Some answers come from cell culture research. Recent studies have found a role for DMT in both the immune response and the anti-stress response of individual human cells.
In immune cells, DMT was shown to activate the production of anti-inflammatory molecules. In a similar study, human neurons in cell culture were deprived of oxygen. While it is tempting to speculate, it is important to keep in mind that neurons in the brain function in a complex, context-dependent way. Observing individual neurons in culture shows scientists what is happening inside them, but says little about how they interact with each other in a living, 3D brain.
Presently, this gap has not yet been bridged. Researchers have not tested Sig1R activity in intact brains undergoing hypoxia or other types of physiological stress. Lacking direct evidence, we may take some hints from brain imaging studies and attempt to connect them with known Sig1R mechanisms. These include centres for perception and processing of negative emotions and sad memories, memory retrieval centres, and the amygdala a brain region commonly associated with social and emotional processing, including fear, anxiety and aggression.
Antonio Inserra, a researcher from Flinders University in Adelaide, attempted to reconcile the molecular and whole-brain perspectives and formulated an intriguing hypothesis about the roles Sig1R could play in these brain activities. He speculates that Sig1R might form complexes with other receptors and boost signal transmission and synaptic plasticity in memory centres, which could help retrieve and reprocess traumatic memories.
He further points out that Sig1R in the nucleus serves as an epigenetic regulator, 9 meaning that it recruits enzymes that add different tags to DNA and histones the proteins around which DNA is coiled in the cell in order to turn genes on and off. It has long been understood that epigenetic mechanisms have an important role in all aspects of memory forming and remodelling. A new study from Dr. His team, supervised by Prof.
Celia Morgan University of Exeter , followed participants in ayahuasca ceremonies in the Amazon to investigate how these experiences impacted their traumatic memories. The participants reported significant, long-lasting decreases in depression, anxiety, and general distress.
They discovered that the Sig1R gene is epigenetically changed in some participants unpublished results presented at the ICPR conference. Since we know the receptor itself is involved in epigenetic modulation, this might be just the beginning. Which other genes do we see epigenetically modified after ayahuasca sessions? No matter what other results come out of this study, it already serves as an important bridge between the lab and the ceremony; between the cell, the brain, and the experience.
The current state of DMT research resembles disjointed puzzle pieces. While there are several indicators that there might be naturally occurring DMT in the human brain, its locations and functions remain elusive.
Nevertheless, a variety of speculative theories have recently surfaced. Could the dying brain be releasing endogenous DMT to keep itself alive for as long as possible? In the cases of neuron survival and memory processing, research so far points towards the multifunctional, mysterious Sig1R receptor as a key actor in these processes. While the intricacies of its molecular mechanisms have yet to be fully described, the multifunctional Sig1 receptor is now firmly established as a target of DMT, and this opens new lines of inquiry.
Perhaps the most exciting new research will include investigations into how DMT and Sig1R affect epigenetic regulation. Information about which genes they activate or deactivate could put the findings from cell culture research into the context of whole organisms.
Epigenetic mechanisms lie at the very foundation of our dynamic interactions with the world, and with our own minds.
Understanding how these mechanisms help store and remodel memories may help us formulate a coherent biological model of the therapeutic effects of the psychedelic experience. For more on this and many other issues in psychedelic research, be sure to check out our INSIGHT conference program and pre-conference workshops.
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Not what you are looking for? This study was carried out in accordance with the recommendations of Good Clinical Practice guidelines, Declaration of Helsinki ethical standards and the NHS Research Governance framework. All subjects gave written informed consent in accordance with the Declaration of Helsinki. The research was conducted under a Home Office license for research with Schedule 1 drugs.
Study procedures consisted of screening and 2 dosing sessions, separated by 1 week. Participants were recruited via word-of-mouth and received an information sheet detailing all study procedures prior to the screening visits.
Informed consent was obtained before screening, which consisted of routine physical tests routine blood tests, electrocardiogram, blood pressure, heart rate, neurological examination a psychiatric interview and examination.
The main exclusion criteria were: an absence of experience with a classic psychedelic drug e. Tests for drug abuse and pregnancy when applicable were performed on screening and study days and participants were required to abstain from using psychoactive drugs at least 7 days prior to study participation. Following screening, participants were enrolled for 2 dosing sessions in which placebo and DMT were administered.
Questionnaires were completed electronically prior to the dosing sessions — which served as baseline correlation measures. Following each dosing sessions, participants completed questionnaires enquiring about subjective experiences during the DMT and placebo sessions. Participants rested in reclined position in a dimly lit room, while low volume music was played in the background in order to promote calm during the session Johnson et al.
Electroencephalogram EEG recordings took place before and following administration of DMT and placebo the relevant findings concerning EEG results will be reported elsewhere.
Participants received one of four doses of DMT fumarate three volunteers received 7 mg, four received 14 mg, one received 18 mg and five received 20 mg via intravenous route in a 2 ml sterile solution over 30 s, followed by a 5 ml saline flush lasting 15 s. Placebo consisted of a 2 ml sterile saline solution, which followed the same procedure Strassman and Qualls, During the first dosing session, all participants received placebo, and 1 week later, DMT. Participants were unaware of the order in which placebo and DMT were administered but the research team was i.
Participants reported feeling the subjective effects of DMT immediately after the 30 s injection or during the flush which came soon after it. Effects peaked at 2—3 min and gradually subsided, with only residual effects felt 20 min post administration. Volunteers were discharged to go home by a study psychiatrist at least 1 h after administration and once all study procedures were completed. Participants were asked to message a member of the research team in order to confirm their safe return and well-being.
To ensure safety, each volunteer was supervised by two researchers and the study physician throughout the dosing session. This is the most widely used scale for NDEs; it was first constructed from a questionnaire based on a sample of 67 participants who had undergone 73 NDEs in total Greyson, The NDE scale consists of 16 items, resulting in a total score representing the global intensity of the experience as well as scores for four subscales: 1 Cognitive , 2 Affective , 3 Transcendental , and 4 Paranormal.
A total score higher or equal to 7 is considered the threshold for a NDE Greyson, The overlap between drug-induced NDEs and other relevant psychological phenomena associated with psychedelic drugs was also addressed.
The MEQ contains 30 items and yields a total score consisting of the average of all items as well as four subscales: Mystical, Positive Mood, Transcendence of Time and Space and Ineffability Maclean et al.
Questionnaires completed at baseline before study visits were used to assess the relationship between personality, suggestibility, delusional thinking and age with the magnitude of the NDE scores. The PDI is a measure of delusional thinking in the general population and contains items related to paranormal phenomena e. Pearson-product moment correlations were used to test for relationships between the relevant variables and main outcomes i.
In order to adhere to statistical principles, one-tailed analyses were performed in cases in which there were clear, evidence-informed hypotheses about the direction of correlations, otherwise two-tailed tests were performed. Participants were mailed a questionnaire that included items about socio-demographic gender, age at interview and clinical time since NDE characteristics.
Post hoc paired t -tests were then performed to compare DMT vs. Separate Pearson-Product Moment Correlations were performed using each of the variables collected at baseline vs. All t -tests were performed under two-tailed analyses. All participants scored above the conventional cutoff above or equal to 7 for a DMT-induced near-death type experience Greyson, One of the 13 participants had a total score of 7 following placebo. Paired t -tests on each of the 16 items comprising the NDE scale were performed in order to assess the specific phenomenological features of the DMT experience.
These results show that near-death experience phenomena were significantly enhanced following DMT administration. Overall these results indicate a high overlap between near-death type experiences, ego-dissolution and mystical-type experiences induced by DMT. With specific regards to the mystical experience, MEQ factors Mystical and Transcendence of Time and Space were most strongly associated with the DMT-induced near-death type experiences.
The transparent red line shows the slope of the r -value discarding the outlier. Participants were selected based on scores above a standard cut-off on the NDE scale of 7 points Greyson, Table 1 and Figure 4 displays the results from separate t -tests performed on each item, subscales and total score.
TABLE 1. This study sought to examine the degree to which features commonly reported in NDEs are elicited by the potent serotonergic psychedelic DMT in a placebo-controlled study. Results revealed that all 13 participants scored above the standard threshold for an NDE in relation to their DMT experiences Greyson, and 15 of the 16 NDE items were rated significantly higher under DMT compared to placebo, with 10 of these reaching statistical significance after multiple testing correction.
Taken together, these results reveal a striking similarity between the phenomenology of NDEs and experiences induced by the classic serotonergic psychedelic, DMT. It is important to acknowledge that the phenomenology of NDEs is still a matter of some investigation. The potential heterogeneity of NDEs cautions us to consider how intra and inter-individual variables, cultural characteristics and the environmental and psychological context in which they take place may influence the content of experiences as well as whether and how they are reported.
Personality has previously been associated with response to psychedelics Studerus et al. Absorption has been linked to a serotonin 2A receptor polymorphism associated with greater signaling Ott et al. Here, we saw a trend toward absorption predicting DMT-induced NDE but this relationship did not quite reach statistical significance, perhaps due to insufficient statistical power or that the use of different doses might have masked this effect.
Recent findings Martial et al. Relatedly, we found a strong relationship between scores of DMT-induced near-death type and mystical-type experiences. The strong overlap between these facets of mystical-type and NDEs may be due to similar items featuring in both scales e. Recent work has consistently shown that the occurrence of mystical-type experiences is predictive of long-term therapeutic benefit from psychedelics Maclean et al.
It is pertinent to ask therefore, what common features shared between these states may be responsible for mediating the apparent long-term psychological benefits that follow them.
Evidence suggests that that the experience of unity — which some have claimed is an inevitable counterpart to ego-dissolution Nour et al. It is possible that complete ego-dissolution and the parallel unitive experience that accompanies it may be the common factor that can bridge between these different states and is also responsible for the longer-term psychological benefits associated with them. Detailed interviewing techniques could serve to improve our characterization of the phenomenology of both the DMT and NDE states Petitmengin, ; Petitmengin and Lachaux, , and future studies of the psychedelic state could benefit from adopting a more dynamic sampling approach, i.
Rudimentary neurobiological models of the NDE have existed for almost 30 years, and have tended to lay emphasis on abnormal serotonergic and medial temporal lobe activity Morse et al. Given strong associations between the temporal lobes and more specifically, medial temporal lobe structures, and unusual psychological experiences such as those featuring within NDEs Carhart-Harris, , we predict that the medial temporal regions may be implicated in some of the content and emotion-rich epochs that arise within the psychedelic state, such as complex imagery, entity encounters, and vivid autobiographical recollections.
The relinquishment of top-down cortical control over temporal lobe activity may be an important component of this mechanism Alonso et al.
Another limitation is that we cannot discount the influence of order effects as placebo sessions were always performed first to avoid carryover and promote comfort for the DMT session and thus, exposure to the NDE scale post placebo may have primed participants to experience NDE-like phenomena ahead of their DMT sessions — although this seems unlikely given the volume of other measures and time between sessions. That one participant scored on the threshold for an NDE in the placebo session suggests that the NDE scale may have a somewhat liberal threshold for determining NDEs — and thus may warrant revision.
As both psychedelics and the NDE phenomena appear to be strongly influenced by contextual factors Kellehear et al. Nonetheless, considering the strong overlap on the items of the NDE scale, the study of such differences might require the use of other methods addressing nuances not explored here e. We should also consider that although the study of the phenomenology of NDEs and psychedelic experiences may inform on each other in a reciprocal way, using one psychological phenomenon to model another, particularly if they are as abstract as the near-death and psychedelic experiences are, these may be fraught with problems see Langlitz, for a detailed reflection on psychedelics as models of other mental and psychiatric phenomena.
For this reason, better understanding their presumed shared neurobiology may provide the necessary bedrock to ground the science of these fascinating states. This study aimed to examine potential overlap between the phenomenology of NDEs and those associated with the potent serotonergic psychedelic DMT. Results revealed an intriguingly strong overlap between specific and broad features of these states, with DMT participants scoring high on a standard measure of NDEs and in a comparable way to people reporting bona fide NDEs, with only subtle differences that might relate more to obvious contextual differences than anything to do with the specific inducers themselves.
Indeed, these present results suggest that certain contextual factors e. Better understanding of both the psychology and neurobiology of dying Borjigin et al.
How extraordinary it is to be here at all. Awareness of death can jolt us awake to the sensuality of existence. CT designed and conducted the research, analyzed the data, and wrote the paper. LR and LW conducted the research.
DE overlooked medical and health standards for the research. DN sanctioned the research. RC-H designed the research and wrote the paper. RC-H was supported by the Alex Mosley charitable trust. This work was supported by the Bial Foundation and the Beckley Foundation. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
The authors would like to thank all study participants, as well as Samuel Turton, Matthew Nour, Camilla Day, and James Rucker for providing medical cover during study procedures. The authors would also like to thank Rick Strassman and Andrew Gallimore for providing advice during the development of early versions of the study protocol.
Alexander, E. London: Piatkus. Alonso, F. Serotonergic psychedelics temporarily modify information transfer in humans. Atasoy, S. Connectome-harmonic decomposition of human brain activity reveals dynamical repertoire re-organization under LSD. Barrett, F. Validation of the revised mystical experience questionnaire in experimental sessions with psilocybin. Support Psychedelic Research. Links All All. Support All All. Science Talk All All. One-pager All All. Music All All.
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