In human, the effects of ayahuasca have been widely reported, and its use has been associated with multiple pharmacological effects. Thus, Rios and Dobkins [14] investigated the effects of ayahuasca on 20 subjects, who presented illusions, synesthesia, and pseudo-hallucinations [14]. Riba [113] studied in six healthy volunteers the tolerability and psychological effects of ayahuasca, containing 0.5 mg/kg to 1.0 mg/kg of DMT; at least in five subjects induced modified state of awareness with psychedelic effects, modifications in perception and thought processes, qualifying to ayahuasca as an experience pleasant and satisfactory [113]. Also, 28 adolescents that ingested ayahuasca wore healthier and thoughtful than others 28 adolescents not exposed to ayahuasca [114].

Dos Santos in 2011, informed in 11 volunteers, that ayahuasca induces moderate impact on the autonomous nervous system and in the activation of the hypothalamic–pituitary–adrenal axis, increasing prolactin levels, blood pressure, and causing mydriasis [115]. Dos Santos [116] also reported in nine volunteers that ayahuasca could cause vomit, inducing psychotropic effect at a dose of 0.75 mg/kg of DMT, as well as increasing brain electrical activity.

Reports indicate that induced a psychedelic change in the anteroposterior coupling of electrophysiological brain oscillations in humans [117], with the decrease of the frequencies [118]. Ayahuasca in 11 volunteers studied by electroencephalography (EEC) induced effect over the 40 Hz band but did not change the alpha, beta, and theta bands (14–30 Hz) [78, 119]. In contrast, ayahuasca induced in the brain, an acute biphasic effect, changing the alpha and beta band at 2 h after ingested [123]; decelerating the binocular rivalry [121, 122] with hallucinogen effect of gamma oscillations in the visual pathways [123], and modifying the state of consciousness [120, 121]. Riba [123], reported in 18 volunteers that ayahuasca containing 0.85 mg DMT/kg, showed activity in region cortical after 60 min administration, with a decrease in delta and theta power activity, which is the general feature of psychostimulants [123]. Meanwhile, in 18 volunteers have been shown that ayahuasca, decreased the amplitude in P50 (inter-stimulus interval typically of 500 ms, leads to a decrease in the amplitude of the second P50 wave), suggesting a suppressing effect of the drug on normal sensory gating in humans [124].

The effects of chronic ayahuasca ingestion have been also well studied, especially at the central nervous system level. Via functional magnetic resonance imaging (fMRI) in ten volunteers, ayahuasca decreased activity through of the default mode network (DMN), suggesting that ayahuasca decrease the activity of core DMN structures. In 22 members of Santo Daime Church that ingested ayahuasca for around 5.3 years, it was found that structures involved in the DMN and attention/cognitive control include the posterior cingulate cortex (PCC) and precuneus and the medial prefrontal cortex (mPFC) [28, 125]. Besides, ayahuasca in other ten volunteers increased the activation of several occipital, temporal and frontal areas, especially zones closed to the processing of contextual association, memory, intentional prospective imagination and vision [76], with inhibition of the receptor 5TH 2A , present mainly in the alpha region in the visual network [126].

Osório et al. [127], reported that ayahuasca ingested by six volunteer whit a diagnosis of recurrent depressive disorder and bipolar depression, at a volume 120–200 mL (2.2 mL/kg body weight), during 21 days, exhibits significant acute antidepressant effects, calling to ayahuasca as a fast antidepressant action agent, due to providing a rapid reduction of depressive symptoms [127]. The group of Ribeiro and Dagalarrondo [128] showed the effect of ayahuasca given during 4 weeks (28 volunteers) and 6 months (23 volunteers) to members of Santo Daime and UDV groups [128, 129]. Volunteers showed visual phenomenon, numinosity, peacefulness, reduction of the intensity of psychiatric symptoms, assertively, serenity and vivacity [130].

Ayahuasca in 15 volunteers (1.0 mg/kg, DMT) interacts with neuronal systems, which is central to interoception and emotional processing as well as point to a modulatory role of serotonergic neurotransmission, notably the inhibition of 5TH- 2A receptor [31, 131], permitting the restoration serotonin level I in the brain [31]. However, in thirteen healthy subjects of UDV church, ayahuasca decreased the concentration extracellular of 5-HT 2A [132] which could explain the results of Santos [133], who reported in nine healthy volunteers from Santo Daime church, that ayahuasca did not decrease the anxiety of the volunteers, who began this study with low levels of anxiety.

Also, ayahuasca mitigated the aggressive personality with extra-sensorial experiences, in a person sentenced to 17 years in prison [131]. It is known, that the activation of the 5-HT 2A receptor is associated with aggression in the people [131]. Although the results are promising, the psychological changes should be observed with caution [133], since, in patients with mental disorders as schizophrenia, the DMT has been involved, a molecule present also in ayahuasca drink [134].

On another context, in six volunteers, smoked ayahuasca was more psychoactive that by via oral, this due to that smoked route initially bypasses the liver altogether, and compounds did not suffer an intense metabolism [135]. Also, Callaway [94] in 15 volunteers reported that harmine induces most profound visionary effects than DMT, which presents an accelerated metabolism that involves CYP2D6. Tetrahydroharmine (THH) gave a pharmacokinetic profile independent of harmine [94]. In other 18 volunteers, ayahuasca induced at 1.5 h, perceptual modification and increases in the rating of positive mood and action; the authors suggested that harmine interacts with DMT at gastrointestinal and liver level, which could impact in their metabolism and, in consequence, in their activity [136]. In general, the ayahuasca is promissory to the clinic practical [137], which should represent an incentive to continue with its pharmacological investigation [1].