From the book’s back matter

Glossary

Plain definitions for the chemical, neuroscientific, clinical and mystical terms used in Seaich’s essay and the editor’s commentary.

Updated November 10, 2026

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Pharmacological & Chemical

Agonist: a molecule that binds to a receptor and activates it, producing a biological response; the classic psychedelics act as agonists at certain serotonin receptors. Contrast antagonist, which binds without activating and so blocks a response.
Alkaloid: a naturally occurring, nitrogen-containing organic compound, often with marked physiological effects on humans. Mescaline, psilocybin, and the ergot precursors of LSD are all alkaloids.
DMT (N,N-dimethyltryptamine): a short-acting tryptamine psychedelic, the principal visionary agent of the Amazonian brew ayahuasca, in which it is combined with a plant that inhibits its breakdown in the gut.
Entheogen: a psychoactive substance used to occasion a spiritual or religious experience. Coined in 1979 by a group of ethnobotanists from Greek éntheos (“the god within,” inspired) and genésthai (“to bring into being”): literally, that which generates the divine within.
Ergot: the fungus Claviceps purpurea, which grows on rye and related grasses and yields lysergic acid, the natural precursor from which LSD is semi-synthesized.
5-HT2A receptor: the serotonin-2A receptor subtype. Agonism at this receptor is now understood to be the principal mechanism by which the classic psychedelics produce their effects.
Hallucinogen: an older umbrella term for substances that alter perception. It is now often considered imprecise, since the classic psychedelics seldom produce true hallucinations — the conviction that an unreal perception is real — so much as visions known to be subjective.
LSD-25 (lysergic acid diethylamide): a semi-synthetic compound first prepared by Albert Hofmann at Sandoz Laboratories in 1938, the twenty-fifth in a series; its profound psychoactivity was discovered by accident in April 1943.
Mescaline: the principal psychoactive alkaloid of the peyote and San Pedro cacti (3,4,5-trimethoxyphenethylamine). Isolated by Arthur Heffter in 1897 and first synthesized in 1919, it is the substance of Huxley’s Doors of Perception and of many of Seaich’s own experiments.
Microdose: a sub-perceptual dose — conventionally about a tenth of an active dose — taken with the intention of subtly influencing mood or cognition without overt intoxication.
Phenethylamine: one of the two great chemical families of psychedelics, including mescaline and MDMA. The other is the tryptamine family.
Psilocybin / psilocin: the active principles of the “magic” mushrooms (Psilocybe). Psilocybin is a prodrug, converted in the body to the active psilocin; both were isolated and named by Albert Hofmann in 1958.
Psychedelic: the class of substances that produce profound, hours-long alterations of perception, thought, and mood, chiefly through serotonin-receptor agonism. Coined by the psychiatrist Humphry Osmond in 1956–57, from Greek psychê (mind, soul) and dêloun (to make manifest): “mind-manifesting.”
Serotonergic: pertaining to the neurotransmitter serotonin (5-hydroxytryptamine). The classic psychedelics act upon the brain’s serotonin systems.
Set and setting: the mindset the participant brings (“set”) and the physical and social environment in which a substance is taken (“setting”). The phrase names the single most important non-pharmacological determinant of a psychedelic experience.
Tryptamine: the chemical family, built on an indole ring, that includes psilocybin, DMT, and (structurally) LSD.

Neuroscience

Default Mode Network (DMN): a set of interconnected brain regions — centered on the posterior cingulate cortex, the medial prefrontal cortex, and the angular gyri — most active during rest, daydreaming, and self-referential thought. It is closely tied to the ordinary sense of a narrative self, and psychedelics acutely loosen its internal connectivity.
Ego dissolution: the acute weakening or temporary loss of the felt boundary between self and world, often reported at higher doses and correlated with the disintegration of the Default Mode Network. Seaich describes the state vividly, decades before it was named or measured.
Entropic brain: the hypothesis, advanced by Robin Carhart-Harris and colleagues in 2014, that the richness of a conscious state corresponds to the entropy — the disorder or uncertainty — of brain activity, and that psychedelics push the brain toward a higher-entropy, less constrained mode.
Functional connectivity: the degree to which the activity of separate brain regions rises and falls in concert over time, typically measured with functional MRI.
fMRI (functional magnetic resonance imaging): a brain-imaging technique that tracks changes in blood oxygenation as an indirect measure of neural activity.
Neural correlate: the specific pattern of brain activity that accompanies a given mental state or experience.
Neuroplasticity: the brain’s capacity to remodel its own connections. Psychedelics are associated with short-term increases in markers of this plasticity, a leading candidate mechanism for their lasting therapeutic effects.
REBUS (“relaxed beliefs under psychedelics”): a 2019 model by Carhart-Harris and Karl Friston proposing that psychedelics relax the grip of the brain’s high-level expectations and beliefs, freeing perception and emotion from habitual top-down control — the “anarchic brain.”

Clinical & Regulatory

Breakthrough Therapy Designation: a U.S. Food and Drug Administration program that expedites the development and review of a drug for a serious condition when early evidence suggests a substantial improvement over existing options. Psilocybin and MDMA therapies have each received it.
Complete Response Letter (CRL): the FDA’s formal notice, at the end of a review cycle, that it will not approve an application in its present form, with the deficiencies specified.
Controlled Substances Act: the 1970 U.S. federal statute that established the system of drug “schedules.”
Psychedelic-assisted psychotherapy: a treatment model that pairs a small number of supervised dosing sessions with structured preparation beforehand and integration afterward.
Schedule I: the most restrictive category under the Controlled Substances Act — defined as high abuse potential, no currently accepted medical use, and a lack of accepted safety. Psilocybin, LSD, MDMA, DMT, and mescaline are so classified at the U.S. federal level.
Treatment-resistant depression: major depression that has failed to respond to an adequate course of, typically, two or more antidepressant medications — the indication for much current psilocybin research.

Mystical, Philosophical & Religious

Archetype: in the analytical psychology of C. G. Jung, a universal, inherited pattern of the psyche, residing in the collective unconscious — a shared substratum beneath the personal unconscious.
Gnosis: Greek for “knowledge”; experiential, revelatory knowledge of divine or ultimate things, as distinct from intellectual belief.
Ineffability: the quality of defying expression in words. William James named it the first of the four marks of mystical experience.
Mana: an impersonal supernatural power or efficacy, a concept drawn from Melanesian and Polynesian thought and introduced to anthropology by R. H. Codrington in 1891. Seaich invokes it among the world’s names for the numinous.
Monism: the metaphysical position that reality is, at bottom, a single substance or unity — the philosophical counterpart of the mystic’s sense of oneness.
Numinous: Rudolf Otto’s term (1917) for the non-rational, awe-inspiring quality of the holy: the mysterium tremendum et fascinans, the mystery that both terrifies and fascinates.
Perennial philosophy: the thesis — named by Leibniz and popularized by Aldous Huxley in 1945 — that the world’s mystical traditions point, beneath their differences, to a single transcendent reality.
Teonanácatl: Nahuatl for “flesh of the gods,” the Aztec name for the sacred psilocybin mushrooms of Mesoamerica.
Transpersonal: pertaining to states and experiences that reach beyond the individual ego or personal identity; the root of the transpersonal psychology later founded by Stanislav Grof and others.
Unitive experience (unio mystica): the experience of merging with all that exists, or with the divine — the dissolving of the boundary between self and cosmos that lies at the heart of mystical report.

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