Neurochemical models of near-death experiences: A large-scale study based on the semantic similarity of written reports

This large-scale data-analytic study compared the semantic similarity of psychoactive trip reports (n≈15,000) and narrative accounts Near-Death Experiences (n=625), and found that ketamine (followed by salvinorin A and DMT) bared the most resemblance to the experience of ‘dying’. The authors speculate that a ketamine model of Near-Death Experiences may indicate a neuroprotective function of endogenous NMDA antagonists released in the proximity of death.

Abstract

Introduction: The real or perceived proximity to death often results in a non-ordinary state of consciousness characterized by phenomenological features such as the perception of leaving the body boundaries, feelings of peace, bliss and timelessness, life review, the sensation of traveling through a tunnel and an irreversible threshold. Near-death experiences (NDEs) are comparable among individuals of different cultures, suggesting an underlying neurobiological mechanism. Anecdotal accounts of the similarity between NDEs and certain drug-induced altered states of consciousness prompted us to perform a large-scale comparative analysis of these experiences.

Methods: After assessing the semantic similarity between ≈15,000 reports linked to the use of 165 psychoactive substances and 625 NDE narratives, we determined that the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine consistently resulted in reports most similar to those associated with NDEs. Ketamine was followed by Salvia divinorum (a plant containing a potent and selective κ receptor agonist) and a series of serotonergic psychedelics, including the endogenous serotonin 2A receptor agonist N,N-Dimethyltryptamine (DMT).

Results: This similarity was driven by semantic concepts related to consciousness of the self and the environment, but also by those associated with the therapeutic, ceremonial and religious aspects of drug use.

Discussion: Our analysis sheds light on the longstanding link between certain drugs and the experience of “dying“, suggests that ketamine could be used as a safe and reversible experimental model for NDE phenomenology, and supports the speculation that endogenous NMDA antagonists with neuroprotective properties may be released in the proximity of death.”

Authors: Charlotte Martial, Héléna Cassol, Vanessa Charland-Verville, Carla Pallavicini, Camila Sanz, Federico Zamberlan, Rocío Martínez Vivo, Fire Erowid, Earth Erowid, Steven Laureys, Bruce Greyson & Enzo Tagliazucchi

Summary

Near-death experiences (NDEs) are comparable among individuals of different cultures, suggesting an underlying neurobiological mechanism. A large-scale comparative analysis of 15,000 reports linked to the use of 165 psychoactive substances and 625 NDE narratives indicated that ketamine consistently resulted in reports most similar to those associated with NDEs.

Throughout known history, humans have shown a tendency towards modifying their ordinary state of consciousness by consuming certain fungi and plant materials. These altered states are often compared to other non-ordinary states of consciousness, such as dreams, nightmares, sleep paralysis, mystical experiences, meditative states.

Dopaminergic stimulants such as methamphetamine can induce psychotic hallucinatory states. The Tukano and Shipibo people believe that ayahuasca allows a transition towards a state of direct communication with the spirits of the deceased, while the Bwiti people use the bark of Iboga to induce “near-death” trances. In contemporary Western society, the experiences elicited by natural and semi-synthetic hallucinogens have been compared to dying. The comparison occurs at a purely psychological level, since these substances are very safe under most circumstances.

Near-death experiences can be described as phenomenological experiences associated with real or perceived proximity to death. These experiences can include leaving the body boundaries, feeling of peace and bliss, traveling through a tunnel or void towards a light, sensing an irreversible threshold, and communicating with sentient and autonomous entities. Researchers have noticed that serotonergic and dissociative psychedelics can induce a subjective NDE phenomenology, which could explain the long-standing association between these psychoactive compounds and the experience of “dying”.

Researchers have found some similarities between NDEs and drug-induced experiences, and have detected overlap between NDE phenomenology and that of a matched group of subjects who experienced a NDE after a life-threatening situation.

Studies have compared NDEs to the phenomenology of drugs such as LSD, dextromethorphan, carbon dioxide, hashish, 5-MeO-DMT, ayahuasca, ibogaine, and others, but there are limitations related to the use of structured questionnaires and biases in the selection of the psychoactive compounds to be contrasted with NDEs.

We retrospectively compared 625 narratives of events classified as NDEs with a large number of reports spanning experiences with 165 psychoactive substances of ten different pharmacological classes. Our results shed light on the possible neurobiological mechanisms underlying the robust and reproducible phenomenology of NDEs.

  1. Materials and methods

We present a corpus of NDE narratives and a corpus of free narratives of experiences with psychoactive compounds. We apply latent semantic analysis to compare the reported experiences.

2.1. NDE corpus

NDE experiencers were recruited via the Division of Perceptual Studies and the GIGA-Consciousness, and completed an anonymous questionnaire. The experiences scored 7 or higher on the NDE Scale, except for 182 accounts that were collected before the development of such a scale. In 13% of cases, the NDE was caused by head injury, in 30% by anesthesia/drug use, and in 10% by cardiac arrest. The NDEs were rated as pleasant in 82% of cases.

2.2. Erowid corpus

The Erowid Experience Vaults contains a large number of curated freely expressed reports associated with the use of different psychoactive substances. The reports were manually classified into the following classes: serotonergic psychedelics, dissociative psychedelics, entactogens, deliriants, depressants/sedatives, stimulants, antipsychotics/antidepressants, oneirogens and others.

The data in the Erowid corpus is summarized with detail in the supplementary material. Serotonergic psychedelics are represented by generic drug names/botanical species, PubChem CID, number of reports, mechanism of action and geographic distribution.

Following previous work, drug categories were determined using a hybrid criterion based on pharmacological action and the subjective effects induced by the substances. Serotonergic psychedelics, dissociative psychedelics, deliriants, stimulants, depressants/sedatives, and prescription antidepressants and antipsychotics were grouped together into one category.

2.3. Corpora preprocessing

The NDE and Erowid corpora were preprocessed using the Natural Language Toolkit (NLTK) in Python 3.4.6. Words describing the nature of the substance being reported were removed from both corpora, but not the drugs themselves nor contextual factors such as the route of administration.

2.4. Latent semantic analysis

We used an index of semantic similarity between narratives to compare the similarity of drug-induced altered states of consciousness to non-ordinary experiences of a different nature. To compute the similarity between documents, we define a term-document matrix A with T rows and D columns, and compute the linear correlation between their corresponding columns in the matrix A. We applied the frequency – inverse document frequency (tf-idf) transform to the corpus, which gives a higher weight to terms that are more specific to a given document, decreasing the weight based on the number of documents in the corpus that contain such term.

To reduce the dimensionality of the semantic space, the term-document matrix was first decomposed into the product of three matrices using Singular Value Decomposition (SDV), and then the rank-reduced term-document matrix was computed using LSA.

2.5. Principal component analysis and automated component labeling

We applied principal component analysis to reduce the term-document matrix into a smaller number of components, and used word2vec to map words into a vector space with the constraint that words appearing in similar contexts are also close in the vector space embedding.

3.1. Similarity between NDE and drug-induced experiences

We performed a SVD on the term-document matrix, and retained the first 20 singular values. This was based on previous research showing adequate results using the same dataset.

We obtained the correlation matrix from computing all pairwise correlations between the columns of the rank-reduced term-document matrix A. NDE reports showed the highest degree of semantic similarity with narratives of dissociative drug experiences.

The most similar substances to NDE narratives were serotonergic psychedelics, including ketamine, S. divinorum, 5-MeO-DMT, Psilocybe spp., DMT, iboga, ibogaine, mescaline and E. peruviana. The least similar substances were either sedatives or stimulants.

The average ranking of dissociatives, deliriants and serotonergic psychedelics in terms of semantic similarity to NDE narratives was higher than that of all other substance categories except deliriants.

3.2. Lexical and semantic similarities between NDE and drug-induced experiences

We ranked terms based on frequency of occurrence in NDE and ketamine reports, and computed the average ranking between both sets of reports to identify terms having a high prevalence in ketamine and NDE reports.

The most frequent terms in both sets of experiences suggest shared phenomenological features associated with an altered state of perception of the self and the environment, and a departure from the everyday contents of conscious mentation.

“Tone/negative”, “make/stuff”, “take/dependency”, “disease/religion”, included terms clearly related to drug abuse, addiction and associated circumstances.

The projection of each category of drugs into the five principal components is shown in Fig. 6B, as well as the projection of NDE narratives into three different components: “look/self”, “disease/religion” and “make/stuff”.

The similarity between NDEs and narratives associated with specific psychoactive substances is evident upon direct inspection, but for the other two substances obvious differences are manifest.

3.3. Robustness vs. number of singular values retained

The correlation coefficient matrix for pairs of vectors containing the rankings of the 165 psychoactive substances obtained using a number of singular values ranging from 5 to 145 shows modest to high correlations. The most similar substances to NDE narratives are ketamine, LSD, ibogaine, L. williamsii and PCP. When the number of retained singular values is changed, the ranking of substances with low semantic similarity to NDE narratives changes.

3.4. Relationship between semantic similarity and NDE metadata

We compared NDEs associated with loss of consciousness due to head injury, anesthesia/drug use, and cardiac arrest to NDEs associated with ketamine. Ketamine emerged in almost all cases as the drug whose reports presented the highest semantic similarity to NDE narratives.

3.5. Replication of results with additional censored terms

We repeated the analysis after censoring the top 500 most relevant terms of each component, and found that ketamine, ayahuasca, S. divinorum, L. williamsii, 5-MeO-DMT, LSD, Cannabis, Psilocybin mushrooms, iboga, nitrous oxide were the most similar drugs to NDEs.

  1. Discussion

Even disregarding processes at the sub-cellular scale, the number of potential physical states of the brain is astonishing, and analogies can be made between a finite set of “altered states” whose underlying neurophysiological correlates are seemingly unrelated.

We addressed the analogy between the experience of dying and the acute effects of certain psychoactive drugs. However, scarce empirical research has been conducted to clarify the nature of this relationship.

The systematic study of reports of individuals who survived close brushes with death suggests an alternative hypothesis, that near death experiences have a common core of robust and reproducible phenomenological features.

Near-death experiences (NDEs) can be investigated using quantitative psychometric scales, and ketamine and DMT induced NDEs can be compared to NDE phenomenology. A wider range of substances is needed to systematically evaluate how such overlap depends on the pharmacological mechanism of action of different drugs.

A comparison between NDEs and drug-induced experiences associated with an ample range of mechanisms of action offers the possibility of indirectly evaluating neurochemical models of NDEs. The author of the study hypothesized that DMT production occurs in the pineal gland. Our study established the similarity between DMT experiences and NDEs by means of free narratives. The application of dimensionality reduction techniques revealed discrete components with similar ratings between DMT experiences and NDEs, especially in components related to alterations in conscious perception of the environment and the self.

Endogenous DMT may have neuroprotective effects at times of stress, mediated via 1 receptor agonism. However, its effects on subjective experience remain to be demonstrated. Ketamine, a synthetic arylcyclohexalamine dissociative anesthetic, was associated with narratives most similar to those of NDEs. This suggests that an endogenous ketamine-like compound is responsible for the remarkable similarities between ketamine-induced experiences and NDEs.

The hypothesis of DMT and endogenous NMDA antagonists as the sole causes of NDEs has received extensive criticism, but ketamine-experiences are the most similar to NDEs regardless of the proximity of death, and OBEs are one of the most salient features of ketamine-experiences.

The ketamine model can be supported by the observation that individuals who experienced both NDEs and ketamine report a remarkable similarity between both experiences, but lacking proper quantification, it is difficult not to dismiss this evidence as anecdotal. Despite the criticism of neurochemical models based on other serotonergic psychedelics, DMT is known to produce more immersive experiences with intense imagery that can include tunnel-like visions and encounters with seemingly autonomous “entities”.

Our analysis included reports from a large number of substances, including dissociatives and deliriants, whose phenomenology is not commonly associated with that of NDEs. However, the semantic similarity between NDEs and reports of deliriant use may be driven by descriptions of real life-threatening situations.

Salvia divinorum, a very potent hallucinogen, can produce intense visual, auditory, somatic and vestibular distortions, similar to cannabis, and may shock unsuspecting users into believing they are close to death. Naloxone, an opiate antagonist, can increase survival time in fatal or near-fatal circumstances, and certain endorphins can mediate NDE-like phenomenology. However, the endorphin model of NDEs presents limitations due to agonism at opioid receptors producing effects that do not resemble the phenomenological features of NDEs.

The PCA decomposition of the narratives revealed similar “fingerprints” for DMT, ketamine and NDEs, in contrast to other two control substances (cocaine and heroin). This suggests that these substances may have therapeutic benefits in reducing the risk of full-blown post-traumatic stress disorder. NDEs are known to produce long-lasting effects, some of which are positive by the experiencers. These effects are similar to those produced by psychedelics, and lend support to Kenneth Ring’s speculation on the “universality” of transcendental experiences. Both psychedelics and near-death experiences can have negative sequelae, such as anger, depression and estrangement from family and friends. However, the positive affect linked to NDE-dissociative episodes mitigates PTSD symptoms. NDE reports had the highest similarity with ketamine-induced experiences even after censoring the 500 most relevant terms.

Neurochemical models of NDEs can be theoretically attractive, but the analyses conducted in the present work neither validate nor refute these models, since no physical examinations of the subjects at the time of the reported NDEs were performed. NDEs can reduce fear of death, which could lead to increased risk-taking behavior. Also, NDE-dissociative episodes might mitigate PTSD symptoms linked to other dissociative experiences, and NDE experiencers seem to endorse more anti-suicidal attitudes as compared to non-NDE experiencers who have come close to death.

Given the nature of our analyses, we are biased towards the discussion of neurochemical models of NDEs. However, unless direct empirical evidence is obtained, we can only affirm that certain drugs have similar phenomenology to NDEs, and that they could be effective tools for the induction of NDEs. Multifactorial explanations for NDE phenomenology have also been proposed, but these explanations only account for some features, while ignoring others that are regarded as the most defining for NDEs. Furthermore, these alternative models must also be understood as speculative, given the lack of experiments performed at time of reported near death. Ketamine increases gamma oscillations and decreases alpha power, while serotonergic psychedelics decrease alpha power and increase gamma oscillations. It is therefore difficult to compare the spectral changes elicited by serotonergic psychedelics and ketamine, and those recorded during the cease of vital functions.

Our study uses retrospective narratives from a large number of participants, which has advantages and limitations. The time between the occurrence of NDEs and participation in the study averages approximately two decades, and the reports may be contaminated by expectation effects and lack laboratory verification of the consumed substances.

The Erowid corpus could be affected by a number of different confounds, but the amount of data is sufficient to expect a meaningful signal.

  1. Conclusion

We have found evidence that ketamine, as well as different serotonergic psychedelics and deliriant alkaloids, can produce an altered state of consciousness resembling near-death. This could have important implications for the pharmacological induction of NDE-like states for scientific purposes and for therapeutic uses in the terminally ill.

Study details

Compounds studied
DMT Ketamine

Topics studied
Neuroscience

Study characteristics
Meta-Analysis Interviews Qualitative

Participants
15625

Authors

Authors associated with this publication with profiles on Blossom

Enzo Tagliazucchi
Enzo Tagliazucchi is the head of the Consciousness, Culture and Complexity Group at the Buenos Aires University, a Professor of Neuroscience at the Favaloro University, and a Marie Curie fellow at the Brain and Spine Institute in Paris. His main interest is the study of human consciousness as embedded within society and culture.

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