Psychopharmacology of Calea zacatechichi A Dream Plant
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Journal of Ethnopharmacology 18 (1986) 229-243 Elsevier Scientific
Publishers Ireland Ltd
PSYCHOPHARMACOLOGIC ANALYSIS OF AN ALLEGED
ONEIROGENIC PLANT: CALEA ZACATECHICHI
LILIAN MAYAGOITIA. Jose-Luis Diaz and Carlos M. CONTRERAS
Departamenta de Psicobiologia y Cunducto, Instituto Mexicano de
Camino a Xochimilco 101, San Lorenzo Huipulco Tlalpan 14370 and
Fisiologia. Instituto de Investigaciones Biomedicas, Universidad
Mexico, Apartado Postal 70228. Ciudad Universitaria, Coyoacan 04510
(Accepted October 8. 1986)
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Calea zacatechichi is a plant used by the Chontal Indians of Mexico to
obtain divinatory messages during dreaming. At human doses, organic
extracts of the plant produce the EEG and behavioral signs of
and induce light sleep in cats. Large doses elicit salivation, ataxia.
retching and occasional vomiting. The effects of the plant upon
discharge frequency were significantly different from hallucinogenic-
dissociative drugs (ketamine. quipazine, phencyclidine and SKF-10017).
human healthy volunteers, low doses of the extracts administered in a
double-blind design against placebo increased reaction time end
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. The subjective reports of dreams
were significantly higher than both placebo and diazepam, indicating
increase in hypnagogic imagery occurring during superficial sleep
Dreams are important in mesoamerican cultures. They are believed to
occur in a realm of suprasensory reality and, therefore, are capable
conveying messages (Lopez-Auatin. 1980). The use of plant preparations
order to produce or to enhance dreams of a divinatory nature
an ethnopharmacological category that can be called "oneiromancy" and
which justifies rigorous neuropharmacological research.
There are several plants used in Indian communities of Mexico to
divinatory messages from dreams. Several puffball mushrooms
(Lycoperdon spp.), wrongly reported as hallucinogens (Ott et al.,
eaten fresh by Mixtec Indians before going to bed in order to dream
1975. 1979). Nahuatl Indians from the Sierra de Puebla use an as yet
unidentified species of Salvia, known by the name of Xiwit, for the
purpose (Tim Knab, pers. commun.). The plant known as Bakana to the
Tarahumara Indians, which has been reported to be an analgesic,
antipsychotic and divinatory agent(Bye. 1979), was later found to be
employed for dreaming during night sleep (William Merrill, pers.
commun.). Finally, Calea zacatechichi Schl. (Compositae) is used in
same context by the Chontal Indians of Oaxaca.
C. zacatechichi is a plant of extensive popular medicinal use in
(Diaz. 1976). An infusion of the plant (roots. leaves and stem) is
against gastrointestinal disorders, as an appetizer. cholagogue,
antidysentry remedy, and has also been reported to be an effective
febrifuge. With other aromatic Compositae, dry C. zacatechichi is used
insecticide (Diet, 1975). There is also some information concerning
psychotropic properties of this plant that require further
(Schultes and Hofmann, 1973).
The pioneer study on the appetizer properties of zacatechichi,
at the Institute Medico Nacional of Mexico, mentioned some
effects (Sandoval, 1882). MacDougall (1968) reported that a Chontal
informant knew that the leaves of the plant were to be either smoked
drunk as an infusion to obtain divinatory messages. Subsequent
interviews with MacDougall's informant and active participation in
ceremonial ingestion revealed that the plant is used for divination
dreaming (Diaz, 1975). Whenever it is desired to know the cause of an
illness or the location of a distant or lost person, dry leaves of the
are smoked, drunk and put under the pillow before going to sleep.
Reportedly, the answer to the question comes in a dream. A collection
interviews and written reports concerning the psychotropic effects of
preparations on 12 volunteers has been published (Diaz. 1975, 1979).
reports and direct questioning disclosed a discrete enhancement of all
sensorial perceptions, an increase in imagery, mild thought
rapid flux of ideas. and difficulties in retrieval. These effects were
by somnolence and a short sleep during which lively dreams were
by the majority of the volunteers. These preliminary observations
suggested that the psychotropic effects of the plant were similar to
interesting from ethnobotanical. psychological and
of the "cognodysleptic" drugs, whose prototype is marihuana (Cannabis
saliva)(Diaz, 1979). The possible effects upon dreaming are the most
C. zacatechichi is a shrub measuring 1-1.5 m in height. The plant has
many branches with oviform and opposite leaves (3-5 cm long and 2-4 cm
wide). The leaves show serrated borders, acute endings and a short
They are rugose and pubescent. The inflorescence is small and dense
(comprising around 12 flowers each) with the pedicels shorter than the
heads (Martinet, 1939). The plant grows from Mexico to Costs Rice in
savannas and canyons (Schultes and Hoffmann, 1973). The name of the
species comes from Nahuatl "zacatechichi" which means "bitter grass'
is the common name of the plant all over Mexico. It is also known with
Spanish names of "zacate de perro" (dog's grass), "hoja madre"
leaf) "hoja de dies" (Cod's leaf), and thle-pela-kano in Chontal Diaz,
Several sesquiterpene lactones had been isolated from the plant.
and ciliarin were identified by Ortega et al. (1970), and the
germacranolides, 1B-acetoxy zacatechinolide and l-oxo zacatechinolide,
Bohlmann and Zdero (1977). Quijano at al. (1977. 1978) identified
caleocromenes A and B and caleins A and B. while Ramos (1979) found
caleicins I and II. Herz and Kumar (1980) isolated acacetin, o-methyl
acacetin, zexbrevin and an analogue, as well as several analogues of
budlein A and neurolenin B, including calein A. C. zacatechichi
show differences in chemical composition, which has led Bohlmann et
(1981) to suggest that chemical taxonomy may help to reclassify the
genus. Further taxonomic work is required since our Chontal informant
distinguishes between "good" and "bad" varieties according to their
In the present paper we report some properties of zacatechichi
upon cat behavior and EEG, human reaction time, nap EEG, and
Materials and methods
Plant collection and extract preparations
"Good" samples of C. zacatechichi were collected under the guidance of
the Chontal informant near Tehuantepec, Oaxaca during November, 1978.
Specimens of this collection were identified by Dr. Miguel Angel
Alfaro at the National Herbarium of Mexico as C. zacatechichi despite
Fact that there were minor morphological differences relative to
collected material. The samples were identical with collections made
area of the isthmus of Tehuantepec.
One kilogram of the dried plant (stem and leaves) was mashed and
extracted with hexane until exhaustion in a Soxhlet apparatus. This
fraction was dried and 308 of an solvent-free hexane extract were
obtained. The remaining material was thoroughly extracted with
and the organic fraction evaporated. This procedure resulted in 86 g
solvent-free gummy residue called the methanol extract. Both extracts
were separated in fractions and packed in gelatin capsules for
pharmacological experiments. The dose was estimated in the following
manner: the human dose for divinatory purposes reported by the Chontal
informant is "a handful" of the dried plant. Since the mean weight of
many handfuls taken by several people was 60 g. we decided that the
average human dose (HD-1) is around 1 g/kg of dried-mashed material.
Therefore, the HD-1 for the hexane extract was 30 mg/kg, and 86 mg/kg
the methanol extract. In the experiments with cats. doses of HD-2. -4.
and -10 of both extracts were used. The EEG; effects of C.
extracts were compared with those elicited by phencyclidine
Laboratories), quipazine (Miles Research Products). ketamine (Parke
Davis) and SKF-10047 (Smith Kline B French), and industrial solvent
toluene. which can produce the appearance of 6 cps spike and wave
activity in the cingulum of cats. During the appearance of this
electrographic activity. animals show "hallucinatory" behavior
et al.. 1979, 1984).
Behavioral toxicology in cats
This first experiment was performed in order to assess the possible
behavioral effects of C. zacatechichi extracts. For this purpose three
cats (3 kg each) were used. Observations were done from 1300 to 1500 h
a sound-attenuated recording chamber (109 x 76 x 74 cm) with a
wall. Each animal was placed in the cage and its behavior was recorded
1 h prior to oral administration of a gelatin capsule (25 x 8 mm)
a zacatechichi extract and 2 h thereafter. Each capsule was placed
the mouth and swallowing was forced by giving 2-3 ml of saline
The extracts (methanol or hexane) and doses (HD-1, HD-2. HD-4. HD-10)
were randomly assigned and tested only once. Two cats were observed
three times and the third animal twice. Between tests each animal was
allowed to rest for 6 days. Sampling ad libitum (Altmann. 1974) was
to evaluate the cats' response. Attention was given to abnormal
such as ataxia, bizarre postures and movements directed to
objects (Fischer. 1969).
EEG activity in cats
Several common EEG effects to a series of hallucinogenic compounds
have been reported by Winters et al. (1972). A dissociative action in
multi-unitary activity between the reticular formation and basolateral
amygdala and a hypersynchronic rhythm (2-3 cpa) in cortical recording
the two most characteristic features. Tracheal administration of
neurotoxic industrial solvents produce limbic discharges while cats
"hallucinatory behavior" (Contreras et al., 1979). The following
was designed to ascertain whether C. zacatechichi extracts share these
Six adult male cats were stereotaxically implanted with stainless
concentric bipolar electrodes in the basolateral amygdala. the septum
cingulum according to the atlas of Snider and Niemer (1961). Epidural
electrodes were placed on the cortex at the marginal circumvolution.
surgery the animals were allowed a & 1 week recovery period. Each cat
used as its own control and the effects of oral administration of
zacatechichi extracts (HD-6) were compared to those of phencyclidine
(400 ug/kg i.m.), quipazine (10 mg/kg i.p.), ketamine (6 mg/kg i.m.)
SKF-10047 (3 mg/kg i.m.). These drugs are dissociative
and produce 6 cps wave-and-spike activity in cingulum recording in
addition to the characteristic hypersynchronic rhythm (Contreras at
1984). In each experiment, control recordings were taken in addition
t 60 min and + 120 min after drug administration.
Reaction Time and Time-lapse estimation in humans
Measurement of reaction time to a light flash and the ability to
fixed lapse times in humans allows the identification of hypnotic
compounds (Fernandez-Guardiola et al., 1972). Objective evaluations of
time perception modification by marihuana have been achieved with the
same technique (Fernandez-Cuardiola et al., 1974). From the
performed in cats it appeared that zacatechichi had hypnotic
Therefore, we chose this experimental paradigm to evaluate human
The study was performed in 5 healthy volunteers (3 women and 2 men.
ages 23-34) according to the procedure described by
et al. (1972, 1974). The subjects were informed about the experiment
the known effects of the plant and a written consent was obtained.
Capsules containing either a Calea extract (HD-1) or placebo were
administered 1 H before the task in a double-blind randomized design,
where neither the volunteers nor the evaluator knew which substance
been ingested. The first session did not involve the administration of
substance in order to habituate the subjects to the experimental
manipulations. Physiological responses recorded included EEG,
electromyogram, electrocardiogram, and galvanic akin response. All
sessions were done at the same time period (1700-1820 h). A complete
session consisted of alternated 10-min periods for reaction-time
and 10-min periods for time-lapse estimation. In the reaction-time
the subjects were instructed to press a button with their dominant
soon as possible after a light wee dashed. Intervals between
Bashes were of 10-s duration. In the following 10 min, alternating
reaction-time periods, the subjects were asked to estimate the dash
intervals by pressing the button each time they thought the light
have been dashed. The entire test lasted 80 min. Analysis of variance
used to assess results between and within individuals, the protected
and Least Significant Difference tests were used in paired
Sleep recordings in humans
The conventional procedure for EEG recording of sleep (Rechtschaffen
and hales. 1968) was used in a similar double-blind randomized design
which. in this case, included a low dose of an active hypnotic drug
(diazepam, 2·5 mg orally). In order to standardize the nap session,
volunteers were asked to reduce their normal sleep time by 2 h the
before testing. The extract, diazepam or placebo capsule was ingested
prior to the recording session (1700-1900 h). The physiological
recorded included respiratory and heart rates, number of nap episodes.
total time spent in wakefulness (W). in slow wave sleep stages (SWS
I to IV) and in rapid-eye-movement sleep (REM) (Rechtschaffen and
1968). The respiratory rate was recorded by means of a thermistor
in the nostril and connected to a polygraph amplifier measuring the
temperature in each inhalation-exhalation cycle. This is an indirect
which provides the frequency and amplitude of respiratory rate. Data
analyses were done by means of factorial analysis of variance (ANOVA).
For paired comparisons, the Student Newman-Keuls test was used.
The psychological effects of Calea extracts were evaluated by the
application of directed questionnaires and analysis of free reports of
subjective sensations and dreams in all human volunteers after the
reaction-time, nap sessions and the following night. Neither the
the interviewer nor the evaluator knew whether the individual had
plant extract, diazepam, or placebo. The results were compared by the
Results and discussion
Behavioral toxicology in cats
Some minor behavioral changes were observed with low doses of both
extracts (HD-1 and HD-2). The cats stared for long periods of time and
30 min after the administration of the zacatechichi extracts
and sleep were frequently observed. The HD-4 and HD-1O doses of the
hexane extract produced ataxia, bilateral contractions of nasal and
maxillar muscles, and stereotyped pendulum head movements. The HD-10
dose also induced salivation with vomiting occurring about 90 min
administration. The methanol extract produced ataxia (HD-4) and
compulsive grooming (HD-2). A common toxic effect of both extracts
(doses HD4 and HD-10) was retching and thick salivation.
It was not clear if these effects were elicited by direct central
system stimulation or in response to local gastric irritation caused
some bitter principle of the plant. This activity was noted by Giral
Ladabaum (1959) and may be responsible for the appetizer properties of
zacatechichi. Stare and pendular head movements can be elicited by
psychoactive drugs such as toluene (Alcaraz et al., 1977; Contreras et
1977), quipazine (Sales et al.. 1966, 1968) and dopamine agonists
1967). These effects are. therefore, not specific for any one of the
classes of psychoactive compounds. Moreover, staring and pendular head
movements may merely be indications of somnolence. In order to analyze
more precisely the neural effects, electrophysiological recordings
taken in free-moving cats.
EEG activity in cats
Both plant extracts produced similar EEG changes which were very
different from the other drugs used(Fig. 1). The hexane extract
cps large voltage rhythms in the cortex, cingulum and septum while the
methanol extract provoked 8 slowing of the EEG rhythm more
predominant in subcortical structures. Somnolence was observed during
the appearance of these changes. A quantitative analysis of frequency
discharge in the cingulum was performed for all drugs tested (Fig. 2).
hexane extract produced only minor changes while the methanol extract
clearly decreased the frequency. This response is in contrast to the
psychodysleptic compounds which produce decreases of 6-7 cps
et al.. 1984).
The results of these experiments show that zacatechichi does not share
the neurophysiological effects of the dissociative psychodysleptics
only induces the behavioral and EEG signs of somnolence and sleep. The
apparent low toxicity of the plant in these experiments and its
ethnobotanical use allowed us to ascertain the hypnotic potency,
inducing effects and other psychotropic properties in human beings.
Reaction time and time-lapse estimation in humans
No differences among the three treatments were found for human
rate, galvanic skin response and EEG recordings. With the methanol
extract, short periods of sleep (stage I) usually appeared between
intervals, and the subjects were awakened by the light. Both extracts
produced a statistically significant slowness of reaction-time (Fig.
250 ms with placebo, 280 ms with hexane extract and 290 ms with
methanol extract (P < 0.01). Similarly, the IO-s lapse was
with the zacatechichi extracts (Fig. 4). The methanol extract
estimation by 3 s on average (P < 0.001). Both extracts increased
respiratory rate, but this change was not significantly different from
The characteristic EEG slowness and the increased reaction times of
subjects treated with both extracts suggested that zacatechichi may
contain hypnotic compounds. Moreover, a larger effect was elicited by
methanol extract suggesting that the active compounds might be found
the polar fractions. An increase in time-lapse estimation and a weak
respiratory analeptic effects have been reported after marihuana
administration (Fernandez-Guardiola et al., 1974).
Sleep recordings in humans
Since the experiment just discussed did not allow an analysis of sleep
stages, the possibility of sleep and dream modifications by
was tested in a nap study conducted in the same human volunteers.
Heart rate, total time and frequency of each stage of sleep did not
change with any treatment in comparison to placebo (Fig. 5). However.
was found that the frequency of W and SWS-IV stages were significantly
modified by treatments (W F(3,32)= 5.28, P < 0.01; SWS-IV F(3,32) =
P<0.05). Post-hoc paired comparisons showed that, upon onset of sleep,
the methanol extract and diazepam increased significantly the
W stages (P < 0.05) when compared to placebo. In contrast, methanol
extract and diazepam decreased significantly (P < 0.05) the number of
SWS-IV stages. The other stages of sleep were not significantly
by treatments. SWS-I and SWS-II showed a alight increase in comparison
to placebo and, in contrast, SWS-III and REM stages decreased
Respiratory rate was significantly modified by treatments (F(3,400)=
79.92, P < 0.005). Paired comparisons showed that the methanol extract
increased (P < 0.05) when compared to all other treatments (Fig. 6).
Although this small increase may lack physiological relevance, it does
suggest a pharmacological effect upon respiratory rate.
These results support the idea that zacatechichi extracts,
the methanol fraction, contain compounds with activity equivalent to
hypnotic diazepam doses. Ingestion of the plant produces a light
state with a decrease of both deep slow-wave sleep and REM periods.
question of the ethnobotanical use and open trial reports of dream
enhancement was studied in the following section by the evaluation of
subjective reports during the sleep study.
The quantitative results concerning hypnagogic imagery and dreams are
summarized in Table 1. Data from the reaction-time and the nap
end the following night were pooled. Significantly more dreams (P <
in comparison to placebo) were reported after the methanol extract.
Similarly, the number of dreams reported during naps was significantly
higher following the administration of the plant extracts than with
diazepam (P < 0.01). It can be appreciated that, although not
the number of dreams reported was greater after the ingestion of Calea
extracts than placebo. A more detailed analysis of dream content is
in Table 2. The number of subjects that did not remember dreaming was
always greater after placebo and diazepam administration and.
the individuals that reported more than one dream per session were
the ones treated with zacatechichi extracts. The dreams reported by
subjects ingesting Calea extracts, were of a shorter content (measured
the number of lines written in the report). Spontaneous reports of
emotions and nightmares were not different among the four treatments.
Nevertheless, with the methanol extract more colors during dreaming
These results show that zacatechichi administration appears to enhance
the number and/or recollection of dreams during sleeping periods. The
are in agreement with the oneirogenic reputation of the plant among
Chontal Indians but stand in apparent contradiction to the EEG sleep-
study results. It is well known that dreaming activity is correlated
REM or paradoxical phase of sleep (Aserinsky and Kleitman, 1953) and
could be expected that a compound that increases dream would also
increase REM stage frequency or duration, as it has been shown to
with physostigmine (Sitaram et al., 1978). In contrast, zacatechichi
increases the stages of slow wave sleep and apparently decreases REM
sleep. This also occurs with low doses 12-10 mg) of diazepam (Harvey,
1982). Despite this similarity in EEG effects, diazepam decreases
reports (Firth, 1974) while zacatechichi extracts enhances them. Such
discrepancy may be explained by the fact that dreaming and imagery are
not restricted to the REM episodes but also occur during slow wave
(SWS I and II) as lively hypnagogic images (Roffwarg et al., 1962).
images are reported as brief dreams and are known to be enhanced by
marihuana (Hollister, 1971). All this suggests that Calea zacatechichi
induces episodes of lively hypnagogic imagery during SWS stage I of
a psychophysiological effect that would be the basis of the
use of the plant as an oneirogenic and oneiromantic agent.
The authors wish to express their gratitude to Dr. Alfredo Ortega for
advice in the preparation of the plant extracts.
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