water 1 gill, and work it in a bowl or mortar until it is dissolved; then pour it into the bottle, and with alcohol of 70 percent proof 1⁄2 pt., rinse the dish, adding the alcohol to the preparation, shaking well, and in 24 hours it will be ready for use. dose—from 10 to 30 drops for adults, according to the strength of the patient, or severity of the pain. thirty drops of this laudanum will be equal to one grain of opium. and this is a much better way to prepare it than putting the opium into alcohol, or any other spirits alone, for in that case much of the opium does not dissolve." the remaining three formulas are copied from an 1890 publication of the day: sydenham's laudanum: "according to the paris codex this is prepared as follows: opium, 2 ounces; saffron, 1 ounce; bruised cinnamon and bruised cloves, each 1 drachm; sherry wine, 1 pint. mix and macerate for 15 days and filter. twenty drops are equal to one grain of opium." rousseau's laudanum: "dissolve 12 ounces white honey in 3 pounds warm water, and set it aside in a warm place. when fermentation begins add to it a solution of 4 ounces selected opium in 12 ounces water. let the mixture stand for a month at a temperature of 86° fahr.; then strain, filter, and evaporate to 10 ounces; finally strain and add 41⁄2 ounces proof alcohol. seven drops of this preparation contain about 1 grain of opium." tincture of opium (laudanum), u.s.p., attributed to the united states pharmacoepia of 1863: "macerate 21⁄2 ounces opium, in moderately fine powder in 1 pint water for 3 days, with frequent agitation. add 1 pint alcohol, and macerate for 3 days longer. percolate, and displace 2 pints tincture by adding dilute alcohol in the percolator." modern status united kingdom opium tincture remains in the british pharmacopoeia, where it is referred to as tincture of opium, b.p., laudanum, thebaic tincture or tinctura thebaica, and "adjusted to contain 1% w/v of anhydrous morphine." it is a class a substance under the misuse of drugs act of 1971. at least one manufacturer (macfarlan smith) still produces opium tincture in the uk as of 2011. "gee's linctus" is also available from most uk pharmacies, especially independent stores. this contains "opium tincture", at 0.083 ml, per 5 ml. united states tincture of opium is available by prescription in the united states. it is regulated as a schedule ii drug (no. 9639) under the controlled substances act. in the united states, opium tincture is marketed and distributed by several pharmaceutical firms, each producing a single formulation of the drug, which is deodorized. each ml contains 10 mg of anhydrous morphine (the equivalent of 100 mg of powdered opium), other opium alkaloids (except noscapine), and ethanol, 19%. it is available packaged in bottles of four us fluid ounces (118 ml) and 16 us fluid ounces (1 us pt; 473 ml). tincture of opium is known as one of many "unapproved drugs" regulated by the u.s. food and drug administration (fda); the marketing and distribution of opium tincture prevails only because opium tincture was sold prior to the federal food, drug & cosmetic act of 1938. its "grandfathered" status protects opium tincture from being required to undergo strict fda drug reviews and subsequent approval processes. however, the fda closely monitors the labeling of opium tincture. bottles of opium tincture are required by the fda to bear a bright red "poison" label given the potency of the drug and the potential for overdose (see discussion about confusion with paregoric below). additionally, in a warning letter to a manufacturer of opium tincture in late 2009, the fda noted that "we found that your firm is manufacturing and distributing the prescription drug opium tincture usp (deodorized – 10 mg/ml). based on our information, there are no fda-approved applications on file for this drug product." pharmacology opium tincture is useful as an analgesic and antidiarrheal. opium enhances the tone in the long segments of the longitudinal muscle and inhibits propulsive contraction of circular and longitudinal muscles. the pharmacological effects of opium tincture are due principally to its morphine content. the quantity of the papaverine and codeine alkaloids in opium tincture is too small to have any demonstrable central nervous system effect. most modern formulations of opium tincture do not contain the alkaloid narcotine (also known as noscapine), which has antitussive properties. even modest doses of narcotine can induce profound nausea and vomiting. since opium tincture is usually prescribed for its antidiarrheal and analgesic properties (rather than as an antitussive), opium tincture without narcotine is generally preferred. this "de-narcotized" or "deodorized" opium tincture is formulated using a petroleum distillate to remove the narcotine. oral doses of opium tincture are rapidly absorbed in the gastrointestinal tract and metabolized in the liver. peak plasma concentrations of the morphine content are reached in about one hour, and nearly 75% of the morphine content of the opium tincture is excreted in the urine within 48 hours after oral administration. medical uses diarrhea opium tincture is indicated for the treatment of severe fulminant (intense, prolific) diarrhea that does not respond to standard therapy (e.g., imodium or lomotil). the usual starting dose is 0.3 ml to 0.6 ml (about six to 12 drops) in a glass of water or juice four times a day. refractory cases (such as diarrhea resulting from the complications of hiv/aids) may require higher than normal dosing, for example, 1 to 2 ml every 3 hours, for a total daily dose of up to 16ml a day. in terminal diseases, there is no ceiling dose for opium tincture; the dose is increased slowly until diarrhea is controlled. neonatal abstinence syndrome opium tincture is used to treat neonatal opioid withdrawal syndrome (nows) when diluted 1:25 (one part opium tincture to 25 parts water). the recommended dose is 0.2 ml of the diluted solution under the tongue every three hours, which may be increased by 0.05 ml every three hours until no objective signs of withdrawal are observed. in no event, however, should the dose exceed 0.7 ml every three hours. the opium tincture is gradually tapered over a 3- to 5-week period, at which point the newborn should be completely free of withdrawal symptoms. hazards potency of laudanum opium tincture is one of the most potent oral formulations of morphine available by prescription. accidental or deliberate overdose is common with opium tincture given the highly concentrated nature of the solution. overdose and death may occur with a single oral dose of between 100 and 150 mg of morphine in a healthy adult who has no tolerance to opiates. this represents the equivalent of between two and three teaspoons (10–15 ml) of opium tincture. suicide by laudanum was common in the mid-19th century. prudent medical judgment necessitates toward dispensing very small quantities of opium tincture in small dropper bottles or in pre-filled syringes to reduce the risk of intentional or accidental overdose. danger of confusion with paregoric in the united states, opium tincture contains 10 mg per ml of anhydrous morphine. by contrast, opium tincture's weaker cousin, paregoric, also confusingly known as "camphorated tincture of opium", is 1/25th the strength of opium tincture, containing only 0.4 mg of morphine per ml. a 25-fold morphine overdose may occur if opium tincture is used where paregoric is indicated. opium tincture is almost always dosed in drops, or fractions of a ml, or less commonly, in minims, while paregoric is dosed in teaspoons or tablespoons. thus, an order for opium tincture containing directions in teaspoons is almost certainly in error. to avoid this potentially fatal outcome, the term "camphorated tincture of opium" is avoided in place of paregoric since the former can easily be mistaken for opium tincture. in 2004, the fda issued a "patient safety" news bulletin stating that "to help resolve the confusion , fda will be working with the manufacturers of these two drugs to clarify the labeling on the containers and in the package inserts." indeed, in 2005, labels for opium tincture began to include the concentration of morphine (10 mg/ml) in large text beneath the words "opium tincture". the fda has also alerted pharmacists and other medical practitioners about the dangers of confusing these drugs, and has recommended that opium tincture not be stocked as a standard item (i.e., that it should not be "on the shelf"), that opium tincture be dispensed in oral syringes, and that pharmacy software alert the dispenser if unusually large doses of opium tincture appear to be indicated. despite the fda's efforts over the past few years, the confusion persists, sometimes with deadly results. the institute for safe medication practices recommends that opium tincture not be stocked at all in a pharmacy's inventory, and that "it may be time to relegate opium tincture and paregoric to the museum of outmoded opioid therapy." despite the risk of confusion, opium tincture, like many end-stage medications, is indispensable for intractable diarrhea for terminally ill patients, such as those with aids and cancer. misinterpretation of "dto" the abbreviation "dto," traditionally used to refer to deodorized tincture of opium, is sometimes also erroneously employed to abbreviate "diluted tincture of opium." diluted tincture of opium, also known as camphorated tincture of opium (paregoric) is a 1:25 mixture of opium tincture to water prescribed to treat withdrawal symptoms in newborns whose mothers were using opioids while pregnant. the united states pharmacopeia and fda recommend that practitioners refrain from using dto in prescriptions, given this potential for confusion. in cases where pharmacists have misinterpreted dto, and given "deodorized tincture of opium" when "diluted tincture of opium" was meant, infants have received a massive 25-fold overdose of morphine, sometimes resulting in fatalities. side effects side effects of laudanum are generally the same as with morphine, and include euphoria, dysphoria, pruritus, sedation, constipation, reduced tidal volume, respiratory depression, as well as psychological dependence, physical dependence, miosis, and xerostomia. overdose can result in severe respiratory depression or collapse and death. the ethanol component can also induce adverse effects at higher doses; the side effects are the same as with alcohol. long-term use of laudanum in nonterminal diseases is discouraged due to the possibility of drug tolerance and addiction. long-term use can also lead to abnormal liver function tests; specifically, prolonged morphine use can increase alt and ast blood serum levels. treatment for overdose life-threatening overdose of opium tincture owes to the preparation's morphine content. morphine produces a dose-dependent depressive effect on the respiratory system, which can lead to profound respiratory depression, hypoxia, coma and finally respiratory arrest and death. if overdose of opium tincture is suspected, rapid professional intervention is required. the primary concern is re-establishing a viable airway and institution of assisted or controlled ventilation if the patient is unable to breathe on their own. other supportive measures such as the use of vasopressors and oxygen may be indicated to treat cardiac and/or pulmonary failure. cardiac arrhythmias or arrest will require advanced life-saving measures. intravenous naloxone or nalmefene, quick-acting opioid antagonists, are the first-line treatment to reverse respiratory depression caused by an overdose of opium tincture. gastric lavage may be of some use in certain cases. fiction literature in mary shelley's novel frankenstein (1818), victor frankenstein takes laudanum as his only means of sleeping and thus preserving his life while in recovery from months of fever and a series of horrible events. in charles dickens's novel oliver twist (1837), nancy gave william "bill" sikes laudanum to keep him asleep while she ran away to meet rose maylie. in uncle tom's cabin (1852), an anti-slavery novel by harriet beecher stowe, an enslaved woman named cassy talks about how she killed her newborn by laudanum overdose to spare him from experiencing the horrors of slavery. in the novel silas marner: the weaver of raveloe by george eliot (mary ann evans) (1861), silas finds and adopts a two-year old girl who had wandered into his house. the girl had been abandoned while walking with her opium-addicted mother, molly farren, who had fallen asleep in the snow and died. earlier in the novel, in chapter 3, it is specified that she uses laudanum.... if molly should take a drop too much laudanum some day, and make a widower of you. a