Pineal Gland DMT in Near-Death and Cross-Cultural Mysticism

Between 1990 and 1995, psychiatrist Rick Strassman ran studies of DMT and psilocybin in human volunteers at the University of New Mexico — the first human research with psychedelic compounds since such research was halted in the early 1970s. [1] [2] In his 1994 dose-response study, the psychological effects of intravenous DMT began almost immediately, peaked at 90 to 120 seconds, and were almost completely resolved by 30 minutes. [3] Three decades of subsequent research [4] [5] [6] have converged on a sharper question — not whether exogenous DMT produces extraordinary states, but whether the human brain makes its own.

In 2018, Timmermann et al. at Imperial College London gave one of four IV DMT doses (7, 14, 18 or 20 mg) to each of 13 healthy participants and recorded significant increases in near-death experience phenomenology on the Greyson scale, with scores correlating to DMT-induced ego-dissolution and baseline trait absorption. [7] In 2019, Dean et al. measured endogenous DMT in living rat brain extracellular fluid at 0.05 to 2.2 nM — comparable to but lower than canonical monoamine neurotransmitters — with both baseline levels and post-cardiac-arrest surges independent of an intact pineal gland. [8] And in 2023, Xu et al., working in Jimo Borjigin’s laboratory, published in PNAS EEG recordings from four comatose dying patients following withdrawal of ventilatory support; two of them showed surges of gamma activity in the temporal-parietal-occipital junction, a region previously associated with dreaming and visual hallucinations. [9]

Strassman’s UNM Clinical Research and the Pineal Hypothesis

Rick Strassman walked into the University of New Mexico School of Medicine in 1990 with federal approval to inject DMT into humans for the first time in over two decades. Between 1990 and 1995, his team administered a series of intravenous DMT doses to a small group of volunteers, generating the first federally sanctioned clinical data on a classic psychedelic in the United States since the early 1970s. The 1994 dose-response study, published in the Archives of General Psychiatry, established the time course that would define DMT research for decades: psychological effects began almost immediately after intravenous administration, peaked at 90 to 120 seconds, and were almost completely resolved by 30 minutes—a profile mirroring DMT blood levels. Strassman and Qualls administered doses of 0.05, 0.1, 0.2, and 0.4 mg/kg to 11 experienced hallucinogen users in a double-blind, saline placebo-controlled design, finding threshold hallucinogenic effects at 0.2 mg/kg and dose-dependent elevation of blood pressure, heart rate, pupil diameter, rectal temperature, beta-endorphin, corticotropin, cortisol, and prolactin. [10] [3]

The instrument Strassman built to capture these acute states, the Hallucinogen Rating Scale, was first developed for the 1994 intravenous DMT dose-response work, in which graded doses of 0.05–0.4 mg/kg were administered to experienced users. [3] A 2024 multistudy reanalysis by Calder, Qualls, Hasler, Elmiger, and Strassman resolved the HRS into 8 factors with good-to-excellent internal consistency, using 991 questionnaires across 13 substances; the “Meaningfulness” factor uniquely differentiated classic psychedelics (psilocybin, DMT) from dissociatives, empathogens, stimulants, and THC. The HRS has since become a principal psychometric instrument for DMT research, validated across multiple studies and substances. [11]

The UNM data did not establish a pharmacological footing for the pineal hypothesis on its own. DMT is an endogenous compound naturally present in human tissues, though its biological purpose remains unclear, and over 60 studies have attempted to correlate endogenous DMT concentrations in blood or urine with psychiatric diagnoses without establishing any clear-cut or repeatable correlation. Whether endogenous DMT release occurs in sufficient concentrations or with sufficient selectivity to produce psychoactive effects remains an open question, directly noted by DMT researchers. [12] The “Spirit Molecule” hypothesis—that the pineal gland produces and releases DMT at birth, during dreaming and near death—is acknowledged in the literature, but a 2018 review by David Nichols found the scientific evidence not consistent with it. [13] Strassman set the hypothesis out in his 2001 book DMT: The Spirit Molecule, a proposal the reviewer Stephen Page describes as explicitly speculative. [14]

What Strassman’s UNM studies did establish was a striking phenomenological map. Phenomenological analyses consistently document entity encounters as a major feature of the DMT experience: a Reddit-based analysis found entity encounters in 45.5% of 3,778 naturalistic inhaled-DMT reports, and a separate naturalistic field study found encounters with “beings” in 94% of 36 post-DMT interviews. [15] [16] Timmermann et al. (2018) demonstrated in a within-subjects placebo-controlled study of 13 participants that IV DMT significantly increased phenomenological features associated with near-death experiences compared with placebo, with significant overlap in nearly all NDE features when DMT-induced states were compared against a matched group of actual NDE experiencers. [7] DMT produces its psychoactive effects primarily through serotonin 5-HT2A receptor agonism, with additional action at sigma-1 receptors and trace amine-associated receptors (TAARs). [12]

The skeptical pushback came organized. David Nichols argued in 2018 that the adult pineal gland produces only about 30 micrograms of melatonin per day, and that the minute concentrations of DMT detected in the brain are insufficient to produce psychoactive effects. [13] A 2026 study by Palner and colleagues could not detect an endogenous DMT pool in rat brain even after inhibiting monoamine oxidase with pargyline, and saw scant evidence that administered DMT is retained in serotonin terminals. [17] The field has settled into three live positions: a strong experiential view (Strassman) holding endogenous DMT plays a substantive role in altered states; a strong skeptical view (Nichols) treating DMT as a low-abundance trace amine inadequate to support experiential claims; and a subtle-physiological view (Frecska, Szabo, Olson and others) holding endogenous DMT may matter through intracellular signaling without reaching psychedelic concentrations. The strongest version of the popular claim—that DMT explains birth, death, and NDEs—requires affirmative answers to detection, biosynthesis, functional role, and psychoactive sufficiency, and the evidence does not resolve all four. [14]

Endogenous DMT in the Mammalian Brain

In the early 1990s, Rick Strassman administered graded intravenous doses of DMT fumarate (0.04–0.4 mg/kg) to twelve experienced hallucinogen users at the University of New Mexico, characterizing the subjective effects — rapidly moving colored visual displays, dissociation, alternating euphoria and anxiety, almost complete resolution by thirty minutes — and building the Hallucinogen Rating Scale to capture them. [3] Beside those clinical sessions stood a hypothesis that would define the next thirty years of debate: that the pineal gland secretes DMT at birth, during dreaming, and near death, producing out-of-body and visionary experiences. Nichols later concluded that the scientific evidence is not consistent with these ideas. [13]

The hypothesis triggered the search for the molecule. Endogenous DMT had first been detected in human blood and urine in 1965 by Franzen and Gross using early chromatographic methods, but live-tissue measurement in brain remained elusive. The breakthrough came in 2013, when Barker, Borjigin, Lomnicka, and Strassman reported the first detection of DMT in rat pineal gland microdialysate using an LC/MS/MS method that also assayed melatonin precursors and metabolites. [18] [19] Six years later, Dean et al. (2019, Scientific Reports) demonstrated that the transcripts for INMT and AADC — the two enzymes required for DMT biosynthesis from tryptophan — are colocalized in rat visual cortex, hippocampus, pineal gland, and choroid plexus, and that extracellular DMT concentrations in the rat cerebral cortex are comparable to those of canonical monoamine neurotransmitters including serotonin. Then came the finding that put the cardiac-arrest hypothesis on the map: DMT levels in the rat visual cortex rose significantly following experimental cardiac arrest, and did so whether or not the pineal gland was intact. Dean et al. put it plainly: the rat brain is capable of synthesizing and releasing DMT at concentrations comparable to known monoamine neurotransmitters. [8]

DMT biosynthetic pathway: tryptophan to tryptamine (AADC), then to N-methyltryptamine and DMT (INMT). Photo: Doctorcito / Wikimedia Commons, public domain. Source

The canonical INMT-catalyzed pathway came under direct assault in 2023. Glynos and colleagues generated an INMT-knockout rat using CRISPR/Cas9 and showed that brain and lung tissues of INMT−/− rats retain tryptamine-dependent methylation activity equal to wild-type — but the enzymatic products are neither N-methyltryptamine nor DMT, and recombinant rat INMT alone is insufficient to produce either. The implication is stark: if INMT is dispensable for endogenous tryptamine methylation, then whatever enzyme is doing the work in the mammalian brain has not yet been identified. [6] A 2026 study (Palner et al., Neuropharmacology) found no endogenous DMT in rat brain even after monoamine-oxidase inhibition with pargyline, and found that escitalopram and dihydrotetrabenazine pretreatment gave scant evidence that injected DMT is retained in serotonin terminals; the authors concluded that DMT is neither formed nor retained in serotonin terminals in the rat brain. [17] The finding that the DMT surge in Dean et al. was independent of the pineal gland, combined with the INMT-knockout result, leaves mammalian DMT biosynthesis in an unsettled state: detected, but enzymatically unaccounted for. [8] [6]

The skeptical case has sharpened in parallel. David Nichols (2018, Journal of Psychopharmacology) made the size-of-the-gland argument: the adult human pineal weighs less than 0.2 g and produces approximately 30 µg/day of melatonin as its principal secretion — a biosynthetic scale that constrains what else the gland could plausibly manufacture. [13] Endogenous DMT in mammalian biological materials is present at picogram to low-nanogram per millilitre concentrations, and in Nichols’s assessment the minute concentrations detected in the brain are not sufficient to produce psychoactive effects. [14] [13] Over sixty studies have attempted to correlate peripheral DMT levels with psychiatric diagnoses, and no clear-cut or repeatable correlation has emerged. [12] Stephen Page’s 2026 online review essay crystallizes the field into four sub-questions — detection, biosynthesis, functional role, and psychoactive sufficiency — and observes that almost all experimental evidence comes from rats while direct human evidence is limited to peripheral fluid detection and mRNA expression in archived autopsy material. [14]

The unresolved question is no longer whether DMT exists in the mammalian brain — it does, measurably, at concentrations comparable to serotonin in rat cortex — but whether it does anything there. [8] Szabo, Frecska, and colleagues have argued for a sub-psychoactive role via sigma-1 receptor activation, demonstrating that DMT robustly increases survival of human iPSC-derived cortical neurons, macrophages, and dendritic cells under severe hypoxia (0.5% O₂) through the Sig-1R, an effect accompanied by reduced HIF-1α expression that the authors read as HIF-1-independent. This positions endogenous DMT as a candidate neuroprotective signal at the point of death rather than a producer of visions. [20] The Strassman “Spirit Molecule” narrative, Nichols’s skeptical quantitative challenge, and the Frecska/Szabo subtle-physiological view via sigma-1 remain the three live positions. [14] The cardiac-arrest DMT surge in rats is real; the pineal hypothesis that motivated the search remains unproven; and the enzyme that actually makes brain DMT in mammals has not been named. [13] [6]

DMT, Near-Death Experiences, and Out-of-Body Phenomenology

On 15 August 2018, a team at Imperial College London published what became the most cited experimental study in this corner of the literature: Timmermann and colleagues administered intravenous DMT to 13 healthy volunteers in a within-subjects, placebo-controlled design and found significant increases in phenomenological features associated with near-death experiences on the Greyson NDE Scale, with significantly larger DMT-versus-placebo scores on 10 of its 16 items, on all subscales and on the total. The overlap between DMT-induced phenomenology and a matched group of actual NDE experiencers was statistically significant across nearly every Greyson item — a striking result, since the Greyson Scale itself is a 16-item instrument with a cut-off of 7 defining an NDE for research purposes. The 2018 study was designed precisely to test whether DMT could serve as an “NDE-mimetic” — a pharmacological probe for the dying-brain state — and the answer, on the surface, was yes. But the Timmermann team also noted that the relationship was modulated by baseline trait “absorption” and delusional ideation, suggesting that personality factors shape how powerfully the DMT experience converges with NDE phenomenology. The result now frames the entire contemporary debate on DMT and near-death phenomenology. [7]

That convergence has a real-world echo. In a naturalistic field study published in 2021, Michael and colleagues observed 36 sessions in which experienced DMT users inhaled 40–75 mg in non-clinical home settings; 94% of reports involved encounters with apparently autonomous “beings”. [16] A larger Johns Hopkins survey of approximately 2,500 DMT users who reported an entity encounter found that the majority described the entity as “conscious, intelligent, benevolent, and sacred,” with 80% saying the experience fundamentally altered their perception of reality and 72% saying the entity continued to exist in “a different plane of reality” — and more than half of prior atheists in the sample reported new belief in a higher power after the experience. [21] A 3,778-report Reddit analysis found entity encounters in 45.5% of cases, with the most common phenotypes being feminine (24.2%), deities (17.0%), and aliens (16.3%). [15] DMT users describe environments with stable structure — alternate dimensions, rooms, tunnels — and entities that interact, communicate, and frequently behave as guides or teachers. The phenomenological stability of these reports across settings and methodologies is what makes them scientifically interesting rather than merely anecdotal.

But here’s the part that doesn’t sit right. Michael, Luke, and Robinson’s 2025 comparative thematic analysis of 36 naturalistic DMT experiences against 34 NDE narratives found that 95% of DMT participants reported at least one canonical NDE theme — Translocation, Bright Light, Sense of Dying, The Void, Disembodiment, Tunnel-like Structures, Light Being-esque Entities, Deceased Family, Life Review-like experiences, and Hyper-empathic Experiences. The authors labeled DMT an “NDE-mimetic” — but the qualifier matters: five classical NDE features were entirely absent from the DMT reports, and DMT exhibited a broader, more prodigious array of stereotypical content than the NDE narratives did. The phenomenology overlaps at the level of the Greyson Scale, but diverges at finer-grained qualitative levels. A 2024 within-subjects comparison by Martial and colleagues reported similar findings — overlap in phenomenology, attribution of reality, psychological insights, and enduring effects, but with persistent differences that resist simple equivalence. The conservative reading: DMT and NDEs share a phenomenological skeleton but diverge on the flesh. The dissenting reading, articulated by philosopher Michael Potts, holds that the differences are substantial enough to undermine any causal inference from DMT to NDEs. [22]

The baseline against which all of this is measured is the prospective NDE literature, anchored by Pim van Lommel’s 2001 Lancet study of 344 consecutive cardiac arrest survivors across ten Dutch hospitals — 62 patients (18%) reported an NDE, of whom 41 (12%) described a core experience, with no correlation between NDE occurrence and duration of cardiac arrest, medication, fear of death, or general physiological factors. [23] The matching phenomenological distribution has been documented in subsequent work: a 2019 large-scale semantic similarity comparison of 625 NDE narratives with about 15,000 reports on 165 psychoactive substances found that hallucinogens as a class produced experiences more similar to NDEs than stimulants, sedatives, or antipsychotics — with ketamine most similar, followed by Salvia divinorum, then serotonergic psychedelics including DMT. [24] [25] The Greyson NDE Scale remains the principal measurement instrument, though Martial and colleagues’ 2020 Near-Death Experience Content (NDE-C) scale — a 20-item instrument with a 5-factor structure and Cronbach α = 0.85 — was developed to address its known weaknesses. [26] Out-of-body experiences, the third pillar of the comparative phenomenology, can be induced in the laboratory by displacing a person’s visual perspective together with correlated multisensory information from the body, and a voluntary out-of-body experience studied with fMRI activated regions overlapping the temporoparietal junction. [27] [28]

The mechanistic story is incomplete. The parallel DMT neuroscience picture is also unsettled: DMT acts primarily as a 5-HT2A agonist, with additional activity at sigma-1 receptors and trace amine-associated receptors [12], and DMT alters cortical travelling waves in a direction consistent with the REBUS model of psychedelic action — decreasing top-down alpha and increasing bottom-up forward wave propagation. [29] What remains unresolved is whether the phenomenological convergence between DMT and NDEs reflects a shared neurochemical substrate, a shared cortical dynamic, or simply convergent phenomenology generated by distinct mechanisms — and whether the dying brain’s gamma surge is signature, artifact, or something in between.

The Eye of Horus, Ajna Chakra, and the Cross-Cultural Third Eye

The Eye of Horus — the wedjat or udjat, “the sound one” — enters the written record in the Pyramid Texts of the Old Kingdom, around 2400 BCE, where it appears as a supreme ritual symbol presented to the deceased king to secure his restoration, transfiguration, and ascent into the sky. The myth underwriting the symbol is mechanical and surgical: Set tears out Horus’s left eye during their contest for the throne, and Thoth the god of wisdom subsequently restores it to wholeness. In funerary practice this logic of restoration was operationalized. Udjat amulets were placed on mummified bodies, commonly over the embalming incision on the left abdomen; the eye was painted on coffins during the First Intermediate Period and Middle Kingdom; and in the Book of the Dead Spell 140 the deceased declares directly, “I am the Eye of Horus, the sound one” — merging human and divine identity to navigate the underworld. A long-held but contested reading also treats the symbol as a mathematical notation, taking the parts of the eye as fractional heqat units — right side 1/2, pupil 1/4, eyebrow 1/8, left side 1/16, curved tail 1/32, teardrop 1/64 — that sum to 63/64, with Thoth, in the tradition retold by modern authors, supplying the missing fraction. Critically, the Eye of Horus (the lunar, restored left eye of Horus) was distinguished from the Eye of Ra (the solar, right-eye disk of violent retribution, associated with lioness/uraeus forms such as Sekhmet, Hathor, Bastet, and Tefnut); conflation is common in popular sources, but the distinction is fundamental to Egyptian theology. [30]

The Hindu counterpart developed along a different trajectory. The “third eye” appears in the iconography of deities — most prominently Shiva — where it symbolizes awakening, enlightenment, and the capacity to perceive realms beyond ordinary sight. In tantric and yogic systems this faculty is located at the Ajna chakra, whose Sanskrit name means “command,” “perceive,” or “guidance”. The canonical textual description comes from the Ṣaṭ-chakra-nirūpaṇa, a section of Pūrṇānanda Yati’s Śrītattvacintāmaṇi, composed in 1577 CE and translated by John Woodroffe in 1919 as The Serpent Power. That predates any Western glandular identification of the gland: Woodroffe’s 1919 edition of the text places the Ajna frontally in the space between the eyebrows and, at the back, with the pineal gland, the pituitary body and the top of the cerebellum. [31] Buddhist and Taoist traditions register analogous but independent concepts — the “Eye of Wisdom” or “Divine Eye” in Buddhism, linked to the doctrine of emptiness, and the “upper dantian” between the eyebrows in Taoism, a focus of meditation and qi cultivation — none of which originally couple the metaphor to a glandular location. [32]

Long before the modern esoteric overlay, the pineal organ itself had accumulated a Western mystical reputation. Galen in the 2nd century CE named it kônarion (“small cone”), after the stone pine, and regarded it as a structural support for blood vessels with no functional role, explicitly rejecting contemporaries who believed it regulated “psychic pneuma”. René Descartes revived the claim in the 17th century, calling the pineal the fundamental seat of the soul and the place where all thought originates, largely because it was the only unpaired structure in the brain. [32] Theosophy’s own correspondence was not stable on this point: in The Chakras, Leadbeater connects the sixth centre, the brow, with the pituitary body and the seventh, the crown, with the pineal gland. [33]

Descartes: The Nervous System. Diagram of the brain and the pineal gland. Photo: Wellcome Collection (L0006584), CC BY 4.0 / via Europeana. Source

Rick Strassman, a psychiatry professor at the University of New Mexico, picked up this braided tradition in the early 1990s. He conducted the first U.S. clinical research program administering DMT to human volunteers since psychedelic research was halted in the early 1970s. [1] The 1994 dose-response study documented subjective effects peaking at 90–120 seconds and almost completely resolved by 30 minutes, with dose-dependent cardiovascular and neuroendocrine responses. [10] [3] Strassman conjectured that the pineal gland produces and secretes endogenous DMT, possibly in surges at birth, death, or near-death. [13] The empirical record that has accumulated since is genuinely mixed and has hardened into three live positions rather than a believer/skeptic binary. [14] Dean et al. (2019) reported that the rat brain synthesizes and releases DMT at concentrations comparable to canonical monoamine neurotransmitters including serotonin, with INMT co-localized with AADC in rat brain and INMT transcripts present in the cerebral cortex, pineal gland, and choroid plexus; crucially, a significant rise in DMT occurred in the rat visual cortex following experimental cardiac arrest independent of an intact pineal gland. In 2013, Barker, Borjigin, Lomnicka and Strassman had reported DMT in rat pineal gland microdialysate. [18] The 2019 follow-up noted that it was unclear whether that DMT came from the pineal, the cortex or both, since the probe passed through both, and found cortical DMT with and without a pineal gland. [8] David Nichols’s 2018 critical review argued the data do not support the popular scenario: the adult pineal weighs less than 0.2 g and produces only about 30 µg of melatonin per day, while detected brain DMT concentrations are not sufficient to produce psychoactive effects. [13] Then a 2026 study by Palner, Cumming and colleagues in Neuropharmacology could not detect an endogenous DMT pool in rat brain even after pargyline (MAO inhibitor) pretreatment, and saw scant evidence that administered DMT is retained in serotonin terminals — directly challenging the Strassman hypothesis at the level of measurable endogenous DMT. [17] And Glynos et al. (2023), generating INMT-knockout rats via CRISPR/Cas9, demonstrated that indolethylamine-N-methyltransferase is not essential for endogenous tryptamine-dependent methylation activity, suggesting an alternative, still-unidentified enzymatic pathway. [6]

The popular linkage of the Eye of Horus to the pineal gland and the linkage of the Ajna chakra to the same gland are both modern Western projections, not attested in the primary ancient Egyptian or classical Sanskrit sources. [34] A 2019 Cureus paper by Mayo Clinic neurosurgeons (ReFaey et al.) proposed that the six heqat fractions of the Eye of Horus, when superimposed on a mid-sagittal section of the human brain, appear to align with specific neuroanatomical features — olfactory trigone, auditory cortex (Brodmann areas 41/42), and adjacent structures. The authors themselves explicitly framed the exercise as “possible scientific speculation” about ancient Egyptian “insight,” not as an established anatomical finding, and acknowledged that they could locate no prior neuroanatomical analysis of the symbol. [35] C.W. Leadbeater’s 1927 monograph described the brow chakra as connected specifically with the pituitary, not the pineal. [33] The eye of Horus, the Ajna chakra, the Cartesian soul, and the pineal DMT hypothesis are four distinct objects of inquiry with separate evidentiary bases, and the evidence has settled into a clearly non-aligned configuration: the Egyptian and Hindu symbols carry rich original meanings in their own corpora; the pineal-soul identification was a Cartesian conjecture that nevertheless propagated; and the strongest modern popular claim — that the pineal produces psychoactive DMT surges at birth, dreaming, or death — is, in Nichols’s assessment, not consistent with the scientific evidence, and the 2026 Palner study could not detect an endogenous DMT pool in rat brain. [13] [17] Endogenous DMT has nevertheless been measured at concentrations comparable to serotonin in the rat cortex and found elevated in the dying rat visual cortex by a mechanism that does not require the pineal. [8] The contemporary state is one of unresolved but narrowing claims rather than vindicated symbology.

Descartes mind and body. Photo: René Descartes / Wikimedia Commons. Drawing from René Descartes’ (1596-1650) in “Treatise of Man” supposing the function of the pineal gland. Source

Connecting the Dots

Timmermann et al. (2018) administered intravenous DMT to 13 healthy volunteers and found significant increases in phenomenological features associated with near-death experiences as measured by the Greyson NDE Scale, with significant overlap between DMT-induced NDEs and a matched group of actual NDE experiencers. [7] A 2025 thematic and content analysis (Michael, Luke, Robinson) comparing naturalistic DMT experiences with NDE narratives found that 95% of DMT participants reported at least one canonical NDE theme — translocation, bright light, sense of dying, void, disembodiment, tunnel-like structures, light-being-esque entities, deceased family, and life review-like experiences. [22] The mundane explanation: DMT acts primarily as an agonist at the 5-HT2A serotonin receptor with additional sigma-1 activity, the receptor through which classic psychedelics such as LSD and psilocybin also act. [12] The pattern that does not fit: Dean et al. (2019) demonstrated that DMT levels in rat visual cortex rose significantly following experimental cardiac arrest, an effect independent of an intact pineal gland [8], and animal models of cardiac arrest show a surge of gamma oscillations that has since been observed in two of four dying patients. [9] Exogenous DMT reproduces much of NDE phenomenology, and the rat data show a DMT surge in the dying brain that does not depend on the pineal; whether such a surge reaches psychoactive levels is not known.

Strassman proposed that the pineal gland produces DMT, which he termed the “spirit molecule,” and speculated that pineal DMT release may underlie near-death and mystical experiences. [14] This framing connects to a popular claim that the Eye of Horus is an ancient Egyptian encoding of the pineal “third eye”, a romantic history with which Nichols opens his skeptical review. [13] The Egyptological record: the Eye of Horus (Wedjat/Udjat) represented protection, healing, and restoration, derived from the myth in which Set tore out Horus’s eye and Thoth restored it; udjat amulets and the painted eye appear on Middle Kingdom coffins and mummy wrappings, and the left eye was associated with the moon. [36] [37] The cited Egyptological sources describe no pineal or third-eye concept for the Eye of Horus. Similarly, the modern Western identification of the Ajna chakra with the pineal gland was developed by Theosophists and shaped by Woodroffe’s 1919 translation “The Serpent Power,” based on Pūrṇānanda Yati’s 16th-century Ṣaṭ-chakra-nirūpaṇa — not by classical yogic texts. [31] [34] The pattern that does not fit: both the “ancient Egyptian third eye” and the modern Ajna-pineal identifications are modern Western syntheses, yet Strassman’s hypothesis is routinely illustrated by appeal to them.

The mundane explanation: the canonical biosynthetic pathway for endogenous DMT is tryptophan → tryptamine via AADC → DMT via INMT-mediated methylation. The pattern that does not fit: Glynos et al. (2023) generated an INMT-knockout rat using CRISPR/Cas9 and showed that brain and lung tissues of INMT−/− rats have tryptamine-dependent methylation activity equal to wild type, but the enzymatic products are neither N-methyltryptamine nor DMT, indicating that INMT is not essential for endogenous tryptamine-dependent methylation and suggesting an alternative enzymatic pathway for endogenous DMT biosynthesis in mammals. [6] Dean et al. (2019) found INMT transcripts in the cerebral cortex, pineal gland and choroid plexus of rats and humans, INMT co-localised with AADC in rat brain, and rat cortical extracellular DMT at concentrations similar to serotonin. [8] Endogenous DMT has also been proposed as an endogenous sigma-1 receptor regulator. [20] The combination — that the enzyme that makes DMT in the mammalian brain has not been identified, and that DMT exists in the rat brain at monoaminergic concentrations — is compatible with a framework in which endogenous DMT, if functional, acts as a sub-psychoactive signal rather than producing psychedelic surges from the pineal at death.

5-HT2A serotonin receptor structure (PDB 6WGT) with bound hallucinogen. Photo: C22H31NO2 / Wikimedia Commons, CC BY-SA 4.0. Source

Out-of-body experiences can be experimentally induced through manipulation of visual perspective in conjunction with correlated multisensory information from the body. [27] The mundane explanation: OBEs are mechanistic consequences of multisensory integration disturbance, not requiring any endogenous hallucinogen release. The independent lines — 5-HT2A pharmacology, multisensory integration, and sub-psychoactive endogenous DMT signaling — suggest a different picture: Strassman’s spirit-molecule framework may capture a real phenomenological signature while assigning it to the wrong anatomical source and the wrong scale of action.

The Other Side

The strongest biochemical objections to the hypothesis that the pineal gland produces behaviorally active endogenous DMT converge on three independent lines of evidence. First, the assumption that indolethylamine N-methyltransferase (INMT) is the key methylating enzyme in the canonical pathway has been directly undercut: Glynos and colleagues (2023) used CRISPR/Cas9 to generate INMT-knockout rats and found that brain and lung tissues of the knockouts still showed tryptamine-dependent methylation activity equal to wild type, with the enzymatic products being neither N-methyltryptamine nor DMT. If INMT is not essential for endogenous DMT biosynthesis, the field’s textbook pathway is at minimum incomplete, and an alternative, still-unidentified enzymatic pathway is implied. [6] Second, the empirical case for detectable endogenous DMT in the mammalian brain has been challenged by Palner and colleagues (2026, Neuropharmacology), who could not detect an endogenous DMT pool in rat brain even after monoamine-oxidase inhibition with pargyline, and saw scant evidence of retention of administered DMT in serotonin terminals, a result in tension with the extracellular DMT that Dean et al. reported in 2019. [17] Third, the pharmacological argument developed by Nichols (2018) remains: the adult human pineal weighs less than 0.2 g, its principal function is to produce about 30 micrograms of melatonin per day, and the minute concentrations of DMT detected in the brain are not sufficient to produce psychoactive effects. [13] Strassman’s original 1990s clinical work and his popularization of the “spirit molecule” framing stand at the origin of popular claims that run ahead of the supporting biochemistry. [14]

The phenomenological evidence linking DMT to NDEs is considerably weaker than it initially appears when subjected to systematic content analysis. Michael, Luke and Robinson (2025) compared 36 naturalistic DMT interviews with 34 NDE narratives and called DMT an “NDE-mimetic”: several classical NDE features (for example light at the end of the tunnel, out-of-body experiences and dramatised returns) were entirely absent from DMT, deceased individuals and life reviews were nearly absent, and DMT showed many features absent from NDEs; the authors conclude endogenous DMT “may only play a small role” in NDEs. [22] The same direction of evidence comes from Martial et al. (2019), whose semantic-similarity analysis of 625 NDE narratives against about 15,000 reports on 165 psychoactive substances placed ketamine as most similar to NDEs, followed by Salvia divinorum, and only then by serotonergic psychedelics including DMT, suggesting that if an endogenous neurochemical substrate for NDEs exists, an NMDA antagonist matches the phenomenology better than DMT. [25] Alternative neurophysiological accounts of the dying brain — including the gamma-coherence surge and the broader neuroscientific NDE models treating NDEs as arising from anoxia/hypercarbia and temporoparietal disruption — require no endogenous DMT release at all. [13]

Increase of cross-regional phase-amplitude coupling at near-death, a figure from Xu et al. (2023, PNAS) on the dying human brain. Photo: Xu et al. 2023, PNAS (Borjigin lab) / Wikimedia Commons, CC BY 4.0. Source

On the ancient Egyptian side, the proposed Eye of Horus = pineal identification does not survive scrutiny against the textual and iconographic sources. The Egyptological sources cited here describe the wedjat as a symbol of protection, healing and restoration rooted in the myth of Set tearing out Horus’s eye, and none of them links it to a pineal-like inner organ, the brow location, or a “third eye”. [36] [37] Nichols (2018), a skeptical review, mentions the Eye-of-Horus equation only as part of the pineal gland’s “romantic history” before rejecting the pineal-DMT hypothesis. [13] ReFaey et al. (2019, Mayo Clinic) superimpose the Eye’s six parts on a mid-sagittal brain section, assigning each to a sense (including Brodmann areas 41/42 for hearing), present this as “possible scientific speculation”, and do not mention the pineal. [35]

The Hindu/Yogic side fares no better once the actual textual history is consulted, because the Ajna = pineal identification turns out to be a Western-Theosophical synthesis rather than a received doctrine. Leadbeater’s 1927 monograph associated the Ajna (brow) chakra with the pituitary body and the crown chakra with the pineal gland [33], and Blavatsky had already related the pituitary and pineal glands to the sixth and seventh centres, so the now-popular pairing of the Ajna with the pineal is not even the Theosophical one. The historical literature is explicit that the modern Western chakra system — including its pineal mappings — is a 19th- and early-20th-century Theosophical construction, not an inheritance from the classical Sanskrit Yoga or Tantric traditions it is now presented as descending from. The classical sources most often cited — the Ṣaṭ-chakra-nirūpaṇa, the Gheranda Samhita, the Hatha Yoga Pradipika, and the Yoga Sutras of Patanjali — do not contain an unambiguous anatomical-pineal identification of the Ajna, and the chakra system itself likely crystallized in the late tantric period rather than as an ancient Vedic inheritance. The “third eye” framing in modern Shaiva iconography (Shiva’s trinetra) is real but functions as a mythological symbol of wisdom and destruction rather than as a documented neuroanatomical reference. Taken together, the Egyptian and Hindu attributions are modern retrojections onto the same Western template, not independent corroborations of the hypothesis. [34]

What We Actually Know

The investigation built a substantial case. Strassman’s 1990–1995 University of New Mexico program gave DMT, and also psilocybin, to human volunteers. [1] Its 1994 dose-response studies characterized IV DMT in detail: effects began almost immediately, peaked at 90–120 seconds and were almost completely resolved by 30 minutes, with hallucinogenic effects at 0.2 and 0.4 mg/kg and dose-dependent elevations across cardiovascular, endocrine, and pupillometric measures. [10] [3] Subsequent work has expanded the case in directions Strassman could not. Timmermann et al. (2018) at Imperial College London found that IV DMT (7–20 mg) significantly increased NDE-phenomenology scores on the Greyson scale in 13 healthy participants compared to placebo, with NDE scores correlating with ego-dissolution, mystical-type experiences, baseline trait absorption, and delusional ideation. [7] Michael, Luke and Robinson (2025) compared 36 semi-structured DMT interviews with 34 written NDE narratives and found 95% of DMT participants reported at least one canonical NDE theme, prompting the authors to coin the compound term “NDE-mimetic” for the relationship — while explicitly concluding endogenous DMT “may only play a small role” in actual NDEs. [22]

The dying-brain evidence is now real, not speculative. Xu et al. (2023), from Jimo Borjigin’s laboratory, recorded EEG in dying human brains and identified surges of gamma wave activity in the temporal-parieto-occipital junction of 2 of 4 comatose patients following withdrawal of ventilatory support, a region previously linked to dreaming, visual hallucinations in epilepsy, and altered states. This builds on animal models of cardiac arrest that had shown a surge of gamma oscillations. [9] Paralleling this, Dean et al. (2019) measured endogenous DMT in living rat brain extracellular fluid at 0.05–2.2 nM — comparable to but lower than canonical monoamine neurotransmitter concentrations — with both baseline levels and post-cardiac-arrest surge independent of an intact pineal gland. [8] Out-of-body experiences can be induced in the laboratory by displacing the visual perspective [27], and a voluntary out-of-body experience studied with fMRI activated regions overlapping the temporoparietal junction. [28] Entity encounters during DMT use are now robustly documented across independent methods: 45.5% of 3,778 r/DMT experiences in Lawrence et al. (2022) [15], 94% of 36 sessions in Michael et al. (2021) [16], and, in the Johns Hopkins survey of about 2,500 DMT users (Davis et al. 2020), a majority describing a “conscious, intelligent, benevolent, and sacred entity,” with 80% reporting fundamental alteration of their perception of reality and 72% saying the entity continued to exist in “a different plane of reality”. [21]

The cross-cultural symbolism evidence is real but narrower than popular treatments suggest. Shiva’s third eye is an established motif of Hindu iconography; in Taoism the corresponding focus is the “upper dantian” between the eyebrows, and in Buddhism the “Eye of Wisdom” or “Divine Eye” is linked to the doctrine of emptiness and developed through meditation. [32] The NDE-C scale (Martial et al. 2020) — a 20-item scale with 5-factor structure, Cronbach α = 0.85, and concurrent validity above 0.76 — represents methodological maturation of NDE measurement. [26]

The speculative tier is where the case thins. The canonical DMT biosynthetic pathway (tryptophan → tryptamine via AADC → DMT via INMT) is now in question after Glynos et al. (2023) demonstrated via three converging methods (radiometric, TLC, uHPLC-MS/MS) that INMT-knockout rat tissues retain tryptamine-dependent methylation activity, but the products are neither N-methyltryptamine nor DMT, and recombinant rat INMT alone is not sufficient for NMT or DMT biosynthesis. [6] INMT tissue distribution shows highest expression in thyroid, adrenal gland, and lung — not pineal. [5] The concentrations of DMT detected in the brain are, in Nichols’s assessment, not sufficient to produce psychoactive effects [13], and over 60 studies have failed to establish a clear-cut or repeatable correlation between peripheral DMT and psychiatric diagnoses. [12] The Egyptian links are weaker than popular accounts imply: a Mayo Clinic mapping of Eye of Horus heqat fractions to the six human senses is presented by its authors as “possible scientific speculation,” not as substantive neuroanatomical finding. [35] The Johns Hopkins findings on ontological belief change derive from an online survey of DMT users who chose to report entity encounters, not a probability sample. Martial et al. (2019) semantic-similarity comparison of 625 NDE narratives against about 15,000 reports on 165 psychoactive substances found ketamine highest in similarity to NDEs, followed by Salvia divinorum, then serotonergic psychedelics including DMT — supporting speculation about endogenous NMDA antagonists rather than DMT. [25] David et al. (2023) report that Ayahuasca-induced Personal Death experiences occur in more than half of ceremony participants and are associated with certainty in continuation of consciousness after death. [38]

The investigation’s strongest open question is the one the rat-human gap creates: whether endogenous DMT concentrations ever reach psychoactive levels in the human brain during birth, death, cardiac arrest, or NDEs remains undetermined, because current data are from rats. Almost all experimental evidence for endogenous DMT comes from rats; direct human evidence is limited to peripheral fluid detection and mRNA expression in archived autopsy material. Page (2026), in an online review essay, frames the contemporary debate as three live positions — Strassman’s strong experiential view, Nichols’ strong skeptical view, and the subtle-physiological view of Frecska, Szabo and others — rather than a believer/skeptic binary. [14] Hidalgo Jiménez and Bouso (2022) argue that the data suggest DMT may be relevant as a neurotransmitter, neuromodulator, hormone, and immunomodulator, which fits the subtle-physiological framing. [4] Borjigin-style gamma surges and Dean-style DMT surges have not been correlated in a single experiment. The hypothesis has accumulated solid phenomenological overlap, plausible cross-cultural parallels, and a real dying-brain neuroscience — but the central causal claim, that the pineal gland releases enough DMT at the moment of death to generate the phenomenology of near-death experience, remains unmeasured in humans.

References

[1] Psychedelic Therapies and Research | School of Medicine — https://hsc.unm.edu/medicine/departments/family-community/research/psychedelic_studies/ (accessed 2026-07-27) [Academic]

[2] UNM Health Sciences Researchers to Test Psychedelic Drugs as … — https://hscnews.unm.edu/news/hsc-newsroom-post-psychedelics (accessed 2026-07-27) [Academic]

[3] Dose-response study of N,N-dimethyltryptamine in humans … — https://pubmed.ncbi.nlm.nih.gov/8297217/ (accessed 2026-07-27) [Academic]

[4] Significance of mammalian N, N-dimethyltryptamine (DMT) — https://www.ovid.com/journals/jpsyc/pdf/10.1177/02698811221104054~significance-of-mammalian-n-n-dimethyltryptamine-dmt-a (accessed 2026-07-27)

[5] Indolethylamine N-methyltransferase — https://www.abcam.com/en-us/targets/indolethylamine-n-methyltransferase/15961 (accessed 2026-07-27)

[6] Nicolas G. Glynos, Lily Carter, Soo Jung Lee, Youngsoo Kim, Robert T. Kennedy, George A. Mashour, Michael M. Wang, and Jimo Borjigin (2023). Indolethylamine N-methyltransferase (INMT) is not essential for endogenous tryptamine-dependent methylation activity in rats. Scientific Reports. DOI: 10.1038/s41598-023-27538-y (accessed 2026-07-27) [Academic]

[7] DMT Models the Near-Death Experience — https://www.frontiersin.org/journals/psychology/articles/10.3389/fpsyg.2018.01424/pdf (accessed 2026-07-27) [Academic]

[8] Jon G. Dean, Tiecheng Liu, Sean Huff, Ben Sheler, Steven A. Barker, Rick J. Strassman, Michael M. Wang, and Jimo Borjigin (2019). Biosynthesis and Extracellular Concentrations of N,N-dimethyltryptamine (DMT) in Mammalian Brain. Scientific Reports. DOI: 10.1038/s41598-019-45812-w (accessed 2026-07-27) [Academic]

[9] Gang Xu, Temenuzhka Mihaylova, Duan Li, Fangyun Tian, Peter M. Farrehi, Jack M. Parent, George A. Mashour, Michael M. Wang, and Jimo Borjigin (2023). Surge of neurophysiological coupling and connectivity of gamma oscillations in the dying human brain. Proceedings of the National Academy of Sciences. DOI: 10.1073/pnas.2216268120 (accessed 2026-10-20) [Academic]

[10] Rick J. Strassman and Charles R. Qualls (1994). Dose-response study of N,N-dimethyltryptamine in humans. I. Neuroendocrine, autonomic, and cardiovascular effects. Archives of General Psychiatry. DOI: 10.1001/archpsyc.1994.03950020009001 (accessed 2026-10-04) [Academic]

[11] The Hallucinogen Rating Scale: Updated Factor Structure … — https://sonar.ch/documents/330977/files/1-s2.0-s2667174324001496-main.pdf (accessed 2026-07-27)

[12] N, N-Dimethyltryptamine (DMT), an Endogenous Hallucinogen — https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2018.00536/full (accessed 2026-07-27) [Academic]

[13] David E. Nichols (2018). N,N-dimethyltryptamine and the pineal gland: Separating fact from myth. Journal of Psychopharmacology. DOI: 10.1177/0269881117736919 (accessed 2026-10-20) [Academic]

[14] Endogenous DMT in Humans: A Critical Review of the State … — https://www.ardmt.com/endogenous-dmt-critical-review/ (accessed 2026-07-27)

[15] David W. Lawrence, Robin Carhart‐Harris, Roland R. Griffiths, and Christopher Timmermann (2022). Phenomenology and content of the inhaled N, N-dimethyltryptamine (N, N-DMT) experience. Scientific Reports. DOI: 10.1038/s41598-022-11999-8 (accessed 2026-07-27) [Academic]

[16] Pascal Michael, David Luke, and Oliver Robinson (2021). An Encounter With the Other: A Thematic and Content Analysis of DMT Experiences From a Naturalistic Field Study. Frontiers in Psychology. DOI: 10.3389/fpsyg.2021.720717 (accessed 2026-07-27) [Academic]

[17] M. Palner, E. Kolesnik, C. Baun, S. N. Poetzsch, and P. Cumming (2026). N,N-dimethyltryptamine (DMT) is neither formed nor retained in serotonin terminals in the rat brain. Neuropharmacology. DOI: 10.1016/j.neuropharm.2026.110874 (accessed 2026-10-20) [Academic]

[18] Steven A. Barker, Jimo Borjigin, Izabela Lomnicka, and Rick J. Strassman (2013). LC/MS/MS analysis of the endogenous dimethyltryptamine hallucinogens, their precursors, and major metabolites in rat pineal gland microdialysate. Biomedical Chromatography. DOI: 10.1002/bmc.2981 (accessed 2026-07-27) [Academic]

[19] Brain hallucinogens: Tryptamines found in pineal gland — https://analyticalscience.wiley.com/content/article-do/brain-hallucinogens-tryptamines-found-pineal-gland (accessed 2026-07-27) [Academic]

[20] The Endogenous Hallucinogen and Trace Amine N … — https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2016.00423/full (accessed 2026-07-27) [Academic]

[21] A spiritual experience - JHU Hub - Johns Hopkins University — https://hub.jhu.edu/magazine/2020/fall/psychedelics-god-atheism/ (accessed 2026-07-27) [Academic]

[22] An encounter with death: a comparative thematic and content … — https://www.frontiersin.org/journals/psychology/articles/10.3389/fpsyg.2025.1532937/full (accessed 2026-07-27) [Academic]

[23] Pim van Lommel, Rob van Wees, Vera Meyers, and Ingrid Elfferich (2001). Near-death experience in survivors of cardiac arrest: a prospective study in the Netherlands. The Lancet. DOI: 10.1016/s0140-6736(01)07100-8 (accessed 2026-10-04) [Academic]

[24] Comparing Near-Death and Psychedelic Experiences — https://psychedelic.support/resources/comparing-near-death-psychedelic-experiences/ (accessed 2026-07-27)

[25] ORBi: Neurochemical models of near-death experiences — https://orbi.uliege.be/handle/2268/231971 (accessed 2026-07-27)

[26] The Near-Death Experience Content (NDE-C) scale — https://pubmed.ncbi.nlm.nih.gov/33227590/ (accessed 2026-07-27) [Academic]

[27] H. Henrik Ehrsson (2007). The Experimental Induction of Out-of-Body Experiences. Science. DOI: 10.1126/science.1142175 (accessed 2026-07-27) [Academic]

[28] Andra Smith and Claude Messier (2014). Voluntary Out-of-Body Experience: An fMRI Study. Frontiers in Human Neuroscience. DOI: 10.3389/fnhum.2014.00070 (accessed 2026-07-27) [Academic]

[29] DMT alters cortical travelling waves — https://elifesciences.org/articles/59784 (accessed 2026-07-27)

[30] Eye of Horus (Udjat): Symbol, Myth, and Mathematics — https://mythologis.com/mythologies/africa-middle-east/egyptian/symbols/eye-of-horus (accessed 2026-07-27)

[31] The Serpent Power: Being the Sat-Cakra-Nirupana and Paduka-PancaKa — Arthur Avalon (John Woodroffe), 1919 — https://archive.org/details/in.ernet.dli.2015.283748 (accessed 2026-10-04)

[32] The Pineal Gland & The Eye of Horus I OBN — https://ophthalmologybreakingnews.com/ophthalmologynews-the-pineal-gland-the-eye-of-horus (accessed 2026-07-27)

[33] The Chakras: a monograph — C. W. Leadbeater, 1927 — https://archive.org/details/x-chakras (accessed 2026-10-04)

[34] The Western chakra system from theosophy to contemporary fringe … — https://www.academia.edu/79444860/The_chakras_beyond_yoga_The_Western_chakra_system_from_theosophy_to_contemporary_fringe_New_Age_thinking (accessed 2026-07-27) [Academic]

[35] The Eye of Horus: The Connection Between Art, Medicine, and … - PMC — https://pmc.ncbi.nlm.nih.gov/articles/PMC6649877/ (accessed 2026-07-27) [Academic]

[36] eye of Horus | Fashion History Timeline — https://fashionhistory.fitnyc.edu/eye-of-horus-3/ (accessed 2026-07-27) [Academic]

[37] The Udjat Eye in Daily Life Marlaina Miller — https://preview.memphis.edu/wmst/student_projects/hist_4057/pdfs/miller.pdf (accessed 2026-07-27) [Academic]

[38] Jonathan David, José Carlos Bouso, Maja Kohek, Genís Oña, Nir Tadmor, Tal I. Arnon, Yair Dor‐Ziderman, and Aviva Berkovich‐Ohana (2023). Ayahuasca-induced personal death experiences: prevalence, characteristics, and impact on attitudes toward death, life, and the environment. Frontiers in Psychiatry. DOI: 10.3389/fpsyt.2023.1287961 (accessed 2026-07-27) [Academic]