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Lactucarium is the milky fluid secreted by several species of
lettuce Lettuce (''Lactuca sativa'') is an annual plant of the family Asteraceae mostly grown as a leaf vegetable. The leaves are most often used raw in Green salad, green salads, although lettuce is also seen in other kinds of food, such as sandwiche ...
, especially ''
Lactuca virosa ''Lactuca virosa'' is a plant in the ''Lactuca'' (lettuce) genus, often ingested for its mild analgesic and sedative effects. It is related to common lettuce (''Lactuca sativa, L. sativa''), and is often called wild lettuce, bitter lettuce, lait ...
'', usually from the base of the stems. It is known as lettuce opium because of its
sedative A sedative or tranquilliser is a substance that induces sedation by reducing irritability or Psychomotor agitation, excitement. They are central nervous system (CNS) Depressant, depressants and interact with brain activity, causing its decelera ...
and
analgesic An analgesic drug, also called simply an analgesic, antalgic, pain reliever, or painkiller, is any member of the group of drugs used for pain management. Analgesics are conceptually distinct from anesthetics, which temporarily reduce, and in s ...
properties. It has also been reported to promote a mild sensation of
euphoria Euphoria ( ) is the experience (or affect) of pleasure or excitement and intense feelings of well-being and happiness. Certain natural rewards and social activities, such as aerobic exercise, laughter, listening to or making music and da ...
. Because it is a
latex Latex is an emulsion (stable dispersion) of polymer microparticles in water. Latices are found in nature, but synthetic latices are common as well. In nature, latex is found as a wikt:milky, milky fluid, which is present in 10% of all floweri ...
, lactucarium physically resembles
opium Opium (also known as poppy tears, or Lachryma papaveris) is the dried latex obtained from the seed Capsule (fruit), capsules of the opium poppy ''Papaver somniferum''. Approximately 12 percent of opium is made up of the analgesic alkaloid mor ...
, in that it is excreted as a white fluid and can be reduced to a thick smokable solid. Although the effect is not that comparable, with opium being so much more potent, it still is effective in people who have no opioid tolerance.


History

"Lettuce opium" was used by the
ancient Egyptians Ancient Egypt () was a cradle of civilization concentrated along the lower reaches of the Nile River in Northeast Africa. It emerged from prehistoric Egypt around 3150BC (according to conventional Egyptian chronology), when Upper and Lower ...
, and was introduced as a drug in the United States as early as 1799. The drug was prescribed and studied extensively in Poland during the nineteenth century, and was viewed as an alternative to opium, weaker but lacking side effects, such as not being highly addictive, and in some cases preferable. However, early efforts to isolate an active
alkaloid Alkaloids are a broad class of natural product, naturally occurring organic compounds that contain at least one nitrogen atom. Some synthetic compounds of similar structure may also be termed alkaloids. Alkaloids are produced by a large varie ...
were unsuccessful. It is described and standardized in the 1898
United States Pharmacopoeia The ''United States Pharmacopeia'' (''USP'') is a pharmacopeia (compendium of drug information) for the United States published annually by the over 200-year old United States Pharmacopeial Convention (usually also called the USP), a nonprofi ...
and 1911 '' British Pharmaceutical Codex'' for use in lozenges,
tincture A tincture is typically an extract of plant or animal material dissolved in ethanol (ethyl alcohol). Solvent concentrations of 25–60% are common, but may run as high as 90%.Groot Handboek Geneeskrachtige Planten by Geert Verhelst In chemistr ...
s, and syrups as a
sedative A sedative or tranquilliser is a substance that induces sedation by reducing irritability or Psychomotor agitation, excitement. They are central nervous system (CNS) Depressant, depressants and interact with brain activity, causing its decelera ...
for irritable cough or as a mild
hypnotic A hypnotic (from Ancient Greek, Greek ''Hypnos'', sleep), also known as a somnifacient or soporific, and commonly known as sleeping pills, are a class of psychoactive drugs whose primary function is to sleep induction, induce sleep and to trea ...
(sleeping aid) for
insomnia Insomnia, also known as sleeplessness, is a sleep disorder where people have difficulty sleeping. They may have difficulty falling asleep, or staying asleep for as long as desired. Insomnia is typically followed by daytime sleepiness, low ene ...
. The standard definition of lactucarium in these codices required its production from ''
Lactuca virosa ''Lactuca virosa'' is a plant in the ''Lactuca'' (lettuce) genus, often ingested for its mild analgesic and sedative effects. It is related to common lettuce (''Lactuca sativa, L. sativa''), and is often called wild lettuce, bitter lettuce, lait ...
'', but it was recognized that smaller quantities of lactucarium could be produced in a similar way from '' Lactuca sativa'' and ''
Lactuca canadensis ''Lactuca canadensis'' is a species of wild lettuce known by the common names Canada lettuce, Canada wild lettuce, and tall lettuce. Its true native range is not clear, but it is considered to be a native of the eastern and central parts of Nort ...
'' var. ''elongata'', and even that lettuce-opium obtained from '' Lactuca serriola'' or ''
Lactuca quercina ''Lactuca quercina'' is a species of wild lettuce native to Europe and Asia. It is an annual or biennial herb in the tribe Cichorieae within the family Asteraceae growing from a taproot to maximum heights of or more. ''Lactuca quercina'' co ...
'' was of superior quality. In the twentieth century, two major studies found commercial lactucarium to be without effect. In 1944, Fulton concluded, "Modern medicine considers its sleep producing qualities a superstition, its therapeutic action doubtful or nil." Another study of the time identified active bitter principles
lactucin Lactucin is a bitter substance that forms a white crystalline solid and belongs to the group of sesquiterpene lactones. It is found in some varieties of lettuce and is an ingredient of lactucarium. It is also found in dandelion coffee. It has b ...
and
lactucopicrin Lactucopicrin (Intybin) is a bitter substance that has a sedative and analgesic effect, acting on the central nervous system. It is a sesquiterpene lactone, and is a component of lactucarium, derived from the plant ''Lactuca virosa'' (wild lettu ...
, but noted that these compounds from the fresh latex were unstable and did not remain in commercial preparations of lactucarium. Accordingly, lettuce opium fell from favor, until publications of the
hippie A hippie, also spelled hippy, especially in British English, is someone associated with the counterculture of the 1960s, counterculture of the mid-1960s to early 1970s, originally a youth movement that began in the United States and spread to dif ...
movement began to promote it in the mid-1970s as a legal drug producing
euphoria Euphoria ( ) is the experience (or affect) of pleasure or excitement and intense feelings of well-being and happiness. Certain natural rewards and social activities, such as aerobic exercise, laughter, listening to or making music and da ...
, sometimes compounded with
catnip ''Nepeta cataria'', commonly known as catnip and catmint, is a species of the genus ''Nepeta'' in the mint family, native plant, native to southern and eastern Europe, northern parts of the Middle East, and Central Asia. It is widely naturalis ...
or damiana. More recent work has confirmed that lactucin and lactucopicrin do have analgesic and sedative properties. The seeds of lettuce have also been used to relieve pain. Lettuce seed was listed as an anaesthetic in
Avicenna Ibn Sina ( – 22 June 1037), commonly known in the West as Avicenna ( ), was a preeminent philosopher and physician of the Muslim world, flourishing during the Islamic Golden Age, serving in the courts of various Iranian peoples, Iranian ...
's ''
The Canon of Medicine ''The Canon of Medicine'' () is an encyclopedia of medicine in five books compiled by Avicenna (, ibn Sina) and completed in 1025. It is among the most influential works of its time. It presents an overview of the contemporary medical knowle ...
'', which served as an authoritative medical textbook from soon after AD 1000 until the seventeenth century.


Contemporary use

Although lactucarium has faded from general use as a pain reliever, it remains available, sometimes promoted as a legal
psychotropic 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 ...
. The seed of ordinary lettuce, '' Lactuca sativa'', is still used in Avicenna's native
Iran Iran, officially the Islamic Republic of Iran (IRI) and also known as Persia, is a country in West Asia. It borders Iraq to the west, Turkey, Azerbaijan, and Armenia to the northwest, the Caspian Sea to the north, Turkmenistan to the nort ...
as a
folk medicine Traditional medicine (also known as indigenous medicine or folk medicine) refers to the knowledge, skills, and practices rooted in the cultural beliefs of various societies, especially Indigenous groups, used for maintaining health and treatin ...
.


Chemical constituents

The chemical constituents of lactucarium that have been investigated for biological activity include
lactucin Lactucin is a bitter substance that forms a white crystalline solid and belongs to the group of sesquiterpene lactones. It is found in some varieties of lettuce and is an ingredient of lactucarium. It is also found in dandelion coffee. It has b ...
and its derivatives
lactucopicrin Lactucopicrin (Intybin) is a bitter substance that has a sedative and analgesic effect, acting on the central nervous system. It is a sesquiterpene lactone, and is a component of lactucarium, derived from the plant ''Lactuca virosa'' (wild lettu ...
and 11β,13-dihydrolactucin. Lactucin and lactucopicrin were found to have
analgesic An analgesic drug, also called simply an analgesic, antalgic, pain reliever, or painkiller, is any member of the group of drugs used for pain management. Analgesics are conceptually distinct from anesthetics, which temporarily reduce, and in s ...
effects comparable to those of
ibuprofen Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is used to relieve pain, fever, and inflammation. This includes dysmenorrhea, painful menstrual periods, migraines, and rheumatoid arthritis. It can be taken oral administration, ...
, and
sedative A sedative or tranquilliser is a substance that induces sedation by reducing irritability or Psychomotor agitation, excitement. They are central nervous system (CNS) Depressant, depressants and interact with brain activity, causing its decelera ...
activity in measurements of spontaneous movements of the mice. Some effects have also been credited to a trace of
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 ...
in ''
Lactuca virosa ''Lactuca virosa'' is a plant in the ''Lactuca'' (lettuce) genus, often ingested for its mild analgesic and sedative effects. It is related to common lettuce (''Lactuca sativa, L. sativa''), and is often called wild lettuce, bitter lettuce, lait ...
'', but the alkaloid was undetectable in standard lactucarium. A crude extract of the seeds was shown to have analgesic and anti-inflammatory effects in standard
formalin Formaldehyde ( , ) (systematic name methanal) is an organic compound with the chemical formula and structure , more precisely . The compound is a pungent, colourless gas that polymerises spontaneously into paraformaldehyde. It is stored as ...
and
carrageenan Carrageenans or carrageenins ( ; ) are a family of natural linear sulfation, sulfated polysaccharides. They are extracted from red algae, red edible seaweeds. Carrageenans are widely used in the food industry, for their gelling, thickening, an ...
tests of laboratory rats. It was not toxic to the rats at a dose of 6 
gram The gram (originally gramme; SI unit symbol g) is a Physical unit, unit of mass in the International System of Units (SI) equal to one thousandth of a kilogram. Originally defined in 1795 as "the absolute Mass versus weight, weight of a volume ...
s per
kilogram The kilogram (also spelled kilogramme) is the base unit of mass in the International System of Units (SI), equal to one thousand grams. It has the unit symbol kg. The word "kilogram" is formed from the combination of the metric prefix kilo- (m ...
. ''Lactuca virosa'' contains
flavonoid Flavonoids (or bioflavonoids; from the Latin word ''flavus'', meaning yellow, their color in nature) are a class of polyphenolic secondary metabolites found in plants, and thus commonly consumed in the diets of humans. Chemically, flavonoids ...
s,
coumarin Coumarin () or 2''H''-chromen-2-one is an aromatic organic chemical compound with formula . Its molecule can be described as a benzene molecule with two adjacent hydrogen atoms replaced by an unsaturated lactone ring , forming a second six-me ...
s, and ''N''-methyl-β-phenethylamine. A variety of other chemical compounds have been isolated from ''L. virosa''. One of the compounds,
lactucin Lactucin is a bitter substance that forms a white crystalline solid and belongs to the group of sesquiterpene lactones. It is found in some varieties of lettuce and is an ingredient of lactucarium. It is also found in dandelion coffee. It has b ...
, is an
adenosine receptor The adenosine receptors (or P1 receptors) are a class of Purinergic receptor, purinergic G protein-coupled receptors with adenosine as the endogenous ligand (biochemistry), ligand. There are four known types of adenosine receptors in humans: Aden ...
agonist ''
in vitro ''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...
'', while another,
lactucopicrin Lactucopicrin (Intybin) is a bitter substance that has a sedative and analgesic effect, acting on the central nervous system. It is a sesquiterpene lactone, and is a component of lactucarium, derived from the plant ''Lactuca virosa'' (wild lettu ...
, has been shown to act as an
acetylcholinesterase inhibitor Acetylcholinesterase inhibitors (AChEIs) also often called cholinesterase inhibitors, inhibit the enzyme acetylcholinesterase from breaking down the neurotransmitter acetylcholine into choline and acetate, thereby increasing both the level an ...
''in vitro''. '' Lactuca floridana'' was found to contain 11β,13-Dihydro-lactucin-8-O-acetate hemihydrate.


Formulations

Lactucarium was used unmodified in lozenges, 30–60 
milligrams The kilogram (also spelled kilogramme) is the base unit of mass in the International System of Units (SI), equal to one thousand grams. It has the unit symbol kg. The word "kilogram" is formed from the combination of the metric prefix kilo- (m ...
(0.5 to 1 
grain A grain is a small, hard, dry fruit (caryopsis) – with or without an attached husk, hull layer – harvested for human or animal consumption. A grain crop is a grain-producing plant. The two main types of commercial grain crops are cereals and ...
), sometimes mixed with
borax The BORAX Experiments were a series of safety experiments on boiling water nuclear reactors conducted by Argonne National Laboratory in the 1950s and 1960s at the National Reactor Testing Station in eastern Idaho.
. However, it was found to be more efficient to formulate the drug in a cough syrup ''(Syrupus Lactucarii, U.S.P.)'' containing net 5% lactucarium, 22% glycerin, 5% alcohol, and 5% orange-flower water in syrup.


References

{{Ancient anaesthesia-footer Analgesics Sedatives Euphoriants Medicinal plants Lactuca