Wild Lettuce

The drug is lactucarium, the milky latex bled from a cut stem and dried into a hard brown mass, with the leaf used as a milder alternative. In nineteenth-century European medicine lactucarium was used as a sedative and analgesic. Physicians regarded it as weaker than opium but free of its side effects ^{22Reference 22Trojanowska A · 2005ReviewLettuce (Lactuca sp.) as a medicinal plant in Polish publications of the 19th century — historical reviewView study →}.

It was also given to quiet coughing and nervous irritation, and to bring on sleep where opium was unsuitable ^{19Reference 19Besharat S et al. · 2009Case reportWild lettuce (Lactuca virosa) toxicity — case seriesView study →}. Older sources add uses in kidney complaints, painful uterine cramps and oedema, drawing on a diuretic reputation ^{19Reference 19Besharat S et al. · 2009Case reportWild lettuce (Lactuca virosa) toxicity — case seriesView study →}.

Contemporary herbal practice uses it mainly for restlessness, poor sleep and mild pain. It is taken as a tea, a tincture or the dried latex in small doses, and occasionally smoked.

In mice, lactucin and lactucopicrin reduced spontaneous movement, a measure of sedation, while the closely related 11β,13-dihydrolactucin did not ^{1Reference 1Wesołowska A et al. · 2006AnimalAnalgesic and sedative activities of lactucin and some lactucin-like guaianolides in mice — animal in vivoView study →}.

Garden lettuce extracts rich in these lactones increased sleep duration and non-REM sleep in rodents and countered caffeine-induced wakefulness ^{2,3Reference 2Kim HW et al. · 2019AnimalEffectiveness of the sleep enhancement by green romaine lettuce (Lactuca sativa) in a rodent model — animal in vivoView study →Reference 3Ahn Y et al. · 2023AnimalHeukharang lettuce (Lactuca sativa) leaf extract displays sleep-promoting effects through GABA-A receptor — animal in vivoView study →}. The effect was blocked by flumazenil, which acts at the benzodiazepine site of the GABA-A receptor. Lactucin and lactucopicrin showed 80.7% and 55.9% affinity for that site ^{2Reference 2Kim HW et al. · 2019AnimalEffectiveness of the sleep enhancement by green romaine lettuce (Lactuca sativa) in a rodent model — animal in vivoView study →}. Romaine lettuce seed and leaf extracts also lengthened sleep in mice ^{5Reference 5Kim HD et al. · 2017AnimalSleep-inducing effect of lettuce (Lactuca sativa) varieties on pentobarbital-induced sleep — animal in vivoView study →}.

In another study, a leaf extract raised GABA-A receptor expression in the brain, and flumazenil cut its effect on sleep time by 45.1% ^{3Reference 3Ahn Y et al. · 2023AnimalHeukharang lettuce (Lactuca sativa) leaf extract displays sleep-promoting effects through GABA-A receptor — animal in vivoView study →}. A separate mouse study linked lettuce’s sleep effect to increased adenosine A1 receptor expression alongside GABA-A subunits ^{4Reference 4Lee M et al. · 2024AnimalLactuca sativa extract enhances sleep duration through upregulation of adenosine A1 receptor and GABA-A receptor subunits in pentobarbital-injected mice — animal in vivoView study →}.

Two small human trials used garden lettuce (Lactuca sativa) seed oil. In 60 people with insomnia, 1,000 mg of the oil daily for a week improved sleep and anxiety scores more than placebo ^{6Reference 6Yakoot M et al. · 2011RCTPilot study of the efficacy and safety of lettuce seed oil in patients with sleep disorders — randomised placebo-controlled trialView study →}. In 50 people with chronic insomnia, a nasal drop combining lettuce seed, saffron and sweet violet oils was followed by lower insomnia scores, but scores also fell in the placebo group; people using the drops cut their use of sleeping pills ^{7Reference 7Taherzadeh Z et al. · 2020RCTEvaluation of sedative effects of an intranasal dosage form containing saffron, lettuce seeds and sweet violet in primary chronic insomnia — randomised, double-blind, placebo-controlled trialView study →}.

Gap: No trial has tested L. virosa itself. The human data come from a different species and preparation, and there is no standardised lactucarium dose.

Lactucopicrin suppresses NF-κB activation in stimulated endothelial cells and macrophages. It does not act on the IKK complex or on p65 DNA binding. Instead, it lowers importin-α3 by destabilising its mRNA and blocks dynein-mediated transport of p65 to the nucleus ^{8,9Reference 8Weng H et al. · 2021AnimalNatural lactucopicrin alleviates importin-α3–mediated NF-κB activation in inflamed endothelial cells and improves sepsis in mice — animal in vivoView study →Reference 9He L et al. · 2021AnimalLactucopicrin inhibits cytoplasmic dynein–mediated NF-κB activation in inflamed macrophages and alleviates atherogenesis in ApoE-deficient mice — animal in vivoView study →}. In chicory-derived form it also modulates the AHR pathway, which links to its NF-κB effect ^{10Reference 10Ávila-Gálvez MÁ et al. · 2025In vitroLactucopicrin: a sesquiterpene lactone with anti-inflammatory activity modulating the crosstalk between NF-κB and AHR pathways — in vitroView study →}.

The effects carry into live mice. Oral lactucopicrin lowered mortality by 30.5% in septic mice, and reduced plaque area in atherosclerosis-prone ApoE-deficient mice ^{8,9Reference 8Weng H et al. · 2021AnimalNatural lactucopicrin alleviates importin-α3–mediated NF-κB activation in inflamed endothelial cells and improves sepsis in mice — animal in vivoView study →Reference 9He L et al. · 2021AnimalLactucopicrin inhibits cytoplasmic dynein–mediated NF-κB activation in inflamed macrophages and alleviates atherogenesis in ApoE-deficient mice — animal in vivoView study →}. It also limited macrophage foam-cell formation by reducing LOX-1 in lipid rafts ^{11Reference 11Li Q et al. · 2022In vitroTerpene lactucopicrin limits macrophage foam cell formation by reducing LOX-1 in lipid rafts — in vitroView study →}.

Lactucin, isolated from Cichorium glandulosum, showed strong anti-neuroinflammatory activity in cultured cells (IC50 1.82 µM) ^{12Reference 12Wei Z et al. · 2024In vitroGuaianolide sesquiterpene lactones from Cichorium glandulosum and their anti-neuroinflammation activities (including lactucin) — in vitroView study →}.

Gap: Every result is for the isolated compound, largely from chicory. No study has tested a whole wild lettuce preparation for anti-inflammatory effect in vivo.

In mice, lactucin, lactucopicrin and 11β,13-dihydrolactucin, isolated from L. virosa and chicory, relieved pain in the hot-plate test at 15 and 30 mg/kg, similar to ibuprofen at 30 mg/kg. At 30 mg/kg in the tail-flick test they matched ibuprofen at 60 mg/kg. Lactucopicrin was the most potent ^{1Reference 1Wesołowska A et al. · 2006AnimalAnalgesic and sedative activities of lactucin and some lactucin-like guaianolides in mice — animal in vivoView study →}.

This single mouse study of isolated compounds is the experimental support. There is no dose-response work and no human data.

Activity-guided fractionation of chicory root isolated lactucopicrin and 8-deoxylactucin as dose-dependent inhibitors of acetylcholinesterase, the enzyme targeted by several Alzheimer’s drugs (IC50 150.3 and 308.1 µM) ^{13Reference 13Rollinger JM et al. · 2005In vitroApplication of the in-combo screening approach for the discovery of non-alkaloid acetylcholinesterase inhibitors from Cichorium intybus (8-deoxylactucin, lactucopicrin) — in vitroView study →}. Calorimetry and docking confirmed lactucopicrin as the stronger inhibitor of the two lactones tested ^{14Reference 14Jaśkiewicz A et al. · 2022In vitroEvaluation of activity of sesquiterpene lactones and chicory extracts as acetylcholinesterase inhibitors in calorimetric and docking simulation studies — in vitroView study →}.

In cultured nerve cells, lactucopicrin promoted neurite outgrowth and raised NGF, BDNF and NT-3 through Ca²⁺/CaMKII/ATF1 signalling ^{15Reference 15Venkatesan R et al. · 2017In vitroLactucopicrin potentiates neuritogenesis and neurotrophic effects by regulating Ca²⁺/CaMKII/ATF1 signaling — in vitroView study →}.

The inhibitory concentrations are in the micromolar range, and everything is cell-based. There is no animal cognition model and no bioavailability data.

Lactucopicrin from L. virosa was cytotoxic to U87Mg glioblastoma cells. It triggered autophagy, G2/M arrest through p53 and p21, and apoptosis. The antioxidant N-acetylcysteine reversed the effect, pointing to reactive oxygen species ^{16Reference 16Rotondo R et al. · 2020In vitroImplication of lactucopicrin in autophagy, cell-cycle arrest and oxidative stress to inhibit U87Mg glioblastoma cell growth — in vitroView study →}.

Lactucin from chicory suppressed gastric-cancer cell growth, arrested the cell cycle and induced apoptosis through MAPK/p38 signalling, and it slowed tumour growth in a mouse xenograft ^{17Reference 17Wei D et al. · 2026AnimalLactucin inhibits growth and induces apoptosis in gastric cancer cells by targeting MAPK signaling — animal in vivo (xenograft)View study →}.

Both are single cell-line studies of isolated compounds.

Screening of chicory root constituents against Plasmodium falciparum identified lactucin and lactucopicrin as the active antimalarial compounds in vitro ^{18Reference 18Bischoff TA et al. · 2004In vitroAntimalarial activity of lactucin and lactucopicrin: sesquiterpene lactones isolated from Cichorium intybus — in vitroView study →}. The compounds are light-sensitive.

Gap: A single in vitro assay of isolated compounds from chicory, with no animal model and no potency comparison against antimalarial drugs.

Sedation. Wild lettuce is generally mild at traditional doses, but it is sedating. Do not combine it with alcohol, benzodiazepines, opioids or other sedatives, and do not take it before driving or operating machinery. This caution rests on its pharmacology; no interaction study has been done.

Overdose. In a case series from northern Iran, eight people aged 12–38 who had eaten a large amount of the raw herb were treated in hospital. Their signs included dry mouth, dilated pupils, urinary retention, agitation, anxiety, blurred vision, hallucinations, vomiting and reduced consciousness. One spent 48 hours in intensive care for prolonged loss of consciousness, and all recovered with supportive treatment ^{19Reference 19Besharat S et al. · 2009Case reportWild lettuce (Lactuca virosa) toxicity — case seriesView study →}. A separate French report describes abuse of the plant ^{20Reference 20Spadari M et al. · 2003Case reportAbuse of Lactuca virosa — case reportView study →}, and it is listed among natural psychoactive substances ^{21Reference 21Lo Faro AF et al. · 2020ReviewBiomedical analysis of new psychoactive substances of natural origin — reviewView study →}.

Allergy. The bitter sesquiterpene lactones (lactucin, lactucopicrin) are potential contact allergens within the daisy family.

Smoking. Smoking any plant material, including dried latex, carries respiratory risk.