DMT, the Near-Death Experience

“I’d be scared”.

“Scared of what?”

“Scared of dying, I guess. Of falling into the void”.

“They say you fly when you die”.

(Feature film: ‘Enter the Void’).

Introduction

Near-death experiences (NDEs) are complex experiential episodes that occur in association with death or the perception that it is impending (Moody, 1975; Greyson, 1983). Prospective studies with cardiac arrest patients indicate that the incidence of NDEs vary between 2–18% depending on what criteria are used to determine them (Parnia et al., 2001; Van Lommel et al., 2001; Schwaninger et al., 2002; Greyson, 2003). Although there is no universally accepted definition of the NDE, common features include feelings of inner-peace, out-of-body experiences, traveling through a dark region or ‘void’ (commonly associated with a tunnel), visions of a bright light, entering into an unearthly ‘other realm’ and communicating with sentient ‘beings’ (Moody, 1975; Ring, 1980; Greyson, 1983; Martial et al., 2017). Reviewing the phenomenology of NDEs, we have been struck by similarities with the experience evoked by the classic serotonergic psychedelic N,N, Dimethyltryptamine (DMT) (Strassman et al., 1994; Strassman, 2001).

Commonly described features of the DMT experience include a feeling of transcending one’s body and entering into an alternative ‘realm’, an acoustic perception of a high pitched ‘whining/whirring’ sound during the onset of the experience, perceiving and communicating with ‘presences’ or ‘entities’, plus reflections on death, dying and the after-life (Sai-Halász et al., 1958; Strassman, 2001; Gouzoulis-Mayfrank et al., 2005). Furthermore, the reported vividness of both subjective experiences have led to NDE experiencers and DMT users describing the states they enter as ‘realer than real’ (for NDEs see Moody, 1975; Thonnard et al., 2013; for DMT see Strassman, 2001).

The term near-death exerpience (NDE) was coined by philosopher Raymond Moody more than 40 years ago (Moody, 1975). Remarkably, the overlap between the phenomenology of the classic serotonergic psychedelic experience and NDEs was highlighted by Moody himself more than 4 decades ago (Moody, 1975) and these similarities have formed the basis of a popular hypothesis on the pharmacology of NDEs, i.e., that endogenous DMT is released in significant concentrations during the dying process (Strassman, 2001), but see (Nichols, 2017) for a critique of this hypothesis. The psychological state produced by the DMT-containing Amazonian brew, ayahuasca (the literal translation of ‘ayahuasca’ from quechua is ‘the vine of the dead’ or ‘the vine of the soul’), has also been linked to themes of death and dying (Shanon, 2005) as have psychedelics in general (Millière, 2017), e.g., with the psychology of psychedelic-induced ‘ego-death’ being likened to that of actual death (Leary et al., 2008).

Both the psychedelic experience and NDEs appear to be sensitive to contextual factors such as prior psychological traits and state (‘set’), the environment (‘setting’) in which the experience unfolds (Metzner et al., 1965; Studerus et al., 2012) – plus the broader cultural context in which they are embedded (Wallace, 1959; Hartogsohn, 2017; Carhart-Harris et al., 2018). For example, controlled research has found that certain personality traits, e.g., ‘absorption’ and ‘neuroticism’ can predict the intensity and quality of a psychedelic experience (Studerus et al., 2012; Carhart-Harris et al., 2015, 2018; Carbonaro et al., 2016; Barrett et al., 2017) while readiness to ‘let go’ and quality of the environment also seems to be predictive of response (Carhart-Harris et al., 2018). In a similar fashion, the prevalence and nature of NDEs appear to be sensitive to environmental, demographic and personality variables, such as etiology and prognosis of the NDE, age, absorption and a propensity to report paranormal experiences (Kohr, 1983; Greyson, 2003). Cultural factors are presumed to influence the psychedelic experience (Carhart-Harris et al., 2018) and have been found to influence the content of NDEs, (Kellehear, 1993; Kellehear et al., 1994).

The near-death experience has been associated with long-term positive changes in psychological well-being and related outcomes; more specifically, greater concern for others, reductions in distress associated with the prospect of dying, increased appreciation for nature, reduced interest in social status and possessions, as well as increased self-worth have all been observed and/or described post NDEs (Noyes, 1980; Ring, 1980; Groth-Marnat and Summers, 1998). Relatedly, recent results from studies with psychedelic compounds have shown similar long-term positive changes. For example, reduced death anxiety (Grob et al., 2011; Gasser et al., 2015; Griffiths et al., 2016; Ross et al., 2016), pro-ecological behavior (Forstmann and Sagioglou, 2017; Nour et al., 2017) and nature relatedness (Lyons and Carhart-Harris, 2018), significant clinical improvements in depressed patients (Osório et al., 2015; Carhart-Harris et al., 2016; Palhano-Fontes et al., 2018) and recovering addicts (Johnson et al., 2014; Bogenschutz et al., 2015; Bogenschutz and Johnson, 2016) and lasting improvements in psychological well-being in healthy populations (Griffiths et al., 2011; Carhart-Harris et al., 2017) have all been observed. Thus, overlap between near-death and psychedelic experiences may extend beyond the acute experience into longer-term psychological changes.

While the subjective effects of DMT have been researched in the past (Strassman et al., 1994; Gouzoulis-Mayfrank et al., 2005), they have tended to be collapsed into broad categories or dimensions of experience (e.g., visual, somatic and emotional effects) as determined by standard ‘altered states of consciousness’ rating scales (Strassman et al., 1994; Studerus et al., 2010). The degree to which DMT specifically induces near-death type experiences has never been directly measured, however.

This current within-subjects, placebo-controlled study aimed to directly measure the extent to which intravenous DMT given to healthy volunteers in a laboratory setting could induce a near-dear type experience as determined by a standard NDE rating scale (Greyson, 1983). Importantly, we also aimed to address how these experiences compared with a sample of individuals who claim to have had ‘actual’ near-death experiences. To our knowledge, this is the first time that the relationship between DMT experiences and (non-drug-induced) NDEs has ever been formally addressed.

We hypothesized that DMT would induce near-death type experiences of an equivalent intensity to those seen previously in the context of ‘actual’ NDEs, and to a significantly greater extent than in the placebo condition. Based on aforementioned work on NDEs, we also hypothesized that age, personality and a propensity toward delusional thinking would correlate with DMT-induced near-death experiences.

Materials and Methods

Experimental Design

Thirteen healthy volunteers participants (6 female, 7 male, mean age: 34.4, SD: 9.1 years) participated in a fixed-order, placebo-controlled, single blind study, approved by the National Research Ethics Service (NRES) Committee London – Brent and the Health Research Authority (HRA). 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 study was sponsored and approved by Imperial College London’s Joint Research and Compliance Office (JRCO) and the National Institute for Health Research/Wellcome Trust Imperial Clinical Research Facility gave site-specific approval for the study. 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.

Screening

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.g., LSD, psilocybin, DMT, ayahuasca), current or previously diagnosed psychiatric illness, immediate family history of psychotic disorder, excessive use of alcohol (>40 weekly units), blood or needle phobia and a significant medical condition rendering volunteers unsuitable for participation (e.g., diabetes, heart condition). 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. The Greyson NDE scale (Greyson, 1983) served as the primary outcome measure.

Study Procedures and Participants

Both dosing sessions took place at the National Institute of Health Research (NIHR) Imperial Clinical Research Facility (CRF). 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., 2008). 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, 1994). 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.e., single-blind study design). The order was fixed in this way to promote safety by developing familiarity with the research team and environment prior to receiving DMT, and to avoid potential carry over effects from receiving DMT first (particularly as the experience is associated with lasting psychological effects – see section “Introduction”).

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.

Main Outcomes and Measures

Acute Outcomes

In order to determine the degree to which DMT induces near-death type experiences, the Near-Death Experience scale (NDE scale; Greyson, 1983) was completed retrospectively once the effects of DMT and placebo had subsided. 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, 1983). 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, 1983).

The overlap between drug-induced NDEs and other relevant psychological phenomena associated with psychedelic drugs was also addressed. Two additional measures were included for this purpose, namely: The Ego Dissolution Inventory (EDI) (Nour et al., 2016) and the Mystical Experiences Questionnaire (MEQ) (Maclean et al., 2013). The EDI contains 8 items and a mean score on all 8 is calculated for a single EDI factor. 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., 2013; Barrett et al., 2015).

Additional Measures

Correlations with personality trait absorption, delusional thinking and age

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. Previous research has identified that the personality trait absorption and reports of so-called ‘paranormal’ phenomena (e.g., telepathic communication, out-of-body experiences) are positively correlated with the NDE scores, while age is negatively correlated with NDE scores (Kohr, 1983; Greyson, 2003). Because reports of paranormal experiences have been associated with magical ideation and schizotypy (Brugger and Taylor, 2003) we used the Peters’ Delusion Inventory (PDI) (Peters et al., 2004) to establish the relationship between this construct and NDE scores. The PDI is a measure of delusional thinking in the general population and contains items related to paranormal phenomena (e.g., belief in telepathy, witchcraft, and voodoo) as well as strength of belief and level of distress associated with these (Peters et al., 2004).

Participants were also asked to complete the modified version of the Tellegen Aborption Questionnaire (MODTAS) (Tellegen and Atkinson, 1974). Pearson-product moment correlations were used to test for relationships between the relevant variables and main outcomes (i.e., the relationship between absorption, delusional thinking and age with NDE scores was analyzed). 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.

Comparison to ‘actual’ NDE group

In order to address the degree of overlap between our results and the features typically reported by people who have reported ‘actual’ NDEs, we conducted a separate comparison with gender and age matched sample of individuals who had completed the NDE scale (and scored above the established cutoff for an NDE) from a few months to 15 years (mean time = 7 years, SD = 6 years) after experiencing a life-threatening episode. This sample was defined as the NDE group (7 female, 6 male, mean age = 36.62, SD = 7.65). NDE experiencers were recruited via the Coma Science Group (GIGA-Consciousness, University and University Hospital of Liège, Belgium) and the International Associations for Near-Death Studies (IANDS France and Flanders). Participants were mailed a questionnaire that included items about socio-demographic (gender, age at interview) and clinical (time since NDE) characteristics. They were then asked to respond to the Greyson NDE scale (Greyson, 1983).

Statistical Analysis

To compare the acute effects of DMT with those of placebo, repeated measures Analysis of Variance (ANOVA) were performed separately on data from the NDE scale and the MEQ, using condition (DMT vs. placebo) and questionnaire subscales as the factors of interest. Post hoc paired t-tests were then performed to compare DMT vs. placebo. In order to dissect the relationship between the DMT and near-death experiences, each item of the NDE scale was also subjected to paired t-tests (DMT vs. placebo). The comparison between the DMT state and ‘actual’ near-death experiences was made by conducting paired t-tests for each NDE scale item, as well as its subscales and total score.

Overlap between MEQ and NDE scale scores was assessed via Pearson-Product Moment Correlation on the main score of the difference between DMT and placebo for both scales, and the same procedure was performed between the EDI and the NDE scale. Independent correlation analyses were performed using the main score of the NDE (DMT-placebo) and each of the MEQ sub-factors in order to determine which of the MEQ sub-factors shows the strongest association with the total NDE scale scores.

Effect sizes were calculated using Cohen’s d for all paired t-tests. Separate Pearson-Product Moment Correlations were performed using each of the variables collected at baseline vs. the total NDE score. All analyses that involved less than 15 comparisons used Bonferroni-correction for multiple comparisons, while those equal/above 15 comparisons used False-Discovery Rate (FDR) correction. All t-tests were performed under two-tailed analyses.

Results

DMT Induces Near-Death Type Experiences

All participants scored above the conventional cutoff (above or equal to 7) for a (DMT-induced) near-death (type) experience (Greyson, 1983). One of the 13 participants had a total score of 7 following placebo. The Analysis of Variance revealed a significant main effect of condition [F(1,12) = 118.95, p = 1.39e^-7], a main effect of NDE subscale [F(4,48) = 59.36, p = 5.39e^-18] and an interaction between condition and NDE subscale [F(3,36) = 11.92, p = 1.4e^-5]. Post hoc t-tests revealed all NDE subscales and the total NDE score to be significantly increased under DMT compared to placebo (p < 0.01 Bonferroni corrected) and the comparison of the total score was significantly higher for DMT compared to placebo (t = 10.91, df = 12, p = 1.39e^-7, Cohen’s d = 3.09). 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. Fifteen of the 16 items were scored higher under DMT than placebo and 10 of these reached statistical significance after correction (p < 0.01 FDR-corrected) (Figure 1). These results show that near-death experience phenomena were significantly enhanced following DMT administration.