Bitter grass

Bitter Grass (Calea ternifolia Kunth, syn. Calea zacatechichi): A Comprehensive Reference

1. Identity and Botanical Classification

Bitter grass is the widely recognized English common name for Calea ternifolia Kunth, a species of flowering plant in the aster family, Asteraceae. It is formally classified as Calea ternifolia (syn. Calea zacatechichi), a species of flowering plant in the aster family, Asteraceae, native to Mexico and Central America, whose English language common names include bitter-grass, Mexican calea, and dream herb.

The former species epithet zacatechichi is a Hispanicized form of the Nahuatl word zacatl chichic, meaning "bitter grass." The plant material of Calea zacatechichi has an intense bitter taste, which directly gives rise to this common name.

The plant has accumulated an exceptionally large number of common and traditional names across different languages and cultures. These include Ahuapatli, Aztec Dream Grass, Bitter Plant, Bitter Plant of the Mountains, Cochitzapotl (Nahuatl), Dog Grass, Dream Herb, Hierba Amarga, Hoja Madre, Leaf of God, Leaf of the Mother, Sacachichic, Tam Huni, Thle-Pelacano (Chontal), Yerba Amarga, Zacate Amargo, and Zacatechichi, among many others.

The plant is an important medicinal species that grows from Mexico to Costa Rica. It is a perennial shrub, native to Mexico and Central America, that grows 1 to 1.5 meters tall with opposite, lanceolate leaves bearing serrated margins. It belongs to the aster family, Asteraceae.

1.1 Common Forms and Preparations

The dried leaves and stems of Calea zacatechichi have been smoked, applied topically, placed under the pillow, made into a tea, and ingested as capsules. These represent both traditional and modern commercial preparation forms. Products such as tablets and tea made from this herb are currently available in the international market.

Isolated reports describe rituals that involve smoking a plant believed to be this species, drinking it as a tea, and placing it under a pillow to induce divinatory or lucid dreams due to its properties as an oneirogen. While quite bitter if brewed in hot water, the bitterness can be considerably masked by brewing with Osmanthus flowers, which have a compatible scent profile.

2. Traditional and Historical Use

2.1 Indigenous and Ritual Use in Mexico

The documentation of bitter grass in historical sources begins in earnest in 19th-century Mexico, with references to even earlier use embedded in Mesoamerican oral and textual traditions. In 1801, Friar Juan Navarro, in his book Historia Natural o Jardín Americano (Natural History or American Garden), referred to "ahuapatli" as a plant suitable for treating stomach complaints; this species was later identified as C. zacatechichi based on analysis of the pictures depicted in the book.

In the 19th century, in the manuscript Lecciones de Farmacología (Pharmacology Lessons) by Oliva (1853), C. zacatechichi was described as a tonic and febrifuge. In 1893, a tincture of C. zacatechichi was registered as an aperitive to treat anorexia and hepatic illnesses in the Formulario de la Facultad Médica Mexicana. At the end of the 19th century, galenical preparations of C. zacatechichi were registered as aperitive and digestive agents in the second and third editions of the New Mexican Pharmacopeia.

The plant is used in traditional medicine and ritual in its native range. The most documented indigenous use involves the Chontal people of Oaxaca. The Chontal people of Oaxaca reportedly use the plant, known locally as thle-pela-kano, during divination. The Chontal people traditionally called this plant thle-pela-kano and employed it specifically for what they termed "clarifying dreams" within divinatory and diagnostic healing contexts; shamans consumed it as a tea or smoked the dried leaves before ritual sleep, seeking guidance through enhanced dream narrative.

The Chontal shamans called it "the leaf of God" and used it for divination, often in rituals intended to connect with the spiritual realm or gain insight into unresolved questions.

2.2 Ethnobotanical Uses Among Specific Peoples

Multiple indigenous groups in Mexico have employed this plant for different, though often overlapping, medicinal purposes. In Mexico, the plant is used as a herbal remedy for dysentery and fever. The Zoque Popoluca people call the plant tam huñi ("bitter gum") and use it to treat diarrhea and asthma, and the Mixe people know it as poop taam ujts ("white bitter herb") and use it for stomachache and fever.

Calea zacatechichi has been used in folk remedies as an appetite stimulant, cleansing agent, calming agent, laxative, and for treatment of diarrhea, dysentery, fever, skin rashes, swollen scalps, "cold stomach," and headache.

The plant is highly valued for rituals and for treating several illnesses including anorexia, upset stomach, diabetes, periodic fevers, diarrhea, bile problems, and skin diseases.

2.3 Pharmacopoeial and Formal Recognition in Traditional Medicine

Beyond folk medicine, bitter grass has had a formal presence in Mexican institutional medicine. Its tincture was registered as an aperitive and digestive agent in 19th-century Mexican pharmacopeial texts, providing an institutional acknowledgment of its traditional roles. It has a long tradition in indigenous culture and is also called the "dream herb" because it temporarily intensifies the clarity of dreams and significantly influences the central nervous system.

3. Key Constituents and Active Compounds

3.1 Sesquiterpene Lactones

Phytochemical research has established that the most pharmacologically significant class of compounds in bitter grass is the sesquiterpene lactones. First reports on the chemical profile of C. zacatechichi evidenced that the plant is particularly rich in sesquiterpene lactones, mainly germacranolides. The plant contains sesquiterpenes and flavonoids as the major constituents.

Chemical investigations led to the isolation of several sesquiterpene lactones including caleolactone C and caleins A and C and analogs; flavonoids; chromenes; and chlorogenic acid. Specifically, C. zacatechichi yielded the sesquiterpene lactone zexbrevin and a new analog, several analogs of neurolenin B including calein A, two analogs of budlein A, and the flavones acacetin and O-methylacacetin.

The sesquiterpenes known as caleicines and caleochromenes may be active in its effects on sleep. The compound that is thought to cause the effects of Calea ternifolia is Caleicine, a prodrug of eugenol and a potent GABA-positive modulator.

Caleicine is thought to cause effects through GABA modulation; however, the effects of Calea ternifolia are not fully understood beyond GABA modulation from Caleicine and other GABAergic compounds.

3.2 Flavonoids

Chemical compounds isolated from this species include flavones such as acacetin and sesquiterpene lactones such as germacranolides. Beyond acacetin, the flavonoid profile extends to other well-characterized compounds: bioassay-guided fractionation identified 6-hydroxyacetyl-5-hydroxy-2,2-dimethyl-2H-chromene, calein C, acacetin, isorhamnetin, and quercetin as the most active α-glucosidase inhibitors, with IC₅₀ values of 0.42, 0.28, 0.16, and 0.53 mmol·L^–1, respectively, compared to acarbose (IC₅₀ = 1.7 mmol·L^–1).

3.3 Chromenes, Coumarins, and Other Constituents

The full chemical profile of C. ternifolia also includes chromenes, coumarins, acetylenes, phenylpropanoids, and flavonoids, giving the plant a rich and diverse phytochemical constitution. The most significant specialized metabolites, however, are the sesquiterpene lactones.

Additional metabolites identified in phytochemical investigations include 6-acetyl-5-hydroxy-2-methyl-2-hydroxymethyl-2H-chromene, herniarin, scoparone, and 4′,7-dimethylapigenin.

3.4 Mechanisms of Action

Pharmacological studies in vitro and in vivo of either preparations or isolated compounds of C. ternifolia have demonstrated antinociceptive, anti-inflammatory, spasmolytic, antiprotozoal, antidepressive, antidiarrheic, anxiolytic, and antidiabetic properties.

Regarding the central nervous system, the primary proposed mechanism involves GABAergic modulation. Caleicine is described as a prodrug of eugenol and a potent GABA-positive modulator. A 2021 rodent study additionally examined the noradrenergic pathway: the study by Martínez-Mota et al. (2021) suggests the involvement of the noradrenergic system in the increase in Slow Wave Sleep episodes and enhanced fast frequencies of the hippocampus during REM sleep in animal models.

For anti-inflammatory activity, sesquiterpene lactones present in Mexican Indian medicinal plants, including those found in Calea species, have been described as potent inhibitors of the transcription factor NF-κB (FEBS Lett. 1997;402:85–90).

For antidiabetic activity, pharmacological results demonstrated that C. ternifolia effectively controlled fasting and postprandial blood glucose levels in animal models, with α-glucosidase inhibition being a key mechanism; calein C, acacetin, isorhamnetin, and quercetin were identified as the most active α-glucosidase inhibitors.

4. Scientific Evidence by Area of Use

4.1 Sleep Architecture and Dream Enhancement (Oneirogenic Effects)

The most studied and best-documented modern pharmacological use of bitter grass is its purported ability to alter sleep architecture and enhance dreaming. This area has the most clinical human data, though the human evidence remains limited to small early studies.

The landmark human study was published in 1986. At human doses, organic extracts of the plant produce EEG and behavioral signs of somnolence and induce light sleep in cats; large doses elicit salivation, ataxia, retching, and occasional vomiting; and the effects on cingulum discharge frequency were significantly different from hallucinogenic-dissociative drugs (ketamine, quipazine, phencyclidine, and SKF-10047). In the same study involving human healthy volunteers, low doses of the extracts administered in a double-blind design against placebo increased reaction time and time-lapse estimation; a controlled nap sleep study in the same volunteers showed that Calea extracts increased the superficial stages of sleep and the number of spontaneous awakenings; and subjective reports of dreams were significantly higher than both placebo and diazepam, indicating an increase in hypnagogic imagery occurring during superficial sleep stages.

In another study, 12 participants were given extracts of Calea ternifolia and experienced effects of mild augmentation of sensorial perceptions, imaginings, thought gaps, and retrieval problems; lethargy and a short sleep with vivid dreams.

According to a 2022 literature review of research on the herb, a few studies did find that its effects can include vivid dreams; however, researchers also found that people who consumed or smoked the herb experienced superficial sleep stages and frequent awakenings, so it remains unclear whether the herb can actually improve or worsen sleep.

Research has found that Calea zacatechichi does not produce the same chemical effect on the brain as hallucinogenic drugs like LSD.

Evidence strength: Rigorous clinical studies on Calea zacatechichi are limited; most findings are based on animal studies showing increased dream activity and REM phase alteration, human self-reports describing vivid dreams and heightened dream awareness, and analysis of chemical constituents supporting its sedative and psychoactive profile. The human evidence derives from a single small early study and limited follow-up; no large randomized controlled trials have been conducted.

4.2 Anxiolytic and Antidepressant Effects

A 2021 study in Journal of Ethnopharmacology specifically investigated anxiolytic and antidepressant properties in rodents. An aqueous extract of Calea zacatechichi (CZ) produced specific and robust anxiolytic- and antidepressant-like effects in mice and rats, similar to those of prototypical drugs, at doses ranging from 0.5 to 50 mg/kg; at 100 mg/kg, CZ produced visible mild sedative effects in rats, associated with a significant increase in Slow Wave Sleep episodes during a 6-hour recording, and enhanced fast frequencies of the hippocampus (gamma-band: 31–50 Hz) during REM sleep.

In healthy human volunteers, the plant has been reported to induce well-being and tranquility, and to facilitate superficial stages of sleep.

Evidence strength: Martínez-Mota et al. (2021) analyzed the anxiolytic- and antidepressant-like effects of a lyophilized aqueous extract from the aerial parts of C. ternifolia in rodents at doses ranging from 0.5 to 50 mg·kg⁻¹, and the study suggests the involvement of the noradrenergic system in Slow Wave Sleep and hippocampal activity during REM sleep in animal models. There are no published clinical trials in humans specifically testing anxiolytic or antidepressant outcomes.

4.3 Antidiabetic and Blood Glucose Effects

The antidiabetic potential of bitter grass has received substantial preclinical attention. The primary mechanisms of action of antidiabetic activity of the plant and its bioactive constituents are through α-glucosidase inhibition, curbing of PPAR-γ, and increased secretion of insulin; scoparic acid A, scoparic acid D, scutellarein, apigenin, luteolin, coixol, and glutinol are among the compounds identified as responsible for these mechanisms of action.

Animal-model data on glucose control are detailed. Demethylisoencecalin (1) and caleins A and C, the major components from an infusion of Calea ternifolia, controlled postprandial glucose levels during an oral sucrose tolerance test (3 g/kg) in normal and nicotinamide/streptozotocin-induced hyperglycemic mice at doses of 3.16–31.6 mg/kg orally, with effects comparable to those of acarbose (5 mg/kg).

These pharmacological results demonstrated that C. ternifolia effectively controlled fasting and postprandial blood glucose levels in animal models.

Evidence strength: Evidence at the preclinical (in vitro and animal) level is substantial and convergent. No adequately powered randomized controlled trials in humans have been published specifically evaluating bitter grass for glycemic control. This plant is used in the treatment of diabetes and is commercialized as a dietary supplement in several countries, but human evidence currently remains insufficient to support therapeutic recommendations.

4.4 Anti-inflammatory and Antinociceptive Effects

Properties associated with the plant's traditional uses that have been demonstrated include spasmolytic, antidiabetic, antidepressant, anti-inflammatory, and antinociceptive effects. The anti-inflammatory mechanism involves, at least in part, NF-κB inhibition by sesquiterpene lactones. Sesquiterpene lactone-containing Mexican Indian medicinal plants and pure sesquiterpene lactones have been described as potent inhibitors of the transcription factor NF-κB.

In vitro and in vivo pharmacological studies of preparations and isolated compounds of C. ternifolia have demonstrated anti-inflammatory and antinociceptive properties.

Evidence strength: The anti-inflammatory and antinociceptive evidence is from in vitro and animal models only. No human clinical trials addressing these endpoints have been published.

4.5 Gastrointestinal Effects

The gastrointestinal applications of bitter grass are among its oldest documented uses, supported by both ethnobotanical records and limited experimental data. Pharmacological studies have demonstrated antidiarrheic and spasmolytic properties in experimental models. Calea zacatechichi has been used in folk remedies as an appetite stimulant, laxative, and for treatment of diarrhea and dysentery.

Evidence strength: Traditional use is well-documented across multiple indigenous groups. Experimental spasmolytic and antidiarrheic data come from in vitro and animal studies; no human clinical trials have been published.

4.6 Antiprotozoal Activity

Non-polar extracts from C. ternifolia showed mild antiplasmodial activity against chloroquine-sensitive (poW) and chloroquine-resistant (Dd2) strains of Plasmodium in preclinical assays. Antiprotozoal properties have been demonstrated in in vitro and in vivo studies of preparations and isolated compounds.

Evidence strength: Preliminary in vitro data only. No clinical trials in humans.

5. Body Systems Associated With Bitter Grass

• Central nervous system: Oneirogenic (dream-enhancing) effects; anxiolytic and antidepressant activity in animal models; modulation of hippocampal activity during REM sleep; GABA-positive modulation by caleicine.
• Endocrine/metabolic system: Antidiabetic activity via α-glucosidase inhibition, PPAR-γ modulation, and insulin secretion stimulation, demonstrated in animal and in vitro models.
• Gastrointestinal system: Spasmolytic, antidiarrheic, aperitive, and digestive applications documented traditionally and in experimental models.
• Immune/inflammatory system: Anti-inflammatory activity via NF-κB inhibition by sesquiterpene lactones; antinociceptive properties in animal models.
• Cardiovascular system: Calea zacatechichi may decrease blood pressure, though evidence is preliminary.
• Hepatic and renal systems: Safety concerns related to potential hepatotoxicity and nephrotoxicity have been raised in preclinical research (see Section 7).

6. Dosage Forms and Reported Dosages

Dosage information for bitter grass comes from three sources: traditional ethnobotanical practice, early clinical research, and preclinical toxicology studies. No standardized or regulatory-approved dose exists.

6.1 Human Study Dosages

In the key human study, low doses of extracts were administered in a double-blind design against placebo and were found to increase reaction time and time-lapse estimation. The specific mg dosage for that human study was not published in the available source text.

The 2021 rodent study by Martínez-Mota et al. analyzed the anxiolytic- and antidepressant-like effects of a lyophilized aqueous extract from the aerial parts of C. ternifolia at doses ranging from 0.5 to 50 mg·kg⁻¹.

Anxiolytic- and antidepressant-like effects in mice and rats were produced at doses of 0.5 to 50 mg/kg; at 100 mg/kg, sedative effects and Slow Wave Sleep increases were observed.

6.2 Preclinical Toxicology Dosages

After administering 8.5 mg/kg of C. ternifolia aqueous extract to rats, reductions in platelets and leukocytes were found, along with increases in urea and the liver enzymes ALT, AST, and ALP.

Pharmacological evaluation of the essential oil of the species at 31.6–316.2 mg/kg orally also produced an important decrement in blood glucose levels during an oral sucrose tolerance test.

6.3 Preparation Forms

Dried leaves and stems of Calea zacatechichi have been smoked, applied topically, placed under the pillow, made into a tea, and ingested as capsules. Products such as tablets and tea made from this herb are currently available in the international market.

7. Safety Considerations and Drug Interactions

7.1 Nephrotoxicity

The most significant experimental safety concern identified in published peer-reviewed research involves renal toxicity. A study published in Evidence-Based Complementary and Alternative Medicine (González-Yáñez et al., 2019) found serious preclinical signals: in vitro, the extract induced eryptosis of 73% at a concentration of 100 μg·mL⁻¹; after administering 8.5 mg/kg of C. ternifolia to rats, a reduction in platelets and leukocytes was found, along with increases in urea and the liver enzymes ALT, AST, and ALP; histological analysis showed spongiform changes in the proximal tubules of renal tissue and a lymphoid infiltrate in liver tissue.

Cellular and mitochondrial functional changes in human proximal tubule HK-2 cells indicated the toxicity of C. ternifolia, and even at low doses, evidence of cellular toxicity was detected; these findings correlated with significantly elevated levels of nephrotoxicity biomarkers, supporting the need to further scrutinize the safety of this herbal dietary supplement.

Based on the study conducted, C. ternifolia should be used for short periods of time because it produces undesirable effects in the liver and kidney of Wistar rats at 8.5 mg/kg. In traditional medicine, this plant is usually used for long periods of time, such as in the control of hyperglycemia, which makes this finding particularly relevant.

7.2 CYP3A4 Enzyme Inhibition (Drug Interactions)

In vitro, the extract inhibited CYP3A by 99% at a concentration of 375 μg/mL. CYP3A4 (cytochrome P450 3A4) is responsible for the metabolism of a large proportion of clinically used drugs, including many immunosuppressants, anticoagulants, antiretrovirals, and cardiovascular medications. Near-complete inhibition of this enzyme at the tested concentration represents a theoretically significant drug–herb interaction risk, though human pharmacokinetic data confirming this interaction in vivo are not currently available.

Toxicological effects reported for C. ternifolia include cytotoxicity, mitochondrial toxicity, inhibition of CYP3A, and eryptosis in vitro.

7.3 Adverse Effects Reported

The safety of Calea zacatechichi has not been fully evaluated in clinical trials; however, there have been reports of hallucinations as well as additional adverse effects of nausea and vomiting. Known side effects include nausea and vomiting related to the taste and mild-to-severe allergic reaction. In animal models, large doses elicited salivation, ataxia, retching, and occasional vomiting.

7.4 Asteraceae Allergy Cross-Reactivity

Calea zacatechichi may cause an allergic reaction in people who are sensitive to the Asteraceae/Compositae family of plants; members of this family include ragweed, chrysanthemums, marigolds, daisies, and many other herbs. This cross-reactivity risk is well-established for sesquiterpene lactone-containing Asteraceae generally. Many compounds or plants containing sesquiterpene lactones are a cause of allergic contact dermatitis in humans.

7.5 Precautions for Specific Populations and Conditions

• There is insufficient information about the use of Calea zacatechichi during pregnancy and breast-feeding.
• Calea zacatechichi may affect the rate of breathing; individuals with breathing disorders such as asthma and COPD should use it cautiously or avoid it.
• The plant may lower blood sugar levels; people with diabetes should use it with caution and watch for signs of hypoglycemia.
• The plant may decrease blood pressure; people with heart conditions or using blood pressure medications should exercise caution.
• Individuals with psychiatric disorders should avoid Calea zacatechichi, as it may cause vivid dreams, disorienting effects, and hallucinations.

7.6 Regulatory Status

C. ternifolia was placed on the prohibited plant list in Poland in 2013. Poland remains the only country in Europe restricting its use, while in the US it is classified as illegal only in Louisiana state. While it is not a controlled substance under federal law in the United States, some states have considered it individually; Louisiana State Act 159 specifies that it is illegal to possess if it is intended for human consumption, but not if intended for ornamental or landscaping use.

8. Summary of Evidence Quality

The overall body of scientific evidence for bitter grass is predominantly preclinical. Properties including spasmolytic, antidiabetic, antidepressant, anti-inflammatory, and antinociceptive effects have been demonstrated in laboratory studies, but human clinical trial data are sparse. The most robust human-level evidence relates to the oneirogenic and sleep-architecture effects from a small double-blind study published in 1986, which requires replication in larger, more rigorously designed trials. The antidiabetic evidence base in animal models is substantial but has not yet been validated in adequately powered human trials. Safety signals from preclinical studies — particularly regarding nephrotoxicity, hepatotoxicity, and CYP3A4 inhibition — are sufficiently serious to warrant caution and further investigation. Many plant-derived compounds show therapeutic potential; however, the assumption that natural products are safe is incorrect.

References

• Wikipedia: Calea ternifolia
• RxList: Calea Zacatechichi — Health Benefits, Side Effects, Uses, Dose & Precautions
• Mayagoitia L et al. (1986). Psychopharmacologic analysis of an alleged oneirogenic plant: Calea zacatechichi. PubMed PMID 3821139
• González-Yáñez et al. (2019). Safety of Aqueous Extract of Calea ternifolia Used in Mexican Traditional Medicine. Evidence-Based Complementary and Alternative Medicine. PMC6944969
• Mossoba ME et al. (2016). Evaluation of "Dream Herb," Calea zacatechichi, for Nephrotoxicity Using Human Kidney Proximal Tubule Cells. PMC5040790
• Contreras-Rosales AJ et al. (2021). Calea ternifolia Kunth, the Mexican "dream herb," a concise review. Canadian Journal of Botany.
• Escandón-Rivera SM et al. (2017). Anti-Hyperglycemic Activity of Major Compounds from Calea ternifolia. Molecules. PMC6155573
• Martínez-Mota L et al. (2021). Calea zacatechichi Schltdl. produces anxiolytic- and antidepressant-like effects, and increases the hippocampal activity during REM sleep in rodents. Journal of Ethnopharmacology. 265:113316.
• GBIF: Calea ternifolia Kunth — Species Page
• González-Yáñez et al. (2019). Safety of Aqueous Extract of Calea ternifolia Used in Mexican Traditional Medicine. Wiley / Evidence-Based Complementary and Alternative Medicine.
• Escandón-Rivera SM et al. (2017). Anti-Hyperglycemic Activity of Major Compounds from Calea ternifolia. Molecules. 22(2):289.
• Healthline: Calea Zacatechichi — What to Know About the "Dream Herb"
• Vencato et al. (2025). Toxic Evaluations of Calea phyllolepis Extracts and In Silico Prediction of Toxicity. Chemistry & Biodiversity. PMC12716012
• Contreras-Rosales AJ et al. (2021). Calea ternifolia Kunth, the Mexican "dream herb," a concise review. ResearchGate PDF.