What then is the reason for the discrepancy between the results of these carefully conducted clinical experiments and the alleged narcotic action as evidenced by Indians and explorers? The following general considerations seem to be relevant. The Indians use the snuff powder for prolonged periods. Intermittant snuffing during 8-10 hours may produce other results than in the clinical experiments, where most of the administered snuff seems to be lost due to vehement sneezing. In this connection one may inquire, why the preparations from the seeds are mostly taken as a snuff, although other ways of administration have also been used (see above). Anatomical reasons have been proposed for the action of certain drugs, such as cocaine, through the nasal mucosa. The following veins communicate directly with the cranial cavity, the concomitant veins of arteriae ethmoidales and a vein "which accompanies a ramification of anterior ethmoidal artery. The last one is an important connection between the nose and the cranial cavity. The vein accompanies the artery through the ethmoidale plate and makes connection within the cranial cavity either with the network of veins of Tractus olfactorius or directly with a bigger vein in the orbital lobe. All the vessels mentioned are accompanied by lymph vessels, and it is conceivable that drugs can act directly on the brain without having to be transported through the general circulation. Experimental proofs for this are, however, lacking and it remains largely a conjecture. Another point worth bearing in mind is the following. The prolonged administration of successive doses of paricd or related snuffs will give the body sufficient time to transform the administered alkaloids into active compounds, maybe 6-hydroxytryptamines as discussed above. It is also conceivable, but entirely unproved, that there may exist a racial difference in the rate of which the tryptaminé derivatives are endogeneously metabolized to psychotomimetically active compounds. A mixed intoxication will also have to be considered. The explorers tell us, that alcoholic beverages are sometimes consumed during the snuffing ceremonies. Also, the admixture of other ingredients to the typical parted powder has been described. The revelation of a hitherto unknown kind of snuff by Zerries and Seitz has largely prompted the present review. Neither in the description of its manufacture nor in the investigation performed does it bear any resemblance to the classical paricá. At the time of writing the analysis of the powder obtained by Seitz has brought to light two tryptamine derivatives. The data from paper' chromatography and fluorescence spectrophotometry clearly indicate, that one of these is dimethyltryptamine. The other compound is a tryptamine derivative substituted in 5-position. It is not identical with bufotenine or serotonin. All availble evidence sofar points to, that this other compound is a 5-substituted tryptamine (Holmstedt 1963). The inability to correlate at the present stage the chemical, and pharmacological experiments with the effects experienced by the Indians has induced some people to think, that the phenomenon is entirely emotional. It is well known in connection with compounds like mescaline, LSD and psilocybin, that the personality of the subject as well as circumstances during the administration influence the result. However, to attribute the widespread use of piptadenia and similar snuffs only to emotional or external circumstances seems extremely unlikely. It is the firm belief of the writers, that paricá is pharmacologically active, even though its subtle pharmacodynamics still have to be elucidated. The difficulties to state explicitly the psychic phenomena experienced by the use of drugs, whether habitforming or not, are apparent. To take an example: The active principles and the general pharmacology of both paricá and tobacco are known. Still it is difficult to give reasons for the widespread use of the latter compound except in such vague terms as that people experience "a feeling of pleasure, relaxation or stimulance". Similar but as yet inexplicable reasons may account for the use of paricá and related compounds in large areas of South- and Central America.