Scopolamine, also known as hyoscine, or Devil's Breath, is a medication used to treat

motion sickness Motion sickness occurs due to a difference between actual and expected motion. Symptoms commonly include nausea, vomiting, cold sweat, headache, dizziness, tiredness, loss of appetite, and increased salivation. Complications may rarely include ...

and postoperative nausea and vomiting. It is also sometimes used before surgery to decrease

saliva Saliva (commonly referred as spit or drool) is an extracellular fluid produced and secreted by salivary glands in the mouth. In humans, saliva is around 99% water, plus electrolytes, mucus, white blood cells, epithelial cells (from which ...

. When used by injection, effects begin after about 20 minutes and last for up to 8 hours. It may also be used orally and as a

transdermal patch A transdermal patch is a medicated adhesive patch that is placed on the skin to deliver a specific Dose (biochemistry), dose of medication through the skin and into the bloodstream. An advantage of a transdermal drug delivery route over ot ...

since it has been long known to have transdermal

bioavailability In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation. By definition, when a medication is administered intravenously, its bioavailability is 100%. H ...

. Scopolamine is in the

antimuscarinic A muscarinic acetylcholine receptor antagonist, also simply known as a muscarinic antagonist or as an antimuscarinic agent, is a type of anticholinergic drug that blocks the activity of the muscarinic acetylcholine receptors (mAChRs). The muscarin ...

family of drugs and works by blocking some of the effects of

acetylcholine Acetylcholine (ACh) is an organic compound that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Par ...

within the

nervous system In biology, the nervous system is the complex system, highly complex part of an animal that coordinates its behavior, actions and sense, sensory information by transmitting action potential, signals to and from different parts of its body. Th ...

. Scopolamine was first written about in 1881 and started to be used for

anesthesia Anesthesia (American English) or anaesthesia (British English) is a state of controlled, temporary loss of sensation or awareness that is induced for medical or veterinary purposes. It may include some or all of analgesia (relief from or prev ...

around 1900. Scopolamine is also the main active component produced by certain plants of the

nightshade family Solanaceae (), commonly known as the nightshades, is a family of flowering plants in the order Solanales. It contains approximately 2,700 species, several of which are used as agricultural crops, medicinal plants, and ornamental plants. Many me ...

, which historically have been used as

psychoactive A psychoactive drug, psychopharmaceutical, mind-altering drug, consciousness-altering drug, psychoactive substance, or psychotropic substance is a chemical substance that alters psychological functioning by modulating central nervous system acti ...

drugs, known as '' deliriants'', due to their antimuscarinic-induced hallucinogenic effects in higher doses. In these contexts, its mind-altering effects have been utilized for recreational and

occult The occult () is a category of esoteric or supernatural beliefs and practices which generally fall outside the scope of organized religion and science, encompassing phenomena involving a 'hidden' or 'secret' agency, such as magic and mysti ...

purposes. The name "scopolamine" is derived from one type of nightshade known as '' Scopolia'', while the name "hyoscine" is derived from another type known as ''

Hyoscyamus niger Henbane (''Hyoscyamus niger'', also black henbane and stinking nightshade) is a poisonous plant belonging to tribe Hyoscyameae of the nightshade family ''Solanaceae''. Henbane is native to temperate Europe and Siberia, and naturalised in Great B ...

'', or black henbane. It is on the

World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...

Medical uses

Scopolamine has a number of formal uses in modern medicine where it is used in its isolated form and in low doses to treat: * Postoperative nausea and vomiting *

Motion sickness Motion sickness occurs due to a difference between actual and expected motion. Symptoms commonly include nausea, vomiting, cold sweat, headache, dizziness, tiredness, loss of appetite, and increased salivation. Complications may rarely include ...

, including sea sickness, leading to its use by scuba divers (where it is often applied as a transdermal patch behind the ear) *

Gastrointestinal The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascular system. ...

spasms *

Renal In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and right in the retrop ...

or biliary spasms * Aid in gastrointestinal

radiology Radiology ( ) is the medical specialty that uses medical imaging to diagnose diseases and guide treatment within the bodies of humans and other animals. It began with radiography (which is why its name has a root referring to radiation), but tod ...

and

endoscopy An endoscopy is a procedure used in medicine to look inside the body. The endoscopy procedure uses an endoscope to examine the interior of a hollow organ or cavity of the body. Unlike many other medical imaging techniques, endoscopes are insert ...

Irritable bowel syndrome Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by a group of symptoms that commonly include abdominal pain, abdominal bloating, and changes in the consistency of bowel movements. These symptoms may ...

* Clozapine-induced drooling *

Bowel The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascular system. T ...

colic * Eye

inflammation Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...

It is sometimes used as a premedication, especially to reduce

respiratory tract The respiratory tract is the subdivision of the respiratory system involved with the process of conducting air to the alveoli for the purposes of gas exchange in mammals. The respiratory tract is lined with respiratory epithelium as respirato ...

secretions in

surgery Surgery is a medical specialty that uses manual and instrumental techniques to diagnose or treat pathological conditions (e.g., trauma, disease, injury, malignancy), to alter bodily functions (e.g., malabsorption created by bariatric surgery s ...

, most commonly by injection. Common side effects include sleepiness,

blurred vision Blurred vision is an ocular symptom where vision becomes less precise and there is added difficulty to resolve fine details. Temporary blurred vision may involve dry eyes, eye infections, alcohol poisoning, hypoglycemia, or low blood pressur ...

, dilated pupils, and dry mouth. It is not recommended in people with angle-closure

glaucoma Glaucoma is a group of eye diseases that can lead to damage of the optic nerve. The optic nerve transmits visual information from the eye to the brain. Glaucoma may cause vision loss if left untreated. It has been called the "silent thief of ...

bowel obstruction Bowel obstruction, also known as intestinal obstruction, is a mechanical or Ileus, functional obstruction of the Gastrointestinal tract#Lower gastrointestinal tract, intestines which prevents the normal movement of the products of digestion. Ei ...

. Whether its use during pregnancy is safe remains unclear, and use during

breastfeeding Breastfeeding, also known as nursing, is the process where breast milk is fed to a child. Infants may suck the milk directly from the breast, or milk may be extracted with a Breast pump, pump and then fed to the infant. The World Health Orga ...

is still cautioned by health professionals and manufacturers of the drug.

Breastfeeding

Scopolamine enters

breast milk Breast milk (sometimes spelled as breastmilk) or mother's milk is milk produced by the mammary glands in the breasts of women. Breast milk is the primary source of nutrition for newborn infants, comprising fats, proteins, carbohydrates, and a var ...

secretion Secretion is the movement of material from one point to another, such as a secreted chemical substance from a cell or gland. In contrast, excretion is the removal of certain substances or waste products from a cell or organism. The classical mec ...

. Although no human studies exist to document the safety of scopolamine while nursing, the manufacturer recommends that caution be taken if scopolamine is administered to a breastfeeding woman.

Adverse effects

Adverse effect incidence: Uncommon (0.1–1% incidence) adverse effects include: * Dry mouth * Anhidrosis (reduced ability to sweat to cool off) *

Tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ...

(usually occurs at higher doses and is succeeded by bradycardia) *

Bradycardia Bradycardia, also called bradyarrhythmia, is a resting heart rate under 60 beats per minute (BPM). While bradycardia can result from various pathological processes, it is commonly a physiological response to cardiovascular conditioning or due ...

Urticaria Hives, also known as urticaria, is a kind of skin rash with red or flesh-colored, raised, itchy bumps. Hives may burn or sting. The patches of rash may appear on different body parts, with variable duration from minutes to days, and typically ...

(hives) * Pruritus (itching) Rare (<0.1% incidence) adverse effects include: *

Constipation Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The Human feces, stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the ...

Urinary retention Urinary retention is an inability to completely empty the bladder. Onset can be sudden or gradual. When of sudden onset, symptoms include an inability to urinate and lower abdominal pain. When of gradual onset, symptoms may include urinary incont ...

Hallucination A hallucination is a perception in the absence of an external stimulus that has the compelling sense of reality. They are distinguishable from several related phenomena, such as dreaming ( REM sleep), which does not involve wakefulness; pse ...

s * Agitation * Confusion * Restlessness *

Seizure A seizure is a sudden, brief disruption of brain activity caused by abnormal, excessive, or synchronous neuronal firing. Depending on the regions of the brain involved, seizures can lead to changes in movement, sensation, behavior, awareness, o ...

s Unknown frequency adverse effects include: * Anaphylactic shock or reactions *

Dyspnea Shortness of breath (SOB), known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing discomfort that ...

(shortness of breath) * Rash *

Erythema Erythema (, ) is redness of the skin or mucous membranes, caused by hyperemia (increased blood flow) in superficial capillaries. It occurs with any skin injury, infection, or inflammation. Examples of erythema not associated with pathology inc ...

* Other hypersensitivity reactions *

Blurred vision Blurred vision is an ocular symptom where vision becomes less precise and there is added difficulty to resolve fine details. Temporary blurred vision may involve dry eyes, eye infections, alcohol poisoning, hypoglycemia, or low blood pressur ...

Mydriasis Mydriasis is the Pupillary dilation, dilation of the pupil, usually having a non-physiological cause, or sometimes a physiological pupillary response. Non-physiological causes of mydriasis include disease, Physical trauma, trauma, or the use of c ...

(dilated pupils) *

Drowsiness Somnolence (alternatively sleepiness or drowsiness) is a state of strong desire for sleep, or sleeping for unusually long periods (compare hypersomnia). It has distinct meanings and causes. It can refer to the usual state preceding falling asleep ...

Dizziness Dizziness is an imprecise term that can refer to a sense of disorientation in space, vertigo, or lightheadedness. It can also refer to Balance disorder, disequilibrium or a non-specific feeling, such as giddiness or foolishness. Dizziness is a ...

Somnolence Somnolence (alternatively sleepiness or drowsiness) is a state of strong desire for sleep, or sleeping for unusually long periods (compare hypersomnia). It has distinct meanings and causes. It can refer to the usual state preceding falling aslee ...

Overdose

Physostigmine Physostigmine (also known as eserine from ''éséré'', the West African name for the Calabar bean) is a highly toxic parasympathomimetic alkaloid, specifically, a reversible cholinesterase inhibitor. It occurs naturally in the Calabar bean and ...

, a cholinergic drug that readily crosses the

blood–brain barrier The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that regulates the transfer of solutes and chemicals between the circulatory system and the central nervous system ...

, has been used as an antidote to treat the

central nervous system depression Central nervous system depression (or CNS depression) is a nervous system disorder characterized by a severely impaired physiological state in which patients may exhibit decreased rate of breathing, decreased heart rate, and loss of consciousnes ...

symptoms of a scopolamine overdose. Other than this supportive treatment,

gastric lavage Gastric lavage, also commonly called stomach pumping or gastric irrigation or gastric suction, is the process of cleaning out the contents of the stomach using a tube. Since its first recorded use in the early 19th century, it has become one of the ...

and induced

emesis Vomiting (also known as emesis, puking and throwing up) is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenteritis, pregna ...

(vomiting) are usually recommended as treatments for oral overdoses. The symptoms of overdose include: * Tachycardia *

Arrhythmia Arrhythmias, also known as cardiac arrhythmias, are irregularities in the cardiac cycle, heartbeat, including when it is too fast or too slow. Essentially, this is anything but normal sinus rhythm. A resting heart rate that is too fast – ab ...

* Blurred vision *

Photophobia Photophobia is a medical symptom of abnormal intolerance to visual perception of light. As a medical symptom, photophobia is not a morbid fear or phobia, but an experience of discomfort or pain to the eyes due to light exposure or by presence o ...

or paradoxical reaction, which can present with

hallucinations A hallucination is a perception in the absence of an external stimulus that has the compelling sense of reality. They are distinguishable from several related phenomena, such as dreaming ( REM sleep), which does not involve wakefulness; pse ...

* Cheyne–Stokes respiration * Dry mouth * Skin reddening * Inhibition of

gastrointestinal motility Gastrointestinal physiology is the branch of Human body, human physiology that addresses the physical function of the Human gastrointestinal tract, gastrointestinal (GI) tract. The function of the GI tract is to process ingested food by mechanical ...

Route of administration

Scopolamine can be taken

by mouth Oral administration is a route of administration whereby a substance is taken through the Human mouth, mouth, swallowed, and then processed via the digestive system. This is a common route of administration for many medications. Oral administ ...

, subcutaneously, in the eye, and

intravenous Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutr ...

ly, as well as via a

Pharmacology

Pharmacodynamics

The pharmacological effects of scopolamine are mediated through the drug's competitive antagonism of the peripheral and central

muscarinic acetylcholine receptor Muscarinic acetylcholine receptors (mAChRs) are acetylcholine receptors that form G protein-coupled receptor, G protein-coupled receptor complexes in the cell membranes of certain neurons and other Cell (biology), cells. They play several role ...

s. Scopolamine acts as a nonspecific muscarinic antagonist at all four ( M₁, M₂, M₃, and M₄) receptor sites. In doses higher than intended for medicinal use, the hallucinogenic alteration of consciousness, as well as the

delirium Delirium (formerly acute confusional state, an ambiguous term that is now discouraged) is a specific state of acute confusion attributable to the direct physiological consequence of a medical condition, effects of a psychoactive substance, or ...

in particular, are tied to the compound's activity at the M₁ muscarinic receptor. M₁ receptors are located primarily in the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...

and are involved in perception, attention, and cognitive functioning. Delirium is associated solely with the antagonism of postsynaptic M₁ receptors; currently no other receptor subtypes have been implicated. Peripheral muscarinic receptors are part of the

autonomic nervous system The autonomic nervous system (ANS), sometimes called the visceral nervous system and formerly the vegetative nervous system, is a division of the nervous system that operates viscera, internal organs, smooth muscle and glands. The autonomic nervo ...

. M₂ receptors are located in the brain and heart, M₃ receptors are in salivary glands and M₄ receptors are in the brain and lungs. Due to the drug's inhibition of various signal transduction pathways, the decrease in

signaling is what leads to many of the cognitive deficits, mental impairments, and delirium associated with psychoactive doses. Medicinal effects appear to mostly be tied to activation of the peripheral receptors and only from marginal decreases in acetylcholine signaling. Although often broadly referred to as simply being 'anticholinergic',

would be more specific and accurate terminology to use for scopolamine, as, for example, it is not known to block nicotinic receptors.

Pharmacokinetics

Scopolamine undergoes first-pass metabolism and about 2.6% is excreted unchanged in urine. It has a bioavailability of 20-40%, reaches peak plasma concentration in about 45 minutes, and in healthy subjects has an average half-life of 5 hours (observed range 2 - 10 hours). Scopolamine is primarily metabolized by the

CYP3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine, which in humans is encoded by ''CYP3A4'' gene. It organic redox reaction, oxidizes small foreign organic molecules ( ...

enzyme, and grapefruit juice decreases metabolism of scopolamine, consequently increasing plasma concentration.

Chemistry

Biosynthesis in plants

Scopolamine is among the secondary metabolites of plants from the

Solanaceae Solanaceae (), commonly known as the nightshades, is a family of flowering plants in the order Solanales. It contains approximately 2,700 species, several of which are used as agricultural crops, medicinal plants, and ornamental plants. Many me ...

(nightshade) family of plants, including

henbane Henbane (''Hyoscyamus niger'', also black henbane and stinking nightshade) is a poisonous plant belonging to tribe Hyoscyameae of the nightshade family ''Solanaceae''. Henbane is native to Temperate climate, temperate Europe and Siberia, and natu ...

(''Hyoscyamus niger''), jimson weed (''

Datura ''Datura'' is a genus of nine species of highly poisonous, Vespertine (biology), vespertine-flowering plants belonging to the nightshade family (Solanaceae). They are commonly known as thornapples or jimsonweeds, but are also known as devil's t ...

''), angel's trumpets (''

Brugmansia ''Brugmansia'' is a genus of seven species of flowering plants in the nightshade family Solanaceae. They are woody trees or shrubs, with pendulous flowers, and have no spines on their fruit. Their large, fragrant flowers give them their common n ...

''), deadly nightshade ('' Belladonna''), mandrake ('' Mandragora officinarum''), and corkwood ('' Duboisia''). Tropane alkaloids biochemistry

The

biosynthesis Biosynthesis, i.e., chemical synthesis occurring in biological contexts, is a term most often referring to multi-step, enzyme-Catalysis, catalyzed processes where chemical substances absorbed as nutrients (or previously converted through biosynthe ...

of scopolamine begins with the

decarboxylation Decarboxylation is a chemical reaction that removes a carboxyl group and releases carbon dioxide (CO2). Usually, decarboxylation refers to a reaction of carboxylic acids, removing a carbon atom from a carbon chain. The reverse process, which is ...

of L-ornithine to

putrescine Putrescine is an organic compound with the formula (CH2)4(NH2)2. It is a colorless solid that melts near room temperature. It is classified as a diamine. Together with cadaverine, it is largely responsible for the foul odor of Putrefaction, putref ...

ornithine decarboxylase The enzyme ornithine decarboxylase (, ODC) catalyzes the decarboxylation of ornithine (a product of the urea cycle) to form putrescine. This reaction is the committed step in polyamine synthesis. In humans, this protein has 461 amino acids ...

. Putrescine is

methylated Methylation, in the chemical sciences, is the addition of a methyl group on a substrate, or the substitution of an atom (or group) by a methyl group. Methylation is a form of alkylation, with a methyl group replacing a hydrogen atom. These term ...

to N-methylputrescine by putrescine N-methyltransferase. A putrescine oxidase that specifically recognizes methylated putrescine catalyzes the

deamination Deamination is the removal of an amino group from a molecule. Enzymes that catalysis, catalyse this reaction are called deaminases. In the human body, deamination takes place primarily in the liver; however, it can also occur in the kidney. In s ...

of this compound to 4-methylaminobutanal, which then undergoes a spontaneous ring formation to N-

methyl In organic chemistry, a methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms, having chemical formula (whereas normal methane has the formula ). In formulas, the group is often abbreviated as ...

- pyrrolium cation. In the next step, the pyrrolium cation condenses with acetoacetic acid yielding hygrine. No enzymatic activity could be demonstrated to catalyze this reaction. Hygrine further rearranges to tropinone. Subsequently, tropinone reductase I converts tropinone to tropine, which condenses with

phenylalanine Phenylalanine (symbol Phe or F) is an essential α-amino acid with the chemical formula, formula . It can be viewed as a benzyl group substituent, substituted for the methyl group of alanine, or a phenyl group in place of a terminal hydrogen of ...

-derived phenyllactate to littorine. A

cytochrome P450 Cytochromes P450 (P450s or CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that mostly, but not exclusively, function as monooxygenases. However, they are not omnipresent; for examp ...

classified as Cyp80F1 oxidizes and rearranges littorine to hyoscyamine

aldehyde In organic chemistry, an aldehyde () (lat. ''al''cohol ''dehyd''rogenatum, dehydrogenated alcohol) is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred ...

. In the final step,

hyoscyamine Hyoscyamine (also known as daturine or duboisine) is a naturally occurring tropane alkaloid and plant toxin. It is a secondary metabolite found in certain plants of the family Solanaceae, including Hyoscyamus niger, henbane, Mandragora officina ...

undergoes

epoxidation In organic chemistry, an epoxide is a cyclic ether, where the ether forms a three-atom ring: two atoms of carbon and one atom of oxygen. This triangular structure has substantial ring strain, making epoxides highly reactive, more so than other ...

catalyzed by 6β-hydroxyhyoscyamine epoxidase yielding scopolamine. Scopolamine biosynthesis

History

Plants naturally containing scopolamine such as ''

Atropa belladonna ''Atropa bella-donna'', commonly known as deadly nightshade or belladonna, is a toxic perennial herbaceous plant in the nightshade family Solanaceae, which also includes tomatoes, potatoes and eggplant. It is native to Europe and Western Asia, i ...

'' (deadly nightshade), ''

'' (angels trumpet), ''

'' (Jimson weed), ''

'', '' Mandragora officinarum'', '' Scopolia carniolica'', '' Latua'' and '' Duboisia myoporoides'' have been known about and used for various purposes in both the New and

Old World The "Old World" () is a term for Afro-Eurasia coined by Europeans after 1493, when they became aware of the existence of the Americas. It is used to contrast the continents of Africa, Europe, and Asia in the Eastern Hemisphere, previously ...

s since ancient times.Armando T. Hunziker: ''The Genera of Solanaceae''. A.R.G. Gantner Verlag K.G., Ruggell, Liechtenstein 2001. Rätsch, Christian, ''The Encyclopedia of Psychoactive Plants: Ethnopharmacology and Its Applications'' pub. Park Street Press 2005 Being one of the earlier alkaloids isolated from plant sources, scopolamine has been in use in its purified forms, such as various salts, including hydrochloride, hydrobromide, hydroiodide, and sulfate, since its official isolation by the German scientist Albert Ladenburg in 1880, and as various preparations from its plant-based form since antiquity and perhaps prehistoric times. In 1899, Dr. Schneiderlin recommended the use of scopolamine and

morphine Morphine, formerly also called morphia, is an opiate that is found naturally in opium, a dark brown resin produced by drying the latex of opium poppies (''Papaver somniferum''). It is mainly used as an analgesic (pain medication). There are ...

for surgical anaesthesia, and it started to be used sporadically for that purpose. The use of this combination in obstetric anesthesiology (childbirth) was first proposed by Richard von Steinbuchel in 1902 and was picked up and further developed by Carl Gauss in

Freiburg Freiburg im Breisgau or simply Freiburg is the List of cities in Baden-Württemberg by population, fourth-largest city of the German state of Baden-Württemberg after Stuttgart, Mannheim and Karlsruhe. Its built-up area has a population of abou ...

, Germany, starting in 1903. The method, which was based on a drug

synergy Synergy is an interaction or cooperation giving rise to a whole that is greater than the simple sum of its parts (i.e., a non-linear addition of force, energy, or effect). The term ''synergy'' comes from the Attic Greek word συνεργία ' f ...

between both scopolamine and morphine came to be known as ''Dämmerschlaf'' (" twilight sleep") or the "Freiburg method". It spread rather slowly, and different clinics experimented with different dosages and ingredients. In 1915, the ''Canadian Medical Association Journal'' reported, "the method asreally still in a state of development". It remained widely used in the US until the 1960s, when growing

chemophobia Chemophobia (or chemphobia or chemonoia) is an aversion to or prejudice against chemicals or chemistry. The phenomenon has been ascribed both to a reasonable concern over the potential adverse effects of synthetic chemicals, and to an irrational ...

and a desire for more natural childbirth led to its abandonment.

Society and culture

Names

Hyoscine hydrobromide is the international nonproprietary name, and scopolamine hydrobromide is the United States Adopted Name. Other names include ''levo''-duboisine, devil's breath, and ''burundanga''.

Australian bush medicine

bush medicine Bush medicine comprises traditional medicines used by Indigenous Australians, being Aboriginal and Torres Strait Islander people. Indigenous people have been using various components of native Australian flora and some fauna as medicine for t ...

developed by Aboriginal peoples of the

eastern states of Australia The eastern states of Australia are the states adjoining the east continental coastline of Australia. These are the mainland states of Victoria, New South Wales and Queensland, and the island An island or isle is a piece of land, dist ...

from the soft corkwood tree ('' Duboisia myoporoides'') was used by the Allies in World War II to stop soldiers from getting seasick when they sailed across the

English Channel The English Channel, also known as the Channel, is an arm of the Atlantic Ocean that separates Southern England from northern France. It links to the southern part of the North Sea by the Strait of Dover at its northeastern end. It is the busi ...

on their way to France during the

Invasion of Normandy Operation Overlord was the codename for the Battle of Normandy, the Allied operation that launched the successful liberation of German-occupied Western Europe during World War II. The operation was launched on 6 June 1944 ( D-Day) with the ...

. Later, the same substance was found to be usable in the production of scopolamine and

, which are used in eye surgery, and a multimillion-dollar industry was built in

Queensland Queensland ( , commonly abbreviated as Qld) is a States and territories of Australia, state in northeastern Australia, and is the second-largest and third-most populous state in Australia. It is bordered by the Northern Territory, South Austr ...

based on this substance.

Recreational and religious use

While it has been occasionally used recreationally for its hallucinogenic properties, the experiences are often unpleasant, mentally and physically. It is also physically dangerous and officially classified as a

deliriant 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 th ...

drug, so repeated recreational use is rare. In June 2008, more than 20 people were hospitalized with

psychosis In psychopathology, psychosis is a condition in which a person is unable to distinguish, in their experience of life, between what is and is not real. Examples of psychotic symptoms are delusions, hallucinations, and disorganized or inco ...

in Norway after ingesting counterfeit

rohypnol Flunitrazepam, sold under the brand name Rohypnol among others, is a benzodiazepine used to treat severe insomnia and assist with anesthesia. As with other hypnotics, flunitrazepam has been advised to be prescribed only for short-term use or by ...

tablets containing scopolamine. In January 2018, 9 individuals were hospitalized in Perth, Western Australia, after reportedly ingesting scopolamine. The alkaloid scopolamine, when taken recreationally for its psychoactive effect, is usually taken in the form of preparations from plants of the genera ''

'' or ''

'', often by

adolescents Adolescence () is a transitional stage of human physical and psychological development that generally occurs during the period from puberty to adulthood (typically corresponding to the age of majority). Adolescence is usually associated with ...

or young adults in order to achieve hallucinations and an

altered state of consciousness An altered state of consciousness (ASC), also called an altered state of mind, altered mental status (AMS) or mind alteration, is any condition which is significantly different from a normal waking state. It describes induced changes in one's me ...

induced by muscarinic antagonism. In circumstances such as these, the intoxication is usually built on a

synergistic Synergy is an interaction or cooperation giving rise to a whole that is greater than the simple sum of its parts (i.e., a non-linear addition of force, energy, or effect). The term ''synergy'' comes from the Attic Greek word συνεργία ' f ...

, but even more toxic mixture of the additional alkaloids in the plants which includes

atropine Atropine is a tropane alkaloid and anticholinergic medication used to treat certain types of nerve agent and pesticide poisonings as well as some types of slow heart rate, and to decrease saliva production during surgery. It is typically give ...

and

. Historically, the various plants that produce scopolamine have been used psychoactively for spiritual and magical purposes, particularly by witches in western culture and indigenous groups throughout the

Americas The Americas, sometimes collectively called America, are a landmass comprising the totality of North America and South America.''Webster's New World College Dictionary'', 2010 by Wiley Publishing, Inc., Cleveland, Ohio. When viewed as a sing ...

, such as Native American tribes like the Chumash. When

entheogenic Entheogens are psychoactive substances used in spiritual and religious contexts to induce altered states of consciousness. Hallucinogens such as the psilocybin found in so-called "magic" mushrooms have been used in sacred contexts since ancie ...

preparations of these plants were used, scopolamine was considered to be the main psychoactive compound and was largely responsible for the hallucinogenic effects, particularly when the preparation was made into a topical ointment, most notably flying ointment.Hansen, Harold A. The Witch's Garden pub. Unity Press 1978 Scopolamine is reported to be the only active alkaloid within these plants that can effectively be absorbed through the skin to cause effects. Different recipes for these ointments were explored in

European witchcraft European witchcraft can be traced back to classical antiquity, when magic and religion were closely entwined. During the Ancient Roman religion, pagan era of ancient Rome, there were laws against harmful magic. After Christianization#Roman Empir ...

at least as far back as the

early modern period The early modern period is a Periodization, historical period that is defined either as part of or as immediately preceding the modern period, with divisions based primarily on the history of Europe and the broader concept of modernity. There i ...

and included multiple ingredients to help with the transdermal absorption of scopolamine, such as animal fat, as well as other possible ingredients to counteract its noxious and dysphoric effects. In the

Bible The Bible is a collection of religious texts that are central to Christianity and Judaism, and esteemed in other Abrahamic religions such as Islam. The Bible is an anthology (a compilation of texts of a variety of forms) originally writt ...

, there are multiple mentions of

Mandrake A mandrake is the root of a plant, historically derived either from plants of the genus '' Mandragora'' (in the family Solanaceae) found in the Mediterranean region, or from other species, such as '' Bryonia alba'' (the English mandrake, in the ...

, a psychoactive and hallucinogenic plant root that contains scopolamine. It was associated with fertility and (sexual) desire for which it was yearned by

Rachel Rachel () was a Bible, Biblical figure, the favorite of Jacob's two wives, and the mother of Joseph (Genesis), Joseph and Benjamin, two of the twelve progenitors of the tribes of Israel. Rachel's father was Laban (Bible), Laban. Her older siste ...

, who was "barren" (infertile) but trying to conceive.

Interrogation

The effects of scopolamine were studied for use as a truth serum in interrogations in the early 20th century, but because of the side effects, investigations were dropped. In 2009, the Czechoslovak state security secret police were proven to have used scopolamine at least three times to obtain confessions from alleged antistate

dissident A dissident is a person who actively challenges an established political or religious system, doctrine, belief, policy, or institution. In a religious context, the word has been used since the 18th century, and in the political sense since the 2 ...

Use in crime

Ingestion of scopolamine can render a victim unconscious for 24 hours or more. In large doses, it can cause respiratory failure and death. The highest prevalence of misuse seems to be recorded in

Colombia Colombia, officially the Republic of Colombia, is a country primarily located in South America with Insular region of Colombia, insular regions in North America. The Colombian mainland is bordered by the Caribbean Sea to the north, Venezuel ...

. Unofficial estimates there put the number of annual scopolamine incidents at approximately 50,000. A travel advisory published by the U.S. Overseas Security Advisory Council (OSAC) in 2012 stated: Between 1998 and 2004, 13% of emergency-room admissions for "poisoning with criminal intentions" in a clinic of

Bogotá Bogotá (, also , , ), officially Bogotá, Distrito Capital, abbreviated Bogotá, D.C., and formerly known as Santa Fe de Bogotá (; ) during the Spanish Imperial period and between 1991 and 2000, is the capital city, capital and largest city ...

have been attributed to scopolamine, and 44% to

benzodiazepine Benzodiazepines (BZD, BDZ, BZs), colloquially known as "benzos", are a class of central nervous system (CNS) depressant, depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed t ...

s. Most commonly, the person has been poisoned by a robber who gave the victim a scopolamine-laced beverage, in the hope that the victim would become unconscious or unable to effectively resist the robbery. Beside robberies, it is also allegedly involved in

express kidnapping Express kidnapping (; ) is a method of abduction where a small immediate ransom is demanded, often by the victim being forced to withdraw money from their ATM account. Known in the United States since at least 1986, they are more commonly assoc ...

s and

sexual assault Sexual assault is an act of sexual abuse in which one intentionally Physical intimacy, sexually touches another person without that person's consent, or Coercion, coerces or physically forces a person to engage in a sexual act against their w ...

. In 2008, the Hospital Clínic in

Barcelona Barcelona ( ; ; ) is a city on the northeastern coast of Spain. It is the capital and largest city of the autonomous community of Catalonia, as well as the second-most populous municipality of Spain. With a population of 1.6 million within c ...

introduced a protocol to help medical workers identify cases. In February 2015, Madrid hospitals adopted a similar working document. Hospital Clínic has found little scientific evidence to support this use and relies on the victims' stories to reach any conclusion. Although poisoning by scopolamine appears quite often in the media as an aid for raping, kidnapping, killing, or robbery, the effects of this drug and the way it is applied by criminals (transdermal injection, on playing cards and papers, etc.) are often exaggerated, especially skin exposure, as the dose that can be absorbed by the skin is too low to have any effect. Scopolamine transdermal patches must be used for hours to days. There are certain other aspects of the usage of scopolamine in crimes. Powdered scopolamine is referred to as "devil's breath". In popular media and television, it is portrayed as a method to brainwash or control people into being defrauded by their attackers. There is debate whether these claims are true.

Research

Scopolamine is used as a research tool to study memory encoding. Initially, in human trials, relatively low doses of the muscarinic receptor antagonist scopolamine were found to induce temporary cognitive defects. Since then, scopolamine has become a standard drug for experimentally inducing cognitive defects in animals. Results in primates suggest that

is involved in the encoding of new information into long-term memory. Scopolamine has been shown to exert a greater impairment on

episodic memory Episodic memory is the memory of everyday events (such as times, location geography, associated emotions, and other contextual information) that can be explicitly stated or conjured. It is the collection of past personal experiences that occurred ...

event-related potential An event-related potential (ERP) is the measured brain response that is the direct result of a specific sense, sensory, cognition, cognitive, or motor system, motor event. More formally, it is any stereotyped electrophysiology, electrophysiologi ...

s, memory retention and free recall compared to

diphenhydramine Diphenhydramine, sold under the brand name Benadryl among others, is an antihistamine and sedative. Although generally considered sedating, diphenhydramine can cause paradoxical central nervous system stimulation in some individuals, particula ...

(an anticholinergic and

antihistamine Antihistamines are drugs which treat allergic rhinitis, common cold, influenza, and other allergies. Typically, people take antihistamines as an inexpensive, generic (not patented) drug that can be bought without a prescription and provides ...

). Scopolamine produces detrimental effects on short-term memory, memory acquisition, learning, visual recognition memory, visuospatial praxis, visuospatial memory, visuoperceptual function, verbal recall, and psychomotor speed. It does not seem to impair recognition and memory retrieval, though. Acetylcholine projections in hippocampal neurons, which are vital in mediating long-term potentiation, are inhibited by scopolamine. Scopolamine inhibits cholinergic-mediated glutamate release in hippocampal neurons, which assist in depolarization, potentiation of action potential, and synaptic suppression. Scopolamine's effects on acetylcholine and glutamate release in the hippocampus favor retrieval-dominant cognitive functioning. Scopolamine has been used to model the defects in cholinergic function for models of Alzheimer's, dementia,

fragile X syndrome Fragile X syndrome (FXS) is a genetic neurodevelopmental disorder. The average IQ in males with FXS is under 55, while affected females tend to be in the borderline to normal range, typically around 70–85. Physical features may include a lo ...

, and Down syndrome. Scopolamine has been identified as a

psychoplastogen Psychoplastogens, also known as neuroplastogens, are a group of Small molecule#Drugs, small molecule drugs that produce rapid and sustained effects on neuronal structure and function, intended to manifest therapeutic benefit after a single admin ...

, which refers to a compound capable of promoting rapid and sustained

neuroplasticity Neuroplasticity, also known as neural plasticity or just plasticity, is the ability of neural networks in the brain to change through neurogenesis, growth and reorganization. Neuroplasticity refers to the brain's ability to reorganize and rewir ...

in a single dose. It has been and continues to be investigated as a rapid-onset

antidepressant Antidepressants are a class of medications used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction. Common side effects of antidepressants include Xerostomia, dry mouth, weight gain, dizziness, headaches, akathi ...

, with many small studies finding positive results, particularly in female subjects.

NASA The National Aeronautics and Space Administration (NASA ) is an independent agencies of the United States government, independent agency of the federal government of the United States, US federal government responsible for the United States ...

agreed to develop a nasal administration method. With a precise dosage, the NASA spray formulation has been shown to work faster and more reliably than the oral form to treat motion sickness. Although a fair amount of research has been applied to scopolamine in the field of medicine, its hallucinogenic (psychoactive) effects as well as the psychoactive effects of other antimuscarinic deliriants have not been extensively researched or as well understood compared to other types of hallucinogens such as psychedelic and dissociative compounds, despite the alkaloid's long history of usage in mind-altering plant preparations.

References

External links

* {{Authority control Carboxylate esters Deliriants Entheogens Epoxides Experimental antidepressants M1 receptor antagonists M2 receptor antagonists M3 receptor antagonists M4 receptor antagonists M5 receptor antagonists Motion sickness Ophthalmology drugs Plant toxins Tropane alkaloids found in Solanaceae Tropane alkaloids Wikipedia medicine articles ready to translate World Health Organization essential medicines