Concept Index

A serotonin receptor subtype (5-HT₁A) involved in anxiety and mood regulation that also modulates psychedelic effects.

A serotonin receptor subtype (5-HT₂A) whose activation is responsible for the characteristic effects of classical psychedelics such as LSD, psilocin, and mescaline.

A serotonin receptor subtype (5-HT₂C) involved in appetite, mood, and the regulation of dopamine release.

An ionotropic glutamate receptor that mediates fast excitatory synaptic transmission in the brain.

The passage of a substance from where it was taken — the gut, nasal mucosa, lung, or skin — into the bloodstream, the first phase of pharmacokinetics and the one route of administration most directly shapes. This is the pharmacological sense used on substance records; in the practice literature the same word names a state of deep, sustained attentional immersion, an unrelated use.

The enzyme that breaks down acetylcholine in the synapse; its inhibition prolongs cholinergic signaling and underlies nerve-agent toxicity.

A metabolite that retains meaningful biological activity at the same or a different target than its parent drug. When an active metabolite contributes substantially to a substance's effect, its own clearance and duration help shape how long that effect lasts.

The enzyme that converts ATP into cyclic AMP, a second messenger carrying a receptor's signal into the cell. Receptors coupled to Gi/o proteins — the opioid and kappa receptors among them — inhibit it, and the resulting fall in cyclic AMP is one of the downstream steps shared across that whole receptor family.

A measure of how strongly a molecule binds to its target, such as a receptor or transporter. Higher affinity means less of the molecule is needed to occupy the target, but affinity alone does not determine what happens once binding occurs.

A substance that binds to and activates a receptor to produce a biological response.

A drug-induced loss of sensation, either confined to one region of the body or accompanied by full unresponsiveness for a procedure. General anesthesia sits at the far end of the depressant continuum running from anxiolysis through sedation and hypnosis; in clinical use it is reached deliberately, with airway and circulatory support already in place.

The action of occupying a receptor without activating it, so the signal the receptor would otherwise carry — including the one an agonist would produce — is blocked. Antagonism at a given receptor is how several compounds in this index produce their effects, and how reversal agents such as naloxone and flumazenil work; whether a block lasts longer than what it displaces is a separate question with clinical consequences.

A substance that binds to a receptor without activating it, blocking the action of agonists.

A laboratory test designed to measure a specific property of a substance, such as how strongly it binds a receptor or how it behaves in a cell line. Assay results are one input among several used to characterize a drug's pharmacology, not a direct description of its effect in a person.

A laboratory measure of how tightly a molecule attaches to a specific receptor or other target, usually derived from a concentration-response curve in that assay. It describes the interaction in isolation and does not by itself predict a substance's potency or effect in a whole organism.

The cavity in a receptor or other protein that a molecule occupies when it binds, formed by the residues lining it and often sitting at the interface between subunits. Its shape determines which molecules fit and how long they remain, which is why a small structural change to a compound can shift affinity and duration out of proportion to its size.

The specific location on a receptor, enzyme, or transporter where a molecule attaches, often a pocket formed at the interface between subunits. Two compounds acting on the same receptor at different sites can produce different effects, which is why pharmacology names the site rather than only the target.

The fraction of an administered dose that reaches systemic circulation in active form, which varies by route of administration.

A molecule that occupies a channel, transporter, or receptor so that it can no longer carry out its normal function. The word names an outcome rather than a single mechanism — an open-channel blocker sits inside the pore, a transporter blocker occludes the substrate path — which is why blockade and antagonism are related but not interchangeable.

The amount of a substance present in brain tissue, as opposed to in the blood. It matters because the brain is where a psychoactive effect is produced and the two figures can diverge widely — a compound may circulate freely and still penetrate poorly — so receptor activity measured in a dish predicts an effect only if the concentration reaching the brain falls in the same range.

How readily and how quickly a substance crosses from blood into brain tissue — a property of the compound, not of the barrier it crosses. It sets the lag between a substance being in the body and being felt, and a slowly penetrating compound can invite redosing before the first amount has taken full effect.

The cannabinoid receptor subtype (CB1), concentrated in the brain, that mediates the psychoactive effects of THC.

The cannabinoid receptor subtype (CB2), found mainly in immune tissue and involved in inflammation rather than intoxication.

An enzyme (catechol-O-methyltransferase) that degrades catecholamines such as dopamine; genetic variation affects prefrontal dopamine levels.

A liver cytochrome-P450 enzyme responsible for metabolizing caffeine and a range of other compounds. Its activity is inducible rather than fixed, rising with tobacco smoke and falling with some medications, so clearance at this enzyme varies with a person's habits and co-medication as well as their genetics.

A liver cytochrome-P450 enzyme that handles a narrower set of drugs than CYP3A4 but is the principal pathway for some of them, methadone among others. It is subject both to marked genetic variation and to mechanism-based inactivation, in which the compound being metabolised disables the enzyme, so repeated exposure can clear more slowly than a first one.

A liver cytochrome-P450 enzyme that metabolizes a range of drugs, including some benzodiazepines and proton-pump inhibitors. Genetic variation makes people poor or ultrarapid metabolizers at this enzyme, so the same intake can be cleared at very different rates by different people.

A liver cytochrome-P450 enzyme that metabolises a substantial share of drugs, including several anticoagulants, anti-inflammatories, and cannabinoids. Common genetic variants leave some people clearing its substrates far more slowly than others, and where a compound's metabolising isoforms have not been established experimentally, its involvement is inferred from related compounds rather than measured.

A liver cytochrome-P450 enzyme that metabolizes many drugs; genetic variation makes individuals poor or rapid metabolizers, altering drug effects and risks.

The most abundant liver cytochrome-P450 enzyme, responsible for metabolizing a large fraction of drugs and a common site of drug interactions.

A protein embedded in a cell membrane that forms a pore allowing specific ions to cross it, opening or closing in response to voltage, a bound molecule, or another signal. Many drugs act by opening, closing, or otherwise modulating ion channels rather than binding a receptor in the classic sense.

The rate at which the body removes a substance, usually expressed as a volume of blood or plasma cleared per unit of time. Clearance is a major factor in how long a drug's presence and effects persist.

A metabolic reaction that splits a molecule in two by breaking a specific bond, such as an ester link or a glucuronide conjugate. It shapes what can be measured as much as what is felt: whether a laboratory cleaves conjugated metabolites before analysis determines which compounds a urine screen is able to find.

The highest concentration a substance reaches in blood after it is taken — the companion parameter to Tmax, which records when that maximum occurs. It summarises exposure at a single moment and says nothing about how long the substance remains present, which is what half-life and clearance describe.

The family of liver enzymes, designated CYP with a number-letter code, that carries out most oxidative drug metabolism in the body. Individual isoforms handle different substrates, so knowing that the family is involved says little until the specific isoform is identified, and much of the corpus records that identification as unmade.

An excitatory (D1-like) dopamine receptor that stimulates cyclic-AMP signaling, involved in motor control, reward, and cognition.

An inhibitory (D2-like) dopamine receptor central to reward and motor function; the primary target of antipsychotic drugs.

The membrane protein (DAT) that clears dopamine from the synapse; the primary target of cocaine and amphetamines.

A state in which the body or mind has adapted to a substance, so that reducing or stopping use causes withdrawal or craving.

A temporary shortfall of a neurotransmitter after a substance has driven it out of storage faster than the neuron can resynthesise and repackage it. It is the usual explanation offered for the low mood, fatigue, and poor concentration that follow heavy stimulant or entactogen use, though the recovery timeline is better documented than the mechanism.

Whether an analytical method can find a substance or its metabolites in a biological sample such as blood, urine, or hair, and at what sensitivity. Routine screens look for a fixed panel of compounds, so a negative result means only that nothing on the panel was found; most substances in this index require a targeted laboratory method to be detected at all.

In a binding assay, the fall in a radiolabeled molecule's binding to a target caused by adding a competing compound, and the measurement from which affinity values are derived. It shows how the two molecules compete at an isolated target; it does not show whether the competitor activates that target or blocks it.

A change to the amount given that is made for a characteristic of the person rather than for the effect sought — most often reduced clearance from impaired kidney or liver function, or another drug competing for the same enzyme. Published adjustments are tied to a measured value such as creatinine clearance, which is why they appear as a table of thresholds rather than a single figure.

A reduction in the number or sensitivity of receptors in response to chronic stimulation — a key mechanism of tolerance.

A compound that produces its effects through two independent pharmacological actions rather than one — receptor agonism alongside monoamine reuptake inhibition, for instance, or transporter blockade at two different transporters. The two contributions can follow different dose-response curves and different interaction profiles, so such a compound need not behave like either of the single-mechanism classes it resembles.

The length of time a substance produces a measurable effect, which depends on factors including its clearance, its metabolites, and how it was taken. It is distinct from how long the substance remains detectable in the body, which can be considerably longer.

How much effect a substance produces once it has bound its target — its intrinsic efficacy — as opposed to how much of it is needed to get there, which is potency. The word carries a separate clinical sense, where efficacy means whether a treatment works for its intended purpose under study conditions; the two are unrelated measures sharing a name, and context decides which is meant.

The movement of a neurotransmitter out of a neuron through a transporter running in reverse — the opposite of the reuptake that transporter normally performs. Compounds producing efflux raise synaptic transmitter levels by a different route than those that merely block reuptake, which is the pharmacological line between a releasing agent and a reuptake inhibitor.

The removal of a substance from the body, taken as metabolism and excretion together — the phase in which concentrations fall once absorption and distribution are finished. Its rate determines how long a compound and its effects persist, and it is normally reported as an elimination half-life rather than as a single time at which a substance is gone.

A protein that speeds up a specific chemical reaction without being consumed by it. In pharmacology, enzymes are usually what break a drug down or build it up into other compounds.

The elimination of a substance or its metabolites from the body, chiefly through the kidneys, liver, or lungs. Along with metabolism, excretion determines how long a drug remains detectable and active.

A formulation engineered to release its drug gradually over hours rather than all at once, so a single unit covers a longer period. The consequence is that one extended-release unit holds more total drug than an immediate-release one, and crushing, chewing, or dissolving it removes the mechanism that was spreading that amount out.

A substance that produces the maximum response a receptor is capable of, and so serves as the reference point against which the efficacy of other compounds at that receptor is expressed. Efficacy is separate from affinity and from potency: a full agonist may bind weakly and still produce the complete effect once enough of it is present.

The point at which tolerance built by previous use has returned to baseline, so a substance produces the response it did before. Reset periods in this reference are mostly community estimates rather than measured figures, and reset is uneven: the tolerance that builds fastest is not always the one that clears first, and behavioural and receptor-level tolerance can recover on different schedules.

An ionotropic GABA receptor forming a chloride channel; the target of benzodiazepines, barbiturates, alcohol, and many sedatives.

A metabotropic GABA receptor that produces slow inhibitory signaling; the target of baclofen and GHB.

A variant in a gene common enough in a population to count as a normal alternative rather than a rare mutation, often sorting people into groups such as poor, intermediate, and rapid metabolizers of a given enzyme. It describes variation at the level of a population, with frequencies that differ between ancestries, unlike a genotype, which is what one individual carries.

The particular gene variants an individual carries, as opposed to the observable trait that results from them. In this corpus the sense is almost always pharmacogenomic: a person's genotype for a metabolizing enzyme can turn the same administered amount into very different exposures, and it accounts for part, though never all, of why responses differ between people.

A Phase II metabolic reaction in which the body attaches glucuronic acid to a compound, making it more water-soluble and easier to excrete. The product is usually inactive, but not always, and a compound can be cleared largely by this route while its Phase I metabolism goes uncharacterized.

The conjugate formed when glucuronic acid is attached to a compound during Phase II metabolism, typically excreted in urine. Glucuronides are usually inactive and are frequently the most abundant marker of an exposure in a urine sample, though detecting one establishes that a compound was present, not when it was taken or how much.

A preparation of liver-cell membrane fragments carrying the enzymes that perform most drug metabolism, used to work out which enzymes act on a compound and what they produce. The results describe what those enzymes can do in a dish; they do not establish what share of an exposure follows that route in a living person.

A reaction in which water splits a chemical bond, most often an ester or an amide, breaking one molecule into two. In this corpus it is usually the activation step for an ester prodrug: enzymes in blood and liver cleave the appended group to release the active compound, so the rate of that cleavage shapes onset and duration.

A chemical reaction that adds a hydroxyl group to a molecule, one of the most common ways the liver modifies drugs during metabolism. The resulting compound is usually more water-soluble and easier for the body to excrete.

The medical condition or circumstance a drug is approved or intended to treat. An approved indication reflects what one country's regulator has reviewed evidence for, not the full range of conditions a substance is prescribed for, studied for, or used for outside medicine.

A substance that increases the amount or activity of a drug-metabolising enzyme, so that other substances cleared by that enzyme are broken down faster and reach lower levels. Induction builds over days and fades over days once the inducer stops, unlike inhibition, which takes effect on the next exposure and is the mirror half of the same interaction pair.

The reduction or blocking of a biological process, such as an enzyme's activity or a receptor's signaling, by another molecule. It is one of the two basic ways a substance can change what the body already does, the other being activation.

A molecule that reduces or blocks the activity of an enzyme, receptor, or transporter it binds to. Many drug interactions trace back to one substance inhibiting an enzyme or transporter that another substance depends on for its own metabolism.

The inhibition constant — the concentration at which a molecule occupies half of a target's binding sites in a competition assay, and the number most receptor binding tables report. A lower Ki means tighter binding, but the value belongs to the assay that produced it: figures for one compound differ across preparations, species, and radioligands, and binding tightly says nothing about what happens once bound.

The amount of a substance sufficient to cause death, sometimes expressed as the median lethal dose (LD₅₀) — the amount at which half of a tested animal population dies. For most compounds in this index no lethal dose has been established in any species, and where an animal figure exists it does not transfer to humans; an absent value indicates that nobody has measured one, not that a substance has no such point.

Proteins in the liver that carry out most of the body's drug metabolism, converting substances into forms that are typically easier to excrete. Genetic differences and other substances can change how active these enzymes are, part of why the same intake affects people differently.

The monoamine oxidase isoform that preferentially metabolizes serotonin and norepinephrine; its inhibition drives the activity of ayahuasca.

The monoamine oxidase isoform that preferentially metabolizes dopamine and phenethylamines; targeted by selegiline in Parkinson's disease.

The account of how a substance produces its effects: which targets it engages and what follows from that engagement. Where direct evidence is missing, effects and risks are sometimes reasoned from mechanism and from what structurally related compounds do; such reasoning is labelled as inference, because a shared mechanism does not guarantee a shared outcome.

The sequence of enzymatic steps by which the body converts a substance into its metabolites. Two substances that share a pathway can compete for the same enzymes, which is one mechanism behind drug interactions.

The set of chemical processes by which the body converts a drug into other compounds, usually making it easier to excrete. The resulting compounds can be inactive, equally active, or more active than the original substance.

A compound the body produces while chemically transforming a drug. Some metabolites are inactive; others carry much of the substance's effect, its duration, or its toxicity, which is why two people who took the same thing can differ.

The membrane proteins that carry serotonin, dopamine, and norepinephrine back into the cells that released them, known as SERT, DAT, and NET. A compound's relative activity across the three is one of the main determinants of whether it presents as a stimulant, as an entactogen, or as neither.

The membrane protein (NET) that clears norepinephrine from the synapse; a target of stimulants and some antidepressants.

An ionotropic glutamate receptor essential to synaptic plasticity and memory; its blockade produces the dissociative effects of ketamine, PCP, and nitrous oxide.

A chemical messenger released by one neuron to signal another, typically by binding a receptor across the synapse. Most psychoactive substances act by mimicking, blocking, or altering the release or reuptake of one or more neurotransmitters.

A chemical reaction in which a molecule loses electrons, often through the addition of oxygen, and one of the most common ways liver enzymes begin breaking a drug down. The resulting metabolites may be inactive, active, or in some cases more toxic than the parent compound.

The substance in the form it was taken, before the body chemically alters it — the counterpart to the metabolites it becomes. The distinction matters for duration and for testing, since a metabolite can outlast the parent compound in the body, carry effects of its own, or be the only form a laboratory method looks for.

The maximum a measured or a felt quantity reaches after a substance is taken — the highest concentration in blood, or the most intense stretch of the subjective experience. The two do not necessarily coincide, and neither marks the end of anything: concentrations, impairment, and after-effects can persist well past the peak.

An interaction in which two substances act on the same receptor, transmitter system, or physiological function, so their effects add to, oppose, or distort one another. It is distinguished from a pharmacokinetic interaction, where one substance changes how much of the other the body takes up, distributes, or clears — here the amount present is unchanged, and what that amount does is not.

An interaction in which one substance changes how much of another reaches the bloodstream or how long it stays there, usually by inhibiting or inducing the enzymes that metabolize it. It is distinguished from a pharmacodynamic interaction, where both substances act on the same system; the two can occur in the same pairing, and the seriousness of any specific pairing is recorded with that pairing and its sources.

What the body does to a substance over time — absorption, distribution, metabolism, and excretion — usually summarised as parameters such as Tmax, Cmax, half-life, clearance, and volume of distribution. It is the counterpart to pharmacodynamics, which describes what the substance does to the body; for many compounds indexed here none of these parameters have been measured in humans.

The attachment of a phosphate group to a protein by an enzyme, switching that protein's activity, location, or binding partners. It is one of the cell's principal control steps and it recurs throughout tolerance mechanisms: kinases phosphorylate a receptor that has been activated repeatedly, which recruits arrestin, pulls the receptor off the cell surface, and blunts the response to the next exposure.

The liquid component of blood in which cells, proteins, and dissolved substances circulate, including drugs and their metabolites. Measuring a substance there is the standard way pharmacology tracks how much of it is in the body over time.

The amount of a substance measured in the liquid portion of blood at a given time, used to track how a drug rises and falls in the body after it is taken. It is a proxy for how much drug is available to act on tissues, not a direct measurement of effect.

A person whose genotype for a drug-metabolising enzyme yields little or no functioning enzyme, so substrates of that enzyme clear slowly and build to higher levels than in most people. The phenotype is defined per enzyme rather than per person, and it inverts for a prodrug, where slow metabolism means less active compound rather than more.

The amount of a substance needed to produce a given effect: a more potent compound reaches that effect at a smaller amount than a less potent one. Potency describes only the amount required, not the character of the effect or its ceiling, which is why a highly potent compound is not thereby a stronger experience — only one in which small differences in amount matter more.

Administration of one substance before another in a study, to test whether the first alters the second's effects. It is the standard design for isolating an interaction mechanism, and what it shows holds for the species, order, and timing tested rather than transferring automatically to other arrangements.

An inactive or less-active compound that the body metabolizes into the active drug, as psilocybin is converted to psilocin.

The share of a substance in the bloodstream that is attached to plasma proteins rather than travelling free. Only the unbound portion can leave the blood to act on tissue or be cleared, so protein binding governs how much of a measured concentration is actually available to do anything.

A radioactively labeled molecule used in laboratory binding assays to measure how a receptor or other target interacts with candidate drugs. Radioligand studies are a primary source of the affinity and selectivity data cited in pharmacology.

The arrival of a substance's effects soon after administration, governed mainly by the route and by how quickly the compound reaches the brain. Onset speed shapes how reinforcing an exposure feels independently of what the compound does once it arrives, which is why the same substance is described differently by route.

A protein, usually sitting in a cell membrane, that a signalling molecule binds to and thereby changes what the cell does. Most psychoactive substances act by binding receptors the body's own neurotransmitters use, so a compound's effects trace largely to which receptor subtypes it reaches and what it does once bound.

The change a receptor undergoes after a molecule binds it, triggering a signal inside the cell. Whether a bound molecule activates a receptor, blocks it, or falls somewhere in between defines much of its pharmacological classification.

The physical attachment of a molecule to a receptor, the first step by which most drugs produce an effect. Binding does not guarantee activation; some molecules attach to a receptor without triggering its downstream signal.

A rapid loss of a receptor's responsiveness while an agonist is still bound, produced by phosphorylation — typically by G-protein-coupled receptor kinases — that uncouples the receptor from its signalling partners. It is the first step in a sequence that also includes internalisation and downregulation, and it reverses on a far shorter timescale than the loss of receptors themselves.

The withdrawal of receptors from the cell surface into the interior of the cell after sustained or beta-arrestin-biased agonist activity. It puts receptors out of reach of the drug and is the molecular basis of tachyphylaxis — tolerance appearing within a single exposure — and is distinct from downregulation, which reduces how many receptors the cell makes.

The share of a receptor population bound by a substance at a given time, as distinct from the total amount of substance present in the body. Occupancy depends on both how much substance is available and its affinity for the receptor.

How long a molecule stays bound to its receptor before dissociating, a kinetic property distinct from how tightly it binds at equilibrium. Slow dissociation can extend a substance's effect beyond what its concentration in blood would predict, though for most compounds here the value has never been measured.

Distinct variants of a receptor family that share a general mechanism but differ in structure, location in the body, or downstream effect. A substance's selectivity among subtypes helps explain why it produces some effects and not others.

A receptor taken together with the signalling machinery it recruits and the downstream effects that follow — the unit at which a drug's action is usually described. A compound may act almost entirely through one receptor system or divide its effects between two, which is part of why the same substance can present a different character as the amount taken changes.

The membrane protein (SERT) that clears serotonin from the synapse; the target of SSRIs and a key site of action for MDMA.

The degree to which a substance acts on one target, such as a specific receptor subtype, while sparing others. A highly selective substance tends to affect fewer systems than one that binds broadly.

Any substance that raises serotonin signalling, whether by releasing it, blocking its reuptake, slowing its breakdown, or acting directly at its receptors. The category gathers compounds from very different classes — antidepressants, opioids, stimulants, psychedelics — which is why serotonin syndrome is discussed at the level of the category rather than of individual drugs.

The combined serotonergic activity produced by everything acting on that system at one time — releasers, reuptake inhibitors, receptor agonists, and drugs that slow serotonin's breakdown. It is an additive concept rather than a measured quantity: it names why several serotonergic agents together carry a risk that none carries alone, without supplying a threshold at which that risk begins.

The forced movement of serotonin out of the neuron and into the synapse, produced when a substance enters the cell and reverses the serotonin transporter rather than simply blocking it. It raises extracellular serotonin further than reuptake inhibition alone, and it is the event underlying the serotonergic load that gives releasing compounds a different combination profile from inhibitors.

The chain of molecular events inside a cell that follows receptor activation, each step triggering the next and amplifying the original signal. Which cascade a receptor sets off depends partly on the molecule that bound it, so two compounds acting at the same receptor can produce different downstream effects.

The condition reached during repeated dosing at which the amount of drug entering the body over an interval equals the amount cleared, so concentrations settle around a stable average instead of climbing. How long it takes to arrive is governed by the substance's half-life rather than by the size of each dose.

A molecule that an enzyme or transporter acts on — the thing being processed, as distinct from an inhibitor or inducer, which changes how fast the processing runs. Identifying a substance as a substrate of a particular enzyme names the route it depends on for clearance, and that dependency is the mechanism behind most metabolic drug interactions.

One of the individual protein chains that assemble into a multi-part receptor or channel, such as the five that form a GABA-A receptor. Which subunits a receptor is built from determines where its binding sites sit and what fits them, so two receptors of the same family can respond to quite different drugs.

Producing effects that mimic activation of the sympathetic nervous system: raised heart rate and blood pressure, dilated pupils, rising body temperature. The word describes a pattern of physiological action rather than a chemical family, so compounds with unrelated structures can be sympathomimetic.

The total amount of a substance that reaches the bloodstream and stays available to the body across an exposure, rather than the concentration at any single moment. It rises when clearance falls — impaired liver or kidney function, or another compound competing for the same enzymes — which is why it is discussed wherever metabolism is altered.

A trace amine-associated receptor that modulates monoaminergic signaling; a target of amphetamines and an emerging antipsychotic target.

A rapid loss of response that develops within a single session or across closely spaced doses, generally through receptor internalisation rather than the slower adaptations behind ordinary tolerance. The timescale is the distinction: tachyphylaxis emerges while the substance is still acting, and re-dosing tends not to restore the original effect.

The effect a substance produces that is the reason for using it medically — analgesia, sedation, relief of mood symptoms — as distinct from its adverse effects. The distinction is one of intent rather than mechanism: the same receptor action can be the therapeutic effect in one context and the adverse effect in another, and tolerance can develop to one while the other persists.

The time from administration to the highest concentration a substance reaches in blood — the peak, in pharmacokinetic notation. It records when a substance is most concentrated, not when its effects are strongest, and the two can diverge; for most compounds in this index Tmax has never been measured in humans.

A diminished response to a substance after repeated use, requiring larger doses for the same effect — a key driver of escalating use.

A protein embedded in a cell membrane that moves specific molecules across it, including many drugs and neurotransmitters. Transporters are common drug targets because blocking or reversing one changes how much of a molecule accumulates inside or outside a cell.

An increase in the number or sensitivity of receptors in response to reduced stimulation, contributing to withdrawal and rebound effects.

A transporter that packages monoamine neurotransmitters into synaptic vesicles; its action is reversed by amphetamines.

A calculated value relating the amount of a drug in the body to its concentration in plasma, used to estimate how widely a substance spreads into tissue versus staying in the bloodstream. A high value suggests a drug accumulates in tissue; a low value suggests it stays mostly in blood.

The cluster of symptoms that appear when a substance the body has adapted to is reduced or stopped; severity and danger vary widely by drug class.

The likelihood that a substance will be used compulsively or non-medically, shaped by its pharmacology, onset, and subjective effects.

Tolerance to one substance that reduces sensitivity to another with a shared mechanism, as among many psychedelics.

The metabolism of an oral drug by the gut and liver before it reaches systemic circulation, often sharply reducing bioavailability.

The time required for the concentration of a substance in the body to fall by half, governing how long effects last and how quickly it clears.

A substance that binds a receptor and produces the opposite effect of an agonist, reducing baseline activity.

An enzyme that breaks down monoamine neurotransmitters; its inhibition (by MAOIs) raises serotonin, dopamine, and norepinephrine and underlies dangerous interactions.

A metabotropic acetylcholine receptor blocked by deliriants such as diphenhydramine and atropine, producing anticholinergic effects.

A rare, life-threatening reaction to antipsychotic (dopamine-blocking) drugs, marked by rigidity, high fever, and autonomic instability.

An ionotropic acetylcholine receptor activated by nicotine, mediating fast cholinergic transmission at neuromuscular junctions and in the brain.

A substance that activates a receptor only partially, producing a submaximal response even when fully bound.

A bodily adaptation to a substance such that stopping or reducing it produces a withdrawal syndrome; distinct from addiction and possible even with appropriate medical use.

The return of symptoms, often more intensely than before, when a substance that suppressed them is stopped.

A substance that causes a neuron to release stored neurotransmitter, as amphetamines do with dopamine and norepinephrine.

A substance that blocks reabsorption of a neurotransmitter into the neuron, raising its concentration in the synapse.

A potentially life-threatening state of excess serotonergic activity — agitation, tremor, hyperthermia, autonomic instability — often from combining serotonergic drugs such as MAOIs with SSRIs or MDMA.

An intracellular chaperone protein acting as a receptor, modulated by DMT and some dissociatives, and implicated in neuroprotection and mood.

The ratio between the dose that causes toxicity and the dose that produces the desired effect; a higher index indicates a wider safety margin.

An inhibitory adrenergic receptor that reduces norepinephrine release; the target of clonidine and dexmedetomidine, used to ease withdrawal and induce sedation.

The binding of an arrestin protein to a receptor that has been activated and phosphorylated, which uncouples it from G-protein signalling, draws it into the cell, and initiates a separate signalling arm of its own. It is one of the two outputs against which biased agonism is described, and it is reported as a measured assay result — including as an absence, when a compound has never been screened for it.

An opioid receptor subtype (δ) involved in analgesia and mood regulation.

An opioid receptor subtype (κ) associated with dysphoria and sedation, and the psychoactive effects of salvinorin A.

The opioid receptor subtype (μ) responsible for the analgesia, euphoria, and respiratory depression of opioids such as morphine and fentanyl.

A neurotransmitter mediating muscle activation, autonomic function, attention, and memory, acting at nicotinic and muscarinic receptors.

The state a receptor or neural pathway enters when a binding molecule or a signal from other neurons causes it to begin producing its downstream effect. The same receptor can be activated to different degrees, which is part of why partial and full agonists behave differently.

A signaling nucleoside that promotes sleep and suppresses arousal as it accumulates during waking hours; caffeine acts by blocking its receptors.

An almond-shaped brain structure central to processing fear, threat, and emotional salience.

An endogenous cannabinoid that binds cannabinoid receptors; its name derives from the Sanskrit 'ananda' (bliss).

The level of physiological and cognitive activation in the body and nervous system, running from drowsiness through alert wakefulness to agitation, and driven largely by noradrenergic signaling. It is a dimension rather than a state, and the same rise can be experienced as focus or as anxiety depending on the person and the setting.

Brain-derived neurotrophic factor — a protein supporting neuron survival, growth, and synaptic plasticity, upregulated by some antidepressants and psychedelics.

The prevention of a receptor, channel, or transporter from carrying out its normal function, typically by a molecule that occupies its binding site without activating it. A blockade opposes the effect that the same site would otherwise produce when activated.

The stalk joining the cerebral hemispheres to the spinal cord, housing the nuclei that govern breathing, heart rate, arousal, and the traffic of signals in both directions. It carries particular weight in drug pharmacology because the respiratory rhythm generators sit there: sedatives and opioids acting on those nuclei reduce the drive to breathe independently of anything felt elsewhere.

A membrane pore that admits calcium ions into a cell when it opens; the voltage-gated form opens in response to electrical change at the nerve terminal and triggers neurotransmitter release. Reducing how often it opens lowers how much transmitter is released, a step shared by opioids acting through their own receptors and by gabapentinoids that bind an auxiliary subunit of the channel itself.

The class of monoamine signalling molecules built on a catechol ring: dopamine, norepinephrine, and epinephrine. They are grouped because many stimulants act on all three through shared transporters and shared metabolism, so an effect described as catecholaminergic rarely belongs to just one of them.

The brain and spinal cord, as distinct from the nerves running through the rest of the body. A substance produces psychoactive effects only if it reaches this compartment, which is why blood-brain-barrier penetration is reported alongside receptor activity: strong binding in a test tube means nothing if the molecule never crosses.

A set of interconnected neurons that work together to carry out a particular function, such as reward processing or the fear response. Circuits, rather than single neurons or single receptors, are the level at which most psychoactive effects are best understood.

The degree to which activity in separate brain regions stays in step, measured as correlation between their signals over time. In this corpus it usually refers to the internal coherence of the default mode network, whose acute breakdown under classic psychedelics tracks reported dissolution of self — a correspondence between a network measure and a subjective report, not an explanation of either.

The outer layered sheet of neurons covering the brain's surface, involved in functions including perception, thought, and voluntary movement. Different cortical regions specialize in different functions, so a substance's effects often trace to which regions it reaches most strongly.

The branching structure of a neuron's dendrites, and the growth of new branches that extends it. Classical psychedelics are described as promoting this growth alongside new dendritic spines — the basis of the psychoplastogen hypothesis — though the evidence comes largely from cell culture and rodent work rather than from human brains.

The concentration of a particular type of receptor, channel, or neuron within a given area of tissue. Density can change with chronic substance exposure, which is one mechanism behind tolerance and withdrawal.

Interference with the normal operation of a neural circuit, network, or signaling pathway, arising from a substance, injury, or disease process. The functional consequences depend on which circuit is affected and how much of its ordinary signaling is displaced.

A catecholamine neurotransmitter central to reward, motivation, and motor control; implicated in the reinforcing potential of stimulants.

The direct measurement of electrical activity in cells and tissue, used in pharmacology to record what a compound does to a receptor or ion channel in real time rather than inferring it from binding data. Recordings are usually made in cell lines or brain slices, and for most compounds in this corpus no electrophysiology data exists at all.

Endogenous opioid peptides that reduce pain perception and produce well-being by acting at opioid receptors.

A catecholamine hormone and neurotransmitter (adrenaline) that mediates acute stress responses, raising heart rate, blood pressure, and blood glucose.

How readily a neuron or a region of cortex fires in response to input, set by the running balance between excitatory and inhibitory signalling. Substances move it in either direction — by reducing inhibition, by adding excitatory drive, or through the rebound that follows adaptation to a depressant — which is why seizure, tremor, and heightened sensory processing recur together as effects.

Neuronal injury or death caused by excessive glutamate signaling and calcium influx.

How much of a gene's protein product a cell actually produces, such as the number of a given receptor type a neuron makes and displays. Expression can change with repeated substance exposure, altering how sensitive a circuit becomes to future exposure.

The principal inhibitory neurotransmitter in the central nervous system; its receptors are the target of benzodiazepines, barbiturates, and alcohol.

The principal excitatory neurotransmitter in the central nervous system, essential to learning and memory; over-activation contributes to excitotoxicity.

An amino acid that acts as an inhibitory neurotransmitter in the spinal cord and brainstem and as a co-agonist at NMDA receptors.

A brain structure essential to memory formation and spatial navigation.

A neurotransmitter and immune signaling molecule regulating wakefulness and allergic responses; sedation from many drugs reflects histamine receptor blockade.

A proposed explanation for how a substance, receptor, or circuit produces an effect, framed so that it can be tested against evidence. Neuroscience discussions often carry several competing hypotheses for the same phenomenon, at different stages of support.

A model of reward that separates the motivational pull toward something — wanting — from the pleasure of getting it — liking — and locates the first in dopamine signalling. It accounts for a pattern reported throughout dependence: the drive to take a substance can grow while the enjoyment of taking it stays flat or fades.

The process by which an experience is encoded into a memory that can later be recalled, depending chiefly on the hippocampus. Several substance classes suppress it while leaving speech and behaviour largely intact, so the gap is generally apparent only afterwards, to the person or to those around them.

The adjustment of a neuron's or circuit's activity up or down, rather than switching it fully on or off. Neuromodulators such as serotonin and dopamine work this way, tuning how other signals are processed rather than carrying a message on their own.

A class of neurotransmitters built around a single amine group — serotonin, dopamine, norepinephrine and their relatives — involved in mood, arousal, appetite, movement, and perception. Most stimulants, antidepressants, and classical psychedelics act somewhere in this system, at its receptors, its transporters, or the enzymes that break it down.

The drive to pursue something, generated largely by dopamine signaling in the pathway running from the midbrain to the forebrain. Dependence research treats it as separable from pleasure: wanting and liking arise from different systems, and repeated exposure can raise one while lowering the other.

The end of an axon, where a neuron packages neurotransmitter into vesicles and releases it into the synapse. It is the site releasing agents act on: they enter the terminal through the same transporters that normally recycle transmitter, then drive the stored supply back out.

A compensatory change in neurons — in receptor number, sensitivity, or signalling — that develops in response to repeated exposure and shifts the baseline the system operates from. It is the mechanism underneath tolerance, withdrawal, and sensitization; where neuroplasticity names a general capacity, this word names an adjustment made against a persistent perturbation.

The formation of new neurons, which continues in limited brain regions in adulthood and may be promoted by some substances.

A nerve cell specialized to receive, process, and transmit signals, chiefly through electrical impulses and chemical messengers released at synapses. Neurons form the networks that make up the brain and nervous system, and drugs act on them by altering these signaling steps.

The brain's capacity to reorganize its structure and connections in response to experience, learning, or injury.

Damage to neurons or their function caused by exposure to a substance, injury, or disease process. It can be reversible or lasting, and evidence for it in humans is often harder to establish than evidence from cell or animal studies.

The presynaptic event in which a neuron empties vesicles of transmitter into the synapse, triggered by calcium entering through voltage-gated channels when an impulse arrives. Many substances act on this step rather than at the receiving receptor — opioids and cannabinoids suppress it presynaptically, while releasing agents drive transmitter out independently of any impulse.

A catecholamine neurotransmitter and stress hormone driving arousal, vigilance, and the sympathetic 'fight-or-flight' response.

A peptide hormone and neurotransmitter involved in social bonding and trust, sometimes implicated in the prosocial effects of MDMA.

The subjective experience of something feeling good, the hedonic component of a drug effect as distinct from the drive to seek it again. The two are separable in the brain, which is why the pleasure of repeated use can diminish while the pull toward it does not.

The magnitude of a neural or physiological system's response to a given stimulus — how strongly the amygdala responds to a threatening face, for instance. Reduced threat reactivity is the mechanism proposed for the relief benzodiazepines produce and for the lowered social defensiveness reported with MDMA, though a smaller response on a scan does not by itself establish what the person experienced.

The brain's response to an experience that reinforces the behavior that produced it, mediated largely by dopamine signaling in circuits connecting the midbrain to the forebrain. Substances that strongly engage this system are more likely to be sought again, which is why it features heavily in dependence research.

Mental activity directed at oneself: recalling one's own past, anticipating one's own future, evaluating how one appears to others. It is the function most consistently attributed to the default mode network, and its reduction is the neural account usually given for ego dissolution under psychedelics.

A progressively stronger response to the same exposure as it is repeated, running in the opposite direction to tolerance. The two can develop at once in different systems, which is how animal work describes stimulant use in which the motivational pull grows while the pleasurable effect fades.

Psychedelics whose primary mechanism is agonism at the serotonin 2A receptor, a category that includes psilocybin, LSD, and DMT. The term distinguishes this group from other substances sometimes loosely called psychedelic that work through different mechanisms.

The overall level of serotonin signalling at the synapse, set by how much transmitter is released, how quickly it is cleared, and how sensitive the receiving receptors are. Compounds raise it by different mechanisms — blocked reuptake, forced release, blocked breakdown — but converge on the same state, which is why serotonin toxicity is discussed as a property of the combined load rather than of any one mechanism.

A monoamine neurotransmitter (5-hydroxytryptamine) involved in mood, perception, sleep, and appetite; the primary target of classical psychedelics and SSRIs.

The formation of new dendritic spines, the small protrusions along a neuron's branches where most excitatory synapses are made. It is a narrower claim than neuroplasticity: showing that a substance increases spine density in cortical neurons establishes a structural change, not that the change accounts for any lasting effect in a person.

The formation of new synapses between neurons, including the growth of the dendritic spines that receive them. It is distinct from neurogenesis, the making of new neurons, and most evidence for substance-driven synaptogenesis comes from animal and cell studies rather than from human brains.

A central relay that filters and routes sensory and motor signals to the cortex; implicated in the sensory gating disrupted by psychedelics.

The process by which a signal passes from one neuron to the next, typically through a neurotransmitter crossing the synapse and binding to a receptor on the receiving cell. Most psychoactive substances act by altering some step of this process rather than acting on neurons directly.

The receptor, tropomyosin receptor kinase B, that BDNF binds to, setting off the intracellular signalling that supports neuron survival and the growth of new synaptic connections. Some psychedelics have been reported to bind it directly rather than only through BDNF, one proposed basis for the lasting structural changes attributed to them — a finding so far from cell and animal work rather than human measurement.

A network of brain regions active during rest and self-referential thought, whose disruption is associated with the ego-dissolving effects of psychedelics.

A brainstem nucleus that is the brain's main source of norepinephrine; hyperactive during opioid withdrawal.

A cellular signalling kinase, the mechanistic target of rapamycin, that governs protein synthesis and cell growth and, in neurons, the formation of new dendritic spines. It appears in this reference as part of the proposed pathway — alongside BDNF and TrkB — by which psychedelics are thought to promote structural plasticity, a hypothesis resting largely on cell and animal work.

A dopamine pathway from the ventral tegmental area to the nucleus accumbens that mediates reward and is central to addiction.

A forebrain structure central to reward and reinforcement, and a key node in the brain's response to addictive drugs.

The frontmost region of the cortex governing executive functions — planning, decision-making, working memory, and impulse control.

Brainstem nuclei that are the principal source of serotonin projections throughout the brain.

A midbrain region that is a primary source of dopamine for the reward system.

The rule-governed systems by which chemical names are built, from formal IUPAC naming to family conventions such as Shulgin's 2C series, the bk- prefix marking a beta-keto analogue, and the -azine suffix of the phenothiazines. A name constructed this way encodes structure, not effect: compounds with closely related names can behave very differently in the body.

The 'handedness' of a molecule that exists as non-superimposable mirror images, which can determine how strongly it acts at a receptor.

The breakdown of a compound into other chemical species, driven by factors such as heat, light, moisture, or reaction with other substances. A degraded sample may contain less of the original compound and unknown breakdown products, which is why storage conditions and age matter for what is actually consumed.

A compound produced by modifying the structure of a parent compound, typically by adding, removing, or replacing one or more atoms. Derivatives can differ substantially from their parent in potency, duration, or selectivity despite the structural resemblance.

One of a pair of molecules that are non-superimposable mirror images; the two forms can differ substantially in potency and effect.

The neutral, non-salt form of a drug, which is typically more lipid-soluble and volatile than its salt and so behaves differently by route of administration.

A member of a series of compounds differing by a repeating unit, such as an added carbon, often with graded changes in potency or duration.

One of two or more compounds with the same molecular formula but a different arrangement of atoms, which can produce markedly different effects.

A measure of how readily a compound dissolves in fats and oils relative to water. Higher lipophilicity generally helps a compound cross cell membranes and the blood-brain barrier, one factor among several that shapes onset and duration.

A deliberate change to part of a molecule's structure, such as adding a substituent or altering a ring. It is the general term for the step that turns one compound into a related one, and even a small modification can shift how a substance behaves in the body.

A discrete, named part of a molecule that is treated as a unit because it behaves as one chemically, such as a ketone moiety or an acetoxy moiety. Naming the moiety is how chemical writing points at the part of a structure responsible for a property; it marks a region of the molecule, not a substance with any separate existence.

How readily a compound crosses a biological membrane, such as a cell wall, the gut lining, or the blood-brain barrier. It follows partly from lipophilicity and from whether the molecule is charged at body pH, but it is not the same property as either: permeability describes movement across a barrier, while solubility describes dissolving in a medium and a lipid-soluble molecule can still cross poorly.

The arrangement of structural features a molecule must present in order to bind a given target and produce an effect — the essential pattern, abstracted from the rest of the molecule. It explains how compounds that look unrelated can act at the same receptor, and it describes what binding requires rather than how strongly it occurs or what follows from it.

The form of a compound in which its basic or acidic group is paired with a counter-ion, such as a hydrochloride, sulfate, or fumarate salt. Salts are generally more water-soluble and more stable in storage than the freebase, and because the counter-ion carries weight of its own, equal masses of salt and freebase do not contain equal amounts of active compound.

The core ring system or structural framework shared by a family of related compounds. Substituents attached to a scaffold can shift potency, selectivity, or duration while leaving the parent structure recognizable.

The chain of atoms attached to a molecule's core ring or backbone, as distinct from that core itself. Much of what separates one member of a chemical family from another sits in the side chain, and changes to its length, branching, or substituents can shift potency, duration, or which targets the compound reaches.

The extent to which a compound dissolves in a given solvent, such as water or fat. It shapes how a substance moves through the body and how it can be formulated, without determining either outcome by itself.

A compound's tendency to resist chemical change under given conditions, such as light, heat, moisture, or pH. A less stable compound degrades faster, which affects storage, shelf life, and how closely a tested sample reflects what is eventually consumed.

The three-dimensional arrangement of atoms in a molecule, including whether a compound has a defined configuration at all or exists as a mixture of mirror-image forms. Where a record does not specify it, the configuration is unstated rather than known to be absent — and because the forms can act differently at a receptor, an unspecified configuration leaves the pharmacology incompletely described.

An isomer with the same atomic connections but a different three-dimensional arrangement, such as mirror-image enantiomers.

The physical size and crowding of a group of atoms, which can obstruct another molecule's access to a nearby site. In this corpus it recurs as the property governing how readily a prodrug's added group is cleaved off: bulkier groups shield the bond, slowing conversion and shifting onset and duration.

The temperature, light, moisture, and atmosphere a compound is kept in, which together govern how fast it degrades. They matter most for compounds prone to oxidation or hydrolysis, where material held warm, damp, or in light can differ in composition from the same material kept cold, dry, and dark.

The pattern linking changes in a molecule's structure to changes in what it does at its targets, mapped by comparing a series of related compounds. It is the reasoning that licenses class-level statements about an untested compound, and inference is what it yields: a predicted profile, not a measured one.

An atom or group of atoms that replaces a hydrogen on a molecule's core structure. Substituents are what turn one member of a chemical family into another, often changing potency, selectivity, or how quickly the body breaks the compound down.

The chemical process of building a compound from simpler starting materials through one or more reactions. It distinguishes compounds manufactured in a lab from those isolated directly from a natural source, even when the resulting molecule is identical.

A specific group of atoms within a molecule responsible for its characteristic chemical behavior and often its pharmacological activity.

An isomer differing in the position of a functional group on the molecule, often altering activity (as among substituted phenethylamines).

A 50:50 mixture of a molecule's two mirror-image forms, whose net effect reflects the contribution of each enantiomer.

Produced by chemically modifying a naturally occurring precursor, combining a natural starting material with laboratory synthesis — as with LSD, derived from ergot alkaloids.

A compound with a molecular structure closely related to another, often differing by a single group; analogs frequently share — but can diverge in — pharmacological effects.

Produced by chemical synthesis in a laboratory rather than extracted from a natural source. A synthetic compound may be structurally identical to a naturally occurring one or entirely novel.

A condition of compulsive substance use despite harm, driven by changes in the brain's reward and motivation circuits; distinct from physical dependence alone.

The basic condition of being conscious of something — surroundings, the body, or one's own mental activity — and the thing most contemplative practice works on directly. It varies in scope and in stability rather than being simply present or absent, which is why this reference records both its narrowing or loss under some substances and its deliberate training in practices.

A broad class of substances that slow activity in the central nervous system, producing effects such as sedation, muscle relaxation, or reduced anxiety. The class spans several different mechanisms and includes both prescribed medications and substances used recreationally.

An improvement in attention, memory, or reasoning above a person's own baseline, attributed to a substance or a device. The claim is made far more often than it is demonstrated: meta-analyses of stimulants in healthy, rested adults find no reliable gain, and the sense of performing better is itself among the effects several of these compounds produce.

An intense subjective urge to use a substance, a central feature of addiction and a common trigger for relapse.

Hallucinogen Persisting Perception Disorder — the persistence or recurrence of visual disturbances such as trails or halos after hallucinogen use has ended.

A sustained affective state that colours experience over hours or days, distinct from a brief emotional reaction to a particular event. It appears on both sides of a substance's arc in this reference — as something a compound lifts or flattens while it acts, and as the low mood commonly reported afterward as monoamine signalling returns toward baseline.

Thinking marked by unfounded suspicion — that others intend harm, that one is being watched or conspired against — occurring on a range from passing wariness to fixed conviction. It names a symptom rather than a diagnosis, it can appear during intoxication in people with no psychiatric history, and when it comes with loss of contact with reality it is a psychiatric emergency.

The processing by which raw sensory input becomes an experienced world of objects, sounds, bodies, space, and time. It is the faculty most visibly altered by the substances and practices indexed here — in vision, in body sense, and in the felt passage of time — which is why effect records treat changes in perception separately from changes in mood or thought.

A mental state involving loss of contact with reality, such as delusions or hallucinations, which some substances can precipitate in vulnerable individuals.

Describing a substance, or an effect, that produces states resembling psychosis — disordered thought, hallucinations, paranoia — in people who have no psychotic illness. Resemblance is all the term claims: these states follow a known exposure and usually resolve as it clears, though psychotomimetic potential is why a history of psychotic illness is recorded as a contraindication for several classes.

The process by which a substance's effects increase the likelihood of repeated use; central to how addictive potential develops.

A return to substance use after a period of abstinence; a common and expected part of recovery rather than a failure.

Whether an experience, a memory, or a mood is felt as pleasant or unpleasant — the positive-to-negative axis of emotion, separate from how intense it is. It is the axis on which set and setting exert much of their influence, and it is what shifts when an emotionally charged memory is recalled in an altered state and stored again with a different feeling attached to it.

A contested term for a state of severe agitation and physiological stress sometimes described in the context of stimulant intoxication.

A pattern of emotional or cognitive reliance on a substance — craving and difficulty functioning without it — without necessarily a physical withdrawal syndrome.

The rate at which blood moves through a tissue or organ, such as the brain, the placenta, or the liver. It sets a limit on how fast some drugs are cleared: for compounds the liver strips out almost entirely on each pass, clearance tracks hepatic blood flow rather than enzyme activity, so anything that changes circulation changes exposure.

The force blood exerts against artery walls, expressed as two numbers: the pressure during each heartbeat and the pressure between beats. It's monitored as a vital sign because many substances shift it upward or downward.

The internal temperature the body maintains through its own regulatory processes. It's tracked as a vital sign because substances, exertion, and environment can all push it outside the range the body normally holds steady.

The end of a cell's viability, either through apoptosis, the ordered self-dismantling a cell carries out, or through necrosis, in which it ruptures and spills its contents. Which route a compound produces, and in which cell type, is the standard readout of in-vitro neurotoxicity work; translating that to a living brain requires assumptions the experiment itself cannot supply.

The capacity of a substance to kill or injure cells, usually measured in cultured cell lines such as neurons or hepatocytes. Such results describe what a compound does to cells at the concentrations applied in the dish, and do not transfer directly to a whole organism, where exposure, metabolism, and distribution all intervene.

The number of times the heart beats each minute, typically measured at the wrist or chest. It's one of the vital signs most often tracked around substance use, since it can rise or fall with the drug itself, with exertion, or with anxiety.

Reduced liver function, whether from disease, injury, or age, in a person taking a substance the liver would ordinarily metabolise. It recurs through the contraindication listings here because impaired clearance leaves a compound and its metabolites present longer than expected — a modifier of exposure, distinct from hepatotoxicity, which is damage the substance itself does to the liver.

A rise in body temperature above what the body's normal regulation maintains, distinct from a fever in that it isn't driven by the immune system. It's a sign clinicians watch for because it can mean the body is losing its ability to cool itself, whether from a substance, exertion, or environment.

A fall in core body temperature below the range the body normally maintains, impairing coordination and judgment before it affects heart rhythm. It appears in this corpus in two distinct roles: as a laboratory measure in animal work, where it is one of the four responses in the cannabinoid tetrad, and as a real-world outcome when a substance produces a sensation of warmth while accelerating heat loss in a cold environment.

The immune system's response to injury, infection, or irritation, involving increased blood flow to the area, recruitment of immune cells, and swelling. It appears in this corpus as a named endpoint in specific tissue — the heart muscle, the bladder lining, the brain — and as an outcome some compounds are reported to reduce; the bare word says nothing about which tissue is involved or whether the process is brief or sustained.

The control of movement that keeps actions smooth, accurate, and correctly timed, depending on the cerebellum, motor cortex, and sensory feedback. Its impairment is among the most commonly reported effects of sedatives, dissociatives, and alcohol, and it can outlast the subjective effects a person is using to judge whether they have returned to baseline.

An imbalance in which reactive oxygen species accumulate faster than a cell's antioxidant defences can neutralise them, damaging lipids, proteins, and DNA. It recurs as a mechanism in accounts of drug-related liver and neuronal injury, usually acting together with other stresses such as energy depletion or raised body temperature rather than on its own.

A selective barrier of tightly joined cells that protects the brain by restricting which substances pass from the blood into neural tissue.

Produced within the body's own physiology rather than introduced from an external source, as with endogenous neurotransmitters and hormones.

Produced by a plant, fungus, animal, or other organism rather than synthesized in a laboratory.

A statutory finding that a substance has an established therapeutic application within a country's own regulatory system — one of the criteria the United States Controlled Substances Act uses in assigning a schedule. The finding is jurisdictional rather than scientific: a compound in ordinary medical use in one country can be classified as having no accepted use in another, and evidence of therapeutic potential does not by itself satisfy the test.

Clauses in drug law that extend control to compounds structurally or pharmacologically similar to an already-scheduled substance without naming each one — the Federal Analogue Act in the United States, the analogue provisions of Canada's Controlled Drugs and Substances Act, and state-level equivalents in Australia. What counts as an analogue is decided jurisdiction by jurisdiction, and often only in court, so a compound can fall under such a provision in one country while remaining unscheduled in another.

The most restrictive tier in the United Kingdom's drug classification system, reserved for substances judged to carry the greatest harm. Classification tiers differ by country, so a Class A designation in the UK has no direct equivalent under other nations' scheduling systems.

The middle tier of the three classes in the United Kingdom's Misuse of Drugs Act 1971, carrying lower maximum penalties than Class A and higher than Class C. Classification tiers are national instruments: a Class B designation describes UK law only and says nothing about how the same compound is scheduled elsewhere.

The least restrictive of the three classes in the United Kingdom's Misuse of Drugs Act 1971, carrying lower maximum penalties than Class A or Class B. The class governs penalties only and sits alongside a separate schedule that governs medical availability, and other countries classify on their own systems, so Class C has no direct equivalent abroad.

Canada's federal drug-control statute, which sorts controlled substances into schedules and sets the offences and penalties attached to each. Its schedules are numbered on their own logic, so a Canadian schedule number carries no equivalence to a United States or United Kingdom classification of the same compound.

The United States federal law that sorts drugs and chemicals into five schedules based on their potential for abuse, accepted medical use, and safety under supervision. Other countries run their own, differently structured scheduling systems, so a substance's schedule under this act says nothing about its status elsewhere.

A United Nations treaty that set up international scheduling for psychoactive substances not covered by earlier drug-control agreements. Signatory countries write their own domestic laws to carry it out, so a substance's international schedule doesn't by itself determine its legal status in any one country.

A compound synthesised so that its structure falls outside the wording of existing controlled-substance law while reproducing the effects of a scheduled drug. The term names a legal relationship rather than a chemistry or a risk profile, and it is temporary by nature — such compounds are typically scheduled within a few years of appearing, and analogue provisions in some countries reach them before that, so the status depends on the jurisdiction and the date.

The United States federal agency that enforces the Controlled Substances Act, moves compounds onto and between schedules, and assigns each controlled substance a numeric drug code. Its authority stops at the border: a DEA schedule or code describes United States status only and says nothing about how the same compound is treated anywhere else.

The regime of international treaties, and the national laws written to implement them, that determines which substances are restricted and on what terms. The treaties set a floor rather than a uniform rule, so countries schedule the same compound differently, and many newer compounds are controlled by national action alone with no international listing at all.

The United States Food and Drug Administration, the agency that decides whether a drug may be marketed there and on what terms, and that governs the designations under which an investigational compound proceeds through trials. Its authority is national and separate from scheduling: a compound can lack FDA authorisation while being marketed elsewhere, and approval status does not determine which schedule it sits in.

A United States statute that extends Schedule I and II controls to compounds substantially similar in chemical structure and effect to an already-scheduled drug, where they are intended for human consumption. It is a prosecutorial provision rather than a list, so whether a given compound falls under it is argued case by case; other countries reach novel compounds through their own differently drawn analogue or blanket provisions.

A statute that shields a person who calls for help during a drug emergency — and often the person they called about — from certain drug charges arising out of that call. Coverage differs sharply by jurisdiction in who is protected, what is protected, and whether the protection reaches past arrest to prosecution; many places have no such law at all.

The statutory intent test several drug laws turn on: a compound sold with no stated purpose, or labelled 'not for human consumption', can fall outside a control that attaches once it is intended to be taken by a person. The label is a legal manoeuvre rather than a description of the product — it carries no information about what a sample contains, and it does not travel with the product across jurisdictions that draw the test differently.

Placement of a substance on a schedule of one of the United Nations drug-control treaties, chiefly the 1961 Single Convention and the 1971 Convention on Psychotropic Substances, usually following a recommendation from the WHO Expert Committee on Drug Dependence. Signatory countries write their own domestic law to give effect to it, so international control sets a floor rather than a uniform status, and the resulting schedule and penalties still differ by jurisdiction.

A regulator's approval permitting a medicine to be sold for stated indications, granted on submitted evidence of quality, safety, and efficacy. It is issued country by country or bloc by bloc, so the same compound can be an approved medicine in one jurisdiction, an unapproved investigational drug in a second, and a controlled substance in a third.

A country belonging to a treaty organization or union, in this corpus most often the European Union, whose drug-control instruments each member state implements through its own national law. EU-level monitoring or a common position does not by itself make a substance controlled, so legal status diverges widely between member states and has to be read country by country.

Laws that control new psychoactive substances as a group — by chemical family, by psychoactive effect, or by a blanket prohibition — instead of naming each compound individually. Which compounds a given statute captures differs by jurisdiction and by how its wording is drafted, so a substance never scheduled by name may still be controlled in one country and uncontrolled in another.

A compound sold as an alternative to a controlled drug and not covered by the existing international drug-control treaties, the working category used by monitoring bodies and by the legislation written to catch such compounds. Some jurisdictions control them compound by compound and others through blanket or analogue provisions, so the same substance can be uncontrolled in one country and prohibited in the next.

Having a controlled substance on one's person or otherwise under one's control, the offence most drug statutes define separately from supply. Where the line falls between personal possession and possession with intent to supply is set jurisdiction by jurisdiction — usually through quantity, packaging, or other evidence of intent — and the penalties attached to each side of it differ widely between countries.

A control regime that bans a substance outright rather than regulating its supply, enacted through national scheduling law and the international drug-control treaties that law implements. What is prohibited, and with what consequences, is set jurisdiction by jurisdiction, so one compound can be prohibited in one country, uncontrolled in another, and available under license in a third.

The pursuit of criminal charges against a person for a drug-related offense, brought by the state rather than a private party. Whether it happens, and how severely, varies widely by substance, quantity, jurisdiction, and enforcement priorities at the time.

In European drug control, the formal procedure by which the EU Drugs Agency — the EMCDDA before it — evaluates the health and social risks of a new psychoactive substance and issues the report a control decision is based on. It is one jurisdiction's mechanism among several: other countries schedule through their own procedures, so a substance assessed in Europe may be controlled, uncontrolled, or never examined elsewhere.

The most restrictive tier of the United States Controlled Substances Act, applied to substances the statute treats as having no accepted medical use. The numeral does not travel — other countries number their schedules differently, and some run the order the other way.

The US Controlled Substances Act tier for substances with a recognised medical use that are also judged to carry a high potential for abuse and severe dependence, such as most strong opioids and pharmaceutical stimulants. Placement is a United States federal classification and reflects a regulatory judgment rather than a measurement of harm; other countries schedule the same compounds differently.

The US Controlled Substances Act tier for substances accepted for medical use whose abuse potential is judged lower than Schedule I or II, with dependence liability described as moderate or low. Placement is a United States federal classification, and a substance can sit here while being tightly restricted or unscheduled elsewhere.

The US Controlled Substances Act tier for accepted medical substances judged to have a low potential for abuse relative to Schedule III, which is where most benzodiazepines and several sedatives sit. The tier describes a regulatory ranking rather than a safety margin, and says nothing about how a substance behaves in combination.

The lowest restriction tier of the US Controlled Substances Act, for accepted medical preparations judged to have the least abuse potential, typically low-concentration formulations of otherwise controlled drugs. Placement is a United States federal classification; the same preparation may be sold without restriction in some jurisdictions and prohibited in others.

A formal decision by a government or treaty body to place a substance under control, or to move it between tiers. Each action binds only the jurisdiction that made it, and the corpus records a recurring sequence: control of one compound is often followed by the appearance of a structurally adjacent successor the wording does not reach.

A scheduling status rather than an omission: a compound that appears on no schedule of a given country's drug law. It is jurisdiction-specific and rarely means unregulated — analogue provisions, blanket psychoactive-substances bans, medicines law, and consumer-safety rules can all still reach a compound that no schedule lists.

Taking a substance by mouth so that it is swallowed and absorbed through the gastrointestinal tract. It is the slowest of the common routes to take effect and the most variable — stomach contents, gut transit, and first-pass metabolism in the liver all shape what arrives — so onset and strength differ more between occasions than with routes that bypass the gut.

Administration by needle directly into tissue or the bloodstream — intravenous, intramuscular, or subcutaneous — bypassing absorption from the gut. It delivers a substance faster and more completely than swallowing does, leaves the least room to change course afterwards, and carries risks belonging to the route rather than the substance, including infection, vein damage, and injury at the site.

Administration by drawing a powder into the nose, where it is taken up through the nasal lining instead of passing through the gut and liver first. Onset is faster than by mouth and the effect usually shorter, and the route carries harms to the nasal tissue of its own, apart from those of the substance.

Administration by injection into a muscle, from which the substance is absorbed into the bloodstream over minutes. Onset is slower than by the intravenous route but no vein is needed, which is why emergency medications such as naloxone and midazolam are supplied in forms that can be given this way by someone without clinical training.

Injection into the abdominal cavity, a route used in rodent research because it is quick and consistent to perform and it bypasses the gut. Results from it do not transfer directly to people: it avoids the first-pass metabolism an oral dose meets, and a compound active by this route in an animal can be inactive when swallowed.

Administration directly into a vein, placing a substance into circulation without absorption from the gut or a mucous membrane. Onset is the fastest of any common route, and there is the least room to change course once it has been given.

The way a substance enters the body, such as swallowing, inhaling, injecting, or absorbing it through a mucous membrane. The route shapes onset, intensity, and duration of effects, and carries risks of its own apart from the substance itself.

Administration by injection into the fatty layer beneath the skin, from which a substance passes into the bloodstream more gradually than by intravenous injection. Onset is slower and less abrupt than an intravenous route, and in this corpus the route appears mainly in animal pharmacology, where it is a standard way of giving a compound.

Administration by holding a substance under the tongue so that it passes through the mucous membrane, bypassing the first-pass metabolism an oral dose undergoes. Some of the material is usually swallowed regardless, so the route rarely acts purely sublingually, and how much goes each way varies with the preparation and how long it is held.

A period during which a substance is not being used, whether chosen, imposed, or part of a recovery course. It is the interval over which withdrawal resolves and some adaptations reverse; how much recovers, and how completely, differs by substance and in several cases is still unsettled in the literature.

The likelihood that a substance will be used in ways departing from medical or intended patterns, assessed from self-administration studies, reinforcement measures, and epidemiological data. It is recorded as a property of the substance, though the outcome depends heavily on route, formulation, and circumstance.

The buildup of a substance or its metabolites in the body when repeated administration outpaces elimination. Concentrations settle higher than a single occasion would produce, so effects and toxicity can emerge days into a pattern that has not otherwise changed.

The smallest amount of a substance that produces its characteristic effects by a given route — a threshold at which something begins to be felt, not a span of amounts. It differs between compounds by orders of magnitude and shifts with route, tolerance, and individual physiology, so it marks a boundary rather than a fixed figure.

The component of a product responsible for its effect, as distinct from fillers, binders, carriers, and plant material. In unregulated supply the label and the active ingredient frequently diverge — in identity, in amount, or in the presence of a second ingredient nobody expected — which is the gap analytical testing exists to close.

A sudden loss of kidney function, identified by a rise in waste products in the blood or a fall in urine output. In drug toxicity it usually arrives by way of something else — muscle breakdown releasing myoglobin, prolonged high body temperature, or circulatory collapse — and it can resolve fully or leave lasting impairment depending on how long the kidneys were injured before treatment.

The harm that can arise from a single episode of use, within the hours the substance is active, as opposed to harm accumulating across repeated exposure. It is frequently driven by circumstance rather than by pharmacology — by where a person is, who is with them, and what they may attempt while impaired.

Harm produced by a single exposure or a short run of them, appearing within hours rather than accumulating over a course of use. It is assessed separately from the effects of repeated exposure, and for many compounds in this corpus it is estimated from animal or in-vitro work because human data does not exist.

The outcome when two substances acting on the same target produce a combined effect equal to the sum of their separate effects. It is the baseline case in interaction arithmetic, set against potentiation, where one compound amplifies the other beyond that sum; which of the two applies to a given pairing is recorded in the interaction layer with its sources.

A substance present in a product other than the one it is sold as, whether added to bulk it out or imitate it, or arriving through contaminated manufacture. Reagent testing gives a presumptive check on what is present but cannot rule out everything else in a sample; identifying an adulterant reliably takes laboratory analysis.

Unwanted effects attributed to a substance, ranging from the mild and self-limiting to the medically serious. The term carries a judgement that the substance caused the effect, which is what distinguishes it from an adverse event, where the link is only temporal.

Harmful occurrences recorded during a study or after a substance is taken, whether or not the substance caused them. The term is deliberately agnostic about cause, which is what separates it from an adverse effect.

What is done in the hours and days after an experience ends — rest, food, sleep, contact with someone, and review of any records made at the time. It is narrower than integration, the longer work of making sense of what happened, and the two are named separately because some practices are described as calling for neither.

Hostile or combative behaviour directed at people or surroundings, seen in stimulant intoxication, in withdrawal, and in states of confusion or fear. In emergency descriptions it sits beside agitation as a state that can no longer be settled by calm contact; the word reports the behaviour, not what is driving it.

A state of motor restlessness and heightened arousal, usually with irritability, difficulty staying still, and subjective unease. It appears in stimulant toxicity, in withdrawal, and in acute anxiety, and matters clinically because sustained agitation adds heat, exertion, and fluid loss to whatever caused it.

The passage carrying air from the mouth and nose to the lungs. It recurs throughout emergency guidance because sedation, seizure, and vomiting can obstruct it, and because obstruction causes harm faster than most other acute problems.

A heartbeat that is irregular, too fast, or too slow because the heart's electrical conduction has been disturbed. The term names a mechanism rather than a level of seriousness: some arrhythmias produce no sensation at all, while others stop the heart from moving blood effectively.

The entry of vomit, fluid, or other foreign material into the airway and lungs instead of the stomach. A sedated or unconscious person loses the reflexes that normally keep the airway clear, and aspiration is a recorded cause of death at exposures the body would otherwise have survived.

Erratic swings in the functions the autonomic nervous system regulates without conscious control — heart rate, blood pressure, temperature, sweating, pupil size. It is a feature of severe toxic states such as serotonin syndrome and neuroleptic malignant syndrome, and it is the instability itself, rather than any single reading, that marks the state as advanced.

A heart rate slower than the person's usual resting range. Like its counterpart tachycardia it is a sign rather than a diagnosis — sedatives, opioid and alpha-2 agonists, athletic conditioning, and vagal responses all produce it — and in depressant contexts it is usually recorded alongside falling blood pressure rather than on its own.

Disease of the heart muscle itself, in which the walls thicken, stiffen, or dilate and the heart pumps less effectively. It appears in this corpus as an outcome attributed to exposure — the dilated form documented in long-term heavy alcohol use, the stress-induced form described after acute catecholamine surges — and not only as a pre-existing condition that shapes how an exposure is tolerated.

Damage to heart muscle or to the electrical conduction that coordinates its beat, caused by exposure to a substance. Much of the evidence for it comes from cell and animal work, such as screening for effects on cardiac ion channels; that establishes a mechanism by which harm could occur, not how often it occurs in people.

Pain, pressure, or tightness felt in the chest, listed across this reference among the signs that mark a drug emergency. It is a symptom rather than a diagnosis: strain on the heart produces it, but so do muscle tension, breathing pattern, and acute anxiety, and the cause cannot be told from the sensation alone.

Damage arising from repeated or prolonged exposure to a substance, as distinct from the acute toxicity of a single occasion. The two can point in different directions: a compound with low acute toxicity may still injure the liver, the kidneys, or cognition over years, and for most novel compounds no chronic data exist at all, which is an absence of evidence rather than evidence of harmlessness.

Use sustained over an extended period rather than on single or occasional occasions. Where the line falls differs by substance and by source; what the term marks is that the effects under discussion are those of repeated exposure — tolerance, neuroadaptation, cumulative organ load — not those of one occasion.

Rhythmic, involuntary muscle contractions produced by an overexcited spinal reflex, most often elicited at the ankle. Along with hyperreflexia and tremor it is one of the neuromuscular signs that separate serotonin toxicity from other causes of agitation and fever, which is why clinicians look for it specifically.

The taking of two or more substances close enough in time that their effects overlap in the body. It names an event rather than a pattern of use, and it is the reason many case reports and post-mortem findings cannot attribute an outcome to any single compound.

The presence in a sample of material that is not the labelled compound — another active substance, a synthesis residue, a heavy metal, a microbial load, or inert filler. It is a property of the supply rather than of the drug, which is why an absence of surveillance data is common and is not evidence that a supply is clean.

A circumstance under which a given substance or treatment is not used — a medical condition, another drug already on board, a stage of life such as pregnancy. Absolute contraindications rule the exposure out; relative ones mean the balance sits against it unless there is a specific reason otherwise.

A tablet or capsule pressed to imitate a pharmaceutical product, carrying the same markings, colour, and shape without the same contents. What it holds is unknown by definition — a different substance, a different amount, or an uneven distribution across a batch — and appearance, imprint, and reagent testing each answer only part of that question.

A pattern in which a substance is taken every day, described by frequency rather than by how long the pattern has run. It is used as a threshold in dependence assessment, alongside symptoms between doses and escalating amounts, because daily exposure leaves little interval in which adaptation can reverse.

A deficit of body water and electrolytes, arising from sweating, exertion, heat, vomiting, or simply not drinking. It is the deficit state rather than the practice of hydration, and it compounds the strain that stimulants already place on temperature regulation and the heart, as well as amplifying ordinary physical discomfort during an experience.

A gap between taking a substance and the first noticeable effect, characteristic of oral and edible routes where absorption and first-pass metabolism come first. The interval is where the specific hazard sits: it invites redosing before the first amount has taken hold, so the total arrives together.

A lasting disturbance of mood, thought, or functioning that follows an experience instead of resolving with it, ranging from prolonged anxiety and disrupted sleep to a frank psychiatric episode. Persistence is what separates it from acute distress: distress ends as the substance clears, destabilization continues past that point.

The clinically supervised process of withdrawing from a substance the body has adapted to, usually with monitoring and often with medication to manage symptoms. In this corpus the word carries that clinical sense — an admission, a service, a phase of care — rather than any cleansing regimen, and whether it is medically indicated depends on the drug class rather than on how severe withdrawal feels.

An episode during a psychedelic or other altered state marked by fear, confusion, grief, or a sense of losing control. The term is used in research and harm-reduction writing in place of 'bad trip' because difficulty and harm are not the same thing: such an episode can be severe and self-limiting, and it can also be the point at which support is needed.

The act of stopping a substance the body has adapted to, whether abruptly or by reducing the amount in stages over time. It is distinct from withdrawal, which is the syndrome that may follow: discontinuation names the decision and the method, and the method shapes how steep that syndrome turns out to be.

A named clinical category describing a pattern of symptoms persistent enough to interfere with functioning. In drug literature it appears in two distinct roles that are often hard to separate: a pre-existing condition that shapes how someone responds, and an outcome attributed to use.

Loss of a clear sense of place, time, or situation, so that a person cannot reliably say where they are or what is happening. It appears across sedatives, dissociatives, deliriants, and high-dose psychedelics, and it is what makes physical injury a leading acute risk even where the substance itself is physiologically well tolerated.

Subjective suffering during or after an experience — fear, dread, panic, grief, confusion. In the psychedelic and drug-effect literature it is kept distinct from harm: distress can be severe and time-limited with no lasting consequence, and it can also be the signal that support or medical attention is needed.

A departure from normal functioning in a named system — vision, sleep, mood, electrolytes — used where the change is observable but does not amount to a diagnosis. The qualifier carries the meaning; the word alone reports only that something has moved off baseline.

The pattern of taking progressively larger amounts over time to reach an effect that a smaller amount previously produced. It appears in this corpus as a marker rather than as a quantity: whether a substance drives escalation is one of the standard indicators used in describing tolerance and dependence.

The span between the smallest amount at which a substance produces its characteristic effect and the largest amount described for a given route. Ranges are population summaries drawn from sources; they do not account for tolerance, individual physiology, or the purity of what a person actually holds.

A deliberate lowering of the amount taken — either stepwise over time, so the body can readapt as use stops, or as a standing adjustment when impaired kidney or liver function would otherwise raise exposure. The two senses share a mechanism but not a purpose, and the tapering sense is measured in weeks to months for drugs with a physical withdrawal syndrome rather than in days.

A situation in which someone who has taken a substance needs medical help now — overdose, but also seizure, chest pain, overheating, unresponsiveness, or a psychological state that cannot be held where they are. The category is deliberately wider than overdose, because the response is the same whatever caused it and because what was taken is often not known at the time.

An effect arising when two or more substances are present together and one alters the action of another, either by changing how it is metabolized or by acting on the same system. Interactions can raise, lower, or change the character of an effect; direction and consequence differ by pairing and are recorded per pairing with their sources.

The supply channels through which a substance actually reaches people, and the patterns of what circulates under which name. Harm reduction tracks it because purity, adulteration, and mislabelling are properties of the market rather than of the compound, so the name on a package predicts its contents only as reliably as that market allows.

Sexual assault committed against a person rendered unable to consent or resist by a substance, whether it was administered covertly or already taken. Detection is constrained by pharmacology and timing: many of the compounds involved clear quickly, so a negative toxicology result some hours later does not establish that nothing was given.

A measured physiological value sitting above its usual range — temperature, heart rate, blood pressure, a liver enzyme, a hormone. Calling something elevated locates a reading relative to a baseline; it says nothing about what produced it or how long it will persist.

A death recorded as related to a substance exposure. Attribution is rarely clean — most reported cases involve more than one substance, an existing medical condition, or circumstances that were never measured — so fatality counts describe what was recorded, not the risk a substance carries on its own.

A sustained sense of depleted physical or mental capacity that rest does not immediately resolve, distinct from ordinary sleepiness. In drug contexts it appears both as an after-effect once a substance clears and as a feature of withdrawal.

A dietary inhibitor of CYP3A4, the enzyme in the gut and liver that handles a large share of drug metabolism; furanocoumarins in the fruit disable the enzyme for a period after it is consumed. It appears alongside pharmaceutical inhibitors in interaction discussions because it slows the clearance of anything metabolised by that pathway, and the size of that effect varies with the product and the amount consumed.

A perception that arises without a corresponding external stimulus and is experienced as genuinely present. It is distinguished from a distortion or pseudohallucination, in which perception is altered or unreal but recognised as coming from one's own mind — the latter is what classic psychedelic experiences more often involve.

Thickening and scarring of the heart valves that prevents them closing cleanly, so blood leaks backwards with each beat. It is the harm associated with sustained activation of the serotonin 2B receptor, established for withdrawn appetite suppressants and long-term ergot medications; for compounds with only weak or partial activity there it remains a theoretical concern, since chronic-exposure data do not exist.

Injury to the liver caused by a substance or its metabolites, detected through blood markers of liver damage or, in serious cases, through loss of liver function. Susceptibility varies with existing liver health and with what else is present, and for some compounds the reaction is idiosyncratic rather than a function of the amount taken.

The body's water and electrolyte balance. It appears throughout drug references because several substances alter thirst, sweating, and the hormonal control of water retention, and because both under- and over-replacement have consequences — which is why it is discussed as a balance rather than a quantity.

Sleeping considerably longer than usual and remaining sleepy through the day despite it. It is a documented feature of stimulant withdrawal, where it appears alongside low mood, flattened pleasure, and increased appetite, and it reflects accumulated sleep debt as much as neurochemical rebound.

Blood pressure sustained above the range considered normal for a person's age and condition. It is generally silent, found by measurement rather than sensation, and it appears in this corpus both as a pre-existing condition that changes how an exposure is tolerated and as an acute effect of some substances.

Blood pressure below the range usual for a person, low enough that organs may not be adequately supplied; it presents as lightheadedness on standing, weakness, pallor, or fainting. It tends to move with slowed heart rate under sedatives and opioids, and it has most consequence in people already low on fluid or taking other things that lower pressure.

A reduced capacity to weigh consequences and assess risk while a substance is acting, often accompanied by disinhibition and overconfidence. It is one of the routes by which harm arrives indirectly — through a decision made during the state rather than through the pharmacology itself — and it tracks subjective feeling poorly.

A measurable reduction in a capacity — reaction time, attention, balance, memory, judgment — relative to a person's own baseline. It tracks subjective feeling poorly: someone can test as impaired while feeling unaffected, and the reverse also occurs.

A conclusion reasoned from available evidence rather than observed directly. In reference data it is the line between what a source states and what someone worked out from related findings, which is why an inferred value is labelled as one instead of being presented as measured.

The state present while a psychoactive substance is acting: reversible changes to perception, mood, coordination, and judgment that resolve as the substance clears. In clinical use the word implies nothing about dose or harm — it names the state, not its severity.

Blood flow to a tissue falling below what its oxygen demand requires, most often because a vessel is narrowed, constricted, or blocked. The qualifier carries the injury — myocardial, cerebral, limb — and it is the mechanism by which strongly vasoconstrictive compounds cause damage at a distance from where they act.

Testing of a sample by an analytical laboratory, typically by chromatography combined with mass spectrometry, to establish what it contains and in what proportion. It is the only form of drug checking that confirms identity rather than narrowing possibilities the way reagent tests do, and access to it varies by country and is often unavailable where samples are actually taken.

A substance's propensity to produce a particular outcome, named by the qualifier in front of it — abuse liability, dependence liability, tolerance liability. It describes a tendency measured across populations, not a prediction about any individual.

A period during which a person cannot be roused and does not respond to voice or touch. Depth and duration carry most of the information: a brief faint from a drop in blood pressure and prolonged unresponsiveness have different causes and different consequences, and the second leaves the airway unprotected.

A substance taken to treat, prevent, or manage a medical condition, whether prescribed or bought over the counter. The category is tracked here because anything a person takes regularly is part of their pharmacology on the day, and because a medication's dosing and metabolism are usually documented in a way that unregulated compounds are not.

A fall in blood pH caused by acid accumulating in the body or bicarbonate being lost, as distinct from acidity driven by a breathing problem. In overdose presentations it is a downstream finding rather than a primary one — muscle breakdown, seizures, poor tissue perfusion, and kidney injury all produce it — and it registers how far a system has been pushed rather than what pushed it.

Mistaking one substance, plant, or fungus for another that resembles it. It is a supply-side risk distinct from adulteration — nothing has been added, but what is held is not what it is believed to be — and it defeats the usual checks when the look-alike shares an appearance, a blotter format, or a molecular weight with the intended compound.

The rate of death within a defined population over a stated period, as distinct from a single recorded death. Mortality figures depend on how the population was drawn and how deaths were attributed, so two sources can report very different rates for the same substance without either being wrong.

Sustained involuntary stiffness of the muscles, with limbs resisting movement and not relaxing between movements the way ordinary tension does. It appears alongside fever and altered mental state in several toxic syndromes, and the rigidity itself generates heat and breaks down muscle tissue.

Death of heart muscle caused by blood flow through a coronary artery being blocked or sharply reduced. It appears here in two roles that are worth keeping apart: an acute event described in stimulant cardiotoxicity, and a recent event in a person's history that is recorded as a contraindication to further sympathomimetic exposure.

The state in which an opioid suppresses the brainstem's drive to breathe faster than the body can compensate: breathing slows, becomes irregular, or stops, and lips and fingertips may turn blue or grey. Breathing rate is the most reliable sign — pinpoint pupils and unresponsiveness support it, while heart rate can stay normal or raised with some compounds — and naloxone reverses it for a shorter time than many opioids remain active.

Exposure beyond what the body can compensate for, producing acute effects that need attention rather than time. What counts as one differs by substance, by route, and by the person — including their tolerance on the day.

The point at which stimulant arousal stops being experienced as focus or energy and becomes restlessness, anxiety, and physical agitation. Where that point falls is not fixed by the compound alone — dose, repeated redosing, and setting all move it, and the same substance is described as prosocial in company and as agitating in isolation.

Help offered by people who have direct personal experience of the situation the other person is in, rather than by clinicians. It works through recognition and practical shared knowledge, and it operates alongside medical care rather than in place of it.

Material manufactured under regulated conditions, with verified identity, purity, and stated content. The term marks a supply distinction rather than a chemical one: where no such supply exists, every batch carries uncertainty about what it is and how much is present, and that uncertainty attaches to any published figure for the compound.

Sustained muscular activity — dancing, walking distances, physical work — treated as a factor in its own right because it adds heat production and fluid loss to whatever a substance is already doing. It is named repeatedly in stimulant safety material because it compounds hyperthermia, particularly together with high ambient temperature.

The leaf, root, bark, seed, or prepared brew that a psychoactive compound is taken in, as opposed to the isolated compound itself. Two things follow: alkaloid content varies between plants, batches, and preparations, so a preparation cannot be verified by reagent testing the way a single compound can; and law often treats the two separately, scheduling the pure compound while leaving the plant that contains it uncontrolled, a split that differs by jurisdiction.

Involving more than one substance within the same period of use, whether taken together or in overlapping windows of effect. The word signals that an outcome cannot be attributed to a single compound, which is why it qualifies terms like polydrug use and polydrug exposure.

An increase in one substance's effect caused by the presence of another, beyond what that substance produces alone. The mechanism is either pharmacokinetic, where one compound slows the other's metabolism and more of it remains available, or pharmacodynamic, where both act on the same receptor or system.

The state of carrying a developing fetus, which appears throughout this reference as a standing contraindication in substance safety listings. For most compounds indexed here the entry records an absence rather than a finding — reproductive and developmental toxicity data have never been published — so the listing rests on mechanism and on what is unknown rather than on observed harm.

The share of a defined population carrying a characteristic — a pattern of use, a condition, an exposure — during a stated window. It says nothing about how many new cases arise, which is incidence, and it moves with how the question was asked and who was surveyed.

The possibility of harm to mental state rather than to the body: anxiety or panic during an experience, low mood or destabilization afterwards, and the aggravation of a condition already present. It is shaped as much by a person's history and setting as by the substance.

Periods in which a person's contact with consensus reality is disrupted — hallucinations, delusions, or disorganized thought — lasting anywhere from hours to weeks. Substance-related episodes are distinguished from primary psychotic illness by their timing relative to exposure, a distinction that is often clear only in retrospect.

A colorimetric drug-checking test in which a drop of reagent applied to a small sample produces a colour change read against a chart. A reagent kit narrows what a sample might be and can reveal that something unexpected is present, but it does not identify a specific compound, measure how much is there, or exclude a second substance in the same sample.

Calm verbal contact and a settled environment offered as the first response to fear or agitation during an experience. It resolves most acute distress on its own; agitation that does not respond to it is treated as a sign that medical help is warranted.

A first-aid position in which an unresponsive but breathing person is laid on their side with the head tilted back and supported, so the tongue cannot block the airway and vomit drains rather than being inhaled. It applies to someone who is breathing on their own, and it holds a person safer while help is on the way rather than treating what caused the state.

The taking of a psychoactive substance outside a medical indication, for its subjective effects rather than to treat a condition. The category is defined by intent and context rather than by the compound itself, so the same substance can sit on either side of the line depending on who is taking it and why.

A further amount taken while a previous one is still active, to extend or restore an effect. It is recorded separately from a first dose because the amounts overlap in ways that are difficult to judge from inside the experience, and because with some compounds the urge to redose is itself a pharmacological effect rather than a decision made fresh.

The act of directing a person to a service that can help — a crisis line, a treatment provider, a support organisation — rather than providing that help directly. A referral names where support exists and on what terms; it is not itself an assessment of what someone needs.

The point at which breathing no longer moves enough oxygen into the blood or clears enough carbon dioxide from it. In depressant contexts it is where progressive respiratory depression ends up, and it differs from that earlier state in that the body has stopped compensating; it is a medical emergency.

The process by which a neurotransmitter released into a synapse is carried back into the cell that released it, ending the signal. Drugs that slow or reverse this transport leave more transmitter in the synapse for longer, which is the mechanism behind several major classes of antidepressants and stimulants.

The breakdown of skeletal muscle tissue, releasing its contents into the bloodstream, where they can injure the kidneys. It follows sustained exertion, muscle rigidity, overheating, or prolonged pressure on a limb from lying still, and it is identified by blood and urine testing rather than by how a person feels.

A burst of synchronised, uncontrolled electrical activity in the brain that produces a change in movement, sensation, or awareness. Not all seizures involve convulsions; some appear as a brief lapse of awareness or an isolated sensory change.

The level of neural excitability at which a person's brain produces a seizure, which some substances, some medications, and withdrawal states lower. It is a relative property rather than a fixed line: a threshold lowered enough to matter in someone with an existing seizure disorder may never be crossed in someone without one.

The act of taking a substance oneself rather than receiving it from a clinician. In pharmacology the word also names a laboratory paradigm in which an animal can administer a compound to itself, used as a measure of how reinforcing that compound is.

Deliberate injury to oneself, or a stated intention to cause it. It appears in this reference as an escalation criterion rather than a diagnosis: in emergency guidance it marks the point at which a situation is treated as needing immediate help regardless of what was taken or how much.

How strongly a particular person or system responds to a given exposure compared with others, whether from genetics, enzyme variation, age, or existing medication. The word carries a second, unrelated sense in research writing: the sensitivity of a test or assay is how reliably it detects what is actually present, which is why a negative result on an insensitive test settles little.

A condition that persists after the acute phase of an illness or exposure has resolved, whether psychiatric, neurological, or physical. The word marks what remains rather than what caused it, and whether a sequela is lasting is usually established only by following someone over time.

The two non-pharmacological factors that shape a psychoactive experience: set, the person's mindset, expectations, and state on the day; setting, the physical and social environment around them. The same substance at the same dose can produce very different experiences as these change.

The graded rating attached to a harm — an interaction, an adverse event, a toxicity finding — describing how serious the outcome is rather than how likely it is. Scales differ between sources, so the same finding can carry different labels in different references.

A sober companion who stays with someone through an experience to provide reassurance, handle practical matters, and act if distress escalates. The role is one of presence and judgement rather than clinical care, and it does not replace medical help when a situation calls for it.

Going without sleep long enough that cognition, mood, and physiological regulation measurably degrade. It appears in this corpus in two roles: as a compounding factor in extended stimulant sessions, where each additional waking hour adds to it, and as a deliberately induced altered state in its own right.

Disturbance of sleep timing, duration, or quality — difficulty falling asleep, fragmented sleep, or sleep that does not restore. It is documented both as an after-effect while a substance clears and as a component of withdrawal and cholinergic rebound, and in contemplative practice it is treated as an early warning sign rather than an incidental complaint.

An informal name a substance circulates under in unregulated markets, coined by sellers or users rather than assigned by any naming convention. The same street name is applied to different compounds in different places and periods, so it records what something is being sold as rather than what it contains.

A sudden loss of blood supply to part of the brain, either because a vessel is blocked or because one has ruptured and is bleeding into tissue. It appears in this corpus as a documented cardiovascular endpoint of stimulant exposure; in any individual case the contribution of a substance is rarely separable from pre-existing vascular risk.

The taking of a psychoactive compound, described without implication about pattern, quantity, or consequence. Clinical and epidemiological writing uses it as the neutral baseline term, reserving separate labels for hazardous patterns and for disorder.

The diagnostic category for a pattern of use that continues despite impairment or harm, defined by criteria covering loss of control, escalating priority over other activities, and physiological adaptation. It is graded by how many criteria are met rather than by which substance is involved, and tolerance or withdrawal alone does not establish it where a substance is taken as prescribed.

A heart rate faster than the person's resting range. It is a sign rather than a diagnosis — stimulants, fever, dehydration, anxiety, pain, and blood loss all produce it, so it indicates that something is driving the heart, not what.

A trained mental-health professional; in this corpus most often one experienced with psychedelic or drug-related material, consulted after an experience rather than during it. Familiarity with altered states is not a regulated credential in most places, so such a description is a claim about experience rather than a licensed qualification.

The capacity of a substance to cause damage to a living system, and the study of how that damage happens. It is exposure-dependent and organ-specific: a compound can leave one system untouched at an exposure that injures another.

The study of how substances injure living systems: the mechanisms of injury, the exposures at which it occurs, and how it is detected and treated. In drug references it supplies both the laboratory findings behind toxicity claims and the analytical testing used to identify what someone actually took.

A recognizable cluster of signs and symptoms characteristic of a class of substances, used in emergency medicine to narrow down an unknown exposure. It identifies a pattern of physiological action rather than a compound, and several drugs, along with some causes that are not drugs at all, produce the same picture.

An involuntary rhythmic shaking of part of the body, most often the hands. It appears in sympathomimetic and serotonergic toxicity alongside agitation and a raised heart rate, and it is one sign among several rather than a measure of how much substance is on board.

A cue — a place, a person, a sensation, a piece of music, an internal state — that precipitates a response such as craving, panic, or the return of a past experience. A trigger sets off a reaction that was already possible; it does not create the underlying susceptibility, which is why the same cue means nothing to most people who meet it.

The factors that place a particular person at greater susceptibility to harm from an exposure than the population average — age, psychiatric or cardiac history, liver function, genetics, isolation, or the setting itself. It names a position relative to a risk, not a fixed trait.

A defined laboratory procedure for identifying or quantifying a compound in a sample, such as chromatography paired with mass spectrometry. Methods are developed to separate compounds that are otherwise easily confused with one another, and each carries its own limits — some apply heat that degrades thermolabile compounds before they can be measured.

A laboratory animal used to study a drug effect that cannot be observed directly in people — reinforcement, tolerance, neurotoxicity, or shifts in reward threshold. Such work establishes that a mechanism operates in that species; differences in metabolism, receptor makeup, route, and dosing schedule mean it does not transfer to humans by itself.

A measurable biological indicator used to stand in for something that cannot be observed directly — an exposure, a physiological process, or a change in the brain. A biomarker is only as informative as the link between it and the thing it represents, and one that reliably shows exposure may say nothing about effect.

A published account of one patient's course, usually written because something unexpected happened. It establishes that an outcome can occur; it establishes nothing about how often, in whom, or why.

A published account of several patients who share a condition, exposure, or outcome, described together without a comparison group. It shows more of a pattern than a single case report, but still can't establish how often something occurs in the wider population.

The staged process by which a compound is tested in humans for a medical use, from first-in-human safety studies through the trials a regulator requires for approval. Most compounds described in this corpus never entered it, which is why their human pharmacology rests on case reports and self-report rather than on trial data.

A study carried out in human participants under a defined protocol, as opposed to laboratory work in cells or animals. Across this corpus the recurring line is that none exists for a given compound, which marks a specific gap: what is known then rests on animal pharmacology, metabolism work, and structural analogy rather than on controlled observation in people.

The United States registry, run by the National Library of Medicine, where clinical trials are recorded with their design, phase, and status, whether or not results are ever published. Across this index it is cited most often for what it does not contain: an absent registration indicates that a compound has never entered formal clinical study, not that a study found nothing.

A group of people followed together in a study because they share a defining characteristic or exposure, either forward in time or reconstructed from existing records. A cohort can show that an exposure and an outcome travel together; on its own it cannot show that one produced the other.

A laboratory paradigm in which an animal learns to associate a distinctive environment with a substance, and the time it later spends in that environment is read as a measure of how rewarding the substance was. It indexes reward learning in animals under controlled conditions, and does not by itself establish that a compound will be used compulsively by people.

A study in which the group receiving a substance is compared against a group that does not, so an observed effect can be separated from what would have happened anyway. It names a design feature, not a guarantee of quality: control alone says nothing about whether participants were randomly assigned, how many were enrolled, or whether anyone was blinded.

The internal state produced by a drug that a trained animal can recognise and report by choosing one response over another, used to ask which known compound a new one resembles. Full substitution shows the two feel alike on the trained cue; it does not establish a shared mechanism, or that the resemblance holds in people.

A trial designed to establish which amounts produce the intended effect and where unacceptable effects begin, usually by escalating in controlled steps in monitored volunteers. Its absence is what this corpus most often has to record for novel compounds: where no dose-finding study exists, circulating figures come from self-reported use, which describes what people took rather than what was found to be tolerated.

A trial design in which neither the participants nor the researchers assessing them know who received the active substance. It removes expectation on both sides, though the blind often breaks when a substance's effects are unmistakable, and a study can be described as double-blind without reporting whether the blind actually held.

A statistic expressing how large a difference between groups is, separately from how many people were studied. It answers a different question from statistical significance — a large effect can be uncertain in a small sample, and a trivial one can be significant in a large one — and it says nothing about whether the difference is one a person would notice.

The body of published work that exists on a question, considered as a whole — how much of it there is, what designs it uses, and where it stops. Describing an evidence base as thin or absent is a statement about what has been studied, not about whether something is safe: an absence of findings is not a finding of absence.

Blood drawn from the femoral vein in the leg, the standard sampling site in postmortem toxicology. It is preferred because concentrations in blood taken from the chest or heart can rise after death as substances diffuse out of nearby organs, though even a femoral value cannot be read as the concentration present at the moment of death.

A rapid side-to-side head movement in mice and rats, counted as a behavioural read-out of 5-HT₂A receptor activation after a compound is given. It is the standard rodent proxy for hallucinogenic activity and is abolished by 5-HT₂A antagonists such as ketanserin, but it registers receptor engagement in an animal, not anything about the experience a person would report.

Carried out outside a living organism — in isolated cells, tissue preparations, or purified enzymes. In-vitro work establishes that a molecular interaction is possible, not that it occurs at concentrations a living body ever reaches, which is why much of this reference marks mechanism and interaction claims as in-vitro only.

Carried out in a living organism, whether an animal or a person, rather than in isolated cells or tissue. An in-vivo finding shows that something happens in a functioning body with intact metabolism, distribution, and clearance, though a result in one species does not carry to another on its own.

The number of new cases of an outcome arising in a defined population over a stated period. It answers a different question from prevalence, which counts existing cases at a point in time; a condition can be uncommon in incidence and common in prevalence when it persists once it appears.

A study designed to measure how two or more substances affect each other's metabolism or effects when taken together, rather than studying either one alone. Findings from one pair of substances, doses, or population don't necessarily generalize to others.

An analytical method that identifies compounds by ionizing a sample and sorting the resulting fragments by mass, usually after a chromatographic separation. It is the reference method behind forensic identification and laboratory drug checking, and it establishes what is present in a sample rather than what that sample will do.

An inactive preparation given in place of the substance under study, so that effects of expectation and setting can be separated from effects of the drug. In trials of substances with obvious subjective effects, participants often work out which arm they are in, which weakens the comparison a placebo is meant to supply.

A study in which one group receives the compound under test and another an inactive substitute, so that outcomes can be compared against what changes without it. Blinding is difficult to maintain when a substance produces unmistakable subjective effects, since participants work out which group they are in, and this is a recognised limitation of the design in psychedelic research.

The original published reports of research — the papers in which a study's own methods and results first appear — as distinct from reviews, textbooks, and databases that summarise them. Reference values are traced back to it wherever possible, and where a value cannot be located there, the absence is recorded rather than filled in from a secondary account.

A study in which participants are assigned by chance to an intervention or a comparison condition, so that differences in outcome are less likely to reflect pre-existing differences between the groups. It is the design that supports causal claims most strongly, which is why the corpus so often records its absence: observational and naturalistic reports describe what happened to people who chose their own exposure, not what a substance does.

A rat or mouse study, the preclinical work behind most of what is known about the compounds in this index: drug discrimination, locomotor activity, self-administration, and tissue distribution. Rodents differ from people in metabolism, receptor makeup, and the routes and schedules used, so a rodent finding describes what a compound does in that species and poses a human question rather than answering one.

A publication that reports information drawn from elsewhere — a review, a textbook, a database entry, a community compilation — rather than presenting original findings of its own. A claim traced only to a secondary source is recorded as such, since a detail can be repeated across many of them without any one having checked it against the original document.

A finding that an observed difference is unlikely to have arisen by chance alone, under the assumptions of the test applied. It is a statement about chance and not about size or importance: a significant result can be too small to notice, and a non-significant one often means the study was too small to detect a real effect rather than that no effect exists.

Reasoning that a compound will behave like a better-studied one because their molecular structures are closely related. It is the weakest evidence class cited in this reference and is labelled as such wherever it is used, since small structural changes can shift potency, selectivity, duration, or toxicity in ways that resemblance does not predict.

The systematic collection of reports of harm once a substance is in use, as distinct from testing it under trial conditions. It can detect effects too rare to appear in a trial, but it depends on someone recognizing an event and reporting it, so it stays silent about compounds that are never prescribed or formally monitored.

A review that fixes its search strategy and inclusion criteria in advance, then assesses every study meeting them, rather than selecting sources at the author's discretion. It sits near the top of the evidence hierarchy but inherits the quality of what it finds: a systematic review of weak or absent studies reports weak or absent evidence.

How well people can take a substance without unwanted effects that lead them to stop — nausea, sedation, headache, discomfort — reported in trials as the counterpart to efficacy. It records what participants would put up with under study conditions, which is a separate question from whether a substance works and from whether it is safe.

The residual state that persists once a substance's main effects have subsided and before a person returns to baseline, often with a character of its own — fatigue, low mood, lingering stimulation, difficulty sleeping. It regularly outlasts the acute phase, so a stated duration understates how long a day is affected; it is distinct from a rebound effect, which is the return of a symptom the substance had been suppressing.

The somatic side of a substance's effects — muscle tension, nausea, jaw tightness, restlessness, a general physical heaviness — described separately from what is happening perceptually or emotionally. The term comes from user reports rather than clinical writing, and accounts of it differ widely between people taking the same compound.

A reported quality of thinking cleanly and being able to follow one's own reasoning, sometimes described as persisting even while perception is markedly altered. It is a subjective account of how cognition feels rather than a measure of how it performs, and the two do not always agree.

The ongoing first-person awareness of oneself and one's surroundings — the field in which perception, thought, feeling, and sense of time appear. It is what this reference is organised around: substances and practices are indexed by how they alter it and by what route the alteration is reached, while the clinical phrase 'loss of consciousness' names something narrower, the absence of responsiveness.

A perception, during or after an altered state, that something about oneself, a relationship, or a situation has become clear. What gets recorded is the report rather than its accuracy — an insight can prove durable and workable, or it can be a conviction that does not hold up once the state has passed.

The ongoing process of making sense of an altered-state experience and working what it revealed into everyday life afterward. Many practitioners treat it as consequential as the experience itself, since insight that isn't carried into daily patterns tends to fade.

The felt magnitude of an experience — how strongly effects register — held as an axis separate from how much was taken, how long it lasts, and what kind of effect it is. Intensity tracks amount only loosely, since physiology, tolerance, setting, and expectation all move it, which is why the same amount is reported at very different strengths by different people and on different occasions.

Attention turned inward onto one's own thoughts, feelings, memories, and motives. It is a frequently reported quality of psychedelic states rather than a guaranteed feature of them; depth varies with the amount taken, the environment, and the person's state going in.

An unbroken chain of teachers through which a contemplative tradition transmits its practices and the authorization to teach them. It functions as the credential in those traditions — teachers are recognized by their own lineage rather than by any secular certification — so it establishes standing within a tradition, not training in psychological safety or clinical care.

The first-person description of what an experience is like, recorded independently of the mechanism producing it. It is what makes two substances with similar pharmacology distinguishable to the person taking them, and it carries the limits of self-report: only what can be noticed, remembered, and put into words.

The altered state produced by a classical psychedelic — changes to perception, thought, emotion, and the sense of self that persist while the substance is active and then recede. The substance sets the duration and the intensity far more reliably than it sets the content, which varies with the person, the setting, and the occasion.

The ongoing background feeling of being a particular person, with a boundary between oneself and everything else. Psychedelics and dissociatives can loosen or dissolve it; the same alteration is reported as relief by some people and as dread by others, and which one occurs tracks preparation and setting more closely than it tracks the compound.

The felt ease of being around other people — more talk, less social guardedness, more warmth toward company. It is a commonly reported effect of entactogens and some stimulants, described here as a subjective quality rather than a measured change in behaviour, and it varies with the social setting as much as with the compound.

What a substance or a practice is like from the inside: perception, mood, thought, and sense of self as the person undergoes them. It is the evidence class this reference sets alongside receptor and pharmacokinetic data — binding figures describe what happens to a molecule, reports describe what happens to a person, and neither predicts the other cleanly.

A subjective sensation of heat spreading through the body or radiating from the chest or face, often reported during the onset of certain substances. It's a felt experience, distinct from any measured change in body temperature.