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Deliriant

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.^[1]^[2] 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.^[1] The pharmacology of deliriants centers on their anticholinergic properties, particularly as competitive antagonists at muscarinic receptors, which disrupts cholinergic signaling essential for cognition, memory, and sensory processing; 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.^[1]^[2] Prominent examples include tropane alkaloids such as atropine, scopolamine, and hyoscyamine, which are naturally occurring in plants of the Solanaceae 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.^[3]^[4] Additionally, certain pharmaceuticals exhibit deliriant effects at high doses, including diphenhydramine (found in over-the-counter antihistamines like Benadryl), which exerts secondary anticholinergic activity leading to similar hallucinatory and delirious states.^[5]^[6] Historically, these compounds have been used medicinally for millennia—tropane alkaloids were documented in ancient Egyptian, Greek, and Indian texts for treating pain, inducing sedation, and even as poisons—while modern applications leverage their anticholinergic actions without the hallucinogenic risks at therapeutic doses.^[3] For instance, atropine is administered intravenously to reverse bradycardia and organophosphate poisoning or topically as a mydriatic for eye examinations, and scopolamine is utilized transdermally to prevent motion sickness and postoperative nausea and vomiting.^[7]^[8] Despite these benefits, deliriants pose significant risks of toxicity, including life-threatening complications like seizures, coma, and cardiovascular instability, and their recreational use is uncommon due to the invariably dysphoric and amnesia-laden experiences they provoke.^[3]^[2]

Definition and Characteristics

Definition

Deliriants are a subclass of hallucinogenic substances that primarily induce a state of delirium, defined as an acute disturbance in attention and cognition characterized by confusion, disorientation, and realistic hallucinations that the user perceives as genuine sensory experiences rather than distortions of reality.^[9] Unlike psychedelics, which typically produce insightful perceptual alterations through serotonin receptor agonism, or dissociatives, which foster a sense of detachment via NMDA receptor antagonism, deliriants disrupt cholinergic signaling in the central nervous system, resulting in dream-like yet often terrifying states of altered consciousness.^[1] Common examples include anticholinergics like atropine and antihistamines such as diphenhydramine.^[9] The core symptoms of deliriant intoxication encompass profound amnesia, heightened suggestibility, and a marked loss of reality testing, often accompanied by potential for violent or bizarre behaviors due to the profound disorientation.^[10] Users may exhibit restlessness, agitation, and hallucinatory experiences that blend seamlessly with perceived reality, leading to impaired judgment and increased risk of harm.^[1] These effects stem from the blockade of muscarinic acetylcholine receptors, though detailed mechanisms are explored elsewhere.^[9] 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 plants and 18,589 to diphenhydramine, with most cases arising unintentionally rather than for psychoactive effects.^[11] More recent data from 2022 indicates 26,248 single exposures to diphenhydramine, highlighting ongoing risks including misuse trends.^[12] Intentional misuse remains uncommon compared to other hallucinogen classes, contributing to its relative rarity in recreational contexts.^[6]

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.^[13] 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.^[14] 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.^[15] 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.^[16] 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.^[17] In 20th-century psychopharmacology, "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 dissociatives based on their confusional rather than perceptual effects.^[4] This nomenclature arose amid post-1950s debates on classifying hallucinogens, where terms like "psychedelic" (coined by Humphry Osmond 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 (hallucinatory agents) separately from inebriants, laying groundwork for later refinements in deliriant terminology.^[18]

Pharmacological Aspects

Mechanism of Action

Deliriants primarily exert their psychoactive effects through competitive antagonism at muscarinic acetylcholine receptors (mAChRs), specifically the M1 through M5 subtypes, which disrupts cholinergic neurotransmission and inhibits parasympathetic nervous system activity.^[19]^[3] This blockade prevents acetylcholine 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.^[20] The extent of receptor inhibition follows a dose-response relationship typical of competitive antagonists, described by the equation:

\% \ inhibition = \frac{[D]}{[D] + IC_{50}} \times 100

where [D] represents the drug concentration and IC_{50} is the concentration producing 50% receptor blockade. For prototypical deliriants like scopolamine, the IC_{50} at muscarinic receptors is approximately 55 nM, reflecting high potency in antagonizing these sites.^[21]^[22] Certain deliriants, notably first-generation antihistamines, additionally antagonize histamine H1 receptors, enhancing sedative effects through suppression of histaminergic arousal pathways in the brain.^[23] Unlike serotonergic hallucinogens that primarily activate 5-HT2A receptors or dissociative agents that block NMDA receptors, deliriants show negligible direct interactions with serotonin or glutamatergic systems, confining their hallucinogenic profile to anticholinergic mechanisms.^[24] 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.^[25] 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.^[26] 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.^[27] Differences in binding profiles exist across deliriant classes: tropane alkaloids like scopolamine 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.^[28]^[29]

Effects

Deliriants induce a range of psychological effects characterized by vivid and realistic hallucinations, often involving nonexistent people, insects, or other entities that users perceive as entirely real.^[30] These hallucinations are frequently accompanied by paranoia, heightened anxiety, and confabulation, where individuals fill memory gaps with fabricated details.^[30] A hallmark feature is amnesia, which prevents users from recalling the deliriant episode, contributing to the disorienting nature of the experience.^[30] Physiologically, deliriant intoxication manifests as the classic anticholinergic toxidrome, encompassing hyperthermia due to impaired thermoregulation, tachycardia from sympathetic overdrive, mydriasis leading to blurred vision, urinary retention, and dry mucous membranes resulting from reduced secretions.^[10] These symptoms are memorably summarized by the mnemonic: blind as a bat (mydriasis and visual disturbances), hot as a hare (hyperthermia), dry as a bone (xerostomia and anhidrosis), red as a beet (flushing), and mad as a hatter (delirium and agitation).^[31] Cognitively, users experience severe impairments in judgment and heightened suggestibility, often leading them to act on hallucinated commands or misinterpret reality, which can result in dangerous behaviors.^[32] The resulting delirium typically persists for 12-48 hours, marked by profound confusion and disorientation.^[33] The progression of effects is dose-dependent: low doses primarily cause sedation and mild confusion, while higher doses escalate to severe agitation, seizures, or coma.^[10] Long-term risks, such as persistent cognitive deficits including memory impairment and executive dysfunction, are rare but have been documented in cases of chronic abuse.^[34] 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 dehydration and intensify physiological distress.^[35] These symptoms arise from muscarinic receptor antagonism in the central and peripheral nervous systems.^[36]

Classification of Deliriants

Anticholinergics

Anticholinergic deliriants represent the largest class of deliriant substances, characterized by their ability to block muscarinic acetylcholine receptors in the central and peripheral nervous systems, thereby inducing a state of profound delirium marked by confusion, hallucinations, and disorientation. These compounds are predominantly tropane alkaloids derived from plants in the Solanaceae family, such as Atropa, Datura, and Hyoscyamus genera, which have been used historically for both medicinal and intoxicating purposes.^[37]^[38] Prominent examples include atropine, extracted from deadly nightshade (Atropa belladonna); scopolamine, obtained from jimsonweed (Datura stramonium); and hyoscyamine, isolated from henbane (Hyoscyamus niger). 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 anticholinergic effects, though they are primarily developed for therapeutic applications like treating Parkinson's disease.^[38]^[9] These substances are noted for their high potency and extended duration of effects, often resulting in delirium lasting from 24 to 72 hours or longer, particularly with scopolamine, due to its strong central nervous system penetration and slow elimination. Plant-based exposures are the most common route, frequently involving accidental ingestion or intentional abuse of wild or cultivated Solanaceae plants, which can lead to unpredictable dosing and severe outcomes.^[39]^[40] The isolation of these alkaloids dates back to the 19th century, 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 motion sickness, highlighting its therapeutic value despite the recognized abuse potential that emerged in reports from the 1960s onward, when recreational misuse of plant sources and pharmaceuticals began to be documented in clinical literature.^[38]^[28]

Antihistamines

Antihistamine deliriants consist of first-generation H1 receptor antagonists characterized by significant off-target anticholinergic activity, which contributes to their hallucinogenic potential at supratherapeutic doses.^[41] Prominent examples include diphenhydramine (commonly marketed as Benadryl), dimenhydrinate (Dramamine), and promethazine, all of which readily cross the blood-brain barrier to exert central nervous system effects.^[42] These agents belong to structural classes such as ethanolamines (e.g., diphenhydramine and dimenhydrinate) or piperazines, features that enhance their lipophilicity and CNS penetration.^[43] Their widespread over-the-counter availability has facilitated frequent misuse, particularly among adolescents seeking altered states.^[44] 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.^[5] 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.^[5] 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.^[41] Developed in the 1940s for managing allergies and motion sickness, these compounds' deliriant properties emerged in medical literature through case reports of adolescent abuse starting in the 1970s.^[45] Antihistamine misuse now represents the majority of over-the-counter deliriant abuse cases, prompting U.S. Food and Drug Administration warnings in the 2010s about severe risks including cardiac arrhythmias and seizures from excessive intake.^[46]^[44]

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 hallucinogen types. One prominent case is muscimol, the primary psychoactive compound in Amanita muscaria 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 delirium without the full anticholinergic syndrome of dry mouth, tachycardia, or mydriasis.^[47] This GABAergic 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.^[48] 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 mushroom exposures in the US, as reported in national health data, often involving gastrointestinal distress followed by neurological symptoms requiring supportive care.^[49] Clusters of cases, such as the acute intoxications documented in Minnesota in 2018 among individuals of Karen ethnicity from Burma 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.^[50] Experimental research in the 2020s has explored synthetic analogs of GABAergic compounds for potential therapeutic modulation of delirium states, though these remain preclinical and do not yet constitute established deliriants. Disputed inclusions in this category involve substances like ibogaine, derived from Tabernanthe iboga, which exhibits a complex profile including sigma receptor agonism and NMDA antagonism, occasionally producing deliriant elements such as oneiric visions and confusion amid its primary dissociative and anti-addictive effects, but is more accurately classified as a oneirogen rather than a pure deliriant.^[51] Similarly, certain anesthetics like ketamine show overlaps with dissociative-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 delirium.

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 Benadryl). This motivation has fueled social media-driven trends, such as the Benadryl challenge that emerged in 2020 on TikTok, where users ingest excessive amounts to induce vivid perceptual distortions.^[46]^[52] Common methods involve oral ingestion of high doses of diphenhydramine, often in the range of several hundred milligrams, or consuming parts of plants like Datura stramonium, 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.^[46]^[52] According to National Institute on Drug Abuse (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 COVID-19 pandemic, 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.^[53]^[54]^[55] Deliriants feature in cultural portrayals of altered consciousness, such as hallucinatory sequences in films depicting substance-induced delirium and oblique references in psychedelic rock music to toxic plants like belladonna.^[56] A major barrier to repeated use is the drugs' reputation for producing highly unpleasant, uncontrollable experiences marked by dysphoria, confusion, and physical discomfort, which often results in low rates of habitual consumption.^[44]

Therapeutic and Medical Contexts

Deliriants, primarily anticholinergic compounds, have established roles in medical practice due to their ability to block muscarinic acetylcholine receptors, which can mitigate specific physiological symptoms in controlled settings.^[8] Scopolamine is approved for preventing postoperative nausea and vomiting, administered via transdermal patches containing 1.5 mg of the base, which deliver approximately 1 mg over 72 hours following an initial loading dose.^[57] Atropine, another key deliriant, is widely used in ophthalmology to dilate pupils for eye examinations and treat conditions like amblyopia by paralyzing the ciliary muscle.^[58] In cardiology, atropine serves as a first-line agent to reverse symptomatic bradycardia by increasing heart rate through vagal blockade.^[59] Historically, hyoscyamine has been employed as an antispasmodic for irritable bowel syndrome, reducing gastrointestinal motility and cramping.^[60] It also finds use in Parkinson's disease management to alleviate rigidity, tremors, and hyperhidrosis by countering excessive cholinergic activity.^[61] In early 20th-century psychiatry and obstetrics, scopolamine combined with morphine induced "twilight sleep" during labor, aiming to provide amnesia and pain relief, though this practice declined due to unpredictable side effects.^[62] 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 Alzheimer's disease by enhancing cognitive function and reducing amyloid-beta pathology, as investigated in preclinical models and early agonist trials.^[63] Regulatory frameworks vary by compound and form; pure hallucinogenic extracts like those from Datura (containing scopolamine and atropine) are not federally scheduled in the US as plants but face state-level restrictions in places like Connecticut and New Jersey, while low-dose antihistamine deliriants, such as diphenhydramine, remain available over-the-counter for allergy relief without hallucinogenic intent. The narrow therapeutic index 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 delirium or cardiovascular complications.^[59] Recent investigations into microdosing deliriants for anxiety, post-2022, remain unproven, with no robust clinical evidence supporting efficacy or safety beyond anecdotal reports.^[64]

Toxicity and Overdose Management

Overdose of deliriants, particularly anticholinergics, can escalate the classic toxidrome to life-threatening manifestations including seizures, coma, and death, often due to respiratory failure or cardiac arrhythmias.^[9]^[33] While fatalities are uncommon, comprising less than 1% of reported cases, severe outcomes arise from central nervous system depression and autonomic instability.^[9] Lethality 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.^[65]^[66] Key risk factors for deliriant overdose include polysubstance use, which exacerbates toxicity through synergistic effects on the central nervous system, and accidental pediatric exposures, such as children mistaking Datura stramonium berries or seeds for toys or food.^[39]^[67] 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.^[9] Management of deliriant overdose prioritizes supportive care, including intravenous fluids for hydration, active cooling measures for hyperthermia, and monitoring for cardiopulmonary complications.^[9] The specific antidote physostigmine, administered at 1-2 mg intravenously over 5 minutes, reverses muscarinic blockade by inhibiting acetylcholinesterase, thereby increasing acetylcholine levels at synapses; repeat dosing may be needed every 20-30 minutes if initial response is inadequate, with atropine kept ready to counter potential cholinergic excess.^[68]^[33] For agitation, intravenous benzodiazepines serve as first-line therapy to control seizures and delirium without worsening anticholinergic effects.^[9] Long-term sequelae from deliriant overdose are rare but may include persistent psychosis with ongoing hallucinations or cognitive impairment, particularly following severe anticholinergic episodes.^[69] 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.^[70]^[9] Prevention efforts focus on public health campaigns targeting over-the-counter (OTC) medication misuse, such as educating pharmacists and communities on the risks of high-dose antihistamines or antimuscarinics, alongside forensic toxicology investigations to identify patterns in accidental deaths and inform policy.^[71]^[72]

Historical and Cultural Significance

Folklore and Occultism

Deliriants, particularly those derived from plants like Datura and belladonna, have long been intertwined with shamanic practices among indigenous groups in Mexico, where they were employed to induce visions for divination and healing. Historical accounts from 16th-century Spanish chroniclers, such as Bernardino de Sahagún, describe Aztec and other Mesoamerican peoples using Datura species in rituals to communicate with deities and ancestors, often preparing infusions or smokes to facilitate altered states interpreted as spiritual journeys.^[73] Similarly, in European folklore during the late 17th century, belladonna was associated with witchcraft accusations, including tenuous links to the Salem trials where hallucinatory symptoms were attributed to sorcery rather than poisoning, though direct evidence remains speculative.^[74] In occult 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 astral projection 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.^[75] The revival of such practices in the 1970s neopagan movement, particularly within Wicca, 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 gnosis.^[76] 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 Brugmansia contributed to tales of "zombie" 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.^[77] Cross-culturally, Datura held ritual significance in Indian tantric practices, where it was offered to deities like Shiva in Ayurvedic-influenced ceremonies to invoke ecstatic visions, though its widespread use postdates early medieval introductions around the 16th century despite earlier textual allusions.^[78] In contemporary occult literature, works like Coby Michael's The Poison Path Herbal (2021) document reconstructed flying ointment recipes using deliriant plants, emphasizing ethical sourcing and harm reduction to avoid toxicity while preserving their mystical heritage.^[76]

Historical Uses and Incidents

The earliest documented uses of deliriants trace back to ancient civilizations, where plants like hyoscyamus (Hyoscyamus niger) were employed for medicinal purposes. The Ebers Papyrus, dating to approximately 1550 BCE, describes powdered hyoscyamus as a remedy to alleviate pain associated with intestinal worms, highlighting its role as a sedative and analgesic in Egyptian pharmacology.^[79] In ancient Rome, mandrake (Mandragora officinarum) was utilized as an anesthetic during surgical procedures. Pliny the Elder, in his Natural History (circa 77 CE), notes that a potion of mandrake 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.^[80] During the medieval and Renaissance 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 alkaloid in belladonna and other Solanaceae 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.^[81] In the 19th and early 20th centuries, deliriants found experimental use in obstetrics, notably through "twilight sleep," a combination of morphine and scopolamine introduced in the 1910s by German physicians Bernhard Kronig and Carl Gauss. This regimen aimed to reduce labor pain and induce amnesia but frequently resulted in delirium, slowed respiration, and infant complications, leading to widespread criticism and eventual decline by the 1920s.^[82] The 1960s counterculture era saw informal experiments with Datura species, particularly among anthropologists and seekers influenced by works like Carlos Castaneda's accounts of Yaqui rituals, where Datura root teas were ingested for visionary experiences, often resulting in severe hallucinations and medical emergencies.^[83] Archaeological evidence further illuminates pre-Columbian Native American uses, with datura seeds and residues identified in sites across the American Southeast and western Mexico, including ceramic vessels and quids from as early as 1000 BCE, indicating ritualistic ingestion for altered states.^[84] Recent developments in the 2020s have prompted regulatory responses to deliriant risks among youth, particularly following teen deaths linked to the TikTok "Benadryl Challenge," where participants ingested excessive diphenhydramine to induce hallucinations; the U.S. Food and Drug Administration issued public warnings in 2020 and monitored ongoing cases, contributing to calls for stricter over-the-counter packaging limits on antihistamines.^[85]

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