|Lycaeum > Leda > Documents > Psychopharmacologic Analysis of an Alleged Oneirogenic Plant: Calea zacatechichi|
Study/Analysis done on the activity of C. zacatechichi - excellent resource
Psychopharmacologic Analysis of an Alleged Oneirogenic
LILIAN MAYAGOITIA. Jose-Luis Diaz and Carlos M. CONTRERAS
From the Journal of Ethnopharmacology 18 (1986) 229-243 Eleavier Scientific Publishers Ireland Ltd
Departamenta de Psicobiologia y Cunducto, Instituto Mexicano de Psiquiatria, Antiguo Camino a Xochimilco 101, San Lorenzo Huipulco Tlalpan 14370 and Departamento de Fisiologia. Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, Apartado Postal 70228. Ciudad Universitaria, Coyoacan 04510 (Mexico, D.F.)(Accepted October 8. 1986)
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.
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.
Plant collection and extract preparations
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
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.
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.
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.
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.
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
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.
advice in the preparation of the plant extracts.
This document Copyright Journal of Ethnopharmacology 18