DMT and the Chemistry of Dying: The Endogenous Psychedelic at the Threshold of Death

Language: en

Overview

In 1990, Rick Strassman, a psychiatrist at the University of New Mexico, received the first federal approval in over 20 years to administer a psychedelic compound to human subjects. The compound was N,N-dimethyltryptamine — DMT — a molecule so potent that it produces a complete transformation of consciousness in under 60 seconds when injected intravenously, and so brief that the experience ends within 15 minutes. Strassman chose DMT not because it was the most popular psychedelic (it was not) but because it was already present in the human body. DMT is an endogenous compound — the brain, the lungs, the liver, and possibly the pineal gland produce it naturally. The question that haunted Strassman was: why?

His hypothesis, developed over decades and detailed in “DMT: The Spirit Molecule” (2001), was provocative: endogenous DMT is released in massive quantities at two critical moments in human life — birth and death — and this release is responsible for the visionary experiences reported at both thresholds. The near-death experience, with its tunnel of light, encounters with beings, life review, and sense of transcendent reality, might be a DMT trip produced by the dying brain.

This hypothesis remained speculative until 2019, when Jimo Borjigin’s team at the University of Michigan published a landmark paper confirming that the rodent brain produces a massive surge of DMT at the moment of cardiac arrest. The chemistry of dying had its first hard data point.

This article examines the DMT-death connection from multiple angles: the pharmacology of DMT, the Strassman studies and their phenomenology, the 2019 rodent data, the pineal gland hypothesis, the remarkable overlap between exogenous DMT experiences and NDEs, and the implications for our understanding of consciousness at the threshold of death.

The Pharmacology of DMT

A Tryptamine Like No Other

DMT (N,N-dimethyltryptamine) is a simple indole alkaloid — structurally related to serotonin (5-HT) and melatonin, with which it shares the tryptamine backbone. It is found throughout nature: in hundreds of plant species, in the venom of certain toads, and in the tissues of mammals, including humans. Its biosynthesis requires only two enzymatic steps from tryptophan (an essential amino acid present in all living organisms): decarboxylation to tryptamine by aromatic amino acid decarboxylase (AADC), then double methylation by indolethylamine-N-methyltransferase (INMT).

INMT, the enzyme that converts tryptamine to DMT, has been found in human lung, liver, blood, brain, and pineal gland tissue. The presence of the biosynthetic machinery in the brain is significant: it means the brain can produce DMT locally, without requiring it to cross the blood-brain barrier from peripheral sources.

Receptor Pharmacology

DMT acts on multiple receptor systems:

Serotonin 5-HT2A receptor. This is the primary target for classical psychedelics (LSD, psilocybin, mescaline) and is likely the main mediator of DMT’s visionary effects. 5-HT2A agonism in the cortex disrupts the default mode network, reduces the brain’s normal predictive filtering, and allows a flood of sensory and associative information into consciousness.

Sigma-1 receptor. DMT is a potent sigma-1 receptor agonist. The sigma-1 receptor is an intracellular chaperone protein involved in calcium signaling, endoplasmic reticulum stress responses, and — critically — neuroprotection during hypoxia. This means DMT may have a dual role: psychoactive (through 5-HT2A) and neuroprotective (through sigma-1). At the moment of death, DMT release could simultaneously produce a visionary experience AND protect neural tissue from hypoxic damage, extending the window of viable consciousness.

Trace amine-associated receptors (TAARs). DMT activates TAAR1, a receptor involved in modulating dopamine and serotonin signaling. This may contribute to the emotional and motivational aspects of the DMT experience.

Other targets. DMT has been shown to interact with glutamate receptors, melatonin receptors, and various ion channels, suggesting a broad pharmacological profile that may account for the richness and complexity of the DMT experience.

Monoamine Oxidase and the Duration Problem

DMT is rapidly metabolized by monoamine oxidase A (MAO-A), which is abundant in the brain and gut. This is why oral DMT is inactive unless combined with a MAO inhibitor (as in ayahuasca, the Amazonian brew that combines DMT-containing plants with MAO-inhibiting plants). When injected intravenously, DMT reaches the brain before MAO can fully degrade it, but the experience is still brief — peaking within 2-5 minutes and resolving within 15.

At endogenous concentrations, DMT is normally broken down so rapidly that it never reaches psychoactive levels. For the death-release hypothesis to work, one of two things must happen: either DMT is released in quantities large enough to overwhelm MAO degradation, or MAO activity is reduced during the dying process (which is plausible, given that hypoxia impairs enzyme function). The 2019 rodent study suggests the former — the surge at cardiac arrest is large enough to produce pharmacologically significant brain concentrations.

The Strassman Studies (1990-1995)

The Protocol

Strassman administered intravenous DMT to 60 volunteers at the University of New Mexico. Subjects received varying doses (0.05 to 0.4 mg/kg) while lying in a hospital bed with eyes covered, in a controlled clinical setting. Physiological measurements (heart rate, blood pressure, pupil diameter, body temperature, cortisol, growth hormone, prolactin, beta-endorphin) were recorded at frequent intervals. Subjective experiences were documented through structured interviews immediately after each session and through the Hallucinogen Rating Scale (HRS), a psychometric instrument Strassman developed for the study.

The Phenomenology

At the threshold dose of 0.2 mg/kg and above, subjects consistently reported experiences that Strassman categorized into several types:

Personal/psychological. Emotional catharsis, life review, insights into personal relationships and patterns. Similar to psychotherapy but vastly accelerated and intensified.

Transpersonal/mystical. Unity experiences, dissolution of self-other boundaries, encounters with a transcendent reality described as “more real than real.” Subjects frequently reported that the DMT realm felt like a more fundamental level of reality than ordinary waking consciousness.

Contact with entities. Perhaps the most distinctive feature of high-dose DMT experiences: encounters with apparently autonomous beings — described variously as elves, angels, aliens, guides, or ineffable presences — that communicated with the subject through telepathy, visual display, or direct energetic transmission. The entity encounters had a quality of “realness” that subjects found deeply disturbing and difficult to dismiss as hallucination.

Near-death-like features. Multiple subjects spontaneously described their experiences in terms identical to NDE accounts: tunnels, light, encounters with deceased persons, panoramic life review, sense of dying and being reborn, feeling of being welcomed into a realm of peace and love.

The NDE Overlap

The overlap between DMT phenomenology and NDE phenomenology is striking and has been systematically analyzed by several researchers:

Feature	NDE	DMT
Tunnel or passage	Common	Common
Bright light	Common	Common
Encounter with beings	Common	Common
Life review	Common	Occasional
Sense of “more real than real”	Universal	Universal
Feeling of peace/love	Universal	Common
Separation from body	Common	Common
Sense of dying	Inherent	Common at high doses
Lasting transformation	Characteristic	Common

A 2018 study by Charlotte Timmermann and colleagues at Imperial College London directly compared DMT experiences (measured with the NDE Scale) and NDE experiences. They found that DMT experiences scored comparably to NDEs on every dimension of the NDE Scale, and that the DMT experience was indistinguishable from the NDE on phenomenological grounds. This does not prove that NDEs are caused by DMT, but it demonstrates that DMT pharmacology can produce the full NDE phenomenological profile.

The 2019 Rodent Study: Hard Evidence

Borjigin’s Discovery

In 2019, Jimo Borjigin’s laboratory at the University of Michigan published a paper in “Scientific Reports” that provided the first direct evidence of endogenous DMT release in the brain at the time of death. Using microdialysis probes implanted in the visual cortex of living rats, the team measured real-time DMT levels during normal waking activity and during experimentally induced cardiac arrest.

The key findings:

1. DMT is present in the rat brain during normal waking. Low but detectable levels of DMT were found in the visual cortex of healthy, awake rats, confirming that the brain produces DMT under normal conditions.

2. DMT levels surge dramatically at cardiac arrest. Within minutes of cardiac arrest, DMT levels in the visual cortex increased by approximately 600% above baseline — a pharmacologically significant surge that would be expected to produce psychoactive effects.

3. The surge occurs in the visual cortex. The visual cortex is the brain region most associated with visual experience. A DMT surge in this specific region could account for the vivid visual imagery (tunnel, light, landscapes, beings) characteristic of both DMT experiences and NDEs.

4. The surge is accompanied by gamma oscillations. Borjigin’s earlier work (2013) had shown that the rat brain produces a surge of synchronized gamma oscillations at the moment of cardiac arrest — electrical activity patterns associated in living brains with conscious experience, perception, and binding. The DMT surge may be driving or co-occurring with these gamma surges.

Extrapolation to Humans

The rodent data cannot be directly extrapolated to humans without confirmation from human studies, which pose obvious ethical challenges (you cannot implant microdialysis probes in the brains of dying humans). However, several lines of evidence support the relevance to humans:

• Human brain tissue expresses INMT (the enzyme that produces DMT) in regions including the pineal gland, choroid plexus, and cortex.
• Human cerebrospinal fluid contains detectable DMT.
• The pharmacological effects of exogenous DMT in humans closely match the phenomenology of NDEs.
• The conditions of cardiac arrest (hypoxia, acidosis, energy failure) that trigger DMT release in rats also occur in human cardiac arrest.

The Pineal Gland Connection

Descartes’ “Seat of the Soul”

Rene Descartes, in the 17th century, identified the pineal gland as the “seat of the soul” — the point of interface between the non-physical mind and the physical brain. His reasoning was partly anatomical (the pineal gland is one of the few brain structures that is not lateralized — it sits at the midline, which Descartes associated with the unity of consciousness) and partly mystical.

Strassman revived the pineal hypothesis in a modern context. The pineal gland produces melatonin from serotonin — and the same enzymatic pathway can produce DMT (via INMT, which is expressed in pineal tissue). The pineal gland is protected behind the blood-brain barrier, is richly vascularized, and has structural features (including pinealocytes that resemble retinal photoreceptors) that suggest a sensory function beyond melatonin production.

The Evidence and Its Limits

The pineal-DMT connection remains largely hypothetical. While INMT expression has been confirmed in the rodent pineal gland (Cozzi et al., 2011; Barker et al., 2012), the quantitative contribution of the pineal to whole-brain DMT levels is unclear. The 2019 Borjigin study showed that DMT surges at death occurred even in pinealectomized rats (rats whose pineal glands had been surgically removed), demonstrating that the pineal is not the sole source of death-related DMT release. Other brain regions (cortex, choroid plexus) and peripheral sources (lung, liver) may contribute.

The pineal gland may not be the exclusive source of endogenous DMT, but its symbolic significance — as the “third eye” in yogic traditions, the seat of the ajna chakra, the organ of inner vision — creates a powerful convergence between the scientific and spiritual dimensions of the DMT-death connection.

The Shamanic Context

Ayahuasca: The Vine of the Dead

Ayahuasca — the Amazonian brew containing DMT and MAO inhibitors — is traditionally called “the vine of the dead” or “the vine of souls.” Indigenous Amazonian peoples have used ayahuasca for centuries (possibly millennia) as a sacrament for communicating with the dead, healing illness, divining the future, and navigating the spirit world. The experience is understood not as a hallucination but as a genuine encounter with non-ordinary reality — a reality that is always present but normally invisible to ordinary consciousness.

The pharmacological parallel is remarkable: the indigenous peoples discovered, through millennia of empirical experimentation, a chemical preparation that produces the same phenomenological experience as dying. The “vine of the dead” is a technology for experiencing death while alive — for visiting the realm that consciousness enters at the threshold of death, and returning with knowledge and healing.

The Death Rehearsal

In shamanic traditions worldwide, the ability to die and return is the central qualification of the shaman. Mircea Eliade documented this in “Shamanism: Archaic Techniques of Ecstasy” (1951): the shamanic initiation involves a death-and-rebirth experience — a visionary death in which the initiate is dismembered, transformed, and reconstituted with new spiritual capabilities. The shaman who has died and returned can guide others through the death transition — they know the territory.

DMT, whether ingested as ayahuasca or released endogenously at death, may be the neurochemical mechanism underlying this shamanic capacity. The shaman’s “death rehearsal” is, pharmacologically, a DMT experience. And the actual death process, when endogenous DMT surges, is a final ayahuasca ceremony — the ultimate journey on the vine of the dead.

The Chemistry of Dying: A Synthesis

The Sequence

Integrating the available evidence, the following sequence is proposed for what happens neurochemically at the threshold of death:

1. Cardiac arrest (or severe physiological crisis) triggers rapid brain hypoxia — oxygen levels plummet within seconds.

2. Hypoxia triggers a cascade of neurochemical events: massive release of glutamate (excitotoxicity), failure of ion pumps, calcium influx, and activation of stress-response pathways.

3. Endogenous DMT synthesis accelerates. The INMT enzyme, present in cortical and subcortical tissue, produces a surge of DMT. The surge may be triggered by hypoxia-related changes in precursor availability, enzyme activity, or MAO impairment. DMT levels in the brain rise to pharmacologically significant concentrations.

4. DMT activates 5-HT2A receptors in the cortex, disrupting the default mode network and the brain’s normal predictive filtering. Simultaneously, DMT activates sigma-1 receptors, providing neuroprotection and potentially extending the window of viable consciousness.

5. Gamma oscillations surge. Borjigin’s 2013 data shows a burst of synchronized gamma activity in the dying brain. This gamma surge, possibly driven by the DMT-mediated disruption of normal cortical dynamics, may represent the neural correlate of the NDE — a final burst of integrated, conscious experience.

6. The NDE unfolds. With the brain’s normal filtering disrupted by DMT, consciousness experiences reality without the usual constraints: the tunnel (neural correlate uncertain but possibly related to cortical disinhibition of visual fields), the light (possibly related to massive activation of the visual cortex), the life review (possibly related to hippocampal activation in the context of cortical disinhibition), the encounters with beings (unknown mechanism, possibly related to 5-HT2A-mediated entity contact as documented in Strassman’s studies), and the sense of transcendent reality (possibly the experience of consciousness freed from the brain’s normal filtering constraints).

7. The process resolves. Either the patient is resuscitated (and reports the NDE) or the neurochemical cascade proceeds to completion and the brain ceases functioning. What happens to consciousness after that point is beyond the reach of current neuroscience.

Implications

For Neuroscience

The endogenous DMT hypothesis provides a specific, testable neurochemical mechanism for NDEs — one that is consistent with the known pharmacology of DMT, the known neurobiology of death, and the documented phenomenology of both exogenous DMT experiences and NDEs. It does not require invoking any mechanism outside of established biochemistry. It makes predictions that can be tested (e.g., that blocking 5-HT2A receptors during cardiac arrest should prevent or alter the NDE).

For Consciousness Research

The DMT-death connection suggests that the brain has a built-in mechanism for producing the most profound altered state of consciousness known to humans — and that this mechanism activates at the most critical moment of biological existence. This is not a malfunction. It is a feature. The brain appears to be designed (by evolution) to produce a specific kind of experience at death — an experience that is consistent across cultures, across conditions, and across the artificial/endogenous divide.

Why? From an evolutionary perspective, there is no obvious survival benefit to a vivid, complex experience at the moment of death. The organism is dying — it will not reproduce or pass on genes based on this experience. One possibility is that the NDE is an epiphenomenon — a by-product of neurochemical processes that serve other functions (sigma-1-mediated neuroprotection, for instance). Another possibility, entertained by the contemplative traditions, is that the NDE serves a function beyond biological survival — that it is a mechanism for consciousness to transition from one state of existence to another.

For the Dying

Perhaps the most important implication is for the dying themselves, and for those who care for them. If the dying brain produces a DMT-mediated experience that is vivid, meaningful, and often profoundly positive, then death may not be the terrifying annihilation that our culture fears. The chemistry of dying may be a chemistry of release — a final psychedelic journey that carries consciousness beyond the body’s dissolution.

This is not a guarantee. Not all NDEs are positive (a minority involve distressing experiences). And the DMT hypothesis does not address what happens after the neurochemical cascade is complete. But it suggests that the dying process itself — the transition from life to death — may be accompanied by a neurochemically facilitated experience of transcendence. If so, the most appropriate response to dying is not terror but preparation — learning, through meditation, through psychedelic experience, through spiritual practice, to navigate the territory that the endogenous DMT will open.

Conclusion

The convergence of Rick Strassman’s clinical research, Jimo Borjigin’s rodent studies, the pharmacology of the sigma-1 receptor, and the phenomenological overlap between exogenous DMT experiences and near-death experiences creates a compelling case that endogenous DMT plays a significant role in the experience of dying. The data is not yet definitive — human confirmation is lacking, the quantitative role of the pineal gland is unclear, and the full neurochemical cascade of death remains incompletely characterized. But the direction of the evidence is clear: the brain produces its own psychedelic compound, releases it in massive quantities at the moment of death, and the resulting experience closely resembles the most profound spiritual experiences reported across human cultures and centuries.

The chemistry of dying is not the chemistry of annihilation. It is the chemistry of transformation. The body’s final act is not to shut down but to open up — to flood the brain with a compound that dissolves the boundaries of ordinary consciousness and reveals a reality that the living brain normally filters out. Whether this reality is neurochemical artifact or genuine contact with a transcendent dimension is a question that science cannot yet answer. But the molecule is there. The surge is documented. And the experience it produces — whether at death or in the laboratory — is consistently described as the most real, most meaningful, and most transformative experience of a human life.