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Scopolamine, also known as levo-duboisine, and hyoscine, is a tropane alkaloid drug with muscarinic antagonist effects. It is obtained from plants of the family Solanaceae (nightshades), such as henbane, jimson weed and Angel's Trumpets (Datura resp. Brugmansia spec.), and corkwood (Duboisia species [1]). It is among the secondary metabolites of these plants. Therefore, scopolamine is one of three main active components of belladonna and stramonium tinctures and powders used medicinally along with atropine and hyoscyamine. Scopolamine was isolated from plant sources by scientists in 1881 in Germany and description of its structure and activity followed shortly thereafter.

Scopolamine has anticholinergic properties and has legitimate medical applications in very minute doses. As an example, in the treatment of motion sickness, the dose, gradually released from a transdermal patch, is only 330 microgrammes (µg) per day. In rare cases, unusual reactions to ordinary doses of scopolamine have occurred including confusion, agitation, rambling speech, hallucinations, paranoid behaviors, and delusions.

Etymology

Scopolamine is named after the plant genus Scopolia. The name "hyoscine" is from the scientific name for henbane, Hyoscyamus niger.

Physiology

Scopolamine acts as a competitive antagonist at muscarinic acetylcholine receptors, specifically M1 receptors; it is thus classified as an anticholinergic, anti-muscarinic drug.

Medical use

In medicine, scopolamine has these uses:

  • Primary:
    • Treatment of nausea and motion sickness
    • Treatment of intestinal cramping
    • For ophthalmic purposes.
    • As a general depressant and adjunct to narcotic painkillers
  • Less often:
    • As a preanesthetic agent
    • As a drying agent for sinuses, lungs, and related areas.
    • To reduce motility and secretions in the GI tract—most frequently in tinctures or other belladonna or stramonium preparations, often used in conjunction with other drugs as in Donnagel original forumulation, Donnagel-PG (with paregoric), Donnabarb/Barbadonna/Donnatal (with phenobarbital), and a number of others
    • Uncommonly, for some forms of Parkinsonism.
    • As an adjunct to opioid analgesia, such as the product Twilight Sleep which contained morphine and scopolamine, some of the original formulations of Percodan and some European brands of methadone injection.
    • As an occasional sedative, and was available in some over-the-counter-products in the United States for this purpose until November 1990.

Nausea

Its use as an antiemetic in the form of a transdermal patch.

Ophthalmic

The drug is used in eye drops to induce mydriasis (pupillary dilation) and cycloplegia (paralysis of the eye focusing muscle), primarily in the treatment of eye disorders that benefit from its prolonged effect, e.g. uveitis, iritis, iridocyclitis, etc.

Memory research

Because of its anticholinergic effects, scopolamine has been shown to prevent the activation of medial temporal lobe structures for novel stimuli during spatial memory tasks.

Addiction

Scopolamine has been used in the past to treat addiction to drugs such as heroin and cocaine. The patient was given frequent doses of scopolamine until they were delirious. This treatment was maintained for two to three days after which they were treated with pilocarpine. After recovering from this they were said to have lost the acute craving to the drug to which they were addicted. [2]

Currently, scopolamine is being investigated for its possible usefulness alone or in conjunction with other drugs in treating nicotine addiction. The mechanism by which it mitigates withdrawal symptoms is different from that of clonidine meaning that the two drugs can be used together without duplicating or canceling out the effects of each other.

Other medical uses

  • It can be used as a depressant of the central nervous system, and was formerly used as a bedtime sedative.
  • Anesthetic; Its use in general anesthesia is favored by some due to its amnesic effect. Scopolamine causes memory impairments to a similar degree as diazepam.[3]
  • In otolaryngology it is used to dry the upper airway (anti-sialogogue action) prior to instrumentation of the airway.
  • In October 2006 researchers at the US National Institute of Mental Health found that scopolamine reduced symptoms of depression within a few days, and the improvement lasted for at least a week after switching to a placebo.[4]
  • Due to its effectiveness against sea-sickness it has become commonly used by scuba divers.[5][6]

Routes of administration

Scopolamine can be administered by transdermal patches,[7] oral, subcutaneous, ophthalmic and intravenous routes. The transdermal patch (e.g. Transderm Scōp) for prevention of nausea and motion sickness employs scopolamine base. The patch is effective for up to 3 days[8]. The oral, ophthalmic and intravenous forms are usually scopolamine hydrobromide (for example in Scopace, soluble 0.4 mg tablets or Donnatal).

Recreational use

The use of medical scopolamine/opioid combination preparations for euphoria is uncommon but does exist and can be seen in conjunction with opioid use. Doses of scopolamine by itself near the therapeutic range create euphoria and anxiolysis of anticholinergic origin, similar to that of some first-generation antihistamines and similar drugs.

Another separate group of users prefer dangerously high doses, especially in the form of datura preparations, for the deliriant and hallucinogenic effects. The hallucinations produced by scopolamine, in common with other potent anticholinergics, are especially real-seeming, with many users reporting hallucinations such as spiders crawling on walls and ceilings, especially in the dark. While some users find this pleasant, often the experience is not one that the user would want to repeat. An overdose of scopolamine is also physically exceedingly unpleasant and can be fatal, unlike the effect of other more commonly used hallucinogens. For these reasons, naturally occurring anticholinergics are rarely used for recreational purposes.

Scopolamine in transdermal, oral, sublingual, and injectable formulations can produce a cholinergic rebound effect when high doses are stopped. This is the opposite of scopolamine's therapeutic effects: sweating, runny nose, abdominal cramps, nausea, vomiting, vertigo, dizziness, irritability, and diarrhea. Psychological dependence is also possible when the drug is taken for its tranquilizing effects.

Use in interrogation

"The Use of Scopolamine in Criminology" by Robert E. House appeared in the Texas State Journal of Medicine in September, 1922 and was reprinted in The American Journal of Police Science, Vol. 2, No. 4, Jul. - Aug., 1931.

The use of scopolamine as a truth drug was investigated in the 1950s by various intelligence agencies, including the CIA as part of Project MKULTRA.

In 2009, it has been proved that Czechoslovak communist secret police used scopolamine at least three times to obtain confession from alleged anti-state conspirators. [9]

"...if you inject it into the spine (amount classified), it causes absolutely incredible pain, accompanied by violent convulsions and seizures. If injected into the spine in the appropriate amount, more than 95% of all prisoners will tell the truth—not something fabricated to stop the pain—within 24 hours"[10]

Criminal use and urban legends

Scopolamine poisoning is sometimes reported as a way used by murderers or robbers, although largely exaggerated in many unfounded rumors. In 1910 it was detected in the remains believed to be those of Cora Crippen, wife of Dr Hawley Harvey Crippen, and was accepted at the time as the cause of her death since her husband was known to have bought some at the start of the year.[11]

There are unfounded circulating rumors that a transcutaneous delivery mechanism using business cards, pamphlets or flyers laced with the drug, could be effective. Indeed, the quantity of toxin diffusing through the skin barrier after one short contact of the fingers with an object is much too small to be readily absorbed in the body and to have any significant effect. The use of burundanga impregnated visit cards to attack and to rob isolated people is often propagated by chain emails and is presently reported as hoax or urban legend by many specialised web sites [12][13][14]. Meanwhile, spiked alcoholic drinks (direct ingestion) could have been occasionally used. In recent years the criminal use of scopolamine has become epidemic in Colombia. Approximately one in five emergency room admissions for poisoning in Bogotá have been attributed to scopolamine.[15] In a bizarre case, a band of female thieves would impregnate their breasts with scopolamine and then would lure potential victims to lick their nipples. "Losing all willpower, the men readily gave up their bank access codes. The breast-temptress thieves then held them hostage for days while draining their accounts."[16] In June 2008, more than 20 people were hospitalized with psychosis in Norway after ingesting counterfeit Rohypnol tablets containing scopolamine. [3]

Shamanic use

In Colombia a plant admixture containing scopolamine called Burundanga has been used shamanically for decades.

Witchcraft and sorcery

Scopolamine was one of the active principles in many of the "flying ointments" used by witches, sorcerers and fellow travellers of many countries and cultures from millennia ago ostensibly down to the late 19th century or even to the present day. Scopolamine and related tropanes contributed both to the flying sensations and hallucinations sought by users of these compounds. Potions, solids of various types, and other forms were also used in some cases.

These ointments could contain any number of ingredients with belladonna, henbane, and other plants of the belladonna and datura families being present almost invariably; they were applied to large areas of the skin with the objective being to see the Gods or spirits, and/or be transported to the Sabbat.

The hallucinations, sensation of flying, often a rapid increase in libido, and other characteristic effects of this practice are largely attributable to the CNS and peripheral effects of scopolamine and other active drugs present in the ointments such as atropine, hyoscyamine, mandragorine, scopoline, solanine, optical isomers of scopolamine and other tropane alkaloids. The inclusion of belladonna/datura type plants amongst the dozens of ingredients in the Haitian zombie drug is thought by some authorities to be at least somewhat likely, although scopolamine-bearing plant matter is almost certainly not the main active ingredient, which has been theorised to possibly be Tetrodotoxin or a related substance.

Adverse effects

The common side effects are related to the anticholinergic effect on parasympathetic postsynaptic receptors: dry mouth, throat and nasal passages in overdose cases progressing to impaired speech, thirst, blurred vision and sensitivity to light, constipation, difficulty urinating and tachycardia. Other effects of overdose include flushing and fever, as well as excitement, restlessness, hallucinations, or delirium. These side effects are commonly observed with oral or parenteral uses of the drug and generally not with topical ophthalmic use.

Use in scuba diving to prevent sea sickness has led to the discovery of another side effect. In deep water, below 50–60 feet, some divers have reported pain in the eyes that subsides quickly if the diver ascends to a depth of 40 feet or less. Mydriatics can precipitate an attack of glaucoma in susceptible patients, so the medication should be used with extra caution among divers who intend to go below 50 feet.

Drug interactions: side effects and use against pain

When combined with morphine, scopolamine is useful for pre-medication for surgery or diagnostic procedures and was widely used in obstetrics in the past; the mixture also produces amnesia and a tranquillised state known as Twilight Sleep, also the name of a proprietary drug available in the past in ampoules of injectable fluid containing morphine sulfate and scopolamine hydrobromide (and in some cases the phenothiazine anti-nauseants prochlorperazine or promethazine as a third ingredient). Although originally used in obstetrics, it is now considered dangerous for that purpose for both mother and baby.

History

Scopolamine was one of the earlier alkaloids isolated from plant sources and has been in use in isolated, purified forms such as free base and various salts, especially hydrochloride, hydrobromide, hydroiodide and sulfate, since its isolation by German chemists in 1881 and in the form of plant-based preparations since antiquity and perhaps pre-historic times.

Scopolamine was one of the active ingredients in Asthmador, an over the counter smoking preparation marketed in the 1950s and 60's claiming to combat asthma and bronchitis.

Scopolamine was used from the 1940s to the 1960s to put mothers in labor into a kind of "twilight sleep" that did not stop pain, but merely eliminated the memory of pain by attacking the brain functions responsible for self-awareness and self-control.

Scopolamine was an ingredient used in some over-the-counter sedatives before November 1990 in the United States, when the U.S. Food and Drug Administration forced several hundred ingredients allegedly not known to be effective off the market. Scopolamine shared a small segment of this market with diphenhydramine, phenyltoloxamine, pyrilamine, doxylamine and other first generation antihistamines, many of which are still used for this purpose in drugs including Sominex, Tylenol PM and NyQuil.

Popular culture

The fictional use of scopolamine as a truth serum is featured in a number of works including Farewell, My Lovely and The Guns of Navarone. In 1957, scopolamine achieved a moderate level of notoriety via its mention in the film I Was a Teenage Werewolf, where Dr. Alfred Brandon uses it as part of his endeavor to regress the titular character to his "primitive roots." According to Dr. Liz Kingsley's film review site And You Call Yourself a Scientist, Brandon's line "Prepare the scopolamine!" is "the only scientifically accurate line in the whole film." In Fear and Loathing In Las Vegas by Hunter S. Thompson, Dr. Gonzo mentions an incident in which he was given an entire datura root as a gift, ate the entire thing at once, and subsequently went blind, had to be taken back to his house in a wheelbarrow, and started making noises like a raccoon. In Carlos Castaneda's series of books The Teachings of Don Juan: A Yaqui Way of Knowledge, the datura plant is the favored shamanic, revelatory drug of the titular character. The book explores, in depth, Castaneda's alleged experiences under the influence of the drug, as well as the alleged rites surrounding its use and preparation. It was also used as an interrogation tool during Episode 9 of NBC's Kidnapped.

References

  1. [1]
  2. Evelyn Clare Pearce (1941). Pearce's Medical and Nursing Dictionary and Encyclopaedia. Faber & Faber. 
  3. Jones DM; Jones ME, Lewis MJ, Spriggs TL. (May 1979). "Drugs and human memory: effects of low doses of nitrazepam and hyoscine on retention.". Br J Clin Pharmacol. 7 (5): 479–83. 
  4. Furey, ML; Drevets, WC (October 2006). "Antidepressant efficacy of the antimuscarinic drug scopolamine: a randomized, placebo-controlled clinical trial". Archives of General Psychiatry, vol 63, p 1121 63: 1121. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?orig_db=PubMed&db=PubMed&cmd=Search&term=%22Archives+of+general+psychiatry%22%5BJour%5D+AND+63%5Bvolume%5D+AND+1121%5Bpage%5D. 
  5. Bitterman N, Eilender E, Melamed Y (May 1991). "Hyperbaric oxygen and scopolamine". Undersea Biomed Res 18 (3): 167–74. http://archive.rubicon-foundation.org/2573. Retrieved 2008-08-13. 
  6. Williams TH, Wilkinson AR, Davis FM, Frampton CM (March 1988). "Effects of transcutaneous scopolamine and depth on diver performance". Undersea Biomed Res 15 (2): 89–98. http://archive.rubicon-foundation.org/2495. Retrieved 2008-08-13. 
  7. White PF, Tang J, Song D, et al. (2007). "Transdermal scopolamine: an alternative to ondansetron and droperidol for the prevention of postoperative and postdischarge emetic symptoms". Anesth. Analg. 104 (1): 92–6. http://www.anesthesia-analgesia.org/cgi/pmidlookup?view=long&pmid=17179250. 
  8. Transderm Scop patch prescribing information
  9. Gazdík, Jan; Navara, Luděk (2009-08-08). "Svědek: Grebeníček vězně nejen mlátil, ale dával jim i drogy [A witness: Grebeníček not only beat prisoners, he also administered drugs to them]" (in Czech). iDnes. http://zpravy.idnes.cz/svedek-grebenicek-vezne-nejen-mlatil-ale-daval-jim-i-drogy-pmd-/domaci.asp?c=A090807_205833_domaci_vel. Retrieved 2009-08-10. 
  10. (Source: classified). http://wikileaks.org/wiki/Torture%2C_interrogation_and_intelligence
  11. "The Trial of H.H. Crippen" ed. by Filson Young (Notable British Trials series, Hodge, 1920), p. xxvii; see also evidence, pp. 68-77.
  12. Hoax: Burundanga Business Card Drug Warning
  13. Urband legend: Burundanga Drug Warning
  14. Snopes.com: Burundanga Business Card
  15. Manuel Uribe G., Claudia L. Moreno L, Adriana Zamora S., Pilar J. Acosta (2005) Perfil epidemiológico de la intoxicación con burundanga en la clínica Uribe Cualla S. A. de Bogotá, D. C. Acta Neurol Colomb, 21, 197-201 [2]
  16. http://www.biopsychiatry.com/scopolamine/borrachero.html

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