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Deliriant
Drug class
Chemical structure of scopolamine, one of the most well-known deliriants.
Class identifiers
SynonymsAntimuscarinic; Anticholinergic; Muscarinic antagonist; Muscarinic acetylcholine receptor antagonist
UseRecreational, medical
Mechanism of actionMuscarinic acetylcholine receptor antagonism
Biological targetMuscarinic acetylcholine receptors
Chemical classVarious
Legal status
Legal status
  • Non-controlled
In Wikidata
The toxic berry of Atropa belladonna which contains the tropane deliriants scopolamine, atropine, and hyoscyamine.

Deliriants are a subclass of hallucinogen. The term was coined in the early 1980s to distinguish these drugs from psychedelics such as LSD and dissociatives such as ketamine, due to their primary effect of causing delirium, as opposed to the more lucid and less disturbed states produced by other types of hallucinogens, where rational thought is better preserved (including the ability to distinguish hallucinations from reality).[1] The term generally refers to anticholinergic drugs, which are substances that inhibit the function of the neurotransmitter acetylcholine.[1]

Common examples of deliriants include plants of the genera Datura and Brugmansia, both containing scopolamine, as well as higher than recommended dosages of diphenhydramine (Benadryl).[2][3] A number of plant deliriants such as that of the Solanaceae family, particularly in the Americas, have been used by some indigenous cultures to reach delirious and altered states of consciousness for traditions or rituals, such as rites of passage, divination or communicating with the ancestors.[4] Despite their long history of use, deliriants are the least-studied class of hallucinogens in terms of their behavioral and neurological effects.[5]

Etymology

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The term was introduced by David F. Duncan and Robert S. Gold due to a characteristic delirium-like effect which is known to manifest as a reoccurring symptom for anticholinergic hallucinogens.[1] The term deliriant originates from delirium (dēlīrĭum) which comes from the Latin verb delirare, which means 'to go off the furrow', 'to derail'. liria (furrow) - The earth thrown up between two furrows, a ridge. ex, e - out of, from. delirio - frenzy, madness, deranged.[5] It is said to be a figurative reference to going off or out of the furrow when ploughing (agricultural) so as to be analogous to the mental aberration that is being in delirium.

Mechanism of action

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The altered state of consciousness produced by common or 'classical' deliriant substances such as scopolamine, atropine and diphenhydramine is mediated through the drug compounds' competitive antagonism of the peripheral and central muscarinic acetylcholine receptors, especially the M1 muscarinic receptor. M1 receptors are located primarily in the central nervous system and are involved in perception, attention, and cognitive functioning.

Delirium is primarily associated with antagonism of postsynaptic M1 receptors.[6][7] However, antagonism of both the M1 receptor and the M2 receptor have been implicated as having negative effects on memory and cognition, and the selective M2 receptor antagonist hyoscyamine has been reported to produce deliriant effects similarly to M1 receptor antagonists.[6][8] Conversely, the M3 receptor has not been implicated in cognition.[8]

The central nervous system actions of deliriants are complex, and other muscarinic acetylcholine receptors, including the M3, M4, and M5 receptors, may also be involved in the effects of the drugs.[9] As an example, the M1, M2, M4 and M5 receptors have all been implicated in regulating dopamine release, with the M1, M2, and M4 receptors having inhibitory effects on dopamine release and the M5 receptor having stimulatory effects.[9]

Peripheral muscarinic receptors are part of the autonomic nervous system. M2 receptors are located in the brain and heart, M3 receptors are in salivary glands and M4 receptors are in the brain and lungs.[7] Scopolamine is a nonspecific muscarinic antagonist at all four (M1, M2, M3, and M4) receptor sites.[10][11] Due to these compounds' inhibition of various signal transduction pathways, the decrease in acetylcholine signaling is what leads to many of the cognitive deficits and mental impairments.[12]

It has also been said that common anticholinergic agents/hallucinogens should be more accurately referred to as antimuscarinics, as for instance these agents do not generally block nicotinic receptors.[7]

Effects

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The hallucinogenic experience and delirium produced, particularly by (M1 inhibiting) anticholinergics is characterized by stupor, agitation, confusion, confabulation, emotional bluntness, dysphoria, memory deficits, incoherency of thoughts, hypoactivity or hyperactivity (mixed delirium), lucid intervals, akathisia, realistic visual hallucinations or illusions (as opposed to the pseudohallucinations experienced on other classes of hallucinogens) and regression to "phantom" behaviors such as disrobing, plucking or interacting with imaginary objects or scenes.[13][7] The effects of these kinds of anticholinergic compounds have also been likened to delirious fevers, sleepwalking, fugue states or psychotic episodes in that the subject has minimal control over their actions and may have little or no recollection of the experience afterwards. This is a notable departure from the effects of serotonergic psychedelics.[3][14]

Scopolamine has been shown to exert a greater impairment on episodic memory, event-related potentials, memory retention and free recall compared to DPH (an anticholinergic and antihistamine).[15] Some antihistamines may also act as deliriants in high doses.[citation needed] Due to scopolamine's prominent amnesiac and impairing effects, it has been used in Colombia for criminal purposes such as 'drugging' individuals, usually perceived as wealthy, and robbing them due to scopolamine's discombobulating effects and enhanced suggestibility.[16] It is usually done by putting the extracted and isolated powder form of the alkaloid in a victim's (alcoholic) drink, oftentimes directly by or with the help of attractive women to act as criminal accomplices to the robbers.[17][18][19]

In Colombia, isolated (powdered) scopolamine has become infamous and is referred to there by several monikers such as Burundanga and "Devil's Breath". It is usually extracted by criminals from the Borrachero Tree and may even occasionally be encountered as a street drug there.[20]

The antimuscarinic plant-based alkaloids scopolamine and atropine are also notorious for their characteristic hyperactive effects and ability to cause stark and dream-like hallucinations.[5][21] The hallucinations themselves are often described by users as disturbing, unpleasant or dark in nature.[22][2][23] Other commonly reported behaviors and experiences include holding conversations with imagined persons or entities, smoking nonexistent cigarettes (even with nonsmokers), visual hallucinations of spiders or shadow figures or being unable to recognize one's own reflection in a mirror.[2] Deliriants in particular appear to be noted for their powerful effects on users' behavior.[5]

Ken Hedges, who was curator of archaeology at the San Diego Museum of Man, and also studied hallucinogen-based Kumeyaay rock art recalled how when he was a student at San Diego's Mount Miguel High School in 1960, two teenage boys in Ojai who sampled datura were found on that town's main street at night; "in a state of mind that could only be called extremely deranged, they were walking from streetlight to streetlight, banging their heads on each pole until they were covered with blood." Hedge claimed that even among Native Americans, "terrifying visions" were often the result for "those who submitted themselves to the plant's power."[24] Anthropological assessment of the sacred Chumash Datura cult in Southern California ascertained that within the tribe, frequent or repeat users of datura tended to gradually become more and more antisocial, often adopting behavior patterns that the rest of the tribe viewed as "capricious malevolence".[25]

During one of his workshops in Hawaii, psychonaut Terence McKenna discussed the effects of the hallucinogenic Solanaceae plants compared to psychedelics, stating that:

"They (solanaceae deliriants) are psychoactive and interesting. I don't know how much is to be learned there. It seems to me it's a path of power, and it's also a path of danger. They're quite peculiar. It's hard to keep control. It's the drug where people invariably tear their clothes off and run into public. I mean, I don't know why they do that but just over and over again you hear stories of people taking their clothes off and then going into public… In Nepal, there is Datura metel, which is the conspecific species to Datura meteloides in North America, and we would grind it up and take the seeds and… it's freaky. It doesn't teach you about higher consciousness, it sort of leads you into a world of twilight confusion and magical and somewhat demonic forces… A lot of sorcery goes on around datura, especially in Latin America. It's a strange world. A world of shadows and forces, and shifting boundaries."

During an on-camera interview, author of The God Molecule: 5-MeO-DMT and the Spiritual Path to the Divine Light, Gerardo Ruben Sandoval Isaac explained that in the Oaxaca "mushroom village" of San José del Pacifico, the psilocybin mushrooms are regarded as being "related to light" and that (Brugmansia) is "related to the darkness" and that they (the tribes) "are aware of the polarity of this flower", further crediting the idea that the hallucinogenic experience produced by deliriants is typically of a "dark" and disturbing nature.[citation needed] When datura was first formally discovered in colonial Jamestown, Virginia in 1676 by English soldiers during Bacon's Rebellion, they spent 11 days in altered mental states after using the leaves of the plant, which they did not know were psychoactive and poisonous, as part of a salad.[26]

Historian Robert Beverley Jr. wrote of the observable effects seen during their intoxicated state; "They (the soldiers) turned natural fools upon it for several days: one would blow up a feather in the air; another would dart straws at it with much fury; and another, stark naked, was sitting up in a corner like a monkey, grinning and making mows (grimaces) at them; a fourth would fondly kiss and paw his companions, and sneer in their faces with a countenance more antic than any in a Dutch droll… They were not very cleanly; for they would have wallowed in their own excrements if they had not been prevented. A thousand such simple tricks they played, and after eleven days returned (to) themselves again, not remembering anything that had passed."[26]

Deliriant substances

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Datura stramonium (jimsonweed) 4-valved seed capsule

Naturally-occurring anticholinergic deliriants are found in the plant species Atropa belladonna (deadly nightshade), various Brugmansia species (Angel's Trumpets), Datura stramonium (Jimson weed), Hyoscyamus niger (henbane), and Mandragora officinarum (mandrake) in the form of the tropane alkaloids scopolamine, atropine, and hyoscyamine. Other, lesser known plant sources of scopolamine and related tropanes include Scopolia carniolica endemic to Europe, Latua endemic to southern Chile, Solandra endemic to Mexico and Duboisia myoporoides, which is endemic to Australia and contains both scopolamine and nicotine.[27][21][28] Scopolamine has often been considered, pharmacologically and psychonautically the premier and paradigmatic deliriant substance, to which all other deliriants and/or antimuscarinic hallucinogens are usually compared.[29][4]

Synthetic compounds such as diphenhydramine (Benadryl), dimenhydrinate (Dramamine), and tropine benzilate are deliriants. Nutmeg, although purportedly not as strong or as unpleasant as diphenhydramine or scopolamine, is considered a deliriant, due to its propensity to cause anticholinergic-like symptoms when taken in large doses.[30] The effects caused by myristicin and elemicin found in nutmeg's essential oil can last up to several days, similarly to the tropane alkaloids found in datura.[31][32] The mushroom referred to as fly agaric with its active agents ibotenic acid and muscimol may also be considered an 'atypical' deliriant, although fly agaric is probably more accurately described as a hypnotic.[33][34]

In rare cases, highly toxic plants from the Aconitum (wolfsbane) genus have been used as "deliriants" by certain groups practicing European witchcraft, the left-hand path or asceticism due to the unpleasant but supposed altered state of consciousness which can be a side effect of wolfsbane poisoning. Plants of the aconitum genus contain the neurotoxin aconitine and in the case of Aconitum ferox, an extremely toxic alkaloid called pseudaconitine, which is in rare cases, taken as an ordeal poison and entheogen on the Indian subcontinent by ascetic groups such as the Aghori, where it may be mixed with other psychoactive plants or poisons such as datura and cannabis. Risk of death is considered very high when taking A. ferox and its use is restricted to only the most experienced adepts of their particular school of Shivaism.[35][36][37]

Recreational use

[edit]
A woman diagnosed with chronic dementia, 1896

Despite the fully legal status of several common deliriant plants and OTC medicines, deliriants are largely unpopular as recreational drugs due to the severe dysphoria, uncomfortable and generally damaging cognitive and physical effects, as well as the unpleasant nature of the hallucinations.[23][22] Anticholinergics are said to be typically responsible for 15–20% of acute poisoning admissions, up to 40% of poisoning admission to intensive care units and 16% of poison centre calls. The anticholinergic syndrome may be accompanied by sedation, coma, seizures and/or cardiovascular toxicity not necessarily mediated by muscarinic antagonism but rather secondary to other drug effects on other receptors or ion channels.[7] In theory, an ideal antidote for the anticholinergic syndrome caused by these particular substances would be a selective M1 receptor agonist. Some are in development but reportedly as of 2016, none are in clinical use.[7]

Ultimately, user reports of recreational deliriant usage on the drug resource website Erowid also generally indicate a firm unwillingness to repeat the experience.[38] In addition to potentially dangerous mental/behavioral effects (accidents during deliriant experiences are common)[39] some tropane alkaloids, such as those found in plants of the Datura genus, are exceptionally toxic and can cause death due to tachycardia-induced heart failure, hypoventilation and hyperthermia even in small doses.[40] Anticholinergics have been shown to increase the risk of developing dementia with long-term use, even at therapeutic doses, therefore they are presumed to carry an even greater risk when used at hallucinogenic dosages.[41][42] Scopolamine in particular has been implemented in scientific models used to study the cholinergic hypothesis for Alzheimer's disease and other related dementias.[43]

Despite these overtly negative effects both on the physical and mental health of the user, usage of deliriants for recreational purposes has still gone on for centuries and was said to be introduced in Europe and surrounding areas by the Romani people, who would smoke or ingest plants such as datura to experience hallucinations.[44] It has been said that certain groups who used deliriant plants, especially in hedgewitchery (wortcunning) practices, would traditionally mix in medicinal or neuroprotective plants either directly during the intoxications or later on to counter negative health consequences or symptoms such as dysphoria or senility.[45][46][47]

Occultism and folklore

[edit]
Preparation for the Witches' Sabbath by David Teniers the Younger. Note on the left, an older witch reading from a grimoire, while anointing the buttocks of a young witch about to fly to the sabbath upon an inverted besom, with a candle upon its twigs

Deliriants such as henbane, belladonna, mandrake, jimsonweed and fly agaric are associated with and featured in many stories and beliefs within European mythology.[48][49][50][47] In ancient Greek myth, wreaths of henbane leaves were used to crown the newly deceased to make them forget their former lives as they crossed or wandered near the River Styx in the underworld.[14] The belladonna plant genus, Atropa is named after the Greek Fate, Atropos, who cut the thread of life.[50] In early medieval times, Mandrake was believed to have commonly grown under gallows where bodily fluids dripped from the bodies of deceased murderers, with some sources stating blood and others claiming semen or urine.[14][51][52]

Tropane-containing nightshades have played an integral role in Old World folklore and European witchcraft.[21][51][45] Henbane is reputed for having been used in Greco-Roman magic during ancient times as well as being associated with black magic and maleficium during the Late Middle Ages.[21] During this period in medieval Europe, the Central European species Scopolia carniolica was also used as an admixture in love potions.[53] Belladonna was purported to aid in the "flight of witches" where they reportedly would experience "bacchanalian carousal" or hallucinatory dreaming.[45][54]

Mandrake (the root of Mandragora officinarum) is mentioned twice in the Bible,[55][56] and was also frequently mentioned as a typical ingredient in flying ointment recipes since at least as far back as the Early Modern Period.[48] During this time period, the New World plant datura stramonium (jimsonweed) was discovered in North America by colonialists and eventually lumped in with the other classic 'witches weeds' of the nightshade family that were endemic to Europe.[48][21] Datura has a long history of usage both in Mexico and the Southwestern United States by indigenous cultures using it for ritualistic, sacred and magical purposes.[57][58][4]

In modern times, both Datura and Brugmansia are still used for sorcery, black magic, and shamanism in Latin America.[59][60] In certain South American countries, members of the Brugmansia genus have been known to be occasionally added to ayahuasca brews by malevolent sorcerers (brujos) or bad shamans who wish to take advantage of unsuspecting tourists. Genuine shamans (curanderos) believe one of the purposes for this is to "steal one's energy and/or power", of which they believe every person has a limited amount.[60]

Since medieval times, extremely noxious plants of the Aconitum (wolfsbane) genus were also associated with folklore and magic and were used for similar purposes as the tropane-containing nightshades.[21] Despite being a highly poisonous and often deadly plant to work with, it was still often included in recipes for flying ointments and magical salves, likely as a way to help counteract both the cardiac and hyperthermic side effects of the scopolamine.[35][45] The aconitum genus (specifically aconitum napellus) was firmly associated with superstition and witchcraft in Europe, particularly when it came to mythos surrounding werewolves and lycanthropy.[61][45] This is believed to have originated at least partially from wolfsbane's alleged tendency to cause paresthesia which supposedly can be reported to feel like one's body is covered in fur.[35] In Greek mythology, the goddess Hecate is said to have invented aconitum which Athena used to transform Arachne into a spider.[62][63]

Classes of deliriants

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See also

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References

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[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Deliriant

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Deliriants are a subclass of hallucinogenic substances characterized by their ability to induce a profound state of delirium through antagonism of muscarinic acetylcholine receptors in the central nervous system, resulting in symptoms such as severe confusion, disorientation, realistic and often nightmarish hallucinations, anterograde amnesia, hyperactivity, and autonomic effects including dry mouth, blurred vision, tachycardia, and hyperthermia. Unlike classic psychedelics that primarily affect serotonin receptors or dissociatives that target NMDA receptors, deliriants produce a dream-like yet terrifying altered state that users often describe as indistinguishable from psychosis, with little insight into the drug-induced nature of the experience. The pharmacology of deliriants centers on their properties, particularly as competitive antagonists at muscarinic receptors, which disrupts signaling essential for , , and ; this mechanism distinguishes them from other hallucinogens and underlies their unique behavioral profile, including impaired sensorimotor gating and altered affective states observed in preclinical models. Prominent examples include tropane alkaloids such as atropine, scopolamine, and hyoscyamine, which are naturally occurring in plants of the family, notably Datura stramonium (jimsonweed) and Brugmansia species, where they serve as chemical defenses but have been exploited for their psychoactive effects since ancient times. Additionally, certain pharmaceuticals exhibit deliriant effects at high doses, including diphenhydramine (found in over-the-counter antihistamines like ), which exerts secondary activity leading to similar hallucinatory and delirious states. Historically, these compounds have been used medicinally for millennia— alkaloids were documented in ancient Egyptian, Greek, and Indian texts for treating , inducing , and even as poisons—while modern applications leverage their actions without the hallucinogenic risks at therapeutic doses. For instance, atropine is administered intravenously to reverse and or topically as a mydriatic for eye examinations, and scopolamine is utilized transdermally to prevent and . Despite these benefits, deliriants pose significant risks of , including life-threatening complications like seizures, , and cardiovascular instability, and their recreational use is uncommon due to the invariably dysphoric and amnesia-laden experiences they provoke.

Definition and Characteristics

Definition

Deliriants are a subclass of hallucinogenic substances that primarily induce a state of , defined as an acute disturbance in and characterized by , disorientation, and realistic hallucinations that the user perceives as genuine sensory experiences rather than distortions of reality. Unlike psychedelics, which typically produce insightful perceptual alterations through serotonin receptor agonism, or , which foster a sense of detachment via NMDA receptor antagonism, deliriants disrupt signaling in the , resulting in dream-like yet often terrifying states of altered . Common examples include anticholinergics like atropine and antihistamines such as diphenhydramine. The core symptoms of deliriant intoxication encompass profound , heightened , and a marked loss of testing, often accompanied by potential for violent or bizarre behaviors due to the profound disorientation. Users may exhibit restlessness, agitation, and hallucinatory experiences that blend seamlessly with perceived , leading to impaired judgment and increased risk of harm. These effects stem from the blockade of muscarinic receptors, though detailed mechanisms are explored elsewhere. Epidemiologically, deliriant exposures are more prevalent in accidental poisonings, particularly from plants containing tropane alkaloids or over-the-counter medications, than in intentional recreational use; for instance, the 2015 American Association of Poison Control Centers reported 576 single exposures to anticholinergic and 18,589 to diphenhydramine, with most cases arising unintentionally rather than for psychoactive effects. More recent data from 2022 indicates 26,248 single exposures to diphenhydramine, highlighting ongoing risks including misuse trends. Intentional misuse remains uncommon compared to other classes, contributing to its relative rarity in recreational contexts.

Etymology

The term "deliriant" derives from the Latin verb delirare, meaning "to deviate from a furrow" (as in plowing) or "to go mad," a metaphorical expression for straying from rational thought, with the noun form delirium entering English in the late 16th century to denote mental derangement. In medical contexts, delirium was first documented by the Roman encyclopedist Aulus Cornelius Celsus in the 1st century AD to describe acute confusional states associated with fever or trauma, building on earlier descriptions by Hippocrates around 400 BC of similar transient mental disturbances. By the 19th century, the adjective and noun "deliriant" emerged in English medical literature around the 1830s, referring to agents or conditions that induce delirium, particularly in toxicology where substances like atropine were classified as causing such states. In psychiatry, the term gained traction during the 1800s as part of evolving classifications of mental disorders, with "delirium" distinguishing acute, reversible confusional psychoses from chronic conditions like dementia, as detailed in early 19th-century texts on insanity. The related term "delirifacient," coined in the 19th century from Latin delirium and faciens ("making"), specifically denoted delirium-inducing substances in pharmacological writing, appearing in medical dictionaries by the mid-1800s to describe toxicants like certain alkaloids. In 20th-century , "deliriant" evolved into a distinct category for psychoactive substances, particularly anticholinergics, with the term introduced by David F. Duncan and Robert S. Gold in 1982 to differentiate them from serotonergic psychedelics and based on their confusional rather than perceptual effects. This nomenclature arose amid post-1950s debates on classifying , where terms like "psychedelic" (coined by in 1957) and "hallucinogen" emphasized mind-manifesting or visual alterations, prompting distinctions for deliriants to highlight their delirium-like profile. Early toxicologists, such as Louis Lewin in his 1924 classification of mind-altering plants, influenced this adoption by grouping phantastica () separately from inebriants, laying groundwork for later refinements in deliriant terminology.

Pharmacological Aspects

Mechanism of Action

Deliriants primarily exert their psychoactive effects through competitive antagonism at muscarinic receptors (mAChRs), specifically the M1 through M5 subtypes, which disrupts and inhibits activity. This blockade prevents from binding to postsynaptic receptors in the central and peripheral nervous systems, leading to a range of physiological and cognitive disruptions characteristic of the deliriant class. The extent of receptor inhibition follows a dose-response relationship typical of competitive antagonists, described by the equation: % inhibition=[D][D]+IC50×100\% \ inhibition = \frac{[D]}{[D] + IC_{50}} \times 100 where [D][D] represents the drug concentration and IC50IC_{50} is the concentration producing 50% receptor blockade. For prototypical deliriants like , the IC50IC_{50} at muscarinic receptors is approximately 55 nM, reflecting high potency in antagonizing these sites. Certain deliriants, notably first-generation antihistamines, additionally antagonize histamine H1 receptors, enhancing sedative effects through suppression of histaminergic arousal pathways in the . Unlike serotonergic hallucinogens that primarily activate 5-HT2A receptors or agents that block NMDA receptors, deliriants show negligible direct interactions with or systems, confining their hallucinogenic profile to mechanisms. Pharmacokinetically, deliriants demonstrate rapid absorption and onset, typically 15–60 minutes after oral ingestion, with effect durations ranging from 4 to 24 hours based on compound-specific factors such as dose and route. Metabolism occurs predominantly in the liver; antihistamine deliriants like diphenhydramine undergo extensive first-pass processing via cytochrome P450 enzymes, mainly CYP2D6, yielding active metabolites with elimination half-lives of 4–8 hours. In contrast, tropane alkaloid deliriants such as scopolamine exhibit quicker clearance, with a serum half-life of 2–3 hours following hepatic biotransformation and renal excretion. Differences in binding profiles exist across deliriant classes: alkaloids like display high-affinity, selective competitive antagonism at muscarinic receptors, while antihistamines engage these sites with lower potency alongside their primary H1 blockade, resulting in more varied pharmacokinetic behaviors.

Effects

Deliriants induce a range of psychological effects characterized by vivid and realistic hallucinations, often involving nonexistent people, , or other entities that users perceive as entirely real. These hallucinations are frequently accompanied by , heightened anxiety, and , where individuals fill memory gaps with fabricated details. A hallmark feature is , which prevents users from recalling the deliriant episode, contributing to the disorienting nature of the experience. Physiologically, deliriant intoxication manifests as the classic anticholinergic toxidrome, encompassing due to impaired , from sympathetic overdrive, leading to , , and dry mucous membranes resulting from reduced secretions. These symptoms are memorably summarized by the mnemonic: blind as a (mydriasis and visual disturbances), hot as a (), dry as a ( and anhidrosis), red as a beet (flushing), and mad as a ( and agitation). Cognitively, users experience severe impairments in judgment and heightened , often leading them to act on hallucinated commands or misinterpret reality, which can result in dangerous behaviors. The resulting typically persists for 12-48 hours, marked by profound and disorientation. The progression of effects is dose-dependent: low doses primarily cause and mild , while higher doses escalate to severe agitation, seizures, or . Long-term risks, such as persistent cognitive deficits including memory impairment and , are rare but have been documented in cases of chronic abuse. Individual variability in effects is influenced by factors such as age (with older individuals more susceptible to severe symptoms), pre-existing tolerance, and co-ingestion of substances; for instance, alcohol can exacerbate and intensify physiological distress. These symptoms arise from muscarinic receptor antagonism in the central and peripheral nervous systems.

Classification of Deliriants

Anticholinergics

deliriants represent the largest class of deliriant substances, characterized by their ability to block muscarinic receptors in the central and peripheral nervous systems, thereby inducing a state of profound marked by confusion, hallucinations, and disorientation. These compounds are predominantly alkaloids derived from plants in the family, such as Atropa, , and Hyoscyamus genera, which have been used historically for both medicinal and intoxicating purposes. Prominent examples include atropine, extracted from deadly nightshade (Atropa belladonna); scopolamine, obtained from jimsonweed (); and hyoscyamine, isolated from henbane (). These natural alkaloids occur in various parts of the plants, including leaves, seeds, and roots, with concentrations varying by species and environmental factors. Synthetic analogs, such as benztropine, mimic the tropane structure and exhibit similar effects, though they are primarily developed for therapeutic applications like treating . These substances are noted for their high potency and extended duration of effects, often resulting in lasting from 24 to 72 hours or longer, particularly with , due to its strong penetration and slow elimination. Plant-based exposures are the most common route, frequently involving accidental ingestion or intentional abuse of wild or cultivated plants, which can lead to unpredictable dosing and severe outcomes. The isolation of these alkaloids dates back to the , with atropine first purified in 1833 from Atropa belladonna by chemists Philipp L. Geiger and Rudolf Brandes, followed by hyoscyamine in 1833 and scopolamine in the 1880s. In modern medicine, scopolamine is employed in transdermal patches for preventing , highlighting its therapeutic value despite the recognized abuse potential that emerged in reports from the onward, when recreational misuse of plant sources and pharmaceuticals began to be documented in clinical literature.

Antihistamines

deliriants consist of first-generation H1 receptor antagonists characterized by significant off-target activity, which contributes to their hallucinogenic potential at supratherapeutic doses. Prominent examples include diphenhydramine (commonly marketed as ), dimenhydrinate (Dramamine), and , all of which readily cross the blood-brain barrier to exert effects. These agents belong to structural classes such as ethanolamines (e.g., diphenhydramine and dimenhydrinate) or piperazines, features that enhance their and CNS penetration. Their widespread over-the-counter availability has facilitated frequent misuse, particularly among adolescents seeking altered states. In high doses, typically ranging from 500 to 1500 mg for diphenhydramine, these antihistamines induce deliriant effects marked by intense sedation surpassing that of pure anticholinergics, alongside realistic hallucinations and cognitive disruption. Users commonly report visual phenomena such as "shadow people" or shadowy figures, often accompanied by dysphoria and confusion, distinguishing these experiences from more euphoric hallucinogens. The onset of peak effects occurs within 1-2 hours, with the deliriant phase lasting 4-8 hours, shorter than many other deliriants due to the drugs' pharmacokinetic profiles. Developed in the 1940s for managing allergies and , these compounds' deliriant properties emerged in through case reports of adolescent abuse starting in the . misuse now represents the majority of over-the-counter deliriant abuse cases, prompting U.S. warnings in the about severe risks including cardiac arrhythmias and seizures from excessive intake.

Other Classes

Beyond the primary categories of anticholinergics and antihistamines, deliriants encompass atypical substances with mechanisms that induce delirium-like states through non-acetylcholinergic pathways, though such examples are rare and often debated due to overlapping classifications with other types. One prominent case is , the primary psychoactive compound in mushrooms, which acts as an orthosteric agonist at ionotropic GABA_A receptors, leading to enhanced inhibitory neurotransmission that manifests as profound disorientation, confusion, and hallucinatory experiences resembling without the full anticholinergic syndrome of dry mouth, , or . This mechanism contrasts sharply with the excitatory blockade seen in classical deliriants, producing sedative-hypnotic effects alongside perceptual distortions that users may not recognize as drug-induced. Unique to this class, muscimol's deliriant effects are linked to sporadic mushroom poisonings, with lower prevalence compared to pharmaceutical deliriants; for instance, accidental ingestions of A. muscaria contribute to a subset of the estimated 100 annual hospitalizations from exposures in the , as reported in national health data, often involving gastrointestinal distress followed by neurological symptoms requiring supportive care. Clusters of cases, such as the acute intoxications documented in in 2018 among individuals of Karen ethnicity from mistaking the mushrooms for edible varieties, highlight the risks in foraging contexts, with symptoms including agitation, hallucinations, and seizures resolving after 24-48 hours without long-term sequelae in most instances. Experimental in the 2020s has explored synthetic analogs of compounds for potential therapeutic modulation of states, though these remain preclinical and do not yet constitute established deliriants. Disputed inclusions in this category involve substances like , derived from , which exhibits a complex profile including receptor agonism and NMDA antagonism, occasionally producing deliriant elements such as oneiric visions and confusion amid its primary and anti-addictive effects, but is more accurately classified as a rather than a pure deliriant. Similarly, certain anesthetics like show overlaps with -induced disorientation but lack the characteristic realistic hallucinations of deliriants. Many purported "other" deliriants, such as various novel psychoactive substances, have been debunked as misclassifications upon toxicological review, emphasizing the need for evidence-based categorization focused on verifiable hallucinatory .

Uses and Risks

Recreational Use

Recreational use of deliriants primarily stems from the pursuit of intense, realistic hallucinations and dissociative "blackout" states, often appealing to adolescents due to the easy availability of over-the-counter substances like diphenhydramine (found in ). This motivation has fueled social media-driven trends, such as the that emerged in 2020 on , where users ingest excessive amounts to induce vivid perceptual distortions. Common methods involve oral ingestion of high doses of diphenhydramine, often in the range of several hundred milligrams, or consuming parts of plants like , including chewing seeds, brewing teas, or smoking dried leaves. These practices typically occur in solitary environments or small groups, with users influenced by online accounts sharing experiences. According to (NIDA) surveys, including Monitoring the Future data, past-year nonmedical use of over-the-counter medications like antihistamines remains low among youth, with rates around 2-4% as of 2024, though specific to deliriants like diphenhydramine, misuse is less commonly tracked but shows stable low prevalence. Temporary increases have been observed during events like the , amplified by discussions on online forums, and as of 2025, reports indicate rising misuse of OTC antihistamines among teens, with an 87% increase in pediatric ingestions from 2015-2024. Deliriants feature in cultural portrayals of altered , such as hallucinatory sequences in films depicting substance-induced and oblique references in music to toxic plants like belladonna. A major barrier to repeated use is the drugs' reputation for producing highly unpleasant, uncontrollable experiences marked by , , and physical discomfort, which often results in low rates of habitual consumption.

Therapeutic and Medical Contexts

Deliriants, primarily compounds, have established roles in medical practice due to their ability to block muscarinic receptors, which can mitigate specific physiological symptoms in controlled settings. is approved for preventing , administered via patches containing 1.5 mg of the base, which deliver approximately 1 mg over 72 hours following an initial . Atropine, another key deliriant, is widely used in to dilate pupils for eye examinations and treat conditions like by paralyzing the . In , atropine serves as a first-line agent to reverse symptomatic by increasing through vagal . Historically, has been employed as an for , reducing gastrointestinal motility and cramping. It also finds use in management to alleviate rigidity, tremors, and by countering excessive activity. In early 20th-century and , combined with induced "twilight sleep" during labor, aiming to provide and relief, though this practice declined due to unpredictable side effects. Ongoing research explores deliriants' potential in neurodegenerative and addictive disorders, tempered by their inherent toxicity. Selective muscarinic modulation, particularly targeting M1 receptors, shows promise for by enhancing cognitive function and reducing amyloid-beta pathology, as investigated in preclinical models and early agonist trials. Regulatory frameworks vary by compound and form; pure hallucinogenic extracts like those from (containing and atropine) are not federally scheduled in the as plants but face state-level restrictions in places like and , while low-dose deliriants, such as diphenhydramine, remain available over-the-counter for relief without hallucinogenic intent. The narrow of deliriants—exemplified by atropine's small margin between effective and toxic doses—poses significant challenges, restricting broader therapeutic exploration and necessitating precise dosing to avoid or cardiovascular complications. Recent investigations into deliriants for anxiety, post-2022, remain unproven, with no robust clinical evidence supporting efficacy or safety beyond anecdotal reports.

Toxicity and Overdose Management

Overdose of deliriants, particularly , can escalate the classic to life-threatening manifestations including seizures, , and , often due to or cardiac arrhythmias. While fatalities are uncommon, comprising less than 1% of reported cases, severe outcomes arise from and autonomic instability. varies by agent; for example, the oral LD50 of atropine in mice is approximately 75 mg/kg, though human fatal doses range widely from 1.6 mg to over 100 mg depending on individual factors. Key risk factors for deliriant overdose include , which exacerbates toxicity through synergistic effects on the , and accidental pediatric exposures, such as children mistaking berries or seeds for toys or food. In the United States, poison control centers receive thousands of annual calls related to anticholinergic exposures, with data from 2015 documenting approximately 14,000 exposures, many involving unintentional ingestions. Management of deliriant overdose prioritizes supportive care, including intravenous fluids for hydration, active cooling measures for , and monitoring for cardiopulmonary complications. The specific antidote , administered at 1-2 mg intravenously over 5 minutes, reverses muscarinic blockade by inhibiting , thereby increasing levels at synapses; repeat dosing may be needed every 20-30 minutes if initial response is inadequate, with atropine kept ready to counter potential excess. For agitation, intravenous benzodiazepines serve as first-line therapy to control seizures and without worsening effects. Long-term sequelae from deliriant overdose are rare but may include persistent with ongoing hallucinations or , particularly following severe episodes. The American Association of Poison Control Centers (AAPCC) guidelines, as reflected in recent annual reports, underscore the role of benzodiazepines in managing acute agitation to mitigate such risks. Prevention efforts focus on campaigns targeting over-the-counter (OTC) medication misuse, such as educating pharmacists and communities on the risks of high-dose antihistamines or antimuscarinics, alongside investigations to identify patterns in accidental deaths and inform policy.

Historical and Cultural Significance

Folklore and Occultism

Deliriants, particularly those derived from plants like and belladonna, have long been intertwined with shamanic practices among indigenous groups in , where they were employed to induce visions for and healing. Historical accounts from 16th-century Spanish chroniclers, such as , describe Aztec and other Mesoamerican peoples using species in rituals to communicate with deities and ancestors, often preparing infusions or smokes to facilitate interpreted as spiritual journeys. Similarly, in during the late 17th century, belladonna was associated with accusations, including tenuous links to the Salem trials where hallucinatory symptoms were attributed to sorcery rather than , though direct evidence remains speculative. In traditions, deliriants featured prominently in "flying ointments" documented in 15th- and 16th-century grimoires and trial records, where atropine-rich plants like henbane and belladonna were smeared on the skin to enable and attendance at witches' sabbaths. These recipes, often involving animal fats as bases, appear in texts like the 1486 Malleus Maleficarum and later inquisitorial accounts, portraying the ointments as tools for transcending the physical realm into supernatural encounters. The revival of such practices in the 1970s neopagan movement, particularly within , saw modern witches experimenting with safer adaptations of these ointments for ritual trance states, drawing from historical sources to reclaim them as aids for personal . Hallucinations induced by deliriants were frequently interpreted in folklore as direct spirit communication or demonic possession, with users experiencing vivid encounters with otherworldly entities that reinforced beliefs in supernatural intervention. In Haitian Vodou myths, scopolamine from plants like contributed to tales of "" states, where victims appeared soulless and obedient, symbolizing the bokor's power to sever the soul from the body through a powder administered post-mortem simulation. Cross-culturally, held ritual significance in Indian tantric practices, where it was offered to deities like in Ayurvedic-influenced ceremonies to invoke ecstatic visions, though its widespread use postdates early medieval introductions around the despite earlier textual allusions. In contemporary literature, works like Coby Michael's The Poison Path Herbal (2021) document reconstructed recipes using deliriant plants, emphasizing ethical sourcing and to avoid toxicity while preserving their mystical heritage.

Historical Uses and Incidents

The earliest documented uses of deliriants trace back to ancient civilizations, where plants like were employed for medicinal purposes. The , dating to approximately 1550 BCE, describes powdered hyoscyamus as a remedy to alleviate pain associated with intestinal worms, highlighting its role as a and in Egyptian pharmacology. In , was utilized as an during surgical procedures. , in his (circa 77 CE), notes that a potion of was administered to patients prior to incisions or punctures to induce insensibility to pain, underscoring its application in early operative contexts despite the risks of toxicity. During the medieval and periods, deliriants such as belladonna (Atropa belladonna) were implicated in assassinations due to their potent toxic effects. A significant pharmacological advancement occurred in 1833 when atropine, the primary active in belladonna and other plants, was isolated by German chemists Philipp L. Geiger and Lorenz Hesse from the roots and leaves of Atropa belladonna, enabling more precise medical applications while revealing its deliriant properties. In the 19th and early 20th centuries, deliriants found experimental use in , notably through "," a combination of and introduced in the 1910s by German physicians Bernhard Kronig and Carl Gauss. This regimen aimed to reduce labor pain and induce but frequently resulted in , slowed respiration, and infant complications, leading to widespread criticism and eventual decline by the . The era saw informal experiments with species, particularly among anthropologists and seekers influenced by works like Carlos Castaneda's accounts of rituals, where Datura root teas were ingested for visionary experiences, often resulting in severe hallucinations and medical emergencies. Archaeological evidence further illuminates pre-Columbian Native American uses, with seeds and residues identified in sites across the American Southeast and western , including ceramic vessels and quids from as early as 1000 BCE, indicating ritualistic ingestion for altered states. Recent developments in the have prompted regulatory responses to deliriant risks among , particularly following teen deaths linked to the "Benadryl Challenge," where participants ingested excessive diphenhydramine to induce hallucinations; the U.S. issued public warnings in and monitored ongoing cases, contributing to calls for stricter over-the-counter packaging limits on antihistamines.

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