# Lactuca serriola (Prickly Lettuce)

**Canonical URL:** https://ingredients.hermeticasuperfoods.com/ingredients/lactuca-serriola
**Data Source:** Hermetica Superfoods Ingredient Encyclopedia
**Updated:** 2026-03-23
**Evidence Score:** 2 / 10
**Category:** Herb
**Also Known As:** Lactuca serriola, Wild Lettuce, Compass Plant, Milk Thistle, Horse Thistle, Prickly Wild Lettuce, Scarole

## Overview

Lactuca serriola, commonly called prickly lettuce, contains lactucin and lactucopicrin — bitter sesquiterpene lactones that interact with central nervous system receptors to produce sedative and anxiolytic effects. These compounds are structurally related to opioid-like molecules and may modulate GABA-A receptor activity, making prickly lettuce a subject of interest for anxiety, seizure, and pain research.

## Health Benefits

["\u2022 May reduce anxiety: In a preclinical mouse study, an n-hexane seed extract (400 mg/kg) increased open arm stay duration by 456.14%, suggesting significant anxiolytic potential (PMID: 36421417). Evidence is preliminary and from animal models only.", "\u2022 May possess anti-seizure properties: In a mouse model of pentylenetetrazol-induced kindling, various seed extracts significantly reduced seizure scores, indicating potential anti-epileptogenic activity. Evidence is preclinical (PMID: 36421417).", "\u2022 May relax smooth muscles: A methanol extract demonstrated spasmolytic effects on isolated rabbit jejunum and trachea tissues, relaxing contractions at concentrations of 0.3\u20133.0 mg/mL. This evidence is from in-vitro tissue studies (PMID: 23662127).", "\u2022 May support vascular health: The methanol extract was shown to relax potassium-induced contractions in isolated rabbit aorta preparations, suggesting a vasorelaxant effect. This is based on preliminary in-vitro evidence (PMID: 23662127).", "\u2022 Provides antioxidant activity: The plant contains high levels of phenolic compounds, which exhibit [free radical scaveng](/ingredients/condition/antioxidant)ing potential comparable to quercetin in laboratory tests. This evidence is from in-vitro analysis (PMID: 23662127)."]

## Mechanism of Action

The primary bioactive compounds in Lactuca serriola — lactucin and lactucopicrin — are guaianolide-type sesquiterpene lactones that are believed to modulate GABA-A receptor activity, enhancing inhibitory neurotransmission similarly to benzodiazepines. Lactucopicrin has also demonstrated acetylcholinesterase inhibitory activity, which may contribute to cognitive and [neuroprotective effect](/ingredients/condition/cognitive)s. Additionally, the n-hexane seed extract contains constituents that may suppress voltage-gated sodium channels, providing a plausible mechanism for the observed anti-seizure activity in preclinical models.

## Clinical Summary

Current evidence for Lactuca serriola is limited to preclinical animal studies with no published human clinical trials. In a mouse model, an n-hexane seed extract at 400 mg/kg increased open-arm stay duration in the elevated plus maze by 456.14%, indicating strong anxiolytic potential (PMID: 36421417). Separate rodent studies have demonstrated anti-seizure activity against pentylenetetrazole-induced convulsions. While these findings are promising, they cannot be directly extrapolated to human efficacy or dosing without controlled clinical trials.

## Nutritional Profile

{"macronutrients": {"protein": "1.2 g per 100 g", "fiber": "1.1 g per 100 g", "carbohydrates": "2.2 g per 100 g", "fat": "0.3 g per 100 g"}, "micronutrients": {"vitamin_A": "7405 IU per 100 g", "vitamin_C": "3.7 mg per 100 g", "vitamin_K": "62.5 mcg per 100 g", "calcium": "36 mg per 100 g", "iron": "0.86 mg per 100 g", "magnesium": "13 mg per 100 g", "potassium": "194 mg per 100 g"}, "bioactive_compounds": {"lactucin": "Present, specific concentration not well-documented", "lactucopicrin": "Present, specific concentration not well-documented"}, "bioavailability_notes": "The bioavailability of vitamins and minerals can be influenced by factors such as preparation method and individual absorption efficiency. The presence of lactucin and lactucopicrin contributes to the plant's potential medicinal properties, though their exact bioavailability is not well-studied."}

## Dosage & Preparation

No human dosage has been established. Dosages studied in preclinical models include 400 mg/kg of n-hexane seed extract for anxiolytic effects in mice and 0.3–3.0 mg/mL of methanol extract in isolated tissue preparations for spasmolytic effects. Consult a healthcare provider before starting any new supplement.

## Safety & Drug Interactions

Lactuca serriola has no established clinical safety profile in humans, as rigorous human trials are lacking. Because its constituents may potentiate GABA-A receptor activity, concurrent use with benzodiazepines, barbiturates, alcohol, or other CNS depressants could theoretically produce additive sedation. Individuals with allergies to plants in the Asteraceae (daisy) family should exercise caution due to potential cross-reactivity with sesquiterpene lactones. Pregnant and breastfeeding women should avoid use entirely given the absence of reproductive safety data.

## Scientific Research

The available research on Lactuca serriola consists entirely of preclinical studies in animal models and isolated tissue preparations (PMID: 36421417, PMID: 23662127). No randomized controlled trials (RCTs) or any other human clinical studies were identified, meaning its effects in humans have not been scientifically validated.

## Historical & Cultural Context

Lactuca serriola has a history of use in folkloric medicine for managing respiratory ailments like bronchial spasm, gastrointestinal issues such as intestinal spasm, and vascular disorders. The specific traditional medicine systems or cultural contexts for this use are not detailed in the available research.

## Synergistic Combinations

L-Theanine, Valerian Root, Magnesium, Chamomile

## Frequently Asked Questions

### What are the active compounds in prickly lettuce?

The primary bioactive compounds in Lactuca serriola are lactucin and lactucopicrin, both guaianolide-type sesquiterpene lactones concentrated in the milky latex (lactuarium) of the plant. Lactucopicrin is structurally similar to ibuprofen's precursor and has demonstrated acetylcholinesterase inhibitory activity in vitro. These compounds are also found in related species like Lactuca virosa, which historically has been used as 'wild opium.'

### Can prickly lettuce help with anxiety?

Preclinical mouse research (PMID: 36421417) showed that an n-hexane seed extract of Lactuca serriola at 400 mg/kg increased open-arm exploration time in the elevated plus maze by 456.14%, a standard anxiolytic behavioral marker. The proposed mechanism involves modulation of GABA-A receptors by its sesquiterpene lactone constituents. However, no human clinical trials have been conducted, so any anxiolytic application in people remains speculative at this stage.

### Is prickly lettuce the same as wild opium lettuce?

Lactuca serriola (prickly lettuce) is closely related to Lactuca virosa, which is commonly called wild opium lettuce or bitter lettuce, but they are distinct species. Both contain lactucin and lactucopicrin in their milky latex, and both have been used historically as mild sedatives. Lactuca virosa generally has higher concentrations of these sesquiterpene lactones and has more historical documentation of sedative use, whereas Lactuca serriola is considered the wild ancestor of cultivated lettuce (Lactuca sativa).

### What is the effective dose of prickly lettuce extract?

No human dose has been established for Lactuca serriola, as all efficacy data comes from animal studies. In the published preclinical anxiolytic study, the effective dose was 400 mg/kg of n-hexane seed extract administered to mice, which is not directly translatable to a human equivalent dose without allometric scaling and clinical validation. Until human pharmacokinetic and dose-finding trials are completed, no safe or effective human dose can be recommended.

### Does prickly lettuce interact with any medications?

Lactuca serriola's sesquiterpene lactones may potentiate the effects of CNS depressants including benzodiazepines (e.g., diazepam), barbiturates, opioids, and sedating antihistamines through additive GABAergic or general sedative mechanisms. Lactucopicrin's acetylcholinesterase inhibitory activity could theoretically interfere with anticholinergic medications or enhance the effects of cholinergic drugs. These interactions are hypothetical based on known mechanisms and have not been confirmed in clinical drug-interaction studies.

### What does the current research evidence show about prickly lettuce's effectiveness?

Most evidence for prickly lettuce comes from preclinical animal studies, particularly in mice, which show potential anxiolytic and anti-seizure properties but cannot be directly applied to humans. Clinical trials in humans are limited, making it difficult to establish definitive efficacy or optimal dosing for therapeutic use. The preliminary nature of available research means more high-quality human studies are needed before strong claims can be made about its effectiveness as a supplement.

### Who should avoid prickly lettuce supplements and why?

Pregnant and breastfeeding women should avoid prickly lettuce due to insufficient safety data in these populations, as the herb traditionally has been used for various physiological effects. Individuals taking sedative, anxiolytic, or anticonvulsant medications should consult a healthcare provider before use, as prickly lettuce may have additive or synergistic effects. People with allergies to plants in the Asteraceae family (ragweed, chrysanthemums) may experience cross-reactivity and should exercise caution.

### What form of prickly lettuce extract shows the most promise in research studies?

N-hexane seed extracts have demonstrated the most notable effects in preclinical studies, with a 400 mg/kg dose showing significant anxiolytic effects in mouse models of anxiety. However, this represents animal research at doses that cannot be directly translated to human supplementation. The bioavailability and effectiveness of different commercial extract forms (aqueous, ethanolic, or hexane-based) in humans remain largely unstudied.

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*Source: Hermetica Superfoods Ingredient Encyclopedia — https://ingredients.hermeticasuperfoods.com*
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