Calea zacatechichi

Calea zacatechichi (Dream Herb): A Comprehensive Reference

1. Identity, Taxonomy, and Nomenclature

Calea ternifolia Kunth (synonym: Calea zacatechichi Schltdl.) is a species of flowering plant in the aster family, Asteraceae. It is native to Mexico and Central America. Its English-language common names include bitter grass, Mexican calea, and dream herb. The synonym Calea zacatechichi Schltdl. remains the name most frequently encountered in pharmacological and ethnobotanical literature, though Calea ternifolia Kunth is recognized as the accepted botanical name under modern nomenclature.

The former species name zacatechichi is a Hispanicized form of the Nahuatl word "zacatl chichic," meaning "bitter grass." The Chontal medicine men, who assert that this plant is capable of "clarifying the senses," call it thle-pela-kano, meaning "leaf of God."

This perennial shrub, native to Mexico and Central America, grows 1 to 1.5 meters tall with opposite, lanceolate leaves bearing serrated margins. The plant belongs to the family Asteraceae, which it shares with genera such as sunflower and daisy. Contrary to the typical flowering of the family, Calea zacatechichi presents trumpet-shaped flowers that are light yellow in color, making it easily distinguishable.

1.1 Common Names and Synonyms

• Accepted botanical name: Calea ternifolia Kunth
• Widely used synonym: Calea zacatechichi Schltdl.
• Chontal name: thle-pela-kano ("leaf of God")
• English common names: dream herb, bitter grass, Mexican calea
• The Zoque Popoluca people call the plant tam huñi ("bitter gum"), and the Mixe people know it as poop taam ujts ("white bitter herb").
• In Mexican markets the plant is also sold under the name "prodigiosa."

1.2 Common Forms and Preparations

Crushed dried leaves are steeped in hot water, and the resulting tea is drunk slowly, after which the user lies down in a quiet place and smokes a cigarette of the dried leaves of the same plant. Exposure through inhalation (smoking) or ingestion (as tea) is primarily used to temporarily intensify lucid dreaming. As a dietary supplement marketed outside of Mexico, the plant is sold as dried loose-leaf herb, encapsulated powder, and standardized extracts (aqueous, methanolic, and dichloromethane) used in laboratory research.

2. Traditional and Historical Use

2.1 Oneiromancy and Divination among the Chontal

Calea zacatechichi is a plant used by the Chontal Indians of Mexico to obtain divinatory messages during dreaming. The more significant botanical and ethnomedical aspects include the discovery of the oneirogenic use (enhancer of dreams) of C. ternifolia by the Chontal Indigenous communities in Oaxaca, Mexico.

Whenever they desire to know the cause of an illness or the location of a distant or lost person, the common ritual is to smoke a cigarette, whilst drinking a tea, both made of Calea zacatechichi, right before going to sleep. Some also report placing the leaf of God under their pillow before sleeping. Reportedly, the answer to the question comes in a dream.

Ritual specialists (curanderos/curanderas) may employ it during illness evaluation, seeking dream imagery that intimates etiologies or therapeutic courses.

2.2 Broader Ethnomedicinal Applications

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.

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, traditionally known as Zacatechichi, thle-pela-kano, or bitter grass, has an extensive popular use in Mexico as an appetizer cholagogue, a cathartic anti-dysentery remedy, and as a sleep inductor.

The plant is commonly used in folk medicine to treat cough, asthma, and gastrointestinal disorders.

2.3 Diffusion Beyond Indigenous Contexts

During the late 20th and early 21st centuries, global interest in oneirogens catalyzed wider circulation of the plant through ethnobotanical literature and commerce, occasionally detaching it from its original ritual frameworks. The leaves and flowers of the plant are now becoming common in online shops. While psychonauts online use the leaves to attempt to induce lucid dreams, in Mexico the plant remains part of traditional medicine for curanderos, treating everything from hangovers to diabetes.

3. Key Chemical Constituents

3.1 Sesquiterpene Lactones

First reports on the chemical profile of C. zacatechichi evidenced that the plant is particularly rich in sesquiterpene lactones, mainly in germacranolides. Sesquiterpene lactones are a large group of over 5,000 compounds particularly abundant in plants of the Asteraceae family. They are characterized by 15-carbon terpenoids consisting of three isoprene units and a lactone ring, with some having an α-methylene-γ-lactone motif with an exo-cyclic double bond conjugated with a carbonyl function.

Germacranolides appear as one of the most frequent types of sesquiterpene lactone found in Calea, with more than 40 isolated compounds from C. pinnatifida, C. ternifolia, C. urticifolia, and C. zacatechichi.

Named germacranolide constituents that have been isolated from C. zacatechichi include: the sesquiterpene lactone zexbrevin and a new analog, several analogs of neurolenin B including calein A, and two analogs of budlein A. Additional sesquiterpene lactones recorded in the literature include: ciliarin, zexbrevin, calein D, 1-β-acetoxyzacatechinolide, calein A, 1-oxo-zacatechinolide, calealactone E, calealactone, and acetoxycaleculatolide.

The major components based on peak volume—calein A, ciliarin, acacetin, and calealactone C—accounted for about 50% of the known compounds and approximately 8% of the total compounds in one mass spectrometric analysis.

3.2 Flavonoids and Phenolic Compounds

Preliminary studies indicate also the occurrence of a series of phenolic constituents, mainly caffeoylquinic acids but also flavonoids, the latter identified as minor constituents. The flavones acacetin and O-methylacacetin have been identified. Chemical compounds isolated from this species include flavones such as acacetin and sesquiterpene lactones such as germacranolides.

LC-MS analysis has revealed the presence of a quinic acid derivative, flavonol derivatives, a flavone derivative, and germacranolides.

3.3 Additional Compound Classes

Other compounds and their biological actions such as calaxin, ciliarin, caleins A and B, caleicins I and II, acacetin, zexbrevin, and neurolenin B were all reported in papers ranging from 1970 to 1980. Bioactive constituents related to the genus's pharmacological properties are mainly sesquiterpene lactones and phenolic derivatives.

4. Mechanisms of Action

4.1 NF-κB Inhibition (Anti-inflammatory)

Bork et al. (1997) found that the ethanolic extract from C. zacatechichi leaves contains biologically active sesquiterpene lactones, which were shown in vitro to inhibit activation of NF-κB, a transcriptional factor and one of the major mediators of inflammatory pathways. A toxicology study has shown that C. zacatechichi can inhibit the transcription factor NF-κB, which is critical to regulating cellular inflammation and other functions.

4.2 Cholinergic and Dopaminergic Pathway Interference

Evidence has been provided that the aerial parts of the plant inhibit both acetylcholinesterase and tyrosinase, potentially linking its psychopharmacological effects to the cholinergic and dopaminergic systems, with an apparent contribution from specific phenolic constituents previously unknown to occur in the species. The detected interference with the cholinergic system, and potentially with the dopaminergic pathway, presumably underlies the empirically claimed dream-inducing effects.

4.3 CNS and Sleep Architecture Effects

At human doses, organic extracts of the plant produce the EEG and behavioral signs of somnolence and induce light sleep in cats. The effects of the plant upon cingulum discharge frequency were significantly different from hallucinogenic-dissociative drugs such as ketamine, quipazine, phencyclidine, and SKF-10047.

The most recent study by Martinez-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.

4.4 α-Methylene-γ-Lactone Reactivity

The α-methylene-γ-lactone group is responsible for most of the biological effects of sesquiterpene lactones via a Michael-type addition. This chemical reactivity underlies proposed anti-inflammatory, antileishmanial, and cytotoxic activities documented for germacranolide compounds from the genus.

4.5 Spasmolytic and Gastrointestinal Effects

C. zacatechichi DCM extract significantly inhibited the contractility of mouse colon in vitro (IC₅₀ = 17 ± 2 μg/ml). Administration of the DCM extract in vivo (200 mg/kg, per os) significantly prolonged the time of whole GI transit.

5. Scientific Evidence by Area of Use

5.1 Oneirogenic Effects (Dream Enhancement and Sleep Architecture)

Human/clinical evidence: The most cited human study is a 1986 double-blind controlled investigation by Mayagoitia, Díaz, and Contreras, published in the Journal of Ethnopharmacology. In 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.

Calea zacatechichi has an extensive popular and ritual use in Mexico. In healthy volunteers, it induces well-being and tranquility senses and facilitates superficial stages of sleep.

Evidence strength: The 1986 Mayagoitia et al. study remains the only formal double-blind human trial specifically examining sleep and dream parameters. It demonstrated modest effects on sleep architecture (increased superficial NREM stages and awakenings), but the study population was small and findings have not been replicated in independent large-scale randomized controlled trials. Overall human evidence is preliminary.

5.2 Anxiolytic and Antidepressant-Like Effects

Animal evidence: A 2021 rodent study by Martínez-Mota et al. in the Journal of Ethnopharmacology evaluated the anxiolytic and antidepressant properties of an aqueous extract. 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. The study aimed to determine anxiolytic and antidepressant-like effects of an aqueous extract in rodents and to analyze their effects on hippocampal activity in the rat sleep-waking cycle.

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. CZ at 100 mg/kg 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 hippocampus (gamma-band: 31–50 Hz) during REM sleep.

Anxiolytic- and antidepressant-like effects of this species, reported for the first time in this study, could improve some aspects of mental health.

Evidence strength: Exclusively preclinical (rodent) evidence. No human clinical trials for anxiety or depression have been published. Evidence is preliminary and cannot be extrapolated directly to human therapeutic use.

5.3 Gastrointestinal (Antidiarrheal, Antinociceptive, Spasmolytic) Effects

Animal evidence: A 2016 PMC-published study by Sałaga et al. evaluated the dichloromethane extract using mouse models mimicking irritable bowel syndrome. Methanolic and DCM (200 mg/kg, per os) extracts were screened for their effect on GI motility in several in vitro tests, and the antidiarrheal and antinociceptive effects were assessed using mouse models.

Some properties associated with the plant's traditional uses have been demonstrated, including spasmolytic, antidiabetic, antidepressant, anti-inflammatory, and antinociceptive effects.

A study found that C. zacatechichi leaves possess antinociceptive and anti-inflammatory activity, which seem to depend on the plant's capacity to prevent the production of PGE2.

Evidence strength: All gastrointestinal evidence is preclinical (in vitro and mouse models). No human clinical trials exist. The findings are consistent with traditional use but require clinical validation.

5.4 Anti-inflammatory Effects

Animal/in vitro evidence: The ethnopharmacology of this plant has reported anti-inflammatory and antihyperglycemic effects, as well as the antileishmanial activity of germacranolides. The aqueous extract of C. zacatechichi was shown to inhibit carrageenan-induced paw edema in preclinical models (Venegas-Flores et al., 2002, Proceedings of the Western Pharmacology Society), consistent with NF-κB inhibition by sesquiterpene lactones.

Evidence strength: Preclinical only. Anti-inflammatory effects are plausible given the established NF-κB inhibitory activity of sesquiterpene lactones present in the plant, but no human trials have been conducted.

5.5 Antidiabetic / Hypoglycemic Effects

Dream herb, Calea zacatechichi, has long been used in traditional folk medicine for a variety of purposes and is currently being marketed in the US for medicinal purposes, including diabetes treatment. Preclinical studies in animal models demonstrated hypoglycemic activity (Roman-Ramos et al., 1992, Archives of Medical Research).

Consumption of C. zacatechichi or its constituents may potentially result in adverse health effects, particularly when used over an extended period to manage hyperglycemia.

Evidence strength: Animal/traditional evidence only. No controlled human clinical trials for antidiabetic effects have been published. The safety concerns identified in nephrotoxicity and hepatotoxicity studies (see Section 7) make the long-term use for glycemic control particularly concerning.

5.6 Antileishmanial Activity

Wu et al. (2011) reported the presence of six germacranolides that were shown to have antileishmanial activity. Studies on germacrolides, which are common components of most herbs in the Calea genus, including C. zacatechichi, have demonstrated the potential for antileishmania effects.

Evidence strength: In vitro and preliminary only. No human clinical data.

5.7 Neuroglial Toxicity (Adverse Effect Area)

Evidence has been provided that the aerial parts of the plant inhibit both acetylcholinesterase and tyrosinase, and collectively these results lay the groundwork for a regulatory framework on the consumption of C. zacatechichi in recreational settings. A 2024 study in Journal of Ethnopharmacology (Garcia et al.) specifically documented neuroglial toxicity in cell-based models, contributing new evidence on the plant's CNS safety profile.

6. Body Systems and Health Areas of Association

• Central Nervous System: Oneirogenic (dream-enhancing), sedative, anxiolytic-like, antidepressant-like, EEG effects on sleep architecture, hippocampal activity modulation during REM sleep, acetylcholinesterase inhibition.
• Gastrointestinal System: Antidiarrheal, spasmolytic, antinociceptive (GI), traditional use for dysentery, stomachache, bile disorders, and anorexia.
• Immune/Inflammatory System: Anti-inflammatory (NF-κB inhibition, PGE2 suppression), traditional use for fever.
• Endocrine/Metabolic: Hypoglycemic/antidiabetic (traditional and preclinical), marketed commercially for diabetes.
• Respiratory: Traditional use for cough and asthma (Zoque Popoluca, Mixe peoples).
• Renal System: Potential nephrotoxicity signal from in vitro and in vivo studies.
• Hepatic System: Potential hepatotoxicity signal from in vivo rat studies.
• Antiparasitic: Antileishmanial activity of isolated germacranolides.

7. Dosages Reported in Studies

The following dosages are reported as stated in the cited studies and refer to experimental or traditional contexts, not recommendations:

• The human dose for divinatory purposes reported by the Chontal people is a handful of the dried plant, but effects can be felt with as little as two to three grams of dried leaf matter.
• 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; the doses ranged from 0.5 to 50 mg·kg⁻¹.
• CZ at 100 mg/kg produced visible mild sedative effects in rats, associated with a significant increase in Slow Wave Sleep episodes during a 6-hour recording.
• Methanolic and DCM extracts at 200 mg/kg per os were screened for their effect on GI motility in mouse models.
• At raised doses of extract of 1,000, 2,600, and 5,000 mg·kg⁻¹, animals exhibited symptoms such as loose stools, pain, and diarrhea soon after taking a dose.
• In the González-Yáñez et al. (2019) safety study, the in vitro extract induced eryptosis of 73% at a concentration of 100 μg·mL⁻¹ and inhibited CYP3A by 99% at a concentration of 375 μg/mL.
• After administering 8.5 mg/kg of C. ternifolia to rats, investigators found a reduction in platelets and leukocytes and an increase in urea and the liver enzymes ALT, AST, and alkaline phosphatase.
• The extract of C. ternifolia at concentrations of 111 and 333 μg·mL⁻¹ caused elevated concentrations of nephrotoxicity-associated biomarkers, detected using human kidney toxicity kits (Mossoba et al., 2016).

8. Safety Considerations and Interactions

8.1 Nephrotoxicity

Researchers at the US FDA Center for Food Safety and Applied Nutrition exposed human proximal tubule HK-2 cells to increasing doses of this herb alongside known toxicant and protectant control compounds to examine potential toxicity effects. They evaluated both cellular and mitochondrial functional changes and found that even at low doses evidence of cellular toxicity was significant. Moreover, these findings correlated with significantly elevated levels of nephrotoxicity biomarkers, lending further support for the need to further scrutinize the safety of this herbal dietary supplement.

Dream herb, Calea zacatechichi, is currently being marketed in the US for medicinal purposes, including diabetes treatment. Despite the inherent vulnerability of the renal system to xenobiotic toxicity, there is a lack of safety studies on the nephrotoxic potential of this herb. Additionally, the high frequency of diabetes-associated kidney disease makes safety screening of C. zacatechichi especially important.

8.2 Hepatotoxicity and Hematological Effects

After administering 8.5 mg/kg of C. ternifolia to rats, investigators found a reduction in platelets and leukocytes and an increase in urea and the liver enzymes ALT, AST, and alkaline phosphatase. Histological analysis showed spongiform changes in the proximal tubules of renal tissue and a lymphoid infiltrate in liver tissue. These results show renal and hepatic toxicity; therefore, more profound research on the toxicity of this plant is needed.

8.3 CYP3A Inhibition and Drug Interaction Risk

In vitro, the extract of Calea ternifolia (C. zacatechichi) induced eryptosis and inhibited CYP3A. The group of enzymes that metabolize xenobiotics are called P450 cytochromes (CYPs), in particular the enzyme CYP3A4. Inhibition of the activity of CYPs causes toxic effects in the body and induction increases its expression, affecting the metabolism, elimination, and efficacy of drugs. The near-complete inhibition of CYP3A at 375 μg/mL in vitro signals a potential for pharmacokinetic drug–drug interactions, particularly with co-administered medications metabolized by CYP3A4/5, though the relevance of this concentration to in vivo human exposure has not been established.

8.4 Eryptosis

In vitro, the extract induced eryptosis (programmed red blood cell death) at 73% at a concentration of 100 μg·mL⁻¹. The clinical significance of this finding at achievable in vivo concentrations remains to be determined.

8.5 Acute Gastrointestinal Adverse Effects

Large doses elicit salivation, ataxia, retching, and occasional vomiting. Known side effects include nausea and vomiting related to the taste and mild-to-severe allergic reaction.

8.6 Neuroglial Toxicity

A 2024 study by Garcia et al. published in the Journal of Ethnopharmacology documented that the aerial parts of the plant inhibit both acetylcholinesterase and tyrosinase, potentially linking its psychopharmacological effects to the cholinergic and dopaminergic systems. The same study provided evidence of neuroglial toxicity in in vitro models, raising questions about CNS safety at higher or prolonged exposures.

8.7 Legal Status

The scarcity of data on the chemical, pharmacological, and toxicological profile of the plant contributes to legal inconsistencies regarding its possession and use. Poland remains the only country in Europe restricting its use, while in the US it is classified as illegal only in Louisiana state.

8.8 State of Overall Evidence and Limitations

In the light of the currently available scientific literature it is difficult to estimate whether therapeutic effects of C. zacatechichi extracts would be affected by CNS-related effects and, if any, which types of extracts are particularly abundant in active compounds. Further chemical analyses of C. zacatechichi are thus urgently needed in order to find all active constituents and identify which of them are responsible for the effects observed in vivo.

The genus Calea contains several potential pharmacophores for drug discovery programmes, notably chromenes as anti-inflammatory and anticancer agents but also for their diverse sesquiterpene lactone constituents. However, prior to the application or recommendation of these species to prevent or treat disease states, additional pharmacological and toxicological studies are essential.

References

• Mayagoitia L, Díaz JL, Contreras CM. Psychopharmacologic analysis of an alleged oneirogenic plant: Calea zacatechichi. Journal of Ethnopharmacology. 1986;18(3):229–243. PubMed PMID: 3821139
• Sałaga M et al. Neuropharmacological characterization of the oneirogenic Mexican plant Calea zacatechichi aqueous extract in mice. Naunyn-Schmiedeberg's Archives of Pharmacology. 2016. PMC4863909
• Sałaga M et al. Calea zacatechichi dichloromethane extract exhibits antidiarrheal and antinociceptive effects in mouse models mimicking irritable bowel syndrome. Naunyn-Schmiedeberg's Archives of Pharmacology. 2015. PMC4561081
• Mossoba ME, Flynn TJ, Vohra S, Wiesenfeld P, Sprando RL. Evaluation of "Dream Herb," Calea zacatechichi, for Nephrotoxicity Using Human Kidney Proximal Tubule Cells. Journal of Toxicology. 2016;2016:9794570. PMC5040790
• González-Yáñez MA et al. Safety of Aqueous Extract of Calea ternifolia Used in Mexican Traditional Medicine. Evidence-Based Complementary and Alternative Medicine. 2019. PMC6944969
• Martínez-Mota L et al. Calea zacatechichi Schltdl. (Compositae) produces anxiolytic- and antidepressant-like effects, and increases the hippocampal activity during REM sleep in rodents. Journal of Ethnopharmacology. 2021;265:113316.
• Garcia MR et al. Mexican calea (Calea zacatechichi Schltdl.) interferes with cholinergic and dopaminergic pathways and causes neuroglial toxicity. Journal of Ethnopharmacology. 2024.
• Mata R et al. Calea ternifolia Kunth, the Mexican "dream herb," a concise review. Botany. 2021;99(12).
• Cota-Juárez et al. The genus Calea L.: A review of isolated compounds and biological activities. Journal of Medicinal Plants Research. 2017.
• Wikipedia. Calea ternifolia.
• GBIF. Calea ternifolia Kunth species page.
• Vencato et al. Toxic Evaluations of Calea phyllolepis Extracts. Chemistry & Biodiversity. 2025. PMC12716012