Ivana Nizetic Kosovic  
Toni Mastelic
Project outline
1 Abstract
2023-04-18
The purpose of this project is to perform meta-research into possible data analytical studies that can be performed using data acquired from various DMT related experiments, i.e., no data analytics study will be performed as part of this project, rather we will try to identify what data analytical studies can be done and with what outcomes and use cases.
2 Team
The project is commissioned by Sandro Mur. The project team is two people, Ivana Nizetic Kosovic as a principal data scientist, and Toni Mastelic as a senior data scientist.
3 Work packages
This project includes five work packages. Both Ivana and Toni will be working on all packages jointly. The packages include:

• WP.1 - Document related work - explore related work, research projects, experiments, technologies, etc. This requires going through the available literature. The goal of this WP is to understand the background story of DMT and find out if there are any
  publicly available datasets as well.
• WP.2 - Document feasible experiments - talk to other scientists to learn what kind of experiments they will or are able to do,
  and what data they can acquire. This requires at least two face to face meetings with other scientists, and perhaps some online
  sessions. The goal of this WP is to get an idea of what data we can get.
• WP.3 - Identify feasible studies - match the scientist’s feedback to feasible data-driven related studies that can be done using
  their data. This also requires investigating existing models or approaches for these studies. The goal of this WP is to identify
  data analytic studies and outcomes we could get from experimental data.
• WP.4 - Explore new directions - explore what additional analytical studies might be performed and what additional data
  would be required to do so. The goal of this WP is to give guidelines on what additional data could be interesting and why.
• WP.F - Write final report - write a report that documents all of the above. Since every WP will result with an intermediate
  report, the goal of this WP is to combine all those findings and present them in a consistent and comprehensive manner.
  Figure 1: Work package execution order
  All work packages will be iterated at least twice in the following manner (Figure 1): First, we explore DMT related work (WP.1). Then, we use this acquired knowledge to talk to other scientists in order to learn about the experiments they will and are able to do (WP.2), after which we go back to the related work and update it (WP.1). Next, we try to match the experiments other scientists will do (i.e., data they will acquire) to the data analytics studies that can be done with this data (WP.3), and then go back to other scientists to confirm this (WP.2). Next, we explore different directions that might require additional experiments/data (WP.4), and compare them with the identified analytical studies (WP.3) to understand additional requirements. Finally, we start writing a final report (WP.F), and based on it we iterate on exploring new directions (WP.4) and include them in the final report (WP.F). 35719WP.1 WP.2 WP.3 WP.4 WP.F2468

1
Ivana Nizetic Kosovic
DMT META-PROJECT
​Toni Mastelic WP.1 Report
Abstract
2023-05-24
DMT Meta-Project study is part of a broader DMT project focusing on research and innovation aspects of DMT and its use in various fields. The goal of this study is to identify possible research and innovation directions that go beyond the current studies being done around the world.
This is the first out of five reports for the DMT Meta-Project documenting the outcomes of WP.1, i.e., documenting the related work. Other work packages include WP.2 Document feasible experiments, WP.3 Identify feasible studies, WP.4 Explore new directions, and WP.F Write final report.
This report is structured as follows. Section 1 explains the position of this study withing the broader DMT project and the structure of the related work relevant for this study. Section 2 covers the related work on bio-chemical properties of DMT, while Section 3 explains the metabolism of DMT. Sections 4 and 5 list relevant research groups around the world working on DMT in the context of its potential usage.

Contents
1  Introduction 2
2  Bio-chemical properties of DMT 2
2.1 NaturaloccurrenceofDMT ................................................ 3
2.2 SynthesisofDMT ..................................................... 3
3  DMT Metabolism 4
3.1Ayahuasca......................................................... 5
3.2 DMTtrip.......................................................... 5
4  Research groups on DMT 5
4.1  ImperialCollegeLondon.................................................. 5
4.2  JohnsHopkinsUniversity ................................................. 6
4.3  UniversityofMichigan................................................... 6
4.4  UniversityofCalifornia .................................................. 6
4.5  King’sCollegeLondon................................................... 6
5  Alternative researchers 6
5.1 DMTxproject ....................................................... 7
5.2 AlienInsect.net....................................................... 7
5.3 Othernotablepeople ................................................... 7
5.4 Othermaterials ......................................................7

1 Introduction
There are two main directions in the broader DMT project that need to be considered, namely (Figure 1):
• Pharmacology - that explores micro level effects of DMT, i.e., its effects on cells, on individual organs and finally on a whole-body, first on animals and then on human beings.
• Phenomenology - that explores macro level effects of DMT, i.e., its effects on brain and senses, through personal experiences of individuals and groups, and all the way up to the exploration of the ”DMT world”.
“DMT world”
Phenomenology Experiences (macro level)
Brain/senses

BIG PICTURE OF DMT STUDIES
Scope of this study
Business potential
Whole-body
Animals
Cells
DMT potential
On one hand, pharmacology takes the bottom-up approach by starting from a cellular level in order to create a track record for DMT research, as well as to prepare everything for human trials. This research is currently led by Josipa Vlainic from IRB. On the other hand, phenomenology takes the top-down approach going from personal experiences of the ”DMT world” towards brain functions and senses in order to identify feasible studies that may open interesting use cases and new business opportunities. This research is currently led by Ivana Nizetic Kosovic and Toni Mastelic.
The goal of the former is to identify a pharmacological research direction that will explore DMT drug potentials that can be used for medicinal purposes, while the latter aims at exploring alternative research directions into spiritual and other worldly dimensions. That said, both directions have to be explored in parallel and complement each other, and finally intersect in order to guide pharmacological experiments with phenomenological findings, and utilize data from pharmacological experiments on phenomenology studies.

SCOPE OF THIS STUDY AND THIS REPORT IN PARTICULAR

This study (i.e, DMT Meta-project) covers the phenomenology part of the broader DMT project, as shown in Figure 1, where this report represents the first out of five reports covering the related work on DMT. Other reports will cover feasible experiments, feasible studies, new directions, and finally provide conclusions. Nevertheless, this report also includes some pharmacological related work that was required for better understanding DMT effects on macro level. Consequently, this report covers bio-chemical properties of DMT (Section 2) in order to understand its origin and effects on human body (Section 3). Also, it includes the list of prominent research groups and individuals exploring DMT potentials, mostly from (but not limited to) the phenomenological point of view (Sections 4 and 5). Finally, the report covers possible research directions and potentially interesting experiments (Section ??). However, more comprehensive analysis of these and possibly other directions will be addressed in future reports as part of DMT Meta-project study.

2 Bio-chemical properties of DMT
DMT, or N,N-Dimethyltryptamine (Figure 2.2), is a naturally occurring psychoactive substance that is found in certain plants and animals. Pyschoactive substance, psychedelics or hallucinogens, are psychoactive compounds that can significantly modify perception, mood, and cognitive processes. Despite their potent effects, these substances are generally considered safe from a physiological standpoint and are not known to cause addiction or dependence ([24][25]).
Figure 2: Structure of indole ring that is common for tryptamines (1) and structure of DMT (2)
DMT itself is a relatively small molecule with a molecular weight of 188.27 g/mol. Its hydrophobic nature allows it to easily cross the blood-brain barrier, meaning it can enter the brain and produce profound psychoactive effects. The log P value of DMT is 2.573, which indicates that it is more soluble in nonpolar solvents than in water [8].

SIMILARITY WITH NEUROMODULATORS

This compound belongs to a group of substances called tryptamines, which contain an indole ring (Figure 2.1) and share structural similarities with neurotransmitters/neuromodulators such as dopamine, serotonin, and melatonin (Figure 3):
• Dopamine is a neuromodulatory molecule that plays a crucial role in various physiological processes, including movement, reward, and motivation.
Pharmacology
(micro level)
Figure 1: Scope of this project within the broader DMT study

2

• Serotonin, on the other hand, is a neurotransmitter that regulates mood, appetite, and sleep. It is often referred to as the body’s natural ”feel-good” chemical due to its ability to induce feelings of happiness and well-being.
• Melatonin is a hormone that is responsible for regulating sleep and circadian rhythms (Figure 3).
  Figure 3: DMT structural relationship with other brain chemicals
• SIMILARITY WITH TRIPTAN DRUGS
• Triptan drugs (Figure 3) are a class of medication commonly used to treat migraines and cluster headaches. They work by constricting blood vessels in the brain and reducing inflammation. Interestingly, triptans are derived from DMT and demonstrate that slight modifications to the chemical structure of DMT can produce non-hallucinogenic analogues that have therapeutic benefits.
• SIMILARITY WITH PSYCHEDELICS
  Functionally, DMT is classified as a serotonergic psychedelic compound. This means that it shares structural and functional similarities with other compounds that are known to produce profound alterations in perception and consciousness. These substances are often referred to as ”mind-manifesting” compounds due to their ability to produce profound changes in thought, emotion, and perception.
  DMT’s chemical structure is particularly noteworthy because it constitutes the core of several other important psychedelic compounds, including LSD, ibogaine, psilocybin, and 5-MeO-DMT (Figure 3). These compounds share a similar indole ring structure with DMT, which is believed to be responsible for their psychoactive properties.

• LSD is a potent psychedelic compound that produces effects similar to those of DMT but with a longer duration of action.
• Ibogaine is a naturally occurring substance found in the iboga plant that has been used traditionally in spiritual and medicinal
  contexts.
• Psilocybinistheactivecompoundfoundin”magicmushrooms”andisknownforitsabilitytoproducevividvisualhallucinations
  and altered states of consciousness.
• 5-MeO-DMT is a derivative of DMT that is known for its intense, short-lived effects.

2.1 Natural occurrence of DMT

OCCURRENCE IN PLANT LIFE
DMT is a naturally occurring substance that is found in more than 50 plant species, mainly in South America. Some of the plants where DMT can be found include Psychotria viridis, Desmanthus illinoensis, Mimosa hostilis, and Phalaris aquatica.

OCCURRENCE IN ANIMALS
In animals, DMT has been found in the skin secretions of certain species of toads, including the Bufo alvarius toad. These toads are sometimes referred to as ”DMT toads” because their secretions contain high concentrations of DMT and other psychoactive compounds. Some people have attempted to extract DMT from the secretions of these toads for recreational use, although this practice is illegal in many countries and can be associated with serious health risks. Additionally, DMT is present in the bodies of many mammalian species.

OCCURRENCE IN HUMANS
DMT has also been detected in the human body in trace amounts, although its exact role is not fully understood. Some researchers have suggested that it may be involved in certain biological functions, such as modulating the activity of serotonin receptors, which are involved in mood regulation.

2.2 Synthesis of DMT
Besides extracting and purifying DMT from nature, it can also be synthesised. And since the structure of DMT is known, there are multiple ways to synthesis it. Here, only three approaches are described.

BIOSYNTHESIS
Biosynthesis of DMT happens as a result of tryptophan metabolisam. The process begins with the decarboxylation of tryptophan, followed by the methylation of tryptamine by an N-methyltransferase (INMT) using S-adenosylmethionine (SAM) as the methyl donor. A second methylation by another enzyme results in the production of DMT [29].
Figure 4: Biosynthesis of DMT from tryptophan

ONE STEP SYNTHESIS
An acidic reductive amination process utilizing tryptamine, formaldehyde, and sodium cyanoborohydride is one of the most straightforward methods for producing DMT with reasonably high yields (around 70 %) in just one step [8]. While it can be
3
performed in a single step, it is a tricky method as it has to happen very fast, and it does not allow intermediate steps for creating DMT derivatives.
Figure 5: One step synthesis of DMT

SYNTHESIS USED BY RICK STRASSMAN
Speeter and Anthony’s chemistry for acylating indole at the 3-position with oxalyl chloride is another widely used method for synthesizing DMT [31]. In this approach, the resulting acyl chloride is reacted with dimethylamine to create an amide that is reduced with lithium aluminum hydride. Despite being a three-step process, this method is reliable and was chosen to produce the DMT for the human clinical trials led by Strassman and colleagues. This approach also allowed for the synthesis of a diverse range of DMT analogues, including those with varying amino groups and indole substitution patterns [4].
Figure 6: Speeter and Anthony‘s synthesis of DMT from indole ring

FINAL STEPS ONCE DMT IS CREATED
Once DMT is synthesized, it must be isolated and purified. Isolation typically involves extracting the DMT free base into an organic solvent such as chloroform. The purification process usually entails sublimating the free base under reduced pressure, or a combination of crystallizing/recrystallizing a DMT salt form. The fumarate salt of DMT is considered one of the most manageable and storable forms, as other salt forms such as acetate, citrate, and hydrochloride tend to be hygroscopic [8]. Like most indole-containing compounds, DMT should be stored in a dark freezer to prevent decomposition.

3 DMT Metabolism
Pineal gland (hrv. epifiza), an organ that forms an integral part of the brain, plays a crucial role in connecting the outside world with the body’s internal physiological and biochemical needs by providing information on circadian and seasonal rhythms. It is a photo-neuro-endocrine organ that is part of the epithalamus and is directly in contact with the pineal recess and the dorsal suprapineal recess containing the choroidal plexus. The pineal gland’s endocrine role is mainly attributed to the secretion of melatonin, an indoleamine with a molecular weight of 232 kDa, and its precursor is tryptophan, which gets hydroxylated and decarboxylated to serotonin before transforming into melatonin due to the methyltransferase-O-hidroxi-indole enzyme (HIOMT)[18].

PINEAL GLAND AND DMT
Moreover, a pineal gland seems to be responsible for the secretion of DMT, a psychoactive substance that is synthetized from tryptophan by the L-amino-acid-decarboxylase and the indoletiamine-N-methyl-transferase (INMT). Although endogenous secretion of DMT is much lower than the doses used in psychoactive purposes, external consumption may significantly increase DMT levels. DMT has been identified in the pineal gland and brain of rats, and proponents of the theory that DMT is produced endogenously in significant amounts point out that the key enzyme necessary for its biosynthesis, INMT, is present throughout the body, with high expression in the lungs.
To achieve psychoactive effects, an effect site concentration of 60 ng/mL or 318 nM of DMT base is required. Gallimore and Strassman developed an infusion protocol that maintains an effect site concentration of 100 ng/mL in a 75 kg subject, starting with an initial bolus of 25 mg infused over 30 seconds, followed by an infusion rate of 4.2 mg/min. These data give an indication of the approximate plasma levels of DMT needed for the extraordinary psychoactive effects of DMT, which would require the pineal gland to rapidly produce about 25 mg of DMT in a minute or two. In comparison, the mean daily output of melatonin from the pineal gland is approximately 30 μg, about 1/1000 of the weight of DMT needed to activate the “DMT world.”
The pineal gland’s significance extends beyond its complex pathways and secretory activity of serotonin, melatonin, and DMT. Its long and mythical history, dating back to pharaonic Egypt, equated it with the eye of Horus, while Ren ́e Descartes regarded it as the ”seat of the soul.” Strassman proposed that the pineal gland excretes large quantities of DMT during extremely stressful life episodes, notably during birth and death, affecting our lingering consciousness. The ”blinding light of pineal DMT” enables the transit of the life-force from this life to the next [26]. Thus, the pineal gland’s multifaceted role is embedded deep in complex neurological, endocrinological, and psychiatric conditions and processes, making it a fascinating subject for further research.

DMT INTERACTION WITH BRAIN FUNTIONS
Scientists have found that DMT can interact with different parts of the brain called receptors, kind of like a key that fits into a lock. The specific receptors that DMT interacts with are called 5-HT2A, 5-HT1A, and 5-HT2C. When DMT interacts with these receptors, it can make them act differently, like turning on a switch.
This can cause the hallucinogenic effects that people experience.
One of the receptors, called 5-HT2A, is especially important for causing the hallucinations. When DMT interacts with this receptor, it can cause an increase in certain chemical reactions in the brain. This can make brain cells called cortical pyramidal neurons more excited, and make them communicate with each other more frequently. Scientists have also discovered that the shape of DMT is very important for it to interact with the 5-HT2A receptor.
In more technical vocabulary, unmetabolized DMT which reaches the brain interacts with different types of receptor, such as serotonin receptors, and it has high affinity for binding in nanomolar concentrations to serveral receptors including 5-HT1A, 5-HT1B, 5-HT1D, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT6, and 5-HT7 receptors [20]. Pharmacological and genetic experiments have shown that DMT’s effects are partially mediated by the 5-HT2A, 5-HT1A, and 5-HT2C receptors, where it acts as an agonist or partial agonist depending on the assay. The hallucinogenic effects of DMT are believed to result primarily from agonism of the 5-HT2A receptor and are modulated by mGlu2/3 receptors. DMT acts as an agonist of 5-HT2A receptors, causing an increase in phosphoinositide hydrolysis and both the frequency and amplitude of spontaneous excitatory postsynaptic currents (EPSCs) in cortical pyramidal neurons. Structure-activity relationship (SAR) studies have shown that the relatively small methyl groups of DMT are critical for achieving high affinity for the 5-HT2A receptor.
4

3.1 Ayahuasca
Ayahuasca, also known under names yag ́e, hoasca, caapi, daime, and natem, is a hallucinogenic herbal preparation with a long traditional use by indigenous tribes of the Amazon Basin for therapeutic and divination purposes. It is a botanical beverage typically prepared from the leaves of Psychotria viridis which contain high amount of the N,N-dimethyltryptamine (DMT) and the stem and bark of Banisteriopsis caapi, the plant source of harmala alkaloids.
Harmala alkaloids act as potent inhibitors of monoamine oxidase A (MAO-A), preventing extensive first-pass degradation of DMT into 3-indoleacetic acid (3-IAA), and enabling sufficient amounts of DMT to reach the brain. DMT has affinity for a variety of serotonergic and non-serotonergic receptors, though its psychotropic effects are mainly related to the activation of serotonin receptors type 2A (5-HT2A). The pharmacological activity of ayahuasca is mostly attributed to the allegedly synergistic interaction between the psychoactive alkaloids of P. viridis and B. caapi. Concomitant intake through ayahuasca allows the delivery of high levels of DMT to the CNS, enabling a potentpsychotropic action.

3.2 DMT trip
A typical psilocybin “trip” will last between two to four hours. In a medical setting, that’s accompanied by four more hours of psychotherapy in order to integrate the experience into the patient’s life. On one hand, DMT typically has an onset and offset time of just 15 to 30 minutes, allowing for faster sessions within the long-term treatment. 1 On the other hand, Ayahuasca effect can last for several hours depending on a dosage, due to its additional properties, i.e., harmala alkaloids that prevent fast degradation of DMT. Nevertheless, as stated by Andrew Gallimore, it would be unwise to draw conclusions about the effects of DMT by relying on the effects of Ayahuasca [15], since other ingredients in Ayahuasca can produce hallucinations.
With other natural psychedelics, such as mescaline or psilocybin, repeated use produces a tolerance effect with each subsequent dose, unless the doses are spaced apart several days. DMT is unique in not displaying such tolerance, so there is no diminishing of effects with repeated doses [34] [33].

4 Research groups on DMT
There are several research groups around the world working on different aspects of DMT. While most of them focus the use of psychedelics in mental health care, the focus of this report is on phenomenological aspects of DMT and its related work. Nevertheless, this report still covers some mental health care use cases as they are sometimes closely related or used as a basis for phenomenological studies. Also, this section contains alternative research groups and individuals as well as some related materials. However, this is by no means a comprehensive list of he related work, as there is a large body of work on DMT that has been done in the last couple of decades, which is out of scope of this study.

4.1 Imperial College London
Imperial College London, Centre for Psychedelic Research2 founded by professor Robin Carhart-Harris3. They focus on two main research themes: the use of psychedelics in mental health care; and as tools to probe the brain’s basis of consciousness. As part of latter theme, they have explored ”DMT world”.

CLASSIFICATION AND MAPPING OF ”DMT WORLD”
When it comes to DMT, they have performed several relevant studies related to classifying DMT experiences and mapping the ”DMT world”. In [22] they have used posts from several thousands of Reddit4 users that used DMT and described their experiences in order to classify different aspects of DMT experiences lasting cca 10 minutes, including seven major thematic domains: (1) physical and somatic experiences; (2) visualizations and imagery; (3) entity encounters including entity phenotype, descriptors, attributes, disposition, and characteristics of the interaction; (4) typology, architectural features, structural characteristics, and scenery of the “DMT world”; (5) alerations in consciousness (including mystical experiences, out-of-body experiences, and ego-dissolution); (6) emotional responses (including positive, rewarding, difficult, and challenging); and (7) statements of profundity. This is a very interesting paper published as a scientific report in Nature.
In [1] they observed cortical travelling waves during DMT trip. The results revealed a spatio-temporal pattern of cortical activation (i.e. travelling waves) similar to that elicited by visual stimulation. While not directly associated with mapping of ”DMT world”, it gives interesting insights into the effects of DMT on visuals.
In another study [27], conducted in 2021 in collaboration with colleagues from Argentina, they examined neural and subjective effects of inhaled DMT in natural settings. Here, they tried to map certain EEG measurements with subjective experiences in non-laboratory conditions in order to test ”set” and ”settings” hypothesis. While having interesting premises, this is not an exceptional read.

SIMILARITY WITH NEAR-DEATH EXPERIENCE
In another paper [35] from 2018, they have compared near-death experiences (NDEs) with DMT experiences on 13 healthy participants, where they have showed high similarities between the two. These findings were also an integral part of their general research on psychedelics effects and the essential importance of context, published also in 2018 [9].

SIMILARITY WITH SLEEP STATE
In their paper [37] from 2019, the authors revealed that DMT significantly alters electrical activity in the brain, characterised by a marked drop off in alpha waves – the human brain’s dominant electrical rhythm when we are awake. They also found a short-lived increase in brainwaves typically associated with dreaming, namely, theta waves.
Furthermore, during DMT trip brain activity becomes more chaotic and less predictable – the opposite to what is seen in states of reduced consciousness, such as in deep sleep or under general anaesthesia. “The changes in brain activity that accompany DMT are slightly different from what we see with other psychedelics, such as psilocybin or LSD, where we see mainly only reductions in brainwaves,” said Christopher Timmermann, from the Centre for Psychedelic Research5.

DEPRESSIVE DISORDERS RELATED RESEARCH
The Imperial team is now exploring how to prolong the peak of the psychedelic experience through continuous infusion with DMT, and some are also advising on a commercially run trial to assess DMT for patients with depression6. They already performed a series of experiments in 2022 [13] and 2023 [14] on how DMT can help fight depression . In their latest publication [36] from 2023,
1 https://finance.yahoo.com/news/imperial-college-london-study-illegal-213716053.html 2 https://www.imperial.ac.uk/psychedelic-research-centre
3 https://www.imperial.ac.uk/people/r.carhart-harris
4 https://www.reddit.com/r/DMT/
5 https://www.imperial.ac.uk/news/193993/ayahuasca-compound-changes-brainwaves-vivid-waking-dream/ 6 https://www.imperial.ac.uk/news/243893/advanced-brain-imaging-study-hints-dmt/
5
they used both EEG and fMRI on 20 healthy patients. Their results revealed that when a volunteer was on DMT there was a marked dysregulation of some of the brain rhythms that would ordinarily be dominant. The brain switched in its mode of functioning to something altogether more anarchic.

OTHER RESEARCH
In their ethnographic study [28] of the use of the hallucinogenic plant brew, ayahuasca, among Palestinians living under Israeli occupation in the West Bank, the authors offer an unique and thought-provoking perspective on the potential of ayahuasca as a tool for social and political transformation, as well as the complex dynamics that arise when marginalized communities engage with practices from other cultures.

4.2 Johns Hopkins University
Johns Hopkins University, Center for Psychedelic and Consciousness Research, led by Roland Griffiths7. While the group mostly works with psilocybin, they have published several journal papers on the work they did with DMT.

SIMILARITIES/DIFFERENCES BETWEEN DMT AND OTHER PSYCHEDELICS
In their paper [3] from 2018, the authors compare mystical experiences occasioned by 5-MeO-DMT and psilocybin, where they concluded that light to common dose of 5-MeO-DMT appears to occasion mystical experiences of a comparatively similar intensity to high-dose psilocybin but with a much shorter duration of action. Consequently, 5-MeO-DMT may have psychotherapeutic applications and could be relatively easier to use in mental health treatment systems. Nevertheless, there are some caveats in this paper as they did not approach it in a systematic manner according to the discussion given in the paper.
In their follow up paper [19] from 2019, they investigated the similarities and differences between naturally occurring ”God encounter experiences” and those that are occasioned by the classic psychedelics psilocybin, LSD, ayahuasca, or DMT. This is a very interesting paper which compares subjective experiences of all those psychedelics as well as non-drug experiences.

DMT FOR DEPRESSION AND ANXIETY
In their other paper [10] from 2019, they examined the feasibility of 5-MeO-DMT being used for treating depression and anxiety. Their findings show that the cca. 80 percent of patients reported condition improvements, which were associated with greater intensity of mystical experiences and higher ratings of the spiritual significance and personal meaning of the 5-MeO-DMT experience. There were no associations between depression or anxiety improvement and the intensity of acute challenging physical/psychological experience during the 5-MeO-DMT experience.

4.3 University of Michigan
University of Michigan, Medical school, Borjigin Lab8 led by Jimo Borjigin explores the effects of endogenous DMT mostly in rats9.

ENDOGENOUS DMT
Together with Steven Barker from LSU and Rick Strassman they published a paper in 2013 [2] showing that pineal gland produces DMT in rats, and that it might be doing the same thing in a human body. Jon Dean, a young scientists made a breakthrough together with Jimo Borjigin, Steven Barker and Rick Strassman in 2019 [11] discovering that DMT is released in mammalian species in the amounts comparable to serotonin.
Lately, the group seems to be having problems with funding, so it is unknown if they have continued working on DMT related topics.
University of Mitchigan, Edward F. Domino Research Center10 led by Edward Domino has some studies on DMT and LSD on rats and cats, however with much earlier dates focusing on its chemical effects, including but not limited to [21] and [23] from 1976, [30] from 1979, and others. However, these studies might be out of date.

4.4 University of California
University of California, Olsen Lab11, led by David Olsen performed several studies with DMT and other psychedelics. Their lab studies a class of compounds that we call psychoplastogens, or small molecules capable of promoting neural plasticity. They examine their potential for treating a wide variety of neuropsychiatric diseases including depression, anxiety disorders, and addiction.

THERAPEUTIC USAGE
In 2018 [6] and 2019 [5], they published two papers in which they examined the effects of DMT on rats with focus on anxiety, mood and depression. In former, they did it with chronic, intermittent micro-dosing.

OTHER CHEMICAL ASPECTS
Moreover, in 2018 [7], they published a survey paper on DMT covering the synthesis of DMT as well as its pharmacology, metabolism, adverse effects, and potential use in medicine.They also discussed the history of DMT in chemical neuroscience and why it is so important to the field of psychedelic science. In another paper [12], they also covered some other chemical reactions of DMT, more specifically with Dichloromethane that would take place during extraction from plant material, biphasic aqueous work-up, or column chromatography purification

4.5 King’s College London
King’s College London, Psychoactive Trials Group12 led by James Rucker and Allan Young. The group has perfomed several trials with psilocybin, as well as one with 5-MeO-DMT in 2021-2022 on healthy humans. It seems they are mostly working with psilocybin. They have a record of a single experiment in 2021-2022 with 5-MeO-DMT on healthy subjects where the researchers assessed
the percentage of participants that experienced any unfavourable and unintended signs, alongside various measures to assess what is happening to the drug when it is taken. Unfortunately, no report or publication was found.

5 Alternative researchers
This section contains alternative research projects and groups as well as notable individuals that have done or are still actively doing research on DMT.
7 https://hopkinspsychedelic.org/griffiths
8 https://borjigin.lab.medicine.umich.edu/publication
9 https://borjigin.lab.medicine.umich.edu/news/endogenous-dmt
10 https://medicine.umich.edu/dept/domino-research-center/message-director 11 https://www.olsonlab.org/publications.html
12 https://www.kcl.ac.uk/research/psychoactive-trials-group
6
5.1 DMTx project
The Extended-State DMT program (DMTx)13 was initiated in February 2016 by Daniel McQueen, co-founder of Medicinal Mindfulness. DMTx is based on the cutting edge pharmacokinetic research of Dr. Andrew Gallimore and the revolutionary DMT research of Dr. Rick Strassman. DMTx program explores legal psychedelic research and exploration opportunities that are congruent with the needs and interests of the psychedelic community.

MATRIX MACHINE
Their intention is to develop new psychedelic-assisted clinical therapies, develop advanced creative problem solving protocols, explore consciousness and the psyche, to try to define the “realness” of the experience, and to potentially develop a medical device, the “Matrix Machine” (a term invented by Dr. Gallimore) that can be used to safely and effectively administer DMTx experiences by a trained DMTx technician.

5.2 AlienInsect.net
Research and web site led by Andrew Gallimore14, a British neurobiologist, pharmacologist, and writer, who is best known for his research on the effects of psychedelic drugs on the brain and consciousness, including DMT. He is a big advocate of alien world theory, that DMT opens the gate to another reality. He is also a strong supporter of the dmatrix machine, a machine that would allow individuals to stay inside ”DMT world” as longs as they want.
Here are his several publications related to this research, while others can be found on AlienInsect.net web site15. Also, he provides a comprehensive (and entirely free!) online course covering the effects of psychedelics on the brain and mind16.

DMT WORLD AND DREAMS
In his paper [15] from 2013, Gallimore describes the functions of a brain, and how it builds a world around itself. He classifies the real world, subjective interpretation of the world, and dream world, i.e., something unrelated to the real world that is only in the mind of a person. Here, Gallimore strongly suggests that ”DMT world” is not a dream world, i.e., hallucination, due to consistency of DMT experiences among different people and the notion that a mind is capable of building it. He also describes a hypothesis that a brain used to secrete DMT during night and serotonin during day, meaning that humans used to have different kind of ”dreams”. This is a very interesting read, and while it covers many biochemical properties and effects of DMT in a brain, it also gives philosophical arguments on ”DMT world”.
In his follow up paper [16] from 2014, Gallimore continues to describe how a human brain constructs the world of reality, and how is this related to a DMT experience.

DMT TECHNOLOGIES
In their paper [17] from 2016, Gallimore and Strassman provide a model for achieving prolonged immersive DMT psychedelic experience using target-controlled intravenous infusion, commonly used when applying anesthesia.

5.3 Other notable people
Since there are many individuals researching DMT (either affiliated with some research institution or not), it is out of scope of this report to go through all of their work. Thus, some prominent individuals related to DMT studies are listed here, while some of their work has been cited throughout this report.

• Rick Strassman17 - an American psychiatrist and psychopharmacologist known for his research on the effects of psychedelic substances, particularly the compound dimethyltryptamine (DMT). Strassman conducted a groundbreaking clinical research study on DMT at the University of New Mexico in the early 1990s. The study aimed to investigate the biological, psychological, and spiritual effects of DMT on human volunteers. It was the first human research study on DMT in over two decades. Strass- man’s research findings were published in his book titled ”DMT: The Spirit Molecule” in 2001 [32]. The book gained significant attention and has since become influential in the field of psychedelic research. In it, Strassman discussed the participants’ experiences with DMT, including reports of encounters with otherworldly entities and profound spiritual experiences.
  While he is listed amongst other notable people, he is the most prominent researcher on the topic of DMT and he probably deserves a section for himself. Nevertheless, since his papers are cited throughout this report, him being the main author or co-author, he was put here to avoid redundancy.
• Terrence McKenna - an American ethnobotanist, philosopher, and writer. He is known for his extensive exploration and advocacy of psychedelic substances, particularly psilocybin mushrooms and DMT. McKenna developed a unique perspective on psychedelics, emphasizing their role in consciousness expansion, cultural evolution, and the exploration of mystical experiences. While he did not conduct formal scientific studies on DMT, he popularized its use and spoke extensively about its effects and transformative potential based on personal experiences and anecdotal evidence.
• Dennis McKenna - the younger brother of Terence McKenna, is an ethnopharmacologist and researcher. He has focused on the study of plant-based medicines and the relationship between plants and human consciousness. Dennis McKenna has conducted scientific research on DMT and other psychedelic substances. In the 1990s, he collaborated with Rick Strassman on the aforementioned groundbreaking DMT research study conducted at the University of New Mexico. Dennis McKenna contributed to the study’s design and helped with data analysis and interpretation.
• Steven Barker - from School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA, performed several studies specifically researching endogenous DMT. He also performed many experiments on rats, and some unpublished studies on LSD trips where he found out that both DMT and 5-Meo-DMT is released during a LSD trip.
• Graham Hancock18 - a British author and journalist who has written extensively about the use of DMT and other psychedelic substances in shamanic practices and the exploration of consciousness. He is the author of the book ”Supernatural: Meetings with the Ancient Teachers of Mankind” which explores the potential of DMT and other psychedelics to reveal new insights into human history and consciousness.

5.4 Other materials
There are some interesting materials relevant for the related topic which do not fit any research project or institutions mentioned above, and are listed here:
13 https://www.dmtx.org/
14 https://www.buildingalienworlds.com
15 https://www.buildingalienworlds.com/writings.html
16 https://www.youtube.com/playlist?list=PLbqdD4EM-aEfmLvbWu8GQDhUII236MZf- 17 https://www.rickstrassman.com/
18 https://grahamhancock.com/
7

• DMT Quest Documentary19 - very interesting documentary on the history of DMT and research paper by Jon Dean, as well meditation techniques that seemingly effect brain gamma waves and DMT.
• Lex Fridman Podcast20 - a podcast run by Lex Fridman, a Russian-American AI researcher and podcast host. He is a research scientist at the Massachusetts Institute of Technology (MIT), where he works in the field of deep learning and artificial intelligence. He has several episodes on DMT trips which are very informative.
• Joe Rogan Experience21 - another podcast hosted by Joe Rogan, an American comedian, podcast host, and UFC commentator. He has several episodes on DMT, which are very informative.
• Vsauce, Ayahuasca22 - famous youtube channel run by Michael Stevens made an half an hour documentary on Ayahuasca, where Michael went to Peru to experience the mind-expanding effects of the psychedelic brew Ayahuasca. He was joined by Imperial College London’s Head of Psychedelic Research, Dr. Robin Carhart-Harris, who measured the impact of Ayahuasca on his brain. The documentary is informative.
  • Erowid.org23 - very interesting web site that contains basic information (laws, effects, dose, etc.) on DTM all in one place, as well documented trips. While it has 00s look, it is an interesting read.

• Josie Kins24 - interesting (pseudo)scientific youtube channel that also references papers from Imperial College London. They try to categorize DMT experience levels, entities, etc.
• Symmetric Vision25 - youtube channel where the author tries to replicate visuals during psychedelics trip, including DMT. References

1. [1]  A Alamia, C Timmermann, R VanRullen, and RL Carhart-Harris. Dmt alters cortical travelling waves. eLife, 9:1–16, 2020.
2. [2]  Steven A Barker, Jimo Borjigin, Izabela Lomnicka, and Rick Strassman. Lc/ms/ms analysis of the endogenous dimethyltryptamine hallucinogens,
   their precursors, and major metabolites in rat pineal gland microdialysate. Biomedical Chromatography, 27(12):1690–1700, 2013.
3. [3]  JosephBarsuglia,AlanKDavis,RobertPalmer,RafaelLancelotta,Austin-MarleyWindham-Herman,KristelPeterson,MartinPolanco,RobertGrant, and Roland R Griffiths. Intensity of mystical experiences occasioned by 5-meo-dmt and comparison with a prior psilocybin study. Frontiers in psychology, 9:2459, 2018.
4. [4]  R. W. BRIMBLECOMBE, D. F. DOWNING, D. M. GREEN, and R. R. HUNT. Some pharmacological effects of a series of tryptamine derivatives. British Journal of Pharmacology and Chemotherapy, 23(1):43–54, 1964.
5. [5]  Lindsay P Cameron, Charlie J Benson, Brian C DeFelice, Oliver Fiehn, and David E Olson. Chronic, intermittent microdoses of the psychedelic n, n-dimethyltryptamine (dmt) produce positive effects on mood and anxiety in rodents. ACS chemical neuroscience, 10(7):3261–3270, 2019.
6. [6]  Lindsay P. Cameron, Charlie J. Benson, Lee E. Dunlap, and David E. Olson. Effects of n,n-dimethyltryptamine on rat behaviors relevant to anxiety and depression. ACS Chemical Neuroscience, 9(7):1582–1590, 2018. PMID: 29664276.
7. [7]  Lindsay P Cameron and David E Olson. Dark classics in chemical neuroscience: N, n-dimethyltryptamine (dmt). ACS chemical neuroscience, 9(10):2344–2357, 2018.
8. [8]  Lindsay P. Cameron and David E. Olson. Dark classics in chemical neuroscience: N,n-dimethyltryptamine (dmt). ACS Chemical Neuroscience, 9(10):2344–2357, 2018. PMID: 30036036.
9. [9]  Robin L Carhart-Harris, Leor Roseman, Eline Haijen, David Erritzoe, Rosalind Watts, Igor Branchi, and Mendel Kaelen. Psychedelics and the essential importance of context. Journal of Psychopharmacology, 32(7):725–731, 2018. PMID: 29446697.
10. [10]  Alan K Davis, Sara So, Rafael Lancelotta, Joseph P Barsuglia, and Roland R Griffiths. 5-methoxy-n, n-dimethyltryptamine (5-meo-dmt) used in a naturalistic group setting is associated with unintended improvements in depression and anxiety. The American journal of drug and alcohol abuse, 45(2):161–169, 2019.
11. [11]  Jon G Dean, Tiecheng Liu, Sean Huff, Ben Sheler, Steven A Barker, Rick J Strassman, Michael M Wang, and Jimo Borjigin. Biosynthesis and extracellular concentrations of n, n-dimethyltryptamine (dmt) in mammalian brain. Scientific reports, 9(1):1–11, 2019.
12. [12]  Lee E Dunlap and David E Olson. Reaction of n, n-dimethyltryptamine with dichloromethane under common experimental conditions. ACS omega, 3(5):4968–4973, 2018.
13. [13]  E Eckernas, C Timmermann, R Carhart-Harris, D Roshammar, and M Ashton. Population pharmacokinetic/pharmacodynamic modeling of the psychedelic experience induced by n,n-dimethyltryptamine - implications for dose considerations. CTS-CLINICAL AND TRANSLATIONAL SCIENCE, 15:2928–2937, 2022.
14. [14]  E Eckernas, C Timmermann, R Carhart-Harris, D Roshammar, and M Ashton. N,n-dimethyltryptamine affects electroencephalography response in a concentration-dependent manner-a pharmacokinetic/pharmacodynamic analysis. CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY, 2023.
15. [15]  Andrew Gallimore. Building alien worlds - the neuropsychological and evolutionary implications of the astonishing psychoactive effects of n,n-dimethyltryptamine (dmt). Journal of Scientific Exploration, 27(3), Oct. 2013.
16. [16]  Andrew R. Gallimore. DMT and the topology of reality. In PsyPress UK Journal, 2014.
17. [17]  Andrew R. Gallimore and Rick J. Strassman. A model for the application of target-controlled intravenous infusion for a prolonged immersive dmt
    psychedelic experience. Frontiers in Pharmacology, 7, 2016.
18. [18]  Bogdan Alexandru Gheban, Ioana Andreea Rosca, and Maria Crisan. The morphological and functional characteristics of the pineal gland. Med.
    Pharm. Rep., 92(3):226–234, July 2019.
19. [19]  Roland R Griffiths, Ethan S Hurwitz, Alan K Davis, Matthew W Johnson, and Robert Jesse. Survey of subjective” god encounter experiences”: Comparisons among naturally occurring experiences and those occasioned by the classic psychedelics psilocybin, lsd, ayahuasca, or dmt. PloS one, 14(4):e0214377, 2019.
20. [20]  Michael J. Keiser, Vincent Setola, John J. Irwin, Christian Laggner, Atheir I. Abbas, Sandra J. Hufeisen, Niels H. Jensen, Michael B. Kuijer, Roberto C. Matos, Thuy B. Tran, Ryan Whaley, Richard A. Glennon, J ́erme Hert, Kelan L.H. Thomas, Douglas D. Edwards, Brian K. Shoichet, and Bryan L. Roth. Predicting new molecular targets for known drugs. Nature, 462(7270):175–181, November 2009.
21. [21]  BEVERLY Kovacic and EDWARD F Domino. Tolerance and limited cross-tolerance to the effects of n, n-dimethyltryptamine (dmt) and lysergic acid diethylamide-25 (lsd) on food-rewarded bar pressing in the rat. Journal of Pharmacology and Experimental Therapeutics, 197(3):495–502, 1976.
22. [22]  DW Lawrence, R Carhart-Harris, R Griffiths, and C Timmermann. Phenomenology and content of the inhaled n, n-dimethyltryptamine (n, n-dmt) experience. SCIENTIFIC REPORTS, 12, 2022.
23. [23]  LJ WANG Lu and Edward F Domino. Effects of iproniazid and tranylcypromine on the half-life of n, n-dimethyltryptamine in rat brain and liver. Biochemical Pharmacology, 25(13):1521–1527, 1976.
24. [24]  David E Nichols. Hallucinogens. Pharmacology & Therapeutics, 101(2):131–181, 2004.

19 https://www.youtube.com/watch?v=My95s6ZryPg&t=4s 20https://www.youtube.com/results?search query=lex+fridman+dmt 21https://www.youtube.com/results?search query=joe+rogan+dmt 22 https://www.youtube.com/watch?v=U3lWVLuc6CE
23 https://erowid.org/chemicals/dmt
24 https://www.youtube.com/@josikinz
25 https://www.youtube.com/@SymmetricVision/search?query=dmt
8

1. [25]  David E. Nichols. Psychedelics. Pharmacological Reviews, 68(2):264–355, 2016.
2. [26]  David E Nichols. N,n-dimethyltryptamine and the pineal gland: Separating fact from myth. Journal of Psychopharmacology, 32(1):30–36, 2018.
   PMID: 29095071.
3. [27]  Carla Pallavicini, Federico Cavanna, Federico Zamberlan, Laura A de la Fuente, Yayla Ilksoy, Yonatan S Perl, Mauricio Arias, Celeste Romero, Robin Carhart-Harris, Christopher Timmermann, and Enzo Tagliazucchi. Neural and subjective effects of inhaled n,n-dimethyltryptamine in natural settings. Journal of Psychopharmacology, 35(4):406–420, 2021. PMID: 33567945.
4. [28]  Leor Roseman and Nadeem Karkabi. On revelations and revolutions: Drinking ayahuasca among palestinians under israeli occupation. Frontiers in Psychology, 12, 2021.
5. [29]  Jon P. Ruddick, Andrew K. Evans, David J. Nutt, Stafford L. Lightman, Graham A.W. Rook, and Christopher A. Lowry. Tryptophan metabolism in the central nervous system: medical implications. Expert Reviews in Molecular Medicine, 8(20):1–27, 2006.
6. [30]  Diane Ruffing, Beverly Kovacic, Sandra Demetriou, and Edward F Domino. Naloxone enhancement of dmt and lsd-25 induced suppression of food-rewarded bar pressing behavior in the rat. Psychopharmacology, 62(3):207–210, 1979.
7. [31]  Merrill Eugene Speeter and William C. Anthony. The action of oxalyl chloride on indoles: A new approach to tryptamines. Journal of the American Chemical Society, 76:6208–6210, 1954.
8. [32]  Rick Strassman. DMT: The spirit molecule: A doctor’s revolutionary research into the biology of near-death and mystical experiences. Simon and Schuster, 2000.
9. [33]  Rick J Strassman. Human psychopharmacology of n, n-dimethyltryptamine. Behavioural brain research, 73(1-2):121–124, 1995.
10. [34]  Rick J. Strassman, Clifford R. Qualls, and Laura M. Berg. Differential tolerance to biological and subjective effects of four closely spaced doses of
    n,n-dimethyltryptamine in humans. Biological Psychiatry, 39(9):784–795, 1996.
11. [35]  C Timmermann, Slater C Timmermann, L Roseman, L Williams, D Erritzoe, C Martial, H Cassol, S Laureys, D Nutt, and R Carhart-Harris. Dmt
    models the near-death experience. Frontiers in Psychology, 9, 2018.
12. [36]  Slater CB Timmermann, L Roseman, S Haridas, F Rosas, L Luan, H Kettner, J Martell, D Erritzoe, E Tagliazucchi, C Pallavicini, M Girn, A Alamia, R Leech, and R Carhart-Harris. Human brain effects of dmt assessed via eeg-fmri. Proceedings of the National Academy of Sciences of USA, 120:1–12, 2023.
13. [37]  Slater CB Timmermann, L Roseman, M Schartner, R Milliere, L Williams, D Erritzoe, S Muthukumaraswamy, M Ashton, A Bendrioua, O Kaur, S Turton, M Nour, C Day, R Leech, D Nutt, and R Carhart-Harris. Neural correlates of the dmt experience as assessed with multivariate eeg. Scientific Reports, 9:1–13, 2019.

9
Ivana Nizetic Kosovic
DMT META-PROJECT
Toni Mastelic
WP.2 Report

Abstract
2023-06-13
DMT Meta-Project study is part of a broader DMT project focusing on research and innovation aspects of DMT and its use in various fields. The goal of this study is to identify possible research and innovation directions that go beyond the current studies being done around the world.
This is the second out of five reports for the DMT Meta-Project documenting the outcomes of WP.2, i.e., document feasible experiments. Previous work package include WP.1 Document related work, while follow up reports include WP.3 Identify feasible studies, WP.4 Explore new directions, and WP.F Write final report.
This report is structured as follows. Section 1 gives wider context for this report as well as information sources from which this report was compiled. Section 2 gives pharmacological project goal, experiments conducted so far, and an overview of planned experiments, all in the context of data acquisition that can be used for phenomenological studies. Finally, Section 3 places these pharmacological experiments in the context of future phenomenological studies, and proposes the way forward.

Contents
1 Introduction 2
1.1 Informationsources .................................................... 2
2 Pharmacological experiments 2
2.1 Projectgoal ........................................................ 2
2.2 Performedexperiments .................................................. 3
2.3 Plannedexperiments ................................................... 4
3 Conclusion 5


1 Introduction
Broader DMT project requires pharmacological approach (Figure 2) to explore DMT in order to create a research track record and establish basis (legislative, etc.) for any further DMT related experiments, especially with humans involved. This approach should serve as a front or a basis for any future phenomenological study as well.
“DMT world”
Phenomenology Experiences (macro level)
Brain/senses
Scope of this study
Business potential
Whole-body
Animals
Cells
DMT potential
Pharmacology
(micro level)
Figure 1: Scope of this project within the broader DMT study
The goal of this report is to document what experiments will be conducted during this pharmacological approach led by Josipa Vlaini ́c from IRB, and what data will be acquired during those experiments. The purpose of this phase is to understand what initial data can be acquired and perhaps even used for some initial phenomenological studies, as well as for steering pharmacological experiments towards future phenomenological studies.
1.1 Information sources
There are several but still limited sources for the information used for compiling this report and summarizing pharmacological experiments that will be performed as part of a broader DMT project, including:
• Online meeting with Paris and Josipa held on May 11, 2023.
• Mail from Josipa to Paris sent on May 04, 2023, and forwarded to the authors of this report on May 22, 2023. • Short Whatsapp message from Paris sent on June 1, 2023.
Based on the information sources, some pharmacological experiments have been performed and some are planned. This report aims to summarize and give structure to the information given by information sources, while providing assumptions where certain information is not provided.
2 Pharmacological experiments 2.1 Project goal
The main goal of pharmacological studies, as derived from the information sources, is to examine the parameters of DMT’s action on reducing oxidative stress levels and how DMT affects cell survival under oxidation conditions. This goal should be the main ground for getting all legal and other approvals for conducting experiments with DMT, especially those on humans.

ABSTRACT

It is believed that a high level of oxidative stress is the basis of many diseases. The goal of pharmacological studies is to determine the time and dose response in oxidative damage to nerve cells - presumably, this should include experiments in which (at least initially) nerve cells are exposed to ”stress”, i.e., some reactive molecules (radicals), and then looking what effects DMT has on it, i.e., does it reduce stress levels; if so, what dose is needed and in what time period. However, the information sources do not specify exactly which tests will be performed to verify the stated.

DETAILS ON OXIDATIVE STRESS, ANTIOXIDANTS, ETC.

Oxidative damage to nerve cells happens when they are exposed to high levels of oxidative stress. This stress occurs when there’s an imbalance between harmful molecules called free radicals and the body’s ability to neutralize them. Free radicals are very reactive molecules that can harm cells, including nerve cells. Nerve cells are sensitive to oxidative stress because of their high metabolism and oxygen needs.When nerve cells are exposed to oxidative stress, free radicals can damage their membranes, proteins, lipids, and genetic material. This damage disrupts the normal function of nerve cells and can lead to neurodegenerative diseases like Alzheimer’s or Parkinson’s.
Cells have various mechanisms and defense systems to cope with oxidative conditions and minimize the damage caused by free radicals and oxidative stress. Here are a few main ways in which cells survive in oxidative conditions:
• Antioxidant enzymes: Cells produce and utilize antioxidant enzymes that neutralize free radicals and other oxidative molecules. Examples of such enzymes include superoxide dismutase, catalase, and glutathione peroxidase. They help convert harmful free radicals into less harmful substances and prevent their accumulation.
• Antioxidant compounds: Cells synthesize and use different molecules that act as antioxidants. For example, vitamin C, vitamin E, glutathione, and carotenoids are some of the antioxidants present in cells. They can neutralize free radicals and help maintain balance in the oxidative environment.
• DNA damage repair: Oxidative stress can cause DNA damage in cells. However, cells have DNA repair mechanisms that help detect and repair such damage. This includes enzymes like DNA repair proteins that can recognize damage, remove it, and repair the damaged DNA segment.
2
• Activation of cellular defense pathways: When cells are exposed to oxidative stress, they can activate various cellular defense pathways to cope with those conditions. Examples of such pathways include nuclear factor kappa B (NF-kB) and nuclear factor erythroid 2-related factor 2 (Nrf2). These factors regulate the expression of genes encoding antioxidant enzymes and other proteins that help reduce oxidative stress.
• Autophagy: Autophagy is the process by which cells recycle damaged components within themselves. This may involve the degradation of damaged proteins, lipids, and organelles that are susceptible to oxidative damage. Autophagy allows the cell to get rid of damaged components and restore its functionality.
These mechanisms work together to protect cells from oxidative damage and maintain their normal function. They are vital for cell survival in conditions of oxidative stress. Following two subsections try to list the experiments that are mentioned in the information sources, as well as explain the type of data they provide.
2.2 Performed experiments
A preliminary study of viability/cytotoxicity (MTT assay) was conducted. While the information sources do not explicitly specify which substance/compound was used, due to the given context DMT is assumed. Nevertheless, the sources do state the cells on which experiments were conducted, namely three cell lines SH-SY5Y, PC12 and P19.

SIMPLIFIED EXPLANATION OF MTT

MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) test measures how metabolically active cells are. It outputs how many cells can convert MTT, a yellow salt, into colored crystals, where more active cells produce more color. MTT test is used to check how many cells are alive and how they grow, or in other words MTT is used to check if the substance being tested is toxic to cells. DETAILED EXPLANATION OF MTT
The viability or cytotoxicity test measures the metabolic activity of the cell. MTT is the chemical name of the tetrazolium salt [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] used as a reagent in this test. MTT salt is yellow in color, which metabolically active cells with preserved mitochondrial function convert into insoluble formazan crystals of purple color, and the reaction itself is catalyzed by enzymes in the cell. The resulting crystals are later dissolved in organic solvents such as dimethyl sulfoxide (DMSO).
The intensity of the color produced by the formazan product is directly proportional to the number of live cells. Therefore, the MTT test provides a measure of cell viability and can be used to assess the effects of various factors such as drug treatments, toxins, or experimental conditions on cell proliferation or cytotoxicity. The resulting colored solution is then quantified spectrophotometrically by measuring absorbance at a certain wavelength of 500-600 nm.
RESULT DATA
The results obtained by this test can be represented numerically, as the absorbance is measured at a certain wavelength, and the result is a numerical value that is proportional to the number of live cells. Higher absorbance indicates greater metabolic activity and a larger number of vital cells, while lower absorbance indicates lower metabolic activity and potentially a smaller number of vital cells. The results of the MTT test can also be graphically presented to illustrate differences in metabolic activity or cell vitality between samples or experimental conditions.
RESULTS METRICS
The IC50 value is often used for analyzing results. The IC50 value (half maximal inhibitory concentration) is a measure of the concentration of a compound or treatment that inhibits a certain biological response or reduces cell viability by 50 percent. It is often used to assess the effectiveness of a drug or compound in inhibiting cell growth or inducing cytotoxic effects. The IC50 value represents the concentration at which the compound achieves half of its maximum inhibitory effect.
The connection between absorbance and IC50 values lies in their association with cytotoxicity. In cytotoxicity tests, absorbance values can be used to generate a dose-response curve, which shows the effect of different concentrations of a compound or treatment on cell viability or metabolic activity. From this curve, the IC50 value can be determined by finding the concentration at which the response (absorbance) decreases by 50 percent. It’s important to note that the IC50 value is not directly derived from absorbance, but is the result of data analysis and determining the point on the dose-response curve.
Figure 2: Example of MTT test results (not from the experiments done by Josipa)
The actual test results are out of scope of this report as they are not relevant at this stage, nor the information sources give or explain the results of these preliminary MTT tests which have been conducted.

CELL LINES USED IN THE EXPERIMENTS

The cell lines used in the experiment include:

• SH-SY5Y cell line - a cell line obtained from a human neuroblastoma tumor cell line (SK-N-SH) taken from the bone marrow of a patient with neuroblastoma (a type of malignant tumor that develops from immature nerve cells; one of the most common tumors in young children). These cells exhibit characteristics similar to immature neurons and are often used as a model for studying neuronal development, neurotoxicity, and neurodegenerative diseases.
• PC12 cell line - a cell line derived from a mouse carcinoma - pheochromocytoma, a rare tumor of chromaffin cells; obtained from the adrenal medulla (the inner part of the adrenal gland responsible for secreting adrenaline and noradrenaline, and for regulating blood pressure as well as responses to stressful situations). These cells have neuronal cell characteristics and are widely used for studying neuronal differentiation, signaling pathways, and neurosecretion. PC12 cells are often used in neurobiology research, including the study of neuronal development, neurotransmission, and neurotoxicity.

3
•
2.3
P19 cell line - a mouse embryonic cell line (an embryonic cell line - a set of cells isolated from a mouse embryo at an early stage of development) of carcinoma derived from teratocarcinoma (a rare type of tumor that arises from germ cells called embryonic cells). These cells have the potential to differentiate into different types of cells (including neurons, heart muscle cells, and adipocytes). P19 cells are often used as a model system for studying cell differentiation and development, particularly in the context of neuronal differentiation.
It’s important to note that the use of embryonic cell lines is regulated by ethical guidelines and regulations in many countries, with an emphasis on adhering to ethical standards in obtaining and using embryonic cells.
Planned experiments
The information sources mention several experiments that are to be done, however they do not provide to much details on them.
CLINICAL TRIAL DISCUSSIONS

• Clinical trials are research studies performed on people that are aimed at evaluating a medical, surgical, or behavioral intervention. They are the primary way that researchers find out if a new treatment, like a new drug or diet or medical device is safe and effective in people. Participation in clinical trials is voluntary and based on the principle of informed consent, meaning participants should be fully aware of the potential risks and benefits of the treatment, the specifics of the trial design, and their rights as participants. However, no more can be said on these as no purpose is given from the information sources.
• No specific experiment is mentioned. However, these will probably be related to the main goal of the pharmacological study.
  Since these should include humans, they are the most interesting experiments for the phenomenological studies, and thus should be coordinated with the phenomenological studies.
  WORK ON CELL CULTURES
  Other experiments focus on working on cell cultures, including but presumably not limited to various tumor-derived cell lines, immortalized cell lines, and primary cell lines. The sources further state that the work should be done with cell models that have specific receptors - specifically sigma and serotonergic receptors. They note that this is not necessarily required, but according to them it is good to have as some baseline.
  • Immortalized cell lines have unlimited division capacity and usually originate from tumor cells, while primary cell lines are isolated from fresh tissue samples and have limited division capacity. However, it is not precisely specified which cells are these and what exactly would be done with them.
  • It is not specified exactly which tests are in question, presumably the MTT test.
  Since it is not clear what tests would be done, it is not clear what data should be the output. If the experiments include MTT, than the same type of data can be expected as from already performed tests.
  WORK ON ORGANOIDS
  Work on organoids is mentioned, however without any details.

• Organoids include three-dimensional cell cultures that develop in vitro and have a similar structure and function as certain organs in the body. They are self-sufficient and self-sustaining microscopic structures that form from pluripotent stem cells or from tissue samples. Organoids contain various types of cells characteristic for a specific organ and can reproduce key characteristics of that organ, such as tissue architecture, cell differentiation, and functionality.
• No tests are described so no further information can be extrapolated.
  Since no specific tests are mentioned, no conclusion on data can be given, nor its further use in phenomenological studies.
  WORK ON TISSUE SECTIONS
  The information sources mention work on tissue sections.
  • The sources do not mention which tissues so no further information can be extrapolated. However, this presumably may be
    some brain tissues. The brain is composed of two main types of tissues: a) gray matter that is primarily made up of neuronal cell bodies, dendrites and synapses, and b) white matter that derives its color from myelin, a fatty substance that surrounds and insulates the axons. Former plays a key role in processing information in the brain, including controlling muscle movement, seeing and hearing, memory, emotions, and speech, while latter helps increase the speed at which electrical signals move along the axon. In addition to these, the brain contains several specialized structures and regions, each with their own specialized types of cells and tissues. For example: the cerebellum, the hippocampus, the hypothalamus and the blood-brain barrier.
  • No details on experiments are provided as well. Nevertheless, these might be some pathohistological tests.
    Without specific tests mentioned, it is impossible to give any guidelines on how outcome data could be further used in phenomenological studies.
    ANALYSIS OF OXIDATIVE PROCESSES
    Analysis of oxidative processes is also mentioned, however again without specific tests mentioned - only explaining that previous research suggests that DMT may have neuroprotective and potentially anticancer effects targeting these processes; it seems that there are no such tests related to DMT in the literature, so the suggestion is to use this as a viable ground to approve testing on humans.

• Resolving oxidative processes caused by injuries refers to mechanisms by which the body tries to cope with oxidative stress and damage that resulted from such stress. Oxidative stress occurs when the balance between the production of free radicals and the body’s ability to cope with them is disrupted. Oxidative stress can cause damage at the level of signaling pathways and cells, which can lead to disturbances in the functionality of the basic building elements of cells, as well as DNA damage and its replication and repair.
  Resolving oxidative processes caused by injuries implies the activation of various mechanisms and pathways that help minimize the harmful effects of oxidative stress and restore normal cell functionality. This may include the activation of antioxidative defense mechanisms, DNA damage repair, restoration of signaling pathways, and other processes aimed at eliminating oxidative stress and restoring normal cell functioning.
• As part of this segment related to oxidative processes, the information sources mention that fMRI (functional magnetic resonance) research could be conducted on targeted nodes - this is not officially stated as a plan, but once human testing is approved, it is non-invasive, so it wouldn’t be a problem to do this.
  fMRI is a brain imaging technique that allows monitoring brain activity through magnetic resonance. It is used for researching brain activity during different mental processes and functions. fMRI can detect changes in blood flow and oxygen in the brain, which is associated with the activation of specific areas of the brain.
  Targeted nodes refer to certain regions or areas of the brain that are targeted or of interest in the research. These brain regions may be associated with certain functions or processes being studied. Using fMRI techniques, researchers can track activity in these targeted nodes and analyze how it changes during certain tasks, states, or manipulations.
  If fMRI is conducted for these studies, than these can certainly be used in phenomenological studies as they contain mass amount of data and potentially useful information.

4
3 Conclusion
By reading the information sources, it is understandable that the pharmacological study has a very clear research direction, namely researching the effects of DMT on reducing oxidative stress levels, which will serve as a basis for all other experiments, including phenomenological studies.
However, the initial experiments that will be conducted on a cell level and animals (presumably pigs) do not seem to be extremely relevant for the phenomenological part of the study as they cannot reveal much on ”DMT world”. Therefore, these experiments should be only followed up by the phenomenological researchers in a lightweight manner, and used as a basis for future approvals. In other words, data coming from these initial pharmacological experiments will probably not be used for phenomenological studies.
Nevertheless, since the information sources mention clinical trials and experiments such as fMRI, this research direction does seem viable for future phenomenological tests. Due to lack of more detailed descriptions of these experiments (presumably due to an early stage of pharmacological study), it is not possible to give any assumptions on how this data could be used at this moment. However, once the pharmacological studies reach the stage of clinical trials and fMRI, both phenomenological and pharmacological studies should be in sync.
5
Ivana Nizetic Kosovic DMT META-PROJECT Toni Mastelic WP.3 Report
Abstract
2023-06-26
DMT Meta-Project study is part of a broader DMT project focusing on research and innovation aspects of DMT and its use in various fields. The goal of this study is to identify possible research and innovation directions that go beyond the current studies being done around the world.
This is the third out of five reports for the DMT Meta-Project documenting the outcomes of WP.3, i.e., identifying feasible studies. Previous work packages include WP.1 Document related work and WP.2 Document feasible experiments, while follow up reports include WP.4 Explore new directions, and WP.F Write final report.
This report is structured as follows. Section 1 explains why data is important and how to get it. Section 2 covers various measurements and measuring instruments that can serve as data sources, while Section 3 lists several publicly available datasets acquired with previously mentioned instruments. Section 4 provides new ideas for DMT related studies that could result with some interesting data in the context of phenomenological studies. Finally, Section 5 gives a conclusion.
Contents

1. 1  Introduction 2
2. 2  Measurements and measuring instruments 2
   1. 2.1  Cellularlevelmeasurements................................................ 2
   2. 2.2  Wholebodylevelmeasurement.............................................. 2
   3. 2.3  DMTlevelmeasurement.................................................. 2
3. 3  Publicly available datasets 3
4. 4  DMT related studies 3
   1. 4.1  Exploresubjectivenessof”DMTworld”.......................................... 3
   2. 4.2  Data/informationextractionfrom”DMTworld” ..................................... 4
   3. 4.3  DecodingrealityusingDMT................................................ 4
   4. 4.4  DMTtechnology...................................................... 4
   5. 4.5  EndogenousDMT ..................................................... 4
5. 5  Conclusion 5

1
1 Introduction
DMT studies include scientists from range of research fields, such as chemists, biologists, neuro-scientists, psychologists etc. Using variety of measuring instruments, the output of any experiment is - data. In technological perspective, data-driven approach emphasizes the collection and analysis of data to inform decision-making. The goal of this report is to identify data sources that can represent various measurements and measuring instruments, publicly available datasets, as well as specific DMT related studies.
2 Measurements and measuring instruments
This section tries to structure and summarize relevant measuring instruments and measurements that may be performed as part of the broader DMT project. It does so by giving emphasise on data that could be acquired using such instruments and measurements.
2.1 Cellular level measurements
Cellular experiments can be performed on single cells, cell cultures, or tissues, depending on the research question and experimental design. There is an overlap between these experiments, and researchers often employ a combination of approaches to gain a comprehensive understanding of biological systems.

• Single cell experiments - Single-cell experiments involve studying individual cells in isolation. These experiments provide insights into cell heterogeneity, gene expression profiles, protein expression levels, and signaling dynamics at the individual cell level. Common tests are: Single-Cell RNA Sequencing (scRNA-seq), single-cell proteomics (mass spectrometry, single-cell Western blotting, or proximity ligation assays), and single-cell imaging (fluorescent microscopy, live-cell imaging, or super- resolution microscopy). Single-cell experiments provide detailed information about individual cell properties but may lack the context of tissue architecture and cell-cell interactions.
• Cell culture experiments - Cell culture involves growing cells in a controlled laboratory environment. Cell culture experiments are commonly used to investigate cellular processes, drug responses, and molecular interactions. Most common tests include: cell viability assays (MTT assay, ATP-based assays, or staining methods like trypan blue exclusion), proliferation (BrdU or EdU incorporation assays to measure DNA synthesis, flow cytometry for cell cycle analysis, and immunohistochemistry for detecting proliferation), differentiation (cell fate mapping, lineage tracing, and gene expression analysis), or apoptosis (Annexin V/propidium iodide staining, TUNEL assay, caspase activity assays). Cell culture experiments offer controlled conditions but may not fully replicate the complex environment found in living organisms.
• Tissue-based experiments - Tissue-based experiments and organ-based experiments involve studying cells within the context of their native tissue or organ structure. Common tests are histology, immuno-histochemistry, in situ hybridization, electron microscopy (EM and TEM), multiphoton microscopy, tissue clearing and 3D Imaging (optical clearing, CLARITY, or iDISCO). Tissue-based experiments capture cellular interactions but can be influenced by the complexity and heterogeneity of the tissue.
  To put these measurements in the context of the previous report (WP.2 Report), MTT assay has already been performed by Josipa, while probably more will be performed on a cellular level before getting approvals for animals, and eventually humans. This is also important for building research track record on DMT. However, from the perspective of phenomenological studies, these measurements are currently of low interest.

2.2 Whole body level measurement
DMT, like other psychedelics and like any other drugs, are typically tested on the whole body level to understand their effects, safety, and potential therapeutic applications. Many of these tests can be applied to mammals in general, but some of the tests are human-specific.
• Basic physiological measurements - Physiological measurements refer to the assessment and quantification of various parameters or processes within living organisms to understand their physiological state, functioning, and responses. This includes: vital signs (heart rate, body temperature, blood pressure, respiratory rate), blood tests (levels of glucose, cholesterol, hormones, enzymes, electrolytes), electrocardiography (heart rate, rhythm), electromyography (muscle function, muscle activity) etc.
• Brain measurements - Brain measurements provide valuable insights into the working of the brain, its connectivity, and its role in various cognitive processes. Common tests are: Structural Magnetic Resonance Imaging (MRI), Functional Magnetic Resonance Imaging (fMRI), Electroencephalography (EEG), Magnetoencephalography (MEG), Positron Emission Tomography (PET), Transcranial Magnetic Stimulation (TMS).
• Psychological tests - These test can be given to a subject before and after the DMT session to measure the cognitive abilities and emotional states. Example of the tests are various IQ and cognitive tests (WAIS), anxiety tests (STAI), emotional state tests (Projective Drawings), language tests (Stroop Test), etc.
• Motor ability tests - Motor ability tests are assessments that evaluate an individual’s physical coordination, dexterity, and motor skills. Example of the tests are: speed of reactions (Finger Tapping Test, Nine-Hole Peg Test), balance tests (TUG test), writing, drawing tests (VMI), etc.
• Descriptions - During the psychedelic sessions, subject can reply to some questions or can describe what he feels or sees. Textual descriptions of the state of the subject during the experiment can be collected (written by the observer or by the person himself).
While initial whole body experiments are commonly performed on animals as reported in WP.2 Report, such as mouse, rat and pig, and are thus of low interest for phenomenological studies, whole body measurements on humans that come later are of great interest to phenomenological studies. Consequently, this and following reports will focus mostly on them.
2.3 DMT level measurement
For many of the experiments, it is necessary to measure DMT level in the brain of the subject. However, the technology is still limited, and the only feasible solution is to measure it indirectly for now. It is also important to test and measure dozing of DMT during the DMT sessions.
• DMT concentration in the blood - Concentrations of DMT in the blood are typically very low, and detecting and accurately quantifying DMT in blood samples can be challenging. DMT is rapidly metabolized in the body, and its levels in the blood can vary depending on factors. Therefore, measuring DMT from the blood is not highly correlated with the DMT in the brain.
• Measuring DMT level in the brain - Tests that measure DMT level in brain are invasive or often impossible to conduct. Some of the examples are cerebrospinal fluid sampling and postmortem analysis. PET imaging can indirectly provide information
2
about the activity and distribution of DMT receptors in the brain (using radiotracers that target the serotonin (5-HT) receptors). • Dozing DMT - DMT can be dozed using various methods (by inhaling, intravenously, intramuscular, orally). Each of the method has its measurement properties and it is important to be able to correlate each other. It is also important to measure the doze to
be able to correlate it to the effect of DMT on the cells or on the body.
This subsection does not necessarily include existing and feasible measurements and related instruments, rather it tries to go
beyond available technology and discuss opportunities on developing such and the benefits (i.e., data) it could bring if such technology would exist.
3 Publicly available datasets
This is the list of datasets that could be useful for analyzing DMT effects in some of the experiments. Most of the datasets are not directly related to DMT nor psychedelics, however they can be useful for preliminary analysis or for directions on analysis of DMT-related data once they are gathered. Also, please not that this is not a comprehensive list of datasets, rather this is an excerpt of such datasets that are available online, that may be used for understanding data format, preparing algorithms and performing initial analysis.
FMRI DATA SOURCES

• The Natural Scenes Dataset1 - public available fMRI measurements of 8 subjects while they viewed thousands of color natural scenes over the course of 30–40 scan sessions. While viewing these images, subjects were engaged in a continuous recognition task in which they reported whether they had seen each given image at any point in the experiment. These data constitute a massive benchmark dataset. More details in [1].
• Bold50002 - public available fMRI dataset collected on 4 subjects, each observing 5,254 images over 15 scanning sessions. More details in [3].
• Generic Object Decoding3 - The dataset consists of pairs of high-resolution stimuli images and the corresponding fMRI recordings. More details in [5].
• CRCNS - Collaborative Research in Computational Neuroscience 4 - the portal that provides a marketplace and discussion forum for sharing tools and data in neuroscience. Some interesting datasets are: vim-1 (dataset contains fMRI responses in human subjects viewing natural images, popular as first demonstration of ”mind reading” 5), vim-2 (This data set contains fMRI responses in human subjects viewing a set of natural movies 6) etc.
• OpenNeuro7 - platform developed by the Stanford Center for Reproducible Neuroscience for data sharing and analysis of raw MRI data. Some of interesting datasets are on fMRI images and corresponding images of human faces [9] and corresponding viewed or imagined object images [6].
  EEG DATA SOURCES
  • DMT-related measurements of EEG8 - public available dataset of EEG measurements from 35 healthy subjects, volunteered to inhale, using pipes, 40 mg of free DMT extracted from the root of Mimosa hostilis. More details in [8].
  TRIP DESCRIPTIONS
  • Erowid.org9 - web site that contains basic information (laws, effects, dose, etc.) on DMT all in one place, as well documented trips.
  • Reddit channel10 - a Reddit channel that contains numerous descriptions of DMT trip experiences, that was also used in this publication [7].
    OTHER INTERESTING SOURCES
    • Symmetric Vision11 - youtube channel where the author tries to replicate visuals during psychedelics trip, including DMT. 4 DMT related studies
    This section contains some initial ideas on DMT related experiments that might help explore phenomenological effects of DMT and perhaps open some new research directions and business opportunities. The ideas are grouped into several categories based on their approach and purpose, and most of them require clinical trials on healthy patients. Also, relevant measurements from Section 2 are also put in the context here.

4.1 Explore subjectiveness of ”DMT world”
Since ”DMT world” seems to be highly affected by set and setting (i.e., individual persona and surrounding environment, respectively), it would be interesting to explore the consistency of ”DMT world” and how it can be stimulated on an individual:

• World consistency - have multiple patients observe the same view (e.g., a picture) and record the differences in their
  perceptions. This could also include micro-dosing approach where a patient receives incremental dozes of DMT in order to examine transitions of those perceptions. This should also include profiling of patients for their cultural and personal backgrounds.
• Spatio-temporal effects - as an extension to the previous experiment, conduct experiments with joint trips in order to examine
  spatial and temporal effects on ”DMT world”, i.e., having multiple patients at the same place at the same time and comparing
  their subjective/objective experiences.
• External stimuli - provide consistent external stimuli to multiple patients during DMT trip to try to impact the perceptions and
  the ”DMT world”, e.g., play calming music to drive patients to the same ”place”. However, since external stimuli may not have an affect during the full DMT trip, micro-dosing could be used here as well.
  1 https://naturalscenesdataset.org/
  2 https://bold5000-dataset.github.io/website/ 3http://brainliner.jp/data/brainliner/Generic Object Decoding 4 https://crcns.org/data-sets
  5 http://crcns.org/data-sets/vc/vim-1
  6 http://crcns.org/data-sets/vc/vim-2
  7 https://openneuro.org/
  8 https://zenodo.org/record/3992359
  9 https://erowid.org/chemicals/dmt
  10 https://www.reddit.com/r/DMT/
  11 https://www.youtube.com/@SymmetricVision/search?query=dmt

3

• Disabled people - explore how (born-)blind people experience DMT trip. What ”visuals” they perceive and what other senses
  are perhaps neglected by visually non-paired people due to strong visuals. This may also include mind-blinded people that
  experience DMT trip in a non visual manner, or perhaps people with other disabilities or illnesses.
• Other senses - as a follow up the previous idea, it would be interesting to investigate how other senses are triggered by DMT,
  since DMT trip seems to be mostly visual experience. This may also be extended to feelings, perceptions, self-awareness,
  purpose, etc.
  The output data of these experiments is mostly in free textual form (i.e., descriptions) where patients (or someone on their behalf)
  document their experiences. Nevertheless, basic physiological measurements should also be collected if possible in order to record physical reactions as well and try to map them to the described experiences.

4.2 Data/information extraction from ”DMT world”
The goal of these ideas is to acquire more information on ”DMT world”, or even more precisely take something (i.e., data/information) from/about ”DMT world”:

• Take pictures/footage - try to reconstruct the visuals seen by patients, i.e., this would be equivalent to bringing a camera to
  the ”DMT world” and taking a picture or footage.
• Record audio - almost all patients report on hearing sounds and voices in ”DMT world”, however this has not been vastly explored. It would be interesting to examine how hearing is triggered during a DMT trip and see if they can be reconstructed. This would be equivalent to bringing a microphone to the ”DMT world” and recording an audio.
• Collect knowledge - prepare a questionnaire to which a patient does not know the answers, and let the patient ask DMT
  entities the questions and collect answers, in order to see if there is some extrinsic knowledge within the ”DMT world”.
• Enhanced abilities - perform IQ, creativity, memory, etc., tests on patients prior and post DMT trips, and examine differences. This would be equivalent of using ”DMT world” as a staging area for new abilities and experiences, just like getting rid of fear
  of flying with hypnosis. Also, both prior and post tests should be repeated periodically during a longer time period, in order to
  learn the trend and long-term effects of DMT.
• Experts as patients - enrol mathematicians, physicists, anthropologists, linguists, etc., in DMT trips to get professional
  descriptions of the ”DMT world”. This is based on documented sightings of fractal shapes, different entities, alien languages,
  etc., something that would be much better described by an expert in the given field.
  First two experiments certainly require brain measurements such as fMRI or EEG, while the next two require psychological tests
  that are conducted before and after a DMT trip. Last experiment requires textual descriptions that can be used for recreating the observed, e.g., drawing fractal shapes, reconstructing alien languages, etc. Lastly, all experiments should perform basic physiological measurements where possible.

4.3 Decoding reality using DMT
The idea behind this section is that by micro-dosing, DMT might serve as a tool to decode hidden meanings of our world and unlock latent human senses or potential.

• Psychedelic cryptography - use elaborate techniques to encode some secrete messages into some form (e.g., image, sound, etc.) and use partial DMT trips (i.e., by using micro-dosing) to decode those messages.
• Decoding existing art - while the following experiment is hard to evaluate, it serves as a follow up of the previous experiment. Namely, try to reveal hidden meaning of existing art and objects, such as mandalas used by yogi, or art by famous artists that
  used psychedelics, such as music by Pink Floyd or the Beatles.
• Superhumans - use partial DMT trips to try to replicate ”superhuman” abilities that are usually exhibited by people with
  autism for instance to learn if DMT enhances perceptions, e.g., fast counting and calculation, IQ tests, etc. Unlike the enhanced
  abilities experiment from Section 4.2, here the psychological tests are performed during partial DMT trips.
  First experiment requires some cryptographic tools in order to create this encrypted forms that will be used in the experiment. The experiment itself should result with descriptions in a structured form that can be matched with the original messages that were encrypted. Second experiment is hard to evaluate as its output in form of descriptions cannot be compared with the groundtruth as it is not known. Last experiment requires motor ability tests as well as psychological tests such as IQ tests. The resulting data can
  be in structured form and the experiments should be repeated several times.

4.4 DMT technology
Since DMT can be considered as a technology that allows one to enter a different realm (real or imaginary), it would be interesting to explore if this technology can be improved and better controlled:

• Reverse engineering - it would be interesting to figure out what is being stimulated and how in order to replace the effects
  with different technology other than chemicals perhaps, i.e., something that allows more control and granularity. This would
  allow creating the same effect or at least a sensation that DMT creates in a controlled manner.
• Incremental dozing - give a patient a small doze of DMT to see how observed reality starts to change. This sounds useful for examining transitional states between sober phase and the full DMT trip, as well as for understanding the limits of minimum
  level of experience and perhaps maximum level of experience, i.e., is there a threshold after which additional dosage of DMT
  does not make a difference.
• Prolonged DMT trips - it seems very important to have longer trips in order to allow ones consciousness to build a model of
  the ”DMT world”, just as the same as one builds a model of this world when being born. Consequently, developing a technology that can have prolonged yet stable DMT trips seems extremely beneficial for future DMT studies.
• Non-hallucinogenic DMT - inspired by Triptan drugs that have similar chemical structure as DMT and have therapeutic benefits, perhaps some other derivatives might be created that can create limited and more controlled DMT trips.
  These experiments are more related to cellular level measurements (Section 2.1), while on humans they would require DMT level measurements discussed in Section 2.3. Alternatively, existing basic physiological measurements may be conducted in order to get at least some baselines.

4.5 Endogenous DMT
It seems there are other ways to enter ”DMT world” or something similar to it without taking external substances. These ideas try to explore those alternative routes to ”DMT world”, which might be strongly related to the endogenous DMT within the human body.
• Natural DMT concentration - compare natural amounts of DMT found in a human body from multiple patients in order to define a DMT baseline and different perceptions of the same thing.
4
• DMT level during sleep state - while there are many papers discussing the similarities and differences between DMT trip and sleep state, it would be interesting to experiment with DMT levels during sleep state. This way, one could test the theory of
DMT being ancestral neuromodulator that used to secreted during sleep.
• DMTlevelduringmeditation-therearemanyreportsthatDMTtrip(oratleastsomethingthatfeelsthesame)canbeachieved through various meditation and breathing techniques. It would be interesting to measure DMT levels during meditation.
• DMT level during near-death experiences - while these can hardly be done on humans, there are some studies done on animals, such as in [2] where scientists have induced cardiac arrest to rats and observed its brain activities. It would be interesting to try to measure its DMT level. There is actually one study done on this topic and it gave very interesting insights, i.e., that the amount of DMT is comparable to serotonin [4].
• DMT level during a psychedelic trip - while this idea may sound redundant, there are several reports (e.g., from Steven Barker, LSU) that during LSD trip the level of endogenous 5-Meo-DMT and DMT increases. So, it would be interesting to learn if LSD or any other psychedelic drug is actually creating a psychedelic experience or is it simply stimulating more secretion of
DMT that produces a psychedelic experience.
These experiments are highly depended on DMT level measurements on humans from Section 2.3, thus they are currently not
fully feasible as those measurements do not still exist or perhaps do not seem advanced enough.
5 Conclusion
The purpose of this report was to identify studies that have not been comprehensively explored elsewhere, while still being feasible with accessible resources.
On one hand, experiments exploring subjectiveness of ”DMT world” (Section 4.1), the extraction of data/information from it (Section 4.2) and the use of DMT to decode reality (Section 4.3) are three main sets of experiments that target at understanding of the ”DMT world” and how it relates to the real world. More importantly, they can and should be conducted on humans as part of clinical studies with a goal of understanding the phenomenological effects of DMT. On the other hand, exploration of DMT technologies (Section 4.4) and endogenous DMT (Section 4.5) focus more on the advancement of pharmacological effects and usage of DMT, and thus can serve as a basis for more robust future experiments and utilization of DMT. Consequently, these may bring benefits to the phenomenological studies in the long run.
Finally, it would be advisable to combine as much experiments as possible in order to reduce their sheer amount, as well as to acquire more diverse data by making all feasible measurements for most of the experiments.
References

1. [1]  Emily J. Allen, Ghislain St-Yves, Yihan Wu, Jesse L. Breedlove, Logan T. Dowdle, Brad Caron, Franco Pestilli, Ian Charest, J. Benjamin Hutchinson, Thomas Naselaris, and Kendrick Kay. A massive 7t fmri dataset to bridge cognitive and computational neuroscience. bioRxiv, 2021.
2. [2]  Jimo Borjigin, Uncheol Lee, Tiecheng Liu, Dinesh Pal, Sean Huff, Daniel Klarr, Jennifer Sloboda, Jason Hernandez, Michael Wang, and George Mashour. Surge of neurophysiological coherence and connectivity in the dying brain. Proceedings of the National Academy of Sciences of the United States of America, 110, 08 2013.
3. [3]  Nadine Chang, John A. Pyles, Austin Marcus, Abhinav Gupta, Michael J. Tarr, and Elissa M. Aminoff. Bold5000, a public fmri dataset while viewing 5000 visual images. Sci Data, 2019.
4. [4]  Jon G Dean, Tiecheng Liu, Sean Huff, Ben Sheler, Steven A Barker, Rick J Strassman, Michael M Wang, and Jimo Borjigin. Biosynthesis and extracellular concentrations of n, n-dimethyltryptamine (dmt) in mammalian brain. Scientific reports, 9(1):1–11, 2019.
5. [5]  Tomoyasu Horikawa and Yukiyasu Kamitani. Generic decoding of seen and imagined objects using hierarchical visual features, 2016.
6. [6]  Tomoyasu Horikawa and Yukiyasu Kamitani. ”generic object decoding (fmri on imagenet)”, 2019.
7. [7]  DW Lawrence, R Carhart-Harris, R Griffiths, and C Timmermann. Phenomenology and content of the inhaled n, n-dimethyltryptamine (n, n-dmt) experience. SCIENTIFIC REPORTS, 12, 2022.
8. [8]  Carla Pallavicini, Federico Cavanna, Federico Zambelan, Laura Alethia de la Fuente, Mauricio Arias, Celeste Romero, Robin Carhart-Harris, Christopher Timmermann, and Enzo Tagliazucchi. Neural and subjective effects of inhaled DMT in natural settings, August 2020.
9. [9]  Rufin VanRullen and Leila Reddy. Reconstructing faces from fmri patterns using deep generative neural networks. CoRR, abs/1810.03856, 2018.

5
Ivana Nizetic Kosovic DMT META-PROJECT Toni Mastelic WP.4 Report
Abstract
2023-06-26
DMT Meta-Project study is part of a broader DMT project focusing on research and innovation aspects of DMT and its use in various fields. The goal of this study is to identify possible research and innovation directions that go beyond the current studies being done around the world.
This is the fourth out of five reports for the DMT Meta-Project documenting the outcomes of WP.4, i.e., exploring new directions. Previous work packages include WP.1 Document related work, WP.2 Document feasible experiments and WP.3 Identify feasible studies, while a follow up report includes WP.F Write final report.
This report is structured as follows. Section 1 puts this report into the context of the previous Report WP.3. Section 2 covers technologies that are suitable for phenomenological studies, including natural language process, generative AI models, compute vision, speech recognition and data analytics in general. Section 3 covers technologies that are suitable for pharmacological studies, including supervised and unsupervised learning used in bio-informatics, and reinforcement learning. Finally, Section 4 gives a conclusion of this report.

Contents
1  Introduction 2
2  Technologies with the potential for PHENOMENOLOGICAL studies 2
2.1  Naturallanguageprocessing ............................................... 2
2.2  Generativemodels..................................................... 2
2.3  Computervision...................................................... 3
2.4  Speechrecognition..................................................... 3
2.5  Dataanalytics ....................................................... 3
3  Technologies with the potential for PHARMACOLOGICAL studies 4
3.1 Bio-informatics(supervisedandunsupervisedlearning)................................. 4
3.2 Reinforcementlearning .................................................. 4 4 Conclusion 4

1
1 Introduction
In the previous report (WP.3), five categories of DMT related studies have been identified, namely:

• Explore subjectiveness of ”DMT world” - this category provides mostly textual descriptions about patients experiences, and
  may provide basic physiological measurements.
• Data/information extraction from ”DMT World” - this category provides brain measurements such as fMRI and EEG,
  psychological tests, textual descriptions, and may also provide basic physiological measurements.
• Decoding reality using DMT - this category outputs results in a textual form, such as descriptions in a structured form, as well
  as motor ability tests and psychological tests.
• DMT technology - this category requires cellular level measurements and DMT level measurements, and may also provide
  basic physiological measurements.
• Endogenous DMT - this category requires DMT level measurements.
  First three categories are more related to the phenomenological studies that may result with advanced insights in to the ”DMT world”, while the last two are more related to pharmacological studies and may result with the advances in applying and using DMT. In this report, data science approaches and related IT technologies that might be interesting or required for pushing DTM
  experiments beyond their current limits are explored. Each technology is described and backed by related work, as well as put into the context of the above mentioned DMT related studies.
• 
  

2 Technologies with the potential for PHENOMENOLOGICAL studies
Most of these technologies are based on machine/deep learning algorithms, so instead of continuously referring to them, following subsections are rather broken into their subbranches based on their purpose and approach.

2.1 Natural language processing
Many of the experiments from phenomenological studies result with descriptions of patient experiences in an unstructured textual form. Moreover, there is a significant body of publications on DMT and its effects. However, processing these materials manually is lots of work and may not be done comprehensively and structurally in a realistic time frame. Consequently, it makes sense to apply natural language processing (NLP) tools for their analysis.

RELATED WORK

Tools such as ChatGPT1 and Bard2 do not require an introduction, and are the best examples of NLP utilization. Along with those commercial solutions, there are also many open source NLPs that can be adapted to specific purposes, such as PrivateGPT3 and LLaMA [11].

EXPLORE SUBJECTIVENESS OF ”DMT WORLD”
Almost all experiments from Report WP.3 that explore subjectiveness of ”DMT World” result with textual descriptions of patients experiences. There are even publications that try to classify and model the ”DMT world” from such descriptions such as [5], and may be used as an additional data input.
Even before performing any of those experiments, a vast amount of online descriptions and official publications may be taken as a data source and be fed into NLP for learning. After that, the model could be asked to provide classifications, explanations, inconsistencies, similarities, etc. in order to extract the objective parts of the ”DMT World” from the subjective ones.
Results from the preliminary study can be used as a baseline once additional experiments are conducted during clinical trials. This is especially important if the clinical trials may not include many patients. Consequently, combining these datasets may provide better results and understanding of the ”DMT World”.
Another use of this DTM enhanced NLP model would be to generate ideas for new experiments and setups for exploring subjectiveness of the ”DMT World”, hence relying on the model that it will recognize some patterns in the descriptions.

COLLECT KNOWLEDGE
Questionnaires that should be prepared for these experiments could be prepared by using NLP software in order to avoid bias; or even used for profiling patients in order to generate common set of questions that fit certain set of experiments.

PSYCHEDELIC CRYPTOGRAPHY
NLP may be used to create a cyphertext that could be read by a patient, and see how much time does it take to do it sober as well as during a partial DMT trip, and compare the results on larger scales with multiple patients and a big set of cyphertexts.

2.2 Generative models
While generative models include variety of machine/deep learning models, only image generation is considered here due to DTM providing mostly visual experiences.

RELATED WORK
Tools such as Midjourney4, DreamStudio5, DALL-E6, etc., also do not need a special introduction, as they have taken the Internet by storm. This tools can be used for generating images based on a textual input.

WORLD CONSISTENCY
These image generative tools may be used for generating images for conducting clinical trials where patients should observe the same view. In order to avoid bias when showing images of real places, these tools can be used for creating images of places and people that do not exist.

EXPERTS AS PATIENTS
Furthermore, along with numerous graphical reconstructions of DMT trips such as Symmetric Vision7, descriptions from the experts could be fed into these tools in order to reconstruct images from the ”DMT World”, i.e., using these tools as sketch artists.

PSYCHEDELIC CRYPTOGRAPHY
Generative AI tools could also be used to generate images with encoded information within them, and see if they can be observed and eventually read by patients during partial DMT trips.
1 https://chat.openai.com/
2 https://bard.google.com/
3 https://github.com/imartinez/privateGPT
4 https://www.midjourney.com
5 https://beta.dreamstudio.ai/generate
6 https://labs.openai.com/
7 https://www.youtube.com/@SymmetricVision/search?query=dmt

2
2.3 Computer vision
Reconstructing visual experiences from human brain activity is important tool to understand ”DMT world”. In recent years, there is a fair amount of papers covering the topic of reconstruction of images presented to a person using fMRI images, regardless of psychedelics.

RELATED WORK
The main idea behind the related work is to feed the deep learning model with fMRI images or EEG measurements, together with the images of certain interest (mostly natural images) that correspond to fMRI or EEG images; and then to use that model to decode new images from fMRI or EEG.
Paper [8] is a survey on different deep learning methods and approaches on this topic. The variety of visual stimuli can be used in an experiment of image reconstruction tasks: from low-level detail images, such as shapes, characters, colors or patterns to high-level detail images with semantics such as faces or natural objects. Although low-level images are interesting in terms of DMT reconstruction of visuals (fractal structures, shapes etc.), if we want to deep dive into the ”DMT world”, the images of natural objects or even videos are of most interest, and the most challenging at the same time. Survey [8] gives an overview of related work in terms of datasets they were used in experiments along with source code availability. Most recent papers (published after survey) with promising results are: [7] [10] [3].
Another approach in decoding images from brain activity is the work described in [9]. Authors have demonstrated the reconstruction of images presented to a person undergoing EEG in real-time. Although their video demonstration 8 seems promising, there is no activity of this group after 2019 when paper was published. Combining fMRI and EEG should also be considered [12].

DATA/INFORMATION EXTRACTION FROM ”DMT WORLD”
The above technologies can be used to reconstruct visuals that people see during a DMT trip. Visuals are mostly images, but it seems that reconstructing the sequence of images (video) might also be possible. Prior to those experiments, images generated from patients’ experiences 2.2 could be used to build a model, so that the model learns not only on realistic images but also on artificial images that are more likely to appear in the ”DMT world”.

DECODING REALITY USING DMT
The same technology can be used to reconstruct what people see during micro-dosing. This experiment can be even more controlled than previous, since we expect to have slight change of the reality, not a completely new world.

SUPERHUMANS
For the experiments that explore so called ”Superhuman” abilities on partial doses of DMT, this technology could be used for the preparation and automation of the experiments themselves. For instance, for visual fast counting or interpreting some images, this technology could be used for performing those counting in real-time, while keeping them random; something that would be extremely hard to perform without such technology.

2.4 Speech recognition
In order to reconstruct an audio from ”DMT world”, it needs to be done from a patient’s brain. There are related studies that use AI in order to do this9.

RELATED WORK
In a paper [1] from 2019 published in Nature as scientific report, the researchers did an experiment by playing recordings of speech to patients with epilepsy who were in the middle of brain surgery. As the patients listened to the sound files, the researchers recorded neurons firing in the parts of the patients’ brains that process sound. They used deep learning in order to reconstruct the speech, which they played back to a group of 11 listeners using synthesizes human voices; those individuals were able to correctly interpret the words 75 percent of the time.
In [2] from 2018, the authors performed an opposite experiment than the above by letting patients during a brain surgery read single-syllable words out loud and recording both the sounds coming out of the participants’ mouths and the neurons firing in the speech-producing regions of their brains. Later, they used machine learning to convert the neural recordings into audio, showing that the results were at least reasonably intelligible and similar to the recordings made by the microphones.
Finally, a paper from 2018 [6] relied on recording the part of the brain that converts specific words that a person decided to speak into muscle movements. The researchers reported that they were able to reconstruct entire sentences (also recorded during brain surgery on patients with epilepsy) and that people who listened to the sentences were able to correctly interpret them on a multiple choice test (out of 10 choices) 83 percent of the time. That experiment’s method relied on identifying the patterns involved in producing individual syllables, rather than whole words.

RECORD AUDIO
This technology could be used for extracting audio from the ”DMT World”, since the related work shows that brain waves could be used for reconstructing words and sentences a patient has heard, as well as those the patient intended to speak. This approach makes it possible to ”record” an entire conversation between the patient and an entity from the ”DMT World”.
All these experiments could be pushed one step forward; instead of only training AI to convert brain waves into audio, it could also be trained to translate the audio into the original text. This way, the whole process would be fully automated and perhaps done in real-time, while the subjectiveness of the listeners would be alleviated.

DECODING REALITY USING DMT
This technology could also be used for encoding/decoding audio encrypted messages. For instance, if the studies would show that the brain waves alter the way the sound is processed in the brain in a consistent and predictable manner for each individual or in general, this could be used for encoding audio by recording it in a partial ”DMT World”, and decoding it the same way. This might be far fetched, however, one has to be open minded when exploring patterns within the ”DMT World”, so this might be a good guideline.

2.5 Data analytics
Not necessarily a part of Artificial Intelligence technologies, nevertheless standard data analytics tools can contribute understanding data that is or will be obtained through these experiments.

EXTERNAL STIMULI
Finding that some external stimuli has made some effect on patients’ ”DMT World” requires correlating data that is generated by that stimuli and basic physiological measurements. For instance, patients’ heart beat slows down after playing soothing music during a DMT trip.
8 https://scitechdaily.com/image-reconstruction-from-human-brain-waves-in-real-time-video 9 https://www.livescience.com/64424-speech-computer-brain-interface.html

3
ENHANCED ABILITIES
Since these experiments require sequential tests over a longer time period, analyzing their results requires smart data analysis of so called ”small data” in order to observe any progress that is statistically relevant.

GENERAL APPLICATION
Since the output of most of these experiments is data measurements, it is expected that the data analytics will be applied in many cases, especially when trying to scientifically prove that there is causality between certain things.

3 Technologies with the potential for PHARMACOLOGICAL studies
These technologies mostly include classic machine learning approaches, where certain data is either used for finding correlations or patterns within data, or utilizing that data for automating certain processes.

3.1 Bio-informatics (supervised and unsupervised learning)
Supervised and unsupervised learning are two branches of machine learning that are commonly used in bio-informatics. Former relies on having groundtruth values which are then correlated with other data, while latter tries to extract patterns without groundtruth.

RELATED WORK
On one hand, supervised learning techniques include support vector machine, random forest, linear regression, logistic regression, etc. On the other hand, unsupervised learning techniques include K-means clustering, hierarchical cluster, principa component analysis, self-organizing maps, etc.

DMT TECHNOLOGY
Without knowing what experiments could/should/will be done on a cellular level and on animals, and what data can be obtained from those experiments, it is impossible to precisely say what could be done with that data. Nevertheless, any acquired data could be used in the context of bio-informatics, which may help speed up any cellular level experiments. e.g., by modelling DMT behavior on a cellular level and running simulations, etc.
Moreover, these machine learning tools might even be used for developing more sophisticated DMT level measurements by finding correlations between different measurements that normally would not be detectable with traditional approaches. For instance, finding that basic physiological measurements (e.g., blood pressure) combined with brain measurements (e.g., fMRI) correlate with DMT level in animals, might be used for building a soft sensor for measuring micro-dosing levels of DMT in humans.

ENDOGENOUS DMT
If DMT level measurements would become accessible and more precise, these machine learning tools might be used for finding correlations, or even perhaps causality between DMT level and other states such as sleep, meditation, near-death experiences, etc. For instance, finding a cause and effect relationship between DMT level and REM phase during sleep.

3.2 Reinforcement learning
Technology that would allow DMT trip to last significantly longer (e.g., several hours) seems to be imperative for the clinical trials and the exploration of phenomenological effects of DMT.

RELATED WORK
Most notable studies and projects that cover this include [4] and DMTx10. However, none of these have applied machine learning techniques in their work, so there is room for improvement here.

PROLONGED DMT TRIPS
It seems that fine tuning the technology for prolonging DMT trips can be improved with AI, e.g., micro dozing DMT based on sensor readings from a patient’s brain and body in general, since not everyone seems to require the same doze level.
While it is not feasible to give any details on what would this actually require due to lack of information on availability of sensory data and their correlation, it can be stated that some form of ML modelling and probably reinforcement learning might be used for controlling the micro dozing process. Nevertheless, for this to happen, data should be acquired using available technology no matter how short DMT trips are.

NON-HALLUCINOGENIC DMT
The same way reinforcement learning could be used for achieving prolonged DMT trips, it can also be used for maintaining stable DMT level without letting a patient enter the ”DMT World”, and thus exploring either therapeutic benefits or phenomenological effects.

4 Conclusion
In this report, several relevant IT technologies have been identified that could be used for advancing the understanding of the ”DTM World”. Moreover, data available online provides an opportunity to start some preparations and analysis immediately in order to obtain some initial results. However, since the report includes a broad range of potential studies, it is not feasible to conduct them all. Consequently, only several most promising studies should be put on a short list and prioritized for further examination. Finally, they should be conducted based on that priority list. Following Report (WP.F) of the DMT Meta-Project will contain that short prioritized list.

References
[1] Hassan Akbari, Bahar Khalighinejad, Jose Herrero, Ashesh Mehta, and Nima Mesgarani. Towards reconstructing intelligible speech from the human auditory cortex. Scientific Reports, 9:874, 01 2019.
[2] Miguel Angrick, Christian Herff, Emily Mugler, Matthew C. Tate, Marc W. Slutzky, Dean J. Krusienski, and Tanja Schultz. Speech synthesis from ecog using densely connected 3d convolutional neural networks. bioRxiv, 2018.
[3] Zijiao Chen, Jiaxin Qing, Tiange Xiang, Wan Lin Yue, and Juan Helen Zhou. Seeing beyond the brain: Masked modeling conditioned diffusion model for human vision decoding. In arXiv, November 2022.
[4] Andrew R. Gallimore and Rick J. Strassman. A model for the application of target-controlled intravenous infusion for a prolonged immersive dmt psychedelic experience. Frontiers in Pharmacology, 7, 2016.
[5] DW Lawrence, R Carhart-Harris, R Griffiths, and C Timmermann. Phenomenology and content of the inhaled n, n-dimethyltryptamine (n, n-dmt) experience. SCIENTIFIC REPORTS, 12, 2022.
10 https://www.dmtx.org/
4

1. [6]  Yulia Oganian and Edward F. Chang. A speech envelope landmark for syllable encoding in human superior temporal gyrus. bioRxiv, 2018.
2. [7]  Furkan Ozcelik, Bhavin Choksi, Milad Mozafari, Leila Reddy, and Rufin VanRullen. Reconstruction of perceived images from fmri patterns and
   semantic brain exploration using instance-conditioned gans. 02 2022.
3. [8]  Zarina Rakhimberdina, Quentin Jodelet, Xin Liu, and Tsuyoshi Murata. Natural image reconstruction from fmri using deep learning: A survey.
   Frontiers in Neuroscience, 15, 2021.
4. [9]  Grigory Rashkov, Anatoly Bobe, Dmitry Fastovets, and Maria Komarova. Natural image reconstruction from brain waves: a novel visual bci system
   with native feedback. bioRxiv, 2019.
5. [10]  Yu Takagi and Shinji Nishimoto. High-resolution image reconstruction with latent diffusion models from human brain activity. bioRxiv, 2023.
6. [11]  Hugo Touvron, Thibaut Lavril, Gautier Izacard, Xavier Martinet, Marie-Anne Lachaux, Timoth ́ee Lacroix, Baptiste Rozi`ere, Naman Goyal, Eric Hambro, Faisal Azhar, Aurelien Rodriguez, Armand Joulin, Edouard Grave, and Guillaume Lample. Llama: Open and efficient foundation language models, 2023.
7. [12]  Tracy Warbrick. Simultaneous eeg-fmri: What have we learned and what does the future hold? Sensors, 22(6), 2022.

​