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Summary
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 somnolence and induce light sleep
in cats. Large doses elicit salivation, ataxia. retching and occasional
vomiting. The effects of the plant upon cingulum discharge frequency were
significantly different from hallucinogenic- dissociative drugs (ketamine.
quipazine, phencyclidine and SKF-10017). In human healthy volunteers, low doses
of the extracts administered in a double-blind design against placebo increased
reaction time end 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. The subjective reports of dreams
were significantly higher than both placebo and diazepam, indicating an increase
in hypnagogic imagery occurring during superficial sleep stages.
Introduction
Dreams are important in mesoamerican cultures. They are believed to occur in a
realm of suprasensory reality and, therefore, are capable of conveying messages
(Lopez-Auatin. 1980). The use of plant preparations in order to produce or to
enhance dreams of a divinatory nature constitutes 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 obtain
divinatory messages from dreams. Several puffball mushrooms (Lycoperdon spp.),
wrongly reported as hallucinogens (Ott et al., 1975), are eaten fresh by Mixtec
Indians before going to bed in order to dream (Diaz, 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 same 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 the same context by
the Chontal Indians of Oaxaca.
C. zacatechichi is a plant of extensive popular medicinal use in Mexico (Diaz.
1976). An infusion of the plant (roots. leaves and stem) is employed against
gastrointestinal disorders, as an appetizer. cholagogue, cathartic. antidysentry
remedy, and has also been reported to be an effective febrifuge. With other
aromatic Compositae, dry C. zacatechichi is used as insecticide (Diet, 1975).
There is also some information concerning psychotropic properties of this plant
that require further clarification (Schultes and Hofmann, 1973).
The pioneer study on the appetizer properties of zacatechichi, conducted at the
Institute Medico Nacional of Mexico, mentioned some psychoactive effects
(Sandoval, 1882). MacDougall (1968) reported that a Chontal informant knew that
the leaves of the plant were to be either smoked or 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 during 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 plant are smoked, drunk and put under the pillow before going to sleep.
Reportedly, the answer to the question comes in a dream. A collection of
interviews and written reports concerning the psychotropic effects of these;
preparations on 12 volunteers has been published (Diaz. 1975, 1979). Free,
reports and direct questioning disclosed a discrete enhancement of all sensorial
perceptions, an increase in imagery, mild thought discontinuity, rapid flux of
ideas. and difficulties in retrieval. These effects were followed by somnolence
and a short sleep during which lively dreams were reported by the majority of
the volunteers. These preliminary observations suggested that the psychotropic
effects of the plant were similar to those interesting from ethnobotanical.
psychological and neuropharmacological of the "cognodysleptic" drugs, whose
prototype is marihuana (Cannabis saliva)(Diaz, 1979). The possible effects upon
dreaming are the most perspectives.
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 petiole. 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 dry savannas and canyons (Schultes and
Hoffmann, 1973). The name of the species comes from Nahuatl "zacatechichi" which
means "bitter grass' and is the common name of the plant all over Mexico. It is
also known with the Spanish names of "zacate de perro" (dog's grass), "hoja
madre" (mother's leaf) "hoja de dies" (Cod's leaf), and thle-pela-kano in
Chontal Diaz, 1975).
Several sesquiterpene lactones had been isolated from the plant. Calaxin and
ciliarin were identified by Ortega et al. (1970), and the germacranolides,
1B-acetoxy zacatechinolide and l-oxo zacatechinolide, by 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 samples show differences in chemical composition, which has led
Bohlmann et al. (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 psychotropic
properties.
In the present paper we report some properties of zacatechichi extracts upon cat
behavior and EEG, human reaction time, nap EEG, and subjective experiences.
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 Martinet Alfaro at the
National Herbarium of Mexico as C. zacatechichi despite the Fact that there were
minor morphological differences relative to previously collected material. The
samples were identical with collections made in the 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 methanol and the organic fraction evaporated. This
procedure resulted in 86 g of a 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 for the methanol extract. In the
experiments with cats. doses of HD-2. -4. -6 and -10 of both extracts were used.
The EEG; effects of C. zacatechichi extracts were compared with those elicited
by phencyclidine (Bio-ceutic 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 (Conteras et al.. 1979, 1984).
Behavioral toxicology in cats
This first experiment was performed in order to assess the possible toxic
behavioral effects of C. zacatechichi extracts. For this purpose three male cats
(3 kg each) were used. Observations were done from 1300 to 1500 h in a
sound-attenuated recording chamber (109 x 76 x 74 cm) with a triple-glass wall.
Each animal was placed in the cage and its behavior was recorded for 1 h prior
to oral administration of a gelatin capsule (25 x 8 mm) containing a
zacatechichi extract and 2 h thereafter. Each capsule was placed inside the
mouth and swallowing was forced by giving 2-3 ml of saline solution. 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 used to evaluate the cats' response. Attention
was given to abnormal behaviors such as ataxia, bizarre postures and movements
directed to non-existing 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 are the two most
characteristic features. Tracheal administration of neurotoxic industrial
solvents produce limbic discharges while cats display "hallucinatory behavior"
(Contreras et al., 1979). The following experiment was designed to ascertain
whether C. zacatechichi extracts share these neurophysiological actions.
Six adult male cats were stereotaxically implanted with stainless steel
concentric bipolar electrodes in the basolateral amygdala. the septum and
cingulum according to the atlas of Snider and Niemer (1961). Epidural electrodes
were placed on the cortex at the marginal circumvolution. After surgery the
animals were allowed a & 1 week recovery period. Each cat was 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.) and SKF-10047 (3 mg/kg i.m.). These drugs are
dissociative psychodysleptics and produce 6 cps wave-and-spike activity in
cingulum recording in addition to the characteristic hypersynchronic rhythm
(Contreras at al., 1984). In each experiment, control recordings were taken in
addition to t 60 min and + 120 min after drug aministration.
Reaction Time and Time-lapse estimation in humans
Measurement of reaction time to a light flash and the ability to calculate 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 experiments performed in cats it appeared that
zacatechichi had hypnotic properties. Therefore, we chose this experimental
paradigm to evaluate human effects. The study was performed in 5 healthy
volunteers (3 women and 2 men. ages 23-34) according to the procedure described
by Fernandez-Guardiola et al. (1972, 1974). The subjects were informed about the
experiment and 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 had been ingested.
The first session did not involve the administration of any 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
evaluation and 10-min periods for time-lapse estimation. In the reaction-time
periods. the subjects were instructed to press a button with their dominant hand
as soon as possible after a light wee dashed. Intervals between consecutive
Bashes were of 10-s duration. In the following 10 min, alternating with the
reaction-time periods, the subjects were asked to estimate the dash intervals by
pressing the button each time they thought the light should have been dashed.
The entire test lasted 80 min. Analysis of variance was used to assess results
between and within individuals, the protected "t" and Least Significant
Difference tests were used in paired comparisons.
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, all volunteers were asked to reduce their
normal sleep time by 2 h the night before testing. The extract, diazepam or
placebo capsule was ingested 1 H prior to the recording session (1700-1900 h).
The physiological variables recorded included respiratory and heart rates,
number of nap episodes. total time spent in wakefulness (W). in slow wave sleep
stages (SWS stages I to IV) and in rapid-eye-movement sleep (REM) (Rechtschaffen
and Kales, 1968). The respiratory rate was recorded by means of a thermistor
located in the nostril and connected to a polygraph amplifier measuring the air
temperature in each inhalation-exhalation cycle. This is an indirect method
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.
Dream reports
The psychological effects of Calea extracts were evaluated by the application of
directed questionnaires and analysis of free reports of the subjective
sensations and dreams in all human volunteers after the reaction-time, nap
sessions and the following night. Neither the subjects. the interviewer nor the
evaluator knew whether the individual had taken a plant extract, diazepam, or
placebo. The results were compared by the binomial test.
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 somnolence 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 after 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 nervous system stimulation or in
response to local gastric irritation caused by some bitter principle of the
plant. This activity was noted by Giral and Ladabaum (1959) and may be
responsible for the appetizer properties of C. zacatechichi. Stare and pendular
head movements can be elicited by several psychoactive drugs such as toluene (Alcaraz
et al., 1977; Contreras et al., 1977), quipazine (Sales et al.. 1966, 1968) and
dopamine agonists (Ernst. 1967). These effects are. therefore, not specific for
any one of the several 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 were
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 induced 3 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 of discharge in the cingulum was performed for all drugs tested (Fig.
2). The hexane extract produced only minor changes while the methanol extract
clearly decreased the frequency. This response is in contrast to the known
psychodysleptic compounds which produce decreases of 6-7 cps (Contreras:- et
al.. 1984).
The results of these experiments show that zacatechichi does not share the
neurophysiological effects of the dissociative psychodysleptics and only induces
the behavioral and EEG signs of somnolence and sleep. The apparent low toxicity
of the plant in these experiments and its history of ethnobotanical use allowed
us to ascertain the hypnotic potency, dream- 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 flash intervals, and the subjects were
awakened by the light. Both extracts produced a statistically significant
slowness of reaction-time (Fig. 3): 250 ms with placebo, 280 ms with hexane
extract and 290 ms with methanol extract (P < 0.01). Similarly, the IO-s lapse
was overestimated with the zacatechichi extracts (Fig. 4). The methanol extract
increased estimation by 3 s on average (P < 0.001). Both extracts increased
respiratory rate, but this change was not significantly different from controls.
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 the methanol extract
suggesting that the active compounds might be found in 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 zacatechichi 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. it 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) = 3.35.
P<0.05). Post-hoc paired comparisons showed that, upon onset of sleep, the
methanol extract and diazepam increased significantly the frequency of 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 modified by treatments. SWS-I and SWS-II showed
a alight increase in comparison to placebo and, in contrast, SWS-III and REM
stages decreased slightly. 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, particularly the methanol fraction, contain
compounds with activity equivalent to sub- hypnotic diazepam doses. Ingestion of
the plant produces a light hypnotic state with a decrease of both deep slow-wave
sleep and REM periods. The 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.
Dream reports
The quantitative results concerning hypnagogic imagery and dreams are summarized
in Table 1. Data from the reaction-time and the nap sessions end the following
night were pooled. Significantly more dreams (P < 001, 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 significant, the number of dreams reported was greater after the
ingestion of Calea extracts than placebo. A more detailed analysis of dream
content is shown in Table 2. The number of subjects that did not remember
dreaming was always greater after placebo and diazepam administration and.
conversely, the individuals that reported more than one dream per session were
always the ones treated with zacatechichi extracts. The dreams reported by
subjects ingesting Calea extracts, were of a shorter content (measured by 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 were mentioned .
These results show that zacatechichi administration appears to enhance the
number and/or recollection of dreams during sleeping periods. The data are in
agreement with the oneirogenic reputation of the plant among the Chontal Indians
but stand in apparent contradiction to the EEG sleep- study results. It is well
known that dreaming activity is correlated to the REM or paradoxical phase of
sleep (Aserinsky and Kleitman, 1953) and it could be expected that a compound
that increases dream would also increase REM stage frequency or duration, as it
has been shown to occur 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 dreaming 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 sleep (SWS I and II) as lively
hypnagogic images (Roffwarg et al., 1962). Such 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 sleep, a psychophysiological effect that would be the
basis of the ethnobotanical use of the plant as an oneirogenic and oneiromantic
agent.
Acknowledgments
The authors wish to express their gratitude to Dr. Alfredo Ortega for advice in
the preparation of the plant extracts.
This document Copyright Journal of Ethnopharmacology 18. |
