IngredientsLactucarium is the dried, hardened milky latex exuded from the stems and leaves of certain wild lettuce species, primarily Lactuca virosa, a biennial herb native to regions including Europe and parts of Asia. It is related to common lettuce (L. sativa), and is often called wild lettuce, bitter lettuce, laitue vireuse, opium lettuce, poisonous lettuce, tall lettuce, great lettuce, or rakutu-karyumu-so.
Lactuca virosa is a woodland cousin of the common salad lettuce (Lactuca sativa) and a member of the sunflower family, Asteraceae. It is biennial, similar to prickly lettuce Lactuca serriola but taller, capable of growing to 200 cm (approximately 80 inches or nearly 7 feet). One of the most distinctive features of Lactuca virosa is its milky latex (lactucarium), which exudes abundantly when cuts are made in stems and leaves, turning brown upon contact with air.
The substance is known by the common name "Lettuce Opium," and its principal constituents include lactucin (C11H14O4), lactucerin (lactucone), lactucopicrin, lactucic acid, and a camphoraceous volatile oil.
All species of Lactuca exude what is known as lactucarium — a potent, milky latex that oozes from the plant when wounded or broken, and some varieties produce copious amounts of this latex. Lactucarium resembles the milky latex harvested from opium poppies and, similarly, can be reduced and dried into a thick solid.
Although the standard definition of lactucarium requires its production from Lactuca virosa, 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.
Lactucarium is described and standardized in the 1898 United States Pharmacopoeia and the 1911 British Pharmaceutical Codex for use in lozenges, tinctures, and syrups as a sedative for irritable cough or as a mild hypnotic sleeping aid for insomnia.
Preparations documented in historical eclectic pharmacy include a Tincture of Lactucarium at 50% strength, at a dose of 30–60 drops. A Syrup of Lactucarium, prepared from the tincture, was also listed, at a dose of 1–3 fluidrachms. The raw dried lactucarium was administered at doses of 5 to 20 grains.
Wild lettuce leaves and stems, lactucarium, and the oil from the seeds are all used medicinally; leaves and stems are traditionally infused as tea or made into an extract. Lactucarium products are also smoked in pipes or heated in small bowls, with the vapors inhaled; these extracts are sometimes combined with damiana distillates, African yohimbe bark, or catnip distillates.
Lettuce opium was used by the ancient Egyptians and was introduced as a drug in the United States as early as 1799. The substance 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 high addictiveness, and in some cases preferable. However, early efforts to isolate an active alkaloid were unsuccessful.
The ancient Egyptians took lactucarium in the form of a medication, as people long believed the herb possessed soporific attributes. The Ancients held the lettuce in high esteem for its cooling and refreshing properties; the Emperor Augustus attributed his recovery from a dangerous illness to it, built an altar to it, and erected a statue in its honour.
Extant documents on traditional Persian medicine refer to many plants that could induce sleep and which were used by pregnant women; in Iran, local herbal shops continue to provide these herbs to pregnant women to treat insomnia. Unani scholars claimed that lettuce and its oil are beneficial in the treatment of insomnia, pain, and early stages of inflammation.
Lactuca virosa was used in the 19th century by physicians when opium could not be obtained. It was studied extensively by the Council of the Pharmaceutical Society of Great Britain in 1911, when two chemicals responsible for the properties of L. virosa — lactucopicrin and lactucin — were identified.
Historically, doctors used wild lettuce as a pain reliever and to treat conditions such as whooping cough, with research studies on its use dating back to 1814. In 1814, a German physician documented several medical accounts of wild lettuce, describing the herb as highly effective for reducing the spasmodic effects of cough on the diaphragm — after administration, the cough was less violent and therefore prevented vomiting.
A pharmaceutical company in the 1930s isolated lactucarium from wild lettuce and created an antitussive drug called Lactucyl.
The drug was described in traditional herbal texts as resembling a feeble opium without its tendency to upset the digestive system, used to a small extent as a sedative and narcotic, and dissolved in wine it was said to be a good anodyne.
A historical eclectic medical text described lactucarium as a non-constipating calmative and feeble hypnotic, sometimes proving useful in insomnia from mental overwork and, as a syrup, in the cough of phthisis.
In the twentieth century, two major studies found commercial lactucarium to be without effect. In 1944, Fulton concluded that "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.
In the United States, the plant experienced a resurgence in popularity in the 1970s. 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.
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 mice.
Lactucin and its derivatives lactucopicrin and 11β,13-dihydrolactucin are characteristic bitter sesquiterpene lactones of Lactuca virosa and Cichorium intybus. The primary chemical components of lactucarium include lactucic acid and lactucerin (comprising 50–60% of the insoluble fraction), alongside the key sesquiterpene lactones that exhibit diuretic, laxative, anticonvulsant, and anti-inflammatory activities.
Analysis of L. virosa has found it to contain lactucic acid, lactucopicrin, 50–60% lactucerin (lactucone), and lactucin.
Besides sesquiterpene lactones, Lactuca virosa contains flavonoids, coumarins, and N-methyl-β-phenethylamine. Additional secondary metabolites include flavonoids such as quercetin and kaempferol, which are glycosylated in various forms across Lactuca species. Coumarins like umbelliferone are also present, isolated from the latex and contributing to the overall phenolic fraction.
The usual constituents of latex also include albumin, mannite, and caoutchouc. Lactucarium contains a high proportion of rubber, mannitol, and lactucerol, which can constitute up to 50% of its composition.
Adenosine receptor agonism: One of the compounds, lactucin, is an adenosine receptor agonist in vitro. Preclinical evidence shows that lettuce extracts improve sleep latency and sleep duration through upregulation of GABA receptor subunits as well as adenosine A1 receptor in pentobarbital-injected mice.
Acetylcholinesterase inhibition: Lactucopicrin, a sesquiterpene lactone, shows potent inhibitory acetylcholinesterase (AChE) activity. Lactupicrin inhibits acetylcholinesterase (AChE) with an IC50 of 150.3 μM.
NF-κB inhibition and anti-inflammatory signaling: Using a TNFα-induced inflammation model in macrophages, endothelial, and intestinal epithelial cells, lactucopicrin was identified as a potent NF-κB antagonist; in silico docking and functional assays revealed lactucopicrin as a novel AHR (aryl hydrocarbon receptor) modulator, and silencing AHR expression attenuated lactucopicrin-mediated NF-κB inhibition, uncovering a previously unrecognized AHR-NF-κB crosstalk mechanism.
Bioavailability considerations: A significant obstacle limiting the pharmacological use of these sesquiterpene lactones is their poor aqueous solubility and low oral bioavailability. Following oral consumption of chicory preparations, a human pharmacokinetic study confirmed only lactucin and 11β,13-dihydrolactucin were detected in circulation at low concentrations, while in vitro fermentation assays demonstrated the conversion of lactucopicrin and lactucin into lactucin-type compounds by the gut microbiota. These findings indicate that chicory sesquiterpene lactones undergo extensive presystemic metabolism involving microbial and phase II conjugation processes, resulting in very low plasma levels.
Hyoscyamine trace alkaloid: Some effects have also been credited to a trace of hyoscyamine in Lactuca virosa, but the alkaloid was undetectable in standard lactucarium.
Animal/Preclinical Evidence: A latex that is called lactucarium can be derived from the extract of the stem secretions of Lactuca virosa; oils and extracts can also be produced from L. virosa, and these oils and extracts have sedative properties in rodents. Lactucin and lactucopicrin, but not 11β,13-dihydrolactucin, showed sedative properties in the spontaneous locomotor activity test.
Human/Clinical Evidence: A double-blind, randomized, placebo-controlled trial on the efficacy and safety of Lactuca sativa L. seeds on pregnancy-related insomnia demonstrated that lettuce seed decreased insomnia during pregnancy and could be recommended as a safe natural remedy for treatment of pregnancy-related insomnia. Specifically, in a prospective randomized clinical trial, 100 pregnant women with insomnia aged 20–45 years were assigned to receive capsules containing 1,000 mg of lettuce seed or a placebo daily for two weeks. The main outcome was the quality of sleep, measured using the Pittsburgh Sleep Quality Index (PSQI). Each group contained 50 participants, and an improvement in the PSQI score was significantly greater in patients receiving lettuce seed than in those receiving the placebo. Only 35 women in each group completed the trial; those in the lettuce group had statistically significant improvement in sleep (p = 0.021). Notably, the lettuce species (Lactuca sativa) used in this trial is different from the wild lettuce species (Lactuca virosa) available as an herbal medicine in the United States.
A further randomized, double-blind, placebo-controlled trial examined lettuce extract (Lactuca sativa, Heukharang variety) in Korean adults. Participants aged 30–65 with poor sleep quality (Pittsburgh Sleep Quality Index (PSQI) > 5) were recruited; over 4 weeks, participants took two capsules daily of either the test extract or placebo, and sleep quality and quantity were assessed using the PSQI, actigraphy, and polysomnography. The adjusted final PSQI scores showed greater improvement in the test group than in the placebo group for global scores (6.48 ± 0.63 vs. 7.41 ± 0.57, p = 0.0462). Regarding actigraphy measurements, the adjusted final means showed significant improvements in the test group compared to the placebo group for total sleep time (421.68 ± 13.29 vs. 386.57 ± 12.27 min, p = 0.0023) and sleep efficiency.
Evidence Assessment: With the exception of a small study on insomnia in pregnant women, there is little clinical evidence to support its use for other indications. Human clinical trials are specifically needed to verify the benefits of wild lettuce (Lactuca virosa) latex (lactucarium proper) for sleep. The available clinical trials used Lactuca sativa seed, not Lactuca virosa latex; accordingly, the evidence base for lactucarium specifically remains preliminary.
Animal/Preclinical Evidence: The compounds showed analgesic effects at doses of 15 and 30 mg/kg in the hot plate test similar to that of ibuprofen (used as a standard drug) at a dose of 30 mg/kg; the analgesic activities of the compounds at a dose of 30 mg/kg in the tail-flick test were comparable to that of ibuprofen given at a dose of 60 mg/kg. Lactucopicrin appeared to be the most potent analgesic of the three tested compounds.
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.
Crude preparations from Lactuca virosa (P-1, P-2, P-3), lactucin, and jacquinelin were investigated pharmacologically in Albino-Swiss mice. Results indicate that P-1, P-2, P-3, and lactucin, but not jacquinelin, show sedative and analgesic properties; the most active preparation at a dose of 2 mg/kg reduced spontaneous locomotor activity, and at a dose of 15 mg/kg produced an analgesic effect.
Human/Clinical Evidence: Many individuals use wild lettuce for pain relief; however, human clinical trials are needed to verify these findings. The analgesic evidence for lactucarium in humans is currently absent from the peer-reviewed literature.
Evidence Assessment: Evidence is animal and in vitro only. No controlled human trials of lactucarium-specific analgesic effect exist in the published literature.
Lactucarium is traditionally documented as a diuretic, laxative, and sedative agent, and is well-referenced for use as an antitussive and to relieve dyspnoea. Due to its relaxing properties, wild lettuce may be beneficial as an antitussive herb; herbalist Christopher Hobbs has described wild lettuce as useful for cough medicine, stating that wild lettuce helps to relax the bronchioles, which works to remedy coughing.
Evidence Assessment: The antitussive use is traditionally documented and supported by historical pharmacopoeial listing, but no modern human clinical trials have confirmed this application. Evidence is historical and anecdotal.
Chronic inflammatory diseases, including inflammatory bowel disease and cardiovascular disease, share inflammation as a central pathological feature. Research published in 2025 identified lactucopicrin as a potent NF-κB antagonist in a TNFα-induced inflammation model across macrophages, endothelial, and intestinal epithelial cells. In silico docking and functional assays additionally revealed lactucopicrin as a novel AHR modulator, and silencing AHR expression attenuated lactucopicrin-mediated NF-κB inhibition. These findings position lactucopicrin as a dual-pathway modulator and highlight the therapeutic potential of sesquiterpene lactones in treating inflammation-driven diseases.
Evidence Assessment: This evidence is entirely preclinical (cell-based and animal), published in 2025 (Journal of Medicinal Chemistry). No human clinical trials of lactucopicrin or lactucarium as anti-inflammatory agents have been conducted.
Folklore reports from Afghanistan described the use of aqueous root extracts of Cichorium intybus as a light-sensitive plant remedy for malaria. Preparative isolation and bioassay against HB3 clone of strain Honduras-1 of Plasmodium falciparum identified the previously known light-sensitive sesquiterpene lactones lactucin and lactucopicrin to be antimalarial compounds. This study verified that there are at least two antimalarial compounds in Cichorium intybus identified as lactucin and lactucopicrin; both had been previously reported in chicory but their antimalarial activity had not previously been confirmed.
Evidence Assessment: Evidence is in vitro (cell culture bioassay against Plasmodium falciparum). No human clinical trials exist. Research is preliminary.
The reported hallucinogenic effect of lettuce opium products is usually mild and appears to be related to the degree of user expectation. There is no pharmacologic basis for the purported hallucinogenic effects of lettuce opium.
There is limited clinical evidence to support specific dose recommendations.
These dose parameters cannot be directly translated to human clinical use, as the clinical dose studies used Lactuca sativa seed, not dried Lactuca virosa latex.
Wild lettuce (Lactuca virosa) can cause toxic effects when eaten. Wild lettuce grows in the north of Iran and some natives consume it unaware of its adverse side effects. Eight patients with manifestations of wild lettuce toxicity were admitted to a general hospital affiliated to the Golestan University of Medical Sciences. All patients recovered, although one had to spend 48 hours in the intensive care unit, and no chronic complications were reported.
A paper published in 2009 described these 8 patients who were apparently admitted after ingesting wild lettuce as a fresh herb, potentially in large quantities. It was speculated that the herb had been harvested before the usual time; usually, wild lettuce is harvested in late summer, but in this case harvesting was suggested to have taken place in May. The paper proposed that this was a case of overdose.
A documented case report titled "The case of the salad shooters: intravenous injection of wild lettuce extract" was published in Veterinary and Human Toxicology in 1998 (vol. 40, no. 5), highlighting the serious risks of parenteral misuse.
Toxic effects from wild lettuce can include sweating, fast heartbeat, pupil dilation, dizziness, ringing in the ears, vision changes, sedation, breathing difficulty, and death. Applying wild lettuce directly to the skin can cause irritation.
A major 20th-century study noted that the active bitter principles lactucin and lactucopicrin from the fresh latex were unstable and did not remain in commercial preparations of lactucarium. This instability is a key factor in interpreting the historical clinical failures of commercial lactucarium products and has important implications for any therapeutic use.
A crude extract was not toxic to rats at a dose of 6 grams per kilogram. This rodent acute-toxicity datum does not establish a human safety threshold.
In the United States, the plant is unscheduled by the Food and Drug Administration (FDA), meaning it is legal to grow, purchase, and own without prescription or license.
Given the documented sedative activity in preclinical models and the mechanism involving adenosine A1 and GABA receptor pathways, several in vivo studies of lettuce extracts report changes consistent with adenosine A₁/A₂A receptor involvement — a plausible pathway for promoting non-REM sleep. These pharmacological mechanisms suggest that additive CNS depression may be possible in combination with other sedative agents or central nervous system depressants, though no controlled human interaction studies have been published.
Health conditions that Lactucarium may help support.
Lactucarium is the dried latex of wild lettuce (Lactuca virosa or Lactuca sativa), historically used in 19th-century European and American medicine as a sedative and hypnotic agent. Active sesquiterpene lactones including lactucin and lactucopicrin have demonstrated sedative activity. Traditional use for insomnia and restlessness is well-documented.
Body systems that Lactucarium may help support.
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