{{Short description|Psychoactive fluid secreted by lettuce}} {{cs1 config|name-list-style=vanc}} {{more medical citations needed|date=September 2015}} {{Infobox botanical product |name = Lactucarium |plant = ''Lactuca'' spp. |part = Latex (see also seeds) |origin = Southern Europe |uses = Analgesic, sleep aid, euphoriant |legal_status=Unscheduled}}
'''Lactucarium''' is the milky fluid secreted by several species of lettuce, especially ''Lactuca virosa'', usually from the base of the stems. It is known as '''lettuce opium''' because of its sedative and analgesic properties. It has also been reported to promote a mild sensation of euphoria.<ref>{{cite web |last=Adams |first=Cecil |date=2005-01-06 |title=Is iceberg lettuce a drug? |url=https://www.straightdope.com/21343701/is-iceberg-lettuce-a-drug |url-status=live |archive-url=https://web.archive.org/web/20230325080152/https://www.straightdope.com/21343701/is-iceberg-lettuce-a-drug |archive-date=2023-03-25 |access-date=2024-02-14 |website=The Straight Dope}}</ref><ref>{{cite journal | vauthors = Spadari M, Pommier P, Canioni D, Arditti J, David JM, Valli M | title = [Abuse of lactuca virosa] | language = French | journal = Presse Médicale | volume = 32 | issue = 15 | pages = 702–3 | date = April 2003 | pmid = 12762295 }}</ref> Because it is a latex, lactucarium physically resembles opium, 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== Mentions of lettuce as a medicinal herb goes back as least as early as the Medieval period in Europe.<ref>{{Citation |last=Noumedem |first=J.A.K. |title=Lactuca sativa |date=2017 |work=Medicinal Spices and Vegetables from Africa |pages=437–449 |url=https://linkinghub.elsevier.com/retrieve/pii/B9780128092866000200 |access-date=2026-05-01 |publisher=Elsevier |language=en |doi=10.1016/b978-0-12-809286-6.00020-0 |isbn=978-0-12-809286-6 |last2=Djeussi |first2=D.E. |last3=Hritcu |first3=L. |last4=Mihasan |first4=M. |last5=Kuete |first5=V.|url-access=subscription }}</ref> The drug was studied in Poland during the nineteenth century, with the studies regarding it as a less potent but less addictive alternative to opium. However, early efforts to isolate an active alkaloid were unsuccessful.<ref>{{Cite journal |last=Trojanowska |first=Anna |date=2005 |title=[Lettuce, lactuca sp., as a medicinal plant in polish publications of the 19th century] |url=https://pubmed.ncbi.nlm.nih.gov/17153150 |journal=Kwartalnik Historii Nauki I Techniki: Kwartal'nyi Zhurnal Istorii Nauki I Tekhniki - |volume=50 |issue=3-4 |pages=123–134 |issn=0023-589X |pmid=17153150}}</ref> It is described and standardized in the 1898 United States Pharmacopoeia<ref name="USP">{{cite web|url=https://www.henriettes-herb.com/eclectic/kings/lactuca_lact_tinc.html|title=King's American Dispensary:Tinctura Lactucarii (U. S. P.)—Tincture of Lactucarium| first1 = Harvey Wickes | last1 = Felter | first2 = John Uri | last2 = Lloyd |year=1898|access-date=2007-05-28}}</ref> and 1911 ''British Pharmaceutical Codex''<ref name="BPC">{{cite web|url=https://www.henriettes-herb.com/eclectic/bpc1911/lactuca.html|title=Lactuca, Lactucarium|author=the Council of the Pharmaceutical Society of Great Britain|year=1911|access-date=2007-05-27}}</ref> for use in lozenges, tinctures, and syrups as a sedative for irritable cough or as a mild hypnotic (sleeping aid) for insomnia. The standard definition of lactucarium in these codices required its production from ''Lactuca virosa'', but it was recognized that smaller quantities of lactucarium could be produced in a similar way from ''Lactuca sativa'' and ''Lactuca canadensis'' var. ''elongata'', and even that lettuce-opium obtained from ''Lactuca serriola'' or ''Lactuca quercina'' was of superior quality.<ref>{{cite book |author=Harvey Wickes Felter |author2=John Uri Lloyd |title=King's American Dispensatory|year=1898|publisher=Ohio Valley Co|location=Cincinnati|pages=1114–1117 |title-link=King's American Dispensatory}} See [https://www.henriettes-herb.com/eclectic/kings/lactuca.html Lactuca.—Lettuce] and [https://www.henriettes-herb.com/eclectic/kings/lactuca_lact_tinc.html Tinctura Lactucarii (U. S. P.)—Tincture of Lactucarium] at Henriette's Herbal Homepage.</ref>
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 and lactucopicrin, 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 movement began to promote it in the mid-1970s as a legal drug producing euphoria, sometimes compounded with catnip or damiana.<ref name="herbs2000">{{cite web|url=http://www.herbs2000.com/herbs/herbs_lettuce_opium.htm|title=Lettuce opium|access-date=2007-05-28}}</ref>{{unreliable source?|date=November 2017}} More recent work has confirmed that lactucin and lactucopicrin do have analgesic and sedative properties.<ref name=Wesolowska/>
The seeds of lettuce have also been used to relieve pain.{{medcn|date=September 2015}} Lettuce seed was listed as an anaesthetic in Avicenna's ''The Canon of Medicine'', which served as an authoritative medical textbook from soon after AD 1000 until the seventeenth century.<ref>{{cite journal | vauthors = Smith RD | title = Avicenna and the Canon of Medicine: a millennial tribute | journal = The Western Journal of Medicine | volume = 133 | issue = 4 | pages = 367–70 | date = October 1980 | pmid = 7051568 | pmc = 1272342 }}</ref>
==Contemporary use== Although lactucarium has faded from general use as a pain reliever, it remains available, sometimes promoted as a legal psychotropic.
The seed of ordinary lettuce, ''Lactuca sativa'', is still used in Avicenna's native Iran as a folk medicine.{{citation needed|date=September 2015}}
==Chemical constituents== [[Image:Lactuca compounds.svg|thumb|Chemical compounds which occur in lettuce: (1) α-lactucerol (taraxasterol); (2) β-lactucerol (lactucon, lactucerin); (3) lactucin; (4) lactucopicrin]] The chemical constituents of lactucarium that have been investigated for biological activity include lactucin and its derivatives lactucopicrin and 11β,13-dihydrolactucin. Lactucin and lactucopicrin were found to have analgesic effects comparable to those of ibuprofen, and sedative activity in measurements of spontaneous movements of the mice.<ref name="Wesolowska"/> Some effects have also been credited to a trace of hyoscyamine in ''Lactuca virosa'', but the alkaloid was undetectable in standard lactucarium.<ref name="BPC" /> A crude extract of the seeds was shown to have analgesic and anti-inflammatory effects in standard formalin and carrageenan tests of laboratory rats. It was not toxic to the rats at a dose of 6 grams per kilogram.<ref>{{cite journal | vauthors = Sayyah M, Hadidi N, Kamalinejad M | title = Analgesic and anti-inflammatory activity of Lactuca sativa seed extract in rats | journal = Journal of Ethnopharmacology | volume = 92 | issue = 2–3 | pages = 325–9 | date = June 2004 | pmid = 15138019 | doi = 10.1016/j.jep.2004.03.016 }}</ref>
''Lactuca virosa'' contains flavonoids, coumarins, and ''N''-methyl-β-phenethylamine.<ref>{{cite web | url = http://www.holistic-online.com/Herbal-Med/_Herbs/h307.htm | work = Holistic Online herb information | title = Wild Lettuce | access-date = 2019-10-31 | archive-date = 2006-01-05 | archive-url = https://web.archive.org/web/20060105201002/http://www.holistic-online.com/Herbal-Med/_Herbs/h307.htm | url-status = dead }}</ref>{{unreliable source?|date=September 2011}} A variety of other chemical compounds have been isolated from ''L. virosa''. One of the compounds, lactucin, is an adenosine receptor agonist ''in vitro'',<ref name=Wesolowska>{{cite journal | vauthors = Wesołowska A, Nikiforuk A, Michalska K, Kisiel W, Chojnacka-Wójcik E | title = Analgesic and sedative activities of lactucin and some lactucin-like guaianolides in mice | journal = Journal of Ethnopharmacology | volume = 107 | issue = 2 | pages = 254–8 | date = September 2006 | pmid = 16621374 | doi = 10.1016/j.jep.2006.03.003 }}</ref>{{Failed verification|date=April 2023}} while another, lactucopicrin, has been shown to act as an acetylcholinesterase inhibitor ''in vitro''.<ref>{{cite journal | vauthors = Rollinger JM, Mocka P, Zidorn C, Ellmerer EP, Langer T, Stuppner H | title = Application of the in combo screening approach for the discovery of non-alkaloid acetylcholinesterase inhibitors from Cichorium intybus | journal = Current Drug Discovery Technologies | volume = 2 | issue = 3 | pages = 185–93 | date = September 2005 | pmid = 16472227 | doi = 10.2174/1570163054866855 }}</ref> thumb|right|''Lactuca virosa''
''Lactuca floridana'' was found to contain 11β,13-Dihydro-lactucin-8-O-acetate hemihydrate.<ref>{{cite journal | vauthors = Fronczek CF, Gomez-Barrios ML, Fischer NH, Fronczek FR | title = 11β,13-Dihydro-lactucin-8-O-acetate hemihydrate | journal = Acta Crystallographica Section E | volume = 65 | issue = Pt 10 | pages = o2564-5 | date = September 2009 | pmid = 21578003 | doi = 10.1107/S160053680903829X | pmc = 2970292 | bibcode = 2009AcCrE..65o2564F }}</ref>
==Formulations== Lactucarium was used unmodified in lozenges, 30–60 milligrams (0.5 to 1 grain), sometimes mixed with borax. 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.<ref name="BPC" />
== References == {{Reflist}}
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Category:Analgesics Category:Sedatives Category:Euphoriants Category:Medicinal plants Category:Lactuca