string of ones and zeros, then reading along it and counting how many genuinely new patterns keep turning up. A repetitive signal produces few new patterns and compresses easily, so it has a low entropy rate. A varied, unpredictable signal keeps producing new patterns, so it has a high entropy rate. In this paper, "neural entropy", "entropy rate", and "Lempel-Ziv complexity" all refer to this same measure. The findings revealed that both the nondual and the low-dose five-MeO conditions significantly decreased average entropy rate compared with their preceding baseline recordings, and displayed similar spatial effects across the scalp. By contrast, the high-dose five-MeO condition significantly increased average entropy rate. All of these comparisons had Bonferroni-corrected P-values below zero point zero one, two-sided. Bonferroni correction is a simple and strict way of adjusting P-values when several tests are run, by effectively dividing the threshold by the number of tests. Two-sided means the test was open to a difference in either direction, up or down. The Methods section names a different correction for these average entropy tests, the false discovery rate. More on that when the Methods are reached.

The bottom half of Figure two, panel B, shows these entropy results. There are three pairs of graphics, one each for nondual meditation, the low dose, and the high dose. Each pair has a split violin plot and a head map. A violin plot shows how values are spread. Its width at each height shows how many measurements had that value, so it looks a little like a violin's body. Here each violin is cut down the middle, with the baseline half in blue on the left and the condition half in red on the right. A dot on each half marks the average. Each violin shows entropy averaged across all channels, and each head map shows the result channel by channel. For nondual meditation, the red half sits lower than the blue half. The average entropy rate falls from roughly zero point four four at baseline to roughly zero point four two five during meditation, with a P-value below zero point zero zero one. For the low dose, the red half also sits lower, falling from roughly zero point four five five to roughly zero point four four five, again with a P-value below zero point zero zero one. For the high dose, the pattern flips. The red half sits higher, rising from roughly zero point four two five at baseline to roughly zero point four four, with a P-value below zero point zero zero one. The head maps agree. The meditation map is mixed in colour and the low-dose map mostly blue, and both carry white dots marking electrodes where entropy fell. The high-dose map is mostly warm and densely covered with red dots, marking electrodes where entropy rose, with a few white dots at the back.

These findings were broadly replicated when each condition was contrasted against the placebo control, especially in alpha and gamma power, as well as in entropy rate. This is shown in Supplementary Figure two, which has the same layout as Figure two, except that each condition is compared with the placebo session after both have been corrected for their own baselines. Against placebo, nondual meditation and the low dose both show raised power in the slow and alpha ranges, up to about ten to twelve hertz, and lowered power in the gamma range above about thirty-five hertz. Their gamma maps are mostly white-dotted, though each has a central patch of red dots. The high dose against placebo again shows lowered power at the very lowest frequencies, then raised power almost everywhere else, peaking in alpha and climbing through gamma. In the entropy panel, nondual meditation and the low dose both show lower entropy change than placebo, each with a P-value below zero point zero zero one. For the high dose, however, the two halves of the violin sit almost level, and the P-value printed on the figure is one. This is worth pausing on. The text says the entropy results were broadly replicated against placebo. But the figure shows that the high dose's rise in average entropy was not significant against placebo. The placebo session's own entropy also rose relative to its baseline, by about as much. So against placebo, only the decreases in average entropy, for meditation and the low dose, held up.

Importantly, when nondual meditation was contrasted against the backwards counting control condition, the effects were broadly similar. However, the significance of the alpha power increase was lost. The authors suggest this points to alpha as a marker of the attentional effort employed in both conditions. Backwards counting from a large number in steps of five takes steady, focused attention. If meditation shows no clear alpha difference from counting, the alpha rise may not be specific to the nondual state. The authors suggest it may instead reflect the effort of holding attention in place. This is shown in Supplementary Figure three. Its line graph has the familiar small peak at around seven to eight hertz, but here that peak is not shaded, meaning it is not significant. From about eight hertz upward, the line sits mostly below zero, and the green shaded region continues all the way to forty-five hertz, deepest in the gamma range. In the head maps, the seven to eight hertz map is warm with no red dots, though a small patch at the back of the head carries white dots. The maps from ten hertz upward are mostly cool and scattered with white dots. The entropy violin shows nondual meditation slightly lower than counting, roughly zero point four two six against zero point four three two, with a P-value of zero point zero two seven. The figure also shows something the text does not mention. Against counting, meditation had significantly lower power from about nine hertz upward, including the ten to twelve hertz range that the authors elsewhere count as high alpha. So the alpha picture is not simply a lost increase.

Overall, the authors conclude, these findings suggest overlapping effects of nondual meditation and the low dose of five-MeO on EEG activity, and differences between these two conditions and high-dose five-MeO.

Next, under the heading "Neural overlaps and differences between nondual meditation and five-MeO", the authors ask whether a computer can tell these states apart, and whether a pattern learned from one state transfers to another. They tested for potential overlaps using a cross-decoding approach between conditions. First, a classifier was trained to distinguish the nondual meditation condition from its preceding baseline. A classifier is a simple machine-learning model. It is shown many short labelled snippets of EEG, some from meditation and some from baseline, and learns which features of the signal best tell them apart. Meditation versus baseline was highly decodable, with a cross-validation score of zero point nine eight. Cross-validation checks that a classifier has learned something real rather than memorising its examples. The data are split into parts, the model is trained on some parts and tested on the part it has not seen, and this is repeated so every part gets a turn as the test set. The Results text calls this zero point nine eight, and the zero point nine one that comes shortly, cross-validation accuracy. The Methods section names the area under the curve, explained in a moment, as the primary metric for the transfer tests. It does not say which measure the cross-validation check used.

Cross-decoding showed significant generalisation to the low-dose five-MeO condition. The meditation-trained classifier could distinguish the low dose from its own preceding baseline, with a P-value of zero point zero zero four after family-wise error correction. Family-wise error correction adjusts for the fact that the same classifier was tested on three different targets. It keeps the chance of any false positive across all three at five percent, rather than five percent for each. In contrast, no significant generalisation was found to either the high dose of five-MeO, with a corrected P-value of one point zero zero, or to placebo, with a corrected P-value of zero point four eight, each against its own baseline.

Confirmatory analyses ran the same idea in reverse. A classifier trained on the five milligram dose versus its baseline was also highly decodable, with a cross-validation score of zero point nine one. It generalised significantly to distinguish nondual meditation from its baseline, with a P-value of zero point zero zero zero one. The authors take this as confirming the overlap of low-dose five-MeO and nondual meditation in brain activity.

Furthermore, gamma power reductions at posterior and right frontal electrodes were the highest contributors to this overlap, for both the nondual and the low-dose five-MeO classifiers. This is shown in Figure three, panel B, which has two halves, one for each classifier. Feature importance measures how much the classifier relies on each type of input when making its decision. Each classifier was given eight types of feature, measured at every electrode. These were power in seven frequency bands, delta, theta, low alpha, high alpha, low beta, high beta, and gamma, plus entropy rate. On the left of each half is a bar chart ranking the eight features. For the meditation classifier, gamma is far ahead with an importance of roughly zero point two six. It is followed by high beta and entropy rate at roughly zero point one three to zero point one four, then delta, low beta, low alpha, and high alpha at roughly zero point zero eight, and theta last at roughly zero point zero six. For the low-dose classifier, gamma again leads, at roughly zero point two eight. It is followed by entropy rate at roughly zero point one eight, high beta and low alpha at roughly zero point one four to zero point one five, and then theta, low beta, delta, and high alpha at roughly zero point one one to zero point one two. Next to each bar chart is a head map of the gamma classifier weights. The classifier weights show which electrodes pushed the decision, and in which direction. Blue and red are opposite directions, and the deeper the colour, the stronger the push. The ten electrodes with the largest weights in either direction are marked with green dots. In both maps, the back of the head is deep blue, and a second blue patch sits over the right side of the forehead. Most of the green dots sit in those two places, along the back of the head and over the right front, which is where the authors locate the gamma reductions driving the overlap.

Finally in the Results, the authors tested the differences between nondual meditation and the two doses of five-MeO head to head. To do this, they first baseline-corrected each condition, to avoid order effects, and then contrasted the corrected conditions directly. The conditions came in a fixed order across three visits. The analysed meditation session and the low dose took place on the same visit, and the high dose came on a later one. Subtracting each recording's own baseline first makes it less likely that shifts between recordings, such as electrode fit or general state, are mistaken for differences between conditions. Compared with low-dose five-MeO, nondual meditation showed significantly larger power at two to five hertz, at six to eleven hertz, at twenty to forty-five hertz over right-side electrodes, and at thirty to forty-five hertz over right frontal electrodes. The same contrast showed significantly lower power for meditation at thirty to forty-five hertz over left frontal and posterior electrodes. Compared with the twelve milligram dose, nondual meditation showed significantly larger power at one to six hertz, widely distributed across the scalp. The same contrast showed significantly less power for meditation in two widely distributed clusters, at five to sixteen hertz and at seventeen to forty-five hertz. All of these comparisons had cluster-corrected P-values below zero point zero five.

Clusters of significantly lower entropy rate were found for nondual meditation compared with both the five milligram and twelve milligram doses of five-MeO, all with cluster-corrected P-values below zero point zero five. However, average entropy was lower for nondual meditation only when compared with the twelve milligram dose, with a Bonferroni-corrected P-value below zero point zero one, two-sided. Figure four, panel B, shows this with two split violin plots of the change in entropy from each session's baseline. Against the low dose, the two halves sit at almost the same level, both just below zero, and the printed P-value is zero point six zero. The head map beside it still shows scattered white dots, which are the local clusters. Against the high dose, the halves separate clearly. The high-dose half sits above zero at roughly plus zero point zero one five and the meditation half below zero at roughly minus zero point zero one five, with a P-value below zero point zero zero one and a head map covered in white dots.

That completes the Results. In the Discussion, the authors step back to ask what these findings mean.

The Discussion opens with a summary. In this study, the authors explored the overlap between meditation and psychedelic drugs by comparing the effects of two doses of five-MeO-DMT with a style of nondual meditation, in an expert meditator with over fifteen years of retreat experience. Their findings showed distinct neural and phenomenological profiles for the states induced by nondual meditation and by a high dose of five-MeO. They also revealed overlaps between meditation and the low dose of five-MeO in several neural features, and in some, but not all, phenomenological features. A cross-decoding machine learning approach confirmed this overlap, with reductions in posterior and right frontal gamma power driving the shared brain activity of nondual meditation and low-dose five-MeO.

Psychometric scores for the subjective effects of five-MeO and nondual meditation revealed both overlaps and differences. High scores for both nondual meditation and five-MeO were found for various features, including positive emotions, timelessness, disembodiment, and a sense of gaining intuitive knowledge. These and other experiences all fall under the Mahamudra category of nyams, an experience or phenomenological feature that stands out because it is especially intense or unusual. While some nyams may indicate progress in meditation, in general they are treated with caution, because they can generate attachment, or "grasping", to such states. In Buddhist terms, grasping means clinging to an experience, fixating on it as something solid, and wanting to hold on to it or have it again. The worry is that a practitioner who chases blissful or dramatic states starts to treat them as the goal, and so loses sight of the actual practice. As such, these remarkable experiences can become a hindrance to the intended endpoint of meditation. For the Mahamudra traditions, that endpoint is the ongoing recognition of the nature of the mind as intrinsically nondual. This recognition in turn enhances traits such as compassion and cognitive flexibility. For this account, the authors again cite Dakpo Tashi Namgyal's Clarifying the Natural State.

Both the high dose of five-MeO and nondual meditation were scored highly for nyams. But only nondual meditation was scored highly for several of its own meditative endpoints: nonduality, clarity of the nature of mind, and spacious mind. This distinction points to a specific difference between psychedelic and nondual meditation practices. Psychedelic practice is frequently linked with transient drug experiences. Nondual meditation, by contrast, is linked to the development of specific traits, especially the capacity for ongoing recognition of nonduality, or the nature of mind, regardless of whether any nyams are occurring. A state is something temporary, like feeling calm this afternoon. A trait is a lasting disposition, like being a calm person. A long-standing question in contemplative science is whether temporary states can be turned into lasting traits. Nyams, or intense experiences interpreted as "spiritual", can be over-emphasised in current psychedelic practices. The authors note this is not dissimilar to the earlier Western assimilation of meditation practices. Here they cite Chogyam Trungpa's book, Cutting Through Spiritual Materialism. However, advanced psychedelic users and practitioners in recreational, therapeutic, and traditional contexts stress the relevance of skilfully integrating such experiences with wider therapeutic, cultural, and ritual practices. The aim is to foster self-exploration, the development of traits, and enhanced individual and social wellbeing, beyond individual transient experiences. Integration is the psychedelic community's term for the work done after an experience, such as reflection, talking it through, and changes in daily life, so that the experience has lasting meaning rather than being a one-off event. With this in mind, the authors say it is important to note that the practitioner's limited prior exposure to psychedelics may have prevented him from framing the psychedelic state as a recognition of nonduality.

Larger scores were found on some items for the high dose of five-MeO, namely sensory disconnection and seeing a white light, and on others for the low dose, namely visual imagery and negative emotional reactions. The phenomenological interviews revealed several features of the self to be disrupted by both the low dose of five-MeO and nondual meditation. The interviews also revealed a contrast in how sensory experience changed. The high dose of five-MeO induced a strong experience of sensory disconnection. The low dose and nondual meditation did not reduce the experience of sensory content, but rather "dereified" it, by removing the conceptualisation of that content. Importantly,

phenomenal distinctions were more strongly reduced under the high dose of five-MeO than during nondual meditation. Yet the analyses revealed that under the high dose, the distinction between contents and the awareness of those contents remained present, albeit in a subtle way. During nondual meditation, that distinction was completely absent. The paper does not say which interview passages show this. One that seems to fit is the high-dose quote from Table one, "it's just awareness of this experience, of these phenomena." Compare that with the meditation quote, "The phenomena, the awareness, are not separated. "

Overall, these phenomenological findings suggest that the self and other contents of experience are dramatically deconstructed both under high doses of five-MeO and during nondual meditation, but that the type of deconstruction is of a different quality. A high dose of five-MeO can dramatically reduce phenomenal distinctions, disconnect the individual from the environment, and collapse self-object distinctions, while still retaining dualistic elements. During nondual meditation, on the other hand, elements pertaining to the self, the environment, and other contents may still be present, yet the habitual distinction, or duality, between subject and object collapses. In this context, a key claim of the Mahamudra tradition is that the meditative state involves an ongoing, conscious recognition that duality is absent. For high-dose five-MeO, this ongoing conscious recognition may be extremely difficult to achieve during the experience itself. Rather, it emerges in subsequent reflection on, or integration of, the experience. Since the meditator was not explicitly instructed to meditate during the five-MeO sessions, whether this recognition can be maintained even at high doses remains an open empirical question warranting further investigation. The Methods are more specific on this point. During the drug and placebo sessions, the practitioner was instructed to avoid meditating.

Intriguingly, some elements of nondual meditation were present under the low dose of five-MeO. These included enhanced equanimity towards the contents experienced, and reduced "labelling", even while contents of the environment were present. Equanimity is an even-minded, non-reactive stance towards whatever arises. Pleasant and unpleasant experiences are both allowed without being pushed away or clung to. In this study, the practitioner used the word for experiencing things without naming or labelling them. These findings suggest that low doses of five-MeO may be used to enhance meditative practice. They could do this by relaxing attentional control and decreasing conceptualisation, while preserving a degree of agency, which is habitually lost at high doses. That preserved agency may then be used to develop the attentional skills required for advanced meditative practices. Agency here means the ability to still direct one's own mind, for example to choose where to place attention, rather than being completely swept along by the drug. This is consistent with reports of increased mindfulness capacities thirty days after a single use of five-MeO in naturalistic settings, including non-judgement, a concept linked with equanimity. Non-judgement is a facet measured by common mindfulness questionnaires. It means noticing thoughts and feelings without evaluating them as good or bad. Naturalistic settings means real-world ceremonies or retreats, rather than a laboratory. Importantly, another report found that increases in non-judgement in the days following five-MeO inhalation were correlated with acute experiences of self-dissolution. Both of these reports come from studies led by Malin Uthaug.

Turning to the brain recordings, the authors note that, compared with baseline, both nondual meditation and the low dose of five-MeO induced similar increases in alpha power, reductions in high beta and gamma power, and decreases in entropy rate. This contrasted with the high dose of five-MeO, which significantly increased gamma power, but also produced large increases in alpha power. These results are consistent with replicated previous findings of increased alpha power during nondual meditation, including work by Enrico Fucci, Antoine Lutz, and colleagues. Lutz is also one of this paper's authors. They are, however, inconsistent with earlier results showing decreased alpha power during five-MeO administration, from the authors' own twenty twenty-five study and from a twenty twenty-five study by Blackburne and colleagues. The preserved alpha power this practitioner showed under five-MeO suggests that expert meditators may retain a developed skill of maintaining attentional control during non-ordinary states, such as those induced by five-MeO and by nondual meditation. Alpha rhythms are widely thought to reflect active inhibition, the brain damping down processing in regions that are not currently needed. So strong alpha can be a sign of controlled, selective attention rather than of idleness. The association between alpha power and attentional control is further strengthened by the finding that the significance of alpha power was lost when nondual meditation was contrasted against backwards counting, since that condition also requires attentional effort.

Consistent with classic accounts of gamma power, including work by Wolf Singer, Pascal Fries, and Nikos Logothetis's group, decreased gamma power during nondual meditation and low-dose five-MeO may index decreased neuronal firing and fewer contents experienced. In experience, these reduced contents would show up as decreased conceptualization and increased equanimity. Singer and Fries are known for linking gamma rhythms to how neurons coordinate their firing. In recordings made inside animal brains, gamma-range activity tends to rise when nearby neurons fire more, and fall when they fire less. The link is less direct for scalp EEG, where gamma is weak and easily contaminated by muscle activity. This kind of evidence is why lower gamma is often read as less local neural activity. This runs the other way from Antoine Lutz's two thousand four finding, mentioned in the Introduction, of high-amplitude gamma in long-term meditators. That study used a different practice, compassion meditation, and this paper does not discuss the difference. The decrease in gamma is consistent with the decreased neural entropy seen during both states, since entropy has previously been associated with richness of perception. Conversely, the high dose of five-MeO induced dissolution of both narrative and embodied self, disconnection from sensory input, and a limitless, spacious "whiteness". These high-dose experiences appear to be indexed by increased neuronal firing and entropy. As a reminder, this entropy increase was measured against the session's own baseline. Against placebo, as Supplementary Figure two showed, it was not significant. Overall, these findings suggest that there are two opposing avenues for achieving states that approximate contentless experience. One is a "saturation" route, involving an overflowing of neuronal firing, shown here by high-dose five-MeO. The other is a "subtractive" route, marked by reduced neuronal firing, characteristic of nondual meditation and low-dose five-MeO. This is the central proposal of the paper. States that approach contentless awareness may be reached either by turning the brain's activity up until it overflows, or by turning it down until little is left to elaborate. The authors stress that the resulting states still differ in quality.

In previous work, the authors found high doses of five-MeO to be linked with an experience of "everything and nothing", which possibly corresponds to an overflowing of experienced contents. It is tempting to suggest that this was also happening here. However, while the practitioner did identify the high-dose state as one of limitless, spacious "whiteness", he did not score highly on "everything and nothing". In Supplementary Figure one, this item reached only roughly twenty-five percent for the high dose and roughly twenty percent for meditation. Future neurophenomenological studies, closely linking brain activity with real-time experience sampling, are required to refine these associations in a larger sample of expert practitioners. Neurophenomenology is an approach, proposed by the neuroscientist Francisco Varela, that treats careful first-person reports and brain measurements as equal partners. Real-time experience sampling means asking the person what they are experiencing during the recording itself, rather than only afterwards.

The machine learning cross-decoder revealed significant overlaps in neural effects between nondual meditation and low-dose five-MeO. Importantly, the classifiers' performance was primarily driven by reductions in gamma power at posterior and right frontal electrodes. These findings could be interpreted as consistent with both states involving reduced neural firing. They also agree with a recent report by Melanie Boly and colleagues identifying posterior gamma power as a neural correlate of experiences of "pure presence" achieved in meditation practice. Reduced firing of this kind, the authors say, is the "subtractive" route they propose here. Pure presence is a term from meditation research for a state of vivid, open awareness without perceptual objects, thoughts, or a sense of self. It is close to what this paper calls contentless awareness. When directly assessing differences between the conditions, the authors found that nondual meditation showed stronger effects than low-dose five-MeO in alpha power, which was increased, and in gamma power, which was mostly decreased. They suggest this indicates that nondual meditation was more effective at achieving the neural profile the two states share. The Results give a more mixed picture of gamma here. Compared with the low dose, meditation had higher power from twenty to forty-five hertz over the right side, and from thirty to forty-five hertz over the right front. It had lower power from thirty to forty-five hertz only over the left front and the back.

Overall, the authors say, these findings corroborate the phenomenological evidence of some overlap between the experiences induced by meditation and by low-dose five-MeO, and ground that overlap in objective neural effects. Furthermore, they lay down a path to explore how low-dose psychedelic use may potentiate meditation practices that are known to take years of training to master. Future work should complement ongoing efforts exploring how psychedelic use may benefit meditation practice, such as studies combining psilocybin with mindfulness training. It should focus on the relative benefits of five-MeO compared with other psychedelics, especially considering its short duration of action and its neurophenomenological profile, which is similar to that of meditation. Conversely, a neurophenomenological study could compare nondual meditation under low-dose five-MeO with nondual Mahamudra meditation without psychedelics. This could help distinguish the intense phenomenological experiences of psychedelics or meditation, which the authors have categorized under the Tibetan term nyams, from the specific target of the meditation. That target is the recognition of nonduality, characterized as the nature of the mind.

The authors then set out some important limitations. This study reports on a single expert practitioner, which restricts how far the findings can be generalized to a larger population. In addition, meditation and psychedelic states differ in their temporal unfolding and in their context. Meditation develops gradually with training, whereas psychedelic states are pharmacologically induced, so their comparison can only ever be partial. The EEG analyses also warrant caution, particularly the reported increases in gamma-band activity, because gamma is highly sensitive to muscle artifacts. Muscles in the scalp, jaw, face, and neck produce electrical activity of their own, much of it in the same fast range as gamma. Tensing the jaw or frowning can therefore look like a gamma increase. The Methods describe removing face and neck electrodes and muscle-contaminated segments to limit this. Nonetheless, the authors note that the decreases in gamma they present are not prone to such confounds. Future studies should examine a wider family of meditation practices and psychedelic drugs, to build a more comprehensive profile of their overlaps and differences.

The Discussion closes by stating that these findings provide the first direct assessment of the similarities and differences between the neural and subjective effects of psychedelics and meditation in an expert practitioner. The results could inform future studies with an expanded sample of individuals to corroborate these findings, which the authors say they intend to carry out.

The final main section of the paper, the Materials and Methods, explains how the study was done. It starts with the participant.

Under the heading "Study participant", the authors describe a fifty-seven-year-old man, recruited based on his meditation expertise. The inclusion and exclusion criteria were having had at least one experience with a psychedelic drug, being physically and mentally healthy, having no history of mental health disorders, and being eighteen to sixty-five years old. The practitioner provided written informed consent. The study was approved by the National Research Ethics Committee London Brent, and also by the Health Research Authority. This means an independent ethics committee reviewed the study before it began, and the national body that oversees health research also approved it. It was conducted under the guidelines of the revised Declaration of Helsinki, from two thousand, the International Committee on Harmonisation Good Clinical Practices guidelines, and the National Health Service Research Governance Framework. The Declaration of Helsinki is the international code of ethics for research on people. Good Clinical Practice is a standard for running studies safely and recording them reliably. Imperial College London sponsored the research, which was conducted under a Home Office licence for research with Schedule one drugs. Schedule one is the United Kingdom's most tightly controlled drug category, which includes most psychedelics. Research with these drugs needs a special licence from the Home Office, the government department that licenses controlled drugs. This study is part of a larger protocol investigating the effects of five-MeO-DMT on the human brain, with the research ethics committee reference twenty-two, L O, zero two three one.

The next part, "Study design", sets out the schedule. The practitioner underwent three meditation sessions and three drug or placebo administrations over three study visits. The first and second visits were separated by a day, whereas the third visit came three days after the second. During the first visit, an eyes-open pilot meditation session in the morning was followed by placebo, which was saline. During the second visit, an eyes-open meditation session was followed by five milligrams of five-MeO. The third visit consisted of an eyes-closed meditation session followed by a twelve milligram dose of five-MeO. Only the second meditation session was analysed, as it was the most highly rated for achieving the target meditative state. The pilot session was rated four out of ten, whereas the second was rated seven out of ten. The second session was also consistent with the eyes-open condition of the five-MeO-DMT and placebo sessions. This matters because closing the eyes by itself strongly boosts alpha power, so an eyes-closed session cannot be fairly compared with eyes-open ones.

Under "Meditation condition", the authors describe that second session. It involved high-density EEG recordings of an eyes-open baseline condition lasting eight minutes. The first part was a mind-wandering condition, in which the practitioner was instructed to let his mind wander by engaging with salient memories or thoughts. This was followed by a backwards counting condition, in which he was asked to count backwards from ten thousand in steps of five. To keep consistency with the drug and placebo conditions, the mind-wandering baseline was used for the main analyses.

Following the baseline recordings, the practitioner meditated for a total of sixty point two minutes. After initial mental preparatory steps, he cultivated mental stability and clarity by allowing the mind to rest in its natural state, without relying on a specific object of attention. During meditation, he signalled every time he began the practice by saying "in" aloud. Whenever he achieved the state of nonduality, or "nature of mind", he was instructed to signal when that moment was done by saying "out". These spoken words act as time stamps, so the brain recording can be lined up with the moments he reports. Throughout the meditation sessions, he maintained a standard cross-legged meditation posture, as seen in the photograph in the first figure.

During the meditation, the practitioner achieved the nondual state seventeen times, lasting on average one hundred ninety-one point five seconds, plus or minus thirty-four point five seconds. Based on his reports, the authors analysed the EEG in eleven-second segments before the end of each nondual state, as signalled by the "out" report. They excluded the one second immediately before each verbal report, to avoid the potential confounder of the readiness potential. That left each segment lasting ten seconds. The readiness potential is a slow build-up of electrical activity over the brain's movement areas before a voluntary action, including speech. It is strongest in the final moments, so cutting the last second removes its largest part, although it can begin earlier.

The subsection "Drug and placebo conditions" comes next. The five-MeO-DMT used, known as BPL-zero zero three, was provided by Beckley Psytech. A Phase one trial of this formulation in healthy volunteers, by James Rucker and colleagues, is cited for it. It was a benzoate powder, administered as a unidose nasal spray delivered by the study medic. Benzoate means the drug was made as a salt with benzoic acid, a common way to give a drug a solid, powder form. A unidose spray is a single-use device that delivers one fixed dose. Two doses were administered, five milligrams at the second visit and twelve milligrams at the third. The placebo, at the first visit, was saline administered as a nasal spray.

The drug and placebo sessions took place in the same room as the meditation sessions. The practitioner sat in a medical chair while continuous high-density EEG recordings took place, starting with an eight-minute baseline and lasting until the effects of five-MeO or placebo subsided. He was instructed to keep his eyes open throughout the session, to engage in a state similar to the baseline recordings of the meditation sessions, and to avoid meditating.

The meditation and the drug and placebo conditions were each followed by completing the visual analogue scales querying several psychological effects, shown in the first figure. Then came a micro-phenomenological interview.

The following subsection is "Micro-phenomenological interviews and analysis". These interviews were used for a fine-grained investigation of aspects of experience previously identified as central to self-deconstruction states induced by five-MeO, in the group's twenty twenty-five paper in Neuroscience of Consciousness. Those aspects include the narrative and embodied dimensions of the self, the distinction between subject and object, and more. The interview first guides the interviewee to immerse himself in the memory of the experience. It then directs preferential attention to the structure of the experience,

rather than its content. In this way, it aims to minimise confabulation and post hoc interpretation. Confabulation is unknowingly filling gaps in memory with plausible but invented detail. These are threats to validity that commonly confound naive subjective reports, as argued by Claire Petitmengin and colleagues. Petitmengin is the researcher who developed the micro-phenomenological interview method, building on earlier work by the French psychologist Pierre Vermersch. Micro-phenomenology has been employed in studies of psychedelic drugs, meditation, and perceptual illusions, such as the rubber hand illusion.

The analysis combined micro-phenomenological analysis with deductive thematic analysis. Deductive thematic analysis looks for themes fixed in advance, rather than letting themes emerge from scratch. In the interviews, a timeline of the experience was established. The practitioner was asked to identify the moments of the meditation or five-MeO-DMT session in which his experience of self was most affected. Once the interviews were transcribed, the passages describing these moments were isolated, using linguistic indicators of temporal shifts to exclude earlier and later moments. These are words marking a change in time, such as "then" or "just before". Following their previous analysis of five-MeO experiences, the authors assessed the presence and form of five broadly studied structures of consciousness in these moments. Those structures were the embodied self, the narrative self, the presence of thought or reflection, sensory disconnection from the environment, and the number of phenomenal distinctions in a specific moment. These are the five rows of Table one.

The subsection "High-density EEG recordings and preprocessing" covers the brain data. Recordings were obtained from an E G I two hundred fifty-six-channel HydroCel Geodesic Sensor Net and a Net Station amplifier at five hundred hertz. The net, made by E G I, is a stretchy web of sponge electrodes soaked in salt solution. Recording at five hundred hertz means five hundred measurements per electrode every second. The data were referenced online at Cz and recorded continuously throughout the conditions. Cz is the electrode on the top of the head. During recording, every other voltage was measured against it, as the zero point.

The data were preprocessed using the FieldTrip toolbox, by Robert Oostenveld and colleagues, implemented in MATLAB. FieldTrip is free software for analyzing brain recordings, and MATLAB is the programming environment it runs in. The data were downsampled to two hundred fifty hertz, demeaned, and then band-pass filtered from zero point five to forty-five hertz. Downsampling from five hundred to two hundred fifty hertz halves the samples per second. That can still capture rhythms up to one hundred twenty-five hertz, well above the forty-five hertz analysed here. Demeaning centres each channel on zero. The filter strips out slow drifts below zero point five hertz and faster noise above forty-five hertz. Channels placed on the neck and face were removed, to improve the subsequent steps. Those electrodes sit over muscles and pick up a lot of muscle noise. Visual inspection was then performed to remove noisy channels, and segments contaminated with gross and muscle artefacts. That is, an analyst checked the recording by eye and cut out the obviously spoiled parts. Independent component analysis was then performed, and components corresponding to cardiac, eye, and residual line-noise artefacts were removed. This method separates the recording into its underlying sources, so that the heartbeat, eye movements, and the hum of mains electricity can be taken out. The removed noisy electrodes were then interpolated, before re-referencing to the average of the electrodes. Interpolation fills in a removed electrode from its neighbors. Re Referencing then measures each electrode against the average of the electrodes, instead of the top of the head.

Under the heading "Spectral and entropy analyses", the authors first define which moments were analyzed. Analysis of the meditation condition used what was estimated as the most certain moment of the practice, the ten seconds preceding the report of coming "out" of the nondual state. Analysis of the placebo and five-MeO conditions focused on the time the practitioner indicated as the most immersive moment of the twelve milligram five-MeO condition. The twelve milligram session was video-recorded, and he then viewed the video to indicate the moments of strongest experience. This corresponded to the period from four point seven to six point nine minutes after drug administration, before he closed his eyes in the twelve milligram session. This does not sit easily with the instruction, described earlier, to keep his eyes open throughout the session. The paper does not say when or why he closed them. Put plainly, this window was chosen from the high-dose video alone. The same four point seven to six point nine minutes after dosing was then used for the five milligram and placebo sessions as well.

Spectral analysis was performed on three-second epochs with fifty percent overlap, using a Hanning-windowed fast Fourier transform from one to thirty hertz, in zero point two five hertz steps. The recording is cut into three-second pieces, each overlapping half of the next. The fast Fourier transform turns each piece into how much of each frequency it contains, and the Hanning window tapers its edges, which reduces power from one frequency leaking into its neighbors. For higher frequencies, from thirty to forty-five hertz, the authors used Slepian multitapers with a spectral smoothing of plus or minus three hertz. Multitapers analyze each piece through several differently shaped windows and average the results. This gives a steadier estimate of fast, noisy rhythms, at the cost of blurring across three hertz either side.

Entropy rate was obtained using the Lempel-Ziv nineteen seventy-six algorithm. The signal was binarized using the mean of each three-second epoch, meaning each point became a one if above that average, and a zero if below. The algorithm, known as L Z seventy-six, then generates a dictionary of unique subsequences, adding each new pattern of ones and zeros as it first appears. This procedure quantifies the temporal diversity of the signal. Normalizing it gives the entropy rate. Normalizing rescales the raw pattern count so that recordings can be compared fairly. On this kind of scale, a completely random signal scores close to one and a perfectly repetitive one close to zero. The paper does not spell out its exact formula.

Independent t-tests were performed on the EEG data, using a cluster-based permutation approach with seven thousand permutations, following Eric Maris and Robert Oostenveld. An independent t-test compares the averages of two separate sets of trials, here condition and baseline. The seven thousand permutations are label shuffles showing what chance alone produces. For each condition, spectral analysis used a data-driven, band-free approach, finding clusters of significance across electrodes and frequency ranges by contrasting the condition's trials against its own baseline. Band-free means no frequency bands were assumed in advance. A similar cluster-based approach was used for entropy rate, following the same procedure, but assessing significance across channels only. Finally, the authors assessed differences in average entropy rate. They first averaged across channels, then contrasted the result against its preceding baseline using a permutation test with ten thousand permutations. The resulting P-values of these average entropy contrasts were then corrected for multiple comparisons with false discovery rate, or F D R, correction. This correction limits the expected share of significant results that are false alarms. The paper is inconsistent here. The Results text, and the captions of Figure two, Figure four, and Supplementary Figure two, all describe the average entropy tests as Bonferroni-corrected. The paper does not say which correction was actually used. All P-values shown are two-sided, meaning a difference in either direction counted.

The final subsection is headed "Cross-decoder". The authors trained a linear, L two-regularised logistic regression classifier to discriminate nondual meditation from its preceding baseline. This simple classifier draws a weighted, straight-line boundary between the two classes. The L two penalty shrinks all the weights toward zero, which makes the model less likely to fit noise in the training data. It used per-trial feature vectors, flattened across electrodes and features. For each trial, all eight features at every electrode were strung together into one long list of numbers. The features were entropy rate and average power in seven frequency bands. These were delta from one to four hertz, theta from four to six hertz, low alpha from six to nine hertz, and high alpha from nine to thirteen hertz. The remaining bands were low beta from thirteen to twenty hertz, high beta from twenty to thirty hertz, and gamma from thirty to forty-five hertz. These bands were selected based on a dominant low alpha peak frequency of eight hertz, and a high alpha peak frequency of ten hertz. Conventionally, theta runs to about eight hertz and alpha from eight to thirteen. These bands instead follow this practitioner's own alpha peaks, which is why seven to eight hertz counts as alpha here.

Features were z-scored using training data only. Z-scoring puts every feature on a common scale. Using only the training data to do it stops information leaking in from the test data. Class imbalance was handled with inverse-frequency class weights. These give the class with fewer trials proportionally more weight, so both classes count equally. A five-fold inner cross-validation on the training set is reported as a learnability check. The training data are split into five parts, each taking a turn as the test part. This check is most likely the source of the cross-validation scores reported in the Results, zero point ninety-eight for the meditation classifier and zero point ninety-one for the confirmatory low-dose classifier. The trained model was then tested on three target contrasts, twelve milligrams of five-MeO, five milligrams of five-MeO, and placebo, each against its own baseline. The primary metric was AUC. Significance was assessed with a Westfall-Young max-statistic permutation test with ten thousand permutations. It shuffled the training labels only, and took the maximum AUC across targets, to control family-wise error. Each of the ten thousand times, the model was retrained on shuffled labels and only the best of its three AUC scores was kept. A real result counted as significant only if it beat nearly all of these best-of-three chance scores. One more technical inconsistency. The paper says all P-values are two-sided, and the Figure three caption labels this test two-sided. But a test that keeps only the highest AUC looks only for scores above chance. That fits the high dose, with an AUC of zero point sixteen, receiving a corrected P-value of one point zero zero. The Methods also leave some reported analyses undescribed. They do not explain the head-to-head comparisons between conditions, the comparisons against placebo and backwards counting, the confirmatory classifier trained on the low dose, or how feature importance was calculated.

The paper's list of fifty-two references is not read out. Citations that mattered were named along the way, and the supplementary figures were described where the main text refers to them.

That is the end of the paper.