1. The psychotropic effects of ayahuasca vs. placebo were demonstrated by means of structured self-assessment instruments both in naive and in experienced ayahuasca users. The tea induces dose-dependent changes in the perceptual, affective, cognitive and somatic spheres, with a combination of stimulatory and psychedelic effects. The overall experience is of longer duration and milder intensity than that previously reported for intravenously administered DMT. 2. The central effects of ayahuasca were objectively measured by means of q-EEG, showing a time pattern which closely paralleled that of subjective effects. Results in the individual q-EEG variables are in line with those previously described for other serotonergic psychedelics and share some features with the profile of effects shown by pro-serotonergic and pro-dopaminergic drugs. 3. The use of the LORETA source location technique identified the EEG power decreases over somatosensory, auditory and visual association cortices, over temporo-parietal heteromodal association cortex and in paralimbic structures with relevant roles in emotion and memory processes. These areas may be involved in the psychological effects elicited by ayahuasca. 4. Diverging effects are observed on each of the two gating measures evaluated. While a decremental effect of ayahuasca on sensory gating was found, no distinct effects were observed on sensorimotor gating. 5. Following the oral administration of ayahuasca, measurable plasma levels were observed for DMT, harmaline and THH. Based on the calculated bioavailability, only a small percentage of the total DMT in ayahuasca appears to reach systemic circulation. The time course of DMT plasma concentrations parallels the evolution of subjective effects, with peak plasma concentrations and peak subjective effects attained at 1.5 h. While harmine was not found in plasma except for a few time points in four of eighteen volunteers, all volunteers showed measurable levels of harmol and harmalol, the O-demethylated analogues of harmine and harmaline. Results suggest an intense first-pass metabolism for harmine. 6. In vivo MAO inhibition following ayahuasca administration could not be firmly and definitely established measuring the excretion of urinary monoamine metabolites. While ayahuasca increased normetanefrine excretion in line with the hypothesis, the levels of the MAO-dependent metabolites did not show the decreases expected for a MAO inhibitor. 7. Ayahuasca-induced increases in cardiovascular measures were moderate and statistical significance could only be demonstrated for DBP. The drug exerts a series of unpleasant somatic-dysphoric effects, the most common of which are altered physical sensations and nausea. However, in contrast with reports from field observations, ayahuasca-induced vomiting was infrequent. Transient disorientation and anxiety experienced by one volunteer was the most disturbing adverse event observed.